Effect of Consultation Number on the Assessment and Treatment of Polycystic Ovary Syndrome.

Background: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare. Methods: This is a multicenter cross-sectional survey. Participants' basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0-50 people/yr, 50-200 people/yr, and >200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis. Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50-200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens. Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.

[Arthroscopic assistance of latissimus dorsi tendon transposition for the treatment of unrepairable rotator cuff tear].

OBJECTIVE: To explore clinical effect of arthroscopy-assisted rotator cuff tendon transfer in treating irreparable rotator cuff tears (IRCT). METHODS: From May 2015 to May 2018, 23 patients with unrepairable rotator cuff tears were treated with arthroscopy-assisted rotator cuff tendon transfer, and 21 patients were followed up finally, including 8 males and 13 females, aged from 48 to 82 years old with an average of(64.3±9.1) years old;the courses of disease ranged from 6 to 36 months with an average of (14.0±6.4) months. American Rotator and Elbow Surgeons Score(ASES) and Constant-Murley score were used to evaluate clinical efficacy before surgery and at the latest follow-up. RESULTS: All 21 patients were followed up for 36 to 54 months with an average of (39.4±4.4) months. Axillary incision of 1 patient was redness, swelling and exudation after surgery, which healed after 3 weeks of dressing change, and exudate culture was negative. At the latest follow-up, MRI showed partial tearing of the metastatic tendon in 2 patients, but pain and movement of the affected shoulder were still better than before surgery. ASES increased from preoperative (41.0±9.6) scores to the latest follow-up (75.6±14.0) scores, and had statistical difference (t=10.50, P<0.01). Constant-Murley score increased from (49.8±7.1) scores before operation to (67.5±11.6) scores at the latest follow-up (t=11.27, P<0.01). CONCLUSION: Arthroscopic assisted latissimus dorsalis tendon transposition restores physiological and anatomical structure of glenohumeral joint by reconstructing balance of horizontal and vertical couples of shoulder joint, thus achieving the stability of the shoulder joint, relieving shoulder pain and improving shoulder joint function.

Contribution of ADD3 and the HLA Genes to Biliary Atresia Risk in Chinese.

Nonsyndromic biliary atresia (BA) is a rare polygenic disease, with autoimmunity, virus infection and inflammation thought to play roles in its pathogenesis. We conducted a genome-wide association study in 336 nonsyndromic BA infants and 8900 controls. Our results validated the association of rs17095355 in ADD3 with BA risk (odds ratio (OR) = 1.70, 95% confidence interval (95% CI) = 1.49-1.99; p = 4.07 × 10-11). An eQTL analysis revealed that the risk allele of rs17095355 was associated with increased expression of ADD3. Single-cell RNA-sequencing data and immunofluorescence analysis revealed that ADD3 was moderately expressed in cholangiocytes and weakly expressed in hepatocytes. Immuno-fluorescent staining showed abnormal deposition of ADD3 in the cytoplasm of BA hepatocytes. No ADD3 auto-antibody was observed in the plasma of BA infants. In the HLA gene region, no variants achieved genome-wide significance. HLA-DQB1 residue Ala57 is the most significant residue in the MHC region (OR = 1.44, 95% CI = 1.20-1.74; p = 1.23 × 10-4), and HLA-DQB1 was aberrantly expressed in the bile duct cells. GWAS stratified by cytomegalovirus (CMV) IgM status in 87 CMV IgM (+) BA cases versus 141 CMV IgM (-) BA cases did not yield genome-wide significant associations. These findings support the notion that common variants of ADD3 account for BA risk. The HLA genes might have a minimal role in the genetic predisposition of BA due to the weak association signal. CMV IgM (+) BA patients might not have different genetic risk factor profiles compared to CMV IgM (-) subtype.

Association analysis and functional follow-up identified common variants of JAG1 accounting for risk to biliary atresia.

