Chinese Medical Journal

Impact of hepatitis C virus genotype 3 on liver disease progression in a Chinese national cohort Background: Hepatitis C virus (HCV) genotype 3, particularly subtype 3b, is increasing in prevalence and distribution in China. This study evaluated the prevalence, regional distribution, clinical characteristics, host factors, treatment outcomes, and disease progression of patients with HCV genotype 3 in China. Methods: A 5-year follow-up was preceded by a cross-sectional study. Treatment choices were at the discretion of treating physicians. Estimated infection time to overall-disease-progression (defined by ≥1 of: newly diagnosed cirrhosis; cirrhosis at baseline, Child-Turcotte-Pugh score increased 2 points or more; progression from compensated cirrhosis to decompensated cirrhosis; hepatocellular carcinoma; liver transplantation; or death) was calculated using the Kaplan-Meier method. Cox regression analyses were conducted to evaluate the risk factors for disease progression. Results: The cross-sectional study enrolled 997 patients, including 91 with HCV genotype 3 infection. Among them, subtype 3b (57.1%) was more dominant than subtype 3a (38.5%). Five hundred and twelve patients were included into the follow-up phase. Among patients analyzed for estimated infection time to overall-disease-progression, 52/304 (17.1%) patients with HCV genotype 1 and 4/41 (9.8%) with HCV genotype 3 (4/26 with genotype 3b, 0/13 with genotype 3a, and 0/2 with undefined subtype of genotype 3) experienced overall-disease-progression. Patients with HCV genotype 3 were younger than those with genotype 1 (mean age: 39.5 ± 8.7 vs. 46.9 ± 13.6 years) and demonstrated more rapid disease progression (mean estimated infection time to overall-disease-progression 27.1 vs. 35.6 years). Conclusions: HCV genotype 3, specifically subtype 3b, is associated with more rapid progression of liver disease. Further analysis to compare HCV subtype 3a and 3b is needed in high prevalence regions. Trial registration: NCT01293279, https://clinicaltrials.gov/ct2/show/NCT01293279; NCT01594554, https://clinicaltrials.gov/ct2/show/NCT01594554.

An epidemiology study of fecal incontinence in adult Chinese women living in urban areas Background: Fecal incontinence (FI) has been shown to be a common symptom in Western countries; however, there is few researches focusing on its epidemic condition in Chinese women. We conducted this national population-based epidemiology study to estimate the prevalence and risk factors of FI among adult Chinese women living in urban regions. Methods: This is a subgroup analysis of a national population-based epidemiology study of FI. Total 28,196 adult women from urban regions of six provinces and municipalities participated in this research from 2014 to 2015. They finished the questionnaire under the direction of trained interviewers. FI was defined as accidental leakage of flatus and/or liquid or solid stool at least once in the past. The FI prevalence trend and risk factors were identified by the Cochran-Armitage test, Chi-square test, and multivariable logistic regression. Results: The prevalence of FI in adult females in urban China was 0.43% (95% confidence interval: 0.35%–0.51%). Among women with FI, 42.96%, 82.96%, and 42.22% reported having leakage of solid, liquid stool, and gas, respectively. The overall FI prevalence and the incidence rate of solid stool/liquid stool/gas leakage increased with age. The mean Wexner score was 4.0% and 12.0% FI patients reported Wexner score ≥9. Body mass index ≥24 kg/m2, pelvic organ prolapses, chronic constipation, chronic cough, alcohol consumption, physical diseases including chronic bronchitis and cancer, gynecological diseases like gynecological inflammation are risk factors for FI. Vaginal delivery was the risk factor for FI in females with labor history. Conclusions: FI was not a common symptom in adult Chinese women living in urban areas and there were some potential modifiable risk factors. Trial Registration: Chinses Clinical Trial Registry: ChiCTR-OCS-14004675; http://www.chictr.org.cn/showproj.aspx?proj=4898

