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 the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application.Methods and Results Recommendations were formulated based on literature review and expert group discussion,and consensus was reached following expert consultation.The consensus recommendations are comprehensive,covering the entire treatment procedures from preoperative assessment and preparation,surgical operation process,postoperative management and traditional Chinese medicine treatment to individualized treatment planning.The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain,reduced the use of opioid drugs,and significantly improved the quality of life and enhanced immune function of the patients.Postoperative follow-up suggested good treatment tolerance among the patients without serious complications.Conclusion The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy.The combined treatment has a high clinical value with a good safety profile for management of cancer pain.

Objective:This study aimed to investigate the association between genetic factors and the risk of developing treatment-resistant depression (TRD), as well as the efficacy of modified electroconvulsive therapy (MECT), with a specific focus on identifying gene polymorphisms that can differentiate TRD from non-TRD.Methods:This case-control study included inpatients with depression in Adult Psychiatry Department, Affective Disorders Department and Geriatrics Department of Guangzhou Medical University Affiliated Brain Hospital from January 2023 to June 2024, as well as healthy individuals undergoing physical examinations in the outpatient department. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was utilized to genotype 16 loci across 10 candidate genes in 107 non-TRD patients, 101 TRD patients and 281 healthy controls. Hardy-Weinberg equilibrium testing, genotype frequency distribution analysis, and genetic association studies were conducted using PLINK software. Univariate binary logistic regression under a dominant model was performed using R software to analyze gene loci associated with non-TRD and TRD.Results:All 16 gene loci in the control group, the TRD group, and the non-TRD group were found to be in Hardy-Weinberg equilibrium ( P>0.05). No significant differences were observed in the genotype distribution of these gene loci across the groups ( P>0.05). Univariate binary logistic regression analysis revealed that individuals with depression carrying the HTR2A-rs7997012 G allele had a significantly lower risk of developing TRD ( OR=0.26, P=0.047). Among the patients receiving MECT, the proportion of G allele carriers who showed improvement at 2, 4, and 6 weeks of treatment was significantly higher compared to those who did not show improvement (96.61% vs. 80.95%, 96.55% vs. 50.00%, 96.59% vs. 46.15%, respectively), with χ2 values of 6.743, 29.295, and 32.300, respectively, and all P values <0.05. Conclusion:The HTR2A-rs7997012 polymorphism may represent a genetic distinction between TRD and non-TRD. Depressed patients with the rs7997012 G allele have a reduced likelihood of developing TRD, moreover, MECT demonstrates superior efficacy in this patient population.

Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.

OBJECTIVE To construct a predictive tool for surgical site infections(SSIs)in spinal surgery for Chi-nese population to provide evidence support for reducing SSIs.METHODS A systematic review of Chinese and English database literature was conducted for Meta-analysis to obtain pooled risk values for influencing factors,and a risk prediction scoring tool was constructed based on the logistic regression model.Patients who underwent spinal surgery and completed postoperative follow-up in a tertiary hospital in Beijing from Jan.to Dec.2021 were selected to validate the predictive effect of the tool.RESULTS The predictive model for SSIs in Chinese spinal sur-gery patients was Logit(P)=—3.47+0.63(age 60 years)+0.31 ×(patient with cardiovascular disease)+0.69 ×(rheumatoid arthritis)+1.07 ×(diabetes)+1.06 ×(operation duration＞3 h)+1.17 ×(preopera-tive albumin＜35 g/L)+0.71 ×(history of spinal surgery)+0.67 ×(carrying internal implants)+0.73 ×(blood transfusion).The total score of the predictive tool was 92,with a cutoff score of≥24.50 indicating high-risk individuals.The area under the curve was 0.733,with the sensitivity 58.30％and the specificity 79.60％.CONCLUSION The established predictive model for SSIs in Chinese spine surgery demonstrates good predictive performance and can be used as a reference assessment tool in clinical practice.

Depression is primarily characterized by persistent low mood,emotional disorders,and loss of interest.Somatization disorder is a type of neurotic disorder,primarily featuring recurrent,varied,and non-organic physical discomfort symptoms.In traditional Chinese medicine,depression with somatization disorder can be classified under the category of"depression"and"hysteria"according to its clinical symptoms.This article focuses on the dynamic evolution of the functions of the kidney,spleen,and liver,and explains the core pathogenesis of depression with somatization disorder based on the theory of"cold water,damp earth,and stagnant wood"proposed by HUANG Yuanyu.It explores the causes and related manifestations.Symptoms mainly characterized by cramps and convulsions can be attributed to the liver;symptoms primarily characterized by heaviness,distension,and dull pain accompanied by weakness can be attributed to the spleen;symptoms primarily characterized by stiffness,reluctance to move or inability to move,and reluctance to extend outward can be attributed to the kidney.Liver depression and spleen dampness,as well as wood depression and earth congestion,are treated by strengthening the spleen and soothing the liver,drying dampness and calming wind,and the modified Xiaoyao Powder combined with Yueju Pill is recommended.Spleen dampness and kidney coldness,earth failure and water overflow,are treated by tonifying the spleen and kidney,warming water and transforming dampness,and the modified Jingui Shenqi Pill combined with Linggui Zhugan Decoction is recommended.Kidney coldness and liver hyperactivity,water not nourishing wood,are treated by warming the kidney and enriching essence,replenishing water and nourishing wood,and the modified Dihuang Yinzi is recommended.This article explores the corresponding etiology,pathogenesis,treatment methods,and prescriptions for depression with somatization disorder,with the aim of providing new insights for clinical diagnosis and treatment.

