Objective: To create a prediction model for stroke risk among middle-aged and elderly populations, so as to provide a basis for early identification of high-risk population for stroke. Methods: From October to December 2023, residents aged ≥45 years in Chongchuan District, Nantong City, Jiangsu Province were selected using a multi-stage stratified random sampling method. The demographic information, life behavior, and chronic disease data were collected through a questionnaire survey. The standardized prevalence of stroke was calculated using data from the seventh National Population Census. The subjects were randomly divided into the training set and the internal validation set according to the ratio of 8∶2. The basic demographic information, life behavior, and chronic diseases of residents aged ≥45 years in Rugao City were collected from July to August 2023 as the external validation set. Predictive factors were selected using multivariable logistic regression model, and a nomogram for stroke among residents aged ≥45 years was established. The prediction effect was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC), calibration curve, and Hosmer-Lemeshow goodness of fit test. Results: A total of 6 290 residents aged ≥45 years were included, including 2 975 males (47.30%) and 3 315 females (52.70%). The average age was (61.90±10.20) years. The prevalence of stroke was 3.80%, and the standardized prevalence was 3.36%. The multivariable logistic regression showed that age, smoking, hypertension, and hyperlipidemia were predictors of stroke risk among residents aged ≥45 years, and the prediction model was ln[p/(1-p)]=-4.619+0.046×age+0.383×smoking+0.887×hypertension+0.678×hyperlipidemia. The AUC values of the training set, internal validation set, and external validation set were 0.748, 0.755, and 0.738, respectively. The consistency indexes were 0.748, 0.755, and 0.738, respectively. The Hosmer-Lemeshow goodness of fit test showed a good fitting effect (P>0.05). Conclusion The prediction model based on age, smoking, hypertension, and hyperlipidemia has good discrimination and calibration, and can be used to predict the risk of stroke among middle-aged and elderly populations aged ≥45 years.

In order to investigate the regulatory effect of Codonopsis saponins on the immunosup-pression caused by H9N2 subtype avian influenza virus(AIV)infection,rat pulmonary microvas-cular endothelial cells(RPMECs)were incubated with different concentrations of Codonopsis sap-onins(5,10 and 20 mg/L).The expression level of PD-L1 was detected by RT-PCR and flow cy-tometry,and the contents of TNF-α,IFN-y and IL-10 in supernatant were detected by ELISA kit.The titer of H9N2 AIV in supernatant was detected by plaque method.Then,a co-culture system of RPMECs and T cells was established using a Transwell plate with an aperture of 8 μm to mimic the migration of circulating T cells across microvessels to the site of viral infection.RPMECs were cultured in the upper chamber of Transwell,inoculated with H9N2 AIV,supplemented with 20 mg/L Codonopsis saponins 1 h later,and T cells 36 h later.After 8 h of treatment,T cells in the lower compartment were collected and the proportions of CD4+T cells and CD8+T cells were detected by flow cytometry,the expression levels of IL-2,IFN-y and granzyme B in the superna-tant were detected by ELISA,and the proportions of perforin-1 positive T cells were detected by flow cytometry.The proliferation activity of T cells was detected with the MTT cell proliferation and cytotoxicity assay kit,and the percentage of apoptotic cells was detected by flow cytometry af-ter staining of T cells with Annexin V-FITC/PI.The experimental results showed that Codonopsis saponins could significantly reduce the expression level of PD-L1,IL-10 and TNF-α in RPMECs in-duced by H9N2 AIV infection,and reduce the apoptosis rate of T cells.However,the expression levels of IL-2,IFN-y,perforin-1 and granzyme B in transendothelial migration T cells and the pro-liferation activity of T cells were significantly increased.In this study,Codonopsis saponins can sig-nificantly inhibit the expression of H9N2 AIV-induced PD-L1 in RPMECs,enhance the antiviral function of T cells migrating across the endothelial layer,and enhance the resistance of host to H9N2 AIV.

