Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Objective To explore causal relationship between 25-hydroxyvitamin D[25(OH)D]and ankylosing spondylitis(AS).Methods Genetic data of 25(OH)D and AS were extracted from the genome-wide association study.The causal effect of 25(OH)D on AS was estimated by MR-Egger regression method,weighted median,inverse variance weighted(IVW),simple mode and weighted mode,and sensitivity analysis was conducted for verification.Results The IVW results indicated that there was a causal relationship between 25(OH)D concentration and AS(OR=0.805,95％CI:0.686-0.944,P=0.008),and the maximum likelihood ratio(OR=0.799,95％CI:0.678-0.940,P=0.007)showed consistent results.The IVW results of the reverse Mendelian randomization study showed that there was no causal relationship between the two(OR=1.019,95％CI:0.995-1.043,P=0.110).In addition,MR-Egger intercept,Cochran Q test,"leave-one-out"and MR-PRESSO analysis showed no horizontal pleipotency or heterogeneity.Conclusion There may be a genetic causal relationship between the concentration of 25(OH)D and the onset of AS.AS cannot cause changes in the concentration of 25(OH)D in the body.

Chronic kidney disease（CKD）has a significant impact on global public health and is one of the important factors leading to the rise of incidence rate and mortality of non communicable diseases.Intestinal microecology is involved in many pathophysiological activities，such as immunity and nutrient absorption.With proposal of the concept of intestine-kidney axis in 2002，researchers found that the decline of glomerular filtration rate led to accumulation of uremic toxins in intestine，destroyed the intestinal mucosal barrier，led to the translocation of toxins，activated the systemic oxidative stress response，further promoted the progress of CKD.This article reviewed the function of gut microbiota，intestine-gut kidney axis，and the application of microbial preparations in CKD.

Objective:To evaluate the efficacy and safety of a China original liquid pulsation system for the treatment of meibomian gland dysfunction (MGD).Methods:A non-randomized controlled clinical trial was conducted.Twenty-two patients (44 eyes) diagnosed with MGD in Eye and ENT Hospital of Fudan University from February to August 2022 were enrolled.The patients were assigned into two groups according to their willingness.Of the 22 patients (44 eyes), 10 patients (20 eyes) in single liquid pulsation system group were treated with single liquid pulsation system for 12 minutes, and 12 patients (24 eyes) in intense pulsed light (IPL) group were treated with a course (4 times) of IPL, warm compresses and meibomian gland massage at three-week intervals.There was no difference in age and other baseline clinical indexes between the two groups (all at P<0.05). The meibum grading, quality grading of tear film lipid layer, Symptom Assessment Questionnaire in Dry Eye (SANDE) questionnaire score, first and average tear breakup time (BUT), corneal fluorescein sodium staining (CFS) score, tear meniscus height (TMH), and the area of meibomian gland loss were determined at baseline, 1 and 3 months after treatment.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Eye and ENT Hospital of Fudan University (No.2021069). Written informed consent was obtained from each patient before any medical examination. Results:Statistically significant group effects and time effects were found in the quality of tear film lipid layer ( Hgroup=4.39, P=0.036, Htime=6.30, P=0.043) and average BUT ( Fgroup=4.41, P=0.038; Ftime=4.08, P=0.049) in the two groups.The meibum grading, first BUT and TMH 1 and 3 months after treatment were significantly better than before treatment in single liquid pulsation system group (all at P<0.05). Compared with before treatment, there was no significant improvement in the meibum grading, distribution of tear film lipid, first BUT and TMH at 1 and 3 months after treatment in IPL group (all at P>0.05). In both groups, the SANDE and CFS scores 1 and 3 months after treatment were better than those before treatment, showing statistically significance (all at P<0.05). In terms of safety, neither instrument-related adverse events nor extra complaints of discomfort were reported in the single liquid pulsation system group.In both groups, the number of patients with positive CFS staining significantly decreased, and no new cases with positive CFS appeared after treatment. Conclusions:This China original liquid pulsation system is a safe and effective physical therapy in improving tear film dysfunction and ocular surface symptoms of MGD patients within 3 months after treatment.

