Objective:To investigate the efficacy of single time intra-articular different concentration of allogeneic bone marrow mesenchymal stem cells ( BM-MSCs ) injection in the treatment of Sprague-Dawley ( SD) rat model of osteoarthritis ( OA) .Methods: In the study, 32 SD rats were equally ran-domized into 4 groups:control group, high concentration group (1 ×107/mL BM-MSCs), low concentra-tion group (5 ×106/mL BM-MSCs) and high vs.low concentration group.The two knees of each rat were set up to a pair.The induction of OA was performed surgically randomly at one side in model group, and bilaterally in the other groups, which were through anterior cruciate ligament transaction ( ACLT) and medial meniscus excising.After the operation, the SD rats were allowed free movement.Four weeks later, different concentrations of allogeneic BM-MSCs isolated from the SD rats, expanded in vitro and suspended in phosphate buffered solution( PBS) were delivered in the articular cavity of both knees;PBS was used as the control.After injection, we excised the femoral nerve and sciatic nerve to disuse the low limb.The cartilage histological sections of knees were scored by Mankin scoring system to assess the se-verity of the pathology.mRNA of collagen Ⅱwas detected by real time polymerase chain reaction ( RT-PCR) .eGFP was detected by fluorescence microscope.Assessments were carried out 4 weeks after the operation in model group, and 3 weeks after injection in the other groups.Results:Mankin scores of the BM-MSCs side and control side were 6.60 ±0.40 vs.10.00 ±0.32 in low concentration group ( P<0.05), and 5.40 ±0.51 vs.9.60 ±0.51 in high concentration group (P<0.05).Mankin scores of high sv.low concentration group were 6.40 ±0.51 vs.7.60 ±0.75 (P>0.05).mRNA expression of collagen Ⅱ of the BM-MSCs side in low concentration group was 106%±1%in contrast to the control side.As in high concentration group it was 108%±1%, and 102%±1%in high vs. low concentra-tion group.Labeled BM-MSCs were detected unexpectedly in the synovial membrane but not in cartilage tissue three weeks from injection.Conclusion:BM-MSCs could promote cartilage repair and inhibit OA progression through a trophic mechanism.There was no difference between the two concentrations.

Objective To investigate the effects of Epimedium ,Astragalus ,Radix Puerariae on DMT1 expression in the cere‐bral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD .Methods A total of 60 specific‐pathogen‐free male APPswe/PS1ΔE9 double transgenic mice aged 6 months were equally and randomly assigned to model ,Epimedium ,Astragalus ,Radix puerari‐ae ,compound and DFO groups .An additional 10 6‐month‐old C57BL/6J mice served as negative control group .Using immunohisto‐chemistry and molecular biology methods to investigate the effects of a compound combining the effective components of Epimedi‐um ,Astragalus ,Radix puerariae on DMT1 expression in the cerebral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD . Results Immunohistochemical staining results revealed that DM T 1 positive cell did not show in negative control group .DM T1 ex‐pression was higher in model group compared with the negative control group .DMT1 expression was lower in the compound and deferoxamine groups than in the model group .No significant difference was detected in DM T 1 expression between deferoxamine and compound groups .RT‐PCR ,Western blot and immunohistochemical staining results showed no significant difference .Conclusion These compounds can downregulate DMT1 expression and inhibit iron overload in the cerebral cortex of mice with Alzheimer′s dis‐ease ,reduce iron overload induced impairment of the central nervous system .

