OBJECTIVE To evaluate the cost-effectiveness of iruplinalkib for ALK-positive non-small cell lung cancer （NSCLC） patients who had not previously received ALK-tyrosine kinase inhibitors （TKIs） from the perspective of the Chinese healthcare system. METHODS Based on the INSPIRE clinical trial， a three-health state partitioned survival model was developed to simulate the progression of disease， with model cycle of 3 weeks and a life-year time range of 15 years； the discount rate was 5%. For the treatment of ALK-positive advanced NSCLC， total cost， quality-adjusted life year （QALY）， and incremental cost- effectiveness ratio （ICER） were compared between iruplinalkib and crizotinib； using 1-3 times China’s per capita gross domestic product （GDP） （89 358-268 074 yuan） in 2023 as the willingness-to-pay （WTP） threshold， the cost-effectiveness of two regimens were compared. The sensitivity analysis and scenario analysis （altering the distribution of survival curves， utility values） were conducted to assess model robustness. RESULTS Compared with the crizotinib regimen， the ICER for the iruplinalkib regimen was 194 412.74 yuan/QALY， which was below the WTP threshold of three times China’s per capita GDP in 2023 yuan）. The results under the scenario of altering the survival curve distribution were consistent with the base case analysis. However， after increasing the utility value of the disease progression state， the ICER exceeded the WTP threshold， and iruplinalkib no longer had a cost-effective advantage. The results of the one-way sensitivity analysis indicated that the cost of iruplinalkib and the utility values of disease progression states had a significant impact on the ICER. The probabilistic sensitivity analysis confirmed the robustness of the base case analysis results. CONCLUSIONS From the perspective of China’s healthcare system， compared with crizotinib regimen， the therapy with iruplinalkib is cost-effective for ALK-positive NSCLC patients who have not previously received ALK-TKIs.

Objective To investigate the safety and efficacy of combined confluence microdissection or balloon dilatation followed by laparoscopic transcystic common bile duct exploration (LTCBDE) in day surgery laparoscopic cholecystectomy. Methods The clinical data of 203 patients with day surgery laparoscopic cholecystectomy combined with LTCBDE from June 2021 to June 2024 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. They were divided into an observation group (59 cases, including 42 cases of confluent microdissection and 17 cases of balloon dilatation) and a conventional group (144 cases) according to the surgical technique used. Baseline characteristics, intraoperative exploration results, operation time, postoperative recovery and complications were compared between the two groups. Results The history of preoperative cholangitis or pancreatitis (P<0.001) was more common in the observation group. And total bilirubin level was significantly higher in the observation group than in the conventional group (P=0.035). The observation group had a longer operative time (P=0.014) and higher hospitalization costs (P=0.001), but there was no difference in intraoperative bleeding and postoperative discharge time. There were no serious postoperative complications in either group. Conclusions Under the premise of strict patient screening, day surgery LTCBDE combined with confluence microdissection or balloon dilatation can effectively solve the problem of difficult choledochoscopic access, with high safety and thoroughness of exploration. Both techniques provide a feasible minimally observation solution for day surgery biliary exploration.