Objective:Analyzing the relationship between negative life events and depressive symptoms in university freshmen,and the mediating effects of neuroticism and the moderating role of exercise frequency.Meth-ods:A sampling of 8 079 university freshmen,and the Patient Health Questionnaire was used to assess depressive symptoms,the Eysenck Personality Inventory-Neuroticism subscale to assess neuroticism,the self-administered questionnaire to assess the number of negative life events that the participants had experienced and the exercise fre-quency.Model 4 in the Process plug-in was used to test the mediating effect of neuroticism,and Model 7 to test the moderating role of exercise frequency.Results:The numbers of negative life events were positively correlated with the depressive symptoms scores(r=0.16,P＜0.01),and were positively correlated with the neuroticism scores(r=0.26,P＜0.01).The neuroticism scores were positively correlated with the depressive symptoms scores(r=0.52,P＜0.01).Neuroticism score partially mediated between negative life events and depressive symptoms score,with a mediating effect of 78.4％,and exercise frequency score moderated between negative life events and neuroti-cism scores(β=-0.05,P=0.032).Conclusion:Negative life events are associated with depressive symptoms,neuroticism plays a mediating role,and exercise frequency could moderate negative life events and neuroticism.

BACKGROUND:Diabetic ulcers are a common complication of diabetes mellitus,which is manifested as foot ulcers complicated with infection,long treatment cycle,high disability rate and mortality rate,and brings a heavy burden to patients and social care. OBJECTIVE:To review the mechanism of action and the latest treatment progress of traditional Chinese medicine(TCM)in the treatment of diabetic ulcers,and to provide a basis for further theoretical research and clinical application. METHODS:CNKI,WanFang Database and PubMed database were searched for relevant literature using the keywords of"diabetic ulcer,medicinal herb,inflammation,interleukin-1β,interleukin-6,tumor necrosis factor,hypersensitive C-reactive protein,γ-interferon,interleukin-4,interleukin-10"in Chinese and English,respectively.The relevant literature in recent years was searched,and finally 75 articles were included for review. RESULTS AND CONCLUSION:The high glucose environment of the body will increase the level of pro-inflammatory cytokines,so that diabetic ulcer wounds are in a state of chronic inflammatory response for a long time,and difficult to heal or even not heal.TCM has summed up a lot of experience in the long-term struggle with diabetic ulcer.At present,TCM divides diabetic ulcers into four syndrome types:dampness and heat poison syndrome,blood and blood stasis obstruction pattern,heat poison injury Yin pattern,and Qi and blood deficiency syndrome,as well as representative prescriptions for treatment.According to their clinical characteristics,diabetic ulcers can be also divided into three stages:primary,middle and late stages.Different treatment methods are proposed:"clear method,""warm and clear combined use"and"maintenance method."Under the guidance of dialectical typing and staging of TCM,TCM monomers,extracts and compounds inhibit the inflammatory response and promote the healing of diabetic ulcers by down-regulating the expression of pro-inflammatory factors and/or up-regulating the expression of anti-inflammatory factors.Compared with modern medicine,TCM has significant advantages in the treatment of diabetic ulcers.There are many TCM monomers,extracts and compounds for the treatment of diabetic ulcers,such as angelica,curcumin,improved Chonghe ointment,Sanhuang blood exhaustion prescription and sore-ulcer I.formula,etc.It has been found that TCM for the treatment of diabetic ulcers is mainly heat-clearing and detoxifying,invigorating blood circulation and removing blood stasis,and amassing sores and muscle-building drugs,and the frequency of use,treatment scope and therapeutic effect of TCM compounds are obviously better than those of TCM monomers and extracts.Among them,the most commonly used are the Sanhuang blood exhaustion prescription and the sore-ulcer I as well as prescription for the treatment of damp heat toxicity syndrome and Zizhu ointment for the treatment of non-ischemic diabetic ulcers.However,there are also some shortcomings in the treatment of diabetic ulcers with TCM.First,there are few clinical syndrome studies on diabetic ulcers.Secondly,there are a wide variety of TCM monomers,extracts and compounds for the treatment of diabetic ulcers,and the relevant research is insufficiently in-depth.Finally,the research on the mechanism underlying TCM treatment of diabetic ulcers is still in the preliminary exploration stage,and the mechanism of action still needs to be further explored.In the future,it is necessary to strengthen the research on the pharmacology of TCM and the clinical syndrome of diabetic ulcers,analyze the potential targets and related signaling pathways of TCM in the treatment of diabetic ulcers,give full play to the therapeutic advantages of TCM with multiple targets,multiple pathways,multiple levels and multiple systems,and develop TCM with significant efficacy,active ingredients and clear targets.

