OBJECTIVE To estimate the cost-effectiveness of penpulimab combined with chemotherapy versus chemotherapy alone in first-line treatment of advanced squamous non-small-cell lung cancer （sq-NSCLC）. METHODS From the perspective of Chinese health system， cost-utility analysis was used to evaluate the cost-effectiveness of penpulimab combined with chemotherapy （paclitaxel + carboplatin） versus chemotherapy （paclitaxel + carboplatin） in first-line treatment of sq-NSCLC. A three-health states Markov model was constructed with R packages， and clinical data used in the model were derived from the AK105-302 clinical trial. Costs and utilities were collected from the open-access database and published literature. The quality-adjusted life-years （QALY） was used as the utility index， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024， equivalent to 287 247 yuan/QALY. The cost-effectiveness of the schemes was evaluated by comparing the incremental cost- utility ratios （ICER） of the two schemes with the WTP threshold. One-way sensitivity analysis and probabilistic sensitivity analysis （PSA） were used to verify the stability of the basic analysis results. RESULTS Compared with chemotherapy， penpulimab combined with chemotherapy increased 0.73 QALY with an incremental cost of 150 681.93 yuan， and the ICER was 206 413.60 yuan/QALY. One-way sensitivity analysis showed that the utility of progression-free survival was the most sensitive factor on ICERs. At the WTP threshold of 3 times China’s per capita GDP， the economic probability of this scheme was 98.80%. At the WTP threshold of 1 times China’s per capita GDP， the probability of ICER being cost-effective was less than 0.01%. CONCLUSIONS For patients with advanced sq-NSCLC， penpulimab combined with chemotherapy is a cost-effective first-line treatment option when WTP threshold is 3 times China’s per capita GDP.

Objective:To predict the mechanism of Panacis Quinquefolii Radix- Acori Tatarinowii Rhizoma (PQ-AT) in the treatment of diabetes encephalopathy (DE) using network pharmacology combined with molecular docking; To conduct experimental verification.Methods:The active components and targets of PQ and AT were screened by TCMSP database. The GeneCards and Disgenet were used to collect DE related target genes. String database and Cytoscape software were used to structure PPI network and perform visualization analysis. The common targets were imported into Metascape platform for GO annotation and KEGG enrichment analysis. Molecular docking was used to verify the binding ability of active components to core targets. Rats were randomly divided into a blank group, a model group, and a low-dose group of PQ-AT (1.08 g/kg), a high-dose group of PQ-AT (2.16 g/kg), and a metformin group (0.18 g/kg) using a random number table. To establish the rat model of diabetes encephalopathy, intraperitoneal injection of streptozotocin was used in addition to the blank group. After a 12-week drug intervention, TNF-α and Cyclooxygenase-2 (PTGS2) protein expression in the cerebral cortex of rats was detected using Western blot.Results:A total of 26 active components in PQ-AT and 107 related targets of DE were obtained, mainly including TNF, JUN, and PTSG2, which were mainly concentrated in TNF signaling pathway, cancer and other signal pathways. Molecular docking showed that the main active components of PQ-AT had relatively stable binding activity with TNF-α and PTGS2. Western blot results shows that compared with the model group, the expressions of PTGS2 and TNF-α significantly decreased in each administration group ( P<0.05 or P<0.01). Conclusion:PQ-AT can act on TNF, CASP3, JUN, STAT3, PTGS2 and other core targets to regulate signal pathways such as TNF, and inhibit inflammatory reaction to achieve the effect of treating DE.

Objective To evaluate the predictive value of CT-enhanced imaging-based radiomics nomogram for the status of microsatel-lite instability(MSI)in colon cancer.Methods A retrospective analysis was conducted on 129 postoperative colon cancer patients with confirmed MSI status.They were randomly divided into a training group(n=90)and a validation group(n=39)at a ratio of 7:3.Radiomics features were extracted from preoperative CT-enhanced images of the patients.The predictive performance of various machine learning algorithms was evaluated using the area under the curve(AUC).A nomogram model was developed by incorporating clinical independent risk factors,and the model's overall performance was assessed using decision curve analysis(DCA).Results Age and lesion site were identified as prominent independent risk factors and utilized in the construction of a clinical model.The light gradient boosting machine(LightGBM)algorithm was chosen for building a radiomics model.As a joint model,the AUC of the nomogram model of 0.917 in the training group and 0.822 in the validation group.The DCA confirmed the substantial clinical applicability of the nomogram model.Conclusion The CT-enhanced imaging-based radiomics nomogram offers a pioneering and individualized predic-tive approach for determining the MSI status in colon cancer.

