OBJECTIVE To investigate the mechanism by which esketamine improves postoperative cognitive impairment in rats with hip fracture based on the AMP-activated protein kinase （AMPK）/silencing information regulatory factor 1 （SIRT1）/ peroxisome proliferator activated-receptor-γ coactivator-1α （PGC-1α） signaling pathway. METHODS Rats with hip fracture surgery were assigned into model group， esketamine group （10 mg/kg）， inhibitor group （250 μg/mL AMPK inhibitor Compound C）， and esketamine+inhibitor group （10 mg/kg esketamine + 250 μg/mL Compound C）， and rats undergoing sham surgery were used as the control group， with 12 rats in each group. New object recognition and Barnes maze experiments were used to E-mail：448231@163.com evaluate cognitive function in rats. The levels of serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β），superoxide dismutase （SOD）， malondialdehyde （MDA）， gamma-aminobutyric acid （GABA）， dopamine （DA） and glutamate （Glu）， and the apoptosis of hippocampal neurons were detected. The pathological morphology of the hippocampal tissue and the ultrastructure of mitochondria were observed. The mRNA expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax），the mRNA and protein expression of AMPK， SIRT1 and PGC-1α， as well as the expression of phosphorylated （p）-AMPK in hippocampal tissue， were detected. RESULTS Compared with the control group， the hippocampal neurons in the model group of rats were disordered， with more neurons necrotic and swollen mitochondria；the new object recognition index， the SOD， GABA， DA levels， Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly reduced， while the latency and number of errors for locating unknown holes， the TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly increased/prolonged （P＜0.05）. Compared with the model group， the esketamine group showed reduced pathological damage to the hippocampal tissue of rats， and the new object recognition index， the SOD， GABA and DA levels， the Bcl-2， AMPK， SIRT1 and PGC-1α mRNA expression levels， and p-AMPK， SIRT1， PGC-1α protein expression levels were significantly increased，while the latency and error frequency for locating unknown holes， TNF-α， IL-1β， MDA and Glu levels， neuronal cell apoptosis rate， and Bax mRNA expression levels were significantly decreased （P＜0.05）；the inhibitor group showed the opposite trend of changes in these indicators compared to the esketamine group （P＜0.05）.AMPK inhibitor could reverse the improvement effect of esketamine on the above indicators after hip fracture surgery in rats （P＜0.05）. CONCLUSIONS Esketamine may improve postoperative inflammatory response and oxidative stress levels in rats with hip fracture by activating the AMPK/SIRT1/PGC-1α signaling pathway， inhibiting neuronal cell apoptosis， improving mitochondrial structure， and promoting postoperative cognitive function recovery.

Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

Objective To explore the neuroprotective role of Rab10 gene in depression and the mechanism mediating its effect.Methods Forty-eight male SD rats were randomized into a control group and 3 chronic unpredictable mild stress(CUMS)groups(n=12).The rats in the latter 3 groups were subjected to injections of normal saline,an adeno-associated viral(AAV)vector,or a Rab10-overexpressing AAV vector in the lateral ventricle after CUMS modeling.The depressive behavioral changes of the rats were assessed using behavioral tests.The TargetScan database was used to predict the miRNA interacting with Rab10 and the binding sites.The interaction between miRNA-103-3p and Rab10 was investigated using dual-luciferase and radioimmunoprecipitation(RIP)assay.The effect of corticosterone treatment on PC12 cell viability was assessed with CCK-8 assay.In corticosterone-stimulated PC12 cells,the changes in BDNF,CREB,p62,Beclin-1,Wnt3a,Gsk3β,phosphorylated(p)-Gsk3β,and β-catenin protein expressions following transfection with the Rab10-overexpressing AAV vector and a miRNA-103-3p inhibitor,alone or in combination,were analyzed using qRT-PCR and Western blotting.Results Injection of Rab10-overexpressing AVV vector into the lateral ventricle significantly improved depressive behaviors of CUMS rats.The mRNA and proteins expression of Rab10 were significantly down-regulated in the hippocampus of CUMS rats and in corticosterone-stimulated PC12 cells.Bioinformatics analysis and the results of double luciferase and RIP experiments confirmed the targeting relationship between miRNA-103-3p and Rab10.In PC12 cells,overexpression of Rab10 or silencing miRNA-103-3p activated the Wnt/β-catenin signaling pathway,up-regulated the expressions of BDNF,CREB and Beclin-1,and down-regulated the expression of p62 protein;silencing Rab10 obviously blocked the effect of miRNA-103-3p inhibitor.Conclusion In mouse models of depression,miRNA-103-3p activates Wnt/β-catenin signaling via targeting rab10 to improve neural plasticity and promotes neural cell autophagy.

