ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Gastric cancer is one of the most common malignant tumors in the digestive system, characterized by high incidence and mortality rates. In recent years, with the rapid develop-ment of molecular immunology, the application of immune checkpoint inhibitors (ICIs) in neoadju-vant therapy has significantly improved pathological response rates and survival outcomes for patients with resectable locally advanced gastric cancer. The authors systematically review current research progress on combination strategies involving immune checkpoint inhibitors in neoadjuvant therapy for locally advanced gastric cancer, aiming to provide an evidence for optimizing individua-lized therapeutic regimens.

Metabolomics covers a wide range of applications in life sciences,biomedicine,and phytology.Data acquisition(to achieve high coverage and efficiency)and analysis(to pursue good classification)are two key segments involved in metabolomics workflows.Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups.However,insufficient feature extraction,inappropriate feature selection,overfitting,or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused.Using two ginseng varieties,namely Panax japonicus(PJ)and Panax japonicus var.major(PJvm),containing the similar ginsenosides,we integrated pseudo-targeted metabolomics and deep neural network(DNN)modeling to achieve accurate species differentiation.A pseudo-targeted metabolomics approach was optimized through data acquisition mode,ion pairs generation,comparison between multiple reaction monitoring(MRM)and scheduled MRM(sMRM),and chromatographic elution gradient.In total,1980 ion pairs were monitored within 23 min,allowing for the most comprehensive ginseng metabolome analysis.The established DNN model demonstrated excellent classification performance(in terms of accuracy,precision,recall,F1 score,area under the curve,and receiver operating characteristic(ROC))using the entire metabolome data and feature-selection dataset,exhibiting superior advantages over random forest(RF),support vector ma-chine(SVM),extreme gradient boosting(XGBoost),and multilayer perceptron(MLP).Moreover,DNNs were advantageous for automated feature learning,nonlinear modeling,adaptability,and generalization.This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples.This established approach holds promise for plant metabolomics and is not limited to ginseng.

Medical linear accelerator is precisely large-scale medical equipment with high integration and complex construction.In use,it is easy to occur fault,and the maintenance process is tedious,and the cost of maintenance is higher.The servicers with medical engineering technique should proficiently know and grasp the structure and principle of this kind of equipment,and respond routine fault,and ensure the quality of accelerator in clinical application.This article analyzed a case of interlocking fault of stand power supply(STPS)of 23EX medical linear accelerator in the department of medical engineering of the Affiliated People's Hospital of Ningbo University.According to the performance of accelerator's fault,and combining the work principle of occurring STPS interlocking fault,the pulse width modulation(PWM)board in auxiliary electronic cabinet of accelerator was located.Its schematic diagram was analyzed and checked.Finally,it was determined that the reason was the field effect tube of PWM board was broken down.The fault was eliminated after the components of occurring fault was replaced.We can increase maintenance efficiency and technical level,and reduce the cost of maintenance for hospital,and ensure its quality in clinical application through quickly locate and resolve faults.

