Objective:To investigate the prevalence of baseline dyslipidemia in HIV-infected people before starting antiviral therapy (ART) in China.Methods:The data were collected from HIV/AIDS ART database of Chinese Disease Prevention and Control Information System. A national sample of HIV- infected people who initiated ART from 2018 to 2023 was used to collect baseline information, including sociodemographic characteristics and laboratory test results. According to the Chinese Lipid Management Guidelines (2023) and the National Cholesterol Education Program Adult Treatment Panel Ⅲ guidelines, triglyceride (TG) ≥1.7 mmol/L or total cholesterol (TC) ≥5.2 mmol/L were identified as dyslipidemia. Statistical analysis was performed with software SAS 9.4. An unconditional logistic regression model was used to analyze the factors influencing TG and TC abnormalities in HIV-infected patients before ART.Results:A total of 359 952 adults infected with HIV were included in this study, the prevalence rate of dyslipidemia was 38.41% (138 263/359 952). The abnormal rates of TG and TC were 31.40% (113 041/359 952) and 13.75% (49 494/359 952), respectively. In all age groups except for the 25-44 age groups, the abnormal rates of TG and TC were higher in HIV-infected women than in HIV-infected men. In HIV-infected patients, women, those aged 45-64 years, those lived in northeast region, those had heterosexual transmission, and those with BMI ≥28.0 kg/m 2, CD4 +T lymphocytes counts ≥500 cells/μl had higher rates of baseline dyslipidemia (all P<0.05). Conclusions:The abnormal rate of TG in HIV-infected people before ART was higher in China from 2018 to 2023, especially in HIV-infected women, and the abnormal rate of TG and TC increased with age. Attention should be paid to the clinical diagnosis and ART selection in the treatment of HIV infection.

Dipeptidyl peptidase 4(DPP4)is one of the binding receptors for the spike(S)protein of porcine hemagglutinating encephalomyelitis virus(PHEV).To identify the key amino acid binding sites at the interface of DPP4 protein and PHEV spike protein and explore the impact of their mu-tations on viral infection,recombinant plasmids of porcine DPP4,murine DPP4 and human DPP4(pDPP4,mDPP4,hDPP4)and spike protein truncations(S311-608,S13-298)were constructed and co-transfected into HEK293T cells to detect the protein binding by co-immunoprecipitation(CoIP).Simultaneously,the expression of PHEV proteins and genes was detected in DPP4-over-expressing HeLa cells infected by PHEV using Western blot and RT-qPCR.homologues were overexpressed in HeLa cells which were not susceptible to and then inoculated with the virus,and.Subsequently,the important pDPP4 amino acid sites at the interaction interface were mutated one by one using a point mutation kit to construct mutant overexpression plasmids.The mutant and wild-type pDPP4 were co-transfected into HEK293T cells with the spike protein truncations re-spectively to assay the protein interaction ability by co-immunoprecipitation.After HeLa cells over-expressing the mutant and wild-type pDPP4 were infected by PHEV,the replication level of PHEV was detected by Western blot and RT-qPCR.Compared with hDPP4,the pDPP4 and mDPP4 had significantly stronger binding to PHEV spike protein,which significantly promote PHEV infection.Moreover,mutation of pDPP4 glycosylation sites significantly enhanced the inter-action with PHEV spike protein,and the mutation of glycosylation sites(N229,N321)dramatical-ly promoted PHEV infection.The above results indicated that DPP4 glycosylation modification plays an important shielding role in the process of PHEV invading target cells mediated by spike protein.

Dipeptidyl peptidase 4(DPP4)is one of the binding receptors for the spike(S)protein of porcine hemagglutinating encephalomyelitis virus(PHEV).To identify the key amino acid binding sites at the interface of DPP4 protein and PHEV spike protein and explore the impact of their mu-tations on viral infection,recombinant plasmids of porcine DPP4,murine DPP4 and human DPP4(pDPP4,mDPP4,hDPP4)and spike protein truncations(S311-608,S13-298)were constructed and co-transfected into HEK293T cells to detect the protein binding by co-immunoprecipitation(CoIP).Simultaneously,the expression of PHEV proteins and genes was detected in DPP4-over-expressing HeLa cells infected by PHEV using Western blot and RT-qPCR.homologues were overexpressed in HeLa cells which were not susceptible to and then inoculated with the virus,and.Subsequently,the important pDPP4 amino acid sites at the interaction interface were mutated one by one using a point mutation kit to construct mutant overexpression plasmids.The mutant and wild-type pDPP4 were co-transfected into HEK293T cells with the spike protein truncations re-spectively to assay the protein interaction ability by co-immunoprecipitation.After HeLa cells over-expressing the mutant and wild-type pDPP4 were infected by PHEV,the replication level of PHEV was detected by Western blot and RT-qPCR.Compared with hDPP4,the pDPP4 and mDPP4 had significantly stronger binding to PHEV spike protein,which significantly promote PHEV infection.Moreover,mutation of pDPP4 glycosylation sites significantly enhanced the inter-action with PHEV spike protein,and the mutation of glycosylation sites(N229,N321)dramatical-ly promoted PHEV infection.The above results indicated that DPP4 glycosylation modification plays an important shielding role in the process of PHEV invading target cells mediated by spike protein.

