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:Sepsis is one of the main causes of mortality in intensive care units(ICUs).Early prediction is critical for reducing injury.As approximately 36%of sepsis occur within 24 h after emergency department(ED)admission in Medical Information Mart for Intensive Care(MIMIC-IV),a prediction system for the ED triage stage would be helpful.Previous methods such as the quick Sequential Organ Failure Assessment(qSOFA)are more suitable for screening than for prediction in the ED,and we aimed to find a light-weight,convenient prediction method through machine learning. METHODS:We accessed the MIMIC-IV for sepsis patient data in the EDs.Our dataset comprised demographic information,vital signs,and synthetic features.Extreme Gradient Boosting(XGBoost)was used to predict the risk of developing sepsis within 24 h after ED admission.Additionally,SHapley Additive exPlanations(SHAP)was employed to provide a comprehensive interpretation of the model's results.Ten percent of the patients were randomly selected as the testing set,while the remaining patients were used for training with 10-fold cross-validation. RESULTS:For 10-fold cross-validation on 14,957 samples,we reached an accuracy of 84.1%±0.3%and an area under the receiver operating characteristic(ROC)curve of 0.92±0.02.The model achieved similar performance on the testing set of 1,662 patients.SHAP values showed that the five most important features were acuity,arrival transportation,age,shock index,and respiratory rate. CONCLUSION:Machine learning models such as XGBoost may be used for sepsis prediction using only a small amount of data conveniently collected in the ED triage stage.This may help reduce workload in the ED and warn medical workers against the risk of sepsis in advance.

In order to establish a rapid,specific and sensitive detection method for Streptococcus equi subspecies zooepidemicus(SEZ)and to understand the infection status of SEZ in horses ente-ring China,specific primers were designed and synthesized based on the conserved gene comB of standard strain SEZ(ATCC 43079)in this work.Then,the pMD19-T-comB recombinant plasmid was constructed and used as a standard positive template.After that,the fluorescence-based quantitative PCR(qPCR)detection method based on SYBR Green Ⅰ dye was established.Totally,477 equine entry serum samples from 6 countries,including Netherlands,Belgium,Japan,Germa-ny,Argentina and New Zealand,during 2018 to 2023,were randomly selected and detected for SEZ by the qPCR method.Results showed that the established qPCR method had specific amplification for only SEZ,which illustrated a good specificity.Sensitivity test of the method showed that the limited detection amount was 4.58 X101 copies/μL.And the repeatability test showed that the coef-ficient of variation of intra-batch repeatability was less than 0.5％,while the inter-batch repeat-ability was less than 3.0％,which indicated good repeatability and high stability.Retrospective a-nalysis showed that totally 11 of 477 positive samples were detected,with a relatively low positive rate of 2.31％(11/477).Among them,all the 40 samples from Netherlands in 2018 were negative(0/40).In the samples of 2019,one positive was detected from Belgium(1/20),while all other 36 samples which form Japan and Germany were negative.In the samples of 2021,three samples(3/34)from Japan and one sample(1/20)from Argentina were positive,and all the other 40 samples from the Netherlands were negative.In the samples of 2022,76 samples from Netherlands were all negative.While in the 2023,5(5/126)of 126 samples from Netherlands and one(1/88)of 88 from New Zealand were found positive with SEZ.To summarize,The SYBR Green Ⅰ qPCR method for the diagnosis of SEZ was successfully established,and it could provide necessary technical support for the rapid quarantine of China's entry-exit and port departments,as well as the epidemiological investigation of the disease.