Objective:To investigate the application and safety of cardiopulmonary bypass precharge with 4% succinylated gelatin during surgery for children with cyanotic congenital heart disease (CCHD).Methods:A prospective case-control study was conducted. One hundred and thirty children with CCHD undergoing cardiac surgery admitted to Shaanxi Provincial People's Hospital in 2021-2024 were selected as study participants. Participants were divided into control group ( n=65) and gelatin group ( n=65) by random number table method based on the principle of matching baseline characteristics between groups. Children in the control group were pre-filled with 10-20 ml/kg of fresh frozen plasma, while the gelatin group was pre-filled with 10-20 ml/kg of 4% succinyl gelatin. Thrombelastogram parameters [fibrin formation time, blood clot strength, fibrinogen maximum amplitude, fibrinogen content], hematological parameters [platelet count, prothrombin time (PT), prothrombin activity (PTA), hemoglobin], myocardial function [troponin, creatine kinase, creatine kinase isoenzyme (CK-MB)] and liver-kidney function were compared before and after treatment.Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:Comparison between groups showed that before treatment, the difference of various thromboelastography parameters, haematological parameters, myocardial function indexes, liver and kidney function indexes were not statistically significant ( P>0.05). Compared to before treatment, R, PTA, troponin and creatine kinase increased in both groups after treatment [control group:(51±4) s vs. (43±3) s, (98±15)% vs. (95±12)%, (0.624±0.085) μg/L vs. (0.040±0.005) μg/L, (711±50) U/L vs. (96±11) U/L, (60±7) U/L vs. (22±4) U/L, t values were -17.92、-2.13、-104.63、-165.15、-57.43, respectively, all P<0.001; gelatin group: (51±4) s vs. (42±3) s, (100±16)% vs. (94±13)%, (0.631±0.113) μg/L vs. (0.041±0.004) μg/L, (717±52) U/L vs.(97±11) U/L, (62±7) U/L vs.(24±4) U/L, t values were -19.79、-3.09、-81.31、-157.70、-54.67, respectively, all P<0.001], while MA, MAf, FLEV, platelet count, PT and hemoglobin decreased [control group: (50±4) mmHg vs. (57±5) mmHg、(5.5±0.9) mmHg vs. (13.8±1.3) mmHg、(1.58±0.22) g/L vs.(2.64±0.31) g/L、(217±21)×10 9/L vs. (275±25)×10 9/L、(13.3±0.5) s vs.(14.7±0.8) s、(116±12) g/L vs.(127±17) g/L, t values were 14.79、61.26、32.25、20.58、17.21、6.09,respectively, all P<0.001; gelato group: (49±3) mmHg vs. (57±5) mmHg、(5.7±0.8) mmHg vs. (14.0±1.4) mmHg、(1.62±0.27) g/L vs.(2.59±0.26) g/L、(214±20)×10 9/L vs.(273±23)×10 9/L、(13.4±0.5) s vs.(14.7±0.8) s、(114±12) g/L vs.(128±17) g/L, t values were 16.34、62.05、29.51、22.77、14.91、7.41, respectively, all P<0.001], but the differences between groups were not statistically significant (all P>0.05). The difference of albumin, alanine aminotransferase, aspartate aminotransferase and creatinine before and after treatment were not statistically significant (all P>0.05). Conclusion:4% succinylated gelatin does not increase the risk of coagulation dysfunction during perioperative period in children with CCHD. It has small influence on liver-kidney function and has high safety.

Purpose To investigate the expression of semaphorin 5 A(SEMA5A)and programmed death ligand-1(PD-L1)and their clinicopathological significance in gastric cancer.Methods Clinical data of 41 cases of gastric cancer tissues and paired adjacent tissues were collected.Immunohistochemical staining and RT-qPCR were used to de-tect the expression levels of SEMA5A and PD-L1,and analysed the correlation between SEMA5A and PD-L1 and clini-copathological features.In addition,we used lentivirus to construct SEMA5A stable low-expression cell lines.RT-qPCR and Western blot were used to analyse the correlation between the expression of SEMA5A and PD-L1 in gastric cancer tissues.Results The high expression rate of SEMA5A was 65.9％(27/41)in gastric cancer tissues and 39.0％(16/41)in paracancerous tissues,respectively.The positive rates of PD-L1 were 58.5％(24/41)and 14.6％(6/41),respectively.RT-qPCR showed that the relative expression levels of SEMA5A mRNA in gastric cancer and paracancerous tissues were 1.30±0.50 and 0.81±0.48,respectively,while the relative expression levels of PD-L1 mRNA were 0.70±0.42 and 0.12±0.09,respectively.SEMA5A expression was correlated with histological typ-ing of gastric cancer and lymph node metastasis(P＜0.05).PD-L1 expression was correlated with tumour size,T stage,and pathological stage of gastric cancer(P＜0.05).Pearson correlation analysis showed a positive correlation between the expression of SEMA5A and PD-L1 mRNA in gastric cancer tissues,and spearman correlation analysis showed that there was no correlation between the expression of the two in paracancerous tissues.Knockdown of SE-MA5A gene in human gastric adenocarcinoma cell lines resulted in down-regulation of PD-L1 expression.Conclusion Both SEMA5A and PD-L1 are highly expressed in gastric cancer tissues,and there is a correlation between the ex-pressions of SEMA5A and PD-L1.They can serve as potential molecular markers for prognostic evaluation and combi-nation therapy of gastric cancer.

Gastric cancer is one of the most common malignant tumors in the digestive system, characterized by high incidence and mortality rates. In recent years, with the rapid develop-ment of molecular immunology, the application of immune checkpoint inhibitors (ICIs) in neoadju-vant therapy has significantly improved pathological response rates and survival outcomes for patients with resectable locally advanced gastric cancer. The authors systematically review current research progress on combination strategies involving immune checkpoint inhibitors in neoadjuvant therapy for locally advanced gastric cancer, aiming to provide an evidence for optimizing individua-lized therapeutic regimens.