Background: Biliary atresia (BA) is a destructive, obliterative cholangiopathy characterized by progressive fibro-inflammatory disorder and obliteration of intra- and extrahepatic bile ducts. The Jagged1 (JAG1) gene mutations have been found in some isolated BA cases. We aim to explore the association of common variants in JAG1 with isolated BA risk in the Chinese Han population. Methods: We genotyped 31 tag single nucleotide polymorphisms covering the JAG1 gene region in 333 BA patients and 1,665 healthy controls from the Chinese population, and performed case-control association analysis. The expression patterns of JAG1 homologs were investigated in zebrafish embryos, and the roles of jag1a and jag1b in biliary development were examined by morpholino knockdown in zebrafish. Results: Single nucleotide polymorphisms rs6077861 [P Allelic = 1.74 × 10-4, odds ratio = 1.78, 95% confidence interval: 1.31-2.40] and rs3748478 (P Allelic = 5.77 × 10-4, odds ratio = 1.39, 95% confidence interval: 1.15-1.67) located in the intron region of JAG1 showed significant associations with BA susceptibility. The JAG1 homologs, jag1a and jag1b genes were expressed in the developing hepatobiliary duct of zebrafish, especially at 72 and 96 h postfertilization. Knockdown of both jag1a and jag1b led to poor biliary secretion, sparse intrahepatic bile duct network and smaller or no gallbladders compared with control embryos in the zebrafish model. Conclusion: Common genetic variants of JAG1 were associated with BA susceptibility. Knockdown of JAG1 homologs led to defective intrahepatic and extrahepatic bile ducts in zebrafish. These results suggest that JAG1 might be implicated in the etiology of BA.

The role of obstetrician-gynecologists and reproductive endocrinologists in the blood glucose management of polycystic ovary syndrome.

Background: This study aimed to compare the differences between reproductive endocrinologists (Repro-Endo) and obstetricians-gynecologists (Ob-Gyn; non-reproductive medicine specialty) in diagnosing, evaluating, and treating PCOS women with insulin resistance (IR).Methods: Repro-Endo and Ob-Gyn in China participated in this survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis.Results: The study analyzed 2412 survey responses (92.3% OB-Gyn; 98.5% women). Physician's age, hospital grade, specialty, and the number of PCOS patients who visit the physicians, revealed that Repro-Endo participants were more likely to suggest an oral glucose tolerance test (OR, 1.727; 95% CI, 1.272-2.345) as their first choice than Ob-Gyn participants. The most common treatments for patients with PCOS were lifestyle modification (>95%) and metformin use (>80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (46.5% vs. 23.5%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (12.5% vs. 1.6%).Conclusion: This survey identified knowledge gaps in metabolic screening for patients with IR and PCOS. Similarly, it highlights the need to improve IR management education for physicians caring for PCOS women.

The Disparity in the Management of Polycystic Ovary Syndrome between Obstetrician-Gynecologists in Different-Level Hospitals under the Hierarchical Medical System.

Background: PCOS is a prevalent endocrine and metabolic disorder in women characterized by abnormal blood glucose, dyslipidemia, and abnormal mental health. To improve patient care, the goal of our study is to find out if there are differences in how PCOS patients are treated at different hospital levels within the hierarchical medical system. Methods: Obstetricians and gynecologists from primary, secondary, and tertiary hospitals were the participants in the survey. The responses provided and collected were analyzed using various statistical techniques like the chi-square test, Fisher exact test, and logistic regression with multiple variables. Results: The investigation examined 2298 survey replies (13.1% primary hospitals, 52.4% secondary hospitals, and 34.5% tertiary hospitals). As hospital grade increases, more participants inquire about a patient's history of unfavorable pregnancies concerning hormone evaluation; the better the hospital's grade, the greater the number of participants who would undergo AMH and androgen-related tests. The higher the hospital level, the more participants would pick the oral glucose tolerance test (OGTT) to determine insulin resistance, the BMI Asian criteria for defining obesity, and blood lipids. Participants in primary (odds ratio (OR) = 0.383, 95% confidence interval (CI) 0.282-0.520) and secondary (OR = 0.607, 95% confidence interval (CI) 0.481-0.765) hospitals were significantly less likely to select OGTT than those in tertiary hospitals. Comparatively, fewer primary hospitals chose to do lipid profiling than tertiary hospitals (OR 0.689, 95% CI 0.523-0.909). With the increase in hospital level, participants were more knowledgeable about the multiple efficacies and dose alternatives of metformin and selected letrozole and assisted reproduction more frequently. Conclusion: Our study uncovered differences in the endocrine evaluation, metabolic screening, and management of PCOS patients across obstetrics and gynecology at various hospital levels. Simultaneously, it underlines the need to improve the hierarchical medical system and close the knowledge gap across hospitals.

