ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective To explore the effects of home-based exercise rehabilitation on cardiac structure, valvular function, and exercise capacity in patients with severe aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). Methods 49 patients with severe AS who underwent TAVR at Zhongshan Hospital, Fudan University, from January 2024 to February 2025 were enrolled. They were divided into an exercise group (n＝25) or a non-exercise group (n＝24) based on participating or not in home-based rehabilitation after TAVR. The exercise group received 12 weeks of home-based exercise training (aerobic exercise plus resistance training every week); the non-exercise group received routine care. Transthoracic echocardiography (TTE) was used to assess cardiac structural parameters before discharge (T0) and after 12 weeks of exercise (T1). Functional outcomes including the 6-minute walk test (6MWT), Duke Activity Status Index (DASI), and Short Physical Performance Battery (SPPB) were compared between the two groups. A linear mixed-effects model was used to analyze the effect of home-based rehabilitation on echocardiographic parameters. Patients were stratified by baseline 6MWT (＜240 m as low-function subgroup, ≥240 m as high-function subgroup) to compare exercise-related outcomes between subgroups. Results At T1, the exercise group had a longer 6MWT distance than the non-exercise group (P＝0.012). The linear mixed-effects model showed that after 12 weeks of exercise, the left ventricular end-diastolic diameter (LVEDD) decreased in the exercise group but slightly increased in the non-exercise group, with a significant difference in changes over time between the two groups (P_interaction＝0.030). The exercise group also showed greater improvement in effective orifice area index (P_interaction＝0.028) and effective orifice area (P_interaction＝0.042) than the non-exercise group. Subgroup analysis revealed that in the low-function subgroup, the exercise group showed greater improvement in the 6MWT (P_interaction＝0.035) and the effective orifice area index (P_interaction＝0.046) compared to the non-exercise group; in the high-function subgroup, the exercise group showed greater improvement only in LVEDD compared to the non-exercise group (P_interaction＝0.046). Conclusions Home-based exercise rehabilitation improves exercise capacity, optimizes left ventricular remodeling, and enhances valvular function in patients with severe AS after TAVR, with greater benefits observed in patients with lower baseline 6MWT.

Objective To investigate the application value of the global myocardial work parameters in the non-invasive pressure-strain loop (PSL) technology for early assessment of left ventricular systolic function in patients with chronic kidney disease (CKD). Methods A retrospective analysis was performed on 74 patients with normal left ventricular ejection fraction (LVEF) who were hospitalized in the Nephrology Department of Zhongshan Hospital (Xiamen Branch), Fudan University, from August 2021 to December 2021. Based on CKD stages, patients were divided into early group (CKD stages 1-3) and advanced group (CKD stages 4-5). Additionally, 30 healthy volunteers matched for age and gender were selected as the control group. General clinical data, routine left ventricular ultrasound indicators, myocardial strain, and global myocardial work parameters were collected and compared among the three groups. Correlation analysis and multiple linear regression were used to assess the influencing factors of myocardial work. Results There were no statistically significant differences in global work index (GWI) and global constructive work (GCW) among the three groups. Compared to the control group, both CKD groups showed significantly reduced global work efficiency (GWE), along with significantly increased global waste work (GWW, P＜0.05). The absolute value of global longitudinal strain (GLS) in the advanced CKD group (n＝42) was significantly lower than that in the early CKD group (n＝32; [﹣17.09±0.82]% vs [﹣18.33±0.90]%, P＜0.05), and GWE was also significantly lower (93.00%[90.00%, 95.00%] vs 96.00%[92.25%, 96.75%], P＜0.05), while GWW was significantly higher than that in the early CKD group (150.00 mmHg%[105.25 mmHg%, 215.00 mmHg%] vs 88.00 mmHg%[64.25 mmHg%, 144.50 mmHg%], P＜0.05). Correlation analysis showed that GWE was negatively correlated with the absolute value of GLS and peak strain dispersion (PSD; r＝﹣0.396, ﹣0.558, P＜0.05), GWW was positively correlated with absolute value of GLS, and PSD (r＝0.341, 0.610, P＜0.01). Multiple linear regression results indicated that PSD was an independent influencing factor for GWE (β＝﹣0.558, P＜0.001) and GWW (β＝0.538, P＜0.001). Conclusions The myocardial work parameters GWE and GWW in non-invasive left ventricular PSL technology can identify subclinical left ventricular systolic dysfunction in patients with CKD early and quantitatively.

The pathogenesis of urolithiasis is not yet clear， and there are obvious limitations in the prevention and treatment of urolithiasis by either Chinese or western medicine. The microscopic pathological changes of the kidney from anatomical perspective have a certain internal connection with viewpoint of “kidney storing insufficiency， and kidney deficiency as the root” in the traditional Chinese medicine （TCM） zang-fu （脏腑） theory. Accordingly， the prevention and treatment of urolithiasis by integrated traditional Chinese and western medicine based on “shen-kidney” theory has been proposed. It is believed that the prevention and treatment of urolithiasis can be divided into two stages， that is expelling stones and preventing stones. In terms of preventing stones from kideny， it is recommended to focus on the early pathological changes of the kidney； for preventing stones from shen， it is advised to prevent and treat urolithiasis from kidney deficiency. The treatment should be time-based and stage by stage. Adhering to the principle of “prevention before disease occurs， prevention is more important than treatment” aims to advance the intervention targets for the prevention and treatment of urolithiasis. Emphasizing on the simultaneous treatment of kidney disease and urolithiasis， it is critical to put focus on the development of calcium-containing crystalline nephropathy in the early stage of stone formation， as well as the fundamental pathogenesis of kidney deficiency in TCM. Shen-kidney theory aims to further promote the integration of traditional Chinese and western medicine in the prevention and treatment of urolithiasis， which may provide certain reference for solving the current dilemma of urolithiasis prevention and treatment.