Objective To investigate the prevalence of scoliosis and congenital heart disease(CHD)and their correlation among children and adolescents of Drung nationality in Yunnan Province.Methods A cross-sectional survey was conducted in November 2022 among all Drung school-aged children and adolescents aged 5-18 years in Gongshan Drung and Nu Autonomous County,Yunnan Province.Visual inspection,Adams for-ward flexion test,and trunk rotation angle(ATR)measurement were comprehensively used for school prelim-inary screening of scoliosis.Individuals who tested positive in the school preliminary screening underwent fur-ther X-ray examination for auxiliary diagnosis.Cardiac auscultation and echocardiography were used for school preliminary screening of CHD.The personal information of the screening subjects,the screening results,etc.were recorded.The prevalence of scoliosis and CHD among children and adolescents of the Drung nationality and the relationship between the two diseases were statistically analyzed,and the positive predictive value of school-based scoliosis screening and its influencing factors were also analyzed.Results A total of 1 036 chil-dren and adolescents of Drung nationality were enrolled,with a mean age of(10.72±3.75)years,icluding 542 males and 494 females.A total of 45 subjects tested positive for scoliosis in the school preliminary screening,with a preliminary positive rate of 4.34%.A total of 22 cases were finally diagnosed with scoliosis,with a prevalence rate of 2.12%.Among them,21 cases were idiopathic scoliosis(accounting for 95.45%),and 1 case was congenital scoliosis(accounting for 4.55%).The prevalence rate was higher in females(2.83%)than that in males(1.48%),higher in the 10 to 18-year-old group(2.30%)than that in the 5 to<10-year-old group(1.87%),and higher in the secondary school group(2.78%)than that in the primary school group(1.78%),hut there were no statistically significant differences(P>0.05).Most idiopathic scoliosis cases were mild(Cobb angle 10° to<20°,90.48%)and classified as Lenke type Ⅴ(57.14%).Two cases of CHD were confirmed,both of which were atrial septal defects,with a prevalence rate of 0.19%.The co-occurrence rate of idiopathic scoliosis and CHD was 4.76%(1/21).The positive predictive value of school-based scoliosis pre-liminary screening was only 48.89%.When the BMI was<18.5 kg/m2,the positive predictive value was sig-nificantly higher than that for BMI≥18.5 kg/m2(P<0.05).Conclusion The prevalence rate of scoliosis a-mong adolescents of the Drung ethnic group in Yunnan Province is 2.12%,predominantly idiopathic scoliosis,with Lenke type V being the most common classification.The prevalence rate of congenital heart disease is 0.19%.BMI is a significant influencing factor for the positive predictive value of school-based scoliosis prelimi-nary screening.

Objective To analyze the risk factors of critically ill patients infected with Acinetobacter bau-mannii(AB)and carbapenem resistant Acinetobacter baumannii(CRAB).Methods From January 2022 to June 2023,the data of Intensive Care Unit(ICU)patients admitted to Second Hospital of Shanxi Medical Uni-versity in Shanxi Province were collected.According to whether they were infected with AB,the patients were divided into an observation group and a control group(98 cases each).The observation group was further di-vided into a carbapenem sensitive Acinetobacter baumannii(CSAB)group(72 cases)and a CRAB group(26 cases).Mann-Whitney U test,chi-square test and other univariate and multivariate binary Logistic regression were used to analyze the risk factors of AB and CRAB infection for critically ill patients.The prognosis was analyzed by Kaplan Meier survival analysis.Results Long stay in ICU,previous use of carbapenem drugs and high Acute Physiology and Health Evaluation(APACHE Ⅱ)score were independent risk factors for AB sus-ceptibility(P＜0.05),while the independent risk factors for CRAB susceptibility were invasive ventilation and delayed surgery(P＜0.01).In addition,CRAB infection,COVID-19 and shock was risk factors for death in critically ill patients,and invasive ventilation,indwelling drainage tube and operation could reduce the risk of death in critically ill patients(P＜0.05).Conclusion ICU stay time,APACHE Ⅱ score,previous use of car-bapenem drugs and invasive ventilation increase the risk of AB and CRAB infection in critically ill patients.In-vasive ventilation,indwelling drainage and early surgery could reduce the risk of death from AB and CRAB in-fection in critically ill patients.

