Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Objective To analyze the imaging features of cerebral small vessel disease in patients with type 2 diabetes mellitus by multimodal MRI.Methods The clinical data of 160 patients with cerebral small vessel disease admitted to our hospital from January to December 2020 were retrospectively analyzed.According to whether they were complicated with type 2 diabetes mellitus,they were divided into the diabetic group and the non-diabetic group,with 80 cases in each group.Both groups underwent multimodal MRI scans.And the severity of lacunar infarction,the severity of subcortical and periventricular white matter lesions,white matter integral and cerebral microbleeds of patients in the two groups were compared.Results The severity of lacunar infarction(χ2=34.076,P=0.001),subcortical white matter lesions(χ2=25.000,P=0.001),periventricular white matter lesions(χ2=22.895,P=0.001)and white matter integral(t=12.370,P=0.001)of patients in the diabetic group were significantly higher than those in the non-diabetic group.No cerebral microbleeds were detected in either group of patients.Conclusion Patients with cerebral small vessel disease and type 2 diabetes mellitus show characteristic multimodal MRI changes.The increase in the number of lacunar infarction lesions and the aggravation of white matter lesions can be used as the characteristic imaging basis for the diagnosis of type 2 diabetes mellitus related cerebral small vessel disease.

Mass vaccination represents a highly effective strategy for accelerating disease control while simultaneously reducing incidence and mortality rates. By developing comprehensive plans and standards for mass vaccination, it is feasible to optimize resource allocation and swiftly enhance vaccination coverage, thereby preventing, controlling, or interrupting outbreaks or epidemics of specific infectious diseases. To standardize the mass vaccination process and establish a population immunity barrier in an orderly, efficient, and safe manner, a panel of experts was convened to develop the Recommendations on Mass Vaccination. These recommendations are grounded in the requirements of relevant policies and regulations in China, as well as the insights gained from the mass vaccination campaign for COVID-19 vaccines conducted in the country. The recommendations outline the system requirements pertaining to initiation conditions, departmental coordination, responsibilities, mobilization, operational specifications, and responses to vaccine reactions, among other aspects of mass vaccination implementation, so as to serve as a reference for future mass vaccination initiatives and the formulation of related policies.

Objective:To investigate the efficacy and safety of sintilimab combined with the SOX regimen for adjuvant treatment of stage Ⅲgastric cancer after D2 radical resection and to provide a reference for individualized clinical treatment.Methods:The clinical data of 245 pa-tients with stage III gastric cancer who underwent D2 radical resection at the 940th Hospital of the Joint Support Force of the People's Liber-ation Army from June 2019 to May 2022 were retrospectively analyzed.The 180 patients who received only the SOX regimen were desig-nated the control group,and the 65 patients who received sintilimab combined with the SOX regimen were designated the experimental group.The 3-year disease-free survival(DFS)rate,overall survival(OS)rate,and adverse reactions among the two groups and different sub-groups(HER-2 positive,dMMR,CPS≥5)were compared.Results:The 3-year DFS(81.5%vs.59.4%)and OS(84.6%vs.70.6%)rates in the experimental group were significantly higher than those in the control group(both P<0.05).Group analysis showed that in patients with CPS≥5,the 3-year DFS(91.5%vs.67.0%)and OS(95.7%vs.71.6%)rates within the experimental group were significantly better than those in the control group(both P<0.05).Intra-group analysis within the experimental group showed that the 3-year DFS rate(91.5%vs.55.6%)and OS rate(95.7%vs.55.6%)of patients with CPS≥5 were significantly better than those of patients with CPS<5(both P<0.05).The overall and grade≥3 incidences of liver and kidney function damage,thyroid dysfunction,colitis,pneumonia,and rash in the experimental group were higher than those in the control group(all P<0.05),while the differences in other adverse reactions,including leukopenia were not statistic-ally significant(all P>0.05).Conclusions:Sintilimab combined with the SOX regimen can significantly improve 3-year DFS and OS rates in pa-tients with stage Ⅲ gastric cancer after surgery,especially in the CPS≥5 subgroup,with significant benefits and controllable safety.