Effect of Low-Power Visible-Light-Activated Photodynamic Therapy (PDT) on Primary Dysmenorrhea: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Primary dysmenorrhea (PD) is one of the most common complaints in women of childbearing age. Therefore, this trial aimed to assess the efficacy and safety of low-power visible-light-activated photodynamic therapy (PDT) in the treatment of primary dysmenorrhea (PD), and to further investigate their possible mechanisms of action. Methods: This study was conducted by using a multicenter, randomized, open, parallel control design. Qualified subjects are randomly assigned to two groups: Group A (low-power visible-light-activated PDT group), Group B (placebo group) and are treated with corresponding protocols for three consecutive menstrual cycles. Baseline data are collected during the trial period. Changes in the scores of VAS scales and the fluctuation of pain factors (PGE2, PGF2α) are recorded before and after the treatment for each group. A comparison of effectiveness in pain control and symptom control is made among the two groups. Results: After treatment, for the PDT group, the scores of VAS scales decline compared with the scores before treatment. The level of pain factors including PGE2 and PGF2α also drops significantly (P < 0.05). There are no serious adverse events during the study. Conclusion: Low-power visible-light-activated PDT is a new type of treatment for primary dysmenorrhea which is safe, effective and does not affect normal pregnancy preparation. It may exert its therapeutic effect by adjusting downward the level of PGE2, PGF2α in the body. These factors can be used not only to study the treatment mechanism for primary dysmenorrhea, but also to serve as quantitative indicators for objective assessment of whether dysmenorrhea is relieved.

Metabolic Landscape of Bronchoalveolar Lavage Fluid in Coronavirus Disease 2019 at Single Cell Resolution.

Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.

miR-204-5p Hampers Breast Cancer Malignancy and Affects the Cell Cycle by Targeting PRR11.

PURPOSE: To unravel mechanisms of miR-204-5p in breast cancer (BC) cells. METHODS: miR-204-5p expression level in BC cell lines was measured by qRT-PCR. Putative binding sites of miR-204-5p on the 3'-untranslated region of PRR11 were predicted by the bioinformatics method and verified by the dual-luciferase method. Protein and mRNA levels of PRR11 in BC were determined by western blot and qRT-PCR. The association between two genes was analyzed by correlation analysis. Cancer cell functions were evaluated through CCK8, flow cytometry, and Transwell approaches. RESULTS: Significant downregulation of miR-204-5p was observed in BC tissue and cells. Cell functional experiments showed the inhibition of miR-204-5p on cell behaviors and cell cycle. PRR11 was the downstream target of miR-204-5p. Inhibition of RPP11 could reverse the impacts of the miR-204-5p inhibitor on cell functions of BC. CONCLUSION: Our study revealed that the miR-204-5p/PRPP11 axis suppressed BC progression, which may provide a novel insight into the regulatory roles of miR-204-5p.

Circular RNA CNOT2 knockdown regulates twist family BHLH transcription factor via targeting microRNA 409-3p to prevent breast cancer invasion, migration and epithelial-mesenchymal transition.

