BACKGROUND:The causal relationship between modifiable factors such as lifestyle,metabolic characteristics,and nutritional intake and joint sports injuries has been increasingly recognized in clinical studies.However,the exact causal relationship between these modifiable factors and joint sports injuries remains unclear. OBJECTIVE:To investigate the causal relationship between modifiable factors and joint sports injuries using Mendelian randomization to provide a basis for sports injury prevention. METHODS:The GWAS dataset of intervening factors and joint sports injuries was obtained from publicly available data.The causal relationships between lifestyle,metabolic characteristics,nutritional intake,and joint sports injuries were explored using the inverse variance weighting method,the MR-Egger method,and the weighted median method.For sensitivity analyses,Cochran's Q test,MR-Egger regression,leave-one-out method,and MR-PRESSO were used to verify the stability and reliability of the results. RESULTS AND CONCLUSION:(1)In terms of lifestyle,coffee(OR=0.29,95%CI:0.10-0.79,P=0.016),and tea consumption(OR=0.41,95%CI=0.19-0.85,P=0.017)were associated with a decreased risk of ankle and foot joint sports injuries,and coffee consumption(OR=3.31,95%CI=1.02-10.73,P=0.046)was potentially causally associated with an increased risk of shoulder joint sports injuries;and never smoking(OR=0.78,95%CI=0.70-0.87,P=1.49×10-5)was significantly causally associated with a decreased risk of ankle and foot joint sports injuries.(2)In terms of metabolic characteristics,calcium levels(OR=0.88,95%CI=0.79-0.98,P=0.017)were potentially causally associated with a decreased risk of wrist and hand joint sports injuries.(3)In terms of nutritional intake,vitamin A intake(OR=1.08,95%CI:1.02-1.13,P=0.007)was potentially causally associated with increased risk of knee joint sports injury.(4)For the sensitivity analysis,Cochran's Q test showed the existence of heterogeneity(P<0.05),so the random effect model was used for the analysis.MR-Egger regression and MR-PRESSO test did not find evidence of pleiotropy(P>0.05),and the leave-one-out method showed that the results were stable after eliminating single nucleotide polymorphisms one by one.(5)This study preliminarily reveals the effects of modifiable factors,such as lifestyle,metabolic characteristics,and nutritional intake,on the risk of joint sports injuries.It provides valuable research evidence and guidance for the prevention of joint sports injuries.

BACKGROUND:Clinical evidences have suggested a correlation between metabolic factors and sarcopenia.Blood metabolites have been found as biological factors underlying the mechanisms of musculoskeletal disorders.However,the causal relationship between blood metabolites and sarcopenia is unclear. OBJECTIVE:To explore the causal relationship between blood metabolites and sarcopenia-related traits through a two-sample Mendelian randomization analysis and to analyze their metabolic pathways. METHODS:A dataset of 486 blood metabolites and sarcopenia-related traits was obtained from public databases.The inverse variance weighting,MR-Egger and weighted median methods were used to assess the causal relationship of blood metabolites with muscle mass and strength across genders.Sensitivity analyses,including heterogeneity and gene pleiotropy,were performed to explore the robustness of the results.Metabolic pathway analysis of potential causal relationships was performed using the Metaboanayst 5.0 tool. RESULTS AND CONCLUSION:A total of 124 metabolites and sarcopenia-related traits were observed to have potential causal relationships(P<0.05).Mannose and 1-arachidonoylglycerophosphocholine were significantly causally associated with an increased muscle mass in males(P<1.03×10-4).Pentadecanoate and glycine were significantly causally associated with decreased muscle mass and muscle strength in females,respectively(P<1.03×10-4).Metabolic pathway analysis identified eight metabolic pathways associated with altered levels of muscle mass and muscle strength in sarcopenia,including the"glyoxylate and dicarboxylate metabolism"and"Glycine,serine and threonine metabolism."The identified metabolites are considered as useful circulating metabolic biomarkers for screening and prevention of sarcopenia in clinical practice,serving as candidate molecules for future mechanistic exploration and drug target selection.