Objective To evaluate the efficacy and safety of a novel intravascular lithotripsy(IVL)balloon—Vesscrack shockwave balloon—for vascular preparation before stent implantation in patients with severe coronary artery calcification(CAC).Methods This was a prospective,single-arm,multicenter study conducted in China from June 2022 to October 2022.Patients with severe CAC were treated with the Vesscrack shockwave balloon for lesion preparation,followed by drug-eluting stent(DES)implantation.Of these,33 patients underwent optical coherence tomography(OCT).The primary endpoint was procedural success,defined as successful stent implantation with residual stenosis≤30％and the absence of in-hospital major adverse events,including cardiac death,target vessel-related myocardial infarction,or target lesion revascularization.Results A total of 170 patients[mean age:(65.9±7.9)years,116 males]were enrolled.After treatment with IVL and DES,the minimum lumen diameter increased significantly compared to baseline[(2.34±0.40)mm vs.(0.95±0.33)mm,P＜0.001],the degree of stenosis was significantly reduced[(13.24±6.60)％vs.(65.18±10.59)％,P＜0.001].Procedural success was achieved in 100％of cases,and device success was 98.8％.The 30-day patient-related cardiovascular clinical composite endpoint(POCE)rate was 0.0,with no target lesion failure,no confirmed or potential thrombotic events were observed.The shockwave energy generator demonstrated excellent stability and ease of use.Among the 33 patients assessed with OCT,after IVL intervention,the maximum calcified area of the lumen[(3.51±1.51)mm2 vs.(2.85±1.80)mm2,P＜0.001],and the minimum lumen area within the target lesion[(3.08±1.04)mm2 vs.(2.02±0.75)mm2,P＜0.001],and after DES intervention,the luminal area of the largest calcified site[(6.59±1.64)mm2 vs.(2.85±1.80)mm2,P＜0.001]and the minimum luminal area within the target lesion[(6.19±1.45)mm2 vs.(2.02±0.75)mm2,P＜0.001]were significantly increased,and the differences were statistically significant.Conclusions The Vesscrack shockwave balloon is effective and safe for vascular preparation in patients with severe CAC prior to stent implantation.It achieves significant calcified plaque modification,high procedural success rates,and minimal complications.

Objective To develop a risk prediction model for ischemic stroke in symptomatic intracranial atherosclerotic stenosis(ICAS)patients based on high-resolution magnetic resonance imaging(HR-MRI)and arterial spin labeling(ASL)imaging.Methods A total of 142 patients were included and divided into acute ischemic stroke(AIS)and transient ischemic attack(TIA)groups based on stroke occurrence.Clinical risk factors,plaque characteristics,and arterial transit artifact(ATA)presence on ASL images were compared between the two groups.Multivariate logistic regression analysis was performed,incorporating clinical risk factors,plaque characteristics,and double post labeling delay(PLD)ATA presence.The predictive value of different models was compared using receiver operating characteristic(ROC)curve and DeLong tests.Results Hypertension,positive lumen remodeling,plaque enhance-ment rate,1.5 s-ATA presence,and 2.5 s-ATA presence were independent risk factors for AIS(P＜0.05).The combination of HR-MRI and ASL imaging predicted AIS most effectively[area under the curve(AUC)=0.908;95％ confidence interval(CI)0.862-0.954].No significant difference was found between the prediction performances of HR-MRI and ASL(95％CI-0.041-0.082,Z=0.659,P=0.509).Conclusion ASL is more convenient than HR-MRI for predicting ischemic stroke in ICAS patients.A model combining plaque characteristics and ATA presence effectively predicts AIS occurrence.

Aim To investigate the effect of metformin on epithelial-mesenchymal transition(EMT)of lung cancer A549 cells and its underlying mechanism.Methods Lung cancer A549 cells were cultured in vitro and treated with metformin.Cell morphology was observed by fluorescence staining.The mRNA expres-sion levels of E-cadherin,N-cadherin,SMA and Vimen-tin were detected by RT-PCR.The regulatory effects of metformin on EMT in A549 cellswere examined by high-throughput sequencing.An EMT model was estab-lished through TGF-β1 induction.Following metformin treatment,the morphology of A549 cells was observed.Western blot was employed to determine the expression levels of NGF,E-cadherin,N-cadherin,SMA and Vim-entin.Additionally,si-NGF transfection was performed to evaluate the protein expressions of E-cadherin,N-cadherin,SMA and Vimentin in A549 cells,and a cell scratch assay was conducted to assess cell migration.Results After metformin treatment,A549 cells exhibi-ted a loss of mesenchymal-like morphology,character-ized by a transition to a round shape,a reduction in colony formation,and decreased adherence.RT-PCR and high-throughput sequencing revealed a down-regu-lation in the expression of genes associated with mesen-chymal transition,including N-cadherin,SMA,and Vim-entin,and an up-regulation in the expression of genes associated with epithelial transformation,such as ZO-1 and E-cadherin.Additionally,the expression of nerve growth factor(NGF)was significantly up-regulated.Following transfection with si-NGF,A549 cells treated with metformin exhibited a down-regulation in the ex-pression of the epithelial marker E-cadherin,concomi-tant with an up-regulation in the expression of stromal markers N-cadherin,Vimentin,and SMA.Conclusions Metformin can up-regulate the expression of E-cad-herin and down-regulate the expression of N-cadherin,Vimentin and SMA in lung cancer A549 cells,thereby inhibiting EMT.Additionally,NGF signaling molecules may play a significant role in this process.

