Objective To analyze the epidemiological characteristics and prognostic factors of acute cardiovascular and cerebrovascular events in Jianyang City from 2020 to 2023. Methods Medical records of acute cardiovascular and cerebrovascular disease patients treated in three hospitals in Jianyang City from January 2020 to December 2023 were selected, and their epidemiological characteristics were analyzed. Multivariate logistic regression was used to analyze the risk factors for mortality. Results From 2020 to 2023, 23000 cases of acute cardiovascular and cerebrovascular events were reported in Jianyang City, with a standardized incidence rate of 508.76/100 000 and a gender ratio of 1.33:1. All diseases and the total standardized incidence rate of men are higher than those of women; ≥ The total incidence rate and all incidence rate of the 85 year old group are the highest; The incidence rate is the highest in 2021, and the incidence rate is the highest in spring and winter. The standardized mortality rate of acute cardiovascular and cerebrovascular events was 108.08/100 000, with significant differences among different ages, disease types, and onset seasons (P<0.05). Multivariate analysis showed that age, onset season, and disease type were independent risk factors for patient mortality (P<0.05). Conclusion From 2020 to 2023, the standardized incidence rate of acute cardiovascular and cerebrovascular events in Jianyang City is higher, which is more common in the elderly population. The risk of men is higher than that of women, and the risk is higher in spring and winter. Age, disease type, and onset season are all directly related to the risk of death. In the future, it is necessary to strengthen the monitoring and prevention of cardiovascular and cerebrovascular diseases, and optimize emergency treatment work in order to improve patient prognosis.

Background and purpose:Silent information regulator proteins(sirtuins,SIRT)are a class Ⅲ histone deacetylases with nicotinamide adenine dinucleotide(NAD+)as coenzyme.YME1 like 1 ATPase(YME1L1)is essential for the maintenance of mitochondrial morphology,function and plasticity.Optic atrophy 1(OPA1)mainly mediates mitochondrial fusion.The aim of this study was to explore the expression of SIRT3 in the endocrine resistance of breast cancer,the relationship between SIRT3 and YME1L1 and OPA1,and the mechanism of SIRT3 in the endocrine resistance of breast cancer.Methods:4-hydroxytamoxifen was used to induce tamoxifen-resistant MCF-7/TAM cells.cell counting kit-8(CCK-8)was used to detect cell proliferation and verify drug resistance.The mitochondrial morphology was observed by transmission electron microscopy(TEM)and immunofluorescence staining.The expressions of SIRT3 and OPA1 were detected by real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.JC-1 staining was used to detect mitochondrial membrane potential,and dihydroethidium(DHE)staining was used to detect reactive oxygen species(ROS)to verify mitochondrial function.SIRT3 was knocked down in drug-resistant cells by RNA interference,and SIRT3 and YME1L1 wild type(WT),simulated acetylation state mutant(MUT K237Q),and simulated deacetylation state mutant(MUT K237R)were overexpressed in parental cells by overexpression plasmid.Immunoprecipitation assay(IP)and immunofluorescence(IF)were used to verify the interaction between SIRT3 and YME1L1.Results:RTFQ-PCR and Western blot results showed that SIRT3 gene expression and protein level was significantly higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in parental cells decreased the sensitivity of breast cancer cells to tamoxifen.Knockdown of SIRT3 in drug-resistant cells enhanced the sensitivity of drug-resistant cells to tamoxifen.DHE staining showed that the ROS level was lower in tamoxifen resistant cells than in parental cells at the same concentration.Transmission electron microscopy and fluorescence staining showed that the mitochondria of the drug-resistant cells were elongated compared with the parental cells.Western blot results showed that the expression level of L-OPA1 protein was higher in drug-resistant cells than in parental cells.Overexpression of SIRT3 in the parental cells resulted in enhanced mitochondrial function and longer mitochondrial morphology compared with the control cells.Western blot showed that the expression of L-OPA1 was upregulated.When SIRT3 was knocked down in drug-resistant cells,the opposite result was obtained.We further verified how SIRT3 regulated OPA1 protein,affected the morphology and function of mitochondria,and promoted drug resistance of breast cancer.Overexpression of YME1L1(wild-type and mutant plasmids)in parental cells showed that overexpression of YME1L1 in the simulated deacetylation state resulted in similar results as overexpression of SIRT3,and overexpression of YME1L1 in the acetylated state resulted in similar results as knockdown of SIRT3.IP assay confirmed the interaction between SIRT3 and YME1L1 in breast cancer cells.The acetylation level of YME1L1 was different at different SIRT3 expression levels.IF assay showed that YME1L1 was co-localized with SIRT3 in MCF-7 cells.Conclusion:SIRT3 is highly expressed in tamoxifen-resistant breast cancer cells.SIRT3 upregulates L-OPA1 expression by deacetylating YME1L1,thereby promoting mitochondrial fusion and enhancing mitochondrial function,and promotes tamoxifen resistance in breast cancer.