BACKGROUND: Endoplasmic reticulum (ER) stress has been proved to be related to the occurrence of diabetes, dilated cardiomyopathy and neurodegenerative diseases. Indeed, it is closely associated with osteoarthritis. OBJECTIVE: To explore the effect of ER stress on the chondrocyte viability as well as the occurrence and development of osteoarthritis in rats. METHODS: Rat chondrocytes were isolated and cultured, and the ER stress in the rat chondrocytes was by 10 mg/L tunicamycin. The expression levels of ER stress markers C/EBP-homologous protein and 78 kDa glucose-regulated protein were detected by western blot assay, and the proliferation and apoptosis of chondrocytes were detected by cell counting kit-8 assay and AnnexinV-FITC flow cytometry, respectively. In the in vivo experiment, 15 Sprague-Dawley rats were selected and subjected to anterior cruciate ligament transection and medial meniscectomy to establish an animal model of osteoarthritis. Tunicamycin, tauroursodeoxycholic acid and PBS (blank control group) were respectively injected into the articular cavity, and then the progression of osteoarthritis was assessed by hematoxylin-eosin staining at 4 weeks after treatment. RESULTS AND CONCLUSION: After addition of tunicamycin, the expression levels of C/EBP-homologous protein and 78 kDa glucose-regulated protein were significantly upregulated, the viability of chondrocytes was decreased gradually, while the apoptotic rate was increased significantly. Results from gross observation and hematoxylin-eosin staining suggested that tunicamycin promoted the progression of osteoarthritis and tauroursodeoxycholic acid delayed the deterioration of cartilage in the rats. These findings indicate that ER stress results in the decreased chondrocyte viability and increased apoptosis, which may be an important pathogenesis of osteoarthritis. Additionally, tauroursodeoxycholic acid can effectively alleviate osteoarthritis induced by ER stress.

Objective:To investigate whether endogenous hydrogen sulfide (H2 S)was involved in the pathogenesis of osteoarthritis (OA)and its underlying mechanism,to detect H2 S and its synthases ex-pression in knee cartilage in patients diagnosed with different severity of OA,and to explore the transcrip-tion and expression of gene MMP-13 in chondrocytes treated with IL-1βor H2S.Methods:Synovial fluids of the in-patients with different severity of OA hospitalized in Peking University First Hospital were collected for measurement of H2 S content using methylene blue assay.Articular cartilages of the patients who underwent knee arthroplasty were collected for the cell culture of relatively normal chondrocytes.The chondrocytes were cultured to the P3 generation and H2 S molecular probes were used for detection of endogenous H2 S generation in the chondrocytes.Immunocytochemistry was used to detect the localization of H2 S synthases including cystathionine β-synthase (CBS),cystathionine-γ-lyase (CSE),and mercap-topyruvate sulfurtransferase (MPST)in OA chondrocytes.Western blot was used to quantify the protein expressions of CSE,MPST,and CBS in cartilage tissues of the patients who were diagnosed with OA and underwent knee arthroplasty.The relatively normal human chondrocytes were cultured to passage 3 and then divided into 4 groups for different treatments:(1 )the normal control group,no reagent was added;(2)the IL-1βgroup,5 μg/L of IL-1βwas added;(3)the IL-1β+H2S group,200 μmol/L of NaHS was added 30 min before adding 5 μg/L of IL-1β;(4)the H2 S group,200 μmol/L of NaHS was added. The transcription and expression of gene MMP-13 in chondrocytes of each group were determined with Real-time PCR and Western blot,respectively.And the total NF-κB p65 and phosphorylated NF-κB p65 in chondrocytes were detected with Western blot.Results:The content of H2 S in the synovial fluid of degenerative knee was (14.3 ±3.3)μmol/L.Expressions of endogenous H2 S and its synthases including CBS,CSE and MPST were present in the cytoplasm of chondrocytes.CSE protein expression in Grade 3 (defined by outerbridge grading)cartilage tissues was significantly increased as compared with that of Grade 1 cartilage tissues (1.67 ±0.09 vs.1.26 ±0.11,P<0.05).However,no significant difference of CBS or MPST expression among the different groups was observed.The expression of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (1 .87 ±0.67 vs.0.22 ± 0.10,P<0.05 ),and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (0.55 ±0.11 vs.1.87 ±0.67,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The transcription of MMP-13 protein in the IL-1βgroup was significantly higher than that in the normal chondrocytes (31.40 ±0.31 vs.1.00 ±0.00,P<0.05), and that in the IL-1β+H2 S group was significantly decreased than that in the IL-1βgroup (24.41 ± 1.28 vs.31.40 ±0.31,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.The total NF-κB p65 in the IL-1βgroup was significantly higher than that in the normal chondrocytes (2.13 ±0.08 vs.0.73 ±0.08,P<0.05),and that in the IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (1 .24 ±0.13 vs.2.13 ±0.08,P<0.05 ),and that in the H2 S group had no significant difference compared with that in the normal control group.The phosphorylated NF-κB p65 in IL-1βgroup was significantly higher than that in the normal chondrocytes (1.30 ±0.13 vs.0.19 ±0.04,P<0.05),and that in IL-1β+H2S group was significantly decreased than that in the IL-1βgroup (0.92 ±0.26 vs.1.30 ±0.13,P<0.05),and that in the H2S group had no significant difference compared with that in the normal control group.Conclusion:H2 S affected the cartilage degeneration by partly inhibiting the degradation of extracellular matrix.

