Chinese General Practice

Advantages，Key Issues and Research Strategies of Traditional Chinese Medicine in the Prevention and Treatment of Bone and Joint Degenerative Diseases　

WEI Xu, HAN Tao, SUN Kai, CHEN Xin, YIN He, ZHU Liguo

2021, 24(35): 4421-4426. DOI: 10.12114/j.issn.1007-9572.2021.01.032

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The treatment of bone and joint degenerative diseases represented by cervical spondylosis，lumbar degenerative diseases，and knee osteoarthritis is mainly non-surgical treatment，which aredominant diseases of Traditional Chinese Medicine orthopedics. Traditional Chinese Medicine，manipulation，acupuncture，and traditional functional exercises are characteristic therapies commonly used in Chinese Medicine，which can significantly improve the clinical symptoms and signs of patients and prevent disease recurrence. At present，the prevention and treatment of bone and joint degenerative diseases with traditional Chinese Medicine still have many problems such as insufficient clinical efficacy evaluation，insufficient application of clinical Biobanks，insufficient research and development of key traditional Chinese Medicine technology and equipment，lack of multidisciplinary collaborative innovation. In order to solve these problems，it is suggested that traditional Chinese Medicine should follow the principle of “evidence-oriented，Chinese and Western medicine consensus” to carry out clinical research，standardize the collection of Chinese Medicine diagnosis and treatment information，build a clinical biological sample library，integrate modern science and technology to develop key Chinese Medicine technical equipment，integrate advantageous resources to achieve a collaborative research organization model，improve the research evidence of traditional Chinese Medicine in the prevention and treatment of bone and joint degenerative diseases，and further improve the level of clinical diagnosis and treatment.

Mechanism of Bushenhuoxue Herbs Mediating Wnt/β-Catenin Signaling Pathway to Delay the Progression of Compression-induced Degeneration of Intervertebral Disc Cartilage Endplate in a Rabbit Model　

HAN Tao，YIN Xunlu，ZHAN Jiawen，WEI Xu，FENG Minshan，YU Jie，LI Xuepeng，CHEN Ming，ZHU Liguo

2021, 24(35): 4427-4436. DOI: 10.12114/j.issn.1007-9572.2021.01.111

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Background　Intervertebral disc degeneration（IDD） is an essential cause of degenerative spine conditions. As endplate plays a vital role in mechanotransduction and nutrient transport in intervertebral discs，endplate degeneration will accelerate IDD. Compound preparations of Chinese Medicine have proven to be uniquely effective for IDD，but the specific mechanism of action is not completely clear. Objective　To observe the effect of Bushenhuoxue herbs on vertebral endplate of spinal motion segment in rabbits under pressure，to clarify the characteristics and mechanism of the medicine in regulating endplate chondrocytes to delay IDD progression. Methods　Forty healthy New Zealand rabbits were randomly divided into control group，herb group，herb inhibition group and herb activation group，with 10 rabbits in each. The model of IDD was created using an in vitro loading and culturing device for spinal motor segments with independent intellectual property rights. HE staining，immunohistochemistry，RT-PCR and Western blot were used for detecting relevant indicators，respectively. Including proteoglycan，typeⅡ collagen，Wnt-3α，β-catenin. Results　（1）Effect of Bushenhuoxue herbs on IDD：① The pathomorphology of the HE stained sample showed that herb group had better dispersion and layer arrangement，and more number of endplate chondrocytes than the control group on the 7th day of culture. The degeneration of endplate cartilage in herb group and control group worsened on the 14th day of culture，but the degree of degeneration of the control group was more obvious. ②Immunohistochemical staining in the sample tissue sections found that herb group had higher level of extracellular matrix proteoglycan expression than control group on the 1st and 3rd days of culture（P<0.05）. On the 7th and 14th days of culture，the level of extracellular matrix proteoglycan expression decreased significantly in herb group and control group compared to the baseline（P<0.05），but showed no significant intergroup differences（P>0.05）. Immunohistochemical staining of type Ⅱ collagen in the sample tissue sections found that herb group had higher level of type Ⅱ collagen expression in extracellular matrix than control group on the 1st and 3rd days of culture（P<0.05）. On the 7th and 14th days of culture，the level of type Ⅱ collagen expression in extracellular matrix declined obviously in herb group and control group compared to the baseline（P<0.05），but it was more reduced in the herb group（P<0.05）. ③The results of RT-PCR showed that compared to the baseline levels，Wnt-3α and β-catenin mRNA expression levels were much lower on the 1st，3rd，7th and 14th days of culture in herb group and control group（P<0.05），and they were more lower in herb group（P<0.05）. ④Western blot test indicated that significant changes were found in Wnt-3α and β-catenin protein expression levels in herb group and control group from baseline to 1，3，7，14 days post-culture（P<0.05）. Herb group demonstrated much higher Wnt-3α protein expression levels and notably lower β-catenin protein expression levels than control group on the 1st，3rd，7th and 14th days of culture（P<0.05）. （2）Mechanism of Bushenhuoxue herbs delaying the progression of IDD：HE staining showed that herb activation group had better integrity and arrangement of endplate cartilage at the 3rd day of culture than herb inhibition group. ②Immunohistochemical staining in the sample tissue sections found that significant differences were found in expression levels of proteoglycan and type Ⅱ collagen in the sample tissue sections between herb group and herb activation group or herb inhibition group（P<0.05）. ③RT-PCR results showed that on the 3rd day of culture，Wnt-3α mRNA expression level showed no significant differences between herb group and herb activation group or herb inhibition group（P>0.05）；the β-catenin mRNA expression level in herb group was much higher than that of herb activation group，but was much lower than that of herb inhibition group（P<0.05）. ④Western blot test indicated that on the 3rd day of culture，the Wnt-3α and β-catenin protein expression levels in herb activation group were similar to those of herb group（P>0.05）. The Wnt-3α protein expression level in herb inhibition group was similar to that of herb group（P>0.05）. The β-catenin protein expression level in herb inhibition group was much higher than that of herb activation group（P<0.05）. Conclusion　Bushenhuoxue herbs could delay the progression of IDD by regulating endplate chondrocytes through Wnt/β-catenin signaling pathway.

