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 From the perspective of China’s health system， to evaluate the economic efficiency of Irinotecan liposome+fluorouracil+calcium folinate+oxaliplatin（NALIRIFOX regimen） versus paclitaxel （albumin-bound） combined with gemcitabine （AG regimen） in the first-line treatment of metastatic pancreatic cancer. METHODS A dynamic Markov model was constructed based on the data from the NAPOLI 3 clinical trial， with a cycle period of 28 days and a simulation time limit of 5 years. Incremental cost-effectiveness ratio （ICER） and quality-adjusted life year （QALY） were used as the model output indicators. The willingness-to-pay （WTP） threshold was set at three times China’s 2024 per capita gross domestic product （GDP）， and a discount rate of 5% was adopted. A cost-utility analysis was conducted to analyze the economic efficiency of the NALIRIFOX regimen compared to the AG regimen. Univariate sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the robustness of the model results， and scenario analysis was conducted by reducing the cost of irinotecan liposome by 60% and 70%. RESULTS The base-case analysis showed that the ICER of the NALIRIFOX regimen was 854 669.96 yuan/QALY compared to the AG regimen， which was greater than the WTP threshold （287 247 yuan/QALY）， indicating that the NALIRIFOX regimen was not economically efficient. The univariate sensitivity analysis results indicated that the discount rate， the cost of irinotecan liposome， the utility value of the progression-free survival state， and the utility value of the disease progression state had a significant impact on the ICER. The probabilistic sensitivity analysis results showed that under the WTP threshold of this study， the NALIRIFOX regimen was not economically efficient compared with the AG regimen. The scenario analysis results indicated that when the price was reduced by 70%， the probability of the NALIRIFOX regimen being economically efficient compared with the AG regimen was 9.60%. CONCLUSIONS From the perspective of China’s health system， when the WTP threshold is set at three times China’s 2024 per capita GDP， the NALIRIFOX regimen is not economically efficient in the first-line treatment of metastatic pancreatic cancer， compared with the AG regimen.

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.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease

Objective:To explore the effects of Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy on Traditional Chinese Medicine (TCM) syndromes scores, cellular immunity and coagulation-fibrinolysis function in patients with primary hepatic carcinoma of spleen-deficiency syndrome.Methods:Prospective cohort study. A total of 85 patients with primary hepatic carcinoma of spleen-deficiency syndrome who met the inclusion criteria in the hospital between March 2018 and March 2021 were divided into 42 cases in control group and 43 cases in observation group according to the random number table method. The control group was given conventional western medicine chemotherapy, and the observation group was given Jianpi Huaji Fuzheng Decoction on the basis of the control group. Both groups were treated for 3 months. Before and after treatment, the TCM syndromes were scored. The levels of CD4 + and CD8 + were detected by flow cytometry with indirect immunofluorescence, and the ratio of CD4 +/CD8 + was calculated. The plasma prothrombin time (PT), fibrinogen (Fg) and coagulation factor Ⅶ (CFⅦ) were detected by automatic blood coagulation analyzer. The toxic and side effects of chemotherapy during treatment were recorded and the clinical efficacy was evaluated. Results:The total effective rate of syndrome efficacy was 95.35% (41/43) in observation group and 78.57% (33/42) in control group ( χ2=3.92, P=0.047). After treatment, the scores of flank pain, lumps, fatigue and jaundice and total score in observation group were significantly lower than those in the control group ( t=2.60, 2.64, 2.85, 2.91, 3.79, P<0.01). The level of CD4 + [(37.68±3.72)% vs. (35.92±3.61)%, t=2.21] and CD4 +/CD8 + [(1.44±0.22) vs. (1.31±0.23), t=2.66] in observation group were significantly higher than those in the control group ( P<0.05), while the level of CD8 + [(26.20±2.72)% vs. (27.44±2.16)%, t=2.32] was significantly lower than that of the control group ( P<0.05). The levels of Fg [(3.11±0.85) g/L vs. (2.74±0.72) g/L, t=2.16] and CFⅦ [(1.76±0.44) mg/L vs. (1.58±0.37) mg/L, t=2.04] were significantly higher than those in the control group ( P<0.05). PT [(14.65±2.72) s vs. (15.91±3.03) s, t=2.02] was significantly shorter than that of the control group ( P<0.05). During treatment, the incidence rate of toxic and side effects of chemotherapy was 11.63% (5/43) in observation group and that in control group was 30.95% (13/42) ( χ2=4.75, P=0.029). Conclusion:Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy can improve the clinical symptoms, promote the recovery of cellular immune function and coagulation-fibrinolysis function, reduce the incidence rates of toxic and side effects of chemotherapy, and enhance the clinical efficacy of patients with primary hepatic carcinoma.