Optimized cutoff maternal age for adverse obstetrical outcomes: a multicenter retrospective cohort study in Urban China during 2011 to 2012 Background: China's two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China. Methods: This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012. Logistic regression was used to assess the adjusted odds ratios (aOR) of adverse outcomes in different age groups in comparison to women aged 20 to 24 years. The adjustments included the location of the hospital, educational level, and residence status. Clinically cutoff age was defined as the age above which the aOR continuously become both statistically (P < 0.05) and clinically (aOR > 2) significant. Results: Overall, 108,059 women were recruited. In primiparae, clinically cutoff maternal ages for gestational diabetes (aOR: 2.136, 95% confidence interval [CI]: 1.856–2.458, P < 0.001), placenta previa (aOR: 2.400, 95% CI: 1.863–3.090, P < 0.001), cesarean section (aOR: 2.511, 95% CI: 2.341–2.694, P < 0.001), hypertensive disorder (aOR: 2.122, 95% CI: 1.753–2.569, P < 0.001), post-partum hemorrhage (aOR: 2.129, 95% CI: 1.334–3.397, P < 0.001), and low birth weight (aOR: 2.174, 95% CI: 1.615–2.927, P < 0.001) were 27, 31, 33, 37, 41, and 41 years, respectively. In multiparae, clinically cutoff ages for gestational diabetes (aOR: 2.977, 95%CI: 1.808–4.904, P < 0.001), hypertensive disorder (aOR: 2.555, 95% CI: 1.836–3.554, P < 0.001), cesarean section (aOR: 2.224, 95% CI: 1.952–2.534, P < 0.001), post-partum hemorrhage (aOR: 2.140, 95% CI: 1.472–3.110, P < 0.001), placenta previa (aOR: 2.272, 95% CI: 1.375–3.756, P < 0.001), macrosomia (aOR: 2.215, 95% CI: 1.552–3.161, P < 0.001), and neonatal asphyxia (aOR: 2.132, 95% CI: 1.461–3.110, P < 0.001) were 29, 31, 33, 35, 35, 41, and 41 years, respectively. Conclusions: Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China. The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.

Homocysteine and IgA nephropathy: observational and Mendelian randomization analyses Background: High levels of plasma homocysteine occur almost uniformly in patients with end-stage renal disease (ESRD). IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis and a common cause of ESRD in young adults. Here, we aimed to detect whether homocysteine was elevated and associated with clinical-pathologic manifestations of IgAN patients and tested its causal effects using a two-sample Mendelian randomization (MR) approach. Methods: For observational analysis, 108 IgAN patients, 30 lupus nephritis (LN) patients, 50 minimal change disease (MCD) patients, and 206 healthy controls were recruited from April 2014 to April 2015. Their plasma homocysteine was measured and clinical-pathologic manifestations were collected from medical records. For MR analysis, we further included 1686 IgAN patients. The missense variant methylenetetrahydrofolate reductase C677T (rs1801133) was selected as an instrument, which was genotyped by TaqMan allele discrimination assays. Results: Majority of IgAN patients (93.52%, 101/108) showed elevated levels of plasma homocysteine (>10 μmol/L). Plasma homocysteine in IgAN patients was significantly higher than that in MCD patients (median: 18.32 vs. 11.15 μmol/L, Z = −5.29, P < 0.01) and in healthy controls (median: 18.32 vs. 10.00 μmol/L, Z = −8.76, P < 0.01), but comparable with those in LN patients (median: 18.32 L vs. 14.50 μmol/L, Z = −1.32, P = 0.19). Significant differences were observed in sub-groups of IgAN patients according to quartiles of plasma homocysteine for male ratio (22.22% vs. 51.85% vs. 70.37% vs. 70.37%, χ2 = 14.29, P < 0.01), serum creatinine (median: 77.00 vs. 100.00 vs. 129.00 vs. 150.00 μmol/L, χ2 = 34.06, P < 0.01), estimated glomerular filtration rate (median: 100.52 vs. 74.23 vs. 52.68 vs. 42.67 mL·min−1·1.73 m−2, χ2 = 21.75, P < 0.01), systolic blood pressure (median: 120.00 vs. 120.00 vs. 125.00 vs. 130.00 mmHg, χ2 = 2.97, P = 0.05), diastolic blood pressure (median 80.00 vs. 75.00 vs. 80.00 vs. 81.00 mmHg, χ2 = 11.47, P < 0.01), and pathologic tubular atrophy and interstitial fibrosis (T) (T0/T1/T2: 62.96%/33.33%/3.70% vs. 29.63%/40.74%/29.63% vs. 24.00%/48.00%/28.00% vs. 14.81%/37.04%/48.15%, χ2 = 17.66, P < 0.01). The coefficient of each rs1801133-T allele on homocysteine levels after controlling age and sex was 7.12 (P < 0.01). MR estimates showed causal positive effects of homocysteine on serum creatine (β = 0.76, P = 0.02), systolic blood pressure (β = 0.26, P = 0.02), diastolic blood pressure (β = 0.20, P = 0.01), and pathologic T lesion (β = 0.01, P = 0.01) in IgAN. Conclusions: By observational and MR analyses, consistent results were observed for associations of plasma homocysteine with serum creatinine, blood pressures, and pathologic T lesion in IgAN patients.