Chemical Constituents of Zhuangyaotongluo Decoction and Its Mechanism of Action in Delaying the Progression of Lumbar Intervertebral Disc Degeneration: a Study Using UPLC-Q-TOF-MS/MS and Network Pharmacology　

SUN Kai，ZHU Liguo，WEI Xu，YIN He，LI Qiuyue，QIN Xiaokuan，YANG Bowen1

2021, 24(35): 4437-4446. DOI: 10.12114/j.issn.1007-9572.2021.01.110

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Background　Zhuangyaotongluo decoction is effective for lumbar intervertebral disc degeneration（LIDD），but its chemical constituents and mechanism of action are unclear. Objective　To ascertain the major chemical constituents of Zhuangyaotongluo decoction，and to explore its potential mechanism of action in delaying the progression of LIDD. Methods　In 2020，Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to analyze the major chemical constituents of Zhuangyaotongluo decoction，and network pharmacology with mass spectrographic analysis was used to ascertain its potential mechanism of action targets. Therapeutic targets for LIDD were collected via checking 5 therapeutic target databases，and the common ones were identified by using Venn diagram analysis. The protein-protein interaction（PPI） networks of these common targets were obtained from the STRING 11.0 database，and the core targets were extracted from them. Finally，GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） were used for analyzing the core targets. Results　Zhuangyaotongluo decoction was found to be composed of 129 chemical constituents by UPLC-Q-TOF-MS. Then 96 common targets were obtained by mapping 203 action targets of Zhuangyaotongluo decoction to therapeutic targets for LIDD. PPI network analysis found that AKT1，INS，IL-6，FOS，and CASP3 were core targets. The GO analysis identified 1 022 biological process information，28 cellular components information，and 51 molecular function information. Analysis using KEGG identified 98 related signaling pathways，mainly including HIF-1 signaling pathway，JAK-STAT signaling pathway，Relaxin signaling pathway，p53 signaling pathway，and MAPK signaling pathway. Conclusion　This study revealed the chemical constituents contained in Zhuangyaotongluo decoction and their action targets，biological pathways and mechanisms of action for delaying LIDD，providing a reference basis for future in-depth analysis of its therapeutic substance basis and mechanisms of action.

Effect of Yishen Yangsui Formula on Expression of Neurotrophic Factorsanditsnerve Repair Effect in Spinal Cord of Rats with Cervical Spondylotic Myelopathy　

TANG Bin，YIN He，YANG Bowen，JIN Zhefeng，QIN Xiaokuan，LIU Zhiwei，WEI Xu，SUN Kai，QI Baoyu，CHEN Xin，ZHU Liguo

2021, 24(35): 4447-4456. DOI: 10.12114/j.issn.1007-9572.2021.01.033

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Background　There are differences in pathological characteristics and treatment strategies between acute spinal cord injury（ASCI） and cervical spondylotic myelopathy（CSM） by chronic compression. Traditional Chinese Medicine （TCM） has unique advantages in the treatment of CSM with extensive clinical application，but there were few studies on the treatment mechanism related to chronic compression of spinal cord. Objective　To study the effect of Yishen Yangsui formula Chinese medicine on the mRNA expression levels of nerve growth factor（NGF），neurotrophic factor 3（NT3），glial cell derived neurotrophic factor（GDNF） and the protein expression and distribution of NGF in the spinal cord of chronic spinal cord compression rats（C5-7），in order to explore the mechanism of TCM promoting nerve repair in CSM. Methods　A total of 96 SPF female SD rats were selected，of which 72 rats were operated by spinal cord compression with water absorbent swelling material polyvinyl alcohol acrylamide in terpenetrating network hydrogel（provided by College of Chemistry，Beijing Normal University），and the remaining 24 rats were operated under sham operation（sham operation group）. The successfully modeled rats were divided into model group（n=24），high concentration herb formula group（n=16），medium concentration herb formula group（n=16），low concentration herb formula group（n=16）. Each group was given intragastric administration of herb formula according to the corresponding concentration（the dose of intragastric administration of rats was calculated by the conversion coefficient of body surface area coefficient 6.3，high concentration was 16.74，medium concentration was 8.37 g•kg-1•d-1 and low concentration was 4.19 g•kg-1•d-1）. After the liquid was concentrated，it was given by intragastric administration in a volume of 1 ml/100 g. The model group and the sham operation group were given the same amount（1 ml/100 g）
of 0.9% sodium chloride intragastric administration once daily. BBB scores of rats in each group were evaluated at 2，4，6，8 and 10 weeks postoperatively. At 2 weeks，6 weeks and 10 weeks after surgery，the distribution of normal nerve cells in the ventral horn of the spinal cord of rats was observed by Nissl staining. The mRNA of NGF，NT3，GDNF was detected by RT-qPCR，the protein expression and distribution in the anterior horn region of the spinal cord of NGF were analyzed by immunohistochemistry. Results　（1）At 2 weeks after operation，BBB score of sham operation group was higher than model group（P<0. 05）；At 4 weeks after operation，BBB score of sham operation group was higher than model group，high concentration herb formula group，medium concentration herb formula group and low concentration herb formula group（P<0.05）；at 6 weeks after operation，BBB score of sham operation group was higher than model group，high concentration herb formula group，medium concentration herb formula group and low concentration herb formula group（P<0.05）；BBB score of model group was lower than that of high concentration herb formula group（P<0.05）；BBB score of high concentration herb formula group was higher than medium concentration herb formula group and low concentration group（P<0.05）；at 8 weeks after operation，BBB score of sham operation group was higher than model group，high concentration herb formula group，medium concentration herb formula group and low concentration herb formula group（P<0.05）；BBB score of model group was lower than high concentration herb formula group（P<0.05）；BBB score of high concentration group was higher than medium concentration herb formula group and low concentration herb formula group（P<0.05）；at 10 weeks after operation，BBB score of sham operation group was higher than model group，high concentration herb formula group，medium concentration herb formula group and low concentration herb formula group（P<0.05）；BBB score of model group was lower than high and medium herb formula concentration group（P<0.05）；BBB score of high concentration herb formula group was higher than low concentration herb formula group（P<0.05）. （2）At 2 weeks after operation，in the sham operation group，the motor neurons in the anterior horn of the spinal cord were normal in shape，with abundant Nissl bodies. In the model group，the neurons in the anterior horn of the spinal cord were small，round and sparsely distributed，and the intracellular Nissl bodies decreased or even disappeared. At 6 and 10 weeks after operation，the neurons in the group of high and medium concentration of herb formula were damaged to a certain extent，but the cell morphology was plump and intracellular Nissl bodies was visible. A small number of vacuoles were observed in the low concentration herb formula group，and the distribution of neuron cells was slightly sparse. The normal cell with Nissl bodies of low concentration herb formula group was less than the high and medium concentration herb formula group（P<0.05）. At 2 weeks after the operation，the number of normal cells in the sham operation group was more than that in the model group（P<0.05）. At 6 weeks after operation，the normal cells in the sham operation group was more than that in the model group，medium concentration herb formula group and low concentration herb formula group（P<0.05）；the normal cell in the model group was less than that in the high herb formula concentration group（P<0.05）；the normal cells in high concentration herb formula group was higher than that in low herb formula concentration group（P<0.05）. At 10 weeks after operation，the normal cells in sham operation group was higher than that in model group and low concentration herb formula group（P<0. 05）；The normal cell in model group was lower than that of high concentration herb formula group（P<0.05）. （3）At 6 weeks after operation，NGF mRNA in high concentration herb formula group was higher than sham operation group，model group and low concentration herb formula group（P<0.05）. NT3 mRNA in high concentration herb formula group was higher than model group（P<0.05）. GDNF mRNA in high herb formula concentration group was higher than sham operation group，model group，medium and low concentration herb formula groups（P<0.05）. （4）The NGF staining of neurons in the anterior horn of spinal cord in the sham operation group and the model group was shallow and sparsely distributed，while the NGF staining of neurons in the anterior horn of spinal cord in the high and medium herb formula concentration groups was obvious and the cell morphology was intact. At 6 weeks after operation，the average integral optical density of NGF in the high herb formula concentration group was higher than that in the sham group and the model group（P<0.05）. Conclusion　By increasing the expression levels of NGF，NT3 and GDNF mRNA in the spinal cord，the Yishen Yangsui formula may improve the limb motor function of the rats with CSM，maintain the number of normal motor neurons in the anterior horn of the spinal cord，and achieve the effect of promoting nerve repair.

