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.

Cholangiocarcinoma(CCA)is a highly malignant digestive system tumor with strong invasiveness and difficulty in treatment.Its high drug resistance,difficulty in early diagnosis,and rapid progression of invasion and metastasis pose signifi-cant challenges to clinical treatment.Research has shown that the development of resistance in CCA is one of the key factors in-fluencing treatment outcomes,with non-genetic factors playing a crucial role in the resistance process.This article summarizes the non-genetic factors contributing to resistance in CCA,and discusses the roles of epigenetic heterogeneity,epigenetic plastici-ty,and the tumor microenvironment in mediating resistance in CCA.The goal is to provide new theoretical insights for overco-ming treatment resistance in CCA.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective:To construct a predictive model for postoperative delirium (POD) in patients undergoing gastrointestinal surgery using machine learning.Methods:This retrospective study used clinical data from patients who underwent gastrointestinal surgery at Subei People′s Hospital between September 2022 and April 2024. The entire dataset was randomly divided into the training and validation sets in an 8∶2 ratio. Multivariate logistic regression analysis was conducted to identify the factors influencing POD. Eleven machine learning models were established and compared. The performance of the models was validated using metrics, including accuracy, precision, recall, Youden′s index, F1 score, Matthews′ correlation coefficient, Kappa coefficient, log loss, and Brier score. Receiver operating characteristic and calibration curves were plotted to assess the discrimination and consistency of the model. Shapley additive explanations were used in Python for interpretative analysis of the model with the best predictive performance, and the importance of the feature parameters was ranked.Results:A total of 1, 785 patients were ultimately included, of which 833 (46.67%) experienced POD. The results of multivariate logistic regression analysis revealed that advanced age, lower preoperative serum calcium ion concentration, postoperative pulmonary infection, and higher preoperative systolic blood pressure were independent risk factors for POD in patients undergoing gastrointestinal surgery, while laparoscopic surgery was a protective factor ( P<0.05). Among the 11 machine learning models, the categorical feature gradient boosting model exhibited the best performance, with an area under the receiver operating characteristic curve of 0.82 (95% confidence interval 0.77-0.87). The ranking of feature importance indicated that age had the greatest contribution in predicting POD. Conclusions:The predictive model for POD established based on the categorical boosting algorithm has higher predictive efficacy and clinical application value in patients undergoing gastrointestinal surgery.

Cholangiocarcinoma(CCA)is a highly malignant digestive system tumor with strong invasiveness and difficulty in treatment.Its high drug resistance,difficulty in early diagnosis,and rapid progression of invasion and metastasis pose signifi-cant challenges to clinical treatment.Research has shown that the development of resistance in CCA is one of the key factors in-fluencing treatment outcomes,with non-genetic factors playing a crucial role in the resistance process.This article summarizes the non-genetic factors contributing to resistance in CCA,and discusses the roles of epigenetic heterogeneity,epigenetic plastici-ty,and the tumor microenvironment in mediating resistance in CCA.The goal is to provide new theoretical insights for overco-ming treatment resistance in CCA.

Dendrobium is the largest genus of the Orchidaceae family.The fresh and dried stems of many species of this genus have been used as Shihu(Dendrobii Caulis)in traditional Chinese medicine,it is known as the foremost of the"Nine Great Herbs of China".Ancient texts highlight its uses for"strengthening yin,enhancing essence,nourishing the five viscera,alleviating fatigue,and dispelling skin heat and prickly heat".Modern research confirms that the polysaccharides and alkaloids it contains have antiviral ef-fects,it can apply in treating immunodeficiency caused by viral infections clinically.While studies are gradually uncovering the antivi-ral mechanisms and material basis of Dendrobium,the lack of systematic analysis and organization has hindered its resource develop-ment.The paper employed CiteSpace software for bibliometric analysis of Chinese and English literature on Dendrobium.It reviewed the herbalism,material basis,and mechanisms of its antiviral properties building upon the systematic review of ancient materia medica and modern literature.Results indicate that Dendrobium can boost vital energy and resist pathogens,showing great potential in antiviral drug development.

Objective:To explore the safety and effectiveness of ileal bypass with stent to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.Methods:From Dec 2021 to Sep 2024, the clinical data of 55 patients undergoing robot anus-preserving surgery and stent ileal bypass for low rectal cancer in the First Affiliated Hospital of Ningbo University was analyzed retrospectively.Results:All the 55 patients successfully completed the operation. Among them, 47 patients underwent low anterior resection and 8 patients did sphincter resection. The total operation time was (207±37)min, the operation time of ileal bypass was (24±3)min, and the intraoperative blood loss was (32±18)ml. After operation, the time of stent disintegration was (23.93± 2.87) days, and the time of catheter removal was (29.55 ± 3.21) days. By postoperative TNM staging, there were 12 cases in T1 stage, 26 cases in T2 and 17 cases in T3. The number of lymph node dissection was (16.84±4.50), 15 cases being positive for lymph node metastasis, 40 cases being negtive for lymph node metastasis, 36 cases were stage Ⅰ, 4 cases were stage Ⅱ and 15 cases were stage Ⅲ. The median follow-up time was 20 (2-35) months. Delayed anastomotic leakage occurred in 1 patient and anastomotic stenosis occurred in 2 patients.Conclusion:Stent ileal bypass is safe and effective to prevent anastomotic leakage in Da Vinci robot anus-preserving surgery for low rectal cancer.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*