Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Tooth pulpitis is a prevalent oral disorder. Understanding the underlying mechanisms of pulpitis and developing effective treatment strategies hold great significance. Ferroptosis has recently emerged as a new form of cell death, but the role of ferroptosis in pulpitis remains largely unknown. In our study, single-cell RNA sequencing (scRNA-seq) was used to identify cellular heterogeneity between 3 pulpitis tissue and 3 healthy pulp tissue, and explored ferroptosis occurrence in pulpitis tissue and inflamed dental pulp cells (DPCs). In scRNA-seq, 40 231 cells (Pulpitis: 17 814; Healthy pulp: 22 417) were captured, and visualized into 12 distinct cell clusters. Differentially expressed ferroptosis-related genes (DE-FRGs) were almost presented in each cluster in pulpitis vs healthy pulp. ROS and Fe²⁺ levels significantly rose, and immunohistochemistry showed low expression of GPX4 and high expression of PTGS2 in pulpitis. In LPS-stimulated DPCs, thymosin α1 increased the expression of GPX4 and FTL, and decreased expression of TNF-α, IL-1β, IL-6, and Fe²⁺ levels. In rat pulpitis models, both prothymosin α (PTMA, precursor of thymosin α1) gelatin sponge placed at the hole of pulp (LPS-P(gs)) and PTMA injection in pulp (LPS-P(i)) significantly reduced infiltration of inflammatory cells and expression of PTGS2, and increased the expression of GPX4. In RNA sequencing, the expression of DE-FRGs were reversed when thymosin α1 were added in LPS-stimulated DPCs. Collectively, single-cell atlas reveals cellular heterogeneity between pulpitis and healthy pulp, and ferroptosis occurrence in pulpitis. Thymosin α1 may reduce ferroptosis in DPCs to alleviate pulpitis and thus potentially has the ability to treat pulpitis.
Ferroptosis/drug effects* ; Dental Pulp/drug effects* ; Animals ; Pulpitis/pathology* ; Rats ; Thymalfasin/pharmacology* ; Humans ; Male ; Thymosin/pharmacology* ; Disease Models, Animal ; Rats, Sprague-Dawley

Objective To investigate the predictive value of serum human epididymis protein 4(HE4)levels in primary Sj?gren's syndrome(pSS)patients for renal injury.Methods A retrospective analysis of 77 pSS patients admitted to the Second People's Hospital of Yichang from September 2021 to August 2023 was performed,including 43 cases of renal injury group 34 instances of non-renal injury group,and 54 healthy physical examination subjects(HCs)as control group.Fasting peripheral venous blood(4ml)was collected to detect the serum levels of HE4,Cys-C,TNF-α,CR,C3,C4,immunoglobulin,Anti-SSA,Anti-SSB and other indicators,and analyzed the value of HE4 in the early diagnosis of kidney injury in pSS patients.Results Compared with HCs,the pSS patients had increased levels of HE4(120.02±103.86 pmol/L vs 57.5±16.52 pmol/L),Cys-C(1.30±0.81mg/L vs 0.87±014 mg/L),and the differences were statistically significant(t=4.382,3.860,all P<0.05).The serum levels of HE4,CR and TNF-α in the renal damage group were higher than those in the non-renal damage group,and the differences were statistically significant(t/χ2=2.552～4.371,all P<0.05).Pearson correlation analysis showed that,the levels of serum HE4,Cys-C,CR and TNF-α were all positively correlated with renal damage in pSS(r=0.287～0.546,all P<0.05).Logistic regression analysis showed that elevated serum HE4 level might be an independent risk factor for inducing renal damage in pSS(Wald χ2=11.932,P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the best cut-offvalue of serum HE4 for the diagnosis of pSS renal damage was 70.46pmol/L,the maximum Youden index was 0.625,AUC(95%CI)=0.876(0.799～0.954).Conclusion The serum HE4 level in patients with pSS is positively correlated with renal injury and has predictive value for the occurrence of renal injury.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