Risk Factors and Predictive Scoring System for Long-term Adverse Cardiovascular Events in Patients with Acute Non-ST Segment Elevation Myocardial Infarction　

LYU Xiao，LI Shuren，LI Wenjing，CHEN Jialun，LIU Ran，MENG Yang，YUAN Zhihui，HAO Xiao，BAI Yuhao，LUO Fei

2021, 24(35): 4457-4462. DOI: 10.12114/j.issn.1007-9572.2021.01.022

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Background　The risk prediction scoring systems for acute coronary syndrome （ACS） have been extensively used for assessing the long-term prognosis of patients with acute non-ST-segment elevation myocardial infarction （NSTEMI）. Both STEMI and NSTEMI belong to ACS，but NSTEMI shows an increasing percentage in ACS，with a possible trend of exceeding the percentage of STEMI. Moreover，they have significant differences in incidence，mortality risk during the acute phase，and long-term prognosis. However，there is no literature about tools for effectively predicting long-term prognosis of patients with NSTEMI. Objective　To identify the risk factors for long-term major adverse cardiovascular events（MACEs） in discharged patients with NSTEMI，and based on this，to develop a predictive scoring system. Methods　Three hundred and twenty-four patients with an admission diagnosis of NSTEMI were recruited from Hebei General Hospital from January 2017 to August 2018. Clinical data were obtained，including age，sex，Killip class，systolic and diastolic blood pressure，heart rate，cardiac function at admission，past medical history（history of old myocardial infarction，PCI，coronary artery bypass grafting，thrombolysis，hypertension，diabetes，hyperlipidemia，chronic kidney disease，old cerebral infarction，cerebral hemorrhage，anemia），smoking，drinking，incidence of in-hospital heart failure，in-hospital medication，GRACE score，left ventricular ejection fraction，hemoglobin，white blood count，lymphocytes，platelet count，alanine aminotransferase，aspartate transaminase，total protein，globulin，albumin，serum creatinine，glomerular filtration rate，electrolytes，blood lipids，and treatment strategies. All cases were followed up till 2020-09-01，during which the incidence of MACEs and all-cause death were recorded. The risk factors of out-of-hospital MACEs were identified，and used to construct a predictive scoring system. Results　（1） Compared with patients without MACEs，those with MACEs had older mean age，higher mean higher prevalence of grade 2-3 hypertension，in-hospital betamethasone treatment，in-hospital heart failure，and non-revascularization treatment，lower prevalence of smoking，as well as lower mean levels of glomerular filtration rate，low-density lipoprotein，lymphocyte count，and hemoglobin（P<0.05）. （2） Multivariate Logistic regression analysis showed lymphocyte count〔OR=0.621，95%CI（0.408，0.946），P=0.026〕，hemoglobin〔OR=0.983，95%CI（0.969，0.996），P=0.013〕，non-revascularization 〔OR=2.030，95%CI（1.153，3.573），P=0.014〕，and the cut-off value of total protein〔OR=2.412，95%CI（1.244，4.675），P=0.009〕were associated with out-of-hospital MACEs in NSTEMI patients.（3） A regression equation based on these risk factors of MACEs was developed：logit（P）=3.98-0.476X1-0.018X2+0.88X3+0.708X4（X1-X4 stand for lymphocyte count，hemoglobin，total protein，and non-revascularization，respectively）. Combined with the risk coefficient β of each factor，a scoring system with a total score of 21 points and a predictive threshold of 9 points was constructed，with an AUC value of 0.704. Conclusion　Long-term MACEs were common in patients with acute NSTEMI，which may be associated with lymphocyte count，hemoglobin，total protein and non-revascularization. Our predictive scoring system for long-term MACEs with a total score of 21 points and a predictive threshold of 9 points，and has good predictive capability.

Interventional Therapy Prevalenceand Influencing Factors in Patients Aged 75 and over with Acute Non-ST Segment Elevation Myocardial Infarction　

LYU Xiao，LI Shuren，SHEN Zexue，HAO Xiao，CHEN Jialun，MENG Yang，LUO Fei，BAI Yuhao，YUAN Zhihui

2021, 24(35): 4463-4468. DOI: 10.12114/j.issn.1007-9572.2021.01.023

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Background　Older age is an independent risk factor of the onset and poor prognosis of acute non-ST-segment elevation myocardial infarction （NSTEMI） patients. Although older age is not alimitingfactor for reperfusion therapy theoretically，the prevalence of reperfusion therapy in Chinese older NSTEMI patients is far lower than that of those in developed countries，so it is necessary to analyze the factors associated with inability to receive reperfusion therapy in such patients. Objective　To analyze the prevalence and associated factors of invasive therapy in patients aged 75 and over with NSTEMI.Methods　Five hundred and thirty-sixcases with an admission diagnosis of NSTEMI were selected from Hebei General Hospital from November 2016 to August 2019. The following variables were collected，including age，sex，Killip class >Ⅱ，admission blood pressure and heart rate，medical history （including history of old myocardial infarction，PCI history，grade 2-3hypertension，diabetes，hyperlipidemia，chronic kidney disease，anemia），smoking，drinking，GRACE score，left ventricularejection fraction，white blood cell count，hemoglobin，platelet count，albumin，fasting blood glucose，serum creatinine，glomerular filtration rate，total cholesterol，triglyceride，high-density lipoprotein，low-density lipoprotein and treatment strategies. The differences between patients under 75 years of age and those aged 75 and over were compared after being matched using the propensity score. Subgroup differences were analyzed between those with interventional therapy and with conservative treatment in the 75-and-over age group. Multivariate Logistic regression analysis was used to explore the influencing factors of invasive treatment. Results　After propensity-score matching，it was found that patients under 75 years of age had higher prevalence of interventional therapy （P<0.05）. Compared with conservative treatment subgroup，interventional therapy subgroup had decreased GRACE score and serum creatinine，and elevated total cholesterol and albumin（P<0.05）. Multivariate logistic regression analysis showed systolic blood pressure〔OR=1.022，95%CI（1.002，1.044），P=0.034〕，GRACE score 〔OR=1.015，95%CI（1.001，1.030），P=0.031〕，albumin level〔OR=0.86，95%CI（0.763，0.969），P=0.013〕，serum creatinine level〔OR=1.018，95%CI（1.000，1.035），P=0.044〕 were associated with interventional therapy. Conclusion　The rate of interventional therapy in elderly patients（age≥75 years old）with NSTEMI is lower. The possibility of receiving invasive therapy may be increased with lower blood pressure and higher albumin，and may be reduced with higher GRACE score and serum creatinine level.

