Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

Objective To explore factors associated with early postoperative hormonal remission in patients with prolactinoma and to develop prediction models based on clinical and radiological features. Methods Data from 107 patients with prolactinoma who underwent transsphenoidal surgery at The First People’s Hospital of Huai’an, Nanjing Medical University between January 2020 and December 2024 was collected, included general clinical characteristics, preoperative laboratory indicators, and imaging features. Based on whether early postoperative prolactin (PRL) levels normalized, patients were divided into a remission group (n=76) and a non-remission group (n=31). Univariate logistic regression was used for preliminary evaluation of candidate variables, followed by LASSO regression for feature selection. Multiple machine learning models were constructed, including logistic regression, random forest, support vector machine, K-nearest neighbors, naive Bayes, decision tree, neural network, and gradient boosting decision tree (GBDT). All models were trained and evaluated using ten-fold cross-validation, with comprehensive assessment of model performance based on the area under the ROC curve (AUC), accuracy, sensitivity, specificity, precision, and F1 score. Results The maximum diameter of tumors in the non remission group was larger than that in the remission group (P=0.019), and the incidence of tumor stroke and preoperative PRL levels were significantly higher than those in the remission group (P＜0.001). Univariate analysis showed that sex, maximum tumor diameter, tumor stroke, and preoperative PRL levels were influencing factors for early postoperative hormone response in patients with prolactinoma (P＜0.05). The comparison results of machine learning models show that the neural network model performs the best (AUC=0.921) and has good clinical application value, followed by the GBDT model (AUC=0.893) and the support vector machine model (AUC=0.884). Other models also show certain predictive ability. Conclusions Sex, preoperative PRL levels, maximum tumor diameter, Hounsfield unit value, and tumor stroke are important factors affecting early hormone response after prolactinoma surgery. The machine learning model constructed based on the above variables has good predictive performance, and performs the best and has good clinical application value.

Objective To explore the principle of antibacterial drug therapy and the strategy of program optimization in elderly patients with Helicobacter pylori（Hp）. Methods The common therapeutic regimen of Hp was summarized, and the better therapeutic regimen of elderly Hp patients was screened ultimately. Results Amoxicillin and cefuroxime were relatively safe compared with other recommended antibacterial drugs. Using other commonly antibiotics for Hp should pay attention to the disease of patients and current drug. Conclusion Elderly patients usually suffered from a variety of diseases and required multiple drugs. The application of therapeutic regimen for elderly patients with Hp should be supposed to fully weigh the risks and benefits.

Objective:To explore and evaluate the optimization and application of case-based learning (CBL) in the reform practice for integrated curriculum of the digestive system.Methods:The 174 undergraduate students majoring in eight-year clinical medicine enrolled in 2019 at the Peking University Health Science Center were selected as research objects. CBL was used in the integration and optimization of the digestive system curriculum. These included increasing class hours, selecting disease modules, lesson preparation involving multi-disciplinary teachers, and joint teaching. Upon completion of teaching, a comprehensive evaluation of teaching effectiveness was conducted through questionnaires administrated to teachers and students, feedback from supervision experts, and scores of students. SPSS 21.0 was used for the t-test and a reliability analysis was conducted on the questionnaire results. Results:Teachers, students, and supervision experts were highly satisfied with CBL. More than 95% of teachers believed that joint teaching facilitated the sharing of diverse professional knowledge among teachers, enhanced the in-depth instruction of imaging knowledge, promoted the transformation of teaching ideas, and improved teaching ability. More than 70% of students agreed that joint teaching deepened their understanding of diseases, stimulated learning interest, and established a theoretical foundation for clinical practice. The average score of class performance was (47.60±2.41) points (a total score of 50 points). The answers of students to case-based questions in final exams were satisfactory. The average score of final evaluation was (82.24±8.82) points.Conclusions:The optimization and application of CBL in the integrated curriculum of the digestive system is highly accepted by teachers and students. This method improves the interest of learning and facilitates the establishment of overall medical thinking and clinical thinking in students.

