Table of Content

20 January 2022, Volume 25 Issue 03

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Review

Current Status and Challenges of Cervical Cancer Treatment：from Clinical Guidelines to Real-world Study

ZHANG Jun

2022, 25(03):  259-263.  DOI: 10.12114/j.issn.1007-9572.2021.02.105

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Cervical cancer is a type of malignancy that severely threatens women's health. For invasive cervical cancer, standardized preoperative staging and assessment are essential before the start of treatment. With regard toearly cervical cancer, surgery is the major treatment, with considerations for the latest updates in relevant guidelines, and the determination of extent of resection as well as the selection of proper surgical approach. For advanced or relapsed cervical cancer, radiotherapy and chemotherapy are the main treatments. However, there are many challenges and controversies regarding the treatment and clinical research of cervical cancer. We mainly discussed the present status and challenges of cervical cancer diagnosis and treatment based on clinical guidelines and practices, aiming at bettering the real-world practice with the support of clinical guidelines.

Article·Reproductive Health Study

Threshold Effect Analysis of Influence of Age on Live Birth Rate in Poor Ovarian Response Patients Treated by Assisted Reproductive Technology

CHEN Ying, LI Fei, DILIXIATI•Abulizi, WU Xiao, REYILA•Mumin, FENG Xingmei, ZHANG Yali

2022, 25(03):  264-269.  DOI: 10.12114/j.issn.1007-9572.2021.02.093

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Pregnancy outcome in patients with poor ovarian response (POR) has always been one of the difficult problems in reproductive medicine, but there is few threshold effect analysis of influence of age on live birth rate in POR patients treated by assisted reproductive technology (ART) .

To analyze the threshold effect of influence of age on live birth rate in POR patients treated by ART.

Among 19 185 women who received routine in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transplantation in Department of Gynaecology and Obstetrics, the First People's Hospital of Shangqiu and Fertility Support Center, the First Affiliated Hospital of Xinjiang Medical University from August 2014 to December 2018, 3 337 patients with POR were selected, and received controlled ovarian stimulation, embryo transplantation by IVF/ICSI and luteal support therapy. The incidence of live birth was analyzed. Univariate and multivariate Logistic analyses were used to analyze the influence of age on live birth in POR patients treated by ART. Moreover, smooth curve fitting and threshold effect analysis were conducted.

Of the 3 337 cases, 1 134 obtained a live birth, the other 2 203 did not, achieving a rate of live birth of 33.98% (1 134/3 337) . Multivariate Logistic analysis result showed that, age was independently associated with live birth in POR patients treated by ART〔OR=0.920, 95%CI (0.902, 0.939) , P<0.01〕. Smooth curve fitting showed that, age was negatively correlated with live birth rate in POR patients treated by ART, but the correlation was not simple linear. Threshold effect analysis results showed that, 32 years old was the threshold for decrease of live birth rate in POR patients treated by ART, namely age did not affect the live birth rate in those ≤32 years old〔OR=1.000, 95%CI (0.998, 1.012) , P=0.38〕, but the live birth rate decreased as age grew in those over 32 years old〔OR=0.800, 95%CI (0.799, 0.823) , P<0.01〕.

Age was an independent influencing factor of live birth in POR patients treated by ART. The live birth rate may decrease as age grows in these patients over 32 years old.

Influence of Two Endometrial Preparation Programs Independent of Endogenous Ovarian Cycle on the Pregnancy Outcome of Thin Endometrial Patients with Freeze-thaw Embryo Transfer

WEI Longlong, ZHANG Cuilian

2022, 25(03):  269-274.  DOI: 10.12114/j.issn.1007-9572.2021.02.075

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Thin endometrium is one of the crucial reasons leading to the reduction of pregnancy rate in patients. The whole embryo freezing is an important strategy in the process of assisting pregnancy in patients with thin endometrium. However, there are still controversies regarding the choice of subsequent freeze-thaw embryo transfer.

To explore the difference between two endometrial preparation programs〔artificial cycle and gonadotropin releasing hormone agonist (GnRH-a) down regulating artificial cycle〕 independent of endogenous ovarian cycle in patients with thin endometrial.

A retrospective analysis of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy treatment was performed in the Reproductive Center of Henan Provincial People's Hospital from December 2016 to July 2019. The whole embryo was frozen due to endometrial thickness less than 7 mm in the month of egg collection, then the clinical data of the freezing-thawing embryo transfer patients were collected by artificial cycle (artificial cycle group, n=409) and GnRH-a down-regulated artificial cycle (GnRH-a down-regulated artificial cycle group, n=103) . Pregnancy results were compared between the two groups of patients.

The average number of transplanted embryos in the artificial cycle group was (1.60±0.49) , while that in the GnRH-a daon-regulated artificial cycle group was (1.66±0.52) , and there was no statistically significant difference between the two groups (P>0.05) . In the artificial cycle group, there were no significant differences in clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and multiple pregnancy rate among those with 1, 2 and 3 embryos transferred, respectively (P>0.05) . In the GnRH-a down-regulated artificial cycle group, there were also no significant differences in clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and multiple fetus rate among those with 1, 2 and 3 embryos transferred, respectively (P>0.05) .

In patients with thin endometrium thickness (≤7 mm) , two endometrial preparation programs (artificial cycle and GnRH-a) independent of endogenous ovarian cycle had similar results in regulating artificial cycle pregnancy. It is not recommended to use GnRH-a combined with hormone replacement in the endometrial preparation program of conventional thin endometrial patients without special medical history such as endometriosis and repeated implant failure.

Microsatellite Instability and Its Clinical Significance in Endometrial Carcinoma

XIAO Jing, WU Ying

2022, 25(03):  275-279.  DOI: 10.12114/j.issn.1007-9572.2021.02.013

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The role of microsatellite instability in the progression of endometrial cancer, a common cancer in women, has obtained increasing attentions in recent years. However, there are few studies regarding the association of microsatellite instability with clinicopathologic features and prognosis in patients with endometrial cancer.