Objective To explore the trend in self-management efficacy and exercise compliance among patients within 6 months after radical resection of lung cancer and analyse the predictive correlation between the factors to provide references for improvement of exercise compliance in patients after lung cancer surgery.Methods Convenience sampling was used to select patients who had surgery of radical resection of lung cancer for the first time in the departments of thoracic surgery of two Grade IIIA hospitals in Nanchong between December 2022 and May 2023.The Chinese-version strategies used by people to promote health(C-SUPPH)and exercise compliance scale were employed to assess the self-management efficacy and patient exercise compliance at four time points:1 day before discharge(T1)and 1 month(T2),3 months(T3)and 6 months(T4)after surgery.A cross-lagged model was constructed to analyse the causal correlation between self-management efficacy and exercise compliance.Results Within 6 months after surgery,both of self-management efficacy and exercise compliance in the patients after radical resection of lung cancer were seen initially increased and then decreased(P<0.05).The cross-lagged model revealed that self-management efficacy and exercise compliance during the early postoperative period(TI-T2)exhibited reciprocal causation(β=0.254,P=0.003;β=0.332,P=0.007).Between T2 and T3,higher self-management efficacy positively predicted an increased exercise compliance(β=0.286,P<0.001).However,during T3 and T4,no predictive relationship was observed between the indicators(P>0.05).Conclusion The self management efficacy of patients after lung cancer sugery is at middle level and their exercise compliance is at low level.This study indicates that the initial levels of self-management efficacy and exercise compliance among patients after radical resection of lung cancer do not necessarily reflect a long-term trend.The predictive correlation between the two factors also varies over the time.Healthcare providers should consider the dynamic changes and individual differences across different stages after surgery,and implement timely and targeted intervention.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective To investigate the effects of amylin,also known as islet amyloid polypeptide(IAPP),on learning and memory abilities and the phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)signaling pathway in APP/PS1 mice.Methods A total of 20 APP/PS1 mice were randomly divided into Alzheimer's disease(AD)group and IAPP group,with 10 mice in each group.The mice in the latter group were given an intraperitoneal injection of 0.5 μmol/L IAPP,and those of the former group received same dose of PBS.Both interventions were given once per day,for 10 weeks.Morris water maze test was used to measure the learning and memory abilities;HE staining was employed to observe the pathological changes in the hippocampus;Transmission electron microscopy was utilized to observe the ultrastructure of hippocampal neurons;Biochemical assay were conducted to detect the contents of glutathione peroxidase(GSH-Px),malondialdehyde(MDA)and superoxide dismutase(SOD)in hippocampal tissues;ELISA was applied to measure the levels of inflammatory factors such as IL-1β,IL-6,and TNF-α as well as content of Aβ42 in hippocampal tissues;And Western blotting was conducted to detect the expression of PI3K/Akt proteins.Results Compared with the AD group,significantly shorter platform latency(P＜0.01),increased number of traversing the platform and longer time to explore the hidden platform(P＜0.01)were observed in the IAPP group,but no such difference was seen in the swimming speed of the mice.HE staining displayed that the IAPP group had more and well-arranged nerve cells in the hippocampal tissue when compared with the AD group(P＜0.05).Lower Aβ protein expression(P＜0.01),reduced oxidative stress and decreased contents of inflammatory factors(P＜0.01)in hippocampal tissue were observed in the IAPP group than the AD group.The IAPP group showed clearer structure of neuronal mitochondria,reduced vacuolization,and better arranged microtubules and microfilaments,and elevated expression of p-PI3K/PI3K and p-Akt/Akt proteins when compared with the AD group(P＜0.01).Conclusion Amylin can reduce oxidative stress and inflammatory responses,improve learning and memory abilities in AD mice,and promote the activity of PI3K/Akt signaling pathway.

