Objectives:To systematically evaluate the effectiveness and safety of sacubitril valsartan in the treatment of heart failure with mildly reduced ejection fraction(HFmrEF).Methods:Computer searches were conducted on PubMed,Embase,China National Knowledge Infrastructure(CNKI),VIP,and Wanfang Data,all from the time of database establishment until December 31,2023.Randomized controlled trials(RCT)of sacubitril valsartan(experimental group)compared to conventional drugs such as renin angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists(control group)for the treatment of HFmrEF were collected.After screening literature and extracting data,meta-analysis was conducted using Stata 15.0 and Rev Man 5.3 software,and bias and sensitivity analyses were published in parallel.Results:A total of 13 RCTs were included,with a total of 1 150 patients.The meta-analysis results showed that all-cause mortality risk of patients(RR=0.63,95%CI:0.45-0.86,P=0.004),and the risk of elevated blood creatinine(RR=0.65,95%CI:0.50-0.84,P=0.001)in the experimental group were significantly lower than those in the control group.The level of six-minute walk test post therapy was significantly higher in the experimental group patients than that in the control group(weighted mean differences[WMD]=66.33 m,95%CI:11.77-120.90,P=0.02).There was no statistically significant difference in the comparison on the readmission rate of heart failure(RR=0.87,95%CI:0.61-1.24,P=0.43),NT-proBNP levels(WMD=319.67 pg/ml,95%CI:-823.36 to 1 462.70,P=0.58),soluble suppression of tumorigenicity 2(sST2)levels(WMD=4.48 μg/L,95%CI:-0.58 to 9.54,P=0.08),incidence of hypotension(RR=1.03,95%CI:0.61-1.76,P=0.90),and incidence of hyperkalemia(RR=0.95,95%CI:0.67-1.33,P=0.75)between the two groups of patients after treatment.The results of publication bias and sensitivity analysis both indicated a high possibility of publication bias,and some indicators had unstable results.Conclusions:Sacubitril valsartan may effectively reduce all-cause mortality,and the risk of elevated blood creatinine in HFmrEF patients,improving their long-term prognosis.However,the incidence of hypotension and hyperkalemia remains unclear.

Objective:To analyze the current status of the standard system construction for smart health and elderly care in China,analyze the framework of the standard system,and propose policy recommendations for the construction of the standard system.Methods:The standard system of smart health and elderly care were searched on the websites of the State Council of China,the National Standard Information Public Service Platform,and the sub-websites of national,industry,local,group,and enterprise standards.Policy text analysis was used to explore the current status and framework of standard system construction.Results:Currently,67 standards related to smart health and elderly care in China were included,including 0 national standards,2 industry standard,10 local standards,31 group standards,and 24 enterprise standards.These standards formed a subsystem that covered general,data,product,platform,and service standards.Conclusion:The construction of the standard system of smart health and elderly care in China has achieved certain results,but there are still shortcomings,and it is necessary to strengthen the top-level design and build a perfect framework of the standard system.