In order to effectively manage the atrial fibrillation patients, West China Hospital has established an integrated general-specialty management model within medical consortium. This model takes the atrial fibrillation-stroke integrated management outpatient clinic as the platform, combines general practice and specialty to provide standardized care for atrial fibrillation patients. The model was characterized by primary diagnosis, two-way referral, up and down linkage, and differential management for acute and chronic conditions. This article, taking West China Hospital as an example, introduces the integrated team of cardiologists and general practitioners in the tertiary hospital with general practitioners in the community, and the preliminary accomplishment in the management of atrial fibrillation within the medical consortium. It would provide a reference for the long-range management of atrial fibrillation in other provinces and cities.

Objective:To investigate the value of serum urea nitrogen on in-hospital death in patients with heart failure.Methods:The clinical data of 9 459 patients with heart failure from January 2013 to December 2018 in Shengjing Hospital of China Medical University were retrospectively analyzed. Among them, 296 cases died in hospital (death group) and 9 163 cases survived (survival group). The clinical data of patients were collected, including general condition, disease history, physical examination, laboratory indicators and relevant physical examination, etc. Correlation was finished with Pearson correlation analysis. Multivariate Logistic regression analysis was used to determine independent risk factors for in-hospital death in patients with heart failure. Receiver operating characteristic (ROC) curve was used to determine the optimal predictive threshold of urea nitrogen for in-hospital death.Results:The in-hospital mortality in patients with heart failure was 3.1% (296/9 459). There were statistical differences in age, hypertension rate, diabetes rate, a history of atrial fibrillation rate, smoking history rate, hemoglobin, albumin, glycosylated hemoglobin, urea nitrogen, creatinine, uric acid, serum potassium, serum sodium, troponin I, N terminal brain natriuretic peptide precursor (NT-proBNP), left ventricular ejection fraction (LVEF) between death group and survival group ( P<0.01 or <0.05), and there were no statistical difference in gender composition, coronary heart disease rate, platelet, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) between 2 groups ( P>0.05). Pearson correlation analysis result showed that the urea nitrogen was positively correlated with age, coronary heart disease, hypertension, diabetes, glycosylated hemoglobin, creatinine, uric acid, serum potassium, troponin I, NT-proBNP, LVEDV and LVESV ( r = 0.130, 0.024, 0.053, 0.128, 0.033, 0.739, 0.468, 0.377, 0.065, 0.432, 0.084 and 0.101; P<0.01 or <0.05); and the urea nitrogen was negatively correlated with gender, history of atrial fibrillation, hemoglobin, platelet, albumin, total cholesterol, LDL-C, serum sodium and LVEF ( r = -0.033, -0.063, -0.272, -0.077, -0.188, -0.070, -0.071, -0.199 and -0.113, P<0.01); and there were no correlation between urea nitrogen and smoking history or triglyceride ( P>0.05). Multivariate Logistic regression analysis result showed that age, hypertension, albumin, urea nitrogen, troponin I and NT-proBNP were independent risk factors for in-hospital death in patients with heart failure ( OR = 1.018, 0.613, 0.924, 1.082, 1.340 and 1.005; 95% CI 1.002 to 1.033, 0.427 to 0.881, 0.889 to 0.961, 1.040 to 1.126, 1.111 to 1.617 and 1.003 to 1.007; P<0.05 or <0.01). ROC curve analysis result showed that the area under the curve (AUC) of urea nitrogen for prediction of in-hospital death in patients with heart failure was 0.737 (95% CI 0.728 to 0.748), and the optimal threshold value was 11.41 mmol/L, with a sensitivity of 60.16% and a specificity of 77.01%; the AUC of NT-proBNP for prediction of in-hospital death in patients with heart failure was 0.726 (95% CI 0.712 to 0.740), and there was no statistical difference in the AUC between urea nitrogen and NT-proBNP ( Z=1.055, P=0.291). Conclusions:Elevated urea nitrogen level is independently associated with an increase in in-hospital mortality in patients with heart failure, and the optimal threshold for predicting in-hospital death is 11.41 mmol/L.

