Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

Objective To explore the clinical and epidemiological characteristics of fosfomycin(FOS)-resistant hy-pervirulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP)strains,as well as potential molecular mecha-nisms of FOS resistance,and provide reference for clinical anti-infection treatment decision making.Methods Through antimicrobial susceptibility testing,non-repetitive hv-CRKP strains from a tertiary first-class hospital from January to December 2023 were screened and collected.The clinical characteristics and antimicrobial resistance were analyzed,and the molecular epidemiological characteristics of FOS non-susceptible hv-CRKP was studied by whole genome sequencing.Results A total of 73 hv-CRKP strains were included in the analysis,out of which 34 strains(46.6％)were resistant to FOS.The incidence of diabetes mellitus in patients in the FOS non-susceptible group was higher than that in the FOS susceptible group(P＜0.05).There was no statistically significant difference among other clinical characteristics.Antimicrobial susceptibility results showed that,except for tigecycline,colistin,cefta-zidime/avibactam,and FOS,the resistance rates of hv-CRKP to other common antimicrobial agents were all＞90％.The detection of capsule serotypes and virulence genes showed that all hv-CRKP were Klebsiella pneumoniae car-bapenemase(KPC)-producing ST11 strains,with the main serotypes being KL64(47.9％)and KL25(52.1％).There was no statistically significant difference in distribution of hv-CRKP capsule serotype between the FOS sus-ceptible and FOS non-susceptible groups.Resistance gene detection results showed that the carbapenem-resistance gene blaKPC as well as FOS resistance genes fosA and fos A6 were widely presented in hv-CRKP,with only one strain carrying the fosA3 gene detected in the FOS non-susceptible group.All 73 hv-CRKP strains carried the Leu359Gln mutation modification in murA,and some had mutations in the transport system-related gene glpT.No other FOS modification enzyme resistance genes were detected,such as fosA2,fosA5,fosA10,fosB,fosC,and fosX.Conclusion hv-CRKP has a high resistance rate to FOS.Modification mutations in murA and glpT,as well as the wide presence of FOS resistance genes fosA and fosA6 are the main mechanisms of FOS resistance in this study.It should be noted that fosA gene may be captured by strong promoters-containing high copy plasmids,lead-ing to FOS resistance.

Objective To explore the clinical and epidemiological characteristics of fosfomycin(FOS)-resistant hy-pervirulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP)strains,as well as potential molecular mecha-nisms of FOS resistance,and provide reference for clinical anti-infection treatment decision making.Methods Through antimicrobial susceptibility testing,non-repetitive hv-CRKP strains from a tertiary first-class hospital from January to December 2023 were screened and collected.The clinical characteristics and antimicrobial resistance were analyzed,and the molecular epidemiological characteristics of FOS non-susceptible hv-CRKP was studied by whole genome sequencing.Results A total of 73 hv-CRKP strains were included in the analysis,out of which 34 strains(46.6％)were resistant to FOS.The incidence of diabetes mellitus in patients in the FOS non-susceptible group was higher than that in the FOS susceptible group(P＜0.05).There was no statistically significant difference among other clinical characteristics.Antimicrobial susceptibility results showed that,except for tigecycline,colistin,cefta-zidime/avibactam,and FOS,the resistance rates of hv-CRKP to other common antimicrobial agents were all＞90％.The detection of capsule serotypes and virulence genes showed that all hv-CRKP were Klebsiella pneumoniae car-bapenemase(KPC)-producing ST11 strains,with the main serotypes being KL64(47.9％)and KL25(52.1％).There was no statistically significant difference in distribution of hv-CRKP capsule serotype between the FOS sus-ceptible and FOS non-susceptible groups.Resistance gene detection results showed that the carbapenem-resistance gene blaKPC as well as FOS resistance genes fosA and fos A6 were widely presented in hv-CRKP,with only one strain carrying the fosA3 gene detected in the FOS non-susceptible group.All 73 hv-CRKP strains carried the Leu359Gln mutation modification in murA,and some had mutations in the transport system-related gene glpT.No other FOS modification enzyme resistance genes were detected,such as fosA2,fosA5,fosA10,fosB,fosC,and fosX.Conclusion hv-CRKP has a high resistance rate to FOS.Modification mutations in murA and glpT,as well as the wide presence of FOS resistance genes fosA and fosA6 are the main mechanisms of FOS resistance in this study.It should be noted that fosA gene may be captured by strong promoters-containing high copy plasmids,lead-ing to FOS resistance.

Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective To investigate the effect of aerobic exercise preconditioning on cardiac function in mice bearing subcutaneous transplantable tumors and explore the potential molecular mechanisms.Methods Twenty-four 6-week-old male BALB/c mice were selected.After an acclimation period,they were randomly assigned to a control group(C),a tumor group(M)and an exercise-preconditioning plus tumor group(EM),each of eight.The EM group underwent a 4-week aerobic exercise interven-tion.Meanwhile,the C group received 0.2 ml of physiological saline injected subcutaneously on the dorsum of the proximal left hind limb,while the M and EM groups were inoculated at the same site with 0.2 ml of a CT26.WT colon carcinoma cell suspension.Three weeks after inoculation,cardiac function was assessed by transthoracic echocardiography.Hearts were then harvested for hematoxylin-eo-sin staining to evaluate cardiomyocyte cross-sectional area(CSA),while Western blot was performed to determine the expression of proteins related to myocardial protein synthesis and degradation.Results(1)Compared with group C,group M exhibited significantly lower body weight and heart weight(P<0.05),and reduced left ventricular ejection fraction(LVEF),fractional shortening(FS)and stroke vol-ume(SV)(P<0.05),as well as cardiomyocyte CSA(P<0.01)and total mTOR(P<0.01),phosphory-lated mTOR(p-mTOR)(P<0.01)and the p-mTOR/mTOR ratio(P<0.05),but a significant increase in the expression of the muscle ring finger 1(MuRF-1)and the muscle atrophy F-box(MAFbx/Atrog-in-1)(P<0.01 and P<0.05,respectively).(2)Compared with group M,group EM showed significant-ly greater heart weight(P<0.05);increased left ventricular posterior wall thickness at end-diastole(LVPWd),LVEF,FS and SV(P<0.05),as well as the larger cardiomyocyte CSA and total mTOR,p-mTOR and the p-mTOR/mTOR ratio(P<0.05),but reduced MuRF-1 and Atrogin-1 expression(P<0.05).Conclusion Four weeks of aerobic exercise preconditioning ameliorated myocardial atrophy and improved systolic cardiac function in mice bearing subcutaneously transplanted CT26 tumors.Such beneficial effects may be associated with exercise-induced down regulation of the protein degradation mediators MuRF-1 and Atrogin-1 and up regulation of total mTOR and p-mTOR.

Objective:To compare the ecchymosis of affected limb in the prevention of deep vein thrombosis using low molecular weight heparin sodium and enoxaparin sodium after total knee arthroplasty.Methods:A total of 160 patients (31 males and 129 females) who underwent unilateral knee replacement in Department of Orthopedics of Chengdu Second People's Hospital from Oct. 2020 to Dec. 2023 were included. According to the random number method, all patients were evenly divided into the low molecular weight heparin sodium group (16 males and 64 females) and the enoxaparin sodium group (15 males and 65 females). All patients were treated with low molecular weight heparin sodium or enoxaparin sodium to prevent deep vein thrombosis in the lower limbs after surgery. The ecchymosis area on the affected limb was observed 7 days after surgery, and the incidence and difference in ecchymosis area between the two groups of patients were statistically analyzed. Simultaneously evaluate whether there are differences in hemoglobin, platelet, and coagulation related indicators between the two groups of patients before and after surgery.Results:There were no significant differences in hemoglobin, platelet, and coagulation parameters between the low molecular weight heparin sodium group and the enoxaparin sodium group before and after surgery ( t=1.13, -0.27, -0.47, 0.27, 0.34, -0.27, -0.89, -0.46, P=0.27, 0.34, 0.64, 0.83, 0.74, 0.97, 0.24, 0.65). The incidence of ecchymosis in patients with low molecular weight heparin sodium group and enoxaparin sodium group was 61.25% and 67.50%, respectively, with no statistically significant difference in the incidence of ecchymosis between the two groups ( P=0.41). The average size of ecchymosis in the two groups of patients was (40.40 ± 60.07) cm 2 and (37.41 ± 43.21) cm 2, respectively. And there was no statistically significant difference in ecchymosis area ( P=0.61) . Conclusion:Both patients had limbs’ecchymosis in the process of preventing deep venous thrombosis of lower limbs after total knee replacement. This indicates that the two anticoagulants had a certain effect on postoperative skin ecchymosis of total knee. And the incidence rate and area of ecchymosis of affected limbs were similar in the two groups.