Association between Discharge Destination and Medium-term Mortality in Elderly Patients with ST-segment Elevation Myocardial Infarction　

WANG Qi，LIN Zhen，CHEN Hairong，ZHOU Yanhui

2021, 24(35): 4469-4474. DOI: 10.12114/j.issn.1007-9572.2021.01.028

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Background　Population ageing has led to an increase in the number of elderly patients with ST-segment elevation myocardial infarction（STEMI） receiving percutaneous coronary intervention（PCI）. Coexistence of diseases，frailty，impaired immunity，poor nutritional status and other conditions may occur in elderly patients，which may have an impact on their recovery and return to their families. There is a lack of a comprehensive assessment on the relationship between this group's discharge destination and prognosis. Objective　To assess the relationship between discharge destination and medium-term mortality in 80-year-old STEMI survivors receiving PCI. Methods　A retrospective analysis was conducted on STEMI patients undergoing PCI in Haikou People's Hospital from December 2015 to December 2018，with the following information collected，including general data〔age，gender，BMI，hospital stays，major medical histories （heart failure，myocardial infarction，PCI，coronary artery bypass grafting，stroke，gastrointestinal bleeding，peripheral arterial disease，dyslipidemia，diabetes，hypertension，smoking，chronic kidney disease，systolic pressure，diastolic pressure，heart rate，Killip classification），proportion of left ventricular ejection fraction（LVEF） <40%〕，laboratory findings〔hemoglobin，albumin，white blood cell count，C-reactive protein，blood glucose，peak CK during hospitalization〕，pathological features of coronary artery〔left main coronary artery（LMCA），left anterior descending artery（LADA），left circumflex artery（LCXA），right coronary artery （RCA），number of patients with 2-vessel disease and time from symptom onset to reperfusion〕，post-discharge medication （aspirin，clopidogrel or ticagrelor，warfarin，new oral anticoagulants，statins，ACEI/ARB，calcium receptor antagonist，β-receptor blocker） and severe debilitating condition. The follow-up started at discharge and ended in December 2020，with the terminal event of being all-cause death. Logistic regression analysis was used to explore the influencing factors of all-cause death. Results　In all，2 450 patients completed thefollow-up，including 2 090 who were discharged to home （home discharge group） and 360 to other facilities （non-home discharge group）. During the follow-up period，370 patients（17.5%） died after discharge，and the most common cause of death was infection（21.6%，80/370），followed by sudden death（18.9%，70/370） and heart failure（16.2%，60/370）. The cardiovascular death rate of the homedischarge group was higher than that of the non-homedischarge group（P<0.05）. Two groups showed significant differences in the cumulative mortality curve（P<0.05）. Univariate Logistic regression analysis showed that non-home discharge，previous heart failure，lesions in the LADA，serum albumin <35 g/L，LVEF<40% may be the risk factors of all-cause death during follow-up （P<0.05）. Further multivariate Logistic regression analysis showed that LVEF<40%〔OR=3.161，95%CI（1.564，6.389），P=0.001〕，previous heart failure〔OR=4.899，95%CI（1.835，13.078），P=0.002〕，non-homedischarge〔OR=2.617，95%CI（1.188，5.765），P=0.049〕，lesions in the LADA〔OR=2.210，95%CI（1.137，4.295），P=0.019〕，albumin level<35 g/L〔OR=2.147，95%CI（1.064，4.330），P=0.033〕 were all risk factors of death during follow-up period. Conclusion　There is a relationship between non-family discharge and an increased risk of medium-term mortalityin STEMI patients over the age of 80. Active searching for causes of non-homedischarge and early delivering targeted interventions may reduce the medium-term mortality in thesepatients.

Effect of Cilostazol on Cardiac Function in Acute Myocardial Infarction Patients with Congestive Heart Failure and Aspirin Intolerance　

HE Mei，LI Feng，HU Houxiang，LIU Fu

2021, 24(35): 4475-4480. DOI: 10.12114/j.issn.1007-9572.2021.01.008

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Background　Aspirin is the cornerstone for treating acute myocardial infarction，but about 2%-9% of patients can develop aspirin intolerance. Cilostazol may be used as an alternative to aspirin，but its cardiovascular safety is unclear. Objective　To investigate the safety of cilostazol in acute myocardial infarction patients with congestive heart failure and aspirin intolerance. Methods　Patients with a primary diagnosis of acute myocardial infarction and congestive heart failure who were hospitalized in three hospitals（Affiliated Hospital of North Sichan Medical College，Pengan County People's Hospital，Changan Branch，the First Affiliated Hospital of Xi'an Jiaotong University） from January 2018 to August 2019 were retrospectively included. All were treated according to the diagnosis and treatment criteria of myocardial infarction. Specifically，those with aspirin intolerance received cilostazol and clopidogrel （cases），and the other received aspirin and clopidogrel（controls），and the two groups were matched based on propensity scores in a 1∶1 ratio. Outcomes were compared between the groups in terms of 1-year cardiac death，1-year readmission for heart failure，left ventricular diastolic diameter，and ejection fraction measured by echocardiography before and after treatment. Multivariate Logistic regression analysis was used to explore factors associated with 1-year cardiac death and heart failure readmission. Results　Of the 5 244 hospitalized cases in the period，3 893 who met the inclusion and exclusion criteria were finally included. After matching，the cases and controls had no statistically notable differences in left ventricular diastolic diameter，and ejection fraction（P>0.05）. But the cases had higher rates of 1-year cardiac death and heart failure readmission（P<0.05）. Multivariate Logistic regression analysis showed that NYHA class ⅢandⅣ，and combined with diabetes were associated with 1-year cardiac death （P<0.05）. NYHA class ⅢandⅣ，diabetes，and cilostazol treatment for more than 90 days were recognized as the influencing factors of heart failure readmission （P<0.05）. Conclusion　It may be safe to use cilostazol in acute myocardial infarction patients with NYHA class Ⅰ and Ⅱ. Given increased safety risks，cilostazol is not recommended for those with NYHA classⅢandⅣ，and combined with diabetes. Moreover，cilostazol is not suggested to be used for more than 90 days，due to increased potential risks of heart failure readmission.

