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 investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P＜0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P＜0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P＜0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P＜0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12％,AUC0-t decreased by 5.05％,AUC0-∞ decreased by 5.01％,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90％confidence interval were 73.13％-115.10％,83.22％-112.28％and 83.40％-112.13％,respectively.Neither was between 85.00％-125.00％.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.

BACKGROUND:Synovitis is involved in all stages of osteoarthritis and is a key factor contributing to the development of osteoarthritis.Studies have shown that circular RNA(circRNA)plays an important role in the proliferation,apoptosis and extracellular matrix degradation of synovial cells and chondrocytes.OBJECTIVE:To observe the effects of circRNA SEC24A on the interleukin-1β-induced proliferation,apoptosis,and expression of inflammatory factors in human synovial fibroblasts.METHODS:Human synovial fibroblasts were divided into four groups,including control group,interleukin-1β group,empty vector group,and sh-circSEC24A group.Except for the control group,the other three groups were induced with 10 ng/mL interleukin-1β for 24 hours to establish inflammatory cell models;the empty vector group and sh-circSEC24A group were infected with empty vector virus and lentiviral vector knocking down circSEC24A.CCK-8 assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis.ELISA was used to detect the levels of matrix metalloproteinase-9,matrix metalloproteinase-13,interleukin-6,and tumor necrosis factor-α in cell supernatant.Western blot assay was used to detect the relative expression levels of Bax,Bcl-2,matrix metalloproteinase-9,matrix metalloproteinase-13,casepase3,cleaved-casepase3,casepase8,and cleaved-casepase8 proteins in cells.RESULTS AND CONCLUSION:(1)qRT-PCR results showed that compared with the normal group,the expression of circSEC24A in human synovial fibroblasts induced by interleukin 1β was significantly up-regulated.(2)The absorbance value of cells in the sh-circSEC24A group detected by CCK-8 assay was significantly higher than that of interleukin 1β group and empty vector group(P＜0.05).The apoptosis rate of sh-circSEC24A group detected by flow cytometry was significantly lower than that of interleukin 1β group and empty vector group(P＜0.05).(3)The levels of tumor necrosis factor α and interleukin 6 in the supernatant of human synovial fibroblasts in the sh-circSEC24A group detected by ELISA were significantly lower than those in the interleukin 1β group and the empty vector group(P＜0.01,P＜0.001).(4)Western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the expression of the pro-apoptotic factor Bax protein in the sh-circSEC24A group significantly decreased,and the expression of the anti-apoptotic factor Bcl-2 protein increased significantly(P＜0.05);apoptosis and related activating factors cleaved-casepase3 and cleaved-casepase8 protein expressions were both reduced(P＜0.05).(5)ELISA and western blot assay results showed that compared with the interleukin 1β group and the empty vector group,the sh-circSEC24A group had lower levels of matrix metalloproteinase 9 and matrix metalloproteinase 13 protein(P＜0.05).These findings indicated that the expression of circSEC24A was abnormally increased in human synovial fibroblasts induced by interleukin 1β.Knocking down circSEC24A expression could promote the proliferation of human synovial fibroblasts and inhibit apoptosis,inflammatory factor release,and extracellular matrix degradation,suggesting that circSEC24A may be an important intervention target for early osteoarthritis.

Over 40%of critically ill patients will develop coagulopathy.Once critically ill patients are complicated with coagulopathy,the incidence of bleeding and mortality can increase by more than 4 times.Early identification of coagulopathy and accurate evaluation of coagulation function are essential for correcting coagulopathy as soon as possible.Therefore,Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association,together with Chinese People's Liberation Army Professional Committee of Critical Care Medicine updated the"Chinese expert consensus on standardized assessment of severe coagulopathy(2025 Edition)"on the basis of the"Consensus of Chinese experts on standardized evaluation of coagulation dysfunction in severe patients"formulated in 2022.This consensus includes four parts:classification and typing,etiology and mechanism,assessment methods,and diagnostic criteria of severe coagulopathy,with a total of 14 recommendations,aiming to provide corresponding guidance for clinical practice.

Objective To investigate the predictors of chronic pain after inguinal hernia surgery.Methods A total of 400 patients with inguinal hernia surgery in our hospital from August 2018 to May 2023 were selected as the study objects.Visual analog scoring(VSA)was used to evaluate postoperative acute pain within 24 h after surgery.The patients were divided into chronic pain group and non-chronic pain group according to whether chronic pain occurred after surgery.Thirty-seven patients with postoperative pain lasting more than 3 months were in the chronic pain group,and the remaining 363 patients were in the non-chronic pain group.Lasso-Logistic regression was used to analyze the predictors of acute and chronic pain after inguinal hernia surgery.Results Univariate analysis showed that there were significant differences in age,BMI,smoking history,preoperative groin pain,intraoperative nerve tension or injury,wound infection and postoperative acute pain between the chronic pain group and the non-chronic pain group(P＜0.05).The data were regularized by Lasso regression,and three representative risk factors of chronic postoperative pain,namely preoperative groin pain,intraoperative nerve pulling or injury,and postoperative acute pain,were selected.Multivariate Logistic regression analysis showed that:Preoperative groin pain(OR=2.548,95％CI1.150-5.647),intraoperative nerve tension OR injury(OR=4.435,95％CI2.084-9.436)and postoperative acute pain(OR=2.242,95％CI1.041-4.829)was the factor of chronic pain after operation(P＜0.05).Conclusion Preoperative groin pain,intraoperative nerve pulling or injury,and postoperative acute pain are the factors affecting chronic pain after inguinal hernia.Identifying high-risk groups and taking targeted measures are helpful to prevent and treat chronic pain after inguinal hernia.

Objective:To evaluate the effect of acupuncture on postoperative delirium (POD) in diabetic patients undergoing surgery under general anesthesia.Methods:In this randomized controlled trial, 92 diabetic patients of either sex, aged 30-80 yr, with a body mass index of 18-28 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective surgery under general anesthesia, were divided into 2 groups ( n=46 each) using a table of random numbers: control group (group C) and acupuncture group (group A). Group A received acupuncture at the Baihui (GV20), Shenting (GV24) and Sishencong (EX-HN1) acupoints before anesthesia. The needles were retained for 30 min, with manual stimulation applied every 10 min for 10 s each time. After 4 stimulations, routine anesthesia was carried out. Group C received routine anesthesia only. Regional cerebral oxygen saturation was recorded on admission to the operating room (T 0), after anesthesia induction (T 1), at the start of surgery (T 2), at the end of surgery (T 3), and immediately after tracheal extubation (T 4). The POD developed within 3 days after surgery was assessed. The occurrence of needle-related adverse effects such as fainting, subcutaneous bleeding, and local paresthesia was recorded. Results:Compared with group C, the incidence of POD was significantly reduced, and the regional cerebral oxygen saturation was increased at T 1, 4 in group A ( P<0.05). Conclusions:Acupuncture can decrease the development of POD in diabetic patients undergoing surgery under general anesthesia, which is related to an increase in regional cerebral oxygen saturation.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.