OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

Ulcerative colitis(UC)is a common disease of the digestive system.Phosphatidylinositol-3-kinase(PI3K)/synuclein/threonine kinase(AKT)is closely related to cell survival,apoptosis,inflammation and other biological processes,and the expression levels of PI3K and AKT significantly increase during the course of UC,with accelerated apoptosis,improved inflammation,and damaged intestinal mucosal barrier function.In recent years,a large number of basic and clinical trials have been conducted on PI3K/AKT signaling pathway in TCM,and the results indicate that PI3K/AKT signaling pathway is expected to be an important potential target for UC treatment.This article analyzed the mechanism of the regulation of PI3K/AKT signaling pathway in TCM from monomer,extract,compound and acupuncture,and suggested that the regulation of this signaling pathway is of great significance for the prevention and treatment of UC,and provide reference for drug development.

Objective To explore the effect of multiparameter electroencephalogram(EEG)-guided anesthesia management on EEG burst suppression(BS)and postoperative delirium(POD)in elderly patients undergoing lower abdominal laparoscopic surgery.Methods A total of 100 elderly patients,48 males and 52 females,aged 65-85 years,BMI 18.5-28.0 kg/m2,and ASA physical status Ⅱ or Ⅲ,were enrolled for lower abdominal surgery under general anesthesia.Patients were randomly divided into two groups:multiparameter group and single parameter group,50 patients in each group.In multiparameter group,multiparameter EEG monitoring with patient statu index(PSI),spectral edge frequency(SEF),burst suppression ratio(BSR)and density spectral array(DSA)were used to guide the depth management of anesthesia.In single parameter group,single parameter PSI was used to guide the depth management of anesthesia.The total area under the hypotensive threshold of MAP(AUTMAP)was calculated,and the amount of anesthetic used during the operation and the use of vasoactive drugs,duration of anesthesia,extu-bation time,duration of PACU stay,and postoperative hospitalisation days were recorded.HR,MAP,PSI,and SEF were recorded before the induction of anesthesia,5 minutes after induction of anesthesia,5,30,and 60 minutes after incision,and at the end of surgery.The incidence,duration,and maximum BSR of in-traoperative BS,as well as the incidence of POD 1,2,and 3 days after surgery were recorded.Results There was no significant difference in AUTMAP values between the two groups.Compared with single parame-ter group,intraoperative propofol and remifentanil dosage were significantly decreased(P＜0.05),awak-ening time,PACU stay,and postoperative hospitalization time were significantly shorter in multiparameter group(P＜0.05),the PSI was significantly increased 5,30,and 60 minutes after incision and at the end of surgery,and the SEF was significantly increased 5 minutes after induction of anesthesia,5,30,and 60 minutes after induction and the end of surgery(P＜0.05).Compared with single parameter group,inci-dence of intraoperative BS was significantly decreased,duration of BS was significantly shorter,smaller maximum BSR was significantly decreased,and incidence of POD on 1 day after surgery in multiparameter group(P＜0.05).Conclusion Anesthesia management guided by multiparameter EEG can inhibit the oc-currence of BS,mitigate the degree of BS,and reduce the incidence of POD in elderly patients undergoing abdominal surgery.

