BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

Objective To explore the trend of lung cancer prevalence and influencing factors in a Hospital of Zigong from 2019-2023. Methods Select 2 835 lung cancer patients in Zigong region admitted to the Zigong Fourth People's Hospital from January 2019 to December 2023, and analyze the changes in the clinical characteristics and age strata of patients in different time periods in this group. Three thousand non-cancer respiratory patients in the same time period were included to compare the differences in patient data and to analyze the influencing factors affecting the changes in the characteristics of lung cancer in this region. Results There was an upward trend in the number of patients with pneumonia included between 2019 and 2023, with the highest volume of patients included in 2021 (609 cases). Over the 5-year period, the percentage of patients aged 0-39 years did not change significantly and accounted for a relatively low percentage. The proportion of patients aged 40-49 years increased (APC=0.69%, t=2.990, P<0.05), and the proportion of patients over 60 years old decreased, but to a lesser extent (APC=-0.25%, t=2.210, P<0.05). There were no significant differences in male percentage, lesion site, distant metastasis, smoking history and tumor diameter among patients in different years (all P>0.05). There were significant differences in TNM stage and lymphatic metastasis among patients in different years (all P<0.05). Compared with 2019, the proportion of early stage and patients with lymph node metastasis showed an upward trend within five years (χ²_{early stage}=9.153, P_{early stage}=0.002; χ²_{lymph node metastasis}=5.848, P_{lymph node metastasis}=0.016). The factor associated with the change in age of lung cancer patients in different years was family history of lung cancer (P<0.01). Factors associated with histologic changes in lung cancer patients in different years were age, family history of lung cancer and smoking history (all P<0.05). Factors associated with changes in TNM distribution in lung cancer patients in different years were age, tumor diameter, family history of lung cancer and lymph node metastasis (all P<0.05). Factors associated with changes in lymph node metastasis in lung cancer patients in different years were tumor diameter and TNM stage (all P<0.05). Conclusion From 2019 to 2023, the age of patients with lung cancer in a Hospital in Zigong area showed a decreasing trend, which may be influenced by family history of lung cancer.Patients with TNM early stage and lymph node metastasis increased respectively, which influenced each other and were interfered by factors of age, tumor diameter, and family history of lung cancer.

BACKGROUND: Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management. CONCLUSIONS The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans ; China/epidemiology* ; Stroke/mortality* ; Rural Population/statistics & numerical data* ; Male ; Female ; Urban Population/statistics & numerical data* ; Middle Aged ; Aged ; Aged, 80 and over ; Adult

Extracellular vesicles (EVs), nanoscale lipid bilayer vesicles actively secreted by organisms into the extracellular environment, are rich in specific bioactive substances, such as proteins, genetic materials and lipids. These vesicles are involved in intercellular interactions and can pass through the blood-brain barrier, and may thus potentially serve as important biological substances for treatment of neurological diseases. In this review, we summarize the biological origin of EVs and their therapeutic potential in neurological diseases, expound the possibility of EV-based treatment of neurological diseases using traditional Chinese medicine, and discuss the challenges and prospects of researches of EVs for the treating neurological diseases.
Extracellular Vesicles ; Humans ; Nervous System Diseases/therapy* ; Medicine, Chinese Traditional

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Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

