Post-stroke cognitive impairment(PSCI)is a prevalent and debilitating complication of stroke that significantly hinders recovery and diminishes patients'quality of life.Repetitive transcranial magnetic stimulation(rTMS),a non-invasive neuromodulation technique,has garnered growing interest for its potential to enhance cognitive function in individuals with PSCI.Concurrently,resting-state functional magnetic resonance imaging(rs-fMRI),as a non-invasive neuroimaging technique,has emerged as a valuable tool for assessing spontaneous neural activity and functional connectivity in the brain.By offering in-sights into the neurobiological mechanisms underlying PSCI and the modulatory effects of rTMS,rs-fMRI provides a foundation for advancing precision-targeted interventions.This review aims to highlight recent progress in applying rs-fMRI to evaluate the efficacy and underlying mechanisms of rTMS in the treatment of PSCI.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.

Post-stroke cognitive impairment(PSCI)is a prevalent and debilitating complication of stroke that significantly hinders recovery and diminishes patients'quality of life.Repetitive transcranial magnetic stimulation(rTMS),a non-invasive neuromodulation technique,has garnered growing interest for its potential to enhance cognitive function in individuals with PSCI.Concurrently,resting-state functional magnetic resonance imaging(rs-fMRI),as a non-invasive neuroimaging technique,has emerged as a valuable tool for assessing spontaneous neural activity and functional connectivity in the brain.By offering in-sights into the neurobiological mechanisms underlying PSCI and the modulatory effects of rTMS,rs-fMRI provides a foundation for advancing precision-targeted interventions.This review aims to highlight recent progress in applying rs-fMRI to evaluate the efficacy and underlying mechanisms of rTMS in the treatment of PSCI.

Cholera toxin B subunit(CTB)can enhance antigen presentation and promote T cell pro-liferation,B cell differentiation and B cell isotype conversion.Moreover,woodchuck hepatitis virus post transcriptional regulatory element(WPRE)can enhance gene expression efficiency by optimi-zing RNA polyadenylation,denuclearization and/or translation.In order to construct porcine epi-demic diarrhea virus like particles(VLPs)chimerized with CTB and WPRE and evaluate their im-munogenicity,the G Ⅱ type PEDV S gene,combined with the elements promoting the protein ex-pression and enhancing immune effects,was synthesized by the company and cloned into pET32a(+).Af-ter double enzyme digestion and gel recovery,the gene named as TSCW was cloned into pFastBacl to construct the recombinant plasmid pFastBac-TSCW.pFastBac-TSCW was further transformed into DH10Bac competent cells to obtain recombinant bacmid Bacmid-TSCW.Subsequently,the Bacmid-TSCW was transfected into sf9 cells to obtain recombinant baculovirus BV-TSCW.After co-infection of BV-TSCW and BV-M into sf9 cells,viral like particles VLP-TSCW was obtained and used to immunize mice to evaluate its immunogenicity.The results showed that the recombi-nant plasmid pFastBac-TSCW and bacmid Bacmid-TSCW were successfully constructed.After transfection of sf9 cells with recombinant baculovirus,significant cytopathic effects were observed.PCR and Western blot results showed that the recombinant baculoviruses existed stably in sf9 cells and the target proteins was also expressed stably.In addition,the electron microscopy results showed that BV-TSCW and BV-M successfully assembled into viral like particles VLP-TSCW.Furthermore,ELISA results indicated that VLP-TSCW induced high level specific antibodies.The above results laid the foundation for further optimization,design and development of PEDV VLPs subunit vaccines.

Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.

