ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.

To satisfy the growing healthcare demands of the public, it is essential to develop a public service platform for vaccination. This initiative aligns with national policies, optimizes resource allocation, innovates service models, enhances service efficiency, and reduces service costs. Drawing on relevant national policies and regulatory requirements, as well as the notable achievements and practical experiences gained through the exploration and innovation of vaccination service models across various regions, this paper proposes expert recommendations. It defines the essential components and functional specifications for public service platforms, focusing on public needs such as electronic vaccination record management, appointment management, the promotion of electronic vaccination certificates, vaccination certificate verification for school enrollment, vaccination site navigation, and science communication and public engagement. The recommendations aim to serve as a reference for the development of vaccination public service platforms nationwide.

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

Medical fiber endoscope is one kind of medical device that utilizes fiber technique to realize visual detection for internal organs or cavities.In clinical applications,medical fiber endoscope not only need to complete fiber optic imaging but also need possess the functions of delivering water and air,and operating device.Therefore,its routine management and maintenance for fault is more and more payed attention by the staffs of using medical fiber endoscope in department.The system of delivering water and air is a key structure for some of medical fiber endoscopes,which has higher maintenance matters and frequency of maintaining fault.Based on the above reasons,this research analyzed the working principle of medical fiber endoscopes,and summarized the ideas and methods of repairing common faults through focused on the structural composition of delivering system of water and air of medical fiber endoscopes,so as to improve the management level for this type of medical device.

Objective·To explore the antitumor effects and potential mechanisms of combining phosphoinositide 3-kinase,FYVE-type zinc finger containing(PIKfyve)inhibitor YM201636 with the stimulator of interferon genes(STING)agonist diABZI in STING pathway-deficient melanoma.Methods·The mRNA and protein expression levels of STING in human cancer cell lines were obtained from the Cancer Cell Line Encyclopedia(CCLE)and UniProt databases.Based on median expression values,melanoma cell lines with high STING mRNA but low protein expression were identified.Quantitative real-time PCR(qRT-PCR)and Western blotting were performed to validate STING mRNA and protein expression in human melanoma cells.The murine melanoma cell line YUMM1.7,characterized by low STING protein expression,was selected through Western blotting.The ability of YM201636 to restore STING protein expression in YUMM1.7 cells was evaluated.STING agonist diABZI was then applied in combination with YM201636 to analyze the synergistic tumor cell-killing effect through CCK-8 assay.Western blotting was used to detect the phosphorylation of TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3),and qRT-PCR was used to evaluate type Ⅰ interferon expression.A mouse melanoma model was established and treated with YM201636,diABZI,or their combination.Tumor volume was measured,and treatment efficacy was assessed.RNA sequencing and immunofluorescence staining were performed to analyze immune cell infiltration in the tumor microenvironment.Results·Database analyses,qRT-PCR,and Western blotting confirmed that some human melanoma cell lines exhibited high STING mRNA expression but low STING protein levels.YM201636 significantly increased STING protein expression in YUMM1.7 cells(P<0.001).Combined treatment with YM201636 and diABZI significantly enhanced phosphorylation of TBK1 and IRF3(P<0.05),indicating effective activation of the STING signaling pathway.This combination also promoted the expression of type Ⅰ interferons(P<0.001)and enhanced tumor cell killing in vitro.In vivo,the combination therapy markedly suppressed melanoma growth compared to monotherapy.Immune profiling of the tumor microenvironment revealed significantly increased infiltration of CD4? T cells and CD8? T cells in the combination treatment group(P<0.05).Conclusion·The PIKfyve inhibitor YM201636 could restore STING protein expression in STING-deficient melanoma and enhance the antitumor efficacy of the STING agonist diABZI,offering a promising therapeutic strategy for tumors with defective STING signaling.

Objectives:To explore the independent and combined effects of sleep duration and physical activity(PA)on the incidence of cardiovascular disease(CVD).Methods:The study subjects were derived from three sub-cohorts of the China-PAR project.Information on sleep and PA was collected from the surveys conducted in 2007-2008,and the incidence and mortality data of CVD were obtained during the follow-up survey from 2012 to 2015.Sleep duration was categorized into≤6 h/d,>6-8 h/d,and>8 h/d,and the PA level was classified according to the tertiles of PA volume(MET-h/d).The Cox proportional hazards model stratified by cohort source was applied to estimate the associations of PA and sleep duration with CVD incidence,coronary heart disease(CHD)incidence,and stroke incidence.Results:A total of 93 933 participants were included.During an average follow-up of(5.82±0.98)years,3 862 CVD events were documented.Compared with the low PA group,the hazard ratios(HRs)and 95%confidence intervals(CIs)of the CVD incidence,CHD incidence,and stroke incidence for the high PA group were 0.73(0.65-0.82),0.62(0.49-0.77)and 0.88(0.76-1.01),respectively.A U-shaped relation between sleep duration and incidence of CVD and stroke was observed.Compared with those who slept for>6-8 h/d,the risk of CVD(HR[95%CI]:1.10[1.00-1.21],P=0.04)and stroke(HR[95%CI]:1.33[1.18-1.49],P<0.01)was higher among participants slept>8 h/d.The risk of CVD,CHD and stroke tended to be higher in the≤6 h/d sleep group.Compared with the high PA combined with>6-8 h/d,the risk of stroke was highest in the high PA combined with>8h/d sleep group(HR[95%CI]:1.74[1.37-2.22],P<0.05),while the risks of CVD(HR[95%CI]:1.69[1.39-2.04],P<0.05)and CHD(HR[95%CI]:1.99[1.41-2.81],P<0.05)were highest in the low PA combined with≤6 h/d sleep group.Conclusions:Adequate physical activity and appropriate sleep duration are associated with lower risk of morbidity from CVD,CHD and stroke.