Objective:To investigate respiratory virus infection in children with septic shock in pediatric care units (PICU) in China and its influence on clinical outcomes.Methods:The clinical data of children with septic shock in children′s PICU from January 2018 to December 2019 in 10 Chinese hospitals were retrospectively collected. They were divided into the pre-COVID-19 and post-COVID-19 groups according to the onset of disease, and the characteristics and composition of respiratory virus in the 2 groups were compared. Matching age, malignant underlying diseases, bacteria, fungi and other viruses, a new database was generated using 1∶1 propensity score matching method. The children were divided into the respiratory virus group and non-respiratory virus group according to the presence or absence of respiratory virus infection; their clinical characteristics, diagnosis, and treatment were compared by t-test, rank sum test and Chi-square test. The correlation between respiratory virus infection and the clinical outcomes was analyzed by logistic regression. Results:A total of 1 247 children with septic shock were included in the study, of them 748 were male; the age was 37 (11, 105) months. In the pre-and post-COVID-19 groups, there were 530 and 717 cases of septic shock, respectively; the positive rate of respiratory virus was 14.9% (79 cases) and 9.8% (70 cases); the seasonal distribution of septic shock was 28.9% (153/530) and 25.9% (185/717) in autumn, and 30.3% (161/530) and 28.3% (203/717) in winter, respectively, and the corresponding positive rates of respiratory viruses were 19.6% (30/153) and 15.7% (29/185) in autumn, and 21.1% (34/161) and 15.3% (31/203) in winter, respectively. The positive rates of influenza virus and adenovirus in the post-COVID-19 group were lower than those in the pre-COVID-19 group (2.1% (15/717) vs. 7.5% (40/530), and 0.7% (5/717) vs. 3.2% (17/530), χ2=21.51 and 11.08, respectively; all P<0.05). Rhinovirus virus were higher than those in the pre-Covid-19 group (1.7% (12/717) vs. 0.2% (1/530), χ2=6.51, P=0.011). After propensity score matching, there were 147 cases in both the respiratory virus group and the non-respiratory virus group. Rate of respiratory failure, acute respiratory distress, rate of disseminated coagulation dysfunction, and immunoglobulin usage of the respiratory virus group were higher than those of non-respiratory virus group (77.6% (114/147) vs. 59.2% (87/147), 17.7% (26/147) vs. 4.1% (6/147), 15.6% (25/147) vs. 4.1% (7/147), and 35.4% (52/147) vs. 21.4% (32/147); χ2=11.07, 14.02, 11.06 and 6.67, all P<0.05); and PICU hospitalization of the former was longer than that of the later (7 (3, 16) vs. 3 (1, 7)d, Z=5.01, P<0.001). Univariate logistic regression analysis showed that the presence of respiratory viral infection was associated with respiratory failure, disseminated coagulation dysfunction, the use of mechanical ventilation, and the use of immunoglobulin and anti-respiratory viral drugs ( OR=2.42, 0.22, 0.25, 0.56 and 1.12, all P<0.05). Conclusions:The composition of respiratory virus infection in children with septic shock is different between pre and post-COVID-19. Respiratory viral infection is associated with organ dysfunction in children with septic shock. Decreasing respiratory viral infection through respiratory protection may improve the clinical outcome of these children.

Objective:To investigate the clinical features, pathogen composition, and prognosis of septic shock in pediatric intensive care units (PICU) in China.Methods:A multicenter retrospective cohort study. A retrospective analysis was conducted on the clinical data of children with septic shock from 10 hospitals in China between January 2018 and December 2021. The clinical features, pathogen composition, and outcomes were collected. Patients were categorized into malignant tumor and non-malignant tumor groups, as well as survival and mortality groups. T test, Mann Whitney U test or Chi square test were used respectively for comparing clinical characteristics and prognosis between 2 groups. Multiple Logistic regression was used to identify risk factors for mortality. Results:A total of 1 247 children with septic shock were included, with 748 males (59.9%) and the age of 3.1 (0.9, 8.8) years. The in-patient mortality rate was 23.2% (289 cases). The overall pathogen positive rate was 68.2% (851 cases), with 1 229 pathogens identified. Bacterial accounted for 61.4% (754 strains) and virus for 24.8% (305 strains). Among all bacterium, Gram negative bacteria constituted 64.2% (484 strains), with Pseudomonas aeruginosa and Enterobacter being the most common; Gram positive bacteria comprised 35.8% (270 strains), primarily Streptococcus and Staphylococcus species. Influenza virus (86 strains (28.2%)), Epstein-Barr virus (53 strains (17.4%)), and respiratory syncytial virus (46 strains (17.1%)) were the top three viruses. Children with malignant tumors were older and had higher pediatric risk of mortality (PRISM) Ⅲ score, paediatric sequential organ failure assessment (pSOFA) score (7.9 (4.3, 11.8) vs. 2.3 (0.8, 7.5) years old, 22 (16, 26) vs. 16 (10, 24) points, 10 (5, 14) vs. 8 (4, 12) points, Z=11.32, 0.87, 4.00, all P<0.05), and higher pathogen positive rate, and in-hospital mortality (77.7% (240/309) vs. 65.1% (611/938), 29.7% (92/309) vs. 21.0% (197/938), χ2=16.84, 10.04, both P<0.05) compared to the non-tumor group. In the death group, the score of PRISM Ⅲ, pSOFA (16 (22, 29) vs. 14 (10, 20) points, 8 (12, 15) vs. 6 (3, 9) points, Z=4.92, 11.88, both P<0.05) were all higher, and presence of neoplastic disease, positive rate of pathogen and proportion of invasive mechanical ventilation in death group were also all higher than those in survival group (29.7% (87/289) vs. 23.2% (222/958), 77.8% (225/289) vs. 65.4% (626/958), 73.7% (213/289) vs. 50.6% (485/958), χ2=5.72, 16.03, 49.98, all P<0.05). Multiple Logistic regression showed that PRISM Ⅲ, pSOFA, and malignant tumor were the independent risk factors for mortality ( OR=1.04, 1.09, 0.67, 95% CI 1.01-1.05, 1.04-1.12, 0.47-0.94, all P<0.05). Conclusions:Bacterial infection are predominant in pediatric septic shock, but viral infection are also significant. Children with malignancies are more severe and resource consumptive. The overall mortality rate for pediatric septic shock remains high, and mortality are associated with malignant tumor, PRISM Ⅲ and pSOFA scores.

