Objective To investigate the causal relationship between circadian rhythm disruption and inflammatory bowel disease(IBD)and the mediating effect of gut microbiota based on Mendelian randomization(MR).Methods Summary statistics of Genome-wide Association Study(GWAS)for circadian rhythm disruption(n=205 527)and IBD(n=214 053)were obtained from IEU OpenGWAS database.Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database(n=18 340).Two-sample MR analysis was used to estimate the genetic correlation and causality between circadian rhythm disruption and IBD,and the mediating effect of the gut microbiota was analyzed by two-step MR analysis.Results There was a suggestive causal relationship between circadian rhythm disruption and IBD(odds ratio=1.255,P＜0.05).Rikenellaceae id.967 played a mediating role in the causal chain between them(the mediating effect was-0.028 740).Sensitivity analysis confirmed that the results were not interfered by level pleiotropy and heterogeneity.Conclusion There is a genetic correlation between circadian rhythm disruption and IBD,and gut microbiota may play a mediating role between them.

Objective To explore the content and the psychometric properties of assessment tools used for evaluating functioning and adaptive behavior in school-age children with intellectual and developmental disabilities within educational settings. Methods The most used assessment tools included Vineland Adaptive Behavior Scales(VABS),Supports Intensity Scale for Children(SIS-C),Strengths and Difficulties Questionnaire(SDQ)and Repetitive Behavior Scale-Revised(RBS-R),for assessing functioning and adaptive behavior children with intellectual and developmental disabili-ties.Employing the framework and methods of the International Classification of Functioning,Disability,and Health(ICF),this research encoded and categorized the assessment dimensions and items of the four tools,and explored their psychometric properties. Results VABS's assessment content was solely focused on activities and participation,including speaking(d330),con-versation(d350),toileting(d530),eating(d550),drinking(d560),basic interpersonal interactions(d710),com-plex interpersonal interactions(d720),changing and maintaining body positions(d410-d429),carrying,moving and handing objects(d430-d449),and walking and moving(d450-d469).SIS-C assessed activities and participa-tion,and environmental factors,including washing oneself(d510),caring for body parts(d520),community life(d910),using transportation(d470),school education(d820),basic learning(d130-d159),looking after one's health(d570),basic interpersonal interactions(d710),and products and technology for education(e130).SDQ fo-cused on body functions,and activities and participation,including emotional functions(b152),global psychoso-cial functions(b122),attention functions(b140),and basic interpersonal interactions(d710).RBS-R focused on body functions,and activities and participation,including involuntary movement reaction functions(b755),invol-untary movement functions(b765),looking after one's health(d570),energy and drive functions(b130),under-taking a single task(d210),carrying out daily routine(d230),attention functions(b140),and handling stress and other psychological demands(d240).VABS was characterized by good specificity and excellent sensitivity.SIS-C demonstrated very good internal consistency,reliability and validity.SDQ was good in internal consistency,with excellent credibility and validity.RBS-R showed good internal consistency,reliability and validity. Conclusion SDQ and RBS-R cover both body functions,and activities and participation,SIS-C covers activity and par-ticipation,and environmental factors,while VABS solely assesses activities and participation.In terms of body functions,the assessment items primarily focus on mental functions(b130-b189)and movement functions(b750-b799).For activities and participation,the tools assess content across eight domains of functioning.Regarding en-vironmental factors,the assessment content mainly includes products and technology for education(e130),as well as design,construction and building products and technology of buildings for public use(e150).VABS,SIS-C,SDQ,and RBS-R are all norm-referenced measures,with moderate to excellent internal consistency,and good to excellent reliability and validity.

Background: Both type 1 diabetes mellitus (T1DM) and metabolic syndrome (MetS) are associated with an elevated risk of morbidity and mortality yet with increasing heterogeneity. This study primarily aimed to evaluate the prevalence of MetS among adult patients with T1DM in China and investigate its associated risk factors, and relationship with microvascular complications. Methods: We included adult patients who had been enrolled in the Guangdong T1DM Translational Medicine Study conducted from June 2010 to June 2015. MetS was defined according to the updated National Cholesterol Education Program criterion. Logistic regression models were used to estimate the odds ratio (OR) for the association between MetS and the risk of diabetic kidney disease (DKD) and diabetic retinopathy (DR). Results: Among the 569 eligible patients enrolled, the prevalence of MetS was 15.1%. While female gender, longer diabetes duration, higher body mass index, and glycosylated hemoglobin A1c (HbA1c) were risk factors associated with MetS (OR, 2.86, 1.04, 1.14, and 1.23, respectively), received nutrition therapy education was a protective factor (OR, 0.46). After adjustment for gender, age, diabetes duration, HbA1c, socioeconomic and lifestyle variables, MetS status was associated with an increased risk of DKD and DR (OR, 2.14 and 3.72, respectively; both P<0.05). Conclusion Although the prevalence of MetS in adult patients with T1DM in China was relatively low, patients with MetS were more likely to have DKD and DR. A comprehensive management including lifestyle modification might reduce their risk of microvascular complications in adults with T1DM.