Objectives:Using data from the heart transplant patient dataset of our center,we aimed to develop a preoperative risk scoring model specifically suitable for the Chinese population undergoing heart transplantation.This model was established to predict the likelihood of graft failure within the first year post-surgery and classify recipients according to their risk level.Methods:A retrospective study was conducted at a single center on 1 210 consecutive heart transplant recipients between June 2004 and December 2022.Risk factor screening was performed using univariate and multivariate logistic regression analyses.Variable selection was carried out through a stepwise backward procedure based on the Akaike Information Criterion(AIC).The regression coefficients obtained from the final model were employed as weighting factors in the multifactor analysis.The study utilized the area under the receiver operating characteristic(ROC)area under curve(AUC)as a metric to evaluate the performance of the model.Patients were stratified into low,medium,and high-risk groups based on the distribution of the calculated scores.Survival analysis was conducted on the various risk groups using the Kaplan-Meier method,with statistical comparisons performed using the log-rank test.A significance level of P<0.05 was deemed statistically significant.Results:A risk scoring model,denoted as the heart transplant(HTx)score,was developed,comprising 11 variables and yielding a total score of 20.6 points.In comparison to the low-risk group,the OR for 1-year graft failure in the medium-risk group was 2.0(95%CI:1.1-3.6,P=0.02),while the high-risk group had an OR of 9.8(95%CI:5.4-17.7,P<0.01).The risk scoring model exhibited strong discriminative ability with an AUC of 0.712(95%CI:0.646-0.778)and an internally validated bias-corrected AUC of 0.713.The results of the Hosmer-Lemeshow goodness-of-fit test indicated that the predictive model demonstrated a strong calibration ability(Hosmer-Lemeshow χ2=2.92,P=0.71).Within the cohort,the AUC values for the IMPACT score,UNOS score,RSS score,Mayo score,BO score,and TRS score models were 0.645,0.651,0.632,0.589,0.610,and 0.604,respectively.These findings suggest that the HTx scoring model exhibited superior predictive performance compared to the aforementioned models in forecasting outcomes within our cohort.The Kaplan-Meier survival analysis revealed statistically significant differences in long-term survival rates between the three risk groups,a noticeable decrease in long-term survival rates were observed with increasing levels of HTx risk stratification(P<0.05).Conclusions:Present results indicate a significant association between the developed HTx risk scores and graft failure within the initial year post-surgery,present model effectively categorizes the heart transplant recipients into low,medium,and high-risk groups and is valuable for risk stratification.

Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

Objective:To investigate the relationship between lipid levels and cognitive impairment in the elderly Chinese population using prospective cohort data.Methods:Based on the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) cohort, this study included 24 380 individuals aged ≥60 years who participated in the cognitive function follow-up survey from 2018 to 2019. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with cognitive impairment defined according to different educational levels: MMSE ≤17 for illiterate individuals, MMSE ≤20 for those with primary education and MMSE ≤24 for those with secondary education or above. Multivariable linear regression and logistic regression models were employed to examine the associations between six baseline lipid indicators and cognitive scores, as well as cognitive impairment. Additionally, restricted cubic splines were used to explore the exposure-dose relationship between lipid levels and cognitive function.Results:The study population had a median follow-up time of 11.6 years, with a baseline age of (59.7±6.8) years. Among the participants, 9 510 (39.0%) were males, and the mean MMSE score was 24.7±6.8. A total of 3 887 individuals (15.9%) were identified as cognitively impaired. The results of multivariable linear regression and logistic regression indicated that total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) levels were not only significantly positively associated with cognitive scores but also significantly associated with a lower risk of cognitive impairment. Each 1 mmol/L increase in these lipid levels corresponded to β values (95% CI) of 0.267 (0.173-0.361), 0.385(0.271-0.499) and 0.331(0.231-0.431), respectively. Each 1 mmol/L increase in these lipid levels corresponded to odds ratio ( OR) (95% CI) values of 0.915 (0.876-0.956), 0.875 (0.830-0.923) and 0.886 (0.848-0.927), respectively. The dose-response curve demonstrated that the negative association was primarily observed within the guideline-recommended optimal lipid level range. Specifically, when LDL-C was less than 3.4 mmol/L and non-HDL-C was less than 4.1 mmol/L, the corresponding OR (95% CI) values were 0.859 (0.796-0.926) and 0.876 (0.818-0.939). Conclusion:Lipid levels exhibit a certain linear negative association with cognitive impairment in elderly Chinese adults, with LDL-C and non-HDL-C demonstrating a stronger effect, particularly within the guideline-recommended optimal range.