Objective:To prepare a novel 68Ga-labeled bicyclic peptide targeting poliovirus receptor related protein 4 (PVRL4, Nectin-4), and evaluate its feasibility for breast cancer imaging via in vitro and in vivo experiments. Methods:A Biotin-modified bicyclic peptide targeting Nectin-4, Biotin-BMIC, was synthesized, and its targeting properties were preliminarily evaluated by in vitro cell staining experiments. BMIC was modified by 1, 4, 7-triazonane-1, 4-diacetic acid (NODA) and the labeling precursor NODA-BMIC was prepared. A potential PET probe targeting Nectin-4, 68Ga-NODA-BMIC was prepared by one-step labeling strategy. The imaging properties of the probe were investigated by in vivo microPET imaging and in vitro experiments in mice bearing breast tumors. Data were analyzed by independent-sample t test and repeated measures analysis of variance. Results:Fluorescence staining of the cells showed that the fluorescently labeled bicyclic peptide, Biotin-BMIC, was highly aggregated in Nectin-4 positive BT474 breast cancer cells compared to those in Nectin-4 negative MDA-MB-231 cells. The uncorrected yield of 68Ga-NODA-BMIC was (71.5±2.2)% and the radiochemical purity was greater than 95%. The specific activity was greater than 3 GBq/μmol. After incubation 10, 30, 60 and 120 min, higher radioactivity uptakes were found in BT474 breast cancer cells compared to those in MDA-MB-231 breast cancer cells respectively ( F=1 302.00, P<0.001). MicroPET imaging showed that the BT474 xenograft tumors were clearly visible with favorable contrast. A significant statistical difference in uptakes between BT474 and MDA-MB-231 xenograft tumor uptake at 10, 30, 60, and 120 min after probe injection respectively was existed ( F=1 826.00, P<0.001). At 60 min postinjection, the uptake value of BT474 tumors was (5.03±0.14) percentage activity of injection dose per gram of tissue (%ID/g), which was significantly higher than that of MDA-MB-231 tumors ((0.19±0.04) %ID/g; t=79.40, P<0.001). Meanwhile, the tumor-to-muscle ratios in the former were also greater than those in the latter ( F=222.00, P<0.001). At 60 min postinjection, the tumor-to-muscle ratio in the former was significantly higher than that in the latter (24.75±3.10 vs 1.30±0.15; t=14.31, P=0.002). The results were consistent with the immunohistochemistry staining. Conclusions:A novel bicyclic peptide PET probe targeting Nectin-4, 68Ga-NODA-BMIC, is easy to be synthesized and owns satisfactory labeling yield and radiological purity. The imaging performance is good and the target tissues could be visualized. It may play a unique role in the diagnosis and treatment of breast cancer.

