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.

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 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.

Objective To investigate the clinical features of cerebral venous sinus thrombosis (CVST)in patients with malignancy as well as its underlying pathogenesis. Methods The clinical data, including clinical presentation, laboratory results, neurological images were retrospectively reviewed in hospital patients with active malignant tumor and cerebral venous thrombosis from January 2006 to December 2016. Results Among the 586 CVST patients, 24 patients (4.10%) were with malignant tumor. Among these 24 patients, there were 8 males and 16 females with an average age of (39.88 ± 21.71) years old. Four patients (16.67%) had the risk factors of cerebral venous sinus thrombosis, while the other 20 patients(83.33%)had not any such risk factors.At the symptom onset of CVST, 22 patients(91.67%) had headache and focal neurological deficit, such as limbs weakness and numbness. The common substyles of malignant tumor were lung cancer (33.33%), breast cancer (29.17%)and acute lymphocytic leukemia(20.83%).Most patients(58.33%)were found to have cerebral metastasis.22 patients (91.67%) had elevated plasma D-dimmer level, and 19 patients (79.17%) had elevated plasma cancer biochemical marker levels.Conclusions Cancer-related CVST had the features including lacking conventional risk factors, elevated plasma D-dimmer and cancer biochemical marker levels.Cerebral metastasis and hypercoagulable state may be responsible for the pathogenesis of CVST.

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: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 investigate the efficacy and safety of intravesical instillation of BCG vaccine in the prevention of early recurrence of middle and high risk non-muscle invasive bladder cancer.Methods From July 2015,patients with non-muscle invasive bladder cancer aged 18-75 years with informed consent were screened and underwent transurethral resection of bladder tumor (TURBT).Immediately intravesical instillation of epirubicin 50 mg was given postoperatively.After pathology was comfirmed,patients was enrolled in group 1 (BCG15) or group 2 (BCG 19) or the control group (epirubicin 18) randomly with SAS 9.3 software.Data of follow-up and Adverse event was collected and analyzed.Results By May 31,2019,531 patients were enrolled in the study.The drop-off rate was 20.1％.167 patients (143 males and 24 females)in group 1,172 patients (141 males and 31 females)in group2 and 84(75 males and 9 females) in the control group with follow-up data were analyzed.There were no significant differences in age,gender,BMI,ECOG score,risk stratification between the three groups (P =0.8641,P =0.2906,P =0.9384,P =0.6126).The median follow-up time makes no statistical difference between the groups (P =0.9251),12.0 (6.0,22.5) months,13.0 (6.0,22.3) months,and 13.0 (7.0,22.3) months.The median recurrence time of the three groups was 4.0 (3.0,6.0) months,4.5 (3.0,9.8) months,4.5 (3.0,8.8) months.There was no statistical difference between the three groups (P =0.2852).Risk stratification in the patients got no significant difference between the three groups (P ＞ 0.05).The 1-year recurrence-free survival rates were 80.0％ in the group 1 and 88.3％ in the group 2 and 73.7％ in the control group.The group 2 was superior to the group 1 and the control group (P =0.0281,P =0.0031).There was no significant difference between group 1 and control group (P =0.2951).There was no significant difference in the cumulative recurrence-free survival between the experimental group 1 and the experimental group 2,(95％ CI 0.80-2.43,P =0.2433).The cumulative recurrence-free survival in the group 1 and the group 2 was better than the control group (95 ％ CI 0.31-0.92,P =0.0266;95 ％ CI 0.20-0.65,P =0.0008).All the cases underwent instillation were analyzed for adverse events.The incidence of overall AE(adverse events) in group 1 was 68.5％ (152/222),the incidence of grade Ⅰ-Ⅱ AE was 53.2％ (118/222),the incidence of grade Ⅲ-Ⅳ AE was 15.3％ (32/222).The incidence of overall AE in the group 2 was 71.8％ (160/223),the incidence of grade Ⅰ-Ⅱ AE was 60.1％ (134/223),and the incidence of grade Ⅲ-Ⅳ AE was 11.7％ (26/223).The overall AE rate in the control group was 53.2％ (59/111),of which the incidence of grade Ⅰ-Ⅱ AE was 42.4％ (47/111),and the incidence of grade Ⅲ-Ⅳ AE was 10.8％ (12/111).There was no difference in the incidence of overall AE between the group 1 and the group 2 (P =0.4497).The incidence of AE in the two experimental groups was higher than that in the control group (P =0.0062,P =0.0008).There was no difference in the incidence of grade Ⅲ-Ⅳ AE between the three groups (P =0.3902).Conclusions BCG(19 instillation schedule) has a better effect on preventing recurrence after 1 year of bladder surgery,which is superior to epirubicin group.The long-term efficacy of BCG in preventing recurrence and the efficacy of different schedules need to be further followed up.The lower urinary tract symptoms,which are mainly urinary frequency,are one of the causes of case fallout and should be fouced in future.Compared with epirubicin,BCG perfusion does not increase the incidence of grade Ⅲ-Ⅳ adverse reactions,and is safe to use.