Objective:To investigate the prevalence of baseline dyslipidemia in HIV-infected people before starting antiviral therapy (ART) in China.Methods:The data were collected from HIV/AIDS ART database of Chinese Disease Prevention and Control Information System. A national sample of HIV- infected people who initiated ART from 2018 to 2023 was used to collect baseline information, including sociodemographic characteristics and laboratory test results. According to the Chinese Lipid Management Guidelines (2023) and the National Cholesterol Education Program Adult Treatment Panel Ⅲ guidelines, triglyceride (TG) ≥1.7 mmol/L or total cholesterol (TC) ≥5.2 mmol/L were identified as dyslipidemia. Statistical analysis was performed with software SAS 9.4. An unconditional logistic regression model was used to analyze the factors influencing TG and TC abnormalities in HIV-infected patients before ART.Results:A total of 359 952 adults infected with HIV were included in this study, the prevalence rate of dyslipidemia was 38.41% (138 263/359 952). The abnormal rates of TG and TC were 31.40% (113 041/359 952) and 13.75% (49 494/359 952), respectively. In all age groups except for the 25-44 age groups, the abnormal rates of TG and TC were higher in HIV-infected women than in HIV-infected men. In HIV-infected patients, women, those aged 45-64 years, those lived in northeast region, those had heterosexual transmission, and those with BMI ≥28.0 kg/m 2, CD4 +T lymphocytes counts ≥500 cells/μl had higher rates of baseline dyslipidemia (all P<0.05). Conclusions:The abnormal rate of TG in HIV-infected people before ART was higher in China from 2018 to 2023, especially in HIV-infected women, and the abnormal rate of TG and TC increased with age. Attention should be paid to the clinical diagnosis and ART selection in the treatment of HIV infection.

Postoperative pulmonary complications and anastomotic leakage are unfavorable prognostic factors in patients with esophageal carcinoma.However,the prognostic importance of pulmonary complications and anastomotic leakage after neoadjuvant treatment in these patients remains unclear.This study aimed to determine the effect of postoperative pulmonary complications and anastomotic leakage on long-term survival after neoadjuvant therapy for esophageal cancer.Our study were recruited 441 consecutive patients who had curative resection following neoadjuvant treatment for esophageal cancer in our institution from 2011-2021.The clinicopathological characteristics and prognosis of these patients were studied in terms of postoperative pulmonary complications and anastomotic leaking.Survival was analyzed using the log-rank test and multivariable Cox regression analysis.Postoperative pulmonary complications and anastomotic leakage were present in 23.8％(n=105)and 5.2％(n=23)of esophageal cancer after neoadjuvant therapy,respectively.In the univariate analyses,pulmonary complications were associated with shorter disease-free survival,while anastomotic leakage was associated with shorter overall survival.Multivariable analysis revealed that pulmonary complications after neoadjuvant therapy were independent adverse prognostic factors for disease-free survival.Taken together,postoperative pulmonary complications and anastomotic leakage ware significantly negatively correlated with disease-free and overall survival,respectively.And the postoperative pulmonary complication is an independent poor prognostic factor of disease-free survival for esophageal cancer following neoadjuvant treatment.

Lipid nanoparticle (LNP) is commonly used to deliver mRNA vaccines. Currently, LNP optimization primarily relies on screening ionizable lipids by traditional experiments which consumes intensive cost and time. Current study attempts to apply computational methods to accelerate the LNP development for mRNA vaccines. Firstly, 325 data samples of mRNA vaccine LNP formulations with IgG titer were collected. The machine learning algorithm, lightGBM, was used to build a prediction model with good performance (R ² > 0.87). More importantly, the critical substructures of ionizable lipids in LNPs were identified by the algorithm, which well agreed with published results. The animal experimental results showed that LNP using DLin-MC3-DMA (MC3) as ionizable lipid with an N/P ratio at 6:1 induced higher efficiency in mice than LNP with SM-102, which was consistent with the model prediction. Molecular dynamic modeling further investigated the molecular mechanism of LNPs used in the experiment. The result showed that the lipid molecules aggregated to form LNPs, and mRNA molecules twined around the LNPs. In summary, the machine learning predictive model for LNP-based mRNA vaccines was first developed, validated by experiments, and further integrated with molecular modeling. The prediction model can be used for virtual screening of LNP formulations in the future.

Objective To explore the role of liver X receptor (LXR) agonist T0901317 on thrombomodulin (TM) expression in human glomerular endothelial cells and the possible mechanisms.Methods Different concentrations of T0901317 were used to stimulate human glomerular endothelial cells for different time,then LXRα,LXRβ expression were detected by using Western blotting analysis;the roles of T0901317 on TM mRNA and TM protein expression were observed by using real-time PCR,Western blotting and immunofluorescence assay.LXRα,LXRβ gene interference segment Si-hLXRα,Si -hLXRβ were transfected into human glomerular endothelial cells with the concentration of 100 nmol/L respectively,then the roles of Si-hLXRα,Si-hLXRβ on the TM protein and TM mRNA expression were assayed by Western blotting and real time PCR.Results Human glomerular endothelial cells expressed LXRα and LXRβ.Compared to the normal cells and DMSO group,T0901317 could significantly promote TM expression in human glomerular endothelial cells (P ＜ 0.05) and showed a time -and dose-dependent manner.TM expression in Si-hLXRα transfected group was significantly lower than that in the control group (P ＜ 0.05),while TM expression in Si-hLXRβ transfected group had no significant difference compared to the control group.Conclusions Human glomerular endothelial cells express LXRα and LXRβ.LXR agonist T0901317 promotes TM expression in human glomerular endothelial cells,which may be mainly through activating LXRa.