Evaluation of Prognosis of Novel Coronavirus Pneumonia Combined with Acute Respiratory Distress Syndrome Patients with the Oxygenation Index and Dispersion Index of Mechanical Ventilation　

WANG Jun，JIANG Shuqing

2021, 24(35): 4481-4484. DOI: 10.12114/j.issn.1007-9572.2021.01.308

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Backgroud In the treatment of severe and severe cases，New Coronavirus pneumonia diagnosis and treatment plan （Trial Seventh Edition） suggested that if the patients did not improve or deteriorate within a short time （1-2 h） after the use of high flow nasal catheter oxygen therapy or non-invasive ventilation，tracheal intubation and invasive mechanical ventilation should be carried out in time. No objective reference indexes have been proposed in the opinions，and the commonly used oxygenation index is insufficient in the clinical application of such patients，so it is particularly important to explore more valuable reference indexes. Objective　To compare the difference of dispersion index and oxygenation index in the prognosis assessment of patients diagnosed with Novel Coronavirus Pneumonia （COVID-19） who have acute respiratory distress syndrome （ARDS） when they are treated with mechanical ventilation. Methods　A retrospective single center study was conducted in 39 patients with ARDS of Novel Coronavirus Pneumonia admitted to ICU with mechanical ventilation of Wuhan Tianyou Hospital from January 25，2020 to March 14，2020. Two of them were lost due to death within 24 hours，patients were divided into survival group （n=11） and death group （n=26） according to their 28-day status. Ventilator parameters and corresponding blood gas values were recorded to study the correlation between dispersion index and oxygenation index and 28 days' prognosis of patients. Results　The worst oxygenation index，the dispersion index，and the worst dispersion index when entering ICU in the survival group were higher than those in the death group （P<0.05）. The sensitivity of the oxygenation index to predict death when entering the ICU was 100.0%，the specificity of the oxygenation index was 46.2%，the area under the ROC curve （AUC） was 0.654，and the difference between AUC and the reference value was not statistically significant （P=0.144）；The sensitivity of the oxygenation index to predict death was 3.8%，the specificity was 100.0%，and the AUC was 0.862 when the oxygenation index was the lowest，comparing with the reference value，the difference was statistically significant （P<0.05）；The sensitivity of the dispersion index to predict death was 7.7%，the specificity was 100.0%，and the AUC was 0.734 when entering the ICU，comparing with the reference value，the difference was statistically significant （P<0.05）；The sensitivity of the dispersion index to predict death was 100.0%，the specificity was 80.8%，and the AUC was 0.902 when the dispersion index was the lowest，comparing with the reference value，the difference was statistically significant （P<0.05）. Conclusion　Dispersion index is a more sensitive and reliable prognostic indicator for ARDS in Novel Coronavirus Pneumonia patients than oxygenation index. The dispersion index is a more sensitive and reliable prognostic evaluation index than the oxygenation index in Novel Coronavirus Pneumonia patients with ARDS.

Comparison of the Predictive Value of GAP Staging and CPI for Risk of Death in Patients with Idiopathic Pulmonary Fibrosis　

CAI Bo，CHEN Xianqiu，YANG Wenlan，YANG Guanghong，HUANG Jin，QUAN Hua，FENG Yonghong

2021, 24(35): 4485-4491. DOI: 10.12114/j.issn.1007-9572.2021.00.598

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Background　Gender，age，and physiologic variables（GAP）staging and composite physiologic index（CPI），are often used alone for predicting the death risk of idiopathic pulmonary fibrosis（IPF），but which is more superior or has higher clinical value is still unclear. Objective　To explore the predictive value of GAP staging and CPI for risk of death in patients with IPF. Methods　A retrospective analysis was done in 200 cases of confirmed IPF with complete clinical data and follow-up records who hospitalized in Shanghai Pulmonary Hospital，Tongji University，from 2012 to 2019〔including 181 men（90.5%），and 19 women（9.5%），with an average age of（66.0±7.6）years（ranging from 41 to 85 years）〕. By using GAP staging，109（54.5%），75（37.5%），and 16（8.0%）cases were classified as at GAP stage Ⅰ，stage Ⅱ，and stage Ⅲ，respectively. And by using CPI score，99（49.5%）and 101（50.5%）cases were evaluated with CPI ≤ 41 points，and >41 points，respectively. Clinical，imaging，and physiological characteristics were compared across GAP stages and CPI groups to find the intergroup differences. Cox regression was used to perform univariate analysis of the prognostic factors of IPF. The area under the ROC curve（AUC）of each of the two models to predict the mortality of IPF patients was calculated to measure the prognostic accuracy. Medcalc was used to quantify the predictive accuracy of the two models for overall IPF mortality，and one-year，two-year，and three-year IPF mortality. Results　Cox regression analysis demonstrated that high GAP score〔HR=1.038，95%CI（1.023，1.054）〕，high CPI score〔HR=1.509，95%CI（1.286，1.771）〕，GAP stage Ⅱ〔HR= 2.622，95%CI（1.536，4.475）〕，GAP stage Ⅲ〔HR=4.002，95%CI（1.947，8.226）〕were independently associated with increased risk of poor prognosis of IPF patients（P<0.05）. For predicting one-year，two-year，and three-year mortality as well as overall mortality of IPF patients，the AUC of GAP staging was 0.685〔95%CI（0.616，0.749）〕，0.675〔95%CI（0.606，0.740）〕，0.642〔95%CI（0.571，0.708）〕，and 0.668〔95%CI（0.598，0.733）〕，respectively，and the AUC of CPI score was 0.750〔95%CI（0.684，0.809）〕，0.745〔95%CI（0.679，0.804）〕，0.735〔95%CI（0.669，0.795）〕，0.745〔95%CI（0.679，0.804）〕，respectively. GAP staging and CPI score had statistically significant differences in the AUC for predicting two-year，and three-year mortality as well as overall mortality of IPF（Z=2.193，P=0.028 3；Z=2.918，P=0.003 5；Z=2.529，P=0.011 4），
but had no statistically difference in one-year mortality（Z=1.799，P=0.072 1）. Conclusion　Both CPI and GAP staging may be efficient prognostic factors for IPF. CPI was significantly better than GAP staging in predicting the overall，two-year，and three-year mortality，but the AUC ranged 0.64 to 0.75，indicating that its prognostic performance may be limited. More practical and feasible death risk prediction models are still needed to be established.

