Objective To explore the intrinsic relationship between circadian clock and cell cycle in osteoarthritis(OA)chondrocytes,especially the regulation of cell cycle-related genes by the clock gene Bmal1.Methods The chondroid ATDC5 cells induced by insulin-transfering-selenium(ITS)were divided into control group,OA group and LV-Bmal1 group.The cell viability of each group was detected by CCK8 method.The expression of Bmal1,Per1,Wee1,Cdk1,Ccnb1 and Mmp13 mRNA in each group was detected by RT-qPCR.The expression of BMAL1,PER1,WEE1,CDK1,CCNB1 and MMP13 protein in each group was detected by Western blot.The effects of Bmal1 on different stages of cell cycle and apoptosis was analyzed by flow cytometry.The regulation of Bmal1 on Per1,Wee1,Cdk1,Ccnb1 and Mmp13 and their roles in OA were analyzed.Results Compared with the normal group,the cell viability of the OA group was increased,the relative mRNA expression of Bmal1 and Wee1 in the OA group decreased,and the relative mRNA expression of Per1,Cdk1,Ccnb1 and Mmp13 increased signif-icantly.The cell viability of LV-Bmal1 group decreased,the relative expression of Bmal1 and Wee1 mRNA in-creased,and the relative expression of Per1,Cdk1,Ccnb1 and Mmp13 mRNA decreased(P＜0.05).Correlation analysis showed that Bmal1 was positively correlated with Wee1 and they were negatively correlated with Per1,Cdk1,Ccnb1 or Mmp13.The results of Western blot showed that protein expression in different groups were con-sistent with the trend of PCR.The results of cell cycle and apoptosis showed that compared with the normal group,the S phase and G2/M phase of the OA group were shortened,the proportion of cells decreased significantly,and the proportion of early and late apoptosis increased.The S phase and G2/M phase of the LV-Bmal1 group were prolonged,the proportion of cells was increased,and the proportion of early and late apoptosis was decreased.Conclusions Circadian clock gene Bmal1 in inflammatory chondrocytes might regulate the expression of cell cycle-related genes.

Objective To investigate the signal abnormality of conus medullaris in patients with overactive bladder(OAB)and un-deractive bladder(UAB)by MRI diffusion tensor imaging(DTI). Methods From May,2021 to April,2023,23 patients with lower urinary tract dysfunction without trauma and supraspi-nal lesions were enrolled(case group).All patients underwent imaging urodynamics and pelvic floor electromy-ography.Based on the bladder contraction during the filling phase of urodynamics,the patients were divided into UAB group and OAB group.Eight healthy subjects were included as the control group.All participants under-went T10 to L5 spinal segment MRI scans and DTI scans.The position of conus medullaris was determined by comparing the DTI sequences with the MRI scans.The fractional anisotropy(FA),apparent diffusion coefficient(ADC),and relative anisotropy(RA)of the conus medullaris intermediate segment were compared. Results Twelve cases were in UAB group,and eleven in OAB goup.Abnormalities were found in the pelvic floor elec-tromyography in the case group.There was significant difference in sacral reflex arc nerve conduction testing be-tween UAB and OAB groups(P = 0.036).Compared with the control group,ADC increased(t = 2.185,P = 0.037)in the case group;FA decreased(t = 3.439,P = 0.005)and ADC increased(t = 4.582,P<0.001)in UAB group. Conclusion DTI is helpful to find the potential lesion of spinal cord in patients with lower urinary tract dysfunction.FA and ADC are valuable indicators for the diagnosis of conus medullaris injury.

