Objective:To investigate the prevalence of cardiometabolic multimorbidity (CMM) in Chinese middle-aged and elderly population, and the associated factors of cognitive function in CMM patients.Methods:It was a cross-sectional study. Data of demographic characteristics, lifestyle, chronic disease, and cognitive function in middle-aged and elderly subjects were obtained from the Harmonized CHARLS D version 2015 database, subjects with emotional and psychiatric disorders and memory-related disorders, and those with missing chronic disease data were excluded. The factors associated with cognitive function in CMM patients were analyzed with generalized linear regression model.Results:A total of 15 007 respondents aged (61.07±9.70) years were included in the analysis, 7 338 (48.9%) of whom were males. There were 3 303 cases of CMM with a prevalence rate of 22.01%, and the proportion of females was 54.9% (1 814/3 033), and the proportion of males was 45.1% (1 489/3 033). Generalized linear regression analysis showed that age, educational level, place of residence, depressive symptoms were correlated with cognitive function scores of CMM patients (all P<0.05). Conclusion:The prevalence rate of CMM in middle-aged and elderly people in China is higher, and age, education level, place of residence, depressive symptoms are associated with cognitive function in CMM patients.

Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective To explore the impact of Shexiang Baoxin Pill(SXBXP,a traditional Chinese patent medicine,broadly applied for the treatment of cardiovascular diseases)on coronary microvascular disease(CMD)and investigate the role and underlying mechanisms of muscone,a key bioactive component of the pills,in the treatment.Methods A total of 16 ob/ob mice(8 weeks old)were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group,receiving 10 mg/kg·d SXBXP or PBS via oral gavage,and another 8 wild-type mice with the same genetic background(WT group)were subjected as a negative control group.Cell model of CMD was established based on mouse coronary microvascular endothelial cells(MCMEC)under ischemia and hypoxic(HI)condition,and the cells were further treated with 20 μg/mL SXBXP(HI+SX)and 30 μmol/L muscone(HI+Muscone),respectively.Echocardiography was carried out for coronary flow reserve(CFR)and left ventricular function,and laser speckle imaging was applied to evaluate myocardial blood flow(MBF).Microvascular density in the heart was evaluated with CD31 immunofluorescence staining.The expression levels of vascular endothelial growth factor(VEGF)in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis.The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.Results In the ob/ob-Control group of mice,the levels of CFR,MBF,and cardiac microvascular density were significantly lower than those in the WT group(P<0.05),and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group(P<0.05),which indicates that SXBXP improves the CMD phenotype.The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice(P<0.05),while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group(P<0.05),illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition(P<0.05).Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC(P<0.05).These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.Conclusion SXBXP can improve CMD.Muscone,as a key component of SXBXP,promotes microvascular angiogenesis by inducing the expression of VEGF,then enhances myocardial perfusion,and consequently alleviates CMD.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Objective:To investigate the prevalence of cardiometabolic multimorbidity (CMM) in Chinese middle-aged and elderly population, and the associated factors of cognitive function in CMM patients.Methods:It was a cross-sectional study. Data of demographic characteristics, lifestyle, chronic disease, and cognitive function in middle-aged and elderly subjects were obtained from the Harmonized CHARLS D version 2015 database, subjects with emotional and psychiatric disorders and memory-related disorders, and those with missing chronic disease data were excluded. The factors associated with cognitive function in CMM patients were analyzed with generalized linear regression model.Results:A total of 15 007 respondents aged (61.07±9.70) years were included in the analysis, 7 338 (48.9%) of whom were males. There were 3 303 cases of CMM with a prevalence rate of 22.01%, and the proportion of females was 54.9% (1 814/3 033), and the proportion of males was 45.1% (1 489/3 033). Generalized linear regression analysis showed that age, educational level, place of residence, depressive symptoms were correlated with cognitive function scores of CMM patients (all P<0.05). Conclusion:The prevalence rate of CMM in middle-aged and elderly people in China is higher, and age, education level, place of residence, depressive symptoms are associated with cognitive function in CMM patients.

Objective To observe the effect of quercetin on mechanical allodynia,astrocyte activation,and upregulation of pain-related transient receptor potential vanilloid 1(TRPV1)and P2X purinoceptor 3(P2X3)in mice with paclitaxel-induced peripheral neuropathy.Methods Twenty-four C57BL/6 mice were divided randomly into control,model,and model+quercetin groups(n=8 mice per group).Paclitaxel(total dose 8 mg/kg)was injected intraperitoneally into mice in the model and model+quercetin groups to establish the model.Mice in the control group were injected intraperitoneally with the same volume of vehicle.On day 8 after the first injection,mice in the model+quercetin group were injected with 60 mg/kg quercetin solution orally and mice in the other groups were injected with the same volume of vehicle.Mechanical pain was measured by the von Frey test.Activation of astrocytes in the spinal dorsal horn was detected by immunofluorescence.Expression levels of TRPV1 and P2X3 in dorsal root ganglia were detected by immunofluorescence and Western Blot.Results(1)Compared with model group,the mechanical pain of mice in model+quercetin group were relieved.(2)Compared with model group,the activation of astrocytes and the expressions of TRPV1 and P2X3 in mice of model+quercetin group were alleviated(P＜0.05).Conclusions Quercetin can significantly reduce mechanical pain in mice with paclitaxel-induced peripheral neuropathy.This mechanism maybe related to alleviating the activation of astrocytes in the spinal dorsal horn and reducing expression of TRPV1 and P2X3 in the dorsal root ganglia.

