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.

OBJECTIVES: To explore the therapeutic mechanism of puerarin for alleviating synovitis in rats with collagen-induced arthritis (CIA). METHODS: In a SD rat model of CIA, we tested the effects of daily gavage of puerarin at low, moderate and high doses (10, 30, and 100 mg/kg, respectively) for 3 weeks, with tripterygium glycosides (GTW, 10 mg/kg) as the positive control, on swelling in the hind limb joints regions evaluated by arthritis index scoring. Mass fraction of the liver of the rats was calculated, and pathologies in joint synovial membrane were observed with HE staining. The expressions of transforming growth factor β‑activated kinase-1 (TAK1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-Bp65 (NF‑κB p65) at the mRNA and protein levels in the synovial tissues were detected using Real-time PCR and Western blotting. RESULTS: Compared with those in the model group, the rats in GTW group and high-dose puerarin group showed significantly reduced mass fraction of the liver. Treatment with GTW and puerarin at the 3 doses all significantly alleviated plantar swelling, lowered arthritis index scores, and improved synovitis in CIA rats (P<0.05), and the effects of puerarin showed an obvious dose dependence. Both GTW and puerarin treatments significantly lowered TAK1, TLR4, and NF‑κB p65 mRNA and protein expressions in the synovium of CIA rats. CONCLUSIONS Puerarin alleviates synovium damages in CIA rats possibly by suppressing the TLR4/NF‑κB signaling pathway via downregulating TAK1 expression.
Animals ; Toll-Like Receptor 4/metabolism* ; Rats, Sprague-Dawley ; Rats ; MAP Kinase Kinase Kinases/metabolism* ; Signal Transduction/drug effects* ; Arthritis, Rheumatoid/drug therapy* ; NF-kappa B/metabolism* ; Isoflavones/therapeutic use* ; Male ; Arthritis, Experimental/drug therapy* ; Transcription Factor RelA/metabolism* ; Synovial Membrane/metabolism*

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 analyze the clinical characteristics of adverse reactions caused by dinutuximab β for the treatment of neuro-blastoma(NB)in China and to provide safety evidence for the rational use of dinutuximab β in clinical practice.Methods:Clinical data were retrospectively collected from 16 pediatric patients with NB who had been treated with dinutuximab β at Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to November 2023,and the adverse reactions caused by dinutuximab β were summarized and analyzed.Results:The male-to-female ratio was 5:3 among the 16 children with NB.The retroperitoneum was the main initial site of involvement,accounting for 75%.Thirteen(81.25%)patients had high-risk NB.The adverse reactions caused by dinutuximab β mainly included decreased hemoglobin,fever,vomiting,and diarrhea.The inci-dence of adverse reactions was highest in the first course of treatment,and the median time of adverse reactions was 2-5 days.Conclu-sion:Targeted monitoring should be carried out at an early stage during dinutuximab β administration.Adverse reactions should be de-tected and managed early to ensure the safety of medication for children.

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 address the bottlenecks in the application of wastewater biological treatment technology under space conditions,an experimental system for the biological treatment of space wastewater was constructed and its biochemical performance examined.The findings of this study will provide technical support for the biological treatment of space wastewater.Methods Based on the Membrane Aerated Biofilm Reactor(MABR)process,a biological treatment experimental system for space wastewater was constructed and conducted the continuous flow test for 77 days to investigate the performance of PVDF and PP membrane modules in the treatment of simulated air condensate.Results The results demonstrated that both membrane modules exhibited an average TOC removal rate of 90%,indicative of their effective organic matter removal capacity.In the air supply mode,the ammonia oxidation capacity was observed to be comparatively lower,whereas in the oxygen source without bubbling mode,the nitrogen oxidation rate and total nitrogen removal rate could be attained above 90%,indicating a notable degree of simultaneous nitrification and denitrification.The results demonstrated that the mode of gas supply had a significant impact on the nitrogen conversion performance.The abundance of nitrogen-converting bacteria in PP membrane module is higher than that in PVDF membrane module,indicating a better nitrogen-converting performance in PP membrane module.Conclusion The constructed wastewater biological treatment system is optimally suited for the treatment of air condensate,thereby offering a novel technical approach for space wastewater treatment.