Objective: To investigate the effects and mechanisms of Astragalus Polysacharin(APS) on the proliferation and metastasis of breast cancer cells by regulating miR-107 and miR-346-mediated macrophage polarization in breast cancer-derived exosomes. Methods: Forty 8-week-old female BALB/c mice were selected and breast cancer xenograft models and 4T1 transplanted tumor models were established. The mice were divided into the control group and the APS group. The APS group mice received daily intragastric administration of APS for 25 days, while the control group mice were given the same amount of normal saline. After all treatments were completed, the mice were euthanized, and tumor tissues were isolated. Western blot and flow cytometry were used to detect the expressions of proliferating cell nuclear antigen(PCNA), Ki-67, CD206, CD163, inducible nitric-oxide synthase(iNOS), and CD86. The apoptosis of single-cell suspensions in tumor tissues was analyzed. Human breast cancer cell line MDA-MB-231 was cultured and stimulated with APS, and exosomes from the cell culture medium were collected. The proliferation, migration, and invasion of cells were detected by CCK-8 assay, scratch assay, permeability chamber cell invasion assay, and qRT-PCR. Differentially expressed genes were screened by bioinformatics. Results : By measuring the expressions of molecules related to breast cancer cell proliferation and metastasis, it was shown that APS treatment reduced the expressions of proliferation-related proteins(PCNA and Ki-67) and metastasis-related proteins(Vimentin) in MDA-MB-231 xenograft tumor tissues; and the polarization of tumor-associated macrophages was observed. APS treatment of 4T1 transplanted tumor tissues could reduce the number of M2 macrophages and increase the number of M1 macrophages, resulting in a decrease in the ratio of M2/M1 macrophages and an increase in cell apoptosis in 4T1 transplanted tumor tissues. The expressions of related proteins iNOS and CD86 increased, and CD206 and CD163 decreased. After APS treatment, the exosomes produced by MDA-MB-231 reduced the polarization of M2 macrophages and affected the expressions of miR-107 and miR-346. Conclusion APS inhibits the polarization of M2 macrophages by regulating the expression of miR-107 or miR-346 in breast cancer cell-derived exosomes, ultimately inhibiting the proliferation and metastasis of breast cancer cells.

ObjectiveTo analyze and validate how Jiawei Sanpian decoction treats migraines by integrating network pharmacology, molecular docking technology, and experimental studies.MethodUsing network pharmacology, the chemical components and core target proteins of the Jiawei Sanpian decoction were analyzed. Key chemical components were docked with core targets using molecular docking, and the results were visualized. Nitroglycerin was injected into the dorsal cervical region to establish a rat migraine model. Finally, experiments were conducted to verify the effects of Jiawei Sanpian on related pathways and targets.ResultsFour notable chemical components were identified, namely, β-sitosterol, quercetin, mairin, and kaempferol. Five representative targets were identified, namely, insulin-like growth factor 1 (IGF-1), matrix metallopeptidase 2 (MMP-2), interleukin-2 (IL-2), superoxide dismutase 2 (SOD2), and inducible nitric oxide synthase (NOS2). Molecular docking results revealed that the minimum binding energies between the four chemical components and the five targets were below −5 kcal/mol, indicating favorable binding activity. Enzyme linked immunosorbent assay (ELISA) results demonstrated the efficacy of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). Real-time quantitative polymerase chain reaction (RT-qPCR) results demonstrated the effectiveness of high-dose Jiawei Sanpian decoction in treating migraine by targeting IGF-1, IL-2, MMP-2, and SOD2 (P .001). After using erastin, the therapeutic effect of Jiawei Sanpian decoction declined.ConclusionThis study provides initial insights into the complex and multilayered therapeutic mechanisms of Jiawei Sanpian decoction in treating migraine, primarily through its diverse components, targets, and pathways. These findings indicate that Jiawei Sanpian decoction may exert its effects mainly through processes linked to the mitochondrial inflammatory pathway, thereby providing therapeutic benefits for migraine.