As the global population continues to age, the incidence of Alzheimer’s disease (AD), one of the most common neurodegenerative diseases, continues to rise significantly. As the disease progresses, the patient’s daily living abilities gradually decline, potentially leading to a complete loss of self-care abilities. According to estimates by the Alzheimer’s Association and the World Health Organization, AD accounts for 60%-70% of all other dementia cases, affecting over 55 million people worldwide. The case number is estimated to double by 2050. Despite extensive research, the precise etiology and pathogenesis of AD remain elusive. Researchers have a profound understanding of the disease’s pathological hallmarks, which include amyloid plaques and neurofibrillary tangles resulting from the abnormal phosphorylation of Tau protein. However, the exact causes and mechanisms of the disease are still not fully understood, leaving a vital gap in our knowledge and understanding of this debilitating disease. A crucial player that has recently emerged in the field of AD research is the α7 nicotinic acetylcholine receptor (α7nAChR). α7nAChR is composed of five identical α7 subunits that form a homopentamer. This receptor is a significant subtype of acetylcholine receptor in the central nervous system and is widely distributed in various regions of the brain. It is particularly prevalent in the hippocampus and cortical areas, which are regions associated with learning and memory. α7nAChR plays a pivotal role in several neurological processes, including neurotransmitter release, neuronal plasticity, cell signal transduction, and inflammatory response, suggesting its potential involvement in numerous neurodegenerative diseases, including AD. In recent years, the role of α7nAChR in AD has been the focus of extensive research. Emerging evidence suggests that α7nAChR is involved in several critical steps in the disease progression of AD. These include involvement in the metabolism of amyloid β-protein (Aβ), the phosphorylation of Tau protein, neuroinflammatory response, and oxidative stress. Each of these processes contributes to the development and progression of AD, and the involvement of α7nAChR in these processes suggests that it may play a crucial role in the disease’s pathogenesis. The potential significance of α7nAChR in AD is further reinforced by the observation that alterations in its function or expression can have significant effects on cognitive abilities. These findings suggest that α7nAChR could be a promising target for therapeutic intervention in AD. At present, the results of drug clinical studies targeting α7nAChR show that these compounds have improvement and therapeutic effects in AD patients, but they have not reached the degree of being widely used in clinical practice, and their drug development still faces many challenges. Therefore, more research is needed to fully understand its role and to develop effective treatments based on this understanding. This review aims to summarize the current understanding of the association between α7nAChR and AD pathogenesis. We provide an overview of the latest research developments and insights, and highlight potential avenues for future research. As we deepen our understanding of the role of α7nAChR in AD, it is hoped that this will pave the way for the development of novel therapeutic strategies for this devastating disease. By targeting α7nAChR, we may be able to develop more effective treatments for AD, ultimately improving the quality of life for patients and their families.

Objective:To investigate the possible mechanism of DiI labeled bone marrow mesenchymal stem cells (BMSCs) in contact co-cultured with neonatal rat cardiomyocytes (CMs) on polycaprolactone (PCL) film to make myocardial patch.Methods:BMSCs from Sprague Dawley rats (aged 5-6 weeks) were isolated, cultured, and characterized for surface marker expression using flow cytometry. CMs from 15 neonatal rats were isolated and cultured. After cultured for 3 generations, BMSCs were labeled with DiI dye. On PCL film, DiI labeled BMSCs were co-cultured with CMs as the experimental group, and CMs were replaced with the same amount of unlabeled BMSCs in the control group. After 24 h of co-culture, the cell growth was observed under fluorescence microscope and the co-culture was observed under scanning electron microscope. Immunofluorescence staining was performed after 7 days to detect myocardial markers, including cardiac troponin T (cTnT) and α-actinin. BMSC differentiation on the PCL film was observed under a fluorescence microscope. The differentiation efficiency of BMSCs into cardiomyoid cells was analyzed by flow cytometry on days 1 and 7 of co-culture. Intercellular dye transfer was observed by staining CMs with calcein and co-culturing them with DiI-labeled BMSCs on PCL film. The cells were stained with immunofluorescence to detect the expression of connexin 43 (Cx43) and observe the relationship between gap junction and contact co-culture.Results:Flow cytometry showed strong positivity for CD90 and CD44 and negativity for CD11b/c and CD45 on BMSCs. After 24 h of co-culture, DiI labeled BMSCs glowed red on the PCL film, while unlabeled CMs did not; the number of cells on PCL film was large and cell morphology appeared normal under scanning electron microscope. On the 7th day of co-culture, some DiI labeled BMSCs expressed cTnT and α-actinin. Flow cytometry showed a higher differentiation rate of stem cells in the experimental group on day 7 compared to the control group ((20.12±0.15)% vs. (3.49±0.20)%, P<0.05). From the second day of co-culture, some BMSCs exhibited green dot fluorescence in Cx43 immunofluorescence staining; and by the third day, dye transfer test showed green fluorescence emission from some BMSCs. Conclusion:Contact co-culture of DiI labeled BMSCs and CMs on PCL film can make myocardial patch. The mechanism of contact co-culture promoting the differentiation and formation of myocardial patch may be associated with gap junctions and intercellular signal pathways mediated by gap junctions.

