OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

OBJECTIVE To evaluate the cost-effectiveness of tislelizumab combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. METHODS The data of RATIONALE-305 study and related literature were used to establish a partitioned survival model from the perspective of China’s health system. The cycle was 3 weeks， the simulation time was set as 10 years， and the discount rate was 5%. The quality-adjusted life years （QALYs） were used as the health outcome indicator to evaluate the cost-effectiveness of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， and one-way sensitivity analysis and probabilistic sensitivity analysis were also conducted. RESULTS The base analysis showed that the patients received more 0.268 QALYs with tislelizumab plus chemotherapy， compared with placebo plus chemotherapy， but the cost increased by 70 404.81 yuan with an incremental cost- effectiveness ratio （ICER） of 262 431.62 yuan/QALY， which was less than three times China’s gross domestic product （GDP） per capita in 2023 as the willingness-to-pay （WTP） threshold （268 074 yuan/QALY）. One-way sensitivity analysis showed that the efficacy value of progress free survive and the price of tislelizumab had a greater impact on the ICER value. The results of probability sensitivity analysis showed that when the WTP threshold was 3 times China’s GDP per capita in 2023， the probability of tislelizumab being cost-effective was 53.3%. CONCLUSIONS When the WTP threshold is 3 times China’s GDP per capita in 2023， tislelizumab plus chemotherapy is cost-effective for first-line treatment of locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma， compared with placebo plus chemotherapy.

Objective To understand the readiness of gynecological wards in conducting the evidence-based practice for the prevention and management of urinary retention after cervical cancer radical resection,and to analyze the influencing factors.Methods The 190 nursing staffs in the gynecological oncology wards of this hospital in June 2020 were selected as the study subjects.The assessment of readiness for evidence-based nursing practice (CREBNA) and general information questionnaire were used to conduct the questionnaire survey,single factor and multiple factor stepwise regression to analyze the influencing factors.Results The score of CREBNA was (135.94±17.83) points,the evidence subscale was (52.41±7.88) points,the organi-zational environment subscale was (40.58±5.01) points and the promoting factors subscale was (42.67±6.24) points.The results of univariate analysis showed that the total score of CREBNA was related to the ed-ucational background,professional title,position,scientific research experience,understand degree on evidence-based and necessity of conducting evidence-based (P<0.05).The multiple stepwise regression analysis showed that the understanding degree on the evidenced-base and necessity of conducting evidence-based were the influencing factors of CREBNA scale (P<0.05).Conclusion The readiness of the evidence-based nursing practice in this study is good and has good feasibility.

Objective To investigate the morphological characteristics of bone marrow in RUNX1-RUNX1T1 fusion gene-positive AML.Methods From January 2017 to January 2023,20 cases of RUNX1-RUNX1T1 fusion gene-positive AML patients newly diagnosed in this hospital were selected as group A,20 cases of AML patients without fusion gene were selected as group B,and 24 cases of PML-RARA fusion gene-positive AML patients were selected as group C.Results of bone marrow morphology,immunology,cytogenet-ics and molecular biology were analyzed retrospectively.The morphological characteristics in similar cases combined with domestic and foreign literature were summarized.Results The number of promyelocytes in group A increased in different degrees,the difference was statistically significant compared with group B(P＜0.05),and the difference was also statistically significant compared with group C(P＜0.001).In group A,some promyelocytes had abnormal morphology,and the mRNA level of fusion gene was positively correlated with the number of promyelocytes(r=0.478,P=0.039).Patients with expressions of CD56,CD19 and c-Kit mutation in group A was much more than that in group B(P＜0.05).No significant difference was detected in remission rate after the first course of chemotherapy between group A and group B(P＞0.05).Besides,the simultaneous expression of CD56 and CD19 in group A was easy to accompany the loss of sex chromosome.Conclusion AML with positive RUNX1-RUNX1T1 fusion gene could be identified with bone marrow mor-phology,immunology,cytogenetics and molecular biology.Granulocyte in the bone marrow is prone to differ-ent degrees of pathological hematopoiesis with great variability.The increased number and abnormal morphol-ogy of promyelocytes in bone marrow may be one of the morphologic features of AML with positive RUNX1-RUNX1T1 fusion gene.

