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 compare the impact of different primary tumor sites on the survival of patients with metastatic urothelial carcinoma(mUC)before and after the approval of immune checkpoints inhibitors(ICIs)based on data from Surveillance,Epidemiology,and End Results(SEER).Methods The mUC cases during 2013 and 2017 in the SEER database were enrolled.Cohorts were defined by primary tumor sites(renal pelvis,ureter,bladder)and then stratified by ICIs availability into non-ICIs era(2013)and ICIs era(2017).The survival differences in each cohort between the two eras were compared,and stratified analysis was performed.The 2-year overall survival(OS)was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards analysis.Results A total of 1750 mUC cases were enrolled,with 785 cases in the non-ICIs era and 965 in the ICIs era.No significant differences existed across different anatomical sites in the non-ICIs era,whether in the whole urinary system or inside bladder.The 2-year survival rates were 23.5％for ureteral cancer,18.0％for renal pelvic cancer,and 15.9％for bladder cancer.Significant prognostic disparities emerged among patients based on primary tumor sites in ICIs era(P＜0.05).The 2-year survival rates were 37.7％for ureteral cancer,25.5％for renal pelvic cancer,and 25.7％for bladder cancer.Further analysis revealed that the OS of the lesions originating from the bladder dome was significantly longer than that of the other bladder subgroups(P＜0.05),while the OS of the lesions in bladder bottom was the shortest.The 2-year survival rates were 52.0％for the bladder dome,13.0％for the bladder body,and 10.7％for the bladder bottom.Conclusion Our study indicates that in the non-ICIs era,there was no significant difference in the prognosis among mUC patients with lesions from different primary sites.In the ICIs era,the OS of ureteral cancer was significantly longer than that of bladder cancer and renal pelvis cancer.As for patients with metastatic bladder cancer,those with tumor located at the top of the bladder had a significantly better prognosis than those with tumors at other sites.

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 compare the impact of different primary tumor sites on the survival of patients with metastatic urothelial carcinoma(mUC)before and after the approval of immune checkpoints inhibitors(ICIs)based on data from Surveillance,Epidemiology,and End Results(SEER).Methods The mUC cases during 2013 and 2017 in the SEER database were enrolled.Cohorts were defined by primary tumor sites(renal pelvis,ureter,bladder)and then stratified by ICIs availability into non-ICIs era(2013)and ICIs era(2017).The survival differences in each cohort between the two eras were compared,and stratified analysis was performed.The 2-year overall survival(OS)was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards analysis.Results A total of 1750 mUC cases were enrolled,with 785 cases in the non-ICIs era and 965 in the ICIs era.No significant differences existed across different anatomical sites in the non-ICIs era,whether in the whole urinary system or inside bladder.The 2-year survival rates were 23.5％for ureteral cancer,18.0％for renal pelvic cancer,and 15.9％for bladder cancer.Significant prognostic disparities emerged among patients based on primary tumor sites in ICIs era(P＜0.05).The 2-year survival rates were 37.7％for ureteral cancer,25.5％for renal pelvic cancer,and 25.7％for bladder cancer.Further analysis revealed that the OS of the lesions originating from the bladder dome was significantly longer than that of the other bladder subgroups(P＜0.05),while the OS of the lesions in bladder bottom was the shortest.The 2-year survival rates were 52.0％for the bladder dome,13.0％for the bladder body,and 10.7％for the bladder bottom.Conclusion Our study indicates that in the non-ICIs era,there was no significant difference in the prognosis among mUC patients with lesions from different primary sites.In the ICIs era,the OS of ureteral cancer was significantly longer than that of bladder cancer and renal pelvis cancer.As for patients with metastatic bladder cancer,those with tumor located at the top of the bladder had a significantly better prognosis than those with tumors at other sites.

