Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

BACKGROUND:Percutaneous vertebroplasty has become the main treatment method for osteoporotic vertebral compression fractures due to its advantages of convenient operation and low trauma.However,the optimal bone cement-vertebral volume ratio has not been determined. OBJECTIVE:To investigate the effect of bone cement-vertebral volume ratio on percutaneous vertebroplasty for osteoporotic vertebral compression fractures. METHODS:The clinical data of 100 patients with single-stage osteoporotic vertebral compression fractures admitted to Xinjiang Bazhou People's Hospital from July 2019 to July 2022 were retrospectively analyzed.All patients received percutaneous vertebroplasty.According to the bone cement-vertebral volume ratio,they were divided into the low volume group(15%≤ratio≤20%)and the high volume group(20%0.05).The vertebral anterior margin height in the low volume group was lower than that in the high volume group at 3 days and 1 year after surgery(P<0.05).The Cobb angle of the injured vertebrae in the low volume group was higher than that in the high volume group at 3 days and 1 year after surgery(P<0.05).(2)There were 10 H-type and 40 O-type bone cement distributions in the low volume group.There were 36 H-type and 14 O-type bone cement distributions in the high volume group,and there was no significant difference in bone cement distributions between the two groups(P<0.05).The bone cement leakage rate in the high volume group and low volume group was 10%and 6%,respectively.(3)It is indicated that both low and high bone cement-vertebral volume ratios can improve postoperative pain and functional dysfunction,but high bone cement-vertebral volume ratio can improve the morphological recovery of injured vertebral,which may be related to the fact that the distribution of bone cement in this group is more H-type.

Objective To investigate the hemodynamic effects of enhanced external counterpulsation(EECP)on cerebral arteries with different stenoses.Methods Zero-dimensional/three-dimensional multiscale hemodynamic models of cerebral arteries with different stenoses were constructed.Numerical simulations of the EECP hemodynamics were performed under different counterpulsation modes to quantify several hemodynamic indicators of the cerebral arteries.Among them,the mean time-averaged wall shear stress(TAWSS)downstream of the stenosis was in the range of 4-7 Pa,a low percentage of TAWSS risk area,and high narrow branch flow were considered to inhibit the development of atherosclerosis and create a good hemodynamic environment.Results For cerebral arteries with 50%,60%,70%,and 80%stenosis,the hemodynamic environment was optimal in counterpulsation mode when the moment of cuff deflation was 0.5,0.6,0.7,and 0.7 s within the cardiac cycle.Conclusions For 50%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.5 s should be selected.For 60%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.6 s should be selected.For 70%or 80%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.7 s should be selected.As stenosis of the cerebral arteries increases,the pressure duration should be prolonged.This study provides a theoretical reference for the EECP treatment strategy for patients with ischemic stroke with different stenoses.

As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

Objective To observe the influence of nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets on pulmonary function and dyspnea symptoms in patients with connective tissue disease-related pulmonary interstitial fibrosis.Methods Patients with connective tissue disease-related pulmonary interstitial fibrosis were divided into treatment group and control group by cohort method.The control group was given basic treatment such as glucocorticoids and immunosuppressants according to the patient's condition;the treatment group was given ethanesulfonate nintedanib soft capsules(100 mg,bid)and tetrandrine tablets(40 mg,tid)on the basis of the control group,and the treatment course was 3 months.The clinical efficacy,severity of dyspnea[modified British Medical Research Council Dyspnea Scale(mMRC)and St.George's Respiratory Questionnaire(SGRQ)],pulmonary function indicators,pulmonary fibrosis score,and blood gas analysis indicators were compared between the two groups,and the safety was assessed.Results A total of 42 cases were included in the treatment group and the control group,respectively.The total effective rates of the treatment group and the control group were 92.86％(39 cases/42 cases)and 76.19％(32 cases/42 cases)respectively(P＜0.05).After treatment,the mMRC scores of the treatment group and the control group were(1.43±0.27)and(1.69±0.31)points;the SGRQ scores were(46.51±4.39)and(51.08±4.76)points;the forced expiratory volume in one second(FEV1)values were(64.96±6.55)％and(58.67±5.01)％;the fibrosis scores were(1.12±0.14)and(1.26±0.18)points;the partial pressure of arterial oxygen values were(80.31±7.03)and(75.02±6.94)mmHg.The above indexes of the treatment group were compared with those of the control group,and the differences were statistically significant(all P＜0.05).There were no adverse drug reactions in the treatment group,and the main adverse drug reactions in the control group were gastrointestinal discomfort.The total incidence rates of adverse drug reactions in the treatment group and the control group were 0 and 2.38％,respectively(P＞0.05).Conclusion Compared with basic treatment,nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets can better improve the pulmonary fibrosis degree and dyspnea degree in patients with connective tissue disease-related pulmonary interstitial fibrosis,and delay the decline of pulmonary function of patients.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Background: We aimed to investigate the characteristics of pediatric ulcerative colitis (UC) at diagnosis in Korea. Methods: This was a multicenter, registry-based, inception cohort study conducted in Korea between 2021 and 2023. Children and adolescents newly diagnosed with UC < 18 years were included. Baseline clinicodemographics, results from laboratory, endoscopic exams, and Paris classification factors were collected, and associations between factors at diagnosis were investigated. Results: A total 205 patients with UC were included. Male-to-female ratio was 1.59:1, and the median age at diagnosis was 14.7 years (interquartile range 11.9–16.2). Disease extent of E1 comprised 12.2% (25/205), E2 24.9% (51/205), E3 11.2% (23/205), and E4 51.7% (106/205) of the patients. S1 comprised 13.7% (28/205) of the patients. The proportion of patients with a disease severity of S1 was significantly higher in patients with E4 compared to the other groups (E1: 0% vs. E2: 2% vs. E3: 0% vs. E4: 24.5%, P < 0.001). Significant differences between disease extent groups were also observed in Pediatric Ulcerative Colitis Activity Index (median 25 vs. 35 vs. 40 vs. 45, respectively, P < 0.001), hemoglobin (median 13.5 vs.13.2 vs. 11.6 vs. 11.4 g/dL, respectively, P < 0.001), platelet count (median 301 vs. 324 vs. 372 vs. 377 × 103 /μL, respectively, P = 0.001), C-reactive protein (median 0.05 vs. 0.10 vs. 0.17 vs. 0.38 mg/dL, respectively, P < 0.001), and Ulcerative Colitis Endoscopic Index of Severity (median 4 vs. 4 vs. 4 vs. 5, respectively, P = 0.006). No significant differences were observed in factors between groups divided according to sex and diagnosis age. Conclusion This study represents the largest multicenter pediatric inflammatory bowel disease cohort in Korea. Disease severity was associated with disease extent in pediatric patients with UC at diagnosis.