Objective:To investigate the epidemiological characteristics of lower extremity deep vein thrombosis (DVT) in patients with femoral fracture.Methods:Retrospectively analyzed were the data of 2,571 patients with femoral fracture who had been treated at the Third Hospital of Hebei Medical University from January 2019 to December 2019. There were 1,079 males and 1,492 females, aged from 14 to 96 years (average, 67.1 years). There were 1,158 femoral neck fractures, 951 femoral intertrochanteric fractures, 309 femoral shaft fractures, and 153 femoral condylar fractures. 2,414 patients were treated surgically while 157 patients non-surgically. Color Doppler ultrasonography of both lower extremities was performed to determine the occurrence of DVT before operation and every week after operation for patients undergoing surgical treatment, and within 48 hours after admission and every week during hospitalization for those undergoing non-surgical treatment. The incidence and location of DVT were recorded for different femoral fractures.Results:The incidence of DVT in this cohort was 35.5%(913/2,517), that of proximal DVT 5.3%(135/2,571), and that of distal DVT 30.3% (778/2,571). In patients with femoral neck fracture, femoral intertrochanteric fracture, femoral shaft fracture and femoral condylar fracture, the incidence of DVT was respectively 28.8% (334/1,158), 44.7% (425/951), 30.7% (95/309) and 38.6% (59/153), the incidence of proximal DVT was respectively 2.7% (31/1,158), 5.6%(53/951), 9.7% (30/309) and 13.7% (21/153), and the incidence of distal DVT was respectively 26.2% (303/1,158), 39.1% (372/951), 21.0% (65/309) and 24.8%(38/153). The incidence of DVT in the femoral vein and above, popliteal vein, tibiofibular vein and intermuscular vein in this cohort was respectively 2.3%(60/2,571), 2.9%(75/2,571), 6.4%(165/2,571) and 23.8%(613/2,571).Conclusions:The incidence of DVT may be high in patients with femoral fracture, and the proximal DVT with a high risk of pulmonary embolism may occur more in patients with femoral condylar fracture.

OBJECT IVE To develop a rapid health technology assessment （rHTA）methodology of drugs based on evidence integration and value judgment ，which is suitable for China ’s national conditions. METHODS The literature review was adopted to study health technology assessment （HTA）and multi-criteria decision analysis （MCDA），and then rHTA method based on China ’s condition was formulated preliminarily with anti-tumor drugs ；the method of rHTA was demonstrated by expert consultation ； finally，the feasibility of rHTA was preliminarily verified taking the drugs for the treatment of non-small cell lung cancer as an example. RESULTS Established rHTA method combined the theory and principles of HTA and MCDA ：HTA method was used to guide the collection and synthesis of literature and real-world evidence ，while MCDA made the value measurements of achievable evidences by various stakeholders from different views ；it established the working process ，evaluation dimensions ，evaluation indicators and scoring system of rHTA. The feasibility of this method was verified by the drug example of treating non-small cell lung cancer. CONCLUSIONS A set of drug-driven rHTA methodology guidance based on HTA and MCDA is established. It can quickly collect and integrate evidence ，and provide evidence support for decision makers in a short time.

OBJECTIVE To investigate the treatment plan for az treonam-resistant metallo- β-lactamase（MBL）-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients. METHODS The clinical data of aztreonam-resistant MBL-producing Klebsiella pneumoniae caused intra-abdominal infection of an infant after liver transplantation were retrospectively analyzed. Abdominal infection occurred after operation. The pathogenic bacterium was MBL-producing K. pneumoniae . The drug sensitivity results showed that the infant was resistant to aztreonam. Based on the results of sensitivity test ，polymyxin B combined with tigecycline were selected as initial regimen. The treatment effect was poor ，with recurrent disease and shock spots. The clinical pharmacist assisted the clinician to formulate treatment regimen of ceftazidime avibactam 0.5 g，q8 h combined with aztreonam 0.18 g，q6 h. Relevant domestic and foreign literature were reviewed ，and the treatment plan of MBL-producing Enterobacteriaceae infection after solid organ transplantation was summarized. RESULTS & CONCLUSIONS The infant was finally cured and discharged with ceftazidime avibatan combined and aztreonam. Several foreign literature reported that ceftazidime avibactam combined with aztreonam could effectively treat the infection caused by aztreonam-resistant MBL-producing Enterobacteriaceae infection in patients with organ transplantation. It is expected to be an effective treatment for aztreonam-resistant MBL-producing Enterobacteriaceae infection in pediatric solid organ transplant recipients.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People′s Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m²·d), which was gradually adjusted to reach a blood concentration of 5-10 μg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

