OBJECTIVE: We aimed to investigate the patterns of fasting blood glucose (FBG) trajectories and analyze the relationship between various occupational hazard factors and FBG trajectories in male steelworkers. METHODS: The study cohort included 3,728 workers who met the selection criteria for the Tanggang Occupational Cohort (TGOC) between 2017 and 2022. A group-based trajectory model was used to identify the FBG trajectories. Environmental risk scores (ERS) were constructed using regression coefficients from the occupational hazard model as weights. Univariate and multivariate logistic regression analyses were performed to explore the effects of occupational hazard factors using the ERS on FBG trajectories. RESULTS: FBG trajectories were categorized into three groups. An association was observed between high temperature, noise exposure, and FBG trajectory ( P < 0.05). Using the first quartile group of ERS1 as a reference, the fourth quartile group of ERS1 had an increased risk of medium and high FBG by 1.90 and 2.21 times, respectively (odds ratio [ OR] = 1.90, 95% confidence interval [ CI]: 1.17-3.10; OR = 2.21, 95% CI: 1.09-4.45). CONCLUSION An association was observed between occupational hazards based on ERS and FBG trajectories. The risk of FBG trajectory levels increase with an increase in ERS.
Humans ; Male ; Adult ; Blood Glucose/analysis* ; China ; Prospective Studies ; Occupational Exposure/adverse effects* ; Risk Factors ; Middle Aged ; Steel ; Fasting/blood* ; Metal Workers ; East Asian People

Investigating the structural characteristics of proton tautomers is of great significance for understanding organic reactions and biochemical processes.In this study,a method based on ion mobility mass spectrometry combined with ab initio molecular dynamics calculations was proposed.The structures of proton tautomers were determined by comparing the experimental and theoretical collision-induced dissociation(CID)mass spectrograms of different proton tautomers.Ion mobility mass spectrometry was used to separate proton tautomerism produced during ionization.The CID mass spectra of each isomer could be obtained after mobility separation.The quantum chemical mass spectrometry(QCXMS)program based on ab initio molecular dynamics calculations was used to calculate the fragmentation process and obtain the theoretical CID mass spectra.The results of experiment and calculation showed that this method effectively solved the issue of difficult identification of proton tautomers.This method was also of great significance for the study of ionization mechanism and organic reaction process using mass spectrometry.

Prediction of the interactions between small molecules and their targets play important roles in various applications of drug development, such as lead discovery, drug repurposing and elucidation of potential drug side effects. Therefore, a variety of machine learning-based models have been developed to predict these interactions. In this study, a model called auxiliary multi-task graph isomorphism network with uncertainty weighting (AMGU) was developed to predict the inhibitory activities of small molecules against 204 different kinases based on the multi-task Graph Isomorphism Network (MT-GIN) with the auxiliary learning and uncertainty weighting strategy. The calculation results illustrate that the AMGU model outperformed the descriptor-based models and state-of-the-art graph neural networks (GNN) models on the internal test set. Furthermore, it also exhibited much better performance on two external test sets, suggesting that the AMGU model has enhanced generalizability due to its great transfer learning capacity. Then, a naïve model-agnostic interpretable method for GNN called edges masking was devised to explain the underlying predictive mechanisms, and the consistency of the interpretability results for 5 typical epidermal growth factor receptor (EGFR) inhibitors with their structure‒activity relationships could be observed. Finally, a free online web server called KIP was developed to predict the kinome-wide polypharmacology effects of small molecules (http://cadd.zju.edu.cn/kip).