ObjectiveTo investigate the prevalence of cardiovascular diseases and their influencing factors in community-based schizophrenia patients in Shanghai, and to provide a scientific basis for the early identification and prevention of cardiovascular disease in this population. MethodsBased on the Shanghai community cohort with severe mental disorders in 2022, a total of 3 954 community-based schizophrenia patients were identified and included in this study through a stratified cluster sampling method. Basic information and relevant clinical data (including metabolic index data) were collected through questionnaire survey, physical examination and laboratory testing. Univariate analyses were performed using the chi-square tests, and multivariate logistic regression analyses were employed to identify influencing factors of comorbid cardiovascular diseases. ResultsA total of 3 954 community-based schizophrenia patients were included, of which a total of 1 237 (31.28%) patients had comorbid cardiovascular diseases. Multivariate logistic regression analyses showed that age 60 years old or above (OR=5.524, 95%CI: 3.716‒8.214), smoking behavior (OR=1.328, 95%CI: 1.042‒1.692), overweight (OR=1.900, 95%CI: 1.046‒3.451) or obesity (OR=2.678, 95%CI: 1.439‒4.985), elevated blood pressure (OR=1.546, 95%CI: 1.294‒1.846), abnormal fasting blood glucose (OR=1.552, 95%CI: 1.322‒1.823) and high-density lipoprotein cholesterol abnormalities (OR=1.283, 95%CI: 1.025‒1.606) were positively associated with the risk of comorbid cardiovascular diseases in patients with schizophrenia, while educational attainment of college/bachelor’s degree or above (OR=0.640, 95%CI: 0.450‒0.910) and being unmarried (OR=0.552, 95%CI: 0.457‒0.667) were negatively associated with the risk of cardiovascular diseases comorbidity. ConclusionAdvanced age, unhealthy behaviors and lifestyles, as well as abnormalities in blood pressure, blood glucose, and blood lipids, could all increase the risk of comorbid cardiovascular diseases in community schizophrenia patients. It is suggested to strengthen the monitoring and management of these risk factors in this population in the future, so as to achieve early detection, early diagnosis and early intervention of cardiovascular diseases.

Objective To explore the relationship between the nutritional risk and the risk of frequent acute exacerbation of chronic obstructive pulmonary disease(COPD).Methods The patients with acute exac-erbation of COPD(AECOPD)hospitalized in the respiratory and critical care medicine department of the First Affiliated Hospital of Xiamen University were collected and divided into the frequent acute exacerbation risk group(FE)and non-frequent exacerbation risk group(NE).The nutritional risk was evaluated by the Nutri-tional Risk Screening Scale-2002(NRS-2002)(1-2 points as no nutritional risk,3-7 points as nutritional risk).The relationship between the two was analyzed by statistics and logistic regression.Results The FE group had longer hospital stay(P<0.01)and a higher proportion of hypertension(P<0.01).In terms of in-flammatory indicators,the neutrophil to albumin ratio(P<0.01)and platelet to lymphocyte ratio(P<0.05)in the FE group were significantly increased.In the aspect of nutritional status,the NRS-2002 score in the FE group showed a higher proportion of nutritional risk population(P<0.01),meanwhile the total protein(P<0.01)and albumin(P<0.05)levels were significantly decreased.After adjusting the confounding factors such as gender,hospitalization duration,inflammatory markers and history of underlying diseases,the full fac-tor logistic regression analysis revealed that the frequent acute exacerbation risk in COPD patients with nutri-tional risk was significantly higher that in the patients with no nutritional risk[odds ratio(OR)=2.948;95%confidence interval(95%CI):1.112-7.816;P<0.05].Conclusion The COPD patients with nutritional risk in NRS-2002 scores exhibit a significantly increased risk of frequent acute exacerbation compared to those without nutritional risk.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

Objective To investigate the predictive value of serum human epididymis protein 4(HE4)levels in primary Sj?gren's syndrome(pSS)patients for renal injury.Methods A retrospective analysis of 77 pSS patients admitted to the Second People's Hospital of Yichang from September 2021 to August 2023 was performed,including 43 cases of renal injury group 34 instances of non-renal injury group,and 54 healthy physical examination subjects(HCs)as control group.Fasting peripheral venous blood(4ml)was collected to detect the serum levels of HE4,Cys-C,TNF-α,CR,C3,C4,immunoglobulin,Anti-SSA,Anti-SSB and other indicators,and analyzed the value of HE4 in the early diagnosis of kidney injury in pSS patients.Results Compared with HCs,the pSS patients had increased levels of HE4(120.02±103.86 pmol/L vs 57.5±16.52 pmol/L),Cys-C(1.30±0.81mg/L vs 0.87±014 mg/L),and the differences were statistically significant(t=4.382,3.860,all P<0.05).The serum levels of HE4,CR and TNF-α in the renal damage group were higher than those in the non-renal damage group,and the differences were statistically significant(t/χ2=2.552～4.371,all P<0.05).Pearson correlation analysis showed that,the levels of serum HE4,Cys-C,CR and TNF-α were all positively correlated with renal damage in pSS(r=0.287～0.546,all P<0.05).Logistic regression analysis showed that elevated serum HE4 level might be an independent risk factor for inducing renal damage in pSS(Wald χ2=11.932,P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the best cut-offvalue of serum HE4 for the diagnosis of pSS renal damage was 70.46pmol/L,the maximum Youden index was 0.625,AUC(95%CI)=0.876(0.799～0.954).Conclusion The serum HE4 level in patients with pSS is positively correlated with renal injury and has predictive value for the occurrence of renal injury.