Alzheimer's disease （AD） is a neurodegenerative disease associated with aging and age-related cognitive decline. It is characterized by insidious onset and progressive development， and has become a major global health and socioeconomic issue. The exact mechanisms underlying AD have not been fully elucidated， and various hypotheses have been proposed by researchers based on different etiologies， including the amyloid β （Aβ） cascade hypothesis， Tau protein hyperphosphorylation hypothesis， mitochondrial dysfunction and oxidative stress hypothesis， and neurotransmitter hypothesis. Therefore， there is an urgent need for comprehensive interventions targeting multiple pathways， links， and targets. Based on traditional Chinese medicine （TCM） theory and modern research findings， kidney-tonifying and anti-aging Chinese medicines have unique advantages of toxicity reduction， long-lasting effects， and treating both the root cause and the symptoms. They have been shown to counteract immune-inflammatory responses， clear reactive oxygen species， exhibit antioxidant properties， inhibit abnormal aggregation of Aβ and Tau proteins， reduce neuronal apoptosis， regulate central neurotransmitters， and modulate gut microbiota in AD. In recent years， stem cell therapy has been explored for the treatment of AD through two strategies： endogenous activation and exogenous transplantation， thereby replenishing and replacing damaged neurons. However， factors such as blood-brain barrier permeability， targeted delivery to the affected area， immune rejection， and cell survival rate can affect the efficacy of stem cell transplantation. Therefore， combining stem cell therapy with medication and other methods can further enhance the effectiveness of stem cell transplantation. Kidney-tonifying and anti-aging Chinese medicines can activate dormant neural stem cells（NSCs） in the body， promote neuroregeneration， and facilitate tissue and organ repair and reconstruction in AD. The combined treatment of these Chinese medicines and stem cell transplantation has shown more significant efficacy compared to either treatment alone. This combination therapy provides a new integration point for the modernization of TCM and offers new ideas and approaches for the prevention and treatment of AD， as well as improving the effectiveness of stem cell transplantation.

Objective:To investigate the clinical effect of composite transplantation of artificial dermis and autologous razor-thin graft combined with vacuum sealing drainage in the repair of joint scar after burn.Methods:The clinical data of patients with scar contracture deformity or scar ulcer after extensive burn admitted to the Department of Burns and Plastic Surgery of No. 926 Hospital of the Joint Logistics Force of PLA from January 2019 to December 2020 were retrospectively analyzed. Patients received one-stage contracture scar excision and release or scar ulcer debridement, Lando ?artificial dermis transplantation combined with vacuum sealing drainage, removal of the silicone membrane after complete vascularization of the wound, and secondary transplantation of autologous razor-thin graft. The survival and long-term appearance of skin graft, formation of scar and function recovery of joint were observed. Results:A total of 32 patients were included, including 24 males and 8 females, aged from 18 to 45 years, with an average age of 33 years. Scars were found in 4 cases of the metacarpophalangeal joint, 4 cases of the wrist joint, 10 cases of the elbow joint, and 14 cases of the knee joint and popliteal fossa. One patient underwent surgery to repair bilateral knee joint scar ulcers simultaneously, resulting in a total of 33 surgical sites. Among them, there were 23 sites of scar contracture deformities, 5 sites of scar ulcers, and 5 sites of scar contracture deformities with scar ulcers. After 2 weeks of artificial dermis coverage, the negative pressure device was removed, and the artificial dermis stent vascularization was good in 32 patients (33 surgical sites). After autologous skin graft transplantation, the survival rate was 100% (33/33). Postoperative follow-up for 3 to 12 months showed that there was no ulceration in the skin graft area, the skin color was close to normal, and there were no obvious scar contractures or hyperplasia. The joint function was satisfactory.Conclusion:The composite transplantation of artificial dermis and autologous razor-thin graft combined with vacuum sealing drainage is good to repair scar contracture or scar ulcer of joint after burn, the skin color and texture after operation, and the recovery of joint function is satisfactory.

Objective:To investigate the clinical effect of composite transplantation of artificial dermis and autologous razor-thin graft combined with vacuum sealing drainage in the repair of joint scar after burn.Methods:The clinical data of patients with scar contracture deformity or scar ulcer after extensive burn admitted to the Department of Burns and Plastic Surgery of No. 926 Hospital of the Joint Logistics Force of PLA from January 2019 to December 2020 were retrospectively analyzed. Patients received one-stage contracture scar excision and release or scar ulcer debridement, Lando ?artificial dermis transplantation combined with vacuum sealing drainage, removal of the silicone membrane after complete vascularization of the wound, and secondary transplantation of autologous razor-thin graft. The survival and long-term appearance of skin graft, formation of scar and function recovery of joint were observed. Results:A total of 32 patients were included, including 24 males and 8 females, aged from 18 to 45 years, with an average age of 33 years. Scars were found in 4 cases of the metacarpophalangeal joint, 4 cases of the wrist joint, 10 cases of the elbow joint, and 14 cases of the knee joint and popliteal fossa. One patient underwent surgery to repair bilateral knee joint scar ulcers simultaneously, resulting in a total of 33 surgical sites. Among them, there were 23 sites of scar contracture deformities, 5 sites of scar ulcers, and 5 sites of scar contracture deformities with scar ulcers. After 2 weeks of artificial dermis coverage, the negative pressure device was removed, and the artificial dermis stent vascularization was good in 32 patients (33 surgical sites). After autologous skin graft transplantation, the survival rate was 100% (33/33). Postoperative follow-up for 3 to 12 months showed that there was no ulceration in the skin graft area, the skin color was close to normal, and there were no obvious scar contractures or hyperplasia. The joint function was satisfactory.Conclusion:The composite transplantation of artificial dermis and autologous razor-thin graft combined with vacuum sealing drainage is good to repair scar contracture or scar ulcer of joint after burn, the skin color and texture after operation, and the recovery of joint function is satisfactory.