Objective:To explore the relieving effect of adhesive Bifidobacterium on constipation and its effect on intestinal flo-ra and intestinal morphology in mice.Methods:Detection of adhesion of 14 strains of Bifidobacterium.Fifty mice were randomly divid-ed into control group,model group,positive drug group,low adhesion group and high adhesion group,with 10 mice in each group.The control group and model group received 0.2 ml sterile double distilled water,the positive drug group received 0.2 ml 1.52 mg/kg lactulose solution,and the low and high adhesion groups received 0.2 ml 109 CFU/ml corresponding to Bifidobacterium solution for 37 days.The constipation model was established from the 31st day.The other 4 groups except the control group were given 0.2 ml 10 mg/(kg·bw)loperamide hydrochloride aseptic aqueous solution for 7 days.After the establishment of the model,each mouse was fed with 0.2 ml activated carbon suspension,and the excretion time of the first black stool was measured.After fasting for 12 hours,the mice were given aseptic double steamed water or loperamide hydrochloride,and 1 hour later,0.2 ml activated carbon suspension was given to the stomach.After 30 min,all the mice were killed.The distance between the intestinal length and the intestinal propul-sion of the activated carbon suspension was measured,and the intestinal propulsion rate was calculated.The fresh feces of mice on the 30th and 36th day were collected within 4 hours,and the fecal moisture content and short chain fatty acid(SCFAs)content were deter-mined.Observation of histology of small intestine by HE staining.The expression of zonula occluden-1(ZO-1)and Occludin was detected by immunofluorescence.Detection of aquaporin,c-kit and serotonin related gene transcription by qRT-PCR.The levels of 5-hydroxytryptamine(5-HT),IL-1β and TNF-α were detected by ELISA.The relative content of intestinal microflora was detected by 16S rRNA high-throughput sequencing.Results:CCFM 622,CCFM 624,CCFM 626,CCFM 641 and CCFM 642 were selected as the bacteria group used in the low adhesion group,and CCFM 16,CCFM 625,CCFM 643,CCFM 666 and CCFM 668 as the bacteria group used in the high adhesion group.Compared with control group,the first black stool excretion time,AQP4,AQP8 mRNA,5-HT,IL-1β and TNF-α levels in the model group,positive drug group,low adhesion group and high adhesion group increased(P<0.05),while the intestinal propulsion rate,fecal water content,ZO-1,Occludin fluorescence intensity,c-kit,5-HT4R,Tph1 mRNA,acetic acid,propionic acid and butyric acid decreased(P<0.05).Compared with positive drug group and high adhesion group,the first black stool excretion time,AQP4,AQP8 mRNA,5-HT,IL-1β and TNF-α in low adhesion group increased(P<0.05),while intestinal pro-pulsion rate,fecal water content,ZO-1,Occludin fluorescence intensity,c-kit,5-HT4R,Tph1 mRNA,acetic acid,propionic acid and butyric acid decreased in low adhesion group(P<0.05).In the control group,the mucosal structure was intact,the small intesti-nal villi were neat and uniform,there was no injury or wrinkle,and the cell structure was intact;in model group,the intestinal villi were seriously ruptured and atrophied,and the goblet cells were incomplete;compared with model group,the morphology of small intestinal villi in positive drug group,low adhesion group and high adhesion group were improved,and the number of goblet cells increased,and the improvement in positive drug group and high adhesion group were more obvious than that in low adhesion group.Compared with control group,the Shannon index and Firmicutes/Bacteroidetes(F to B)ratio in model group decreased(P<0.05),and there were differences in genus level(P<0.05).Compared with model group,Shannon index and F to B ratio increased in positive drug group,low adhesion group and high adhesion group(P<0.05).The sample points in the model group could be distinguished from the control group,positive drug group,low adhesion group and high adhesion group,but the coincidence degree of sample points in control group,positive drug group,low adhesion group and high adhesion group were higher.Conclusion:Bifidobacterium can regu-late intestinal flora of constipation mice,improve intestinal running efficiency and protect intestinal mucus barrier.Bifidobacterium with high adhesion is better than Bifidobacterium with low adhesion in relieving constipation in mice.

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

Objective:To introduce the application of sleeve reconstruction with bovine pericardium in the reoperation of Behcet's disease with advanced aortic annulus invasion, and to report our experience and the early outcomes.Methods:From August 2012 to May 2022, 19 patients with Behcet's disease developed perivalvular leakage after previous surgery underwent aortic root replacement. They were analyzed retrospectively. Fifteen out of 19 cases underwent conventional aortic root replacement, 4 cases with advanced aortic annulus invasion underwent sleeve reconstruction with bovine pericardium. The medical records were reviewed. Demographic and perioperative data were collected, which included the aortic crossclamp time, intraoperative RBC consumption, length of ICU stay, and major postoperative complications.Postoperative follow-up was accomplished through telephone visit.Results:The median age was 39(36, 42) years old. Five were female. The median interval of diagnosis of perivalvular leak from index surgery was 5(3, 14)months. There was no perioperative death. Fifteen patients underwent conventional aortic root replacement. One patient had intraoperative ECMO impant due to low cardiac output as well as another one had IABP support. CABG was performed in 5 patients. One patient underwent permanent pacemaker implantation after surgery. The median follow-up time for the 15 patients was 55.00(29.25, 71.25)months. Two patients were lost during follow-up. One patient died of infection 3 years after surgery. One patient developed perivalvular leak. Two patient developed distal anastomotic pseudoaneurysm which need reintervention. The median follow-up time for the 4 patients with sleeve reconstruction was 5.5(5, 11.25)months. One patient underwent tracheotomy. Perivalvular leakage and pseudoaneurysm were not appreciated. Four patients were in NYHA class Ⅰ-Ⅱ.Conclusion:The sleeve reconstruction with bovine pericardium is safe and effective in reoperation treating patients with Behcet's disease and advanced aortic annulus invasion.