Objective:To investigate the clinical value of thromboelastogram in early diagnosis of deep vein thrombosis (DVT) in patients undergoing free flap surgery of lower extremity.Methods:A retrospective study was conducted to analyze the 192 patients undergoing surgical repair of soft tissue defects at lower extremity with free anterolateral femoral flap at Department of Orthopaedics, Tongji Hospital from January 2018 to June 2022. There were 117 males and 75 females, with an age of (45.6±12.7) years and an area of skin defects ranging from 5 cm × 3 cm to 18 cm × 9 cm. The patients were divided into 2 groups according to whether DVT occurred on the first day after surgery. In the DVT group of 22 patients, there were 14 males and 8 females, with an age of (47.7±14.3) years; in the DVT-free group of 170 patients, there were 103 males and 67 females, with an age of (45.3±12.5) years. The 2 groups were compared in terms of reaction time, coagulation time, maximum amplitude and coagulation angle in the thromboelastogram. Diagram of receiver operating characteristic (ROC) curves was used to evaluate the predictive value of thromboelastography in assessing the risk of DVT after surgery.Results:The 2 groups were comparable because there was no significant difference in the baseline information or operation time between them ( P>0.05). The reaction time [(5.21±0.85) min] and coagulation time [(1.12±0.30) min] in the DVT group were significantly shorter than those in the DVT-free group [(6.48±0.06) min and (1.60±0.03) min], and the maximum amplitude [(71.45±1.17) mm] and coagulation angle [69.54° (64.59°, 76.64°) ] in the DVT group were significantly larger than those in the DVT-free group [(66.63±0.40) mm and 64.92°(54.11°, 74.21°)] (all P<0.05). The optimal cut-off points in the ROC diagram were 5.46 min at reaction time, 1.52 min at coagulation time, 72.31 mm at maximum amplitude and 59.89° at coagulation angle. The sensitivity and specificity of detecting DVT on the first day after surgery were 80.7% and 71.6%, respectively, according to the combination of the best cut-off points in the ROC diagram and all the indexes in the thromboelastogram. Conclusion:Thromboelastogram is of a great value for the diagnosis of lower extremity DVT, and of a positive significance for the prevention of serious complications after surgery in patients undergoing free flap surgery of lower extremity.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg^-1） group， and a Mori Folium water extract （4.0 g·kg^-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.

The Genome Warehouse (GWH) is a public repository housing genome assembly data for a wide range of species and delivering a series of web services for genome data submission, storage, release, and sharing. As one of the core resources in the National Genomics Data Center (NGDC), part of the China National Center for Bioinformation (CNCB;https://ngdc.cncb.ac.cn), GWH accepts both full and partial (chloroplast, mitochondrion, and plasmid) genome sequences with different assembly levels, as well as an update of existing genome assemblies. For each assembly, GWH collects detailed genome-related metadata of biological project, biological sample, and genome assembly, in addition to genome sequence and annotation. To archive high-quality genome sequences and annotations, GWH is equipped with a uniform and standardized procedure for quality control. Besides basic browse and search functionalities, all released genome sequences and annotations can be visualized with JBrowse. By May 21, 2021, GWH has received 19,124 direct submissions covering a diversity of 1108 species and has released 8772 of them. Collectively, GWH serves as an important resource for genome-scale data management and provides free and publicly accessible data to support research activities throughout the world. GWH is publicly accessible at https://ngdc.cncb.ac.cn/gwh.

BackgroundThe influence of different right ventricular lead locations on ventricular arrhythmias (VTA) in patients with a cardiac resynchronization therapy (CRT) is not clear. This study aimed to evaluate the influence on VTA in patients with a CRT when right ventricular lead was positioned at the right ventricular middle septum (RVMS) and the right ventricular apical (RVA).

MethodsA total of 352 patients implanted with a CRT-defibrillator (CRT-D) between May 2012 and July 2016 in the Department of Cardiology of Anhui Provincial Hospital were included. Two-year clinical and pacemaker follow-up data were collected to evaluate the influence of the right ventricular lead location on VTA. Patients were divided into the RVMS group (n = 155) and the RVA group (n = 197) based on the right ventricular lead position. The VTA were compared between these two groups using a Kaplan-Meier curve and Cox multivariate analysis.