Objective:To discuss the effect of royal jelly acid(10-HDA)on the proliferation and migration of the human colon cancer SW620 cells based on the network pharmacology,and to clarify its related molecular mechanism.Methods:The active ingredients such as 10-HDA and their corresponding targets were retrieved by using the keyword"royal jelly"from the Traditiomal Chinese Medicine Systems Pharmacology(TMSCP)Database and the Traditiomal Chinese Medicine Integrated Database(TCMID);the small molecule targets were predicted by the Swiss Target Prediction Database.The GeneCards Database and the Online Mendelian Inheritance in Man(OMIM)Database were used to obtain the targets with the keyword"Colon Cancer";the protein-protein interaction(PPI)network was constructed by using the String Database and Cytoscape 3.8.0 Software to screen the core targets;the Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were analyzed by Metascape Database;the specific ingredient 10-HDA was screened for the in vitro activity experiments.The human colon cancer SW620 cells with good growth status were divided into control group and different doses(1,5,10,15,and 20 mmol·L-1)of 10-HDA groups.The viabilities of the cells in various groups were detected by MTT method and the survival rates of the cells were calculated.The SW620 cells were divided into control group,low dose(5 mmol·L-1)of 10-HDA group,middle dose(10 mmol·L-1)of 10-HDA group,and high dose(15 mmol·L-1)of 10-HDA group;Hoechst33342 staining method was used to observe the morphology of the cells in various groups;cell scratch test was used to detect the scratch healing rates of the cells in various groups;flow cytometry was used to detect the percentages of the cells at different cell cycles in various groups;biochemical method was used to detect the activities of total antioxidant capacity(T-AOC)and superoxide dismutase(SOD)in the cells in various groups;Western blotting method was used to detect the expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),cysteine-containing aspartate proteolytic enzyme-9(Caspase-9),glycogen synthase kinase 3β(GSK3β),β-catenin,and cyclin D1 proteins in the cells in various groups.Results:Six active ingredients of royal jelly were screened out by the TCMSP Database,and 28 core targets of 10-HDA in the treatment of colon cancer were obtained.The GO function enrichment analysis mainly included the signaling pathways such as cell proliferation and apoptosis.The KEGG signaling pathway enrichment analysis included the cell cycle,prostate cancer,cell senescence,and p53 signaling pathways;the GSK3β/β-catenin signaling pathway was closely related to the cell cycle.Compared with control group,the viabilities of the cells in 5,10,15,and 20 mmol·L-110-HDA groups were decreased in a dose-dependent manner(P<0.05 or P<0.01),the numbers of apoptotic cells in different doses of 10-HDA groups were significantly increased,and the scratch healing rates of the cells were significantly decreased(P<0.05 or P<0.01);the percentages of the cells at S phase in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),the activities of T-AOC and SOD in the cells in different doses of 10-HDA groups were significantly decreased(P<0.05 or P<0.01).Compared with control group,the expression level of Bcl-2 protein in the cells in low dose of 10-HDA group was significantly decreased(P<0.01),and the expression level of GSK3β protein was significantly increased(P<0.05);compared with control group,the expression levels of Bax,Caspase-3,Caspase-9,and GSK3β proteins in the cells in middle and high doses of 10-HDA groups were significantly increased(P<0.05 or P<0.01),and the expression levels of Bcl-2,β-catenin,and CyclinD1 proteins were significantly decreased(P<0.01).Conclusion:10-HDA can significantly inhibit the proliferation and migration of the colon cancer cells and promote the apoptosis and oxidation levels of the colon cancer cells,and its mechanism may be related to the activation of the GSK3β/β-catenin signaling pathway.