Objective:To investigate changes in arterial acid-base and electrolytes after repeated episodes of ventricular fibrillation (VF) and defibrillation in a swine model.Methods:Sixteen Peking white swine, weighting (32±2.5) kg, were placed with temporary pacemaker electrodes via the left femoral vein into the right ventricle after anesthesia. Then VF was electrically induced by using a programmed electrical stimulation instrument. An arterial cannula was inserted into the left femoral artery to measure mean arterial blood pressure and cardiac output using a PiCCO monitor, with blood samples collected. The pigs were randomly divided into two group: the manual defibrillation group (MD, n=8) and the automated external defibrillation group (AED, n=8). The first defibrillation was attempted with the manufacturer’s dose (150 J) for 15 s after the successful induction of VF in the MD group. If spontaneous circulation was not recovered, 2-min chest compression and subsequent defibrillation (200 J) were attempted. For the AED group, the defibrillation was delivered following voice prompts of the AED. After the return of spontaneous circulation, the pig was allowed to stabilize for 30 min, followed by the induction of the next episode of VF. The above process was repeated five times. Arterial blood gas, cardiac biomarkers, and hemodynamic variables were measured at 30 min after the return of spontaneous circulation. Results:All pigs were successfully induced VF five times and defibrillated successfully. There were no significant changes in heart rate and mean arterial blood pressure between the two groups after repeated episodes of VF and defibrillation. Compared with baseline measurements, cardiac output tended to decrease after repeated episodes of VF and defibrillation but was not statistically significant (all P>0.05). There were no significant differences in arterial pH, HCO 3-, sodium, and lactic acid in the two groups between each measurement time point and baseline values after repeated VF (all P>0.05), but potassium levels in the two groups decreased with time, and the difference was statistically significant compared with the baseline measurement (all P<0.05). There were no significant differences in myoglobin, creatine kinase isoenzyme-MB, and cardiac troponin I for the two groups compared with baseline values after repeated episodes of VF and defibrillation or various episodes of VF between the two groups (all P > 0.05). Conclusions:Repeated episodes of VF and defibrillation have no significant effect on pH balance, but significantly decrease blood potassium. Clinical approaches (MD vs. AED) do not affect defibrillation effect, with no significant differences in hemodynamic variables and myocardial injuries.

Sepsis is a hot and difficult research topic in the field of acute and critical care all over the world. Sepsis mortality remains high despite ongoing guideline updates. This situation has prompted the research thinking of Western medicine to change from one-sided pursuit of killing pathogenic microorganisms to regulating the body′s immune response, and change from focusing on local pathological changes to focusing on the internal connection of systemic organs. They put forward theories such as liver-renal syndrome, cardio-renal syndrome, and lung-gut axis, which are consistent with the overall concept of traditional Chinese medicine. The research fields, goals, and treatment objects of traditional Chinese medicine and Western medicine are the same, so Integrative traditional Chinese and Western medicine in the treatment of sepsis has important application value and broad development space. In the process of sepsis treatment, we must make full use of modern technology, and at the same time give full play to the advantages of traditional Chinese medicine, to reduce the fatality rate. Only in this way can we contribute to the protection of human health.