Objective:To investigate the clinical effect and short-term and long-term effect of total hip replacement (THA) and hemiarthroplasty of hip (HA) in elderly patients with femoral neck fracture (FNF).Methods:59 elderly patients with FNF in South District of Guang′anmen Hospital, Chinese Academy of Traditional Chinese Medicine from March 2017 to January 2019 were retrospectively analyzed. The observation group ( n=29) was treated with THA; The control group ( n=30) was treated with HA. The operation related indexes, short-term and long-term clinical effect (average follow-up of 24.1 months), hip function improvement, pain and complications were compared between the two groups. Short term and long-term clinical effects: the short-term and long-term clinical effects of the two groups were observed by the Harris Hip Score (HHS) of the first month, the third month, the sixth month, the ninth month and the first year after operation. Results:Both THA and HA were effective on elderly FNF, but the effective rate of THA (96.6%) was significantly higher than that of HA (90.0%), with statistically significant difference ( P<0.05); in terms of operation related indicators, compared with the control group, the observation group had longer operation time [ (104.46±3.24)min vs (84.34±3.64)min], more amount of bleeding [(296.64±15.16)ml vs (281.44±12.16)ml], lower postoperative drainage volume [(101.24±4.15)ml vs (74.56±3.24)ml], while the functional recovery of the observation group was better than the control group by HHS ( P<0.05); the postoperative complications and HHS score of observation group were significantly lower than the control group ( P<0.05). Conclusions:THA has the advantages of low complication, fast functional recovery and better effect. The clinical decision should be based on the patient′s physical condition. THA should be used for elderly patients with good basic condition, good surgical tolerance and more daily activities. HA should be used for elderly patients with poor basic condition, low surgical tolerance and less daily activities.

Objective:This study sought to investigate the feasibility, anatomical indications and operating points of transcatheter aortic valve replacement (TAVR) procedure in the treatment of pure aortic regurgitation (AR).Methods:The medical records of 4 elderly patients with pure AR who were treated in the cardiology department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from March 2020 to March 2021 were retrospectively analyzed. All patients were implanted with self-expandable valve stents via peripheral artery approach for TAVR treatment. The feasibility, anatomical indications and key points of TAVR were analyzed.Results:The 4 patients with pure AR who were carefully screened had an average age of 66 years, and all achieved TAVR treatment success without serious perioperative complications and death. Postoperative examination and follow-up data showed that cardiac functions and cardiac remodeling indexes were significantly improved.Conclusions:This exploratory study shows that TAVR is technically feasible and effective treatment option for selected elderly patients with native pure AR, which is worthy of further study.