Objective:To explore the association between the variability of triglyceride glucose index (TyG) and the risk of type 2 diabetes mellitus(T2DM).Methods:This study was a retrospective cohort study. A total of 22 929 community-dwelling elderly (aged≥60 years) who received annual health check-ups in Kunshan city of Suzhou Municipality during 2014 to 2021 were enrolled in the study. Fasting triglycerides and blood glucose were measured during annual physical check-ups and the TyG was calculated, the standard deviation of TyG measurements in three consecutive physical check-ups was used as the indicatior of TyG long-term variability. According to the quartile of TyG long-term variability, the study subjects were divided into four groups, namely Q 1 (0-0.14), Q 2 (>0.14-0.22), Q 3 (>0.22-0.33), Q 4 (>0.33-1.90). The outcome variable was the occurrence of T2DM. The relationship between TyG variability and T2DM incidence was analyzed by multivariate Cox regression. Results:In the study cohort 11 518 (50.2%) were females and the mean age was (67.42±5.35) years. By the end of follow-up, 2 934 cases of new T2DM were diagnosed, with an oveall incidence rate of 12.8%. After adjusting for multiple confounders and average TyG, long-term variability of TyG was significantly associated with T2DM risk ( HR=1.83, 95% CI: 1.51-2.20). The risk of T2DM in Q 4 group was significantly higher than that in Q 1 group ( HR=1.33, 95% CI: 1.19-1.47). Kaplan-Meier survival curve showed that long-term variability of TyG was significantly correlated with the cumulative risk of T2DM incidence ( P<0.001). Conclusions:TyG variability is an independent risk factor for T2DM, suggesting that attention should be paid not only to specific time-point TyG levels but also to TyG fluctuation for early identification of T2DM risk.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system has been widely used for genome engineering and transcriptional regulation in many different organisms. Current CRISPR-activation (CRISPRa) platforms often require multiple components because of inefficient transcriptional activation. Here, we fused different phase-separation proteins to dCas9-VPR (dCas9-VP64-P65-RTA) and observed robust increases in transcriptional activation efficiency. Notably, human NUP98 (nucleoporin 98) and FUS (fused in sarcoma) IDR domains were best at enhancing dCas9-VPR activity, with dCas9-VPR-FUS IDR (VPRF) outperforming the other CRISPRa systems tested in this study in both activation efficiency and system simplicity. dCas9-VPRF overcomes the target strand bias and widens gRNA designing windows without affecting the off-target effect of dCas9-VPR. These findings demonstrate the feasibility of using phase-separation proteins to assist in the regulation of gene expression and support the broad appeal of the dCas9-VPRF system in basic and clinical applications.
Humans ; Transcriptional Activation ; RNA, Guide, CRISPR-Cas Systems ; Gene Expression Regulation ; CRISPR-Cas Systems/genetics*

BACKGROUND: Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults. METHODS: From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines. RESULTS: The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients. CONCLUSION The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.
Humans ; Diabetes Mellitus, Type 2/diagnosis* ; Cross-Sectional Studies ; Mutation ; Prevalence ; Phenotype

BACKGROUND: Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes. METHODS: We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS). RESULTS: In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was l.89 with 95% confidence interval (95% CI) l.46-2.45 (HbAlc-CV l.47, 95% CI l.26-l.72; HVS l.67, 95% CI l.34-2.09). CONCLUSIONS High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes.
Humans ; Adult ; Diabetes Mellitus, Type 2/complications* ; Glycated Hemoglobin ; Cardiovascular Diseases/etiology* ; Risk Factors ; Blood Glucose