Objective:To compare the prognosis of patients with hepatolithiasis-associated intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV)-associated ICC after radical resection.Methods:The clinicopathological and survival data of 69 patients with ICC undergoing radical resection in the Department of Hepatobiliary and Pancreatic Surgery, Lihuili Hospital Affiliated to Ningbo University from January 2012 to February 2024 were retrospectively analyzed, including 40 males and 29 females, aged (62.9±10.2) years. Patients were divided into the stone group ( n=40, with hepatolithiasis) and HBV group ( n=29, with HBV). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival rate comparison. Cox proportional hazard regression model was used for multivariate analysis to analyze the effect of hepatolithiasis and HBV on the prognosis. Results:The median overall survival of ICC patients in the stone group was 16 months, and that in the HBV group was 27 months. The 1-, 3-, and 5-year cumulative survivals of the stone group were 56.6%, 23.2%, and 10.3%, respectively, which were lower than those of the HBV group (72.0%, 50.7%, and 43.4%, respectively, χ2=5.95, P=0.015). The median recurrence-free survivals (RFS) of the stone group and the HBV group were 12 months and 23 months, respectively. The 1-year and 3-year RFS of the stone group were 49.2% and 18.1%, which were lower than those of the HBV group (65.0% and 39.8%, respectively, χ2=3.94, P=0.047). Univariate analysis showed that hepatolithiasis was assciated with prognosis ( χ2=5.95, P=0.015). Multivariate Cox regression analysis showed that hepatolithiasis and hepatitis B virus infection had no effect on the prognosis of ICC patients after surgery (all P>0.05). Conclusion:Compared to HBV infection, ICC patients with hepatolithiasis have a worse prognosis. Hepatolithiasis and HBV infection have no effect on the prognosis of ICC after radical resection.

Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).
Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve Insufficiency ; Diffusion Magnetic Resonance Imaging ; Aortic Valve Stenosis ; Stroke

Objective:To study the teaching effect of the teaching method of case-based learning (CBL) combined with team-based learning (TBL) based on the standard patient (SP) in the clinical teaching of department of intensive care medicine.Methods:A total of 60 medical students clinically studying in the department of intensive care medicine were randomly divided into 2 groups, with 30 students in each group. The two groups received the clinical teaching through the lecture-based learning (LBL) teaching method and the CBL combined with TBL based on SP teaching method respectively. By evaluating the clinical synthesis ability of the students of two groups and the satisfaction survey of the two teaching methods, the teaching effect was evaluated. SPSS 19.0 statistical software was used to perform Chi-square test and t-test. Results:Compared with LBL teaching method, the students who accepted the CBL combined with TBL based on SP teaching method had significantly better clinical comprehensive ability ( P < 0.05), mainly in their clinical thinking ability [(4.18±0.55) vs. (3.66±0.47)], clinical skills [(4.03±0.61) vs. (3.59±0.52)] and communication ability with patients [(4.11±0.58) vs. (3.74±0.50)]. In addition, student satisfaction with teaching methods was also higher ( P <0.05), especially in the satisfaction of learning interest [(4.38 ± 0.72) vs. (3.65±0.56)], self-learning ability [(4.24±0.71) vs. (3.91±0.52)], clinical thinking ability [(4.09±0.66) vs. (3.22±0.54)], communication ability [(4.42±0.60) vs. (3.67±0.48)], and team cooperation spirit [(4.15±0.58) vs. (3.78±0.51)]. Conclusion:The teaching method of CBL combined with TBL based on SP is feasible and has good teaching effect in the clinical teaching of department of intensive care medicine.

Objective:To evaluate the effectiveness and prognosis of emergent transcatheter aortic valve replacement (TAVR) and to provide standardized procedural suggestion for the development of emergent TAVR in China.Methods:From January 2020 to April 2021, 12 patients who underwent emergent or salvage TAVR in the Second Affiliated Hospital Zhejiang University School of Medicine were retrospectively enrolled from the TORCH registry (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population, a prospective cohort study; NCT02803294). Baseline, periprocedural and 30-day follow up data were collected. Post-operative data were compared with pre-operative data using Paired-Samples test.Results:Patients’ median Society of Thoracic Surgeons score (STS score) was 15.432%. There was a significant decrease of mean gradient after emergent TAVR procedure (1.69 m/s vs. 4.90 m/s, P<0.01). During the 30-day follow up, there were 1 patient (8.3%) died and 2 patients received permanent pacemaker implantation. No disabling stroke, acute kidney injury, major vascular complication occurred during the first month after emergent TAVR. Among the survival patients, there was a significant releasing of heart failure symptoms to New York Heart Association function stage Ⅰ/Ⅱ in 81.8% patients at 30-day follow up. Left ventricular ejection fraction also improved significantly from (47.4±9.5)% to 58.8±8.0% ( P= 0.026). The mean gradient were (1.57±0.30) cm 2 and no patients had a moderate or severe paravalvular leakage. Besides, a significant decrease of pro-B-type natriuretic peptide (1 089.9 pg/mL vs. 12 215.5 pg/mL , P=0.001) and troponin T (0.020 ng/mL vs. 0.337 ng/mL, P=0.003) were found at 30 days after emergent TAVR. Conclusions:For patients with severe aortic stenosis and acute cardiac decompensated, emergent TAVR is a safe and effective rescue treatment.