Objective To establish female and male bovine collagen-induced arthritis(CIA)models and compare the effects of gender differences on joint and extra-articular manifestations of the CIA model.Methods The CIA model was induced by injection of bovine type Ⅱ collagen and Freund's complete adjuvant into female and male SD rats.The general condition,arthritis index,foot swelling,serum proinflammatory factors and plasminogen activator inhibitor levels,spleen index,knee and ankle joint pathologies,right rear paw bone destruction,and pulmonary interstitial lesions were evaluated.Results The arthritis index of female CIA rats was significantly higher than that of male CIA rats on day 21 after initial immunization(P＜0.05),but no significant difference was found in the degree of foot swelling between the two groups at any time point(P＞0.05).Serum tumor necrosis factor α,interleukin-1β,and the spleen index of female CIA rats were significantly higher than those of male CIA rats(P＜0.05,P＜0.001).No significant difference was found in plasminogen activator inhibitor levels(P＞0.05).The scores of inflammatory cell infiltration and synovial hyperplasia in the knee and ankle pathologies of female CIA rats were significantly higher than those of male CIA rats(P＜0.05),and cartilage damage of the knee joint and bone damage of the right rear paw of female CIA rats were significantly higher than that of male rats(P＜0.05).Both male and female CIA rats showed pulmonary interstitial inflammatory cell infiltration and mild fibrosis,but the pulmonary interstitial lesions in females were more severe than those in males.Conclusions Female and male CIA models established in SD rats have arthritis and pulmonary interstitial lesions,but the lesion degree in female CIA rats is more serious.When using CIA models for RA-related research,attention should be focused on the effect of gender differences.

Sphincter of Oddi dysfunction (SOD) refers to the abnormal physiological function of sphincter of Oddi, which causes a series of syndromes in biliary tract, pancreas and liver. At present, the related research of SOD is becoming a hot spot, but its pathogenesis is not clear. This article will review the domestic and international literatures on SOD, review the advantages and disadvantages of experimental animals such as rabbits, dogs and guinea pigs, and analyze the characteristics of drugs and surgical modeling, so as to provide references for future related model establishment.

Objective:To compare the efficacy of closed-loop target-controlled deep versus moderate neuromuscular blockade in gynecological laparoscopic surgery.Methods:This was a prospective study. Fifty American Society of Anesthesiologists Physical Status classification I or Ⅱ patients, aged 18-64 yr, with body mass index of 18-30 kg/m 2, scheduled for elective gynecological laparoscopic surgery in the General Hospital of Tianjin Medical University from March 2020 to March 2021, were allocated into 2 groups ( n=25 each) using a random number table method: closed-loop target-controlled moderate neuromuscular blockade group (group TOF) and closed-loop target-controlled deep neuromuscular blockade group (group PTC). Rocuronium was given by closed-loop target-controlled infusion in both groups. In group TOF, the target muscle relaxation was considered as train-of-four stimulation (TOF) of 1 or 2. In group PTC, the target muscle relaxation was considered as post-titanic count of 1 or 2. The score for operator′s satisfaction with muscle relaxation, grading, satisfaction rate, mean pneumo-peritoneum pressure, consumption of rocuronium, recovery index, recovery time to a TOF ratio 0.9 and time to extubation were recorded. The postoperative visual analogue scale score for abdominal pain and use of rescue analgesics were recorded, and the occurrence of complications such as shoulder pain, arm pain, nausea, vomiting and hypoxemia was also recorded within 48 h after surgery. Results:Compared with group TOF, the score for operator′s satisfaction with muscle relaxation, grading and satisfaction rate were significantly increased, the mean pneumo-peritoneum pressure was decreased, the total and average consumption of rocuronium was increased, the recovery time of a TOF ratio 0.9 was prolonged, and the postoperative visual analogue scale score for abdominal pain and usage rate of flurbiprofenate were decreased in group PTC ( P<0.05). There were no significant differences in the recovery index, tracheal extubation time or postoperative incidence of hypoxemia, shoulder pain, arm pain and nausea and vomiting between the two groups ( P>0.05). Conclusions:Compared with the closed-loop target-controlled moderate neuromuscular blockade, the closed-loop target-controlled deep neuromuscular blockade provides more satisfactory surgical conditions for gynecological laparoscopic surgery, decreases pneumoperitoneum pressure and reduces related complications, without increasing the development of postoperative adverse reactions.

Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosup-pression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P＜0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P＜0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P＜0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These find-ings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.