Objective:To compare the therapeutic efficacy, safety and drug cost between generic enteric-coated mycophenolate sodium (EC-MPS) and branded EC-MPS in immunosuppressive treatment for adult recipients of renal transplantation (RT) .Methods:From January, 2022 to October, 2023, 60 adult RT patients were continuously enrolled and randomized into two groups. Patients receiving generic EC-MPS were selected as cohort 1 (n=30) while those taking branded EC-MPS designated as cohort 2 (n=30). Hepatic/renal function, blood routine parameters, drug concentrations, adverse events (AEs) and drug costs were recorded and compared between two cohorts at baseline (<3 days before/after day of RT, W0), week 1 (W1), week 4 (W4), week 8 (W8), week 12 (W12) and week 24 (W24) post-RT.Results:Only urine protein was elevated at W24[0.4 (0-0.6) vs 0 (0-0.2) g/24 h, P=0.049]in cohort 1 as compared with cohort 2. Aspartate aminotransferase at W12 (15.6±3.3 vs 20.3±9.7 U/L, P=0.010), leucocyte count at W1 (8.4±2.3 vs 10.1±3.8 ×10 9/L, P=0.045) and platelet count at W1 (158.5±51.5 vs 185.8±46.8 ×10 9/L, P=0.036) all declined in cohort 1 as compared with cohort 2. However, these parameters at other timepoints did not vary between two cohorts (all P>0.050). In addition, blood concentration of MPS after dosing, area under the concentration-time curve and trough concentration of tacrolimus at different timepoints were not different between two cohorts (all P>0.050). Similarly, helper T cells (Th), suppressor T cells (Ts), Th/Ts and B cells at W4/12 did not vary between two cohorts (all P>0.050). Concerning drug cost, no difference existed in the number of tablets or length of stay between two cohorts (both P>0.050). However, cost of EC-MPS (￥1 333.5±419.6 vs ￥2 368.6±596.0, P<0.001) and total cost during hospitalization (￥96 403.3±29 159.8 vs ￥117 062.8±28 782.1, P=0.001) were lower in cohort 1 than cohort 2. The most common AEs in cohort 1 included acid regurgitation (n=19, 63.3%), hypoalbuminemia (n=16, 53.3%), anemia (n=12, 40.0%) and hypokalemia (n=11, 36.7%). And the most common AEs in cohort 2 included acid regurgitation (n=20, 66.7%), anemia (n=14, 46.7%) and hypoalbuminemia (n=9, 30.0%). Notably, the incidence of all AEs was not different between two cohorts (all P>0.050) . Conclusion:Generic EC-MPS has comparable therapeutic efficacy and safety profile with lower drug cost in adult RT patients. It provides more options for maintenance treatment in RT patients.

Objective To investigate the effects of different sterilization methods on the quality of Astragali Radix decoction pieces by comparing the properties,odor,fingerprint,sterilization effect,extract and active component contents of Astragali Radix decoction pieces,and to further optimize the best sterilization process parameters of Astragali Radix decoction pieces.Methods The effects of moist heat sterilization,irradiation sterilization and dry heat sterilization on the quality of Astragali Radix decoction pieces were compared,and the best sterilization method was selected.Based on this,taking the content of astragaloside IV,the content of isoflavone glucoside,the total content of the two and the sterilization rate as the assessment indicators,taking the sterilization temperature,sterilization time and material thickness as the assessment factors,on the basis of the single-factor test,the response surface method was used to optimize the optimal dry heat sterilization process of Astragali Radix decoction pieces.Results The dry heat sterilization method was selected to sterilize Astragali Radix decoction pieces.The best process for dry heat sterilization was as follows:the sterilization temperature of 113℃,sterilization time of 5.1 h,and the material thickness of 19 mm.Conclusion Considering the sterilization effect,the influence on the content of active ingredients,operability and cost,selecting dry heat sterilization is the best sterilization method for Astragali Radix decoction pieces,and the optimal sterilization process is stable and feasible,with good repeatability,which can provide scientific basis for its industrial production application.