To investigate the microsatellite instability and its clinical significance in patients with endometrial carcinoma.

A total of 248 endometrial cancer patients who underwent surgery in Shiyan People's Hospital Affiliated to Hubei University of Medicine from January 2015 to December 2020 were selected. Their cancer tissue specimens were collected to detect the expression of MLH1, MSH2, MSH6 and PMS2 by immunohistochemistry. Relations of microsatellite instability with clinicopathologic features and prognosis were analyzed.

The rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 32.6% (78/239) , 22.2% (53/239) , 2.9% (7/239) and 65.7% (157/239) , respectively, in patients with endometrioid adenocarcinoma. For those with endometrial squamous cell carcinoma, the rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 5/5, 3/5, 5/5 and 4/5, respectively. And rates of lost expression of MLH1, MSH2, MSH6 and PMS2 were 4/4, 2/4, 3/4, and 2/4, respectively, in those with endometrial clear cell carcinoma. The rates of lost expression of MLH1, MSH2, MSH6 and PMS2 varied significantly by the pathological pattern of endometrial carcinoma (P<0.05) . The prevalence of high-level microsatellite instability (MSI-H) , low-level microsatellite instability (MSI-L) and microsatellite stability (MSS) was 19.7% (47/239) , 34.7% (83/239) and 45.6% (109/239) , respectively, in patients with endometrioid adenocarcinoma. The prevalence of MSI-H, MSI-L and MSS was 4/5, 1/5 and 0, respectively, in patients with endometrial squamous cell carcinoma. And that of MSI-H, MSI-L and MSS was 3/4, 1/4 and 0, respectively, in patients with endometrial clear cell carcinoma. The prevalence of MSI-H, MSI-L and MSS differed significantly by the pathological pattern of endometrial carcinoma (P<0.05) . The prevalence of MSI-H, MSI-L and MSS was associated with the depth of myometrial invasion (P<0.05) , but was not associated with age and degree of histologic differentiation of endometrial cancer (P>0.05) . There were no significant differences of Kaplan-Meier curves for overall survival and disease-free survival in endometrial cancer patients with MSI-H, MSI-L and MSS (P>0.05) . Cox proportional hazards regression analysis results showed that the expression of mismatch repair protein was not the independent influencing factor for disease-free survival (P>0.05) , but for overall survival (P<0.05) in patients with endometrial cancer.

Microsatellite instability is correlated with the progression and prognosis of endometrial cancer, so detecting it may have some referential value for clinical prevention and treatment of endometrial cancer.

Clinical Evaluation of High-risk HR-HPV E6/E7 mRNA Detection during Pregnancy

YANG Yongmei, WANG Fengying, LIAO Qinping, XIAO qun, KANG Ning, WU Jie

2022, 25(03):  280-284.  DOI: 10.12114/j.issn.1007-9572.2021.02.030

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It is necessary to differentiate high-risk human papillomavirus (HR-HPV) infection and cervical lesions during pregnancy using an effective measure, so as to guide personalized diagnosis and treatment and to reduce unnecessary invasive examinations during pregnancy.

To assess the value of HR-HPV E6/E7 mRNA detection in differentiating HR-HPV infection and cervical lesions during pregnancy by comparing efficacy between it and HR-HPV DNA testing.

Participants were healthy women with singleton pregnancy (20-45-years old) selected from Department of Obstetrics and Gynecology of Capital Medical University Xuanwu Hospital during January 2016 to January 2019. All had file creation and underwent regular prenatal examination, and those with abnormal liquid-based cytology and HR-HPV DNA testing results further underwent colposcopy with biopsy taken for pathological examination (serving as a gold standard) , and performed HR-HPV E6/E7 mRNA detection in cervical exfoliated cells collected as samples. Pathologically detected CIN Ⅱand Ⅲ were defined as high-grade cervical lesions.

Of the 1 058 participants, 118 had cytological abnormalities and/or HPV 16 and 18 infections, and 84 of them consented to perform colposcopy with biopsy pathological results successfully obtained. The prevalence of HR-HPV E6/E7 mRNA positivity was lower than that of HR-HPV DNA positivity in women with CINⅠ, normal cervical epithelium or cervicitis detected by pathological examination (P<0.05) . In contrast, the prevalence of HR-HPV E6/E7 mRNA positivity was similar to that of HR-HPV DNA positivity in those with CINⅡ and Ⅲ detected by pathological examination without statistical difference (P>0.05) . In predicting CINⅡ and Ⅲ, the HR-HPV DNA testing had a sensitivity of 89.7% (26/29) , a specificity of 21.8% (12/55) , a positive predictive value of 37.1% (26/69) , and a negative predictive value of 75.0% (12/29) , and the HR-HPV E6/E7 mRNA detection had a sensitivity of 65.5% (19/29) , a specificity of 54.5% (25/55) , a positive predictive value of 43.0% (19/44) , and a negative predictive value 75.0% (25/40) . McNemar's test revealed that HR-HPV E6/E7 mRNA detection had a lower sensitivity but a higher specificity than HR-HPV DNA testing in diagnosing CINⅡ and Ⅲ (P<0.05) .

HR-HPV E6/E7 mRNA detection may have an increased specificity in diagnosing CINⅡandⅢ than HR-HPV DNA testing, so it may be used in HR-HPV positive cases for differentiating HR-HPV infections and cervical lesions to avoid unnecessary invasive examinations during pregnancy.