Objective·To establish a mouse model with dormant cancer and no obvious metastasis by combining the preimmune strategy with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.Methods·The KPC1199 mouse pancreatic cancer cell line was transfected with the mVenus-p27K-cell G0 phase indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system to construct a stable expression cell line,KPC1199-PDL.After being cultured in the serum-free condition,KPC1199-PDL cells were sorted into mVenus(+)cells and mVenus(-)cells by flow cytometry,and the expression of G0 phase-related genes was verified by real-time fluorescence quantitative PCR(qPCR).Sensitivity of KPC1199-PDL cells to diphtheria toxin(DTX)and ganciclovir(GCV)was evaluated by CCK-8 assay.A transsplenic portal vein-hepatic metastasis model was constructed in wild-type C57BL/6 mice to validate the function of KPC1199-PDL cells in vivo by immunofluorescence technology.The KPC1199-PDL cells were injected subcutaneously into C57BL/6 mice,followed by in situ injection of DTX and GCV to ablate subcutaneous tumors 5 d later,to obtain preimmunized mice.The transsplenic portal vein-hepatic metastasis models were constructed in these mice.Bioluminescence imaging was used to evaluate subcutaneous tumor ablation and hepatic metastasis in the mice,and immunofluorescence assay was used to detect the distribution and dormant state of tumor cells in the livers of preimmunize mice.Results·The three tool systems were stably expressed in KPC1199-PDL cells,and their proliferative ability was not affected.In the serum starving condition,some KPC1199-PDL cells expressed the mVenus protein,indicating entry into the G0 phase;the mVenus(+)cells sorted out by flow cytometry exhibited significantly higher expression of G0 phase-related genes(all P<0.05)and significantly lower expression of the proliferation-related gene compared with mVenus(-)cells(P<0.05).The CCK-8 assay demonstrated high sensitivity of KPC1199-PDL cells to DTX and GCV.In vivo experiments confirmed that KPC1199-PDL cells could be effectively traced through tdTomato protein expression,and could indicate entry into the G0 phase through mVenus protein expression.Following subcutaneous tumor implantation and drug ablation,preimmunized mice were successfully obtained.In the subsequent transsplenic portal vein-hepatic metastasis model,no metastatic signals were observed in the liver by bioluminescence imaging,but single or small clusters of G0 phase tumor cells expressing both mVenus and tdTomato,not expressing the proliferation marker Ki67,were detected in liver tissue sections by immunofluorescence analysis.Conclusions·A recognizable and traceable dormant cancer model is constructed with the combination of the preimmune mouse model of pancreatic cancer,the mVeneus-p27K-indicator system,the DTR-HSV/TK suicide gene system,and the Luc2-tdTomato tracer system.

Objective:To summarize the best evidence for exercise intervention in elderly patients with sarcopenia in intensive care unit (ICU) through literature search, and provide a reference for clinical implementation of early exercise intervention in this population through evidence-based practice.Methods:① Summary of best evidence: relevant literature on exercise intervention for elderly patients with sarcopenia in ICU, including guideline, evidence summary, expert consensus, systematic review, and original study [quasi-experiment and randomized controlled trial (RCT)] from UpToDate Clinical Advisor, Ovid database, National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed/Medline, SinoMed, CNKI, Wanfang Database, VIP, and Yimai Tong Guideline Network were systematically searched. The search period covered from the establishment of these databases up to August 24, 2023. The quality of the literature was evaluated by two researchers with methodological expertise in evidence-based medicine, and the evidences were extracted and summarized. ② Evidence-based practice: the elderly patients with high risk of sarcopenia who had been hospitalized in the ICU for more than 7 days from January to April 2024 were enrolled as the research subjects, and they were divided into a control group and an intervention group using convenience sampling method. The control group received routine intensive care nursing. The intervention group implemented exercise intervention based on the actual situation of the patients, the baseline review was conducted before evidence application, and the effectiveness of evidence application at 7 days and 14 days was evaluated.Results:① A total of 19 pieces of literature were included, including 4 guidelines, 1 summary of evidence, 4 expert consensuses, 4 systematic reviews, and 6 original studies (1 quasi-experiment, 5 RCT). After literature quality evaluation, all 19 articles were enrolled. Finally, 31 pieces of best evidence were extracted from eight aspects, including assessment and diagnosis, multidisciplinary cooperation, indication, preparation before intervention, intervention program, safety monitoring, post-intervention evaluation, and special task. ② Finally, a total of 30 patients were enrolled in the intervention group, of which 17 completed 14 days of rehabilitation exercise, and 13 completed 7 days of rehabilitation exercise. Twenty-seven patients were enrolled in the control group, of which 17 completed 14 days of monitoring, and 10 completed 7 days of monitoring. Clinical evidence application results showed that the patients in the intervention group did not experience adverse events such as increased heart rate, extubation, or physical discomfort. The skeletal muscle mass index (SMI) in both groups was gradually decreased with the prolongation of intervention duration, but the 7-day SMI in the intervention group was significantly higher than that in the control group (kg/m 2: 8.61±2.66 vs. 6.65±1.50, P < 0.01). Conclusion:By summarizing the best evidence and evidence-based practice of exercise intervention for elderly patients with sarcopenia in ICU, this study confirmed the feasibility due to safe and effective of implementing early exercise intervention for elderly sarcopenia patients in ICU.