Objective:To investigate the long term outcome of artificial urinary sphincter implantation for patients with stress urinary incontinence.Methods:The data of 46 patients who underwent artificial urethral sphincter implantation in China Rehabilitation Research Center from April 2002 to April 2022 were retrospectively analyzed.The patients’ age ranged from 19-80 years old (median 45.6 years). There were 45 males and 1 female. The history of illness was 8 months to 33 years. The patients category were urethral injuries associated urinary incontinence ( n=24), neurogenic urinary incontinence ( n=9) and post-prostatectomy incontinence ( n=13). Preoperative daily pad usage was 3.5±1.0. The impact of incontinence on the quality of life (QOL)measured by the visual analogue scale (VAS)was 7.1±1.2. All 46 patients underwent artificial urethral sphincter implantation, of which 20 patients were treated with anticholinergic drugs (5 cases) or urinary tract related surgery (urethral stenosis incision in 2 cases, sphincterectomy in 3 cases, urethral dilation in 5 cases, urethral calculus lithotripsy in 1 case, and augmentation cystoplasty in 4 cases) before artificial urethral sphincter implantation. Of the 45 male patients, 25 patients had the transperineal approach and 20 had the trans-scrotal approach. The female case had a trans-retropubic approach. Different cuffs size was used based on individual circumference of bulbar urethra (45 male cases: 4.5cm in 16 cases, 4.0cm in 29 cases; one female case: 8.0cm). Long-term surgical efficacy was evaluated. Assessments included postoperative urinary continence (socially continent: one pad per day or less; complete dry: wearing no pads), artificial urinary sphincter status and complications. The influences of patients of different etiologies, surgical approaches and cuff size on surgical results were compared. Results:The mean follow-up time was 7.1 years ranged from 6 months to 19 years. At the latest visit, 32 patients (69.6%) maintained the primary functional artificial urinary sphincter. Three patients (6.5%) had artificial urinary sphincter revisions and maintained continence with the new device. 11 patients (23.9%) removed the artificial urinary sphincter because of post-complications. Thirty-five patients were socially continent, of which 16 patients were totally dry, leading to the overall social continent rate as 76.1%(35/46). There was a significant reduction in pad usage to 1.2±0.6 diapers per day ( P<0.001). The impact of incontinence on the QOL measured by the VAS dropped to 2.6±1.9 ( P<0.001). The complication rate was 32.6%(15/46), including infections ( n=4), erosions ( n=5), mechanical failure ( n=3), dysurie ( n=2) and urethral atrophy ( n=1). There were no significant differences in social continent rate between patients with different etiologies[75.0%(18/24)vs. 66.7%(6/9) vs. 84.6%(11/13)], perioperative complications [37.5%(9/24)vs. 33.3%(3/9) vs. 23.1%(3/13)] and device re-intervention rate[37.5%(9/24) vs. 33.3%(3/9)vs. 15.4%(2/13)]. There were no statistically significant differences in postoperative complete dry rate [32%(8/25)vs. 40%(8/20), P=0.76] and postoperative device failure free rate [60%(15/25)vs. 80%(16/20), P=0.20] between trans-perineal group and trans-scrotal group. There was no statistically significant difference in postoperative social continent rate between 4.5cm cuff and 4.0 cuff[75%(12/16) vs. 65.5%(19/29), P=0.74]. Conclusions:Artificial urethral sphincter implantation is an effective treatment for stress urinary incontinence due to intrinsic sphincter deficiency. There was no difference in the continent rate and complication rate between patients of different etiologies, different surgical approaches and cuff size selection.

Objective:To explore the effect of cloud follow-up system in post-hospital follow-up management of hyperuricemia gout patients.Methods:Using the convenient sampling method, a total of 120 gout patients who were discharged after treatment in Taizhou Central Hospital in June 2021 were selected as the research objects and they were randomly divided into the control group and the experimental group according to the random number table method, with 60 cases in each group. The control group carried out routine follow-up, while the experimental group carried out follow-up based on cloud follow-up system. The serum uric acid level and self-management ability of gout patients were compared between the two groups before and after 6 months of follow-up.Results:After 6 months of follow-up, the serum uric acid levels of the control group and the experimental group were lower than those before follow-up and that of the experimental group was lower than the control group, and the differences were statistically significant ( P<0.05) . After 6 months of follow-up, the self-management ability score of the experimental group was higher than that before follow-up and higher than that after follow-up of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The new follow-up model based on cloud follow-up system is helpful to improve the self-management ability of gout patients and reduce the blood uric acid level of gout patients.

Objective    To explore the clinical value of soluble suppression of tumorigenesis-2 (sST2) in replacement of N-terminal fragment of the brain natriuretic peptide precursor (NT-proBNP) in cardiac function evaluation in renal failure patients after cardiac surgery. Methods    Sixty patients with renal insufficiency after cardiac surgery from January 2019 to June 2019 were divided into a test group, including 34 males and 26 females, with an average age of 49-78 (63.3±4.5) years. Another 60 patients with normal renal function were divided into a control group, including 37 males and 23 females, with an average age of 53-77 (61.7±3.8) years. The perioperative left ventricular ejection fraction, cardiac troponin T, creatine kinase-MB, sST2 and NT-proBNP were compared. Results    In patients of the test group, the NT-proBNP level increased significantly during perioperative period, and the change range was different from other cardiac function indexes. The change of sST2 in perioperative period was similar to other cardiac function indexes, which could reflect the change degree of cardiac function after operation. Conclusion    sST2 is more important to reflect the change degree of cardiac function in patients with renal dysfunction after cardiac surgery than NT-proBNP.