Numerous studies have manifested that cicular RNA (circRNA) is closely associated with the development of breast cancer (BC), but the specific mechanism has not been fully clarified. The purpose of this study was to investigate the effect of circCNOT2 on BC invasion, migration and epithelial mesenchymal transition (EMT) and its potential molecular mechanism. The results assured that circCNOT2 and Twist Family BHLH Transcription Factor (TWIST1) were elevated in BC, while microrNA (miR)-409-3p was reduced. CircCNOT2 was positively correlated with TWIST1 and negatively correlated with miR-409-3p. Elevated circCNOT2 is associated with poor prognosis of BC. Knockdown circCNOT2 or augmented miR-409-3p could promote apoptosis but repress proliferation, invasion, migration and EMT of BC cells. In addition, overexpression of circCNOT2 or TWIST1 accelerated BC invasion, migration and EMT, which could be reversed by simultaneous transfection of miR-409-3p-mimic. Further dual luciferase reporting and RNA-pull down assay clarified that circCNOT2 acted as a competing endogenous RNA of miR-409-3p to mediate TWIST1 expression. In conclusion, the results of this study suggest that circCNOT2 affects the biological behavior of BC via regulating the miR-409-3p/TWIST1 axis, and may be applied as a potential therapeutic target for BC later.

Association Analysis of Variants of DSCAM and BACE2 With Hirschsprung Disease Susceptibility in Han Chinese and Functional Evaluation in Zebrafish.

Hirschsprung disease (HSCR) has a higher incidence in children with Down syndrome (DS), which makes trisomy 21 a predisposing factor to HSCR. DSCAM and BACE2 are close together on the HSCR-associated critical region of chromosome 21. Common variants of DSCAM and rare variants of BACE2 were implicated to be associated with sporadic HSCR. However, the submucosal neuron defect of DS mouse model could not be rescued by normalization of Dscam. We aimed to explore the contribution of DSCAM and BACE2 to the development of the enteric nervous system (ENS) and HSCR susceptibility. We genotyped 133 tag single-nucleotide polymorphisms (SNPs) in DSCAM and BACE2 gene region in 420 HSCR patients and 1,665 controls of Han Chinese. Expression of DSCAM and BACE2 homologs was investigated in the developing gut of zebrafish. Overexpression and knockdown of the homologs were performed in zebrafish to investigate their roles in the development of ENS. Two DSCAM SNPs, rs430255 (P Addtive = 0.0052, OR = 1.36, 95% CI: 1.10-1.68) and rs2837756 (P Addtive = 0.0091, OR = 1.23, 95% CI: 1.05-1.43), showed suggestive association with HSCR risk. Common variants in BACE2 were not associated with HSCR risk. We observed dscama, dscamb, and bace2 expression in the developing gut of zebrafish. Knockdown of dscama, dscamb, and bace2 caused a reduction of enteric neurons in the hindgut of zebrafish. Overexpression of DSCAM and bace2 had no effects on neuron number in the hindgut of zebrafish. Our results suggested that common variation of DSCAM contributed to HSCR risk in Han Chinese. The dysfunction of both dscams and bace2 caused defects in enteric neuron, indicating that DSCAM and BACE2 might play functional roles in the occurrence of HSCR. These novel findings might shed new light on the pathogenesis of HSCR.

Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial.

AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of intervention, while only one of 10 fatty liver participants in control group disappeared. CONCLUSIONS: In addition to improving the menstrual cycle, KD had the additional benefits of reducing blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional pharmacological treatment in women with PCOS and liver dysfunction who were obese.

Common variation of the NSD1 gene is associated with susceptibility to Hirschsprung's disease in Chinese Han population.

