OBJECTIVE To prepare nanoparticle-based targeting preparation loaded with triptolide （TP）， and evaluate its quality， targeting ability and cytotoxic effects. METHODS Polymer nanoparticles carrying TP-targeted folic acid （FA） receptor （TP@PLGA-PEG-FA） were fabricated using poly （lactic-co-glycolic acid）/polyethylene glycol/FA （PLGA-PEG-FA） as the carrier by emulsion and volatilization technique. The morphology and distribution were observed， and their particle size， Zeta potential， polydispersity index （PDI）， drug loading capacity and encapsulation efficiency were measured. Their stability， blood compatibility， in vitro drug release， uptake by RAW264.7 cells （localization with fluorescent dye Cy3.5）， and in vitro cytotoxicity were evaluated. RESULTS TP@PLGA-PEG-FA exhibited spherical shape and uniform distribution， with particle size of （122.60±0.02） nm， Zeta potential of （－17.6±0.6）mV， and PDI of 0.26±0.02； drug loading capacity and encapsulation efficiency of TP were measured to be （7.78±0.05）% and （68.62±0.03）%， respectively. The hemolysis rates of 100， 200， 300， 400 µg/mL TP@PLGA- PEG-FA were 0.77%， 0.92%， 1.34% and 1.63%， respectively. There were no significant changes in particle size， PDI and Zeta potential when TP@PLGA-PEG-FA were placed in 4 ℃ water for 14 days and in DMEM culture medium containing 10% fetal bovine serum at 37 ℃ for 12 h. The cumulative release rate of TP@PLGA-PEG-FA was （84.83±0.29）% in phosphate buffer at pH5.5 for 72 h， which was significantly higher than the cumulative release rates in phosphate buffer solutions at pH7.4 and 6.5 for 72 h （[ 42.37±0.35）% and （63.83±0.29）% ， respectively] （P＜0.05）. Activated RAW264.7 cells took up significantly more Cy3.5@PLGA-PEG-FA than they took up Cy3.5@PLGA-PEG-FA+free FA and Cy3.5@PLGA-PEG. When the mass concentration of TP was≥15.63 ng/mL， the survival rates of activated cells in the TP@PLGA-PEG-FA groups were significantly lower than those of the same mass concentration of free TP groups （P＜0.05）. CONCLUSIONS The prepared TP@PLGA-PEG-FA has high stability， good blood compatibility， active targeting and cytotoxicity to inflammatory cells.

Various types of industrial parks in Shanghai play an important role in promoting industrial upgrading and technological progress， yet they are also fraught with occupational health hazards. To effectively promote workplace health and enable various industrial parks to play a positive role， the Shanghai Municipal Government has proposed accelerating the construction of healthy industrial parks. To meet the requirements for the scientific and standardized construction of healthy parks， the Shanghai Municipal Center for Disease Control and Prevention has compiled the Guidelines for Healthy Industrial Park Construction（Guidelines）. Adhering to the overall principles of scientific， feasibility， advancement， and standardization， the Guidelines address three construction levels： industrial parks， employers， and employees. They set clear requirements for organizational management， healthy environments， health services， health activities， and occupational health in the workplaces， respectively. The Shanghai healthy industrial park evaluation form was provided as an informative appendix for the Guidelines. The Guidelines offer a scientific basis for standardizing and guiding the construction of healthy industrial parks， providing new solutions and technical support for urban occupational health management.

Alzheimer disease(AD),commonly known as senile dementia,is the most common type of dementia,resulting in progressive impairment of cognitive function,and is often accompanied by a variety of psychiatric symptoms,such as agitation.Agitated symptoms in AD patients often cause an increasing burden on caregivers,and current psychiatric medications may exacerbate adverse effects such as cognitive impairment and motor retardation in patients.Therefore,non-drug intervention is a very important adjuvant treatment option.This article reviews the clinical manifestations,possible mechanisms,drug therapy and non-drug intervention measures of agitation in order to provide reference for more effective treatment of AD.

Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.

Cognitive impairment is a kind of senile disease that leads to the decline of personality and behavior ability of the elderly,which seriously affects the quality of daily life of patients.The prevalence rate of the disease increases year by year with the acceleration of the aging process of the society,and its incidence is affected by many risk factors.At this stage,the curative effect for middle and advanced patients is poor.So early identification and intervention to delay the progression of cognitive impairment have become the focus of relevant research.Blood pressure variability can lead to damage of target organs such as heart,brain tissue and kidney,which is closely related to cognitive impairment.In order to expand a new perspective of early intervention in cognitive impairment,this paper reviews the effects of blood pressure variability on different cognitive impairment and its possible pathogenic mechanism.

Red blood cells(RBCs)are the primary mediators of oxygen transport in the human body,and their function is mainly achieved through conformational changes of hemoglobin(Hb).Hb is a tetramer composed of four subunits,with HbA being the predominant Hb in healthy adults,existing in two forms:tense state(T state)and relaxed state(R state).Endogenous regulators of Hb conformation include 2,3-diphosphoglyceric acid,carbon dioxide,protons,and chloride ions,while exogenous regulators include inositol hexaphosphate,inositol tripyrophosphate,benzabate,urea derivative L35,and vanillin,each with different mechanisms of action.The application of Hb conformational regulators provides new insights into the study of hypoxia oxygen supply issues and the treatment of sickle cell disease.