Objectives:To explore the effects of interatrial shunt on cardiac function and clinical prognosis of patients with heart failure with reduced ejection fraction(HFrEF). Methods:This study was a prospective single-arm study.From December 2021 to December 2022,15 consecutive patients with HFrEF from Beijing Anzhen Hospital were enrolled in this study.Interatrial shunt was performed with a D-Shant atrial shunt device.Right heart catheterization was performed before and immediately after device implantation,pulmonary capillary wedge pressure(PCWP),mean right atrial pressure(RAP),interatrial gradient pressure,mean pulmonary artery pressure,total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),cardiac index(CI),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured.Patients were followed-up for 12 months after procedure,changes in cardiac structure and function were evaluated by echocardiography.NYHA classification,6-minute walking distance(6MWD),and Kansas City cardiomyopathy questionnaire(KCCQ)were observed.All-cause mortality and rehospitalization for heart failure served as clinical endpoints. Results:Interatrial shunt procedure was successful in all patients.Compared with preoperative value,PCWP,interatrial gradient pressure,mean pulmonary artery pressure,and TPR were significantly decreased,while Qp/Qs was significantly increased immediately after procedure(all P<0.01).There were no significant changes in RAP,PVR,and CI post procedure(all P>0.05).There were no significant differences in shunt size,shunt velocity,and shunt pressure difference between postoperative immediately and at 12-months follow-up(all P>0.05).At 12 months,left ventricular ejection fraction was significantly higher than baseline level(P<0.05),and there were no significant changes in right atrial diameter and right ventricular fractional area change(both P>0.05).Compared with preoperative status,NYHA classification was improved,KCCQ score was increased,and the number of patients with 6MWD>450 m was increased at 12 months(all P<0.05).N-terminal pro-B-type natriuretic peptide value was significantly decreased at 12 months(P<0.05).No patient died during the 12-months follow-up period,and there were no device-related adverse events.Two patients experienced hospital readmission for heart failure. Conclusions:Implantation of interatrial shunt device could effectively improve hemodynamic parameters in patients with HFrEF and is related to significantly improved cardiac function at 12-months follow-up.

Objective:To investigate the efficacy and safety of liposomal amphotericin B (L-AmB) for the salvage treatment of invasive fungal disease (IFD) in patients with hematological diseases.Methods:Data were retrospectively collected from 80 patients with hematological issues treated with L-AmB between June 2023 and December 2023 after failure of previous antifungal therapy. Baseline patient information, clinical efficacy, and factors affecting the efficacy of L-AmB were analyzed by logistic regression. Moreover, adverse effects associated with L-AmB were evaluated.Results:Among the 80 patients, 9 (11.2%) had proven IFD, 43 (53.8%) had probable IFD, and 28 (35.0%) had possible IFD. The efficacy rate of L-AmB salvage therapy for IFD was 77.5%, with a median daily dose of 3 (range: 1-5) mg·kg -1·d -1 and a median dosing course of 14 (range: 8-25) days. Multivariate logistic regression analysis showed that the disease remission status ( OR=4.337, 95% CI 1.167-16.122, P=0.029) and duration of medication ( OR=1.127, 95% CI 1.029-1.234, P=0.010) were independent factors affecting the efficacy of L-AmB. The incidence of infusion reactions associated with L-AmB, including fever and chills, was 5.0%. The incidence of hypokalemia was 28.8% (predominantly grades 1-2), and the incidence of nephrotoxicity was 11.3% (predominantly grades 1-2) . Conclusion:L-AmB is safe and effective in the treatment of patients with IFD who are intolerant to or who have experienced no effect of previous antifungal therapy, with a low rate of adverse reactions.

Diabetic retinal neurodegeneration is a serious complication of diabetes mellitus, manifested by apoptosis and gliosis, and its pathogenesis is closely related to the oxidative stress induced by high glucose levels. The increase in blood glucose in the body leads to excessive production of reactive oxygen species and the downregulation of antioxidant defense signaling pathways, which leads to oxidative stress in the body, which in turn induces apoptosis, mitochondrial damage and autophagy, resulting in diabetic retinal neurodegeneration. Antioxidant stress therapy with gene therapy, flavonoids, recombinant Ad-β-catenin carriers, and autophagy inducers to exert neuroprotective effects. In the future, more clinical trials are needed to explore the effective dosage and side effects of drugs, and to develop new drugs and treatment strategies for oxidative stress to prevent and treat diabetic retinal neurodegeneration and protect retinal nerve function.