Objective To study the effect of neuromodulatory protein-1(NRG-1)in inhibiting sepsis induced myocardial injury and its mechanism.Methods The rat sepsis model was established by cecal ligation and puncture(CLP).SD rats were divided into the sham operation group,sepsis group,sepsis+NRG group(rhNRG,10 μg/kg).After 12,24 h of successful modeling,the heart and peripheral serum of the surviving rats in each group were taken respectively.The HE staining was used to observe the changes of cardiac tissue morphology and structure,and ELISA was used to detect the expression levels of creatine kinase(CK),crea-tine kinase MB isoenzyme(CK-MB),sensitive troponin Ⅰ(cTnⅠ)in serum,tumor necrosis factor-α(TNF-α)in cardiac tissue and IL-6 expression level;Western blot was used to detect the phosphorylation protein ki-nase B(p-Akt),phosphorylation glycogen synthase kinaseβ(p-GSK3β),B-cell lymphoma/leukemia-2(Bcl-2)and Bax protein expression in rat myocardial tissue.Results After 12,24 h of modeling,compared with the sham group,the expression levels of CK,CK-MB and cTnⅠ in serum,TNF-α,IL-6 and Bax protein in myocar-dial tissue in the sepsis group all were significantly increased(P＜0.05),while the expression levels of p-Akt and p-GSK3β in myocardial tissue were significantly decreased(P＜0.05).After 12,24 h of modeling,com-pared with the sepsis group,the expression levels of CK,CK-MB,cTn Ⅰ in the serum and the expression levels of TNF-α,IL-6 in the myocardial tissue of the sepsis+NRG group were significantly decreased;after 24 h of modeling,compared with the sepsis group,the expression level of Bax protein in myocardial tissue of the sep-sis+NRG group was decreased,while the p-Akt,p-GSK3β expression levels were increased(P＜0.05).The pathological results showed that compared with the sham operation group,the sepsis group produced signifi-cant lesions;compared with the sepsis group,the lesions in the sepsis+NRG group were alleviated.Conclusion The expression levels of related biomarkers in septic myocardial injury have change.NRG-1 could improve the cardiac function through Akt/GSK3β pathway,inhibit the related proinflammatory factors and reduce the myocardial tissue damage.

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

Objective To find out the willingness to choose old-age care mode and the influencing factors of the elderly in the younger age group.Methods A multi-stage stratified whole cluster random sampling method was used to conduct a questionnaire survey on the willingness of the younger elderly in Zhangye City.Results The proportion of low-aged elderly in Zhangye City who chose family old-age care was the highest,and factors such as who they relied on to solve their old-age problems,opinions on moving into old-age care institutions,knowledge of the combination of medical care and nursing care,loneliness,and the number of chronic illnesses affected the willingness of low-aged elderly to live in old-age care.Conclusion In Zhangye City,family care is the main mode of old-age care for low-aged elderly.In the future,the relevant government departments should take into account the diversified needs of the elderly and the characteristics of the influencing factors,in order to realise the precise supply of the demand for elderly care services for the elderly.

Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.

Objective To investigate the risk factors of short-term adverse prognosis and the predictive value of Charlson comorbidities index(CCI)in patients with central pulmonary embolism(PE).Methods 115 cases of central PE patients were retrospectively analyzed.According to the adverse prognosis during hospitalization,the subjects were divided into adverse event group and no adverse event group.The clinical characteristics of the ad-verse event group were analyzed.Multivariate Logistic regression analysis was performed for statistically significant indicators.Results The most common clinical symptoms of central PE patients were chest distress or dyspnea(77.4％ ),followed by cough(35.7％ ),chest pain(28.7％ ),syncope(9.6％ )and hemoptysis(7.8％ ).There were no statistically significant differences in gender,smoking history,drinking history,symptoms and signs between the two groups.In univariate analysis,CCI,grouping score of thrombus location,white blood cell count,neutrophil count and urea nitrogen were associated with adverse events in central PE patients,with statistical signif-icance(P＜0.05).After Logistic regression multivariate analysis,increased neutrophil count(OR=1.494,95％ CI:1.073-2.080,P=0.017)was an independent risk factor(P＜0.05).The CCI in the group with adverse e-vents was higher than that in the group without adverse events(P=0.004).Multivariate analysis showed that in-creased CCI(Oβ=1.342,95％ CI:1.022-1.763,P=0.034)was an independent risk factor,and the risk of adverse events increased by 34.2％ for every one-point increase in CCI.The thrombus location score of the group with adverse events was significantly higher than that of the group without adverse events(OR=2.586,95％ CI:1.366-4.896,P=0.004),and the risk of adverse events increased 1.586 times with each increase of thrombus location score.Conclusion Increased neutrophil count,CCI,and thrombus location score are associated with poor short-term prognosis in central PE patients.