ResultsWhen the left ventricular lead location was not considered, RVMS and RVA locations did not affect VTA. However, the subgroup analysis results showed that when the left ventricular lead was positioned at the anterolateral cardiac vein (ALCV), the RVMS group had an increased risk of ventricular arrhythmias and appropriate defibrillation (hazard ratio [HR] = 3.29, P = 0.01 and HR = 4.33, P < 0.01, respectively); when the left ventricular lead was at the posterolateral cardiac vein (PLCV), these risks in the RVMS group decreased (HR = 0.45, P = 0.02 and HR = 0.33, P < 0.01, respectively), and when the left ventricular lead was at the lateral cardiac vein, there was no difference between the two groups. In regard to inappropriate defibrillation, there was no significant difference among all these groups.

ConclusionsWhen the left ventricular lead was positioned at ALCV or PLCV, the right ventricular lead location was associated with VTA and appropriate defibrillation after CRT. Greater distances between leads not only improved cardiac function but also may reduce the risk of VTA.

OBJECTIVETo investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection.

METHODSThe Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant.

RESULTSAfter EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant inhibitory effect on the proliferation of Caco-2 cells in a dose-dependent manner. The survival rates of the cells were significantly lower than those in the control group (P<0.05). The EPA treatment (100 and 200 μmol/L) groups had a significant increase in cell apoptosis rate compared with the control group (P<0.05). The 6- and 12-hour E.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (P<0.05). The Caco-2 cells treated with E.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated Caco-2 cells (P<0.05). The Caco-2 cells treated with E.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed a reduction in the secretion of TNF-α with the increasing concentration of EPA and had significantly lower secretion than the Caco-2 cells treated with E.coli LF82 alone (P<0.05).

CONCLUSIONSEPA can effectively prevent the destruction of tight junction of intestinal epithelial cells induced by E.coli LF82 infection and inhibit the secretion of inflammatory factors. Therefore, it has a certain protective effect on intestinal mucosal barrier.

Apoptosis ; drug effects ; Caco-2 Cells ; Eicosapentaenoic Acid ; pharmacology ; Escherichia coli ; pathogenicity ; Humans ; Intestinal Mucosa ; metabolism ; microbiology ; RNA, Messenger ; analysis ; Tight Junctions ; drug effects ; Tumor Necrosis Factor-alpha ; secretion ; Zonula Occludens-1 Protein ; genetics

Objective To improve the load resistance ability of students in teenager aviation schools and carry out specialized training for the body situation and shape of students.Methods We selected students from 14 teenager aviation schools and measured their height,weight,and the circumferences of necks,chests,upper-arms,waists,hips,and thighs.We compared the data of these students from different areas and the parameters were analyzed statistically by correlation analysis.Results Totally 411 students from 6 southern schools and 403 students from northern schools were investigated.Their average body height,weight and body mass index (BMI) were (172.3 ± 4.39) cm,(62.7 ± 7.3) kg,and (21.1 ± 2.23)kg/m2 respectirely.Students from northern schools were taller and heavier than those from southern schools (P ＜ 0.05).There was no difference between students from northern and southern schools in BMI.Compared with the domestic average levels of height,weight and chest circumference of teenagers aged 14 to 17,students of teenager aviation schools were higher,but there was no difference in weight or chest circumference.The average circumferences of the chest,neck,left upper-arm,right upper-arm,waist,hip,left thigh and right thigh were (83.1 ± 5.06),(34.7 ±3.07),(25.2±2.33),(25.5 ±2.30),(73.4 ±6.73),(89.7 ±5.89),(50.1 ±5.22),and (50.2 ±5.27)cm,respectively.According to the data,students from northern schools had a bigger chest circumference and thigh circumference but a smaller neck circumference and upper-arms circumference than those from southern schools (P ＜ 0.05).The correlation coefficient between BMI and the circumferences of the chest,neck,left upper-arm,right upperarm,waist,hip,left thigh and right thigh was 0.2201,0.1066,0.2466,0.2499,0.2291,0.2149,0.2299,0.2264,respectively.All of them were statistically significant (P ＜ 0.0001).Conclusion Load resistance related parameters of students in teenager aviation schools are not different from the domestic levels,which points to the urgent need for load resistance ability training for these students.Some parameters vary between areas.BMI is positively related to those load resistance parameters.Based on regional variations and regularities found in this study,specialized load resistance ability training could be made more efficient.