Article·Enteropathy Study

Efficacy and Safety of Wuling Capsule Combined with Fupentixol and Melitracen Tablets in Active Ulcerative Colitis Patients Accompanied with Anxiety and Depression

MO Dayu, LIU Yingchao, WANG Feida, NI Siyi, SHEN Yan

2022, 25(03):  285-292.  DOI: 10.12114/j.issn.1007-9572.2021.02.067

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Psychotherapy is an important component of the treatment program for inflammatory bowel disease (IBD) , a common chronic incurable digestive system disease accompanied with psychosomatic disorder, which involves ulcerative colitis (UC) . Wuling capsule has proven to be effective in multiple gastrointestinal diseases with psychosomatic disorders, but there are rare studies about its effect on improving the condition, anxiety and depression of UC patients.

To investigate the efficacy and safety of Wuling capsule with Fupentixol and melitracen tablets in active UC patients with anxiety and depression.

A total of 120 active UC patients with anxiety and depression were selected from Gastroenterology Clinic or Inpatient Department of the Second Affiliated Hospital of Zhejiang Chinese Medical University and Zhejiang Provincial Tongde Hospital from January 2019 to December 2020, and equally, double-blindly randomized into control group, Deanxit group, Wuling capsule group and combination group, receiving Mesalazine sustained-release tablets (hereinafter referred to Mesalazine) , Mesalazine with Fupentixol and melitracen tablets, Mesalazine with Wuling capsules, Mesalazine with Fupentixol and melitracen tablets and Wuling capsules, respectively. All of the four groups were treated for 8 consecutive weeks as a course. Pre- and post-treatment main clinical symptom score, modified Mayo score, inflammatory response indicators, Zung Self-rating Anxiety Scale (SAS) score, Zung Self-rating Depression Scale (SDS) score, and Inflammatory Bowel Disease Questionnaire (IBDQ) score were compared across the four groups. Meanwhile, safety evaluation for the four treatments was conducted.

Finally, 113 cases (except Wuling capsule group containing 29 cases, other three groups containing 28 cases) who completed this study were included for analysis. Compared with other three groups, combination group showed lower post-treatment diarrhea score, mucus with blood and pus in stools score, abdominal pain score and total score of clinical symptoms, modified Mayo score, erythrocyte sedimentation rate, serum levels of C-reactive protein, tumor necrosis factor-α and interleukin-6, as well as SAS and SDS scores, and higher scores of bowel, systemic, emotional and social domains and total IBDQ score (P<0.05) . One control group case had abdominal distension and one Deanxit group case had hyposomnia during treatment, but were spontaneously relieved.

In active UC patients accompanied with anxiety and depression, Wuling capsule with Fupentixol and melitracen tablets could relieve the clinical symptoms, severity of condition, inflammatory response, anxiety and depression disorders, improve the quality of life, with relatively high safety. Therefore, Wuling capsule may be a choice for optimizing the comprehensive treatment plan of UC.

N-of-1 Trial of Jianpiqingrehuashi Granular Decoction with Mesalamine in the Treatment of Ulcerative Colitis in Remission with Spleen Deficiency-induced Damp-heat Syndrome

PENG Bin, WEN Yi, ZHANG Shijing, LIN Wenjia, LI Huibiao, CAI Jiazhong, LIU Shiying, LUO Jianfeng, LUO Yongxin, ZHENG Xiaomei, PAN Simin, CHEN Xinlin, HOU Jiangtao

2022, 25(03):  293-297.  DOI: 10.12114/j.issn.1007-9572.2021.02.106

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The patient with ulcerative colitis (UC) in remission has a long course of disease, and needs a long-term maintenance treatment. Traditional Chinese medicine (TCM) has proved to be partially effective in treating UC in remission, but the efficacy of Jianpiqingrehuashi granular decoction (JPQRHSGD) against UC in remission is not yet clear.

To evaluate the efficacy and safety of JPQRHSGD with mesalamine versus mesalamine in the treatment of UC in remission using an N-of-1 trial.

An N-of-1 trial was conducted between June 2020 and March 2021. Participant was an outpatient with UC in remission with spleen deficiency-induced dampness-heat syndrome who was selected from the First Affiliated Hospital, Guangzhou University of Chinese Medicine. The patient received a treatment program, namely four rounds of treatment without washout consisting of eight cycles〔each round includes two cycles, that was, one-month intervention treatment (use of JPQRHSGD with mesalamine) alternating with one-month control treatment (taking mesalamine only) 〕. Efficaciesof two types of treatment were evaluated by of the TCM Syndrome Score (TCMSS) , Bristol Stool Form Scale (BSFS) , visual analogue scale (VAS) for abdominal pain and diarrhea, and Short Health Scale (SHS) . Safety was also compared between the two treatments.

The total TCMSS in intervention period was significantly lower than that in control period (P<0.05) . In particular, the symptoms of diarrhea, abdominal distension and fatigue of the limbs were improved more obviouslyin intervention period (P<0.05) . The improvements of total BSFS score, and diarrhea VAS score in intervention period were better than those in control period (P<0.05) . However, abdominal pain VAS score in intervention period was worse than that in control period (P<0.05) . The improvement of SHS score in intervention period was better than those in control period (P<0.05) . No treatment-related adverse events were reported.

The JPQRHSGD with mesalamine improved the clinical symptoms of the UC patient in remission with spleen deficiency-induced dampness-heat syndrome, with relatively high safety.

Immunological Mechanism of Faecal Bacterial Transplantation in the Intervention of Ulcerative Colitis

WENG Jianfeng, XU Jia, LIU Peng, GE Wei, CHEN Jiaohua, PENG Yingying, HU Jiali, CUI Manman, ZHANG Leichang

2022, 25(03):  298-304.  DOI: 10.12114/j.issn.1007-9572.2021.02.069

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Ulcerative colitis is listed as one of the modern refractory diseases by the World Health Organization. At present, Western medicine still has many shortcomings in its treatment, and studies have shown that fecal bacterial transplantation (FMT) has a certain effect on it, but the mechanism is not clear.

FMT was used to treat mouse ulcerative colitis model to verify the efficacy and possible mechanism of FMT.