Objective·To evaluate the clearance and pharmacokinetics/pharmacodynamics(PK/PD)of antibiotics from the perspective of protein binding rates in critically ill patients undergoing intermittent hemodialysis(IHD),in order to explore the association between protein binding rate and dialysis clearance of antibiotics,and to provide theoretical basis for developing antibiotic dosing regimens during hemodialysis.Methods·Nineteen patients undergone low-flux hemodialysis and received antibiotic therapy at the Department of Nephrology,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,were enrolled and divided into the meropenem group(n=7),the vancomycin group(n=5)and the ceftriaxone group(n=7)according to the type of antibiotics.A liquid chromatography with tandem mass spectrometry(LC-MS/MS)method was established to detect meropenem,vancomycin,and ceftriaxone in human plasma/serum and dialysate.A two-compartment pharmacokinetic model was established using MATLAB.Instantaneous and total dialysis clearance rates were calculated,and PK/PD parameters were analyzed.Results·No significant differences were found in the clinical characteristics of subjects among the three groups.The dialysis clearance rates were as follows:meropenem group(5.14?5.97 L/h)>vancomycin group(2.87?3.77 L/h)>ceftriaxone group(1.21?1.90 L/h),with statistically significant differences(P<0.001).All three antibiotics showed good fit in the two-compartment pharmacokinetic model with a dialysate chamber(fval%<2),and the calculated PK/PD parameters were consistent with previous literature.For meropenem,the fraction of time that the free drug concentration remained above the minimal inhibitory concentration(%fT>MIC)values were 95.2%,60.8%and 32.4%at minimal inhibitory concentration(MIC)values of 2,8 and 16 μg/mL,respectively.For ceftriaxone(free concentration),the%fT>MIC values were all above 45.0%at MICs of 0.25,4 and 16 μg/mL.For vancomycin,only 14.0%of the trough concentrations reached the target range of 15?20 mg/L.Conclusion·The three antibiotics are well described by the two-compartment model.The plasma protein binding rate has a significant effect on the dialysis clearance of antibiotics in low-flux IHD,with higher protein binding associated with lower clearance.The regimens of meropenem(0.5 g/d)and ceftriaxone(2.0 g/d)are generally effective among patients undergoing low-flux IHD,while the vancomycin regimen with a loading dose of 1.0 g and a maintenance dose of 0.5 g/2 d carries a risk of treatment failure.

Objective To compare TyG index between the patients with CHF and ADHF to eluci-date the metabolic difference between these two stages.Methods A total of 1156 HF patients ad-mitted in Taizhou People's Hospital between January 2020 and December 2022 were enrolled,and according to 2021 ESC Guidelines for Diagnosis and Treatment of Acute and Chronic Heart Fail-ure,they were divided into CHF group(365 cases)and ADHF group(791 cases).The clinical da-ta,results of laboratory tests,and cardiovascular history were collected,and TyG index was calcu-lated.All-cause death outcome was observed in ADHF patients during a follow-up of 1 year.Results The TyG index was significantly lower in the ADHF group than the CHF group[8.27(7.99,8.62)vs 8.35(8.04,8.75),P=0.001].In the ADHF group,the TyG index was positively correlated with SBP,DBP,TC,TG,LDL-C,FPG,HbA1c,BMI,and LVEF,and negatively with age(P＜0.01).In the CHF group,the index was positively correlated with DBP,TC,TG,LDL-C,FPG,BMI,and HbA1c,and negatively with age(P＜0.05,P＜0.01).Both univariate and multiva-riate logistic regression analyses indicated that the TyG index was a protective factor for ADHF(OR=0.647,95％CI:0.503～0.832,P=0.001;OR=0.694,95％CI:0.536～0.898,P=0.005).Multivariate logistic regression analysis showed that the index in ADHF patients was a protective factor for one-year all-cause mortality(OR=0.483,95％CI:0.254-0.916;P=0.026).Conclusion TyG index might be regarded as an important marker for assessing the metabolic status in HF patients and predicting the prognosis in ADHF patients.

Objective To study the effect and duration of point-of-use filters on the improvement of endoscopic fi-nal rinse water quality.Methods The final rinse water end at the gastroscope manual cleaning workstation in the Endoscopy Centre of the First Affiliated Hospital with Nanjing Medical University was selected to install a tap ter-minal filter;five specimens of final rinse water were collected consecutively before the installation,immediately after the installation,and 1-11 weeks after the installation.At each sampling time,the staff responsible for clea-ning and disinfecting were asked whether the flow rate of discharged water could satisfy the working demand;the final rinse water was inoculated on R2A culture medium with membrane filter method,bacterial colony forming unit(CFU)was calculated after 30℃ incubation for 5 days.Results The qualified rates of endoscopic final rinse water before point-of-use filter installation was 0,immediately after and 1-9 weeks after installation were both 100％,10 and 11 weeks after installation were 80.0％and 20.0％,respectively.The mean CFU of endoscopic final rinse wa-ter before point-of-use filter installation was 102 CFU/100 mL,immediately after and 1-9 weeks after installation were both ≤2 CFU/100 mL,10 and 11 weeks after installation were 8 and 18 CFU/100 mL,respectively.The feedback from the cleaning and disinfection staff before installation,immediately after installation,and 1-11 weeks after installation indicated that the flow rate of discharged water gradually slowed down over time,but could still meet the work requirements.Conclusion The point-of-use filter can quickly and effectively improve the quality of endoscopic final rinse water,with use duration of up to 9 weeks after installation;Its biggest advantage is that it can serve as the final barrier to all integrated measures,playing a supplementary role in case of any problems occu-rring in the front-end process,and ensuring the microbial quality of the final rinse water to the greatest extent possible.

Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.

Aim To evaluate the ameliorative effects of different ratios of Renshen-Huangjing(RH) on SPS-induced PTSD-like behaviors in mice,and to investi-gate the action mechanism using bioinformatics analysis and experimental studies.Methods The aqueous ex-tract was extracted in four ratios of RH in a total weight of 60 g,i.e.1∶0(RH1),2∶1(RH2),1∶2(RH3),and 0∶1(RH4).The extraction rates of Rg1,Rb1,and polysaccharides from different ratios of RH were then detected using UPLC-UV method.The SPS model was established,and RH1,RH2,RH3 and RH4(400 mg·kg-1)were administered by intragas-tric gavage for 14 day,followed by behavioral tests to e-valuate the PTSD-like behaviors.The serum CORT,IL-1β and IL-10 were determined by ELISA.The possible targets of action were analyzed using bioinformatics.The expression levels of Calpain-1,PSD95,BDNF and GluN2B in the hippocampus were detected by Western blot.Results The SPS model induced PTSD-like be-haviors in mice.Serum levels of CORT and IL-1β in-creased and level of IL-10 decreased in SPS model.After treatment with different ratios of RHs,RH2 showed the best therapeutic effect,which was manifes-ted in the suppression of PTSD-like behaviors,the re-duction of CORT and IL-1β levels,and the promotion of IL-10 levels;160 overlapping targets might explain the therapeutic effects of RH on PTSD,and these tar-gets were enriched in inhibiting synaptic damage,exer-ting antioxidant properties and suppressing neuroin-flammation,respectively.RH2 prevented the SPS-in-duced decrease in the expression of Calpain-1,PSD95,BDNF and the elevation of GluN2B.Molecular docking showed strong binding of Rg1 and Rb1 to Calpain-1,PSD95,and BDNF,respectively.Conclusions The a-queous extract of RH in a 2∶1 ratio can more effec-tively prevent SPS-induced PTSD-like behaviors,and its effect may be related to targets such as Calpain-1,PSD95,BDNF and GluN2B.

Objective:To investigate the therapeutic effect of combined extracranial-intracranial revascularization on elderly patients with symptomatic chronic internal carotid artery occlusion, and to evaluate its safety and efficacy in the elderly population.Methods:A retrospective analysis was conducted on 35 elderly patients(aged ≥60 years)who underwent combined extracranial-intracranial revascularization for symptomatic chronic internal carotid artery occlusion in the Department of Neurosurgery, Renmin Hospital of Wuhan University from January 2017 to June 2022.The clinical data during hospitalization, as well as the follow-up data within 2 years after operation, were collected and analyzed.Results:A total of 35 cases of combined extracranial-intracranial revascularization were performed on 35 patients.The age at surgery ranged from 60 to 74 years(mean age 65.5 ± 4.2 years). The incidence of reversible neurological deficits within 2 weeks postoperation was 34.3%, and the incidence of focal cerebral infarction within 30 days postoperation was 5.7%.The patency rate of the bridging vessel was 97.1% at 3 months postoperation., and the incidence of focal cerebral infarction during the follow-up period of 30 days to 2 years postoperation was 2.9%.At 3 months after surgery, computed tomography perfusion imaging showed that regional cerebral blood flow(rCBF), regional cerebral blood volume(rCBV), regional mean transit time(rMTT), and regional time to peak(rTTP)were improved compared with those before surgery.The modified Rankin scale score decreased compared to preoperative values, while the Montreal Cognitive Assessment showed improvement in cognitive function compared to preoperative levels(all P<0.05). From 6 months to 1-year postoperation, cerebral angiography showed that 38.7% of the patients had neovascularization of Matsushima grade A or grade B. No cases of cerebral hemorrhage or death was observed during the treatment and follow-up. Conclusions:Combined extracranial-intracranial revascularization is safe and effective for elderly patients with symptomatic chronic internal carotid artery occlusion, which can improve the patient′s hemodynamic disorders, prevent infarction events, and improve the patients′ neurological function and cognitive ability.