AIM:To investigate whether total alkaloids of Cocculus orbiculatus(COTA)attenuate ulcerative colitis(UC)in mice via PINK1/parkin mitophagy pathway.METHODS:Sixty C57BL/6 mice were randomly divided into normal control group,model group,positive drug mesalazine group,and low-,medium-and high-dose(0.162,0.324 and 0.486 g/kg)COTA groups,with 10 mice in each group.Except for normal control group,the mice in all groups were given free access to 3%dextran sulfate sodium(DSS)solution for 7 consecutive days to establish a UC model in mice,and were then treated with COTA or mesalazine via oral gavage.The general condition of the mice was observed,and the colon length and disease activity index(DAI)score were determined.Colon histopathological damage was observed by HE staining.The serum levels of interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pro-tein levels of PINK1,parkin,microtubule-associated protein 1 light chain 3(LC3),P62 and beclin-1 in colon tissues were determined by Western blot.The protein expression of LC3 and parkin was detected by immunofluorescence.RE-SULTS:Compared with normal control group,the mice in model group showed varying degrees of soft stools or bloody stools,decreased body weight(P<0.05),increased DAI score,shortened colon length(P<0.05),and obvious pathologi-cal damage in the colon tissue.The serum levels of IL-1β,IL-6 and TNF-α were elevated(P<0.05).The protein levels of parkin,PINK1,LC3-II and beclin-1 were significantly decreased(P<0.05),while P62 protein expression was in-creased(P<0.05).Immunofluorescence showed a small number of autophagosomes in the colon tissue.In contrast,com-pared with model group,the mice in total alkaloids of Cocculus orbiculatus groups exhibited increased body weight(P<0.05),decreased DAI score,increased colon length(P<0.05),and reduced levels of IL-1β,IL-6 and TNF-α(P<0.05).The protein levels of parkin,PINK1,LC3 and beclin-1 were elevated(P<0.05),while P62 expression was re-duced(P<0.05),with numerous autophagosomes visible in the colon tissue via immunofluorescence.CONCLUSION:Total alkaloids of Cocculus orbiculatus can enhance the expression of mitophagy-related proteins PINK1,parkin,LC3 and beclin-1,activate mitophagy,and reduce the expression of inflammatory factors,thereby attenuating the inflammatory re-sponse in the colon mucosa of DSS-induced UC mice.

Objective To explore the value of analysis on the incidence of healthcare-associated infection(HAI)based on disease diagnosis-related grouping(DRG),case mix index(CMI),and relative weight(RW).Methods All discharged cases,DRG and HAI status in a tertiary first-class general hospital from January 1 to December 31,2023 were analyzed retrospectively.Incidences of HAI in different departments were adjusted and compared by CMI.Incidences of HAI in different DRG groups were adjusted by RW.Results Among the 47 695 cases included in the analysis,757 were HAI cases,including 225 DRG groups.The department of critical care medicine had the highest incidence of HAI(11.98％).After CMI adjustment,departments with higher incidence of HAI were main-ly the department of respiratory and critical care medicine(3.96％),department of critical care medicine(3.04％),and department of neurology(2.85％),et al.DRG groups with the top five high incidence of HAI were AH11(tracheotomy and with ventilator support ≥96 hours or extracorporeal membrane oxygenation[ECMO],accompa-nied by major complications and comorbidity[MCC],50.00％),BC29(ventricular shunt and revision surgery,31.43％),BB21(craniotomy other than trauma,accompanied by MCC,27.56％),BB11(craniotomy of brain trauma,accompanied by MCC,26.32％),and GB1A(major surgery of esophagus,stomach,and duodenum,accompanied by major or moderate complications and comorbidity,16.00％).After RW adjustment,the DRG groups with the top five high incidence of HAI were ES21(respiratory system infection/inflammation,accompanied by MCC,5.89％),BR21(cerebral ischemic disease,accompanied by MCC,5.17％),FR11(heart failure,shock,accompanied by MCC,4.80％),BC29(4.57％)and AH11(3.57％).Conclusion Analyzing the incidence of HAI based on CMI and RW can help to identify key departments and disease groups for infection prevention and control,and provide reference for precise prevention and control of HAI in the new era.

ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.