ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

Objective To investigate the influence of plasma infusion during orthotopic liver transplantation on the incidence of acute kidney injury (AKI) in recipients. Methods Cinical data of 473 liver transplant recipients who underwent orthotopic liver transplantation at Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2016 to December 2020 were retrospectively collected. The study included 354 recipients who received plasma infusion during the operation (plasma group) and 119 recipients who did not receive plasma infusion during the operation (control group). Preoperative conditions, donor conditions, intraoperative conditions, main outcome indicators and secondary outcome indicators of the two groups were analyzed and compared. Receiver operating characteristic curve was drawn to calculate the maximum cut-off value of intraoperative plasma infusion volume that affected the occurrence of AKI within 7 days after surgery. Logistic regression analysis was performed to analyze the correlation between intraoperative plasma infusion volume and the incidence of AKI within 7 days after surgery. Results Before propensity score matching, the incidence of AKI within 7 days after surgery and the incidence of grade Ⅲ AKI in the plasma group were higher than those in the control group (both P<0.05). After propensity score matching, 62 recipients were included in each group. There was no statistically significant difference in the incidence of AKI within 7 days after surgery between the plasma group and the control group, but the incidence of grade Ⅲ AKI within 7 days after surgery in the plasma group was higher than that in the control group (P=0.041). Logistic regression analysis showed that intraoperative plasma infusion volume >900 mL was a potential risk factor for AKI within 7 days after surgery (odds ratio=1.936, 95% confidence interval 1.193-3.142, P=0.007). There were no statistically significant differences in the incidence of 365-day postoperative fatality, reperfusion syndrome, and postoperative 30-day complications between the two groups before and after propensity score matching. In addition, the postoperative albumin, fibrinogen levels, and international normalized ratio in the plasma group were better than those in the control group before and after matching (all P<0.05). Conclusions Large amount of intraoperative plasma infusion is associated with an increased risk of grade Ⅲ AKI after orthotopic liver transplantation. Intraoperative plasma infusion volume >900 mL may increase the risk of AKI within 7 days after surgery.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveThis paper aims to explore the risk factors for chronic atrophic gastritis （CAG） with turbidity toxin accumulation syndrome and establish a prediction model. MethodsClinical data of 180 patients with CAG who participated in the "clinical study of Xianglian Huazhuo Particles blocking CAG cancer transformation" of Hebei Sheng Zhong Yi Yuan from July 2021 to March 2022 were collected. After confounding factors were controlled by propensity score matching， patients were divided into a training set （namely dev） and a validation set （namely vad） in a seven to three ratio. The risk factors for CAG with turbidity toxin accumulation syndrome in the training set were investigated by using univariate Logistic regression analysis and least absolute shrinkage and selection operator （namely Lasso） regression algorithms. Subsequently， a model， named model 1se， was developed by using the training set data to predict the risk factors for CAG with turbidity toxin accumulation syndrome. The accuracy of the prediction model was assessed by using various methods， including the receiver operating characteristic （ROC） curve， Hosmer-Lemeshow test （H-L）， calibration plot， and decision curve analysis （DCA）. ResultsAge， body mass index （BMI）， family history of cancer， job and life satisfaction， yellow and greasy fur with slippery pulse， and heavy body sensation were independent risk factors of the model. The prediction model showed excellent predictive value for both the training and validation sets. ConclusionThe established prediction model for CAG with turbidity toxin accumulation syndrome has high discrimination and excellent calibration， which could provide an excellent clinical basis for disease diagnosis and individualized treatment of patients.

ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis （UC） by bioinformatics and animal experiments. MethodsThe differentially expressed genes （DEGs） in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus （GEO）， and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes （DEARGs）. DEARGs were imported into Metascape and STRING， respectively， for gene ontology/Kyoto Encyclopedia of Genes and Genomics （GO/KEGG） enrichment analysis and protein-protein interaction （PPI） analysis. Finally， 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator （LASSO） regression and receiver operating characteristic curve （ROC） analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-， medium-， and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 （Caspase-1）， cathepsin B （CTSB）， C-C motif chemokine-2 （CCL2）， CXC motif receptor 4 （CXCR4）， and hypoxia-inducing factor-1α （HIF-1α） in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction， respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis， LASSO regression， and ROC analysis， the core DEARGs （Caspase-1， CCL2， CTSB， and CXCR4） were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells， M0 macrophages， M1 macrophages， and dendritic cells in the colonic mucosal tissue of UC patients had significant differences， and core DEARGs had significant correlations with these immune cells. This result， combined with the prediction results of network pharmacology， suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group， the model group showed up-regulated protein and mRNA levels of caspase-1， CCL2， CTSB， CXCR4， and HIF-1α， which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1， CCL2， CTSB， and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.

Extramedullary plasmacytoma(EMP)is a malignant neoplasm characterized by monoclonal plasma cell proliferation originating outside the bone marrow and hematopoietic tissues.The co-occurrence of multiple myeloma(MM)with mammary EMP is clinically rare.This case report describes the diagnostic and therapeutic management of a middle-aged female patient with MM and mammary EMP,accompanied by a litera-ture review.The patient presented with persistent fever and was found to have a right breast mass via PET/CT during routine follow-up for MM.The lesion was biopsy-confirmed as mammary EMP,and the patient subse-quently underwent chemotherapy.This case highlights the critical importance of differential diagnosis between breast cancer and rare hematologic metastatic tumors in early prevention of disease progression.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

Background and Aims:Infected necrotizing pancreatitis(INP),particularly with diffuse distribution,is a life-threatening condition.The optimal initial intervention-minimally invasive step-up therapy vs.direct open necrosectomy-remains controversial.Moreover,the impact of necrosis morphology("wet"or"dry")and the presence of severe acute pancreatitis(SAP)on treatment selection has not been fully clarified.This study aimed to compare the efficacy and safety of these two approaches in diffuse INP and to evaluate the guiding value of CT-based necrosis type and SAP status in clinical decision-making.Methods:A retrospective analysis was conducted on 458 patients with diffuse INP admitted to the Third Xiangya Hospital of Central South University from January 2012 to March 2023.Patients were divided into a minimally invasive step-up group(n=256)and a direct open surgery group(n=202).SAP was defined according to the determinant-based classification,and necrosis was categorized as"wet"or"dry"based on CT features.The primary endpoint was a composite of death or major complications,while secondary endpoints included mortality,length of hospital stay,and incision-related complications,were compared between the two groups,with subgroup analyses performed accordingly.Results:Overall,the open surgery group had higher rates of the primary endpoint(62.4%vs.48.1%,P=0.003)and mortality(27.2%vs.16.8%,P=0.008)compared with the step-up group.Among SAP patients,the step-up approach resulted in a significantly lower primary endpoint rate(66.7%vs.97.7%,P=0.003).In non-SAP patients,the primary endpoint rates were similar,but open surgery was associated with a shorter hospital stay[(36.5±10.4)d vs.(45.6±18.6)d,P<0.001]and higher incidences of wound infection and incisional hernia(both P<0.001).Multivariate analysis identified infection onset time,effusion characteristics,gas bubbles,and necrosis location as independent predictors of prolonged hospitalization in the step-up group(all P<0.05).Patients with"wet"necrosis benefited more from the step-up approach,whereas those with"dry"necrosis experienced shorter hospitalization following open surgery.Conclusion:For diffusely distributed INP,treatment strategies should be individualized based on SAP status and necrosis liquefaction/imaging characteristics.The step-up minimally invasive approach is preferred for SAP patients and those with"wet"necrosis on CT,while direct open necrosectomy may be advantageous for"dry"necrosis(particularly with limited liquefaction)by shortening hospital stay and reducing certain major outcomes,though at the cost of increased incision infection and incision herina.CT imaging features and SAP classification can serve as valuable tools for risk stratification and guiding individualized timing and modality of intervention.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