Objective To investigate the correlation between immune cells and the occurrence of cardiovascular disease(CVD)in patients with human immunodeficiency virus/acquired immunodeficiency syndrome(HIV/AIDS),and to construct a risk prediction model.Methods A total of 280 HIV/AIDS patients treated from June 2024 to August 2025 were selected as the research subjects and divided into a training set(n=200)and a test set(n=80)at a ratio of 5:2.The patients in the training set were subdivided into a CVD subgroup(n=60)and a non-CVD subgroup(n=140)according to whether they developed CVD.The baseline characteristics and immune cells of the two groups were compared,and the longitudinal trajectory changes of immune cells in the CVD subgroup and the non-CVD subgroup were analyzed.LASSO regression analysis was used to screen the independent influencing factors of CVD,multivariate Logistic regression analysis was used to screen the independent risk factors for the occurrence of CVD,and a risk prediction nomogram model was constructed.The area under the receiver operating characteristic(ROC)curve(AUC),Hosmer-Lem show test,calibration curve,and decision curve were used to compare the risk prediction nomogram model with the general cardiovascular risk assessment model,to evaluate its discrimination,goodness-of-fit,and clinical utility.Results There were significant differences in the baseline characteristics and immune cells between the two groups(P<0.05).The longitudinal trajectory plots revealed that the CD4+count,CD8+count,and CD4+/CD8+level in the CVD group exhibited substantial fluctuations,while the trajectories of these parameters in the non-CVD group remained relatively stable.After LASSO regression analysis screened out 11 non-zero coefficient variables,multivariate logistic regression analysis showed that age,hypertension,total cholesterol,smoking,high-sensitivity C-reactive protein,CD4+count at the time of HIV diagnosis,CD8+count at the time of HIV diagnosis,and globulin were all independent influencing factors for the occurrence of CVD in HIV/AIDS patients(P<0.05).The AUC of the risk prediction nomogram model was 0.960 in the training set and 0.914 in the test set,indicating good discrimination of the model.The Hosmer-Lem show test and calibration curve showed good accuracy and consistency of the model,and the decision curve showed a high net benefit value,indicating good clinical utility.Conclusion The CVD risk in HIV/AIDS patients is jointly affected by immune dysfunction and traditional metabolic factors.The risk prediction nomogram model constructed significantly improves the accuracy of risk prediction of CVD and can provide a basis for early identification of high-risk patients and the formulation of individualized intervention strategies.

Objective To explore the risk factors for noncontiguous spinal fractures(NSFs)in the elderly.Methods The clinical data of 614 elderly patients with spinal fracture from January 2013 to December 2019 were analyzed retrospectively.Patients were divided into the NSFs group and the Non-NSFs group according to whether NSFs occurred or not.Univariate analysis and multivariate Logistic regression analysis were used to screen the risk factors of NSFs.Results Univariate analysis showed that female(P=0.003),high-energy violent injury(P=0.032),osteoporosis(P=0.004),fracture in spring(P=0.020),and previous spinal fracture history(P<0.001)were associated with the occurrence of NSFs.Multivariate Logistic regression analysis showed that fracture in spring(P=0.024),previous spinal fracture history(P<0.001)and high-energy violent injury(P=0.038)were the independent risk factors for the occurrence of NSFs in the elderly.Conclusion High-energy violent injury,fracture in spring and previous spinal fracture history are the independent risk factors for the occurrence of NSFs in the elderly.Therefore,elderly patients with the above risk factors should be examined more carefully and comprehensively to avoid missed diagnosis and delayed diagnosis.In order to reduce the incidence of this disease,corresponding measures should be taken according to the preventable risk factors.