Objective:To investigate the correlation between serum NOD-like receptor protein 3 (NLRP3) levels and serum lipids in metabolic-associated fatty liver disease (MAFLD) before and after a single high-fat meal.Methods:A retrospective cohort study was conducted. Sixty-three MAFLD patients (MAFLD group) and fifty-four healthy subjects (CON group) recruited from February 2019 to December 2019 at Hebei Provincial People's Hospital were included. The baseline data were compared between the two groups, and a single high-fat meal trial was conducted. The levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and NLRP3 were measured at 2 h, 4 h, and 6 h after fasting and a high-fat meal. Multiple linear regression analysis was used to evaluate the influencing factors of area under the operating curve (AUC NLRP3) of serum NLRP3 subjects. Logistic regression analysis was used to evaluate the correlation between serum AUC NLRP3 and the risk of MAFLD. Results:The levels of TC, TG, LDL-C, and NLRP3 were significantly higher in the fasting group than the CON group at 2 h, 4 h, and 6 h after a meal [TC (mmol/L), fasting: (5.29±1.01) vs. (4.28±0.62), 2 h: (5.24±0.98) vs. (4.25±0.62), 4 h: (5.38±1.04) vs. (4.26±0.63), 6 h: (5.54±1.07) vs. (4.41±0.65); TG (mmol/L), fasting: (2.67±0.96) vs. (0.92±0.33), 2 h: (3.91±1.35) vs. (1.69±0.59), 4 h: (5.09±1.7) vs. (1.91±0.93), 6 h: (5.36±2.27) vs. (1.75±1.03); LDL-C (mmol/L), fasting: (3.47±0.74) vs. (2.65±0.49), 2 h: (3.36±0.71) vs. (2.58±0.49), 4 h: (3.30±0.71) vs. (2.55±0.47), 6 h: (3.36±0.74) vs. (2.63±0.48); NLRP3 (ng/L), fasting: (84.63±12.96) vs. (56.71±11.37), 2 h: (106.06±17.76) vs. (69.12±14.92), 4 h: (89.78±15.98) vs. (57.74±12.34), 6 h: (80.03±13.61) vs. (54.06±10.35); P<0.001], while the HDL-C level was significantly lower than the CON group [HDL-C (mmol/L), fasting: (1.14±0.24) vs. (1.33±0.29), 2 h: (1.14±0.24) vs. (1.33±0.29), 4 h: (1.09±0.24) vs. (1.27±0.28), and 6 h: (1.05±0.26) vs. (1.29±0.30); P<0.001]. Serum AUC NLRP3 was significantly correlated with AUC TG and AUC LDL-C (AUC TG: B=7.391, 95% CI:5.662-9.12; AUC LDL-C: B=6.559, 95% CI:3.052-10.065; P<0.001) after adjusting for confounding factors, and it was identified as an independent influencing factor for MAFLD ( OR=1.039, 95% CI:1.007-1.071; P=0.015). Conclusion:The serum NLRP3 levels before and after a single high-fat meal are significantly associated with elevated TG and LDL-C levels, and may influence the progression of MAFLD.

The functional health and stability of the oral and maxillofacial system is one of the basic goals of orth-odontic treatment.Currently,it is believed that,in general,the condyle is located in the center of the joint fossa when the mandible is in an intercuspal position(ICP)in healthy normal people.At this time,the function of the temporoman-dibular joint(TMJ)is stable.Due to orthodontic tooth movement and subsequent occlusal changes,patients with maloc-clusion may experience related remodeling of the temporomandibular joint,especially changes in the position of the con-dyle.The position of the mandibular condyle is traditionally evaluated using a condylar position indicator.However,this method lacks consistency in obtaining condylar position changes.In recent years,in the clinical application of orthodon-tic treatment,cone beam computed tomography(CBCT)has become the first choice for examination.CBCT can accurate-ly measure the interarticular space and determine changes in condylar position.This article reviews the CBCT assess-ment of condylar position and related research on condylar position changes in patients with malocclusion before and af-ter orthodontic treatment.The literature review results indicate that there are differences in the condylar position of pa-tients with different malocclusions,and the condylar position may also change before and after orthodontic treatment.With a lower radiation dose,CBCT has higher accuracy in evaluating the condylar position in patients with malocclu-sion who undergo orthodontic treatment,thus promoting further study of the mechanism of condylar position changes in patients with malocclusion in the future and providing more accurate and personalized guidance for patient treatment.