Development and Validation of a Clinical Prognosis Scoring System for HIV/AIDS Patients with Community-acquired Pneumonia　

FU Kai，FU Yongjia，WANG Lingqin，QIN Jinyu，MENG Dali，JIANG Zhongsheng

2021, 24(35): 4492-4498. DOI: 10.12114/j.issn.1007-9572.2021.00.579

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Background　Community-acquired pneumonia（CAP） is the most common opportunistic infection among people with human immunodeficiency virus（HIV）/acquired immune deficiency syndrome（AIDS）. Evaluating disease severity and scoring short-term mortality will greatly help physicians to make objective decisions during the initial visit of HIV/AIDS patients with CAP，which is crucial to patient prognosis. Objective　To develop and verify a clinical prognosis scoring system for HIV/AIDS patients with CAP. Methods　Clinical data of 615 HIV/AIDS patients with CAP（455 in modeling group，and 160 in validation group） recruited from Liuzhou People's Hospital from 2016 to 2019 were retrospectively analyzed，including demographics，underlying diseases，24-hour post-admission vital signs，clinical laboratory results（routine blood test，liver and kidney function tests，blood gas analysis），imaging examination and so on. Multivariate Logistic regression analysis of the clinical data of modeling group was conducted to screen for independent risk factors of clinical prognosis to develop a clinical prognosis scoring system. Kaplan-Meier survival analysis was used to compare the worsening mortality between different risk groups rated by the scoring system. And the predictive performance of the scoring system was tested by using the data of validation group. Results　Patients with improved and deteriorated conditions had significant differences in the prevalence of admission to the ICU，disturbance of consciousness，respiratory rate>30 breaths per minute，hypotension，platelet blood count（PLT）<100×109/L，hematocrit （HCT） <35%，pH<7.35 or >7.45，partial pressure of oxygen （PaO2） <60 mm Hg，oxygen saturation（SaO2）<93%，urea nitrogen（BUN）>7 mmol/L，lactate dehydrogenase（LDH）>230 U/L，seralbumin（ALB）<30 g/L，total bilirubin（TBil）>34.2 μmol/L，alanine aminotransferase（ALT）>40 U/L，aspartate aminotransferase（AST）>40 U/L，serum sodium（Na）<135 mmol/L or>145 mmol/L，and CD4 lymphocyte count<50 cells/mm3 （P<0.05）. Multivariate Logistic regression analysis identified 10 risk factors for prognosis: admission to the ICU，disturbance of consciousness，hypotension，PLT<100×109/L，HCT<35%，SaO2<93%，LDH>230 U/L，ALT>40 U/L，Na<135 mmol/L or >145 mmol/L and CD4 lymphocyte count <50 cells/mm3. These 10 factors were included in the prognosis scoring system and assigned the value of 6，2，1，1，2，3，1，2，2，1，respectively，and mortality risks assessed using the system were stratified into low risk（0-6 points），medium risk（7-12 points）and high risk（more than 12 points）. Kaplan- Meier survival analysis showed that the worsening mortality varied significantly across different risk groups（χ2=87.634，P<0.001）. In predicting the mortality risk，the scoring system had an AUC of 0.858 with 77.9% sensitivity and 78.4% specificity in modeling group，and had an AUC of 0.820 with 73.7% sensitivity and 77.6% specificity in validation group. Conclusion　Our clinical prognosis scoring system based on with risk factors for CAP in HIV/AIDS has been confirmed with good predictive ability.

Analysis of Epidemiological Characteristics of 581 Children with Kawasaki Disease in Gansu　

WU Jinzhi，DENG Haimei，MIN Li，WANG Jin，NIU Shaomin，LIU Yahong，YANG Yinan，DONG Xiangyu

2021, 24(35): 4499-4505. DOI: 10.12114/j.issn.1007-9572.2021.01.031

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Background　Kawasaki disease （KD） is a systemic vasculitis associated with coronary artery lesion （CAL），which can lead to cardiomyopathy，myocardial infarction and death. At present，the incidence of KD is increasing year by year and has become the most common cause of acquired heart disease in children，significantly affecting the occurrence of long-term cardiovascular events during adulthood. Understanding the epidemiological characteristics and influencing factors of the disease is of great significance for reducing the incidence of the disease. Objective　To discuss the epidemiological characteristics of KD in Gansu from three aspects：demographic characteristics，time distribution and regional differences，in order to provide scientific basis for the management and prevention of KD in the western region. Methods　The 581 children with KD admitted to the Lanzhou University Second Hospital from January 2012 to December 2019 were selected as the research objects. According to the CAL status of the selected children within 1 month，the children with KD were divided into KD combined with CAL （CAL group） and without CAL （NCAL group）. According to the age of onset，they were divided into four age groups：≤1 year old，>1-3 years old，>3-6 years old and >6 years old. A unified questionnaire was used to collect general information （age，gender，ethnicity，time of onset，etc.） and thecoronary artery color Doppler ultrasound results. Results　（1）Demographic characteristics：among the 581 hospitalized children，the median age of onset of KD was 1.9 （1.2，3.2）years old. The ratio of male to female was about 1.9∶1 and the proportion of males decreased linearly with the increase of age （χ2trend=5.100，P<0.05）. （2）Temporal distribution：the overall number of KD showed an upward trend in different years （χ2trend=122.348，P<0.001）. There were significant differences in the distribution of KD cases in each season（χ2=12.418，P<0.05）. The proportion of children in spring was negatively correlated with their age groups（rs=-1，P<0.001），of which in autumn was positively correlated with the age groups（rs=1，P<0.001）. （3）Regional differences：combined with the geographical location，natural conditions and the current situation of regional economic and social development，Gansu Province was divided into five regions：Hexi，Longzhong，Longdong，Longdongnan and ethnic regions. According to the daily living expenses of urban residents，the average wage of workers and the level of social and economic development，Gansu Province was divided into four types of economic areas from high to low. The number of medical cases increased year by year in Longzhong region（χ2trend=86.011，P<0.001），Longdongnan region （χ2trend=23.848，P<0.001） and ethnic region （χ2trend=17.463，P<0.001）. The number of medical cases in economic class one （χ2trend=54.551，P<0.001），economic class two （χ2trend=20.586，P<0.001），economic class three （χ2trend=14.844，P<0.001） and economic class four （χ2trend=36.013，P<0.001） increased year by year. （4）Influencing factors：the number of KD cases of combined CAL （χ2trend=95.041，P<0.001） and NCAL （χ2trend=38.719，P<0.001） between different years showed an upward trend，especially in the CAL group （χ2trend=9.502，P<0.05）；multivariate Logistic regression analysis showed that age〔OR=3.011，95%CI（1.313，6.907）〕，gender〔OR=1.634，95%CI （1.137，2.349 ）〕and four economic areas〔OR=1.772，95%CI（1.172，2.679）〕were the independent risk factors of CAL. Conclusion　The number of patients with KD in Gansu had a tendency of growth by year，especially in the CAL group.The burden of disease was severe，especially in economically underdeveloped areas. In order to reduce the incidence of KD and its complications，it is necessary to increase public awareness of the severity of the disease，and properly increase prevention and control efforts for male infants in summer （try to intervene in advance for people at high risk of KD，such as immune regulation），establish and improve the KD follow-up mechanism，strengthen the training of primary physicians，conducting multi-center research and continuously monitorthe epidemiological characteristics of KD to obtain important information related to the best prevention strategy，early diagnosis，treatment timing and treatment choice.