From December 2019 to April 2020, 60 mice were divided into normal control group (Control group) , ulcerative colitis model group (Model group) , ulcerative colitis model + fecal bacteria transplantation treatment group (Model+FMT group) and ulcerative colitis model + 5-aminosalicylic acid (5-ASA) treatment group (Model+5-ASA group) by random number table method, each of 15 mice. Control group did not make any intervention; Model group prepared mouse ulcerative colitis model; after successful modeling, the Model+FMT group was given 0.2 ml of fecal bacteria solution per enema; after successful modeling, the Model+5-ASA group was given 0.019 5 g/ml 5-ASA enema. The ultrastructural changes of intestinal tissue through transmission electron microscope, flow cytometric detection of blood helper T cell (Th) -17, Th-1, Th-2, Treg cell content changes, and enzyme-linked immunosorbent assay (ELISA) were observed to detect serum interferon γ (IFN-γ) , interleukin (IL) -2, IL-17, IL-4, IL-10, transforming growth factor β (TGF-β) level changes.

Intestinal tissue transmission electron microscopy ultrastructure showed that the Model group was successfully modeled; the microvilli in the Model+FMT group and Model+5-ASA group were denser, with normal morphology, more goblet cells, slight swelling of mitochondria, and insignificant rough endoplasmic reticulum lesions. The Th17 cell content of the Model+FMT group was higher than that of the Control group and lower than that of the Model group; the Th17 cell content of the Model+5-ASA group was lower than that of Control group, Model group and Model+FMT group. The Th1 cell content of Model+FMT group and Model+5-ASA group were lower than those of Control group and Model group, respectively; Th2 cell content of Model+FMT group was lower than that of Control group and higher than that of Model group, and Th2 cell content of Model+5-ASA group was lower than that of Control group and higher than that of Model group and Model +FMT group. Treg cell content in Model+FMT group and Model+5-ASA group were lower than that of Control group and higher than that of Model group (P<0.05) . IFN-γ cell content in Model+5-ASA group was lower than that of Model group. IL-2 cell content in Model+FMT group and Model+5-ASA group was lower than that of Model group; the IL-17 cell content of Model+FMT group and Model+5-ASA group were lower than those of Control group and Model group, respectively. The IL-17 cell content of Model+5-ASA group was lower than that of Model+FMT group; the IL-4 cell content of Model+FMT group was lower than that of Control group and higher than that of Model group. The IL-4 cell content in the Model+5-ASA group was higher than that in the Model group; the IL-10 cell content in the Model+FMT group was higher than that in the Control group and the Model group, and the IL-10 cell content in the Model+5-ASA group was higher than that in the Model group; the content of TGF-β cells in the Model+FMT group and Model+5-ASA group were lower than those in the Control group and higher than those in the Model group (P<0.05) .

FMT can improve the symptoms of ulcerative colitis in mice. It is speculated that it may be achieved by adjusting the balance of Th1/Th2 cells and the ratio of Th17/Treg cells to achieve the purpose of treatment.

Article

Predictive Value of Combined Use of Ultrasonographic Indicators for Central Lymph Node Metastasis in Papillary Thyroid Carcinoma

ZHANG Xiaomei, KANG Yanfei, SANG Tian, CHENG Jing, LI Qiaoli, CAO Yuwen, MA Jinmei, SHI Linan, LI Wenxiao, LI Jun

2022, 25(03):  305-311.  DOI: 10.12114/j.issn.1007-9572.2021.02.109

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The treatment scheme for papillary thyroid carcinoma (PTC) patients is related to whether lymph node metastasis is prevalent or not. The routine ultrasound indicator used alone has proven to have a low sensitivity to predict the presence of lymph node metastasis in PTC.

To explore the value of combined use of ultrasonographic indicators in predicting central lymph node metastasis in PTC.

Clinical data of PTC patients (n=446) with thyroid surgery and central neck dissection were collected retrospectively from the First Affiliated Hospital of Shihezi University School of Medicine from March 2013 to May 2020, involving sex, age, and ultrasonographic features 〔diameter of nodule, number of nodules, location of single and multiple nodules, internal composition, internal echo, boundary, margin, micro calcification, anteroposterior and transverse diameter (A/T) ratio, posterior echo attenuation, capsular invasion〕. Postoperative pathological results confirmed that 159 cases (35.65%) with central lymph node metastasis and other 287 (64.35%) without. Unconditional stepwise binary Logistic regression was used to explore the factors associated with central lymph node metastasis. Receiver operating characteristic (ROC) analysis was performed to estimate the predictive value of each indicator for central lymph node metastasis.

Patients with and without central lymph node metastasis had significant differences in sex ratio, distribution of age, thyroid nodule diameter, margin conditions, and A/T ratio, as well as prevalence of micro calcification and capsular invasion (P<0.05) . Binary Logistic regression analysis showed that male 〔OR=1.727, 95%CI (1.059, 2.816) 〕, <45 years old 〔OR=2.690, 95%CI (1.728, 4.187) 〕, diameter of the thyroid nodule >10 mm 〔OR=2.385, 95%CI (1.544, 3.684) 〕, and capsular invasion 〔OR=1.773, 95%CI (1.153, 2.724) 〕 were independently associated with increased risk of central lymph node metastasis (P<0.05) . And the Logistic regression algorithm was: Logit (P) =-1.627+0.546×sex +0.989×age+0.869× (thyroid nodule diameter) +0.572× (capsular invasion) . In predicting central lymph node metastasis, the AUC of combination of four indicators in the algorithm was 0.695〔95%CI (0.650, 0.738) 〕, with 67.92% sensitivity, and 61.67% specificity, and 0.32 optimal cut-off value. The AUC of the combination of four indicators was larger than that of sex, age, thyroid nodule diameter, or capsular invasion alone (Z=4.137, 3.682, 3.070, 3.679, P<0.05) .