Objective To investigate the influencing factors of opioid analgesics need within 48 hours after arthroscopic rotator cuff repair.Methods Clinical data of 90 consecutive arthroscopic rotator cuff repairs by the same operator from March 2017 to July 2022 were retrospectively analyzed.The patients were divided into opioid group(62 patients)and control group(28 patients)according to whether they used opioid analgesics within 48 hours after surgery.The control group consisted of patients who did not use analgesics or who had good analgesic effects with conventional analgesic regimens(non-steroidal anti-inflammatory drugs or non-opioid central analgesics)after surgery,and the opioid group consisted of patients who required opioid analgesics as assessed by the surgeon or who need opioid analgesics because of inefficacy of conventional analgesic regimens.The following factors were selected as independent variables:gender,age(whether≥65 years old),duration of disease(whether≥4 weeks),body mass index(BMI)(whether≥25),occupation(whether employed),with or without a history of smoking and alcohol consumption,hypertension,diabetes,heart disease,and trauma,duration of surgery(whether≤180 min),number of torn tendons(whether≥2),number of screws(whether≥2),large nodular osteophyte,and whether there was moderate-to-severe impingement.Single factor analysis was used to screen the factors influencing the need for opioid analgesics within 48 hours after arthroscopic rotator cuff repair.Results The results of univariate analysis showed that among the above independent variables,only the number of torn tendons≥2 was the factor affecting the need for opioid analgesics within 48 hours after arthroscopic rotator cuff repair(OR = 5.263,P = 0.007).Conclusions Patients with rotator cuff tears with≥2 tendons had more severe pain within 48 hours after rotator cuff repair,requiring opioid analgesics.Focus should be placed on postoperative pain in such patients,and a diverse analgesic regimen should be used early.

Objective:To retrieve and obtain relevant evidence of intra-abdominal pressure-oriented enteral nutrition assessment and management in patients with intra-abdominal hypertension, in order to provide evidence-based evidence for clinical medical staff to make enteral nutrition-related clinical decisions for patients with intra-abdominal hypertension.Methods:Systematic retrieval of Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Literature, UpToDate, PubMed, Cochrane Library, BMJ Best Practice and other English data, as well as domestic and foreign guidelines such as American Society for Parenteral and Enteral Nutrition, Scottish Intercollegiate Guidelines Network, etc. All evidence available on the Internet in both Chinese and English on intra-abdominal pressure-guided enteral nutrition strategies in adults with intra-abdominal hypertension, study types including clinical decision-making, systematic reviews/meta-analyses, evidence summaries, expert consensus, guidelines or related to the subject of this study closely related high-quality original research. The retrieval time was from the establishment of the database to November 2021. The literature evaluation tool was selected according to the research type. Two researchers trained in the evidence-based system independently evaluate the quality of the included literature, fully considering the clinical situation and expert opinions, and completed the evidence. Extracted and summarized.Results:Totally 13 articles were finally included, including 5 guidelines, 3 expert consensuses, 1 evidence summary and 4 original studies, and 29 evidence-based practice evidence of enteral nutrition in patients with intra-abdominal hypertension were collected, including the monitoring timing of enteral pressure, the pressure of enteral high pressure and the way of enteral nutrition, the pressure measurement of the abdominal cavity, the setting of abdominal pressure, the temperature conditions for early start of enteral nutrition, the selection of enteral pressure, the temperature setting of enteral nutrition nine aspects such as speed and regulation of internal nutrition and abdominal compartment syndrome prevention.Conclusions:This study summarizes the best evidence of intra-abdominal pressure management and enteral nutrition therapy in patients with intra-abdominal hypertension, and provides evidence-based basis for risk management, standardizing clinical practice, and ensuring treatment safety. In the stage of evidence transformation, clinical medical staff need to comprehensively weigh the benefits and risks of early enteral nutrition, and integrate evidence in combination with clinical practical application scenarios, so as to form a standardized early enteral nutrition management plan suitable for patients with intra-abdominal hypertension.

High-quality clinical practice guidelines are of great significance for standardizing the clinical diagnosis and treatment process and improving the overall quality of health care. The Appraisal of Guidelines for Research & Evaluation InstrumentⅡ (AGREEⅡ) is one of the recognized tools for the evaluation of the quality of clinical practice guidelines. It has been translated into Chinese and is widely used in guideline formulation and quality evaluation. This article intends to take the comparatively high-quality clinical practice guidelines in the field of esophageal cancer screening in China, i.e. "Expert Consensus on Early Esophageal Cancer and Precancerous Lesion Screening in China (2019, Xinxiang)" as an example, to interpret the use of AGREEⅡ item by item, which might provide a reference for medical and health workers to better understand and use the assessment tool.