Objective To analyze peripheral blood hemogram, lymphocyte micronucleus and chromosomal aberrations of radiologists, so as to provide basis for occupational protection and health monitoring of radiologists. Methods Lymphocyte micronucleus, chromosome and blood hemogram analysis were performed on 127 radiologists who received health examinations in 2015, 2017 and 2019, and they were assigned to the radiation group. In addition, 133 medical staff with no history of radiation exposure were selected as the control group. Results The micronucleus rate and chromosome aberration rate of the radiation group were higher than those of the control group, and the white blood cell and platelet counts were lower than those of the control group, both of which were statistically significant (P < 0.05). The total number of white blood cells in peripheral blood of 127 radiologists decreased gradually with the increase of exposure time to ionizing radiation, and the chromosome aberration rate increased gradually, all of which had statistical significance (P < 0.05). The rate of chromosomal aberration was higher in radiologists with damage work age of more than 20 years than in the low-work age group, and there was no statistical significance between different damage work age (P > 0.05). The chromosome aberration rate of nuclear medicine and interventional therapy was higher than that of other types, with statistical significance (P < 0.05). Conclusion Long-term exposure to low-dose ionizing radiation can reduce the total number of white blood cells and increase the chromosome aberration rate of radiologists. It is necessary to strengthen the protective measures for radiologists to reduce the degree of ionizing radiation damage, especially to strengthen the occupational protection for radiologists in nuclear medicine and interventional therapy.

Objective:To study the relationship between morphologic classification and prognosis of patients with intrahepatic cholangiocarcinoma (ICC).Methods:The clinicopathologic data of 125 ICC patients who underwent R 0 resection at the Ningbo Medical Center Li Huili Hospital from January 2011 to May 2019 were retrospectively analyzed. This cohort consisted of 67 males and 58 females, aged 26.0 to 82.0 (63.5±9.5) years old. Based on the resected specimens, the patients were divided into the mass forming type, periductal infiltrating type and mixed type. The survival rates and recurrence-free survival outcomes of the patients among the three types were compared, and the risk factors that influenced prognosis were analyzed. Results:Using the predetermined inclusion and exclusion criteria, 16 patients with missing data and other causes of death were excluded from the initial 125 patients. Also, as the number of the mixed type was small, these patients were excluded. Finally 62 patients in the mass forming type and 42 patients in the periductal infiltrating type were analyzed. In the mass forming group, there were 32 males and 30 females, aged (63.1±9.1) years. In the perivascular infiltration group, there were 22 males and 20 females, aged (64.1±10.2) years. The 1-, 3-, 5-year survival rates of the mass forming group were 78.1%, 33.2%, 18.9% (median survival 25 months). The 1-, 3-, 5-year survival rates of the periductal infiltrating type were 63.3%, 8.3%, 6.1% (median survival 15 months). There were statistically significant differences between the two groups ( P<0.05). The median recurrence-free survival for the mass forming and the periductal infiltrating groups were 18 and 11 months, respectively, with a statistically significant differences between them ( P<0.05). Univariate and multivariate analysis showed that TNM staging Ⅲ~Ⅳ ( HR=2.966, 95% CI: 1.549-5.679) and periductal infiltrating type ( HR=2.403, 95% CI: 1.236-4.670) were independent risk factors for survival of these patients after operations. TNM staging Ⅲ~Ⅳ ( HR=2.466, 95% CI: 1.325-4.589), low grade differentiation ( HR=0.528, 95% CI: 0.299-0.934) and periductal infiltrating type ( HR=2.432, 95% CI: 1.295-4.565) were independent risk factors for relapse-free survival of these patients ( P<0.05). Conclusions:Morphological classification was found to be an independent risk factor for prognosis of ICC patients in this study, with significantly worse long-term prognosis when compared with the mass forming type.

OBJECTIVE:To observe clinical efficacy and safety of salvianolate in the treatment of acute exacerbation of chron-ic obstructive pulmonary disease(AECOPD). METHODS:80 AECOPD patients were selected and randomly divided into observa-tion group and control group,with 40 cases in each group. Both groups received mechanical ventilation. Control group was given routine treatment of theophyllinum,bronchodilators and glucocorticoid;treatment group was additionally given Salvianolate injec-tion 200 mg,qd,ivgtt,on the basis of control group. Clinical efficacy was observed in 2 groups,blood hemorheology indexes were also observed before and after treatment. The mechanical ventilation time,ICU residence time and ADR were recorded in 2 groups. RESULTS:Clinical total effective rate of observation group was 95.00%,which was significantly higher than 70.00% of control group,with statistical significance(P<0.05). Before treatment and 2 d after treatment,blood rheology indexes of treatment group were improved significantly(all P>0.05),and whole blood reduction viscosity of control group was improved significantly(P<0.05). Mechanical ventilation time and ICU residence time of treatment group was significantly shorter than that of control group (P<0.05). No ADR was found in 2 groups. CONCLUSIONS:Salvianolate can significantly improve the blood coagulation status of AECOPD patients receiving invasive mechanical ventilation,and has the advantages of good clinical efficacy and low cost of medical treatment.