Severe acute pancreatitis (SAP) is a serious disease commonly encountered in the emergency department and can precipitate systemic inflammatory response syndrome and multiple organ dysfunction syndrome with high morbidity and mortality. However, its etiology and pathogenesis are complex and have not been fully elucidated. Clinical studies can provide some data on the etiology, pathophysiology, and outcome associated with the disease. However, research on SAP cannot be carried out in humans directly for ethical considerations. It is very important to establish an appropriate animal model of SAP to elucidate its pathogenesis and seek innovative therapeutic methods. In this paper, we reviewed the latest research progress at home and abroad in animal models of SAP over the past several years.

Objective:To investigate the therapeutic effect of Ningmitai Capsules(NMT)on chronic prostatitis/chronic pel-vic pain syndrome(CP/CPPS)and its action mechanism.Methods:We equally randomized fifteen 6-8 weeks old male Wistar rats into a sham operation,a model control and an NMT group,and established a CP/CPPS model in the rats by intra-prostatic injection of complete Freund adjuvant(CFA).We treated the rats in the sham operation and model control groups by injection of aseptic phosphate buffer saline(PBS)and 50 μl complete Freund adjuvant(CFA),respectively,into the ventral lobe of the prostate followed by gavage with purified water from the second day after surgery,and those in the NMT group with 50 μl CFA injected into the ventral lobe of the prostate followed by gavage with 3 ml NMT suspension at 400 mg/kg/d from the second day after surgery.After 4 weeks of treatment,we killed the animals and collected the serum and prostatic tissue samples for evaluation of the severity of prostatitis by histopathological grading of chronic prostatitis through HE staining,determination of the mRNA expressions of inflammatory factors by real-time quantita-tive PCR,measurement of the activities of related antioxidant enzymes with testing kits,and detection of the expressions of the related targets in the signaling pathways by Western blot.Results:Histopathological examination revealed different degrees of inflammatory cell infiltration in the mesenchyme,inflammatory vacuoles,irregularly shaped acini in the model control group,with a significantly higher inflammation score than in the sham operation group(P＜0.05),and reduced infiltrating lymphocytes,inflammatory vacuoles and inflammation score in the NMT group compared with those in the model controls(P＜0.05).Compared with the rats in the sham operation group,the model controls showed remarkably up-regulated expressions of IL-1 β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),decreased contents of superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)(P＜0.05),and increased content of malondialdehyde(MDA)(P＜0.05).Compared with the model controls,the rats treated with NMT exhibited markedly reduced expressions of IL-1β,IL-6,IL-10,IL-17A,TNF-α and IFN-γ(P＜0.05),increased contents of SOD,CAT and GSH-Px(P＜0.05),decreased content of MDA(P＜0.05),up-regulated expressions of nuclear factor red 2-related factor 2(n-Nrf2)and heme oxygenase-1(HO-1)(P＜0.05),and down-regulated expression of NF-κB P-P65(P＜0.05).Conclusion:NMT plays anti-oxidation and anti-inflammation roles in the pathogenesis of CP/CPPS,possibly by activation of Nrf2 and suppression of NF-κB signaling pathways.