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION Chictr.org, ChiCTR 1800018895.
Humans ; Aged ; Sarcopenia/diagnosis* ; Deep Learning ; Aging ; Algorithms ; Biomarkers

Objective:To investigate the correlation between the degree of hepatic fibrosis and early neurological deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS) and its predictive value.Methods:Patients with AIS received intravenous thrombolysis at Nanjing Jiangbei Hospital from January 2018 to March 2023 were retrospectively included. Hepatic fibrosis-4 index (FIB-4) was used to evaluate the degree of hepatic fibrosis in patients. FIB-4 ≥ 2.67 was defined as severe hepatic fibrosis. END was defined as an increase of ≥4 from baseline on the National Institutes of Health Stroke Scale (NIHSS) score within 24 h after intravenous thrombolysis. The relevant factors of END were analyzed through univariate analysis and multivariate logistic regression model. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of FIB-4 for END. Results:A total of 313 patients were included, of which 184 (58.8%) were male, aged 64.8±11.8 years old. The median baseline NIHSS score was 6 (interquartile range, 4-9), and the median FIB-4 was 1.76 (interquartile range, 1.28-2.56). Forty-five patients (14.4%) experienced END. Multivariate logistic regression analysis showed that after adjusting for other confounding factors, higher FIB-4 was significantly independently correlated with END (odds ratio 2.121, 95% confidence interval 1.422-3.162; P=0.001). ROC curve analysis shows that FIB-4 has a good predictive value for END (the area under the curve 0.689, 95% confidence interval 0.595-0.784; P=0.001). The optimal cutoff value of FIB-4 was 1.82, and its sensitivity and specificity in predicting END were 71.1% and 54.9%, respectively. Conclusion:FIB-4 has good predictive value for END in patients with AIS after intravenous thrombolysis.

Objective:Heme chloride(Hemin)is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs.This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice,and explore its role in anti-plateau hypoxia. Methods:Thirty male BALB/c mice were randomly divided into a blank group,a positive drug group(acetazolomide,200 mg/kg),a Hemin low-dose group(15 mg/kg),a Hemin medium-dose group(30 mg/kg),and a Hemin high-dose group(60 mg/kg)with intraperitoneal injection.The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened.Thirty-six male BALB/c mice were randomly divided into a blank group,a hypoxia group,a positive drug group,and a Hemin high-dose group.The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)levels of myocardium,brain,lung,and liver tissues were measured in different groups with hypoxia for 24 h.The degree of histopathological damage of mice was observed with HE staining.The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Results:Compared with the blank group,the survival time of mice in the positive drug group,the Hemin medium-dose group,and high-dose group was significantly extended(all P<0.05),with the highest prolongation rate in the Hemin high-dose group.Compared with the hypoxia group,mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue,and a significant decrease in MDA content of lung tissue(all P<0.05).The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver,heart,brain and lung tissues of mice with hypoxia,and the most obvious effect on that of the brain tissue. Conclusion:Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia,and has obvious protective effect on tissue damage caused by hypoxia.

Background Long working hours are a common occupational health risk factor. The problem of long working hours and its impact on health of medical staff cannot be ignored. Objective To investigate long working hours in medical staff of tertiary grade A hospitals in Shanghai, and evaluate the relationships of long working hours with occupational stress and fatigue accumulation. Methods A total of 1531 medical staff in departments of emergency, internal medicine, surgery, intensive care unit (ICU), anesthesiology, and obstetrics and gynecology from 6 hospitals in 6 districts of Shanghai were selected using stratified random sampling. A structured questionnaire was used to collect information on social demographics, occupational characteristics, andbehavior and lifestyle. The Core Occupational Stress Scale (COSS) and the Self-diagnostic Questionnaire on the Accumulation of Fatigue of Laborers were used to assess occupational stress and fatigue accumulation condition. Chi-square test and Kruskal-Wallis H test were used to analyze the distributions of long working hours, occupational stress, and fatigue accumulation, log-binomial models were used to analyze the relationships of long working hours with occupational stress and fatigue accumulation, and job title stratified models were also constructed. Results The average weekly working hours of the study subjects was (47.84±11.40) h, 65.90% of the medical staff worked more than 40 h every week. The percentages of the weekly working hours categories of 41-48 h, 49-54 h, and ≥55 h were 31.42%, 13.46%, and 21.03%, respectively. The positive rates of occupational stress and fatigue accumulation were 25.87% and 65.64% respectively, and the differences among different age, gender, job title, education, length of service, and shift system groups were statistically significant (P<0.05). The results of log-binomial regression showed that after adjusting for gender, age, monthly income, marital status, education, physical exercise, smoking, job position, length of service, and shift system, weekly working hours were an influencing factor of occupational stress and fatigue accumulation (P<0.05). Compared with weekly working hours≤40 h, the risk, PR(95%CI), of reporting occupational stress and fatigue accumulation increased to 2.595 (1.989, 3.385) and 1.578 (1.349, 1.845) times respectively for weekly working hours≥55 h (P<0.001). The results of job title stratification analysis showed that the risk of occupational stress among physicians, nurses, and medical technicians increased when weekly working hours≥55 h versus ≤40 h, and the PR (95%CI) values were 2.003 (1.383, 2.902), 1.971 (1.068, 3.636), and 2.770 (1.220, 6.288), respectively (P<0.05). The risk of fatigue accumulation was increased in physicians when weekly working hour≥55 h versus ≤40 h, with a PR (95%CI) value of 1.594 (1.208, 2.103) (P<0.001). Conclusion Long working hours are common among medical personnel and related to the occurrence of occupational stress and fatigue accumulation.