Epidemiological Characteristics and Influencing Factors of Low Birth Weight Infants in Hebei Province　

LI Sisi，JIN Ying，DUAN Ya，ZHANG Cui，TIAN Meiling，MA Xuyuan，Wang Li

2021, 24(35): 4506-4511. DOI: 10.12114/j.issn.1007-9572.2021.00.582

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Background　Low birth weight infants often have chronic intrauterine hypoxia，their perinatal mortality rate is high，and the long-term physical development is backward and the risk of neurodevelopmental abnormalities is also high. Objective　To analyze the epidemiological characteristics of low birth weight infants and related factors affecting low birth weight infants in Hebei Province. Methods　The maternal and child monitoring information management system of Hebei Province was used to collect data of pregnant women at 37 weeks and above from 22 monitoring sites including 7 provincial and municipal hospitals and 15 county-level hospitals in Hebei Province from 2013 to 2017. Survey indicators included maternal age，birth year，birth season，urban-rural and rural grade distribution of birth hospitals，number of birth checkups，pregnancy times，parity times，fetal gender，the combination with gestational hypertension，gestational diabetes，heart disease and kidney disease，placental abruption，placenta previa，prolonged pregnancy and other related factors. Multivariate Logistic regression was used to analyze the influencing factors of low birth weight infants. Results　Among 250 304 full-term newborns，3 482 cases were low birth weight，with an incidence of 1.39%. There were statistically significant differences in the incidence of low birth weight infants among pregnant women of different ages，birth years，birth seasons，birth regions，urban-rural and rural grade distribution of birth hospitals（P<0.05）. The incidence of low birth weight was the highest（1.65%）among pregnant women with childbearing aged ≥40 years，and the lowest（1.29%）among women aged 30 to 34. The incidence of low birth weight infants was highest in 2015（1.56%）and lowest in 2017（1.29%）. The incidence of low birth weight infants was highest in spring（1.47%）and lowest in autumn（1.29%）. The city of Cangzhou had the highest incidence of low birth weight（1.82%），while Xingtai had the lowest incidence（0.82%）.The incidence of low birth weight infants in provincial and municipal hospitals（1.71%）was higher than that in township hospitals（1.13%）. The incidence of low birth weight infants was highest in tertiary hospitals（1.94%）and lowest in primary hospitals（0.98%）. There were statistically significant differences in age distribution，number of antenatal examinations，the number of pregnancy and parity，fetal sex，proportion of gestational hypertension，proportion of heart disease，proportion of kidney disease，proportion of placental abruption，proportion of placenta previa and proportion of prolonged pregnancy between the low birth weight group and non-low birth weight group（P<0.01）. There was no significant difference in education level and proportion of gestational diabetes mellitus（P>0.05）. Multivariate Logistic regression analysis showed that lower education level of pregnant women，fewer times of birth check-up，female fetus，delivery in provincial and municipal hospitals，gestational hypertension，heart disease，placental abruption，placenta previa were independent risk factors for low birth weight（P<0.05）. Multiple pregnancies，gestational diabetes mellitus and prolonged pregnancy were independent protective factors for low birth weight infants（P<0.05）. Conclusion　The incidence of low birth weight infants varies significantly in time，region and population. Individualized preventive measures should be taken for different regions and populations，such as timely pregnancy and standardized prenatal examination，early detection of potential high-risk factors，timely prevention and treatment to reduce the incidence of low birth weight infants.

Analysis of Gene Carrier and Characteristics for Neonatal Thalassemia in Baisha Li Autonomous County，Hainan Province in 2020　

SHI Haijie，ZHAO Zhendong

2021, 24(35): 4512-4515. DOI: 10.12114/j.issn.1007-9572.2021.01.401

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Background　Since 2012，Hainan Province has been committed to prenatal thalassemia screening to reduce the low birth rate of thalassemia children. However，the prevention and control of neonatal thalassemia is still a weak board in our province. Objective　To investigate the carrying status of thalassemia-causing genes and genetic characteristics of thalassemia in Baisha Li Autonomous County，Hainan Province. Methods　According to the principle of voluntary informed consent，912 newborns born in themidwifery Baisha Li Autonomous County of Hainan Province units in 2020 were collected with dried blood spots on the heels. Fluorescent PCR melting curve method was used to detect the common thalassemia genes in Chinese，and some samples were verified by PCR + flow-through hybridization method. Genetic testing kits suggested that samples with suspected new mutations were sent to the genetic company for analysis and verification. Results　（1）Among the 912 samples，608 thalassemia genes were detected，the carrying rate of thalassemia genes in the newborn population in Baisha Li Autonomous County was 66.7% （608/912）. The number of α，β，and α compound β thalassemia genes detected were 521，25，and 62，respectively. The top three genotypes of α-thalassemia gene detected were –α3.7/αα（26.3%）, -α4.2/αα（23.8%），and αWSα/αα（12.7%），respectively. Three rare genotypes of thalassemia gene，-α4.2/HKαα，c.118C>T，and c.309C>T，were also detected.（2） Divided by ethnicity groups，the thalassemia gene carrier rates in newborn populations of Han，Li and other ethnic minorities were 51.5% （175/340），76.7% （414/540） and 59.4% （19/32），respectively. Conclusion　The thalassemia gene carrier rate is high in the newborn population of Baisha Li Autonomous County，Hainan Province，and the thalassemia genotypes are abundant. The alpha thalassemia genotype is the most common，and the Li nationality newborn population has the highest carrier rate.

System Evaluation of Digital Cognitive Behavioral Therapy for Insomnia　

WANG Yueying，MU Yunping，YIN you，ZHU Bingqian

2021, 24(35): 4516-4524. DOI: 10.12114/j.issn.1007-9572.2021.01.027

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Background　Digital cognitive behavioral therapy for insomnia（dCBT-I） has been increasingly used worldwide. dCBT-I developed in China is unique in its cultural and medical background，however，its effect on insomnia remains to be examined. Objective　To evaluate the effect of dCBT-I in Chinese adults，thereby providing further evidence for the management of insomnia. Methods　A systematic search was performed in 10 electronic databases，including CNKI，Wanfang，VIP，SinoMed，PubMed，EMBase，CINAHL，Web of Science，Cochrane，and PsyINFO from inception to December 2020. Only randomized controlled trials（RCTs） conducted in Chinese adults with insomnia were included. The involved patients receiving dCBT-I（experimental group） were compared to those receiving non-dCBT-I（control group）. Primary outcomes included sleep quality，Insomnia Severity Index（ISI），sleep duration，sleep efficiency，and sleep onset latency. Secondary outcomes included beliefs and attitudes about sleep，anxiety，and depression. Two investigators performed the study selection，data extraction，and quality appraisal separately. Version 2 of the Cochrane risk-of-bias tool for randomized trials（ROB2） was used for quality appraisal. Revman 5.4 was used for Meta-analysis. Results　Seven RCTs consisting of 957 participants were included. One had moderate risk of bias and six had high risk. Based on the meta-analysis，compared to medication treatment，dCBT-I resulted in better sleep efficiency〔WMD=4.63，95%CI（0.63，8.63），P=0.02〕，sleep onset latency〔WMD=-12.18，95%CI（ -20.48，-3.88），P=0.004〕，and wake after sleep onset〔WMD=-17.18，95%CI（-30.29，-4.08），P=0.01〕. Similarly，compared to those receiving non-active treatment，those receiving dCBT-I showed better sleep efficiency〔WMD=8.94，95%CI（1.64，16.24），P=0.02〕，sleep onset latency〔WMD=-14.71，95%CI（-27.61，-1.81），P=0.03〕，insomnia severity（assessed using the ISI）〔WMD=-3.73，95%CI（ -6.57，-0.88），P=0.01〕，and overall sleep quality（assessed using the PSQI score）〔WMD= -2.21，95%CI（ -3.04，1.38），P<0.000 01〕. In addition，compared to routine sleep education，dCBT-I improved overall sleep quality（assessed using the PSQI score）（t=3.231，P=0.002）. dCBT-I and medication treatment resulted in similar improvements in anxiety and depression （pre-post treatment comparison，P<0.05）. dCBT-I also improved beliefs and attitudes about sleep （pre-post treatment comparison，P<0.05） and showed greater improvements than non-active treatment（P<0.01）.Conclusion　Currently，dCBT-I is delivered via various forms and platforms in China，without a consistent and standardized protocol. Overall，dCBT-I could improve short-term sleep quality among Chinese adults with insomnia. Larger studies using both objective and subjective measurements of sleep are warranted to examine the long-term effect of dCBT-I.