OBJECTIVE To observe the intervention effect of puerarin on the rats with bacterial periodontitis by reg-ulating nucleotide-binding oligomeric domain-like receptor protein 3/Caspase-1(NLRP3/Caspase-1)signaling pathways.METHODS Totally 44 male SPF rats were chosen as subjects and were divided into the blank group,the model group,the puerarin group and the puerarin plus inhibitor group.The models of rats with bacterial periodon-titis were successfully established.The periodontal indexes and alveolar resorption were observed and compared a-mong the groups.RESULTS The sulcus bleeding index(SBI)and plaque index(PLI)scores of the model group and the puerarin plus inhibitor group were higher than those of the blank group;the NLRP3 level was 0.87±0.09 in the model group,0.85±0.08 in the puerarin plus inhibitor group,higher than 0.18±0.03 in the blank group;the Caspase-1 level was 1.15±0.11 in the model group,1.03±0.10 in the puerarin plus inhibitor group,higher than 0.35±0.04 in the blank group.The trabecular separation spacing(Tb.Sp),cemento-enamel junction-facial bone crest(CEJ-FBC),interleukin--1β(IL-1β)level,interleukin-6(IL-6)level,tumor necrosis factor-α(TNF-α)level and osteoclast counts of the model group and the puerarin plus inhibitor group were higher than those of the blank group;while the trabecular thickness(Tb.Th),bone volume/tissue volume(BV/TV)and bone mineral density(BMD)of the model group and the puerarin plus inhibitor group were lower than those of the blank group.The SBI and PLI scores of the puerarin group were lower than those of the model group;the NLRP3 level of the puerarin group was 0.20±0.04,lower than 0.87±0.09 of the model group;the Caspase-1 level of the puerarin group was 0.37±0.05,lower than 1.15±0.11 of the model group.The Tb.Sp,CEJ-FBC,IL-1βlevel,IL-6 lev-el,TNF-α level and osteoclast counts of the puerarin group were lower than those of the model group;while the Tb.Th,V/V and BMD of the puerarin group were higher than those of the model group.The SBI and PLI score of the puerarin plus inhibitor group were higher than those of the puerarin group;the NLRP3 level of the puerarin plus inhibitor group was 0.85±0.08,higher than 0.20±0.04 of the puerarin group;the Caspase-1 level of the pu-erarin plus inhibitor group was 1.03±0.10,higher than 0.37±0.05 of the puerarin group.The Tb.Sp,CEJ-FBC,IL-1β level,IL-6 level,TNF-α level and osteoclast counts of the puerarin plus inhibitor group were higher than those of the puerarin group,while the Tb.Th,V/V and BMD of the puerarin plus inhibitor group were low-er than those of the puerarin group,there were significant differences in the above comparisons(P＜0.05).CONCLUSIONS Puerarin can effectively reduce the periodontal plaque index and bleeding index of the rats with bacterial,reduce the levels of inflammatory factors and alleviate the damage of tissue.The action mechanisms may be associated with the NLRP3/Caspase-1 signaling pathways.

In recent years,protein and polypeptide drugs have developed rapidly and have been widely used to treat cancer,hepatitis,and other diseases.The activity of proteins and polypeptides is closely related to their structure.Protein structures can be divided into four levels:primary,secondary,tertiary,and quaternary structures.The primary structure determines the advanced structure and biological functions of proteins.To ensure drug safety,it is necessary to carry out structural characterization and quality control.The advanced structure is the basis for proteins to express their functions and activities,and changes in spatial structure can lead to alterations in functions.This article reviews the progress of research on the primary and advanced structure characterization of proteins and polypeptides,including techniques such as reversed-phase high-performance liquid chromatography,Edman degradation,mass spectrometry,and spectroscopy.It aims to provide a reference for the structural characterization and quality control of other protein and polypeptide drug products.

Objectives:To systematically evaluate the effectiveness and safety of sacubitril valsartan in the treatment of heart failure with mildly reduced ejection fraction(HFmrEF).Methods:Computer searches were conducted on PubMed,Embase,China National Knowledge Infrastructure(CNKI),VIP,and Wanfang Data,all from the time of database establishment until December 31,2023.Randomized controlled trials(RCT)of sacubitril valsartan(experimental group)compared to conventional drugs such as renin angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists(control group)for the treatment of HFmrEF were collected.After screening literature and extracting data,meta-analysis was conducted using Stata 15.0 and Rev Man 5.3 software,and bias and sensitivity analyses were published in parallel.Results:A total of 13 RCTs were included,with a total of 1 150 patients.The meta-analysis results showed that all-cause mortality risk of patients(RR=0.63,95%CI:0.45-0.86,P=0.004),and the risk of elevated blood creatinine(RR=0.65,95%CI:0.50-0.84,P=0.001)in the experimental group were significantly lower than those in the control group.The level of six-minute walk test post therapy was significantly higher in the experimental group patients than that in the control group(weighted mean differences[WMD]=66.33 m,95%CI:11.77-120.90,P=0.02).There was no statistically significant difference in the comparison on the readmission rate of heart failure(RR=0.87,95%CI:0.61-1.24,P=0.43),NT-proBNP levels(WMD=319.67 pg/ml,95%CI:-823.36 to 1 462.70,P=0.58),soluble suppression of tumorigenicity 2(sST2)levels(WMD=4.48 μg/L,95%CI:-0.58 to 9.54,P=0.08),incidence of hypotension(RR=1.03,95%CI:0.61-1.76,P=0.90),and incidence of hyperkalemia(RR=0.95,95%CI:0.67-1.33,P=0.75)between the two groups of patients after treatment.The results of publication bias and sensitivity analysis both indicated a high possibility of publication bias,and some indicators had unstable results.Conclusions:Sacubitril valsartan may effectively reduce all-cause mortality,and the risk of elevated blood creatinine in HFmrEF patients,improving their long-term prognosis.However,the incidence of hypotension and hyperkalemia remains unclear.