Objective To construct a prediction model for post-neoadjuvant therapy recurrent laryngeal nerve lymph node(RLN LN)status via clinical and CT image data in esophageal cancer patients pre-neoadjuvant therapy.Methods A retrospective analysis was conducted on 403 patients with locally advanced esophageal cancer who received neoadjuvant therapy and radical resection for esophageal cancer.All patients were divided into a training cohort(n=270)and a validation cohort(n=133)randomly according to a 2:1 ratio.Clinical and imaging features associated with positive RLN LN pathology were selected by univariate analysis.Multivariate logistic stepwise regression model was used to construct the prediction model.The prediction ability of the model was evaluated by receiver operating characteristic(ROC)curve.Results The basic model included neoadjuvant therapy and RLN LN short diameter,with an area under the curve(AUC)of 0.7(training cohort)and 0.65(validation cohort).The final prediction model included neoadjuvant therapy,human albumin,platelet count,largest lymph node enhancement characteristics,whether the largest lymph node was in the recurrent laryngeal region,and RLN LN short diameter,with AUC of 0.83[95％confidence interval(CI)0.768-0.899]and 0.76(95％CI 0.645-0.887)for the training and validation cohorts,respectively.Conclusion The model based on clinical data and imaging features pre-neoadjuvant therapy for esophageal cancer can assist in clinically predicting the post-neoadjuvant therapy RLN LN status.

BACKGROUND:There are many treatment methods for knee osteoarthritis,among which electroacupuncture,as an important non-drug treatment,is effective in the treatment of knee osteoarthritis,but its exact mechanism is not clear. OBJECTIVE:Effect of electroacupuncture on the expression of p53 and P21 in articular cartilage and subchondral bone of aged rats with knee osteoarthritis. METHODS:Eight 6-month-old male Sprague-Dawley rats were included in the young group and sixteen 24-month-old male Sprague-Dawley rats were randomly divided into old group(n=8)and electroacupuncture group(n=8).The rats in the electroacupuncture group received electroacupuncture stimulation once a day,5 days a week,for 8 continuous weeks,and the other two groups did not do any treatment.Eight weeks later,the level of type Ⅱ collagen C-terminal peptide in peripheral blood was detected by ELISA,the morphology of left knee cartilage and subchondral bone was observed by safranin O-fast green staining,the degree of knee cartilage degeneration was evaluated by modified Mankin's score,the microstructure of left knee cartilage and subchondral bone was detected by micro-CT,and the expression levels of matrix metalloproteinase 13,P53,P21 Mrna and protein were detected by RT-PCR and western blot respectively. RESULTS AND CONCLUSION:Compared with the young group,the level of C-terminal peptide of type Ⅱ collagen in the peripheral blood was increased in the old group(P<0.05).The micro-CT results showed that the bone volume fraction,bone mineral density and the number of bone trabeculae were decreased in the old group compared with the young group(P<0.05),while the trabecular separation increased(P<0.05).Safranin O-fast green staining showed that in the old group,the surface layer of cartilage was uneven with fissures,the morphology of chondrocytes was irregular and stained unevenly,the boundary between the cartilage and subchondral bone was blurred,and the matrix loss was serious.The Mankin's score was higher in the old group than the young group(P<0.05).The expression of matrix metalloproteinase 13,P53,P21 at Mrna and protein levels increased in the old group compared with the young group(P<0.05).Compared with the old group,electroacupuncture decreased the level of C-terminal peptide of type Ⅱ collagen(P<0.05),increased the bone volume fraction,bone mineral density and the number of bone trabeculae(P<0.05),and decreased the trabecular separation(P<0.05).Safranin O-fast green staining showed that in the electroacupuncture group,the surface of cartilage was smooth and red staining was uniform,and the cell morphology and structure were between the young group and the old group.Following electroacupuncture treatment,the Mankin's score(P<0.05),matrix metalloproteinase 13 and P21 Mrna expression(P<0.05),and matrix metalloproteinase 13 and P53 protein expression decreased(P<0.05),while there was a decreasing trend of P53 Mrna and P21 protein expression,but with no statistical significance(P>0.05).To conclude,electroacupuncture may delay articular cartilage degeneration and subchondral osteoporosis in aged rats by inhibiting the expression of P53 and P21,so as to protect joints and delay joint aging.