Objective To explore the mechanism of electroacupuncture in alleviating hyperlipidemia in a rat model by modulating mammalian target of rapamycin complex 1(mTORC1)-mediated lipophagy in hepatocytes.Methods A total of 30 SD rats were randomly divided into blank(n=6)and modeling groups(n=24)using the random number table method.A hyperlipidemic rat model was established by feeding rats a high-fat diet(feeding for 8 weeks).After successful modeling,the modeling group was randomly divided into the model,electroacupuncture,mTORC1 inhibitor,and electroacupuncture+mTORC1 agonist groups,with six rats in each group.Except for the blank group,all other rats were fed with high fat diet.Rats in the electroacupuncture and electroacupuncture+mTORC1 agonist groups received electroacupuncture intervention at bilateral"Fenglong"(ST40)acupoints(dilatational wave 2 Hz/100 Hz,current intensity 1 mA)for 30 min once daily.Rats in the mTORC1 inhibitor group received intraperitoneal injections of the mTORC1 inhibitor,rapamycin(2 mg/kg),once daily.Rats in the electroacupuncture+mTORC1 agonist group received intraperitoneal injections of the mTORC1 agonist MHY1485(10 mg/kg)once daily.The interventions were administered for five consecutive days per week for 4 weeks.Upon completion of the intervention,the following analyses were performed:serum contents of total cholesterol(TC),triglycerides(TAG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),free fatty acids(FFA),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)were measured using a fully automated biochemical analyzer.Hepatic histopathological changes and lipid deposition were observed using hematoxylin-eosin and oil red O staining.The liver condition was observed and the liver index was calculated.Hepatic TC and TAG levels were measured using an enzyme-linked immunosorbent assay.The ultrastructure of the liver tissue was observed using transmission electron microscopy,and the mean fluorescence intensity of perilipin 2(PLIN2)and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ in the liver tissue was detected using immunofluorescence.Protein expression of LC3-Ⅱ/LC3-Ⅰ,phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR,and mTORC1 in liver tissue was detected using Western blotting.Results Compared to the blank group,the model group rats showed increased serum TC,TAG,LDL-C,ALT,AST,and FFA levels,along with decreased HDL-C levels(P<0.05).The liver index and hepatic TC and TAG levels were also elevated(P<0.05).Histological examination of liver tissue revealed substantial lipid accumulation,numerous lipid droplets within hepatocytes,abnormal mitochondrial morphology,and scarce autophagic vacuole.The mean fluorescence intensity of PLIN2 increased,whereas that of LC3-Ⅱ decreased(P<0.05).Additionally,the LC3-Ⅱ/LC3-Ⅰ ratio was reduced,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression were increased(P<0.05).Compared to the model group,rats in the mTORC1 inhibitor and electroacupuncture groups exhibited decreased serum TC,TAG,LDL-C,ALT,AST,and FFA levels(P<0.05),along with a reduced liver index and hepatic TC and TAG levels(P<0.05).Histological examination showed markedly attenuated lipid accumulation and visible autophagic vacuole in the hepatocytes.The mean fluorescence intensity of PLIN2 decreased,whereas that of LC3-Ⅱ increased(P<0.05).Moreover,the LC3-Ⅱ/LC3-Ⅰ ratio increased,whereas the p-mTOR/mTOR ratio and mTORC1 protein expression decreased(P<0.05).In comparison with both the electroacupuncture and mTORC1 inhibitor groups,the electroacupuncture+mTORC1 agonist group demonstrated increased serum TAG,TC,LDL-C,ALT,AST,and FFA levels(P<0.05)as well as elevated liver index and hepatic TC and TAG levels(P<0.05).Liver tissues exhibited aggravated lipid deposition and absence of autophagic vacuole in liver cells.The mean fluorescence intensity of PLIN2 was enhanced,whereas that of LC3-Ⅱ was reduced(P<0.05).Furthermore,the LC3-Ⅱ/LC3-Ⅰ ratio decreased,and the p-mTOR/mTOR ratio and mTORC1 protein expression increased(P<0.05).Conclusion Electroacupuncture at"Fenglong"(ST40)may improve blood lipid levels in hyperlipidemic rats by inhibiting mTORC1 and promoting hepatocyte lipophagy.