Objective:To investigate the influence of different test conditions on the particle size distribution of elemene emulsion injection measured by laser light scattering method.Methods:The method of particle size deter-mination of elemene emulsion injection was explored.The test conditions were as follows:shading rate 5％-10％,absorption rate 0.000 1-0.1,refractive index1.52-1.54,mixing speed 800-1 600 r·min-1,balance time 0.5-1 min.After the methodology verification,3 batches of elemene emulsion injection were taken and deter-mined on the Bettersize 2600 laser particle size distribution instrument(wet method).Results:Measurement results of 3 batches of samples:d(0.1),d(0.5),d(0.9),d(0.99)were 252,251,213 nm;354,351,316 nm;543,532,476 nm;979,953,887 nm.Conclusion:This test method can be used to determine the particle size distribution of elemene emulsion injection with good reproducibility.

Cirrhotic portal hypertension (CPH) is a manifestation of decompensated liver cirrhosis, with ascites, portal collateral circulation formation, hypersplenism and splenomegaly as the typical clinical symptoms. In recent years, the incidence of CPH has been increasing year by year, and the treatment of CPH has gradually become a hot issue in medical research. In order to further explore the diagnosis and treatment scheme of CPH. We briefly describe the pathophysiological mechanism and diagnosis of CPH, and the current situation of CPH treatment and the new progress of internal and external treatment were reviewed.

Objective:To construct machine learning-based delirium prediction models for ICU patients with multiple trauma and evaluate their prediction efficiency.Methods:A retrospective case-control study was conducted to analyze the clinical data of 417 ICU multiple trauma patients admitted to the First Affiliated Hospital of Zhengzhou University from July 2019 to June 2022, including 305 males and 112 females, aged 18-88 years [(47.8±15.7)years]. The score of acute physiology and chronic health status assessment II (APACHE II) was 0-50 points [(9.80±0.29)points]. The patients were randomly divided into training set ( n=291) and test set ( n=126) with a ratio of 7∶3. The demographic data, past history, treatment and laboratory results of the patients were collected. Lasso regression analysis was applied to screen variables that were significantly correlated to the incidence of delirium in the training set and the variables were then included into the machine learning models. Six machine learning methods including the random forest, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor were used to construct the delirium prediction models for ICU multiple trauma patients. The accuracy, sensitivity, precision, F1 fraction and area under the curve (AUC) of the receiver′s operating characteristics (ROC) curve were calculated by using the data in the test set to evaluate the prediction efficiency of the models. Results:With regards to the six prediction models, namely random forests, gradient boosting tree, extreme gradient boosting, logistic regression, support vector machine and K nearest neighbor prediction models, the accuracy in the test set was 0.70, 0.68, 0.69, 0.73, 0.70 and 0.60 respectively; the sensitivity was 0.74, 0.80, 0.81, 0.86, 0.85 and 0.69 respectively; the precision was 0.72, 0.69, 0.70, 0.73, 0.71 and 0.65 respectively; the F1 fraction was 0.73, 0.74, 0.75, 0.79, 0.78 and 0.67 respectively; the AUC was 0.72, 0.73, 0.72, 0.80, 0.74 and 0.64 respectively. Among them, the logistic regression model had the best discriminability.Conclusion:Delirium prediction models for ICU patients with multiple trauma have been successfully constructed, among which the logistic regression model has the best prediction efficiency and can serve as an effective tool for early prediction and prevention of delirium in the clinical care of patients with multiple trauma.