BACKGROUND:Increasing studies have found that estrogen has a certain correlation with tendinopathy,but for a long time,there are few experiments and summaries of estrogen in tendinopathy,which makes it difficult for specialists and scholars in related fields to fully understand the research status. OBJECTIVE:To summarize the current clinical or preclinical original research,so as to summarize the role of estrogen in tendinosis,and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future. METHODS:Relevant literature in PubMed,Web of Science,CNKI,WanFang,and VIP databases were searched by computer.Search time was from January 2008 to September 2023.The search terms were"oestrogen,estrogen,estrogen receptor,tendinopathy,tendonopathy,sinew,tendon,tendons,myotenositis"in English and"estrogen,estrogen receptor,tendinosis,tendon,tendinitis"in Chinese.According to the selection criteria,the search results were screened and excluded,and finally 60 documents were included for review and analysis. RESULTS AND CONCLUSION:In vivo studies have shown that estrogen can promote tendon anabolism.In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis,but most of the experiments are limited to animal models.Estrogen receptor β acts more in tendon injury and repair processes,but estrogen receptor α has not been found to have a major impact on tendon injury.The expression of estrogen receptor β can repair the tendon by affecting the formation of fat,the deposition of type I collagen and reducing the apoptosis of tendon cells,while its over-expression may promote inflammation and angiogenesis,thus promoting the inflammatory process and playing a role in tendon injury.Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon,decrease the elasticity of tendon,inhibit the synthesis and metabolism of the tendon,which is not conducive to the repair of tendon injury,while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells.At present,the molecular mechanism of estrogen in tendon injury has not been fully explained.More experiments focus on tendon collagen synthesis,cell proliferation and apoptosis.Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis,E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways,and high levels of estradiol reducing the level of free-circulating insulin-like growth factor.Various estrogens,including endogenous estrogens and phytoestrogens,are beneficial to the repair of tendinopathy at normal levels,and estrogen receptor β mainly affects the formation of fat,the deposition of type I collagen and the reduction of apoptosis of tendon cells through,which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy.

Objective To explore the mechanism of Dahuanglinxian Capsule for intervening gallstone formation by regulating the expression levels of ABCB11 and ABCC2 mRNA and protein.Methods Forty male C57BL/6 mice were divided into the normal group(group N),model group (group M),ursodeoxycholic acid group (group U) and Dahuanglinxian Capsule treatment group (group D),10 cases in each group.The group N was fed with normal diet,while the group M,U and D were fed with lithogenic fodder for 8 weeks.Meanwhile the group U and D were given the medication intervention,once daily,for continuous 8 weeks of gavage.After successful modeling,mRNA and protein expression levels of ABCB11 and ABCC2 were detected by RT-PCR and immunohistochemistry.Results Compared with the other three groups,the expressions of ABCB11 and ABCC2 mRNA gene and protein in M group were significantly reduced(P＜0.01);while,there was no statistical difference in the expressions of ABCB11 and ABCC2 mRNA and protein between the group D and N(P＞0.05).Conclusion Dahuanglinxian Capsule can prevent the gallstone formation by regulating the expression of ABCB11 and ABCC2 mRNA and protein.

We isolated and identified the bacterial pathogen in a pyogenic balanoposthitis patient and investigated the drug resistance and its mechanism of the isolate.Urethral secretions and balanus pustule liquids were collected for microscopic examination after Gram-staining and detection of mycoplasma using Mycoplasma IST 2 kit.The two samples were inoculated on Columbia blood plate,N.gonorrhoeae selective plate and chromID Candida plate for isolation.The obtained colonies were identified by VITEK 2-compact automatic bacterial detection and analysis system.Moreover,PCR was performed to detect 16S rRNA gene of N.gonorrhoeae in the samples and colonies.KB method was applied for detecting susceptibility of five common antibiotics against the isolate.The β-lactamase and extended spectrum β-lactamase confirmatory tests were used to investigate the enzyme production of the isolate as well as drug resistance-associated tetM,TEM,mefA and ermF genes in the isolate were detected by PCR.Results showed that all the clinic samples showed negative for mycoplasma.All the isolating cultivation results of urethral secretions were negative while the balanus pustule liquids provided positive isolating cultivation in the blood and selective plates.The VITEK 2-compact system and 16S rRNA-PCR revealed that the isolated strain belongs to N.gonorrhoeae.The isolate can produce β-lactamases and resist to penicillin G,ciprofloxacin and tetracycline.The tetM,TEM,mefA and ermF genes could be found in the isolate's genome.The patient's balanoposthitis is caused by infection of N.gonorrhoeae.The multidrug resistance of Neisseria gonorrhoeae isolate is closely associated with its carried resistant genes.