Being male, age <45 years old, thyroid nodule diameter>10 mm, and capsular invasion were independent risk factors for central lymph node metastasis in PTC, and the value of combined use of them had a higher predictive value for central lymph node metastasis.

Clinical Characteristics and Treatment of Acute Intermittent Porphyria in Chinese Individuals

LI Qingyang, LI Ru, REN Yi, YANG Jing

2022, 25(03):  312-319.  DOI: 10.12114/j.issn.1007-9572.2021.02.097

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China's research on acute intermittent porphyria (AIP) is relatively limited. Due to most medical workers' insufficient understanding, AIP is easily misdiagnosed, and mistreated, leading to delayed appropriate treatment.

To analyze the clinical data of Chinese individuals with AIP with hydroxymethylbilane synthase (HMBS) gene mutation who were reported in published studies, improving medical workers' understanding of AIP.

Databases of PubMed, CNKI, Wanfang Data and CQVIP were searched for published articles about Chinese AIP cases from inception to June 30, 2021. Literature screening based on the inclusion and exclusion criteria of this study and data extraction were performed by two researchers, separately. Information regarding general data, clinical manifestations, results of laboratory tests, treatments, and gene mutations of AIP patients was analyzed.

A total of 32 articles were included, containing 65 AIP patients (56 females and 9 males) with the age mostly between 20-39 years old 〔83.1% (54/65) 〕. Most of AIP patients' admission were for abdominal pain〔63 cases (96.9%) 〕, often accompanied by nausea, vomiting, and constipation. 56.9% (37/65) of AIP patients suffered from central neuropathy, disturbance of consciousness (25 cases) , epileptiform seizures (22 cases) and respiratory muscle paralysis (6 cases) . 13.8% (9/65) of patients experienced peripheral neuropathy including fatigue (6 cases) and limb numbness (4 cases) . 30.8% (20/65) of patients had autonomic neuropathy such as hypertension and tachycardia. 9.2% (6/65) of patients experienced spirit symptoms, such as depression, anxiety and hallucination. Thirty-five patients had generated multiple acute attacks of AIP. In some patients, the onset of AIP may have been related to menstruation (9 cases) , pregnancy and childbirth (4 cases) , fatigue (3 cases) , alcohol consumption (2 cases) , and dieting (1 case) . 25 patients developed hyponatremia. There were 11 cases of anemia and 11 cases of abnormal liver function. Six patients were in abnormal renal function. 1 case was caught in disorder of cortisol rhythm. Twenty-seven patients received carbohydrate loading therapy, and 25 of them were improved. Two patients were treated with carbohydrate loading combined with heme therapy, and 1 eventually improved. A total of 26 HMBS gene mutations were included in the study, where in the p.R173W, p.R173Q, p.T269R, p.W283X and p.A330P mutations were detected in multiple patients. And different patients with the same gene mutation may also show different clinical phenotypes.

AIP is a disease with complex and variable clinical manifestations and heterogeneous severity of disease. The acute attack of AIP should be considered if patients, especially young female patients, are clinically found to be with unexplained abdominal pain, epileptiform seizures, disturbance of consciousness, hypertension, tachycardia and hyponatremiain. Currently, carbohydrate loading therapy is mainly applied to control the attack of AIP in China. In terms of factors affecting the clinical phenotype of AIP, further exploration still needs to be carried out.

Modified Electroconvulsive Therapy in Patients with Schizophrenia：Curative Effect and Responses of Neurotransmitters in Brain and Different Brain Regions

FAN Guihong, HE Jun, PANG Gaofeng, LI Chen, JIANG Lushan, FANG Huimin, WANG Zhou

2022, 25(03):  325-330.  DOI: 10.12114/j.issn.1007-9572.2021.02.027

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Neurotransmitters in multiple brain regions in schizophrenia patients have been extensively studied using encephal of luctuograph in terms of functional features, and also been explored using modified electroconvulsive therapy (MECT) regarding their responses to MECT, but responses of neurotransmitters in a specific region to MECT have been rarely examined.

To examine pre- and post-treatment changes of neurotransmitters in brain and different brain regions in patients with schizophrenia with MECT, and to investigate the possible neurobiological mechanism of MECT.

Fifty-one schizophrenia patients were recruited from Changzhou Dean Hospital from January 2019 to December 2020. All of them had signed the written informed consent form of receiving MECT prior to the participation in the study, and received MECT with unchanged antipsychotic medications during the study period. Scores of new 5-factor model of the PANSS (20 items) , neurotransmitters in brain and different brain regions 24 hours before the first MECT and 24 hours after the end of MECT were compared among all patients.

Compared with those 24 hours before the first MECT, scores of positive factor, negative factor, hostile excitement, anxiety and depression, cognitive and total PANSS score, as well as gamma-aminobutyric acid (GABA) in brain and left posterior brain region, and glutamate (Glu) in left posterior brain region significantly decreased, but dopamine (DA) in brain and right frontal brain region significantly increased 24 hours after the end of MECT (P<0.05) .

MECT has certain anti psychotic effect in patients with schizophrenia, its neurobiological mechanism may be related with the influence on GABA and DA in brain, GABA and Glu in left posterior brain region, as well as DA in right frontal brain region.

Effect of Acupuncture as an Adjuvant Therapy for Intravenous Thrombolytic Treatment on Peripheral Inflammatory Factors and Neurologic Function in Patients with Acute Ischemic Stroke

CHEN An, CAO Xiao, ZHANG Huilin, LIAN Jianfeng

2022, 25(03):  331-335.  DOI: 10.12114/j.issn.1007-9572.2021.02.098

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Acupuncture has proved effective in reducing inflammatory cytokine levels. However, it is still unclear about its improvement on the neurologic function and activities of daily living as well as over all clinical efficacy in patients with acute ischemic stroke.