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

Objective:To explore the characteristics of Lowe syndrome, as well as OCRL1 gene mutation and its relationship with phenotype. Methods:Children diagnosed with Lowe syndrome during their visit to Nanfang Hospital of Southern Medical University (4 cases) and the First Affiliated Hospital of Sun Yat-sen University (3 cases) from January 2009 to January 2019 were included. The clinical data and peripheral blood samples were collected, and the sequence analysis of OCRL1 was performed after genomic DNA extraction. Then the clinical features of the children and the relationship between OCRL1 mutation and clinical phenotype were analyzed. Results:Seven patients from 6 families who presented with Lowe syndrome were included. All of them had different degrees of ocular-neural-renal symptoms. Six cases from 5 families had congenital cataract and neonatal hypotonia, one case from another family only had a thin lens without cataract. Four cases had nystagmus and 2 cases had glaucoma. Six cases from 6 families had psychomotor retardation and had proximal tubular impairment, included low-molecular-weight proteinuria (LMWP). Serum aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) were increased in all 6 patients who were tested. Mutations of OCRL1 were detected in all the 6 families, which located in exon 10, 13, 16, 18, 22 and 23 respectively. The mutations of c.891 G>T, c.1682_1683insAA and c.2564_2567del are novel. Conclusions:Three OCRL1 novel mutations in 6 Chinese Lowe syndrome families are identified. The clinical manifestations in different mutations of OCRL1 are heterogeneous. The mutations of c.891 G>T in exon 10 without congenital cataract is rare in clinical.

From May 2014 to January 2018, 6 patients with severe flexion contracture deformity caused by palmar cicatricial hyperplasia of adjacent 2 or 3 fingers were admitted to the Yidu Central Hospital of Weifang. There were 4 males (8 fingers) and 2 females (5 fingers), aged 13-51 years.The degrees of flexion of proximal interphalangeal joint of affected fingers and metacarpophalangeal joint were respectively 60-90°and 60-80°, and the total degree of passive extension of metacarpophalangeal joint, proximal interphalangeal joint, and distal interphalangeal joint was from -180 to -120°. After scar resection, tendon release, and extension of affected fingers, bone and/or tendon were exposed, and the wound area was 4.0 cm×2.0 cm-8.5 cm×4.0 cm.The wound was repaired with trifoliated flap composed of fibular flap of great toe, abdominal flap of the second toe, and plantar metatarsal flap, with flap area of 4.5 cm×2.5 cm-9.0 cm×4.5 cm.The plantar metatarsal wound of the donor site was sutured directly, and the remaining wound was repaired with full-thickness skin graft from the outside of the thigh. All the wounds of patients were healed. All flaps survived and had good blood circulation without vascular crisis after operation.During follow-up of 6 months to 2 years, the flaps were with good appearance, no swelling, similar in color to the surrounding skin, soft in texture, good in sensations of touch and pain, and the distance of discrimination of 6-8 mm. The active and passive flexion and extension of the affected fingers were good, and there was no dysfunction in the donor site of foot, only with slight scar. The article showed that trifoliated flap from toe web is one of the best methods to repair the severe contracture flexion deformity of fingers caused by severe cicatricial hyperplasia of palmar side, especially the soft-tissue defect of the skin after the cicatricial hyperplasia of adjacent 2 or 3 fingers is removed.

The influence of β-cell function on cardiovascular autonomic neuropathy (CAN), an important diabetes-related complication, is still unclear. In this study, we aimed to investigate the association between residual β-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN+ group (diabetic patients with CAN, n = 20) and a CAN- group (diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured. Homeostasis model assessment-beta cells (HOMA-B) and HOMA-insulin resistance (IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN- group, the CAN+ group had significantly lower fasting plasma insulin (6.60 ± 4.39 vs 10.45 ± 7.82 μ/L, P = 0.029), fasting C-peptide (0.51 ± 0.20 vs 0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B (21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio (r = 0.24, P = 0.043) and the 30:15 test (r = 0.26, P = 0.023). Further analysis showed that fasting C-peptide (OR: 0.041, 95% CI 0.003-0.501, P = 0.012) and HOMA-B (OR: 0.965, 95% CI 0.934-0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values < 0.67 nmol/L were more likely to have CAN than those with C-peptide levels ≥0.67 nmol/L (OR: 6.00, 95% CI 1.815-19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased β-cell function was closely associated with CAN in this population.
Adult ; Asian Continental Ancestry Group ; Blood Glucose ; analysis ; Diabetes Mellitus, Type 2 ; complications ; metabolism ; Diabetic Neuropathies ; etiology ; Fasting ; physiology ; Female ; Glucose ; metabolism ; Humans ; Insulin ; metabolism ; Insulin Resistance ; physiology ; Insulin-Secreting Cells ; metabolism ; Male ; Middle Aged

