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.

Transient receptor potential vanilloid-1(TRPV1) channel is a non-selective ligand-gated cationic channel with multiple activation mechanisms in the transient receptor potential subfamily. In recent years, a large number of studies have found that TRPV1 plays an important role in the field of cardiovascular diseases such as hypertension and atherosclerosis. With the in-depth study of traditional Chinese medicine, it has been found that Chinese medicine monomers and their active components can activate or inhibit TRPV1 channels, which has certain potential in the study of cardiovascular diseases. In this paper, the role of TRPV1 channel in cardiovascular diseases and the research progress of traditional Chinese medicine prevention and treatment of cardiovascular diseases based on TRPV1 channel are reviewed, in order to provide new ideas for prevention and treatment of cardiovascular system diseases.

Objective:To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria ( N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods:The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results:The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion:The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Smart manufacturing still remains critical challenges for pharmaceutical manufacturing. Here, an original data-driven engineering framework was proposed to tackle the challenges. Firstly, from sporadic indicators to five kinds of systematic quality characteristics, nearly 2,000,000 real-world data points were successively characterized from Ginkgo Folium tablet manufacturing. Then, from simplex to the multivariate system, the digital process capability diagnosis strategy was proposed by multivariate C_pk integrated Bootstrap-t. The C_pk of Ginkgo Folium extracts, granules, and tablets were discovered, which was 0.59, 0.42, and 0.78, respectively, indicating a relatively weak process capability, especially in granulating. Furthermore, the quality traceability was discovered from unit to end-to-end analysis, which decreased from 2.17 to 1.73. This further proved that attention should be paid to granulating to improve the quality characteristic. In conclusion, this paper provided a data-driven engineering strategy empowering industrial innovation to face the challenge of smart pharmaceutical manufacturing.

Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10^-15 g/L, and the quantitative limit reached 1.0 × 10^-13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (K_D) of 5.701 × 10^-11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a K_D of up to 4.181 × 10^-10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Objective:To analyse the factors associated with the selection of breast- conserving surgery in early female patients with breast cancer.Methods:The targeted patients were females diagnosed with early-stage breast cancer and received surgical treatment at Fujian Provincial Hospital from January 1, 2015, to December 31, 2019. The targeted patients' clinical, demographic, and social-economic characteristics were extracted from the hospital health information system. Relevant information of their attending surgeons was collected through a smart-phone based self-respond online survey. We performed multivariate logistic regression to explore the associated factors with breast-conserving surgery (BCS) decision-making.Results:The age of the patient and attending surgeon and the economic development level of the patient's residence area were the associated factors with BCS decision-making of female early-stage breast cancer. By controlling the other factors unchanged, patients from middle-income areas were more likely to accept BCS ( OR=1.91, 95% CI: 1.01-3.62, P=0.05) than those from low-income areas. When the attending surgeon was at the average age of 45 years old, increasing of 1 year age of patient led to 4% decrease of the probability of BCS (95% CI: -0.07 - -0.01, P=0.01). When the patient was at the average age of 52 years old, increasing of 1 year age of the attending surgeon reduced 10% of the probability of BCS (95% CI: -0.19 - -0.01, P=0.03). The interaction effects related to the age of attending surgeon and patient for some observations to choose BCS were statistically significant, and the average interaction effect was 0.06% ( Z=2.11, s x =0.000 3, P<0.05). Conclusion:To promote breast-conserving surgery in the indicated early female patients with breast cancer, it is necessary to consider factors from both the surgeons and the patients.