Single-port laparoscopy-assisted vaginal repair of a cesarean scar defect: a single-center retrospective study Background: The incidence of uterine cesarean scar defect (niche) is high, and some patients require surgery. Single-port laparoscopy can reduce post-operative pain, and provide better cosmetic effects. This study was performed to evaluate the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scar defect (niche) in women after cesarean section. Methods: This study included 74 patients who were diagnosed with uterine cesarean niche at the Shanghai First Maternity and Infant Hospital from January 2013 to June 2015. Thirty-seven patients underwent single-port laparoscopy-assisted vaginal surgery as the case group, and the remaining patients underwent vaginal repair surgery as the control group. We collected data from the inpatient and follow-up medical records. The clinical characteristics of these two groups were compared. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and multivariate analyses. Results: Patients who underwent single-port laparoscopy-assisted vaginal repair had a significantly longer operation time (2.3 [2.0–2.7] vs. 2.0 [1.6–2.3] h, P = 0.015), shorter gas passage time (1.2 [1.0–1.5] vs. 1.7 [1.0–2.0] days, P = 0.012), shorter hospital stay (3.1 [3.0–4.0] vs. 4.5 [4.0–6.0] days, P = 0.019), and fewer complications (0 vs. 4 cases). Univariate analysis showed that depth of the niche (P = 0.021) the mild adhesiolysis score (P = 0.035) and moderate adhesiolysis score (P = 0.013) were associated with the bladder injury. Multivariate analysis showed that the moderate adhesiolysis score (P = 0.029; 95% confidence interval, 1.318–3.526) was the strongest independent predictor of bladder injury. Conclusion: This study confirmed the safety and superiority of single-port laparoscopy-assisted vaginal repair of uterine cesarean scars.

Sphingosine-1-phosphate signal transducer and activator of transcription 3 signaling pathway contributes to baicalein-mediated inhibition of dextran sulfate sodium-induced experimental colitis in mice Background: Baicalein has been shown to have anti-inflammatory and anti-tumor activities. However, the mechanisms underlying its anti-inflammatory effect on colitis remain unclear. Methods: A dextran sodium sulfate (DSS)-induced model of acute colitis was established in BALB/c mice (6–8 weeks old, weighing 18–22 g). Six groups of mice received: (1) water for 10 days (control), n = 6; (2) DSS 4% solution in the drinking water for 7 days, followed by normal water for 3 days, n = 7; (3), (4), and (5) as for group 2 plus baicalein (10, 20, 40 mg/kg) administered once daily starting on day 1, n = 6; and (6) as for (2) plus 5-aminosalicylic acid (50 mg/kg) administered once daily starting on day 1, n = 6. Body weights, stool consistency, and hematochezia were recorded, and the severity of colitis was evaluated using a disease activity index. On day 11, the mice were euthanized, and organs and blood were collected for analysis. Serum inflammatory factors were detected by enzyme-linked immunosorbent assay; CD11b-positive cells were analyzed by immunofluorescence microscopy; expression of retinoic-acid-receptor-related orphan nuclear receptor gamma, sphingosine kinase 1 (SPHK1), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) was detected by immunohistochemistry; and expression of nucleotide-binding oligomerization domain 2 (NOD2), SPHK1, sphingosine 1-phosphate receptor 1 (S1PR1), total STAT3, and p-STAT3 were detected by western blotting analysis. Inter-group differences were compared using Student's t test. Results: Baicalein treatment dose-dependently reduced DSS-induced weight loss (P < 0.01 or P < 0.05), splenomegaly (P < 0.01), and colonic damage, as reflected by amelioration of diarrhea, rectal bleeding, and colonic ulceration, congestion, edema (shown as colon length, P < 0.05 or P < 0.01), and inflammatory cell infiltration. Baicalein also significantly decreased the levels of inflammatory mediators in the serum (P < 0.01) and colon, and significantly inhibited expression of NOD2 SPHK1, S1PR1, and p-STAT3 in the colon (P < 0.05). Conclusions: Baicalein treatment ameliorated colitis in mice by inhibiting S1P-STAT3 signaling, suggesting that this flavonoid might be beneficial in the treatment of colitis.

