ObjectiveObesity has been identified as one of the most important risk factors for cognitive dysfunction. Physical exercise can ameliorate learning and memory deficits by reversing synaptic plasticity in the hippocampus and cortex in diseases such as Alzheimer’s disease. In this study, we aimed to determine whether 8 weeks of treadmill exercise could alleviate hippocampus-dependent memory impairment in high-fat diet-induced obese mice and investigate the potential mechanisms involved. MethodsA total of sixty 6-week-old male C57BL/6 mice, weighing between 20-30 g, were randomly assigned to 3 distinct groups, each consisting of 20 mice. The groups were designated as follows: control (CON), high-fat diet (HFD), and high-fat diet with exercise (HFD-Ex). Prior to the initiation of the treadmill exercise protocol, the HFD and HFD-Ex groups were fed a high-fat diet (60% fat by kcal) for 20 weeks. The mice in the HFD-Ex group underwent treadmill exercise at a speed of 8 m/min for the first 10 min, followed by 12 m/min for the subsequent 50 min, totally 60 min of exercise at a 0° slope, 5 d per week, for 8 weeks. We employed Y-maze and novel object recognition tests to assess hippocampus-dependent memory and utilized immunofluorescence, Western blot, Golgi staining, and ELISA to analyze axon length, dendritic complexity, number of spines, the expression of c-fos, doublecortin (DCX), postsynaptic density-95 (PSD95), synaptophysin (Syn), interleukin-1β (IL-1β), and the number of major histocompatibility complex II (MHC-II) positive cells. ResultsMice with HFD-induced obesity exhibit hippocampus-dependent memory impairment, and treadmill exercise can prevent memory decline in these mice. The expression of DCX was significantly decreased in the HFD-induced obese mice compared to the control group (P<0.001). Treadmill exercise increased the expression of c-fos (P<0.001) and DCX (P=0.001) in the hippocampus of the HFD-induced obese mice. The axon length (P<0.001), dendritic complexity (P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P<0.001) in the hippocampus were significantly decreased in the HFD-induced obese mice compared to the control group. Treadmill exercise increased the axon length (P=0.002), dendritic complexity(P<0.001), the number of spines (P<0.001) and the expression of PSD95 (P=0.001) of the hippocampus in the HFD-induced obese mice. Our study found a significant increase in MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of HFD-induced obese mice compared to the control group. Treadmill exercise was found to reduce the number of MHC-II positive cells (P<0.001) and the concentration of IL-1β (P<0.001) in the hippocampus of obese mice induced by a HFD. ConclusionTreadmill exercise led to enhanced neurogenesis and neuroplasticity by increasing the axon length, dendritic complexity, dendritic spine numbers, and the expression of PSD95 and DCX, decreasing the number of MHC-II positive cells and neuroinflammation in HFD-induced obese mice. Therefore, we speculate that exercise may serve as a non-pharmacologic method that protects against HFD-induced hippocampus-dependent memory dysfunction by enhancing neuroplasticity and neurogenesis in the hippocampus of obese mice.

Objective:To establish a human buccal mucosa squamous cell carcinoma (BMSCC) cell line SCC117 in China, analyze and identify its basic biological characteristics.Methods:A 59-year-old Chinese male patient with BMSCC in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology in January 2011 was included in this study, his surgical specimens were primary cultured in vitro by improved tissue block culture method. The BMSCC cell line SCC117 was established after continuous passage and stable growth. The morphological characteristics of the cells were observed by light and electron microscope, and their basic biological characteristics were analyzed by growth curve, chromosome karyotype and xenotransplantation tumorigenicity in nude mice experiment. The expressions of cytokeratin (CK14), tumor-related proteins retinoblastoma tumor suppressor protein (RB), P53, E-cadherin, P21, phosphatase and tensin homolog deleted on chromosome ten (PTEN) were detected by immunohistochemical and human papilloma virus (HPV) were tested by PCR. SCC117 was identified by short tandem repeat (STR) analysis of genomic DNA. Results:SCC117, a human BMSCC cell line, had been continuously subcultured in vitro for more than 150 generations. The cells grew in polygonal mosaic and lost contact inhibition, the typical desmosomes and tensional fibrils were observed by electron microscope, and CK14 was positive by immunohistochemistry. The doubling time was 40.16 h, the chromosome mode of the cell line was concentrated between 67 and 69, hypo-triploid. All 4 nude mice inoculated with SCC117 cells developed tumors, indicating that the SCC117 cell line had the ability of xenogeneic tumorigenesis. The histopathological type of the transplanted tumor in nude mice was consistent with that of the primary tumor tissue, both of which were squamous cell carcinoma. The immunohistochemical results showed that in both human primary tumor and the transplanted tumor tissue in nude mice, RB, P53, and E-cadherin were all positive, P21 was weakly positive, while PTEN was negative. SCC117 was tested negative for the presence of HPV. STR sequence analysis showed that SCC117 cell line originated from primary tumor tissue and was not cross-contaminated by other cell lines. Conclusions:The human BMSCC cell line SCC117 was successfully established in China, which could provide a new experimental model for the study of oral SCC without HPV infection, especially BMSCC.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To investigate the impact of air pollution on dynamic changes in lung function and further explore the association between genetic factors and lung function and its changes.Methods:Research data were from 14 506 participants in the United Kingdom Biobank with two complete baseline and follow-up lung function tests. Particulate matter [including particulate matter with aerodynamic diameter ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10)], nitrogen dioxide (NO 2), and nitrogen oxides (NO x) concentrations were estimated using land-use regression models. Annual changes in lung function were calculated based on baseline and follow-up lung function tests. Polygenic risk scores (PRS) of lung function [forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), and the ratio of FEV 1 to FVC (FEV 1/FVC)] were constructed by genetic variations. The association between air pollution concentrations and lung function changes was analyzed by multiple linear regression models, and the impact of genetic factors on lung function and its changes was also assessed. Results:PM 2.5, PM 10, NO 2, and NO x showed a negative correlation with FVC changes [PM 2.5: -6.66 (95% CI: -9.92- -3.40) ml/year; PM 10: -0.40 (95% CI: -0.77- -0.03) ml/year; NO 2: -1.84 (95% CI: -2.60- -1.07) ml/year; NO x: -1.37 (95% CI: -2.27- -0.46) ml/year]. Additionally, PM 2.5, PM 10and NO 2 were also negatively correlated with changes in FEV 1 [PM 2.5: -3.19 (95% CI: -5.79- -0.59) ml/year; PM 10: -3.00 (95% CI: -5.92- -0.08) ml/year; NO 2: -0.95 (95% CI: -1.56- -0.34) ml/year]. PRS of lung function were positively correlated with baseline lung function (FVC, FEV 1, and FEV 1/FVC) and lung function changes (all β>0, all P<0.001). In different PRS stratification analyses, the effect of air pollution on lung function changes remained significant, and there was no apparent heterogeneity. Conclusions:PRS of lung function are significantly associated with baseline and lung function changes. Long-term exposure to air pollution accelerates the decline of lung function indicators such as FVC and FEV 1. The effects of air pollution are consistent in individuals with different genetic risk scores.