Objective　To analyze the clinical features, etiological examination, laboratory examination, imaging examination, and treatment of patients with diabetes combined with Klebsiella pneumoniae liver abscess (KPLA), and to provide a reference for clinical work. Methods　The clinical data of patients with diabetes combined with KPLA in the First People's Hospital of Neijiang City from 2021 to 2022 were retrospectively analyzed. Results　Among the 12 patients with diabetes combined with KPLA, there were 8 males and 4 females, aged 47-74 years old. Five cases were combined with biliary tract diseases, 3 cases were combined with syphilis, and 2 cases were combined with hepatitis B.The main clinical manifestations included fever (12 cases), anorexia (10 cases), stomachache (6 cases), dizziness (2 cases), weakness (3 cases), cough and sputum (2 cases), disturbance of consciousness (2 cases), and visual impairment (1 case). Laboratory test results showed an increase in the percentage of neutrophils, glycosylated hemoglobin, transaminase, C-reactive protein, and procalcitonin, as well as a decrease in platelets and albumin. Abdominal CT findings were predominantly unilateral lesions, mostly found in the right liver, mainly manifested as mass, flaky, and nodular shadows. Two patients presented with invasive syndromes, 2 cases had lung abscesses, and 1 case had concomitant endophthalmitis and meningitis. The etiological examination of 12 patients with Klebsiella pneumoniae showed that they were all sensitive bacteria. After actively controlling blood glucose, effectively using antibiotics, and performing liver puncture and drainage, 11 cases improved, while 1 case was left with permanent blindness. Conclusions　The clinical features of diabetes combined with KPLA are atypical and easy to misdiagnose, thus early imaging and etiological examination should be performed. Aggressive glucose control, and selection of sensitive antimicrobial drugs based on drug sensitivity tests combined with liver abscess puncture and drainage can help to improve the prognosis.

Objective To compare the efficacy of retroperitoneal robot-assisted laparoscopic partial nephrectomy(RALPN)in the treatment of ventral and dorsal renal tumor.Methods The clinical data of 131 patients with renal tumor who underwent retroperitoneal RALPN at our hospital during Jan.2021 and Feb.2024 were retrospectively analyzed.The patients were divided into the ventral renal tumor group(n=35)and dorsal renal tumor group(n=96)according to preoperative images.Perioperative outcomes and prognosis were compared between the two groups.Results All 131 surgeries were successfully completed without conversion to open surgery or abdominal organ injury.There were no significant differences in warm ischemia time[median(interquartile range,IQR):20(16.75)min vs.22(IQR:15.25)min],operation time[57.0(IQR:29.5)min vs.58.5(IQR:39.75)min],estimated intraoperative blood loss[50(IQR:80)mL vs.50(IQR:80)mL],proportion of patients with intraoperative blood transfusion(0 vs.2.1％),proportion of patients using four arms during operation(42.9％vs.37.5％),postoperative reduction of hemoglobin(Hb)[(-12.9±9.0)g/L vs.(-11.5±9.4)g/L],reduction of estimated glomerular filtration rate(eGFR)[(-3.8±12.4)mL/min vs.(-7.0±13.6)mL/min],postoperative hospital stay[4(IQR:0)d vs.4(IQR:2)d],and proportion of meeting"Trifecta"criteria(94.3％vs.86.5％,P＞0.05).During the median follow-up of 9.8(5.5,24.0)months,no death occurred,and no recurrence or metastasis were observed except that bone metastasis occurred in 1 patient in the dorsal renal tumor group.Conclusion Both ventral and dorsal renal tumors can be treated with retroperitoneal RALPN,and the surgical outcomes of both are comparable.

Acromioclavicular joint dislocation is a common clinical condition in shoulder injuries, causing shoulder pain, swelling, and tenderness, and leading to limitations in abduction, elevation, forward flexion, and extension of the upper limb, which severely affects the patient′s daily life. Rockwood type ⅢB to type Ⅵ acromioclavicular joint dislocations, involving coracoclavicular ligament rupture, often require surgical treatment. Coracoclavicular fixation or ligament reconstruction, by reconstructing the coracoclavicular ligament, restores the vertical stability of the acromioclavicular joint and is more in line with the anatomical structure of the joint, which has been widely accepted by clinical physicians and patients. However, in recent years, there have been reports questioning its adequacy in horizontal stability. This article aims to review the treatment of acromioclavicular joint dislocations with coracoclavicular fixation and coracoclavicular ligament reconstruction and to discuss the future prospects of this approach.