Objective:To compare the ecchymosis of affected limb in the prevention of deep vein thrombosis using low molecular weight heparin sodium and enoxaparin sodium after total knee arthroplasty.Methods:A total of 160 patients (31 males and 129 females) who underwent unilateral knee replacement in Department of Orthopedics of Chengdu Second People's Hospital from Oct. 2020 to Dec. 2023 were included. According to the random number method, all patients were evenly divided into the low molecular weight heparin sodium group (16 males and 64 females) and the enoxaparin sodium group (15 males and 65 females). All patients were treated with low molecular weight heparin sodium or enoxaparin sodium to prevent deep vein thrombosis in the lower limbs after surgery. The ecchymosis area on the affected limb was observed 7 days after surgery, and the incidence and difference in ecchymosis area between the two groups of patients were statistically analyzed. Simultaneously evaluate whether there are differences in hemoglobin, platelet, and coagulation related indicators between the two groups of patients before and after surgery.Results:There were no significant differences in hemoglobin, platelet, and coagulation parameters between the low molecular weight heparin sodium group and the enoxaparin sodium group before and after surgery ( t=1.13, -0.27, -0.47, 0.27, 0.34, -0.27, -0.89, -0.46, P=0.27, 0.34, 0.64, 0.83, 0.74, 0.97, 0.24, 0.65). The incidence of ecchymosis in patients with low molecular weight heparin sodium group and enoxaparin sodium group was 61.25% and 67.50%, respectively, with no statistically significant difference in the incidence of ecchymosis between the two groups ( P=0.41). The average size of ecchymosis in the two groups of patients was (40.40 ± 60.07) cm 2 and (37.41 ± 43.21) cm 2, respectively. And there was no statistically significant difference in ecchymosis area ( P=0.61) . Conclusion:Both patients had limbs’ecchymosis in the process of preventing deep venous thrombosis of lower limbs after total knee replacement. This indicates that the two anticoagulants had a certain effect on postoperative skin ecchymosis of total knee. And the incidence rate and area of ecchymosis of affected limbs were similar in the two groups.

Objective To investigate the effects of aerobic exercise and different exercise habits on skeletal muscle function and the possible molecular mechanisms in colorectal cancer-loaded mice.Methods Thirty-five 5-week-old BABL/c male mice were acclimatized to feeding for 1 week and then divided randomly into the following groups:control(D),tumor(M),exercise preconditioning(QAM),lifetime exercise(AM),and exercise(HAM)groups(n=7 mice per group).Mice in the QAM and AM groups underwent aerobic exercise regimen 1 from weeks 2～6.At week 7,mice in the experimental groups received 0.2 mL of CT26 colon cancer cell suspension subcutaneously in the dorsal aspect of the left hind limb,while control mice received 0.2 mL of saline at the corresponding site.Mice in the AM and HAM groups were subjected to aerobic exercise regimen 2 for weeks 7～9.The general status and skeletal muscle mass and function were monitored in all mice throughout the experiments.After completion of the experiment,samples were collected and the cross-sectional area of gastrocnemius muscle fibers(CSA)was measured by hematoxylin and eosin staining and expression levels of proteins related to synthesis and catabolism of the gastrocnemius muscle were analyzed by Western Blot.Results(1)The weight ratio of the gastrocnemius muscle was significantly lower in mice in the M,QAM,and HAM groups compared with group D,and was significantly higher in AM mice compared with M,QAM,and HAM mice.(2)Grip strength,endurance,skeletal muscle circumference,and CSA were significantly lower in group D mice compared with the other groups,and was most enhanced in group HAM.Endurance and CSA were consistently enhanced in groups QAM,AM,and HAM.(3)Muscle RING-finger protein-1(MuRF1)expression levels were significantly lower in groups M,QAM,AM,and HAM than in group D,significantly lower in groups AM and HAM than in group M,and significantly lower in group HAM than in group QAM.(4)Fibronectin type Ⅲ domain-containing protein 5(FNDC5)expression levels were significantly lower in group M than in groups D and QAM.(5)Peroxisome proliferator-activated receptor gamma coactivator 1-alpha expression levels were significantly lower in the QAM and HAM groups compared with group M.(6)Expression levels of phospho(p)-AMP-activated protein kinase(AMPK)/AMPK and p-AMPK were significantly higher in group QAM than in groups D and M,p-AMPK expression significantly lower in groups AM and HAM was than in group QAM,and AMPK expression was significantly lower in groups QAM,AM,and HAM than in group D.Conclusions Exercise preconditioning and continuous aerobic exercise can improve skeletal muscle mass and function in CT26 colon cancer-loaded mice by activating AMPK phosphorylation to stimulate skeletal muscle secretion of FNDC5,thereby regulating the expression of MuRF1 protein.

Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.