To research and design a new type of distal radial artery puncture compression hemostatic device,to solve the problem of distal radial artery puncture and compression hemostat that has not been clinically applied in China.The hemostatic device was mainly composed of hemostatic part,pressure regulating part,fixing part and visual window.The hemostatic device can accurately compress the puncture point,and it was convenient for medical staff to observe the wound through the visual window,find out abnormal conditions such as bleeding or hematoma in time,and take measures to deal with them,which greatly improved the hemostatic effect and comfort of the postoperative puncture point.The new hemostatic device has the advantages of reasonable design and simple clinical operation,which is worthy of clinical promotion.

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Aim To investigate the shared transcriptional characteristics of non-alcoholic fatty liver disease(NAFLD)and atherosclerosis(As)using bioinformatics techniques.The goal is to identify potential mechanisms and key targets of As that are linked to NAFLD through gene crosstalk analysis of both diseases.Additionally,the study will validate the expression levels of these key targets in animal tissues and human serum samples.Methods The gene ex-pression profiles of NAFLD(dataset GSE89632)and As(dataset GSE43292)were obtained from GEO database.Differ-ential gene analysis and weighted gene co-expression network analysis were conducted to identify common genes between the two diseases.These shared genes were further analyzed using the String database for protein interaction analysis and R software.Core genes were identified through calculations in Cytoscape software,validation with external datasets(GSE100927),and machine learning techniques(LASSO regression).Finally,key core genes were determined by crea-ting nonalcoholic fatty liver and As mouse models on a high-fat diet and collecting peripheral serum samples from patients with NAFLD and coronary heart disease(CHD).Results Seventy-five shared genes were identified between the two diseases,with major enrichment pathways including cytokine-cytokine receptor interaction,IL-17 signaling pathway,lipid and atherosclerosis,and NF-κB signaling pathway.Through integration of multiple bioinformatics methods,two core genes(MMP-9 and CCL3)were identified.Subsequent animal experiments demonstrated a significant increase in MMP-9 and CCL3 levels in the liver and aortic sinus of mice fed with high-fat diet,MMP-9 and CCL3 levels in the liver tissue of high-fat diet-fed mice were 2.43 times(P＜0.001)and 1.35 times(P＜0.01)higher than the control group,in the aortic sinus tissue,MMP-9 and CCL3 levels were 2.10 times(P＜0.001)and 1.58 times(P＜0.01)higher.Human serum sample verification further supported these findings,showing MMP-9 and CCL3 levels in patients with both NAFLD and CHD to be 1.21 times(P＜0.01)and 1.29 times(P＜0.01)higher than in patients with CHD alone.Conclusion This study identified MMP-9 and CCL3 may play key roles in NAFLD-related As,providing potential targets for the study of NAFLD-related As.

Objective:To observe the clinical efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)in the treatment of adult acute myeloid leukemia(AML)patients who are unfit for intensive chemotherapy.Methods:The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected,and the efficacy and safety were analyzed retrospectively.Results:After one course of treatment with VEN and AZA,16 out of 21 unfit AML patients reached complete remission(CR)/CR with incomplete hematologic recovery(CRi),2 patients reached partial remission(PR),the overall response rate(ORR)was 85.7％.Among the 16 patients with CR/CRi,13 achieved minimal residual disease(MRD)negativity.Among the 11 patients with adverse prognosis,8 achieved CR/CRi.By the deadline of follow-up,the median overall suivival(OS)of the entire cohort was not reached,with 1-year OS rate of 61.7％.The main adverse events of VEN combined with AZA were myelosuppression,gastrointestinal reactions and infections.There were 13 cases of leukopenia,7 cases of neutropenia,7 cases of anemia,4 cases of thrombocytopenia,and these hematologic adverse events were all grade 3-4.There were 11 cases with gastrointestinal reactions and 7 cases with infections.The above adverse events were controllable and tolerable.No tumor lysis syndrome or infection related death occurred.Conclusion:VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML,and it shows a good safety profile.