Objective:To evaluate the detection accuracy of hepatitis B virus (HBV) serological markers among grassroots medical institutions in the demonstration areas of infectious diseases.Methods:A fixed sampling method was used among the followed-up hepatitis B cohort in general population of six infectious disease demonstration areas nationwide. Blood samples of chosen objects were collected, in which HBsAg and anti-HBs were tested by grassroots medical institutions and were also parallely tested by the third-party platform. The test results were compared between the two groups. Statistical analyses were conducted by SAS 9.4 software.Results:A total of 5 756 and 5 263 samples of HBsAg and anti-HBs were successfully tested, respectively. Comparing the results of HBsAg and anti-HBs from grassroots medical institutions with the results from the third platform, the agreement of HBsAg and anti-HBs was 97.13% and 77.33%, respectively. The Kappa value was 0.56 (95% CI 0.50-0.62) for HBsAg and 0.54 (95% CI 0.52-0.56) for anti-HBs, respectively; and the McNemar tests indicated the difference between the results (all P<0.01). There were also significant differences in agreement of testing results with the third platformin among different regions ( P<0.05 or <0.01). The Kappa values indicated that Jiangsu province and Guangdong province had high accordance rates of HBsAg (0.87 and 0.81, respectively), and Gansu province and Guangdong province had high accordance rates of anti-HBs (Both were 0.74). Regarding the results from the third platform as the standard, the sensitivity of HBsAg testing in grassroots medical institutions was moderate (40.51%) and the specificity was well (99.96%). The sensitivity of anti-HBs testing was substantial (73.18%) and the specificity was well (84.31%). Guangdong province (Youden index: 0.69) and Jiangsu province (Youden index: 0.80) had high identification ability for HBsAg, and for indicator of anti-HBs, Gansu province (Youden index: 0.78) and Guangdong province (Youden index: 0.76) had high identification ability. Conclusion:There are certain differences in results of HBV serological markers tests between the grassroots medical institutions in the demonstration areas of infectious diseases and the third platform. Current testing strategies in grassroots medical institutions are suitable for identifying people without hepatitis B infection, while it is necessary to pay attention to the situation of potential false negative error.

Objective To observe the multimodal imaging characteristics of combined hamatoma of the retina and retinal pigment epithelium (CHRRPE).Methods A retrospective case study.From January 2013 to December 2017,6 CHRRPE patients (6 eyes) diagnosed in Department of Ophthalmology,Sun Yat-sen Memorial Hospital were included in the study.There were 4 males and 2 females,with the mean age of 12.0±8.10 years.There were 5 eyes with BCVA ≤0.1,1 eye with BCVA＞ 1.0.Corneal fluoroscopy showed 1 eye with an external oblique 15°,and the remaining eye had no abnormalities in the anterior segment.All eyes underwent fundus color photography,FAF,FFA,ICGA,OCT and color Doppler flow imaging (CDFI).The multimodal imaging characteristics were observed.Results All the affected eyes CHRRPE were located in the posterior pole and showed mild elevation.Most of the retinal neuroepithelial layers had different degrees of hyperplasia,vascular tortuosity and retinal folds.Of the 6 eyes,4 eyes (66.7％) involving the macula and optic disc,only 2 eyes (33.3％) involving the macula.OCT showed that the structure of the neuroepithelial layer was unclear and the signal intensity was uneven;it involved 2 eyes of the whole retina (33.3％) and only 4 eyes of the neuroepithelial layer (66.7％).FFA and ICGA showed that the choroidal background fluorescence of the early lesions was weakened,and the lesions showed slightly weak fluorescence;the late telangiectasia fluorescein was obviously leaked,and the lesions were stained with fluorescence.FAF mainly appears as weak autofluorescence with a small amount of strong autofluorescence.CDFI has no characteristic performance.Conclusions CHRRPE is mainly a membrane-like hyperplasia without angiogenesis,involving the retinal neuroepithelial layer,and may also involve the entire retina.OCT is dominated by strong reflection;AF,FFA and ICGA are mainly weak fluorescence.