In recent years,protein and polypeptide drugs have developed rapidly and have been widely used to treat cancer,hepatitis,and other diseases.The activity of proteins and polypeptides is closely related to their structure.Protein structures can be divided into four levels:primary,secondary,tertiary,and quaternary structures.The primary structure determines the advanced structure and biological functions of proteins.To ensure drug safety,it is necessary to carry out structural characterization and quality control.The advanced structure is the basis for proteins to express their functions and activities,and changes in spatial structure can lead to alterations in functions.This article reviews the progress of research on the primary and advanced structure characterization of proteins and polypeptides,including techniques such as reversed-phase high-performance liquid chromatography,Edman degradation,mass spectrometry,and spectroscopy.It aims to provide a reference for the structural characterization and quality control of other protein and polypeptide drug products.

ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

Background Exposure to air pollutants increases the risk of diseases in multiple systems, including respiratory and cardiovascular systems, yet its association with neurological diseases remains unclear. Objective To quantitatively evaluate the association between short-term exposure to air pollutants and outpatient and emergency visits for neurological diseases, identify potential susceptible populations, and quantify associated disease burden. Methods Daily 24-hour average concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO), daily maximum 8-hour average concentration of ozone (O₃), daily meteorological data (24-hour average temperature, 24-hour average relative humidity), and data on daily outpatient and emergency department visits for neurological diseases from two hospitals in Conghua District, Guangzhou, China, were collected from 2015 to 2022. A time-stratified case-crossover design was adopted, and a conditional Poisson regression model was constructed to analyze the association between air pollution exposure and neurological disease visits. Two-pollutant models and sensitivity analysis were used to validate model stability. Stratified analyses by season (cold season: from November to March; warm season: from April to October), sex (male, female), and age (≤45 years, 46–60 years, ≥61 years) were performed to identify vulnerable group. Additionally, the number and proportion of neurological disease visits attributable to short-term air pollutant exposure were calculated. Results A total of 72 673 outpatient and emergency department visits for neurological diseases were included during the study period. Most of the patients were middle-aged and elderly individuals (69.89% were over 45 years old) and females (60.25%). The results of single-pollutant models showed that for each interquartile range (IQR) increase in exposure to PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃, the risk of outpatient and emergency department visits for neurological diseases increased by 7.54% (95%CI: 4.69%, 10.46%), 6.66% (95%CI: 3.92%, 9.46%), 16.72% (95%CI: 10.58%, 23.19%), 8.12% (95%CI: 4.82%, 11.53%), 5.60% (95%CI: 2.34%, 8.97%), and 6.11% (95%CI: 2.91%, 9.40%), respectively. The results of the two-pollutant model showed that the association between PM_2.5 and SO₂ exposure and outpatient and emergency department visits for neurological diseases were relatively stable. The stratified analyses showed that the effect of SO₂ was stronger in the cold season. It was estimated that 8.32% (95%CI: 5.55%, 10.96%) and 6.65% (95%CI: 4.27%, 8.96%) of the outpatient and emergency department visits were attributable to short-term exposure to SO₂ and PM_2.5, respectively. Conclusion Exposure to PM_2.5 and SO₂ is associated with increased risks of outpatient and emergency visits for neurological diseases. SO₂ shows stronger effects during the cold season, and exposure to air pollution contributes to up to 8.32% of neurological disease visits.