【Objective】 To introduce a surgical technique modified by our center, the establishment of a robot-assisted radical prostatectomy (RARP) channel with extraperitoneal three-port method, and discuss its methods, skills, safety and efficacy. 【Methods】 Clinical data of 21 patients with early and intermediate prostate cancer treated with this surgery during Aug.2022 and Jun.2023 were retrospectively analyzed.Surgical time, intraoperative bleeding volume, postoperative complications, drainage tube retention time, postoperative hospital stay, and follow-up results were observed. 【Results】 All 21 cases of surgery were successfully completed by the same surgeon, without peritoneal rupture or addition of auxiliary holes.The time to establish the extraperitoneal gap and install robotic arm was 20.2 (16.0-28.0) min, the operation time was 107.0(60.0-161.0) min, the amount of intraoperative bleeding was 52.8 (31.0-121.0) mL.All patents resumed eating and drinking the next day after operation.The drainage tube indwelling time was 3.9 (2.0-6.0) d, and the postoperative hospital stay was 4.9 (3.0-7.0) d.No serious complications occurred.The urinary catheter was removed 10 days after operation.One month after operation, 20 patients (95.2%) achieved satisfactory urinary control.The postoperative pathology was prostate adenocarcinoma in all cases, with negative margins, and the prognostic grouping of ISUP was 2 cases in group 1, 6 cases in group 2, 10 cases in group 3, 2 cases in group 4, and 1 case in group 5. 【Conclusion】 RARP by extraperitoneal three-hole method is safe and feasible, with exact establishment of extraperitoneal space, few collisions between instruments, low surgical costs, fast postoperative intestinal recovery, aesthetic incision, and satisfactory recovery of urinary control.

Objective To deeply analyze the problems of public hospitals in medical service satisfaction,construct a more applicable and explanatory service satisfaction evaluation model,and provide reference for the improvement path of patients'medical service satisfaction.Methods Based on the ESCI model,this paper puts forward a research hypothesis,compiles the"Medical Service Satisfaction Evaluation Scale of Public Hospitals in S City",selects S public hospitals as the research object,and evaluates medical service satisfaction from the perspective of patients.Results At present,the main problems affecting the improvement of patients'satisfaction with medical service management in public hospitals in S city are as follows:it is urgent to improve the diagnosis and treatment technology in terms of hardware quality and optimize the environmental hygiene of public hos-pitals,and it is an urgent task to shorten the waiting time for medical treatment in software quality.The score of medical service satisfaction evaluation of S public hospitals was 3.76,and the satisfaction of patients in S public hospitals with their medical serv-ices was at a moderately low level.Conclusion In view of the above problems,it is recommended to strengthen the construction of key specialties,strengthen the construction of talent team,optimize the medical process,open digital linkage services,and strengthen service management,so as to promote the improvement of patients'satisfaction with medical services.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

OBJECTIVE: To report on two children with Kabuki syndrome due to variants of the KMT2D gene and summarize their clinical and genetic characteristics. METHODS: Two children who had presented at the Ningbo Women and Children's Hospital respectively on August 19 and November 10, 2021 were selected as the study subjects. Clinical data were collected. Both children were subjected to whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing. RESULTS: Both children had featured motor and language developmental delay, facial dysmorphism and mental retardation. Genetic testing revealed that both had harbored de novo heterozygous variants of the KMT2D gene, namely c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*), both of which were rated as pathogenic variants based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The c.10205del (p.Leu3402Argfs*3) and c.5104C>T (p.Arg1702*) variants of the KMT2D gene probably underlay the pathogenesis in these two children. Above finding has not only provided a basis for their diagnosis and genetic counseling, but also enriched the spectrum of KMT2D gene variants.
Child ; Female ; Humans ; Abnormalities, Multiple/genetics* ; Intellectual Disability/genetics* ; Genetic Counseling ; Genetic Testing ; Mutation

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

As a common psychiatric disorder, the etiology and pathogenesis of depression are complex and not yet fully elucidated.The diagnosis of depression mainly depends on the patients’ medical history, clinical symptoms and related examinations.Identification of biomarkers will provide important clues for the specific diagnosis and targeted treatment of depression.In addition to the widely recognized neurotransmitter dysregulation, hypothalamus-pituitary-adrenal axis hyperactivity, neuroplasticity, and neuro-inflammation theory, oxidative stress is also involved in the pathogenesis of depression in multiple ways.Many studies showed that the heat shock protein 70(HSP70)levels will increase in early stage to cope with the stress in patients with depression.However, lower HSP70 levels are often correlated with more severe depressive symptoms.HSP70 may be involved in depression through multiple pathways of oxidative stress, glucocorticoid receptors, neuroinflammation and neuroplasticity.Furthermore, increasing HSP70 expression results in significant improvement in depression-like behavior in animals.Thus, HSP70 possesses potential value as an early warning marker for depression as well as a therapeutic target.