BACKGROUND:Various clinical strategies for the treatment of tendinopathy have good short-term effects but poor long-term effects,and some studies have proven that mitochondria are closely related to the occurrence and development of tendinopathy.However,the relationship between mitochondria and tendinopathy and mitochondria-targeting therapeutic strategies for tendinopathy have not been summarized so far,which is not good for specialists and scholars in related fields to understand the recent research situation.OBJECTIVE:To review the existing clinical or preclinical original studies,in order to summarize the relationship between mitochondrial dysfunction and tendinopathy and the mitochondria-targeting methods for the treatment of tendinopathy,and to provide certain prospects for the evaluation and management of mitochondria in tendinopathy in the future.METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2009 to March 2024,and the search terms were"tendinopathy,tendon injuries,tendon,tendons,mitochondria,mitochondria dysfunction,mitochondria disease"both in English and Chinese.According to the exclusion and inclusion criteria,62 articles were finally included for review and analysis.RESULTS AND CONCLUSION:(1)In clinical tendinopathy patients or tendinopathy models,mitochondrial dysfunction is common,mainly represented by excessive production of reactive oxygen species,decreased activity of superoxide dismutase,ridge clutter and decreased number of mitochondria,which indicates that mitochondrial dysfunction will occur due to tendon injury,thus further worsening tendinopathy and forming a vicious cycle.(2)When the tendon has not been injured or tendinopathy has not yet occurred,the mitochondrial function will be affected by various internal and external factors,resulting in tendinopathy.This indicates that the normal tendon will be damaged,lesioned or even ruptured due to the abnormal function of the mitochondria.(3)Mechanical tensile stress,advanced glycosylation end products,aging and other internal and external factors are the main causes of mitochondrial dysfunction,and these factors will damage and weaken the biological activity and mechanical properties of normal tendons through molecular mechanisms such as apoptosis,inflammation and respiratory chain damage,and thereby induce tendinopathy.(4)According to molecular mechanisms,mitochondria-targeting therapies mainly include mitochondrial transfer/transplantation,transplantation,targeted antioxidants,etc.(5)This review mainly aims at clinical patients with tendinopathy or animal models with similar modeling methods,providing a reliable idea for clinical exploration of the pathogenesis of tendinopathy and targeted therapies for tendinopathy.However,the disadvantage is that the included studies are mainly animal experiments,and there is a lack of more clinical trials for verification.

Objective To investigate the role of matrix GLA protein(MGP)in the pathogenesis of idiopathic calcium oxalate kidney stones(ICOS),and to find potential biomarkers for early diagnosis and disease evaluation.Methods A total of 120 patients admitted to our hospital from September 2021 to September 2023 were prospectively included,of which 60 patients with ICOS were in the calculus group and 60 patients without calculus were in the control group.Serum biochemical indexes and immunohistochemical scores of the two groups were detected,urinary MGP levels were determined by ELISA,and MGP mRNA and protein expression in renal papilla tissues were detected by qPCR and Western blot.The independent risk factors of ICOS were screened by Logistic regression analysis,and the prediction model was drawn by nomogram.Results Compared with control group,urinary MGP content in calculus group was decreased[(1 805.91±244.44)pg/ml vs.(2 014.79±252.14)pg/mnl,P＜0.05).Expression of MGP mRNA and MGP protein in renal papillae decreased(0.89±0.15 vs.1.00±0.00,P=0.001)and decreased(0.87±0.18 vs.1.00±0.00,P＜0.05).MGP immunohistochemical scores of renal tissue were decreased[4(2-6)scores vs.6(4-8)scores,P＜0.001].Multivariate analysis showed that urinary calcium(OR=1.370),urinary MGP(OR=1.127),renal papilla MGP relative expression level(OR=27.532)and renal tissue MGP immunohistochemical score(OR=1.359)were independent risk factors for ICOS.Area under ROC curve of the nomogram prediction model built based on the above factors is 0.839,indicating that the model has good differentiation ability in risk prediction.Conclusion MGP is closely related to the pathogenesis of ICOS.Urinary and renal tissue MGP levels may be potential biomarkers for early diagnosis and disease assessment of ICOS.

The development of surgery brings about the transformation of surgeons′ con-cepts, and in turn, each renewal of surgical concepts propels progress of surgical techniques. These two aspects complement each other. The treatment of hepatocellular carcinoma is a comprehensive therapy centered on surgery. With the deepening understanding of liver anatomy, the surgical methods have evolved from initial local resection to anatomical liver resection, and then to resection of the tumor-bearing portal vein territory. In recent years, with the emergence of hepatic membrane anatomy, portal plate theory, and three-dimensional visualization, the theoretical and technical systems of laparoscopic anatomical liver resection has become more and more mature. Based on own experience and literature reports, the authors systematically elaborate on the construction of theoretical and technological systems of laparoscopic anatomic liver resection for hepatocellular carcinoma, for reference by colleagues.