BACKGROUND: Hirschsprung's disease (HSCR) is the most common congenital cause of intestinal obstruction in children. Sotos syndrome (SoS) is an overgrowth disorder with constipation and sometimes accompanied by HSCR. NSD1 gene mutation is the main cause of SoS. We aimed to investigate association of NSD1 common single nucleotide polymorphisms (SNPs) with HSCR susceptibility in Chinese Han population. METHOD: We genotyped 15 SNPs encompassing NSD1 gene region in 420 HSCR patients and 1665 controls on Fludigm EP1 platform. Association analysis was performed between cases and controls. RESULT: Rs244709 was the most associated SNP with HSCR susceptibility of the sample set (PAllelic = 9.69 × 10-5, OR = 1.37, 95% CI: 1.17-1.61). Gender stratification analysis revealed that NSD1 SNPs were associated with HSCR in males, but not in females. The nonsynonymous coding SNP rs28932178 in NSD1 exon 5 represented the most significant signal in males (PAllelic = 6.43 × 10-5, OR = 1.42, 95% CI: 1.20-1.69). The associated SNPs were expression quantitative trait loci (eQTLs) of nearby genes in multiple tissues. NSD1 expression levels were higher in aganglionic colon tissues than ganglionic tissues (P = 3.00 × 10-6). CONCLUSION: NSD1 variation conferred risk to HSCR in males, indicating SoS and HSCR may share common genetic factors. IMPACT: This is the first study to reveal that NSD1 variation conferred risk to Hirschsprung's disease susceptibility in males of Chinese Han population, indicating Sotos syndrome and Hirschsprung's disease may share some common genetic background. This study indicates more attention should be paid to the symptom of constipation in patients with Sotos syndrome. Our results raise questions about the role of NSD1 in the development of enteric nervous system and the pathogenesis of Hirschsprung's disease.

Peritumoral Enhancement for the Evaluation of Myometrial Invasion in Low-Risk Endometrial Carcinoma on Dynamic Contrast-Enhanced MRI.

OBJECTIVES: To explore the clinical value of subendometrial enhancement (SEE), irregular thin-layered peritumoral early enhancement (ITLPE) and focal irregular peritumoral early enhancement (FIPE) on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for myometrial invasion in patients with low-risk endometrial carcinoma. METHODS: Seventy-seven patients with low-risk endometrial carcinoma who preoperatively underwent DCE-MRI were included. Two radiologists independently evaluated and recorded the occurrences of SEE, ITLPE and FIPE on DCE-MRI in all patients. Interobserver agreement was calculated between the two radiologists, and the relationships between SEE, ITLPE, FIPE, and myometrial invasion were analyzed based on histologic findings. For statistically significant findings, the sensitivity and specificity were calculated, and the differences in myometrial invasion evaluations were analyzed. For those with no statistical significance, images were compared with the histopathologic sections. RESULTS: Inter-observer agreement was good (k = 0.80; 95%CI, 0.577-0.955) for SEE, and very good (k = 0.88; 95%CI, 0.761-0.972) (k = 0.86; 95%CI, 0.739-0.973) for ITLPE and FIPE. After consensus, SEE was identified in 12/77 (15.6%) patients; ITLPE and FIPE were found in 53/77 (68.8%) and 30/77 (39.0%) patients, respectively. SEE and ITLPE were significantly correlated with myometrial infiltration (P = 0.000), but FIPE were not (P = 0.725).The sensitivity and specificity of SEE and ITLPE for myometrial invasion in patients with low-risk endometrial carcinoma were 95.0 and 52.9%, and 85.0 and 88.0%, respectively. The area under the curve (AUC) of SEE and ITLPE for myometrial invasion were 0.740 (95%CI, 0.584-0.896), and 0.866 (95%CI, 0.763-0.970), respectively. The sensitivity and specificity were statistically different between SEE and ITLPE for the detection of myometrial invasion (P = 0.031, 0.016). According to the comparison between FIPE and histopathologic findings, the irregular endomyometrial junction was found in 30/77 (38.9%) cases, 24/30 (80.0%) with myometrial infiltration and 6/30 (20.0%) cases without myometrial infiltration. CONCLUSIONS: FIPE was the irregular endomyometrial junction. It can be found in patients with or without myometrial infiltration and may lead to the overestimation of myometrial invasion by SEE on DCE-MRI. ITLPE presented high diagnostic performance and specificity for myometrial invasion in patients with low-risk endometrial carcinoma.