To explore the effects of acupuncture as an adjuvant therapy for intravenous thrombolytic treatment on peripheral inflammatory cytokines and neurologic function in acute ischemic stroke patients.

Acute ischemic stroke patients who were treated in Hai'an Traditional Chinese Medicine Hospital from March 2018 to March 2021 were selected, and divided into a control group (intravenous thrombolytic treatment with urokinase and ulinastatin) and an acupuncture group (intravenous thrombolytic treatment with urokinase and ulinastatin and acupuncture) by the order of admission. The treatment for both groups lasted for four consecutive weeks. The levels of peripheral CRP, TNF-α, IL-1β, IL-6, and IL-8 were compared at baseline, two and four weeks of treatment between the groups. Activities of Daily Living Scale (ADL) and NIH Stroke Scale (NIHSS) were used to assess pre- and post-treatment activities of daily living and neurologic function, respectively. Clinical efficacy was evaluated.

A total of 324 patients were included, equally divided into control and acupuncture groups. Both groups had no significant differences in sex ratio, mean age, time interval between symptom onset, the first medical visit, incidence of hypertension, diabetes mellitus and hyperlipidemia (P>0.05) . The levels of peripheral CRP, TNF-α, IL-1β, IL-6 and IL-8 demonstrated no significant intergroup differences at baseline (P>0.05) , but they decreased more obviously at two and four weeks of treatment in the acupuncture group (P<0.05) . The ADL and NIHSS scores were similar in both groups at baseline (P>0.05) , but ADL score increased and NIHSS score decreased significantly in acupuncture group at four weeks of treatment (P<0.05) . The overall clinical efficacy of the acupuncture group 〔91.36% (148/162) 〕 was significant higher than that of the control group 〔79.01% (128/162) 〕 (χ²=9.783, P=0.002) .

As an adjuvant therapy for intravenous thrombolytic treatment, acupuncture could enhance the treatment effects on reducing peripheral inflammatory cytokines, and improving neurologic function recovery as well as activities of daily living, indicating that it may have a good clinical efficacy.

A Longitudinal Study of Physical Activity Patterns and Change Trajectory during Pregnancy

LI Jing, MA Qili, LIANG Yaling, CHEN Weiya, CAI Wenzhi

2022, 25(03):  336-340.  DOI: 10.12114/j.issn.1007-9572.2021.02.039

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Physical activity during pregnancy has recently been considered as an essential part of reproductive health, and pregnant women are encouraged to adopt an active lifestyle instead of traditionally restricting their activities. Studies from abroad have shown that pregnancy physical activity gradually decreases with the progress of pregnancy. Domestic studies on the patterns and changes of pregnancy physical activity are still insufficient.

To explore the pattern of physical activity in the first, second and third trimesters of pregnancy, and its change trajectory, providing a reference for the formulation of targeted interventions.

Convenience sampling was used to select low-risk pregnant women from Obstetric Clinic, Jiangmen Wuyi Hospital of Traditional Chinese Medicine from May 2017 to May 2018. All had a health file created at 6-13⁺⁶ weeks' gestation at the first antenatal examination. A self-developed questionnaire was used to collect general demographic data. The Chinese version of the Pregnancy Physical Activity Questionnaire was used to investigate physical activity in the first, second and third trimesters of pregnancy. Patterns and changes of physical activity were analyzed by the stage of pregnancy.

Among the 312 participants, except for 48 excluded cases and 15 dropouts, the other 249 who completed the survey were finally included. The average weekly metabolic equivalent of task (MET) values for the respondents in the first, second and third trimesters of pregnancy were 201.7, 188.6, and 177.2 MET-hours, respectively. Sedentary activity, light-intensive activity, moderate-intensive activity, and vigorous-intensive activity accounted for 17%, 60%, 21.2%-24.4%, and less than 1% of the energy expenditure attributable to total activity, respectively. In terms of activity type, household/caregiving, occupational, transportation and sports/exercise accounted for 48%, 40%, 9%, and less than 3% of the energy expenditure attributable to total activity, respectively. The differences in MET values of sedentary activity, light-intensive activity, moderate-intensive activity, and vigorous-intensive activity, household activity, sports/exercise, and total activity across three stages of pregnancy were statistically significant (P<0.05) . Among which, the MET values of sedentary activity, moderate-intensive activity, household activity, and total activity in the third trimester were much lower than those in the first trimester, with a statistically significant difference (P<0.05) .

To improve maternal and infant health, healthcare workers should encourage pregnant women to reduce their sedentary time, and give them individualized physical activity recommendations and guidance. The second trimester may be the best time to promote physical activity.

Analysis of Characteristics and Influencing Factors of Hearing Impairment in Patients with Polycystic Ovary Syndrome

XIE Zhijia, ZHANG Lei, CHEN Xin, CHANG Tao

2022, 25(03):  341-345.  DOI: 10.12114/j.issn.1007-9572.2021.02.047

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Hearing impairment in patients with polycystic ovary syndrome (PCOS) has been confirmed, However, the influencing factors of hearing impairment in PCOS patients have not been fully explained.

To explore the characteristics of hearing impairment in patients with PCOS and analyze its influencing factors.

203 PCOS patients (406 ears) diagnosed in the Department of Gynecology, Suzhou Ninth People's Hospital from March 2018 to February 2021 were selected as the PCOS group. At the same time, 30 healthy women (60 ears) were selected as the control group. The audiology examination results of the two groups were compared. Logistic regression analysis was used to explore the influencing factors of hearing impairment in PCOS patients.