BACKGROUND:Due to the very limited ability of articular cartilage to repair itself,articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own,which triggers or aggravates osteoarthritis and even leads to severe disability.Therefore,the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE:To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS:Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023,and bibliometric and visualization analyses were carried out using VOSviewer,Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION:The annual publication volume in the field of articular cartilage repair shows an overall increasing trend,with the United States,China,and Germany being the top three countries in terms of publication volume,and the research institutions focus on universities and hospitals,with Harvard University,New York Hospital for Special Surgery,and Shanghai Jiao Tong University being the top three institutions in terms of publication volume.AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field,and BIOMATERIALS is the journal with the highest number of citations in the field."Injectable hydrogels for cartilage and bone tissue engineering"is the most cited document published in the last decade,and the author with the most publications is Madry Henning,an active author in the field.The active authors in this field have formed a number of stable research teams with each other,and the cooperation between different teams needs to be further strengthened.Intra-articular injections,high tibial osteotomies,hydrogels,drug delivery,inflammation,cartilage regeneration,and scaffolds are the current hot topics of research in this field,and the application of 3D printing technology,bio-inks,silk proteins,injectable hydrogels,and exosomes in articular cartilage repair may be the frontier of research in this field.Integrating various innovative technologies and methods for more effective,durable and functional cartilage tissue regeneration and repair,and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field.

Objective:To explore the performance and value of urine DNA methylation technology in non-invasive diagnosis of upper tract urothelial carcinoma (UTUC).Methods:A retrospective analysis was conducted on the of 107 patients with UTUC (UTUC group) and 121 patients with benign upper urinary tract diseases (control group) admitted to Sun Yat sen Memorial Hospital and Peking University First Hospital from August 2019 to March 2021. There were 64 males (59.8%) and 43 females (40.2%) in the UTUC group, with the age of (67 ± 10) years old.There were 50 cases (46.7%) of ureteral cancer, 42 cases (39.3%) of renal pelvis cancer, and 15 cases (14.0%) of renal pelvis cancer combined with ureteral cancer.45 cases (42.0%) of non muscular infiltrative UTUC, 51 cases (47.7%) of muscular infiltrative UTUC, and 11 cases (10.3%) of unclear stage.There were 14 cases (13.1%) with low tumor grade and 93 cases (86.9%) with high grade. There were 81 males (66.9%) and 40 females (33.1%) in the control group, with the age of (52 ± 14) years old.There were 104 cases (86.0%) of urinary stones, 13 cases (10.7%) of ureteral stenosis or polyps, and 4 cases (3.3%) of simple hydronephrosis. Sixty cases (56.1%) in the UTUC group and 11 cases (9.1%) in the control group underwent urine cytology examination. Seventy-two cases (67.3%) in the UTUC group and 9 cases (7.4%) in the control group underwent urine in situ fluorescence hybridization (FISH) examination. Quantitative PCR detection based on ONECUT2 and VIM gene methylation was performed on urine sediment samples from both groups. If ≥ 1 gene was positive, it was determined as positive, and if both genes were negative, it was determined as negative. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of urine cytology, FISH, and urine DNA methylation tests were evaluated based on pathological or clinical diagnosis criteria.Results:The overall sensitivity of urine DNA methylation test was 84.1%, specificity was 90.9%, accuracy was 87.7%, positive predictive value was 89.1%, and negative predictive value was 86.6%, respectively. It's sensitivity and accuracy were significantly higher than that of urine cytology (43.3%, P<0.05)(52.1%, P<0.05)and FISH (69.4%, P<0.05)(71.6%, P<0.05). The accuracy was significantly higher than that of urine cytology (52.1%, P<0.05) and FISH (71.6%, P<0.05); There was no statistically significant difference in specificity between urine cytology (100.0%) and FISH (88.9%) ( P>0.05). The results of subgroup analysis showed that the diagnostic sensitivity of urine DNA methylation test for tumors in different locations was 74.0% (37/50 cases) for ureteral cancer, 90.5% (38/42 cases) for renal pelvis cancer, and 100.0% (15/15 cases) for renal pelvis cancer combined with ureteral cancer.The diagnostic specificity for different benign diseases was 92.3% (96/104 cases) for urinary stones, 84.6% (11/13 cases) for ureteral stenosis and polyps, and 75.0% (3/4 cases) for simple hydronephrosis. The diagnostic sensitivity of urine DNA methylation test for low-grade UTUC was 64.3%, significantly higher than that of urine cytology (20.0%) and FISH(36.4%)( P<0.05). The diagnostic sensitivity for high-level UTUC was 87.1%, which was higher than that of urine cytology (48.0%) and FISH (75.4%)( P<0.05). The diagnostic sensitivity for non muscular invasive UTUC was 77.8%, which was significantly higher than that of urine cytology (29.2%) and FISH (64.5%)( P<0.05). The diagnostic sensitivity for myometrial infiltrative UTUC was 88.2%, which was superior to urine cytology (53.6%) and FISH (72.7%)( P<0.05). The sensitivity and specificity of urine DNA methylation test in Sun Yat-sen Memorial Hospital of Sun Yat-sen University were 83.0% and 92.0%, respectively.It’s sensitivity and specificity in Peking University First Hospital were 85.2% and 85.7%, respectively. Conclusions:The urine ONECUT2 and VIM gene methylation assay have high sensitivity and accuracy in upper urinary tract urothelial carcinoma, which are superior to urine cytology as well as FISH.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Alzheimer's disease (AD) is one kind of degenerative diseases of the central nervous system, constituting a major social problem and economic threat around the world. Early diagnosis and intervention are the keys to its prevention and treatment. The traditional diagnosis system based on clinical experience and biomarkers has many limitations. A completely new "digital biomarkers" diagnostic system based on wearable devices is being constructed with the rapid development on artificial intelligence, 5G network and other technologies. This article will comprehensively describe the research progress on wearable devices which used to capture different cognitive-related signals such as memory, visual space, speech, executive functions in the construction of AD "digital biomarkers" diagnosis system, and forecast its application prospect in the future diagnosis, prevention and treatment of AD.

BACKGROUND: Resting heart rate (RHR) is considered as a strong predictor of total mortality and hospitalization due to heart failure in hypertension patients. Bisoprolol fumarate, a second-generation beta-adrenoreceptor blockers (β-blocker) is commonly prescribed drug to manage hypertension. The present study was to retrospectively evaluate changes in the average RHR and its association with cardiovascular outcomes in bisoprolol-treated coronary artery disease (CAD) patients from the CAD treated with bisoprolol (BISO-CAD) study who had comorbid hypertension. METHODS: We performed ad-hoc analysis for hypertension sub-group of the BISO-CAD study (n = 866), which was a phase IV, multination, multi-center, single-arm, observational study carried out from October 2011 to July 2015 across China, South Korea, and Vietnam. Multivariate regression analysis was used to identify factors associated with incidence of composite cardiac clinical outcome (CCCO), the results were presented as adjusted odds ratio (OR) along with 95% confidence interval (CI) and adjusted P value. RESULTS: A total of 681 patients (mean age: 64.77 ± 10.33 years) with hypertension from BISO-CAD study were included in the analysis. Bisoprolol improved CCCOs in CAD patients with comorbid hypertension, with RHR <65 and <70 beats/min compared with RHR ≥65 and ≥75 beats/min, respectively, in the efficacy analysis (EA) set. In addition, it lowered RHR in both intent-to-treat (ITT) and EA groups after 6, 12, and 18 months of treatment. Further, RHR 70 to 74 beats/min resulted in significantly higher risk of CCCOs EA set of patients (adjusted OR: 4.34; 95% CI: 1.19-15.89; P = 0.03). Also, events of hospitalization due to acute coronary syndrome were higher when RHR 69 to 74 beats/min compared to RHR <69 beats/min in ITT patients. CONCLUSION Bisoprolol can effectively reduce RHR in Asian CAD patients with comorbid hypertension and hence, improve CCCO without affecting their blood pressure.