Periprosthetic joint infection （PJI） following joint arthroplasty is devastating and technique-demanding. At present， the surgical treatment for PJI includes debridement， antibiotics， and implant retention （DAIR）， single- or two-stage revision， arthrodesis， and amputation. DAIR is appealing to both surgeons and patients as it can avoid unnecessary implants removal， making it less time-consuming and less invasive. In this article， we review the current knowledge in surgical timing， intraoperative details and antibiotics strategy of DAIR.

Objective: To investigate the clinical characteristics of abnormal liver function in patients with advanced esophageal squamous carcinoma treated with programmed death-1 (PD-1) antibody SHR-1210 alone or in combination with apatinib and chemotherapy. Methods: Clinical data of 73 patients with esophageal squamous carcinoma from 2 prospective clinical studies conducted at the Cancer Hospital Chinese Academy of Medical Sciences from May 11, 2016, to November 19, 2019, were analyzed, and logistic regression analysis was used for the analysis of influencing factors. Results: Of the 73 patients, 35 had abnormal liver function. 13 of the 43 patients treated with PD-1 antibody monotherapy (PD-1 monotherapy group) had abnormal liver function, and the median time to first abnormal liver function was 55 days. Of the 30 patients treated with PD-1 antibody in combination with apatinib and chemotherapy (PD-1 combination group), 22 had abnormal liver function, and the median time to first abnormal liver function was 41 days. Of the 35 patients with abnormal liver function, 2 had clinical symptoms, including malaise and loss of appetite, and 1 had jaundice. 28 of the 35 patients with abnormal liver function returned to normal and 7 improved to grade 1, and none of the patients had serious life-threatening or fatal liver function abnormalities. Combination therapy was a risk factor for patients to develop abnormal liver function (P=0.007). Conclusions: Most of the liver function abnormalities that occur during treatment with PD-1 antibody SHR-1210 alone or in combination with apatinib and chemotherapy are mild, and liver function can return to normal or improve with symptomatic treatment. For patients who receive PD-1 antibody in combination with targeted therapy and chemotherapy and have a history of long-term previous smoking, alcohol consumption and hepatitis B virus infection, liver function should be monitored and actively managed in a timely manner.
Humans ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Esophageal Neoplasms/pathology* ; Prospective Studies ; Programmed Cell Death 1 Receptor/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Liver Diseases/etiology*

Objective: To explore the relationship between extracellular enzymes activity and virulence of Candida glabrata clinical isolates based on the infection model of Galleria mellonella larvae. Methods: Using experimental research methods, 71 strains of non-repetitive Candida glabrata were collected from Qinghai Provincial People's Hospital from June 2021 to January 2022. Bovine serum protein agar medium, egg yolk agar medium, sheep blood agar medium, Tween-80 agar medium and triglyceride agar medium were used to detect the aspartyl protease activity, phospholipase activity, hemolysis activity, esterase activity and lipase activity of Candida glabrata. Median lethal concentration (LC₅₀) was calculated by using 1.25×10⁸ CFU/ml,2.50×10⁸ CFU/ml,3.75×10⁸ CFU/ml,5.00×10⁸ CFU/ml suspension of Candida glabrata ATCC2001 to infect Galleria mellonella larvae. Histopathological and etiological analysis was performed to determine whether the infection model was successfully established. The clinical isolates of Candida glabrata were configured to infect Galleria mellonella larvae with LC₅₀ concentration to detect the pathogenicity of Galleria mellonella larvae.Spearman test or Pearson test were used to analyze the correlation between the extracellular enzyme activity of Candida glabrata clinical isolates and the pathogenicity of Galleria mellonella larvae. Results: 71 strains of Candida glabrata isolated clinically were detected to have low hemolytic activity after 2 days of culture. Aspartyl protease was detected after 4 days of culture, among which 7 strains (9.86%), 19 strains (26.76%) and 45 strains (63.38%) showed low, medium and high aspartyl protease activity. After 7 days of culture, 71 strains did not detect phospholipase, esterase and lipase activities. Candida glabrata on Galleria mellonella larvae of LC₅₀=2.5×10⁸ CFU/ml Fungal spore were found in the intestinal tissue pathological section of Galleria mellonella larvae in the experimental group, and Candida glabrata was identified by the microbial Mass Spectrometry after culture, while no fungi were found in the pathological section and culture of the control group. Spearman test shows that, there was a linear positive correlation between aspartyl protease activity and the survival rate of Galleria mellonella larvae (r = 0.73, P<0.01), the difference was statistically significant.Pearson test shows that, there was no significant linear relationship between hemolytic activity and survival rate of Galleria mellonella larvae (r = 0.16, P = 0.34), the difference was not statistically significant. Conclusion: The clinical isolates of Candida glabrata in this study had aspartyl protease activity and low hemolytic activity, but no phospholipase, esterase and lipase activity. The activity of aspartyl aspartyl protease of Candida glabrata was positively correlated with the pathogenicity of Galleria mellonella larvae.
Animals ; Sheep ; Larva/microbiology* ; Virulence ; Candida glabrata ; Agar ; Moths/microbiology* ; Esterases ; Aspartic Acid Proteases ; Lipase