Objective: To explore the clinical and pathological features and mutational types and their relations with WT1 mutation-associated nephropathy (WT1MAN). Methods: The clinical and pathological data and the results of WT1 mutation analysis of the cases from Nanfang Hospital of Southern Medical University, Sun Yat-sen Memorial Hospital and The First Affiliated Hospital of Sun Yat-sen University whom we recruited recently and reported during the last ten years were analyzed. Results: Totally, 20 cases (6 males and 14 females), included 5 newly diagnosed cases, were recruited. (1) Ten children were diagnosed with Denys-Drash syndrome (DDS): The median onset age of proteinuria was 1 year and 7 months. Diffuse mesangial sclerosis (DMS) were revealed in 3 cases, minimal lesions (MCD) in 4 cases, and focal segmental glomerulosclerosis (FSGS) in 1 case; renal pathology was not available in the other 2 cases. Glomerular basement membrane (GBM) thickening was observed in 2 cases. Calcineurin inhibitors (CNIs) were administered in 5 cases, complete remission of proteinuria was observed in 3 cases, partial remission in the other 2 cases. Genetic analysis revealed that six cases had WT1 missense mutation, 3 had nonsense mutation, and 1 had frameshift mutation. (2) Two cases were diagnosed with Frasier syndrome (FS): proteinuria was observed at 1 year and 1 month of age and 1 year and 9 months of age, respectively. FSGS with GBM layering were observed in both cases. They progressed to ESRD at 1 year and 6 months of age and 6 years and 6 months of age, respectively. CNI was tried in 1 case with partial proteinuria remission. Both patients were detected to have WT1 splice mutation. (3) Isolated nephropathy (IN) was observed in 8 cases: three had splice mutation, 5 had missense mutation. Of the 3 patients with splice mutation, one was found to have nephropathy and renal failure at the age of 5 months. The other two cases (1 was FSGS and another MCD), both had GBM layering. CNIs were tried on both of them, one got partial remission with normal renal function at the age of fourteen years, the other one had no response and entered ESRD at the age of 6 years and 9 months. Of the 5 cases with missense mutation, 3 had DMS, 2 of them entered ESRD within 6 months of age, another case had DMS entered ESRD at 9 years of age. One case with FSGS, was treated with CNIs and got complete remission. Conclusions Slow progression (7/10) nephropathy was observed in DDS patients. Missense mutation (11/20) was the most common type of WT1 variants, followed by splice mutation (5/20) in this group of patients. Early onset nephropathy (4/5), rapid progression (4/5) and GBM layering (4/4) wereobserved in patients with splice mutation. CNI was effective in reducing or even eliminating proteinuria in WT1 MAN patients (8/9).

Endothelial to mesenchymal transition(EndMT) plays a major role during organism development, and also contributes to several adult cardiovascular diseases.EndMT-derived fibroblast-like cells are common in atherosclerotic lesions.Pro-atherosclerosis factors, such as oxidative stress, hypoxia, inflammatory cytokines and oscillatory fluid shear stress can promote EndMT.EndMT is closely associated with plaque calcification, and unstable and ruptured plaque phenotype that may prone to cause clinical events.EndMT may be another key step in the prevention and treatment of atherosclerosis.Here, we reviewed the role played by endothelial-to-mesenchymal transition(EndMT) and its key regulators in atherosclerosis.

Objective: To observe the effect of oxidative-low density lipoprotein (ox-LDL) injured human leukemia mononuclear cells (THP-1) adhesion to human umbilical vein endothelial cells (HUVECs)in vitrowith the intervening function of dredging collateral drug, tongxinluo (TXL) and ginsenoside (Rb1). Methods: Cell injury was induced by ox-LDL treatment. The cells were divided into 4 groups:①Normal control group,②Injury model group, the cells were cultured by ox-LDL,③TXL group, the cells were cultured with both ox-LDL and TXL,④Rb1 group. HUVEC viability was measured by MTS assay, adherence rate of THP-1 cells to HUVECs was tested by vital cell staining. The contents of monocyte chemoat-tractant protein (MCP-1), soluble vascular cell adhesion molecule (sVCAM-1), soluble inter vascular cell adhesion molecule-1 (sICAM-1) and E-selectin in HUVEC conditioned medium were detected by ELISA; protein expressions of CCR2, VLA4 and Mac-1 in THP-1 cells were examined by Western blot analysis. Results: Compared with Control group, HUVEC viability was decreased in Injury model group (100 ±1.31) % vs(75.57 ± 1.02) %, while increased in both TXL and Rb1 groups (99.25 ± 1.40) % and (99.48 ± 2.15) %; Injury model group showed elevated adherence rate of THP-1 cells to HUVECs, while the adherence rates were reduced in both TXL and Rb1 groups. Compared with Injury model group, TXL group and Rb1 group showed decreased levels of MCP-1, sVCAM-1, sICAM-1 and E-selectin in HUVEC conditioned medium; decreased protein expressions of CCR2, VLA4 and Mac-1 in THP-1 cells. Conclusion: TXL and Rb1 could protect HUVECs, reduce ox-LDL injury induced vascular endothelial cell adhesion and decrease relevant receptor expression in monocytes; therefore, inhibit injured monocytes adherence to vascular endothelial cells.