Objective To investigate the relationship between the expression of NOD-like receptor protein 3 (NLRP3) inflammasome in colonic mucosal tissues of ulcerative colitis (UC) patients and UC mice model and the activity of UC.Methods From December 2016 to January 2018,at Department of Gastroenterology,the First Affiliated Hospital of Zhejiang Traditional Chinese Medicine University,60 patients with UC were recruited,of which 15 cases at remission phase,15 cases at mild activity phase,and 15 cases at moderate activity phase,and 15 cases at severe activity phase;and 15 healthy subjects were selected as healthy control group.UC mice models were established by dextran sulfate sodium (DSS).Forty-eight BALB/c mice were divided into 2.5％ DSS group,5.0％ DSS group and 7.5％ DSS group and control group.The colon tissues of UC patients and UC mice models were pathologically scored.The expression of NLRP3,cysteinyl aspartate specific proteinase 1 (caspase-1) and apoptosis-associated speck-like protein containing CARD (ASC)at mRNA level in colon tissues of UC patients and UC mice models were determined by real time fluorescence quantitative polymerase chain reaction (PCR).The expression of NLRP3,caspase-1 and ASC at protein level in colon tissues of UC patients and UC mice models were detected by Western blotting.One-way analysis of variance and SNK-t test were performed for statistical analysis.Results The histopathological scores of colon tissues of UC patients at remission phase,at mild activity phase,at moderate activity phase,at severe activity phase and healthy controls were 2.37 ± 0.46,4.84 ± 1.29,6.82 ± 0.96,9.42 ± 1.13 and 1.23 ± 0.55,respectively;the differences were statistically significant (F =67.68,P ＜ 0.01).The higher the degree of inflammation,the higher the pathological score,and the differences were statistically significant (all P ＜ 0.05).The pathological scores of colon tissues of mice in the 2.5％ DSS group,5.0％ DSS group and 7.5％ DSS group were 4.54±0.74,6.02± 1.00 and 8.43 ± 1.46,respectively;the higher the dose of DSS,the higher the pathological score,and the differences were statistically significant (all P ＜ 0.05).The expression of NLRP3 at mRNA level of UC at remission phase,mild activity phase,moderate activity phase,severe activity phase and healthy controls were 1.15 ±0.10,1.49 ±0.13,2.00±0.25,2.05 ±0.33 and 0.61 ±0.09,respectively;the expression ofcaspase-1 at mRNA level were 1.13 ±0.08,1.51 ±0.19,2.10 ±0.23,2.88 ±0.33 and 0.61 ±0.11,respectively;the expression of ASC at mRNA level were 1.12 ± 0.08,1.88 ± 0.33,2.53 ± 0.22,3.20 ± 0.24 and 0.59 ± 0.12,respectively;the differences between groups were statistically significant (F =108.43,63.25 and 105.25,all P ＜ 0.01).The higher the degree of inflammation,the higher the mRNAexpression levels of NLRP3,caspase-1 and ASC,and the differences were statistically significant (all P ＜0.01).The higher the dose of DSS,the higher the protein expression levels of NLRP3,caspase-1 and ASC at mRNA level.The higher the degree of inflammation,the higher expression of NLRP3,caspase-1 and ASC in colon tissues of UC patients.The higher dose of DSS,the higher the protein expression levels of NLRP3,caspase-1 and ASC in colon tissues of mice.Conclusions The expression level of NLRP3 inflammasome is different in different stages of UC,the higher degree of inflammatory activity,the higher the expressie level.It is helpful to evaluate the activity of UC by detecting the expression level of NLRP3 inflammasome.