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 investigate the clinico-pathological characteristics, outcomes and their predictors in malignant hypertension related kidney injury with and without primary glomerular diseases. Methods: Patients with clinical diagnosis of malignant hypertension, biopsy-proven kidney injury caused by malignant hypertension and complete clinical data from January 2010 to December 2018 were retrospectively analyzed. According to clinical and renal pathology, patients were divided into malignant hypertension related kidney injury without primary nephropathy group and with primary nephropathy group. Clinico-pathological characteristics and outcomes were evaluated and compared between malignant hypertension related kidney injury with and without primary glomerular diseases. Results: Totally 31 biopsy-proven kidney injury patients were analyzed. Among them, there were 18 cases with primary glomerular diseases and 13 cases without primary glomerular diseases, with age of (32.5±6.5) years old and (34.7±8.1) years old, respectively. There were 12 males in both group. The proportion of primary IgA nephropathy was higher (16/18) in the group of malignant hypertension related kidney injury with primary glomerular diseases. Malignant hypertension with primary glomerular diseases patients had lower plasma albunin level [(32.7±6.4) g/L vs (38.5±7.3) g/L, P=0.027], higher 24-hour proteinuria level [(4.03±2.71) g vs (1.45±0.98) g, P=0.002] and higher incidence rates of dysmorphic hematuria (14/18 vs 0, P=0.001) than those without primary glomerular diseases patients. Glomerular sclerosis, mesangial proliferation, tubular atrophy and interstitial fibrosis were more severe in malignant hypertension with primary glomerular diseases patients (all P<0.05), but the ischemic wrinkling of glomerular capillary was more severe in malignant hypertension without primary glomerular diseases (P<0.01). There were no differences of acute or chronic malignant hypertensive injury in small artery and in afferent arterioles between the two groups. Cox regression analysis showed that loss of brush-border with flattening of tubular epithelium was the predictor for renal partial recovery (HR=5.956, 95% CI 1.198-29.614, P=0.029). Kaplan-Meier analysis showed that malignant hypertension patients with primary glomerular diseases had shorter renal survival time than those without primary glomerular diseases [(24.1±9.3) months vs (56.6±12.4) months], and accumulative renal survival rate of malignant hypertension patients with primary glomerular diseases was lower than that without primary glomerular diseases (11.6% vs 53.3%, Log-rank χ²=5.022, P=0.025). Multivariate Cox regression analysis showed that severe tubular atrophy and interstitial fibrosis were independent risk factors for end-stage renal disease in malignant hypertension patients (HR=5.870, 95% CI 1.372-25.112, P=0.017). Conclusions Malignant hypertension with primary glomerular diseases patients have more severe clinico-pathological renal impairment and poorer prognosis of long-term renal survival than those without primary glomerular diseases. Acute renal tubular injury (loss of brush-border with flattening of tubular epithelium) is the only predictor of renal function improvement in patients with malignant hypertension and renal impairment within one year. Tubular atrophy/interstitial fibrosis is a risk factor for end-stage renal disease in patients with malignant hypertension. Renal biopsy is an indispensable tool for predicting short-term and long-term renal outcomes.