Semaphorin 3A-hypoxia inducible factor 1 subunit alpha co-overexpression enhances the osteogenic differentiation of induced pluripotent stem cells-derived mesenchymal stem cells in vitro Background: Mesenchymal stem or stromal cells (MSCs) derived from the induced pluripotent stem cells (iPSCs) have uniform biological activity, which makes the clinical application of MSCs in bone repair possible. Culturing the iPSC-MSCs onto osteoconductive materials is a promising tissue engineering-based strategy in bone regeneration. The aim of this work was to evaluate the effects of semaphorin 3A (Sema3A) and hypoxia inducible factor 1 subunit alpha (HIF1α) co-overexpression on the survival and osteogenic differentiation of iPSC-MSCs. Methods: Sema3A and HIF1α were linked together with the three (GGGGS; G, glycine; S, serine) peptide fragment, and their co-expression in iPSC-MSCs was mediated by a lentiviral vector. The fusion protein retained the immune reactivity for both Sema3A and HIF1α as determined with Western blotting. iPSC-MSCs were infected with overexpression lentivirus (oeLenti) as negative control, oeLenti-Sema3A, oeLenti-HIF1α or oeLenti-Sema3A-HIF1α lentiviruses. Results: Sema3A overexpression alone promoted the osteogenic differentiation of iPSC-MSCs (the activity and/or expression of osteoblast markers, such as alkaline phosphatase, osteopontin, and osteocalcin, were upregulated), and suppressed cell survival. The Sema3A-HIF1α fusion protein showed a comparable osteoconductive effect to that of Sema3A without reducing cell survival. We further seeded iPSC-MSCs modified by SemaA-HIF1α overexpression onto hydroxyapatite (HA) scaffolds, and evaluated their growth and differentiation on this three-dimensional material. Additional data indicated that, as compared to iPSC-MSCs cultured in ordinary two-dimensional dishes, cells cultured in HA scaffolds grew (blank vs. HA scaffolds: 0.83 vs. 1.39 for survival) and differentiated better (blank vs. HA scaffolds: 11.29 vs. 16.62 for alkaline phosphatase activity). Conclusion: Modifying iPSC-MSCs with pro-osteogenic (Sema3A) and pro-survival (HIF1α) factors may represent a promising strategy to optimize tissue engineering-based strategy in bone repair.

Gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diet on glycemic control in overweight and obese adults: a systematic review and meta-analysis of clinical trials Background: The hypocaloric diets improve glycemic status in obese individuals, but the response to hypocaloric diets in fat mass and obesity-associated gene (FTO)-rs9939609 gene variant is unknown. This systematic review and meta-analysis aimed to assess the gene-diet interaction of FTO-rs9939609 gene variant and hypocaloric diets on glycemic control in overweight and obese adults. Methods: Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science, Embase, Scopus, and Google scholar were searched up to December 2018, for relevant clinical trials. Mean changes in fasting blood sugar (FBS), serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were extracted. Results: The pooled analysis of nine studies showed that there was no significant difference between AA/AT and TT genotypes in FBS (weighted mean difference [WMD] = 0.01, 95% confidence interval [CI]: –1.08, 1.10, P = 0.984) and serum insulin (WMD = 0.20, 95% CI: –0.85, 1.26; P = 0.707) after intervention hypocaloric diets. The overweight/obese participants in AA/AT group showed the greatest reduction in HOMA-IR compared with TT genotype following intervention, and this difference was not statistically significant (WMD = –0.38, 95% CI: –0.94, 0.16, P = 0.167). Conclusion: This meta-analysis suggests that there was no significant difference between AA/AT and TT genotypes of FTO-rs9939609 on FBS, serum insulin level, and insulin resistance in response to hypocaloric diets.

Human immunodeficiency virus prevention strategies in China This paper reviews the current epidemics of human immunodeficiency virus (HIV) infection in China, particularly the globally available prevention strategies developed and implemented. This review focuses on HIV prevention measures in general, such as education, testing, and counseling and in specific responses to transmission modes, such as blood safety, harm reduction for people who inject drugs, and condom promotion to reduce sexual transmission. We also assess newly developed prevention measures, such as prevention treatment, pre-exposure prophylaxis, post-exposure prophylaxis, male circumcision, and promising potential future preventions, including microbicides and vaccines. Based on this assessment, we provide recommendations for their implementation in China. We conclude that there is no magic bullet for HIV prevention, particularly sexual transmission of the disease, but only a combination of these prevention strategies can control the HIV epidemic.

Artificial intelligence in gastrointestinal endoscopy: general overview Artificial intelligence (AI) is now a trendy subject in clinical medicine and especially in gastrointestinal (GI) endoscopy. AI has the potential to improve the quality of GI endoscopy at all levels. It will compensate for humans’ errors and limited capabilities by bringing more accuracy, consistency, and higher speed, making endoscopic procedures more efficient and of higher quality. AI showed great results in diagnostic and therapeutic endoscopy in all parts of the GI tract. More studies are still needed before the introduction of this new technology in our daily practice and clinical guidelines. Furthermore, ethical clearance and new legislations might be needed. In conclusion, the introduction of AI will be a big breakthrough in the field of GI endoscopy in the upcoming years. It has the potential to bring major improvements to GI endoscopy at all levels.