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.

Bow hunter's syndrome,also referred to as rotational vertebral artery occlusion syndrome,is a rare etiological factor of posterior circulation infarction.This article reported a case of a young male patient who experienced recurrent posterior circulation infarctions caused by bilateral bow hunter's syndrome.Carotid ultrasonography confirmed a marked reduction in blood flow velocity in both vertebral arteries during neck rotation.High-resolution MR angiography and CT angiography of the head and neck revealed dissection involving the V3 segment of the left vertebral artery.The findings suggested that bow hunter's syndrome may be associated with thrombus formation secondary to repetitive mechanical compression of the vertebral artery intima,which could potentially lead to arterial embolism and subsequent cerebral infarction.This paper presents the patient's diagnostic and therapeutic course and includes a review of relevant literature aimed to enhance clinical awareness and understanding of this uncommon condition.

Objective To explore the disinfection effect of periodic hypochlorous acid infusion on water supply pipelines.Methods Water specimens from 6 water outlets of central sterile supply department were collected at baseline for microbial culture.After introducing a slightly acidic hypochlorous acid water generator,water speci-mens were collected every 10 days.Continuous disinfection with hypochlorous acid was carried out on the 1st-3rd day,and discontinued on the 4th-10th day.Water specimens of 6 water outlets were collected on the 1st,4th,7th,and 10th day of each cycle,in total 3 cycles.Microbial culture and metagenomic next-generation sequencing(mNGS)analysis were conducted simultaneously on all water specimens from the outlets of the endoscope cleaning tank.Results Before disinfection of the pipeline,a total of 18 bottles of water specimens were collected.Bacterial count of water specimens from 10 bottles(55.56％)was between 102 and 104 CFU/mL,mainly Sphingomonas ad-hesins and Bacillus cereus.After disinfection,only 2 out of 72 water specimens(2.78％)exceeded the bacterial lim-it.The mNGS results showed that three most dominant bacterial genera in the pre-disinfection water specimens were Sphingomonas,Methylobacterium,and Ralstonia,with stringent mapped reads number(SMRN)ranging from 10 000 to 100 000;while the most dominant bacterial genera in post-disinfection water specimens were Lacto-baci-llus,Ralstonia,Acinetobacter,and Bradyrhizobium.PCoA analysis showed that there was a statistically sig-nificant difference in β-diversity of water specimens before and after disinfection(P＜0.05).Conclusion Periodic hypochlorous acid infusion disinfection can effectively remove bacterial biofilms in water pipelines,but there is a risk of bacterial biofilm recovery during disinfection suspension.In the future,monitoring and management of medical water should be strengthened.

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.

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.

Objective To explore the disinfection effect of periodic hypochlorous acid infusion on water supply pipelines.Methods Water specimens from 6 water outlets of central sterile supply department were collected at baseline for microbial culture.After introducing a slightly acidic hypochlorous acid water generator,water speci-mens were collected every 10 days.Continuous disinfection with hypochlorous acid was carried out on the 1st-3rd day,and discontinued on the 4th-10th day.Water specimens of 6 water outlets were collected on the 1st,4th,7th,and 10th day of each cycle,in total 3 cycles.Microbial culture and metagenomic next-generation sequencing(mNGS)analysis were conducted simultaneously on all water specimens from the outlets of the endoscope cleaning tank.Results Before disinfection of the pipeline,a total of 18 bottles of water specimens were collected.Bacterial count of water specimens from 10 bottles(55.56％)was between 102 and 104 CFU/mL,mainly Sphingomonas ad-hesins and Bacillus cereus.After disinfection,only 2 out of 72 water specimens(2.78％)exceeded the bacterial lim-it.The mNGS results showed that three most dominant bacterial genera in the pre-disinfection water specimens were Sphingomonas,Methylobacterium,and Ralstonia,with stringent mapped reads number(SMRN)ranging from 10 000 to 100 000;while the most dominant bacterial genera in post-disinfection water specimens were Lacto-baci-llus,Ralstonia,Acinetobacter,and Bradyrhizobium.PCoA analysis showed that there was a statistically sig-nificant difference in β-diversity of water specimens before and after disinfection(P＜0.05).Conclusion Periodic hypochlorous acid infusion disinfection can effectively remove bacterial biofilms in water pipelines,but there is a risk of bacterial biofilm recovery during disinfection suspension.In the future,monitoring and management of medical water should be strengthened.

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.

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.