OBJECTIVE: To investigate the relationship among the gross motor function classification system (GMFCS)and the development of hip joint and lumbar spine in children with spastic cerebral palsy. METHODS: The clinical data of 125 children with spastic cerebral palsy admitted from January 2018 to July 2021 were retrospectively analyzed. There were 85 males and 40 females, aged from 4 to 12 years old with an average of (8.4±2.9) years. According to GMFCS, the patients were divided into gradeⅠ, Ⅱ, Ⅲ and Ⅳ groups. There were 27 cases in gradeⅠgroup, 40 cases in gradeⅡgroup, 35 cases in grade Ⅲ group and 23 cases in grade Ⅳ group. The migration percentage(MP), central edge angle(CE), neck-shaft angle(NSA), acetabular index(AI) were measured by the radiograph of pelvis, abnormal parameters were selected to evaluate the relationship between different GMFCS grades and hip joint development. Lumbar sagittal Cobb angle, lumbar sacral angle, lumbar lordosis index and apical distance were measured by lateral lumbar radiographs to evaluate the relationship between different GMFCS grades and lumbar spine development. RESULTS: ①Among the 125 spastic cerebral palsy children, there were 119 cases of pelvic radiographs that met the measurement standards. In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, MP was (22.72±3.88), (26.53±4.36), (33.84±4.99), and (49.54±7.87)%, CE was(30.10±6.99) °, ( 22.92±4.19) °, ( 17.91±5.50) °, and (-0.70±17.33)°, AI was (16.41±2.77) °, (20.46±4.63) °, (23.76±5.10) °, and ( 29.15±7.35)°, respectively, there were significant differences between the two comparisons (P<0.05). And the higher GMFCS grade, the greater MP and AI, and the smaller CE.The NSA was(142.74±10.03) °, (148.66±9.09) °, (151.66±10.52) °, and (153.70±8.05)° in four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively. The differences between the two comparisons of the GMFCS gradeⅠgroup and the other three groups were statistically significant (P<0.05). NSA of GMFCSⅠgroup was significantly lower than that of the others, there was no significant difference among other groups(P>0.05). ② Among the 125 spastic cerebral palsy children, there were 88 cases of lumbar spine radiographs that met the measurement standards. ③The lumbar sagittal Cobb angle was(32.62±11.10) °, (29.86±9.90) °, (31.70±11.84) °, and (39.69±6.80)° in the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, respectively;GMFSS of grade Ⅳ group was significantly higher than that of other three groups, there was significant difference between the two comparisons (P<0.05);there were no significant differences between other groups (P>0.05). In the four groups with gradeⅠ, Ⅱ, Ⅲ, Ⅳ, the lumbosacral angle was (31.02±9.91) °, ( 26.57±9.41) °, (28.08±8.56) °, and ( 27.31±11.50)°, the lumbar lordosis index was (4.14±12.89), (8.83±13.53), (13.00±11.78), and (10.76±9.97) mm, the arch apex distance was (9.50±6.80), (6.68±3.20), (7.16±4.94), and (6.62±4.13) mm, respectively, there were no significant differences between the two comparisons(P>0.05). CONCLUSION ①In children with GMFCS gradeⅠ-Ⅳ, the higher the GMFCS grade, the worse the hip develops. ② Children with GMFCS grade Ⅲ-Ⅳ may be at greater risk for lumbar kyphosis.
Male ; Female ; Humans ; Child ; Child, Preschool ; Lordosis ; Retrospective Studies ; Cerebral Palsy ; Hip Dislocation ; Lumbar Vertebrae/diagnostic imaging* ; Muscle Spasticity