Compared with the control group, there was no statistically significant difference in the hearing threshold of PCOS patients with low and medium frequencies (0.25-2.00 kHz) (P>0.05) . The hearing thresholds of high frequency (4.00 kHz, 8.00 kHz) and extended high frequency (10.00-20.00 kHz) in the PCOS group were higher than those in the control group (P<0.05) . Auditory impairment accounted for 25.62% (52/203) in the auditory valve test of 203 PCOS patients. The longer the course of PCOS, the higher the incidence and severity of hearing impairment (χ² _trend=42.475, P<0.001) . The incidence of insulin resistance in PCOS patients with hearing impairment was significantly lower than that in patients without hearing impairment (χ²=12.765, P<0.001) ; the C-reactive protein (CRP) , homocysteine (Hcy) , fasting blood glucose (FBG) , and triacylglycerol (TG) indexes of PCOS patients with hearing impairment were higher than those of non-hearing impairment patients (t=2.490, 2.819, 2.419, 4.436, P<0.05) . Logistic regression analysis showed that the course of disease and insulin resistance, CRP, Hcy, FBG, TG indicators are all influencing factors of hearing impairment in PCOS patients (P<0.001) .

The course of the disease and insulin resistance, elevated CRP, high blood sugar, high expression of Hcy, and dyslipidemia in PCOS patients are the influencing factors of hearing impairment in PCOS patients. Clinical measures should be taken according to various incentives to prevent or delay the occurrence and development of hearing loss in PCOS patients.

Evidence-based Medicine

Prevalence of Osteoporosis in Chinese Elderly People: a Meta-analysis

ZHU Jieyun, GAO Min, SONG Qiuyun, JI Pan, LI Hongyuan, ZHONG Zhimei, SHEN Yin

2022, 25(03):  346-353.  DOI: 10.12114/j.issn.1007-9572.2021.02.083

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The prevalence of osteoporosis is high and increases gradually with age. Osteoporosis and its related fractures have exerted a heavy economic burden on patients' families, and the society, so it is urgent to prevent and treat osteoporosis. Understanding osteoporosis prevalence is a prerequisite for containing osteoporosis in China.

To understand osteoporosis prevalence in Chinese elderly people through a meta-analysis.

PubMed, CNKI, Wanfang Data Knowledge Service Platform and VIP databases were searched to collect cross-sectional studies about osteoporosis prevalence in Chinese elderly people published from January 1, 2000 to March 20, 2021. Data from eligible studies were extracted, and methodological quality of these studies was assessed. Meta-analysis was performed by using Stata 12.0.

A total of 48 studies involving 68 932 cases were included. Meta-analysis showed that the overall prevalence of osteoporosis in Chinese adults aged ≥60 years was 37.7%〔95%CI (33.8%, 41.7%) 〕. Subgroup analyses indicated that osteoporosis prevalence in Chinese adults aged ≥60 years was 35.9%〔95%CI (31.1%, 40.8%) 〕 from 2010 to 2020, while that was 39.6%〔95%CI (33.4%, 45.9%) 〕 between 2000 and 2009. Osteoporosis prevalence in this age group in southern and northern China was 39.7%〔95%CI (34.0%, 45.5%) 〕, and 35.7%〔95%CI (30.1%, 41.2%) 〕, respectively. Osteoporosis prevalence in men, and women of this age group was 27.3%〔95%CI (23.9%, 30.7%) 〕 and 48.4%〔95%CI (42.7%, 54.1%) 〕, respectively. The prevalence of osteoporosis in those aged 60-69, 70-79, and over 80 was 32.2%〔95%CI (28.6%, 35.7%) 〕, 41.9%〔95%CI (36.9%, 46.9%) 〕 and 51.8%〔95%CI (43.9%, 59.7%) 〕, respectively.

Current evidence shows that the prevalence of osteoporosis in Chinese older adults is 37.7%, and it increased with age.

Urease Breath Test and Stool Antigen Test Diagnose Helicobacter Pylori Infection in Patients with Bleeding Peptic Ulcer：a Meta-analysis

LIAO Guibin, GONG Jiaqian, ZHAO Lina, HOU Jiangtao, ZHENG Hongming, LI Yiting, WU Yuan, CHEN Bin

2022, 25(03):  354-362.  DOI: 10.12114/j.issn.1007-9572.2021.02.086

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In patients with peptic ulcer bleeding (PUB) , intragastric blood and unavoidable medicine, including acid suppressive agent are suspected as limitary factors to diagnose Helicobacter pylori (H.pylori) infection correctly. The research conclusions about the accuracy of urease breath test (UBT) and stool antigen test (SAT) in patients with PUB are inconsistent.

To clarify the accuracy of UBT and SAT for H.pylori infection in PUB patients.

PubMed, EMBase, the Cochrane Library, Web of Science, CNKI, Wanfang Data Knowledge Service Platform, China Biomedical Literature Database (CBM) were retrieved by computer for relevant articles related to the diagnosis of H.pylori infection by UBT and/or SAT published from the establishment of the database to March 31, 2021. The QUADAS-2 tool was used to evaluate the quality of the extracted literature. The bivariate mixed-effects regression model and network meta-analysis model (NMA) were used to synthesize diagnostic test data. Meta-regression and subgroup analysis were performed to explore the sources of heterogeneity.

A total of 18 articles were included, with a total of 25 studies and 1 105 patients. Meta-analysis results showed that the combined sensitivity of UBT and SAT for diagnosing H.pylori infection in PUB patients were 0.90〔95%CI (0.79, 0.95) 〕 and 0.89〔95%CI (0.81, 0.94) 〕, the combined specificity were 0.91〔95%CI (0.86, 0.95) 〕 and 0.75〔95%CI (0.59, 0.87) 〕, the combined diagnostic odds ratio were 88.89〔95%CI (31.01, 254.82) 〕 and 24.35〔95%CI (13.76, 43.09) 〕, the combined positive likelihood ratio were 10.07〔95%CI (6.07, 16.71) 〕 and 3.60〔95%CI (2.11, 6.12) 〕, the combined negative likelihood ratio were 0.11〔95%CI (0.05, 0.24) 〕 and 0.15〔95%CI (0.09, 0.24) 〕, the area under the SROC curve were 0.93〔95%CI (0.90, 0.95) 〕 and 0.91〔95%CI (0.88, 0.93) 〕. Meta regression showed that the sampling time had an impact on the sensitivity heterogeneity of UBT and SAT, and the sampling time and the H.pylori infection criterion had an impact on the combined specificity heterogeneity of UBT. The Deek funnel chart indicated that there was no potential publication bias among the included researches (P_UBT=0.53, P_SAT=0.64) .