OBJECTIVE To explore the possible mechanism of Qingchang Huashi Formula in the treatment of ulcerative colitis(UC).METHODS Fifty C57BL/6 male mice were randomly divided into a control(Ctrl)group,a model group,a low-dose Qingchang Huashi Formula group,a high-dose Qingchang Huashi Formula group,and a 5-aminosalicylic acid(5-ASA)group based on body weight.The UC model was established in mice by drinking 3%dextran sulfate sodium(DSS)for 6 d.On d7 and d8,DSS was withdrawn and ultrapure water was given daily.Ultrapure water or different drugs were administered orally throughout the experiment:Ctrl and model groups received 0.2 mL of ultrapure water,while the low-dose and high-dose Qingchang Huashi Formula groups re-ceived 6 and 12 g·kg-1,respectively,and the concentration of 5-ASA was 100 mg·kg-1.Body weight and fecal characteristics of the mice were recorded daily,and the experiment ended on d9.Serum was collected from mice for serum metabolomics and inflam-matory factor expression analysis.The colons of the mice were isolated and their lengths were measured,and the distal colon was ob-tained for pathological analysis.The livers and colons of the mice were isolated for subsequent total bile acid analysis.RESULTS Compared with the Ctrl group,the model group mice showed a significant decrease in body weight and colon length(P<0.000 1),a remarkable increase in disease activity index(P<0.000 1).The concentration of inflammatory factors IL-1β and TNF-α was signifi-cantly increased(P<0.000 1).High-dose and low-dose Qingchang Huashi Formula,as well as 5-ASA could significantly alleviate the loss of body weight,increased DAI,colon shortening,and disappearance of colon tissue morphology in mice.Through ELISA tes-ting,it was found the concentration of IL-1β and TNF-α was remarkably decreased after Qingchang Huashi Formula and 5-ASA treat-ment(P<0.01,P<0.000 1).Through LC-MS analysis of serum metabolites and KEGG enrichment analysis,we found that interven-tion with Qingchang Huashi Formula could significantly affect the primary bile acid synthesis,secondary bile acid synthesis and bile se-cretion.Using total bile acid reagent kit,we found that the total bile acid in the liver of colitis mice did not show significant changes when compared with the Ctrl group of mice,and the concentration of total bile acid in the serum was significantly reduced,the concen-tration of TBA in the colon was significantly increased(P<0.05).After intervention with the Qingchang Huashi Formula,the concen-tration of total bile acid in the serum of mice was significantly increased,while the concentration of total bile acid in the colon was re-duced(P<0.05).Compared with mice in Ctrl group,the levels of deoxycholic acid(DCA)and taurine deoxycholic acid(TDCA)in serum of colitis mice were significantly reduced(P<0.05).After intervention with Qingchang Huashi Formula,the levels of DCA,TD-CA and Ursodeoxycholic acid(UDCA)in serum of mice were restored(P<0.01).CONCLUSION Qingchang Huashi Formula can effectively relieve DSS-induced colitis in mice,reducing immune inflammatory response,reregulating the disorder of serum metabolism and enterohepatic circulation.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