Association of Variants in PLD1, 3p24.1, and 10q11.21 Regions With Hirschsprung's Disease in Han Chinese Population.

Background and Aims: Hirschsprung's disease (HSCR) is a rare genetically heterogeneous congenital disorder. A recent study based on whole genome sequencing demonstrated that common variants at four novel loci, which contained two intronic variants on CASQ2 and PLD1, and intergenic variants located between SLC4A7 and EOMES at 3p24.1, and between LINC01518 and LOC283028 at 10q11.21, were associated with HSCR susceptibility. To validate these associations with HSCR susceptibility, we performed a case-control study in a Han Chinese sample set. Methods: We selected four previously identified single nucleotide polymorphisms (SNPs) for replication, along with tag SNPs to cover the four associated regions. In total, 61 SNPs were genotyped in 420 HSCR patients and 1,665 healthy controls from the Han Chinese population. Results: None of the 14 tag SNPs in the CASQ2 gene region, including the previously associated rs9428225, showed an association with HSCR. Among the 24 tag SNPs from the SLC4A7-EOMES region at 3p24.1, rs2642925 [odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.10-1.79; P Additive = 0.007] and the previously associated SNP rs9851320 showed a suggestive association (OR = 1.22, 95% CI = 1.01-1.47; P Additive = 0.042). A non-synonymous SNP, rs2287579, in PLD1 showed a suggestive association with HSCR susceptibility (OR = 1.71, 95% CI = 1.18-2.46; P Additive = 0.004). Additionally, the previously associated PLD1 SNP rs12632766 showed a suggestive significance (OR = 1.20, 95% CI = 1.01-1.42, P Additive = 0.038). In the LINC01518-LOC283028 region at 10q11.21, three SNPs meet the study-wide significance threshold. Rs17153309 was the most associated SNP (OR = 1.60, 95% CI = 1.34-1.90; P Additive = 1.13 × 10-7). The previously associated SNP rs1414027 also showed significant association (OR = 1.43, 95% CI = 1.20-1.70, P Additive = 3.92 × 10-5). Two associated SNPs at 10q11.21 (rs1414027 and rs624804) were expression quantitative trait loci in digestive tract tissues from GTEx databases. Conclusions: Our results confirmed that variants of the LINC01518-LOC283028 region were associated with HSCR in the Han Chinese population. Additionally, the susceptibility of SNPs in the LINC01518-LOC283028 region were associated with the expression levels of nearby genes. These results provide new insight into the pathogenesis of HSCR.

Clinical Validation of the Chinese Version of Patient Completed Caprini Risk Assessment Form.

To create and validate patient-completed Caprini risk score (CRS) tools for Chinese people. We revised Chinese patient-completed CRS form according to previously published studies. We prospectively recruited 70 internal medical patients and 70 surgical patients. The average age of these patients was 54.26 ± 15.29 years, 54.29% of them were male and 80% of them had education beyond high school. The study compared: (1) patient-completed CRS and physician-completed CRS; (2) the final value of physician-completed CRS (physician-completed CRS + body mass index) and CRS in the electronic medical record (EMR) system. Patient-completed CRS was 3.71 ± 3.63, patients spent 3.60 ± 1.24 minutes, 57.14% patients were at high-highest risk; physician-completed CRS was 3.84 ± 3.63, physicians spent 2.11 ± 1.13 minutes, 59.28% patients were at high-highest risk; the final value of physician-completed CRS was 4.12 ± 3.62, 63.58% patients were at high-highest risk; CRS value in the EMR system was 4.07 ± 3.58, 65% patients were at high-highest risk. There were strong positive correlations (P < .0001) between patient-completed CRS and physician-completed CRS (r = 0.978, κ = 0.76) and between the final value of physician-completed CRS and CRS in EMR (r = 0.994, κ = 0.97). This study successfully developed and validated a Chinese patient-completed CRS that we found can replace physician-completed CRS. This results in considerable time saving for physicians and this process should increase the percentage of patients having complete risk assessment when they are admitted to the hospital.