Effects of High-intensity Interval Training Versus Moderate-intensity Continuous Training on Cardiorespiratory Fitness in Patients with Coronary Heart Disease：a Meta-analysis　

LI Daxin，ZHU Junying，CHEN Ping

2021, 24(35): 4525-4534. DOI: 10.12114/j.issn.1007-9572.2021.01.222

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Background　Among cardiovascular diseases，coronary heart disease（CHD）is the leading cause of death globally，with stubbornly high prevalence and incidence. Exercise has been widely concerned as an important intervention for CHD，and it is essential to choose an appropriate exercise rehabilitation program. Both high-intensity interval training（HIIT）and moderate-intensity continuous training（MICT）have proved to be effective in improving the cardiorespiratory fitness in CHD，but which is more superior is still a controversial. Objective　To explore the effect of HIIT versus MICT on cardiorespiratory fitness in CHD，providing a basis for the formulation of an appropriate exercise rehabilitation program for patients with CHD. Methods　Databases of PubMed，EMBase，The Cochrane Library，Web of Science，China Biomedical Literature Database，CNKI，CQVIP and Wanfang Data knowledge service platform were searched from inception to November 2020 for randomized controlled trials（RCTs）about effects of HIIT versus MICT on cardiorespiratory fitness in patients with CHD. Information including the first author，year of publication，country，size，gender，and age of the sample，type，duration，frequency，and program（HIIT or MICT）of the intervention，and outcomes 〔peak oxygen uptake（VO2peak），oxygen uptake at the anaerobic threshold（VO2AT），maximum heart rate（HRmax），blood pressure，respiratory exchange ratio（RER），minute ventilation-to-carbon dioxide output（VE/VCO2）slope，resting heart rate（HRrest）〕 was collected. Methodological quality was evaluated by Cochrane risk-of-bias tool. Statistical analysis was carried out using Review Manage 5.3 and Stata 15.1. Results　A total of 12 RCTs were included，among which 3 were rated low risk of bias，8 were rated moderate risk，and 1 was rated high risk，involving 618 cases（305 with HIIT，and 313 with MICT）. Meta-analysis showed that HIIT elicited more notable effects in improving patients' VO2peak 〔MD=1.63，95%CI（0.64，2.62），P=0.001〕、VO2AT〔MD=2.62，95%CI（0.82，4.42），P=0.004〕、HRmax〔MD=5.41，95%CI（2.28，8.53），P=0.000 7〕 and systolic blood pressure 〔MD=3.16，95%CI（0.26，6.06），P=0.03〕 than MICT. But both of HIIT and MICT demonstrated no significant differences in improving RER〔MD=0.01，95%CI（-0.01，0.03），P=0.27〕，VE/VCO2 Slope〔MD=-0.26，95%CI（-1.87，1.34），P=0.75〕，HRrest〔MD=1.19，95%CI（-0.42，2.80），P=0.15〕 and diastolic blood pressure 〔MD=2.56，95%CI（-0.21，5.32），P=0.07〕. Subgroup analysis found that compared with MICT，HIIT had more statistically significant effects in improving VO2peak，RER，VO2AT and HRmax in patients with at least 12 weeks of intervention（P<0.05）. However，there were no statistically significant differences between HIIT and MICT in improving the above-mentioned indicators in those with intervention less than 12 weeks. Conclusion　For CHD patients，HIIT may be more effective in improving VO2peak，VO2AT，HRmax and blood pressure. And the intervention effects of HIIT on cardiorespiratory fitness will be more significant if the intervention lasts for 12 weeks or longer.

Recent Developments in Enhanced External Counterpulsation Therapy for Atherosclerotic Cardiovascular Disease　

CAI Xiaona，HE Yiping，ZHAI Xiaoya，PENG Fang

2021, 24(35): 4535-4539. DOI: 10.12114/j.issn.1007-9572.2021.01.107

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Atherosclerotic cardiovascular disease is a systemic disease characterized by chronic atherosclerosis，which may result in coronary artery disease，ischemic stroke，transient ischemic attack and peripheral artery disease，seriously affecting human health. Enhanced external counterpulsation is a safe，noninvasive，and effective assisted circulation technique. We reviewed a series of recent advances in enhanced external counterpulsation for atherosclerotic cardiovascular disease，including reducing the risk of atherosclerotic cardiovascular disease，clinical use for refractory angina pectoris，ischemic cerebrovascular disease，and atherosclerosis of the lower extremity，and discussed relevant mechanisms of action.
Atherosclerosis；Enhanced external counterpulsation；Coronary artery disease；Stroke；Ischemic attack，transient；Peripheral arterial disease；Atherosclerotic cardiovascular disease；Review

Research Progresses on the Role of Glucose-6-phosphate Dehydrogenase in Tumors　

SUN Jian, MAO Xingxing, LONG Yuanyuan, SHA Mengqi, LIU Xiping, CHEN Yan, HUANG Pei

2021, 24(35): 4540-4548. DOI: 10.12114/j.issn.1007-9572.2021.01.404

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Tumorigenesis is a dynamic and complex progress． The change in energy and metabolism is one of the basic characteristics of the tumor. Metabolic reprogramming meets the needs of energy and biosynthesis of rapidly proliferated tumor cells. The pentose phosphate pathway（PPP）with glucose-6-phosphate dehydrogenase（G6PD）as the rate-limiting enzyme is an important branch of glucose metabolism，and play a vital role in the synthesis of nucleotides，lipids，and other biomolecules and the maintenance of redox homeostasis. However，our understanding of the role of G6PD in tumors needs to be further strengthened. We reviewed the metabolic changes and signal pathways associated with the expression and activity of G6PD in tumors，and found that targeting G6PD could not only inhibit the rapid development of tumor but also could enhance the sensitivity of tumors to other chemotherapeutics and radiotherapy.

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