Objective:To explore the composition of oral microbiome in patients of long-term survival after liver transplantation, and compare the diversity and distribution of oral microbiome in liver transplant patients with or without liver cancer.Methods:This is a cross-sectional study. Clinical data of 20 patients of long-term survival after liver transplantation from Beijing Chaoyang Hospital Affiliated to Capital Medical University from July 2023 to October 2023 were continuously collected, including 13 males and 7 females, aged 55 (48, 60) years. There were eight patients with hepatocellular carcinoma (HCC) undergoing liver transplantation and 12 non-HCC liver transplant patients. Oral microbiome was analyzed by 16S rDNA gene sequencing, and the diversity analysis and LEfSe analysis were performed.Results:The top ten groups of bacteria in the HCC and non-HCC liver transplant patients were both Bacteroidota, Firmicutes, Proteobacteria, Actinobacteria, Fusobacteriota, Patescibacteria, Campylobacterota, Cyanobacteria, spirochaetota, and Aenigmarchaeota. The top ten genus levels of bacteria in the HCC and non-HCC liver transplant patients were both Haemophilus, Porphyromonas, Gemella, Fusobacterium, Actinomyces, Prevotella, Rothia, Streptococcus, Neisseria. By LEfSe analysis, we found the enrichment of Flavobacteriales, Flavobacteriaceae, Capnocytophaga, Mogibacterium_timidum, Capnocytophaga_leadbetteri, Campylobacter_showae in the HCC group, while the enrichment of Veillonella_atypica, Prevotella_histicola in the non-HCC group.Conclusion:The main microbiome was similar between HCC and non-HCC liver transplant patients, but there were also some differences in microbiome communities.

Objective:To explore the safety and therapeutic effect of probiotics combined with ornithine aspartate on patients with liver cirrhosis complicated by hepatic encephalopathy.Methods:72 patients with hepatic encephalopathy hospitalized in the Affiliated Hospital of North China University of Technology from January 2017 to December 2021 were randomly. According to the principle of comparability between groups in terms of gender and age, the group was divided into an observation group (36 cases) and a control group (36 cases) using a random number table method. The control group was treated with ornithine aspartate, while the case group was treated with probiotics combined with ornithine aspartate. The curative effect of the two groups of patients and the changes of serum inflammatory factors, intestinal flora and intestinal mucosal barrier function were observed.Results:The total effective rate of the case group was higher than that of the control group [97.22%(35/36) vs 83.33%(30/36)], The difference between groups is statistically significant (χ 2=2.53, P=0.112). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood ammonia, interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor (TNF) in the two groups-α (TNF-α)、C-reactive protein (CRP), enterobacter, enterococcus content, endotoxin, D-lactic acid, diamine oxidase, and digital connection test (NCT) time were lower than before treatment [(-130.89±31.67) U/L vs (-98.64±43.41) U/L,(-137.81±31.92) U/L vs (-79.58±45.42) U/L, (-57.13±21.07) μmol/L vs (-45.92±18.11) μmol/L,(-164.06±19.30) μmol/L vs (-148.98±12.97) μmol/L, (-5.35±2.30) ng/L vs (2.18±2.77) ng/L,(-5.51±2.07) μmol/L vs (-3.72±1.50) ng/L, (-12.60±3.65) ng/L比(-7.97±5.86) ng/L, (-45.95±20.34) mg/L vs (-21.14±19.09) mg/L, (-2.70±1.53) vs (-1.31±2.47), (-2.50±1.26) vs (-1.39±1.97),(-0.32±0.09) EU/ml vs (-0.19±0.09) EU/ml, (-47.58±18.52) nmol/L vs (-32.31±22.21) nmol/L,(-3.44±1.06) U/ml vs (-1.86±1.30) U/ml, (-31.75±10.09) s vs (-14.58±10.10) s] and the scores of bifidobacterium, lactobacillus, and digital sign test (DST) were higher than before treatment [(2.77±1.76) vs (1.13±2.06), (3.23±1.61) vs (1.06±2.31), (32.58±5.72) vs (16.33±6.16)]. After treatment, ALT, AST, TBIL, blood ammonia, IL-6, IL-8, TNF in the case group-α, CRP, Enterobacter, Enterococcus content, endotoxin, D-lactic acid, diamine oxidase, NCT time were lower than those in the control group, and bifidobacterium, lactobacillus, DST scores were higher than those in the control group, with statistically significant differences(t-values of 3.60, 6.29, 2.42, 3.89, 5.28, 4.21, 4.03, 5.34, 2.87, 2.86, 6.11, 3.17, 5.63, 7.21, 3.61, 4.64 and 11.59. P-values of 0.001, <0.001, 0.018, <0.001, <0.001, <0.001, <0.001, <0.001, 0.005, 0.006, <0.001, 0.002, <0.001, <0.001, 0.001, <0.001, and <0.001). Conclusions:Micro-ecological preparation combined with ornithine aspartate has a significant therapeutic effect on patients with hepatic encephalopathy, which can significantly improve liver function and cognitive function of patients, reduce blood ammonia level, inhibit inflammatory reaction, improve intestinal flora and intestinal mucosal barrier function, with good safety, and is worthy of clinical promotion.