Background With the rapid development of the food delivery industry, take-away deliverymen become an essential component of urban logistics. However, high labor intensity, unstable income, and extended working hours place them at considerable risk of occupational burnout. Available studies have paid insufficient attention to the mental health of this population, and effective predictive or preventive approaches remain limited. Objective To understand the status of occupational burnout among take-away deliverymen, identify influencing factors based on restricted cubic spline analysis, and develop a predictive model to provide a theoretical basis for improving their mental health. Methods A cross-sectional survey was conducted among full-time take-away deliverymen registered to the "Ele.me" and "Meituan" platforms in Hangzhou between September 1 and November 30, 2024, using both online and offline approaches. A questionnaire covered sociodemographic, household, and occupational information, and the Maslach Burnout Inventory–General Survey were used in this survey. Univariate analyses and logistic regression were used to identify factors associated with burnout and to construct a predictive model. Model performance was evaluated using receiver operating characteristic (ROC) curve and calibration curve. Furthermore, restricted cubic spline was used to further explore the relationship between age, working hours, and occupational burnout. Results Among the 1192 participants, 735 (61.66%) experienced occupational burnout. The logistic regression model indicated that older age (OR=1.021, P=0.010), educational attainment of college level or above compared to junior high school or below, (OR=2.837, P<0.001), and longer daily working hours (OR=1.081, P=0.001) were positively associated with occupational burnout. In contrast, work experience of 3−5 years (OR=0.666, P=0.016) and more than 5 years (OR=0.382, P<0.001) compared to those with <3 years, as well as providing three social insurances (OR=0.655, P=0.006) or five social insurances (OR=0.478, P<0.001) compared to those without any social insurances coverage, were negatively associated with occupational burnout. The predictive model based on these variables achieved an area under the curve (AUC) of 0.783 (95% CI: 0.756~0.809), and good agreement between calibration curves. The restricted cubic spline analysis revealed that the risk of occupational burnout was highest among delivery workers aged 33−46 years. Those with daily working hours between 3.5 and 8.1 h had a lower risk, while the risk significantly increased when working hours exceeded 8.1 h per day. Conclusion The prevalence of reporting occupational burnout among take-away deliverymen in Hangzhou is high. The developed predictive model provides valuable insights for the prevention and control of burnout in this population. Measures such as optimizing social security systems, rational work schedule allocation, and enhancing psychological support may help reduce occupational burnout among take-away deliverymen.

Objective To develop an endothelialized microfluidic chip model that simulates the spatial architecture and bioactivity of retinal vasculature,enabling thrombosis modeling and thrombolytic efficacy validation.Methods A tri-level microvascular network chip(300/200/100 μm diameters)with bifurcated architecture was fabricated using soft lithography.Human retinal microvascular endothelial cells(HRMECs)were perfused into channels,with endothelial coverage monitored via phase-contrast microscopy and F-actin staining.Cellular bioactivity was assessed using mitochondrial membrane potential probes(5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide,JC-1)and nitric oxide(NO)quantification.Fresh blood samples from 10 healthy donors(Yongchuan Hospital Affiliated to Chongqing Medical University,March to June 2024)were perfused with digital injection pump to mimic blood flow in human body into 3 experimental groups:normal whole blood,and TNF-α-activated endothelium+normal blood,TNF-α-activated endothelium+TNF-α-treated blood.Three inlet blood flow rates of 37.8、11.1 and 3.5 μL/min were set in each group.Two experimental groups,normal saline and recombinant human tissue-type plasminogen activator(rtPA),were established using the endothelialized microfluidic thrombosis model to validate thrombolytic efficacy.Endothelial functional impacts were assessed through integrated DAPI/NO staining and thrombosis model analysis across 3 intervention phases:pre-thrombosis,post-thrombosis,and post-thrombolysis.Results A tri-level microfluidic vascular model(300/200/100 μm diameters)was successfully constructed.In 72 h after endothelial cell perfusion,complete channel coverage was achieved,with phase-contrast microscopy and F-actin staining confirming confluent cellular alignment.JC-1/NO assays validated preserved endothelial bioactivity.Compared with the whole blood group,both TNF-α-activated endothelium+normal blood and TNF-α-activated endothelium+TNF-α-treated blood groups exhibited significantly increased thrombus occupancy rates at identical flow rates(all P<0.001).Notably,TNF-α-activated endothelium+TNF-α-treated blood group demonstrated the highest thrombus ratio at 3.5 μL/min(P<0.001).The rtPA group showed superior thrombolytic efficacy versus saline(P<0.001).Endothelial monolayer integrity was maintained across intervention phases,with thrombosis triggering significant NO elevation(P<0.001).Conclusion Our retinal vasculature-mimetic microfluidic model enables precise thrombosis modeling and drug evaluation,providing new methodology for studying retinal vascular occlusive diseases.