Association of common variation in ADD3 and GPC1 with biliary atresia susceptibility.

Biliary atresia (BA) is an idiopathic neonatal cholestatic disease. Recent genome-wide association study (GWAS) revealed that common variation of ADD3, GPC1, ARF6, and EFEMP1 gene was associated with BA susceptibility. We aimed to evaluate the association of these genes with BA in Chinese population. Twenty single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 340 BA patients and 1,665 controls. Three SNPs in ADD3 were significantly associated with BA, and rs17095355 was the top SNP (PAllele = 3.23×10-6). Meta-analysis of published data and current data indicated that rs17095355 was associated with BA susceptibility in Asians and Caucasians. Three associated SNPs were expression quantitative trait loci (eQTL) for ADD3. Two GPC1 SNPs in high linkage disequilibrium (LD) showed nominal association with BA susceptibility (PAllele = 0.03 for rs6707262 and PAllele = 0.04 for rs6750380), and were eQTL of GPC1. Haplotype harboring these two SNPs almost reached the study-wide significance (P = 0.0035). No association for ARF6 and EFEMP1 was found with BA risk in the current population. Our study validated associations of ADD3 and GPC1 SNPs with BA risk in Chinese population and provided evidence of epistatic contributions of genetic factors to BA susceptibility.

CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition.

Intestinal villus atrophy is a major complication of total parenteral nutrition (TPN). Our previous study revealed that TPN-induced villus atrophy is accompanied by elevated expression of CUGBP, Elav-like family member 1 (CELF1); however, its mechanism of action has not been fully understood. Herein, we report a pivotal role of CELF1/p53 axis, which induces a sustained antiproliferative signal, leading to suppressed proliferation of intestinal epithelial cells (IECs). By using a rat model of TPN, we found synchronous upregulation of CELF1 and p53 in jejunum mucosa, accompanied by a 51% decrease in crypt cell proliferation rate. By using HCT-116 cells as an IEC model in vitro, we found that the expression of CELF1 altered dynamically in parallel to proliferation rate, suggesting a self-adaptive expression pattern in IECs in vitro. Furthermore, ectopic overexpression of CELF1 elicited a significant antiproliferative effect in HCT-116, Caco-2, and IEC-6 cells, whereas knockdown of CELF1 elicited a significant proproliferative effect. Moreover, cell-cycle assay revealed that ectopic overexpression of CELF1 induced sustained G2 arrest and G1 arrest in HCT-116 and IEC-6 cells, respectively, which could be abolished by p53 silencing. Mechanistically, polysomal profiling and nascent protein analysis revealed that regulation of p53 by CELF1 was mediated through accelerating its protein translation in polysomes. Taken together, our findings revealed a sustained suppression of IEC proliferation evoked by CELF1/p53 axis, which may be a potential therapeutic target for the treatment of TPN-induced villus atrophy.-Yan, J.-K., Zhang, T., Dai, L.-N., Gu, B.-L., Zhu, J., Yan, W.-H., Cai, W., Wang, Y. CELF1/p53 axis: a sustained antiproliferative signal leading to villus atrophy under total parenteral nutrition.

Tooth loss as a risk factor for dementia: systematic review and meta-analysis of 21 observational studies.

BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.

A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women.

OBJECTIVE: To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs). METHODS: From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P <0.01) and there was no significant difference between groups (P >0.05), except that KMI of HYKT group was higher after 3-month treatment (P <0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P <0.01); and HT had a better performance than HYKT in improving hot flush (P <0.05). MENQOL were significantly improved in both groups after treatment (P <0.01); but there was no significant difference between two groups (P >0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P <0.01). CONCLUSIONS: HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.