Objective Evaluation of the effect of manual reduction with small external fixation on the treatment of elderly Barton fractures.Methods A total of 244 elderly patients with Barton fractures were divided into conservative group (n=126) and operation group (n=118) according to random number table. The conservative group was treated by with manual reduction with small external fixation, and the operation group was treated with open reduction and internal fixation. The complications of the patients, the time of fracture healing, hospitalization time and treatment cost were recorded.The wrist function was evaluated by PRWE wrist score system and Wrightington wrist function score system.The clinical efficacy was evaluated by Gartland-Werley Colles fracture evaluation method.Results The excellent and good effect rate was 91.3% (115/126) in the conservative group and 97.5% (115/118) in the operation group. There was no significant difference between the two groups(χ2=0.857,P=0.354). One year, 6 months, 3 months and 6 weeks after treatment, in the conservative group, the PRWE score (10.4 ± 7.9, 19.1 ± 8.0, 40.5 ± 7.8, 55.7 ± 8.1vs. 80.8 ± 8.2,F=113.665), wrightington score (8.2 ± 3.7, 13.2 ± 4.0, 21.4 ± 3.9, 26.3 ± 4.2vs. 30.1 ± 4.2,F=121.348) were significantly lower than those before treatment (P<0.01). And in the operation group, the PRWE score (10.2 ± 7.8, 15.0 ± 8.0, 26.5 ± 8.0, 44.7 ± 8.2vs. 79.6 ± 8.6,F=81.411), Wrightington score (8.1 ± 3.8, 12.1 ± 4.0, 16.5 ± 4.0, 20.6 ± 4.3vs. 29.8 ± 4.6,F=69.113) were significantly lower than those before treatment (P<0.01). But there was no significant difference in PRWE score and Wrightington scores between the two groups after treatment (t=0.149, 0.104,P=0.881, 0.917, respectively). In the conservative group, the hospitalization time (5.28 ± 2.10 dvs. 12.8 ± 2.21d,t=25.260) was significantly shorter than that of the control group (P<0.01), and the treatment cost (3.26 ± 0.93 thousandvs. 28.66 ± 1.04 thousand,t=200.369) was significantly lower than that in the control group (P<0.01). The overall incidence of complication was 8.7% (11/126) in the conservative group and 17.8% in the surgery group (21/118). There was significant difference between the two groups(χ2=4.396,P=0.036).Conclusions The manual reduction with small splint external fixation was simple, low cost, small trauma, short hospitalization time, and less complications.

AIM To investigate the effects of Sanqi Huayu Oral Liquid (Notoginseng Radix et Rhizoma,Corydalis Rhizoma) on femoral shaft comminuted fracture caused by trauma in perioperative period of high-risk groups.METHODS One hundred and twenty patients meeting the inclusion criteria were randomly and equally divided into treatment group and control group.The control group was treated by low molecular weight heparin calcium injection,while the treatment group was additionally given Sanqi Huayu Oral Liquid.Two groups' levels of serum IL-6,TNF-α and D-D were detected on pre-operation and the 1 st,3rd,7th after operation,respectively.Additionally,the adverse drug reactions were also observed.RESULTS There were no statistically significant differences in the levels of serum IL-6,TNF-α and D-D between the two groups before operation.The first day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups showed increasing trends,which had similar elevated levels without statistically significant differences.The third day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups presented downward trends,but those in the treatment group were decreased more markedly with statistically significant differences.Furthermore,the seventh day after operation,the levels of serum IL-6,TNF-α and D-D between the two groups were lower than those before the operation,and these indices in the treatment group were lower than those in the control group with statistically significant differences.CONCLUSION Sanqi Huayu Oral Liquid can not only effectively reduce the levels of serum IL-6,TNF-α and D-D in perioperative period of high-risk groups,but also prevent the formation of deep vein thrombosis.

Objective To analyze the clinically isolated bacterial distribution and drug resistance characteristics in the our hospital during 2016 to provide the pathogenic drug resistance monitoring data for rational bacterial drugs use in clinic.Methods The clinicaly submitted samples were performed the pathogenic bacterial isolation according to the routine method.The isolated pathogens were identified by the Vitek2-Compact system and the drug susceptibility test was performed by adopting the MIC and KB methods.The results were statistically analyzed by adopting the WHONET5.6 software.Results A total of 2 214 non-repeat strains of bacteria were isolated in 2016,including 1 614 strains of Gram-negative bacilli,accounting for 72.9％,600 strains of Gram-positive bacteria,accounting for 27.1 ％.The top five isolated bacteria were Klebsiella pneumoniae,Escherichia coli,Pseudomonas aeruginosa,Acinetobacter baumannii and Staphylococcus aureus.The detection rates of ESBLs producing Escherichia coli and Klebsiella pneumoniae were 51.8％ and 27.6％ respectively.The detection rates of methicillin-resistant Staphylococcus aureus (MRSA) was 26.5％.No vancomycin or linezolid resistant staphylococcal strains were found.Conclusion The main isolated pathogens in our hospital are dominated by Gram-negative bacteria.Hospital should strengthen reasonable and standardized use of antibacterial drugs to reduce the generation of drug resistant bacterial strains.