The aim of this study is to determine the diversity of virulence genes carried by different vancomycin-resistant enterococci (VRE),which will provides a basis for studying pathogenic mechanism of VRE.Microdilution-based drug sensitivity test was applied to detect the vancomycin resistance of 490 Enterococcus faecium isolates and 862 Enterococcus faecalis isolates in Zhejiang area.The seven virulence genes (ace,asa1,cylA,efaA,esp,gelE and hyl) in the isolates of VRE were detected by PCR.According to the results of drug sensitivity test,10％ of the E.faecium isolates (49/490) and 0.8％ of the E.faecalis (7/862) were identified as VRE.In the vancomycin-resistant E.faecium isolates,five isolates were negative for any of the target genes and the other 44 isolates were positive for asa1,esp,gelE and hyl genes alone,in which the esp (73.5％,36/49) and hyl (53.1％,26/49) were the predominant genes and single or double virulence genes acted as the major carrying models.Except for the hyl gene,the vancomycin-resistant E.faecalis isolates were positive for the other six pathogenic genes,and the isolates could carry 3-6 pathogenic genes.All the data indicate that E.faeciurn is the major species of VRE in the local area,and the carrying rate,types and models of virulence genes in the vancomycin-resistant E.faecium and E.faecalis isolates are obviously different.

Objective To evaluate and analyze the diagnostic accuracy of 256-slice computed topographic angiog-raphy (CTA) and coronary angiography (CAG) in patients with coronary artery disease (CAD). Methods One hundred and one patients (suspected CAD and confirmed CAD with re-examination) underwent the 256-slice CTA and CAG were includ-ed in this study. The coronary artery imaging data of 101 patients were retrospectively collected and analyzed. Calculations for accuracy were conducted on a segmental basis. A total of 1 313 comparable segments were evaluated. The accuracy of 256-slice CTA was evaluated in the diagnosis of moderate and severe stenosis of coronary artery(stenosis in segments of cor-onary artery≥50%). The values for diagnostic accuracy of 256-slice CTA were analyzed, including mild stenosis: ＜50%, moderate stenosis:50%~75%, severe stenosis:76%~100%and complete occlusion. Results The sensitivity of 256-slice CTA for diagnostic accuracy to coronary heart disease was 94.87%, and the specificity was 52.17%. The positive predictive value was 87.06%and the negative predictive value was 75.00%. The accuracy rates of 256-slice CTA for evaluating the cor-onary artery stenosis were:mild stenosis (44.23%), moderate stenosis (44.23%), severe stenosis (40.00%) and total occlusion of coronary artery (51.77%), respectively. Conclusion The diagnostic value of 256-slice CTA for the degree of coronary ar-tery stenosis is insufficient, which can be used as a potential alternative screening examination to detect coronary artery ste-nosis in suspected patients and a method of re-examination in low risk patients with CAD.

Objective To compare the efficiency and safety of aspirin-dipyridamole and warfarin in the prevention of thromboembolism in patients with nonvalvular atrial fibrillation(NVAF)and high risk factors.Methods One hundred and forty NVAF patients with high risk factors were randomly divided into two groups.Warfarin group[78 cases international normalized ratio(INR)2.0-3.0,for the patients older than 75 years,INR ranging from 1.6 to 2.5]and combination group(62 cases received aspirin 160 mg once every day plus dipyridamole 160 mg 3 times every day).The incidence of death,thromboembolism(including stroke and peripheral arteries embolism)and hemorrhage events were observed.Results Followed-up 12-28 months.In warfarin group,3 cases lost,2 cages had stroke,2 cases suffered from serious bleeding events,6 cases had minor bleeding events.In combination group,2 cases lost,6 cases had stroke,and 2 cases suffered from peripheral arteries embolism events,3 cases had minor bleeding events,but no serious bleeding events occurred.The incidence of thromboembolism in warfarin group wag,lower than that in combination group[2.7%(2/75)vs 13.3%(8/60),P<0.05].There was no significant difference of the bleeding rate between the two groups[10.7%(8/75)vs 5.0%(3/60),P>0.05].Conclusions Warfarin anticoagulative therapy is more effective than aspirin and dipyridamole antiplatelet dual therapy for the prevention of thromboembolism events in patients with NVAF and high risk factors.The major bleeding events in warfarin group occurs in patients with INR>3.0,so under intensive monitoring(INR 2.0-3.0),warfarin therapy is effective and safety.