Objective:To investigate the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) bridging to chimeric antigen receptor T cell (CAR-T) immunotherapy for follicular lymphoma (FL) transformed to B-lymphoblastic leukemia/lymphoma (B-LBL).Methods:The diagnosis and treatment of 1 patient with FL transformed to B-LBL admitted to the First Hospital of Soochow University in August 2020 were retrospectively analyzed and the literature was reviewed.Results:The male patient was 65 years old, and was diagnosed as FL (stage Ⅳ group A, FL international prognostic index -1 score 3 points, high-risk group) in August 2020. And then he was given 6 courses of RB (rituximab combined with bendamustine) regimen, with complete remission (CR) at mid-term and end-stage PET-CT, followed by regular maintenance therapy with rituximab every 2 months, and disease progressed after 4 courses of maintenance therapy. According to the results of histopathology and bone marrow aspiration in December 2021, he was diagnosed B-LBL involving the bone marrow. Partial remission was achieved after induction therapy with zanubnulindb combined with hyper CVAD (cyclophosphamide + doxorubicin + vindesine + dexamethasone) regimen, followed by auto-HSCT bridging to CAR-T treatment targeting CD19 and CD22, which proceeded smoothly with cytokine release syndrome grade 0, immune effector cell-associated neurotoxicity syndrome grade 0. The patient successfully underwent hematopoietic reconstruction and orally taken ibrutinib after discharge. PET-CT indicated CR 2 months after transplantation and he was still in disease-free survival state.Conclusions:The prognosis of FL transformed to B-LBL is poor, and auto-HSCT bridging to CAR-T can improve the prognosis and prolong the survival time of patients who cannot undergo allogeneic hematopoietic stem cell transplantation.

Objective To investigate and analyze the level of homocysteine(Hcy)in Tibet and to analyze the differences of Hcy level in different altitude regions,genders and ages,and thus to provide the prevalence profile of hyperhomocysteine and the differences in relevant tests between HHcy(hyperhomocysteinemia)and non-HHcy pop-ulations.Methods Totally 1 615(male n＝585)subjects were selected from Ngari,Lhasa,Shigatse and Nyingchi plat-eau areas of Tibet by stratified cluster sampling.Serum Hcy level was analyzed and the difference of Hcy level in pop-ulations located at different altitude plateau areas,gender groups were found.The prevalence of hyperhomocysteine and related test were analyzed.Kruskal Wallis test was used to compare Hcy levels in different altitudes,genders and age groups,and Pearson Chi-square test was used to compare HHcy prevalence.Variance analysis was used for the differences of different test indicators between non-HHcy and HHcy populations.Results The level of Hcy in differ-ent regions and different genders were statistically significant,which was higher in males than that in females,and higher in Lhasa and Shigatse than in Nyingchi and Ngari.There was difference in serum HHcy prevalence among dif-ferent genders,regions and age groups.Males showed a higher level than females,people from Lhasa and Shigatse showed a higher level than those from Nyingchi and Ngari.Conclusions The incidence of hyperhomocysteinemia in Tibet is statistically significant in different areas,different genders and different age groups.So this study provides a scientific basis for the rational use of Hcy as an indicator in clinical practice of prevention and treatment of related diseases in plateau areas.

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

Objective To establish a high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the simultaneous determination of seven vitamin Bs(VBs)in rat plasma.Methods The plasma samples were pretreated using the protein precipitation method.The chromatographic separation was achieved using an Agilent ZORBAX SB-Aq column(2.1 mm×150 mm,3.5 μm),with a mobile phase composed of 0.01%formic acid(A)and methanol(B)in a gradient elution mode.The flow rate was set at 0.3 mL·min-1 and the column temperature was maintained at 30℃.Mass spectrometric detection was performed using positive ion mode in multiple reaction monitoring.2,4,5,6-Deuteronicotinamide was used as the internal standard.Results Methodological validation results showed that the lowest limits of quantitation(LOQs)for the seven VBs ranged from 7.5 to 300 ng/mL,while the highest LOQs ranged from 1 000 to 20 000 ng·mL-1.Within a certain concentration range,all compounds showed a good linearity(r2>0.992 2).The accuracies ranged from 86.0%to 117.6%,and both intra-and inter-batch precision were less than 20%.Additionally,all analytes demonstrated extraction recoveries greater than 86.1%.No significant matrix effects were observed,and the stability was good.The established validation method was successfully applied to the pharmacokinetics study of single intragastric administration of VB solution in SD rats.Conclusion The analytical method established in this study is simple,rapid,sensitive,and exclusive for the simultaneous determination of VB in real plasma samples.This LC-MS/MS method provides a new analytical tool for further exploring the physiological and pathological effects of VB.