Objective:To investigate the long-term outcome and prognostic indicators of diffuse pro-liferative lupus nephritis (DPLN).Methods:The primary endpoint of long-term follow-up and factors pos- sibly influencing the outcome were analyzed retrospectively in DPLN patients admitted to the First Affiliated Hospital of Wenzhou Medical University between Jan 1, 2000 and Dec 31, 2014. Patients were classified into three groups according to the evaluated glomerular filtration rate(eGFR) on the first day of admission: eGFR≥60 ml·min -1·1.73 m -2 (regular illness group); 15 ml·min -1·1.73 m -2≤eGFR<60 ml·min -1·1.73 m -2 (serious illness group); eGFR<15 ml·min -1·1.73 m -2 or dialysis (critical illness group). Clinical, histological, and outcome differences among the three groups were evaluated and compared using one-way analysis of variance (ANOVA) , χ2 test, Kaplan-Meier survival curve and Cox reggression analysis. Results:167 DPLN patients were studied [155 women; mean age (30±10) years; mean follow-up of (61±45) months]. Renal and patient survival of all patients was 86% at 5 years and 79% at 10 years. Kaplan-Meier analysis showed the renal and patient survival rate at 10 years in the regular illness group, serious illness group and critical illness group was 91%, 70% and 8%, respectively ( χ2=121.93, P<0.01, overall); regular illness group vs serious illness group ( χ2=4.05, P<0.05); regular illness group vs critical illness group ( χ2=97.05, P<0.01); serious illness group vs critical illness group ( χ2=52.28, P<0.01). Multivariable Cox regression analysis found that haematoglobin (Hb)<80 g/L [ HR=2.7, 95% CI(1.2, 6.3), P=0.019], eGFR<60 ml·min -1·1.73 m -2 [ HR=4.1, 95% CI(2.0, 8.2), P<0.01] and large crescents ≥30%[ HR=1.8, 95% CI (1.1, 2.9), P=0.021], were risk factors for the long-term outcome. Conclusion:DPLN patients with normal or slightly decreased renal function have a better long-term prognosis. Moderate to severe impairment of renal function, anemia and large crescents are associated with poor outcome.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective: To evaluate one-stage repair of leg open fracture with soft tissue defect by fixation plus skin flap. Methods: From January 2011 to January 2018, 34 patients with leg open fracture plus soft tissue defect were treated at Department of Orthopedics, The Second Affiliated Hospital to Harbin Medical University. They were 31 males and 3 females, aged from 13 to 54 years(average, 35 years). According to the Gustilo classification, the defects were type ⅢA in 31 cases and type ⅢB in 3 cases. The wound size ranged from 6 cm×3 cm to 25 cm×10 cm. All patients were treated with emergency fracture fixation and flap repair by one stage after thorough debridement. Internal bone plating was performed in 32 patients and external fixation at a single arm in 2 patients. All defects were repaired with a free anterolateral thigh flap. Flap survival, vascular crisis and bone infection were followed up postoperatively. Results: All the free flaps survived in the 34 cases with no vascular crisis. These patients were followed up for 6 months to 3 years (average, 10 years). The flaps healed well, with good appearance and soft texture. No bone infection occurred at the defective sites. After postoperative rehabilitation, the knee extension ranged from 160° to 180°, knee flexion from 90° to 110°, ankle dorsal extension from 90° to 110°, and ankle plantar flexion from 100° to 120°. Conclusion Soft tissue defects in leg open fracture can be effectively treated by flap repair after thorough debridement at the same time of fracture fixation, because the primary wound healing can avoid infection and lead to fine survival of the flap.