In patients with PUB, UBT had a promising performance for the diagnosis of H.pylori infection. Because of the high number of false-positive results, SAT was not recommended for use in patients with PUB alone. At the same time, in order to avoid the impact of PPI on the detection results, it was recommended to perform the diagnostic tests as soon as possible under the condition of stable hemodynamics.

Research of Typical Cases

Non-clostridial Gas-forming Infection in Diabetes：Clinical Analysis of Two Cases

WU Yuan, LYU Hongjun, YAO Xiaoli, LIU Juan

2022, 25(03):  363-367.  DOI: 10.12114/j.issn.1007-9572.2021.02.014

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Non-clostridial organism can produce pneumoderma by breaking down sugar and other substrates in necrotic tissues, and non-clostridial gas-forming infection is usually seen in diabetic patients with poor glycemic control. The differential diagnosis between clostridial and non-clostridial gas-forming infection relies on etiological examination results, but the key to successful treatment is timely empiric broad-spectrum antibiotic treatment and emergency surgical debridement in the absence of a definitive etiologic diagnosis. This paper reported two cases of non-clostridial gas-forming infection in diabetes, and reviewed relevant literature, aiming to improve clinicians' understanding of this disease.

Lenalidomideas a Second-line Therapy Achieves Long-term Remission in Elderly Patients with Relapsed/Refractory Multicentric Castleman's Disease：a Report of Two Cases and Literature Review

TANG Yangming, SHI Renzhou, LAN Mei, LI Xuejun, WEN Zonghua, LU Xiaochen

2022, 25(03):  368-372.  DOI: 10.12114/j.issn.1007-9572.2021.02.061

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No standard therapy is recommended for elderly multicentric Castleman's disease (MCD) patients who failed to the first-line treatment or relapsed. Lenalidomide has been reported to be effective for relapsed/refractory MCD in foreign countries, but its effect on this disease has been rarely reported in China. We reported two elderly patients with relapsed/refractory MCD presented with long-term remission after second-line treatment with lenalidomide, and reviewed relevant literature, then suggested that lenalidomide showed encouraging efficacy in patients with MCD, which may be an attractive alternative for relapsed/refractory MCD. Elderly patients with MCD may be more likely to benefit from lenalidomide-based treatment because of the poor general condition and various complications.

Cutting Edge

Developments in the Role of Iron Imbalance in the Pathogenesis of Alzheimer's Disease

GUO Shuang, CHEN Fengyan, YIN Xiang, WANG Lu, GUO Xuefeng, YU Qiming, ZOU Zhenyou, SHU Wei

2022, 25(03):  373-379.  DOI: 10.12114/j.issn.1007-9572.2021.02.031

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Iron load is closely associated with the initiation and progression of Alzheimer's disease (AD) . Although age-dependent deposition of β-amyloid (A β) in senile plaques (SPs) , and neurofibrillary tangles (NFTs) formed by accumulation of hyperphosphorylated tau proteins are two major pathological features of AD, there are still many different views on the inducing factors of SPs and NFTs. We reviewed the new developments in the relationship between imbalance of brain iron homeostasis and the pathogenesis of AD, with a summary presented as follows: (1) Age-related iron deposits in different brain regions may damage normal cognitive function and behavior. (2) Iron imbalance and oxidative stress may together or independently promote Aβ overproduction by activating β- or γ-secretases and inhibiting α-secretase, and also cause tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β, cyclin-dependent protein kinase-5, and inhibiting protein phosphatase 2A. Iron imbalance-induced changes will in turn aggravate brain iron deposition and distribution. The vicious circle between iron imbalance and Aβ/tau anomalies may eventually lead to AD. (3) Iron overload may also directly or indirectly injure organelles, causing endoplasmic reticulum stress, mitochondrial and autophagy dysfunction, and damaging synaptic function via inducing or aggravating the aggregation or accumulation of A βand tau. At the same time, hydroxyl radicals produced via the Fenton reaction associated with abnormal iron metabolism, may trigger oxidative stress, destroy the structure and function of cell lipids, protein and DNA, eventually leading to cell death. (4) Given the limitations and side effects of long-term application of traditional iron chelators, alpha-lipoic acid and lactoferrin as self-synthesized naturally small molecules, are expected to be applied to clinical practice, for they have shown very intriguing biological activities in blocking Aβ-aggregation, tau hyperphosphorylation and neuronal damage. We believe that iron-targeted therapies are a promising direction for the treatment of AD.

Latest Research on the Neuroprotective Mechanism of Short-chain Fatty Acids in Stroke and Its Relation with Post-stroke Cognitive Impairment

LIU Huanhuan, LI Ruiqing, SU Kaiqi, YUAN Jie, LI Qi, FENG Xiaodong

2022, 25(03):  380-386.  DOI: 10.12114/j.issn.1007-9572.2021.00.569

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Post-stroke cognitive impairment is one of the common complications of stroke, seriously affecting patients' ability to perform activities of daily living. Recent studies about microbiota-gut-brain axis have found that gut microbiota and their metabolites play an important role in the development of neurological diseases. Short-chain fatty acids, the main metabolites of gut microbiota, are key transmitters of gut-brain communication, which have a neuroprotective effect in stroke, yet the mechanism of action is not fully clear. This paper presents a review of the neuroprotective mechanism of short-chain fatty acids in stroke, and its relation with post-stroke cognitive impairment, providing evidence for studying the pathogenesis and treatment of stroke.