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Objective The present study aimed to investigate the molecular characterizations and virulence factors mediating adhesion of S.agalactiae.Methods All the 6 GBS strains from maternity ward, 4 isolated from the blood of neonates and 2 isolated from the vaginal secretions of their mothers, were performed antimicrobial susceptibility tests through disk diffusion method,and analyzed by multilocus sequence typing(MLST)and pulse field gel electrophoresis typing(PFGE)to determine the relationship between the strains and whether it was nosocomial infection or not.The S.agalactiae isolates were subjected to capsular genotyping by PCR.Determinants of adherence factors were also detected by PCR and sequencing,including surface proteins and pilus-like structures.Results The results of antimicrobial susceptibility tests of 7 /13/37/66 are the same,while 142 and 158 are the same but different from the other 4 strains.The MLST results indicate that 7 /13/37/66 are of the same sequence type ST-12,while 142 and 158 are ST-19.PFGE results have further proved that 7/13/37/66 are of the same clone type,and 142 and 158 were another clone type.The strains of 7/13/37/66 are serotype Ib,and contain bac,bca,and alp2/3 genes,while 142 and 158 are serotype III and contain ε gene.All the six strains contain PI-1 and PI-2a genes.Conclusions There are not only vertical but also horizontal transmissions in the 4 cases,which may be a nosocomial infection event.Six strains all contained primary adhesion factor of S.agalactiae: surface proteins and pilus-like structures,which indicates that all the 6 strains has a strong toxicity in adhesion and spread.The hospitals should reinforce the prenatal examination of S.agalactiae and control the nosocomial infection.

Objective To explore the clinical application of case teaching method combined with clinical pathway in pediatrics teaching.Methods 103 students in pediatric practice from September 2016 to September 2017 were enrolled as the study object,who were divided randomly into observation group (52 cases) and control group (51 cases).Routine teaching method was adopted in the control group,while case teaching method combined with clinical pathway was adopted in the observation group.In addition,100 cases of children in need of rescue were selected for each group and the students were divided into two or three in a group to participate in the rescue.If the student could complete the rescue with the assistance of supervisor,he will be considered as playing a leading role in rescue process.Otherwise,another supervisor would join to lead the rescue,and the student would assist by the side,who will be considered as playing an auxiliary role in rescue process.The results of examination,classroom participation,homework,the rescue performance and the satisfaction of teaching were compared between two groups.Results The scores of theoretical course,case analysis and skill operation in the observation group was significantly higher than that of the control group (P＜0.05).The scores of classroom attendance,classroom activity and homework quality in the observation group was significantly higher than that of the control group (P＜0.05).Success rate of rescue conducted by students in the observation group was significantly higher than that in the control group(P＜0.05).The teaching satisfaction of the observation group was also significantly higher than that of the control group (P＜0.05).Conclusion The application of case teaching method combined with clinical pathway teaching model in pediatrics teaching is effective and worthy of popularizing,which can obviously improve teaching quality,arouse students' interest in teaching process,and improve students' professional quality.

Objective To compare the clinical effects of palpation, ultrasound and electromyography (EMG) guided injection of botuli-num toxin type A (BTX-A) on spastic equinovarus in stroke patients. Methods Stroke patients with equinovarus were randomly assigned to palpation-guided group (n=19), ultrasound-guided group (n=21) and EMG-guided group (n=19). All of the patients received injection of BTX-A 300 U in gastrocnemius, soleus and tibialis posterior, guided in their own ways. They were measured with modified Ashworth Scale (MAS), Physician Rating Scale (PRS), speed of gait, passive range of motion (PROM) of ankle dorsiflexion and eversion before and 2 weeks, 4 weeks, 8 weeks, and 12 weeks after injection. Results Compared with the baseline, all the indexes significantly improved after in-jection in all the groups (P<0.05). Compared with the EMG-guided group, the ultrasound-guided group improved significantly MAS at 4 weeks, PROM of ankle eversion at 4 and 12 weeks (P=0.046, P=0.008, P=0.038). Compared with the palpation-guided group, the ultra-sound-guided group improved significantly in MAS (P=0.015), PRS (P=0.01), PROM of ankle dorsiflexion and eversion (P=0.003, P=0.011) at 4 weeks, in MAS (P=0.002) and PROM of ankle dorsiflexion (P=0.022) at 8 weeks, in MAS (P=0.011) and PROM of ankle ever-sion (P=0.018) at 12 weeks. Compared with the palpation-guided group, the EMG-guided group improved significantly in PRS at 4weeks, PROM of ankle dorsiflexion at 4 and 8 weeks (P=0.048, P=0.08, P=0.026). There was no significantly difference in the variations with the time among 3 groups. Conclusion The correction of equinovarus in stroke patients can be obtained by BTX-A injection with any type of guidance technique. Ultrasound-guided technique is considered a valid alternative, which has a slight advantage over EMG-guided tech-nique. Both the EMG-and ultrasound-guided techniques obtained superior results to palpation-guided technique.