Objective To investigate the protective effect and mechanism of astragaloside Ⅳ(AS-Ⅳ)on the pulmonary arterial hypertension(PAH)model induced by monocrotaline(MCT)/monocrotaline pyrrole(MCTP)in SD rats/human pulmonary artery endothelial cell(HPAEC).Methods In vivo experiment,60 male SD rats were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(20 mg/kg)group,AS-Ⅳ medium-dose(40 mg/kg)group,AS-Ⅳ high-dose(80 mg/kg)group,or sildenafil(Sil,100 mg/kg)group,with 10 rats in each group;except for the control group,PAH rat models were established by single intraperitoneal injection of MCT(60 mg/kg)in other groups.In vitro experiment,HPAECs were randomly assigned to control group,PAH model group,AS-Ⅳ low-dose(10 μmol/L)group,AS-Ⅳ medium-dose(20 μmol/L)group,MCTP+AS-Ⅳ high-dose(40 μmnol/L)group,or p38 mitogen-activated protein kinase(MAPK)signaling pathway inhibitor(SB203580,5 μmol/L)group;except for the control group,in vitro PAH cell models were established by MCTP(60 μg/mL)induction for 24 h in other groups.In vivo experiments,after 4 weeks of drug intervention,the right ventricular systolic pressure(RVSP)and mean pulmonary artery pressure(mPAP)of rats were measured by hemodynamic methods,the right ventricle hypertrophy index was measured by weighing methods,the percentage of pulmonary arteriole wall thickness to outer diameter(WT％)and percentage of the wall area to total vascular area(WA％)were observed by hematoxylin-eosin staining,the expression of cysteine aspartic acid specific protease 3(caspase 3)protein in lung tissue was observed by immunohistochemistry(IHC),and the apoptosis of lung tissue cells was detected by TUNEL assay.In vitro experiments,JC-1 staining was used to detect the mitochondrial membrane potential in cells,and immunofluorescence was used to detect caspase 3 protein expression.In vitro and in vivo experiments,Western blotting was used to detect the expression of caspase 3,B-cell lymphoma gene 2(Bcl-2),Bcl-2 associated X protein(Bax),p38 MAPK,and phosphorylated p38 MAPK proteins in lung tissue and HPAECs.Results In vivo experiments,the RVSP,mPAP,and right ventricle hypertrophy index were decreased in the Sil group and each dose group of AS-Ⅳ(all P＜0.01);the WA％and WT％of each dose group of AS-Ⅳ were decreased(all P＜0.01),the expression of caspase 3 protein in lung tissue was decreased(all P＜0.01),and the apoptosis of lung tissue cells was decreased(all P＜0.01).In vitro experiments showed that after intervention with each dose of AS-Ⅳ and SB203580,the mitochondrial membrane potential of HPAEC was increased(all P＜0.01)and the expression of caspase 3 was decreased(all P＜0.01).In vivo and in vitro experiments,each dose of AS-Ⅳand SB203580 reduced the expression of Bax and phosphorylated p38 MAPK proteins,and increased the expression of Bcl-2 protein(all P＜0.01).Conclusion AS-Ⅳ reduces apoptosis by inhibiting p38 MAPK signaling pathway,improving PAH in SD rats.

Objective The effects of carrimycin(CAM)on the biological functions of intrahepatic cholan-giocarcinoma HuCCT1 cells were examined through in vitro experiments,and a preliminary investigation was conducted into its mechanism of action.Methods The intrahepatic cholangiocarcinoma cell line HuCCT1 was selected for the study.The effect of CAM on cell viability was assessed using the CCK-8 assay,and the IC50 concen-tration was determined accordingly.The impact of CAM on cell migration was evaluated through a scratch wound healing assay.In addition,the effect of CAM on clonogenic ability was examined using a colony formation assay.Cell invasion capacity was assessed using a Transwell invasion assay.Flow cytometry was employed to analyze the effect of CAM on cell cycle progression.Furthermore,Western blotting was conducted to evaluate the expression levels of key proteins associated with epithelial-mesenchymal transition and the cell cycle.Finally,the influence of CAM on the AXL/c-Myc/c-Met signaling axis was also investigated.Results Compared with the control group,CAM significantly inhibited the proliferation of HuCCT1 cells in a concentration-dependent manner(P<0.05).Plate cloning assays demonstrated that CAM markedly suppressed the colony-forming ability of HuCCT1 cells(P<0.05).Scratch wound healing assays confirmed that CAM treatment significantly reduced the migration speed and narrowed the migration area of HuCCT1 cells(P<0.05).Flow cytometry analysis revealed that CAM treatment led to a significant increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase(P<0.05).Western blot analysis further confirmed that the expression levels of key regulatory proteins CCND1 and CDK4,which are involved in the G1/S phase transition,were down-regulated,while the expression of p21 was up-regulated(P<0.05).Transwell invasion assays indicated that CAM inhibited the invasive capacity of HuCCT1 cells.Consis-tently,Western blot results showed that E-Cadherin expression was increased(P<0.05),whereas the expression levels of N-Cadherin and Vimentin were decreased(P<0.05).Moreover,Western blot analysis verified that the expression of AXL,c-Met,and c-Myc was up-regulated in HuCCT1 cells treated with AXL recombinant protein(P<0.05).However,co-treatment with CAM and AXL recombinant protein significantly attenuated the expression of these proteins(P<0.05).Conclusions CAM inhibits the proliferation,migration,and invasion of intrahe-patic cholangiocarcinoma HuCCT1 cells,thereby demonstrating antitumor effects,which may be associated with the AXL/c-Met/c-Myc signaling pathway.