AIM: To establish an ultra high performance liquid chromatography (UPLC) method for the determination of micafungin in plasma of critically ill patients. And to establish a model for estimating the area under the concentration-time curve (AUC) of micafungin by limited sampling strategy. METHODS: Patients with severe infection were administrated with micafungin once a day, 1 h for each infusion. The blood samples were collected before administration and 1, 2, 4, 8, 12, 24 h after administration and were measured by UPLC. The pharmacokinetic parameters were calculated by Phoenix winnonlin 6.4, and the drug concentrations at 2-4 blood collection points were analyzed with SPSS 22.0 to establish limited sampling models. RESULTS: The calibration curve was linear over a concentration range of 1.0 to 50 μg/mL (r

Objective To detect the expression of EIF5A2 in hepatocellular carcinoma(HCC) and to explore its relation with clinicopathological characters and prognosis of HCC patients. Methods The expression of EIF5A2 mRNA and protein in 12 pairs of fresh HCC and corresponding non-tumor tissues adjacent to the cancer was examined by qRT-PCR and Western blot. The expression level of EIF5A2 in 284 pairs of HCC and adjacent non-tumor tissues was detected by IHC staining. Then we analyzed between EIF5A2 expression and clinical pathological parameters and prognosis of HCC patients. Results The relative expression levels of EIF5A2 mRNA and protein in fresh HCC tissues were significantly higher than those in the corresponding adjacent non-tumor tissues (t=5.305, P=0.0003; t=10.120, P < 0.001); EIF5A2 expression in 284 HCC tissues was significantly higher than that in the corresponding adjacent non-tumor tissues (z=-12.186, P < 0.001). The expression of EIF5A2 was significantly correlated with tumor size (χ²=13.079, P < 0.001), tumor multiplicity (χ²=4.589, P=0.032) and differentiation degree (χ²=4.844, P=0.028). The 3- and 5-year overall survival time and disease-free survival time of the patients with high expression of EIF5A2 were significantly shorter than those with low expression of EIF5A2 (P < 0.001). EIF5A2 was an independent prognostic factor affecting the 3- and 5-year overall survival time and disease-free survival time of HCC patients (P < 0.05). Conclusion The up-regulation of EIF5A2 expression may be related with the occurrence and development of hepatocellular carcinoma. The high expression of EIF5A2 is an independent influence factor for poor prognosis and EIF5A2 can be used as a potential molecular marker for predicting the prognosis of HCC patients.

Objective:To detect the expression of Myc-induced nuclear antigen 53 (Mina53) and liver tissue >5 cm from the edge of the tumor (LTM5), and analyze its relationship with tumorigenesis, clinicopathological characteristics, and patient survival and prognosis in hepatocellular carcinoma (HCC).Methods:The expression levels of Mina53 mRNA and protein in 18 pairs of fresh HCC and LTM5 were assessed by qRT-PCR and Western blot, respectively. The expression of Mina53 in 284 pairs of HCC and LTM5 sample was determined by immunohistochemistry. Paired-sample t-test was used for the comparison of measurement data among groups, and heterogeneity of variance was tested using Wilcoxon rank-sum test. χ2 test was used for the comparison of measurement data among groups. Kaplan-Meier method and log-rank test were used for survival analysis. Cox regression model was used for single factor and multi factor analysis. Results:The relative expression levels of Mina53 mRNA and protein in 18 fresh HCC tissues were significantly higher than those in LTM5 tissues (mRNA: -4.41 ± 1.48 and -5.93 ± 1.65, t = 3.100, P = 0.007; protein: 1.12 ± 0.29 and 0.46 ± 0.21, t = 10.616, P < 0.001). The relative expression level of Mina53 in 284 HCC tissues was higher than that of LTM5 ( z = -18.739, P < 0.001). The expression level of Mina53 was associated with tumor size ( χ2 = 5.474, P = 0.019), vascular invasion ( χ2 = 8.965, P = 0.003), pathological grade ( χ2 = 12.006, P = 0.002), and TNM stage ( χ2 = 16.686, P < 0.001). The overall postoperative survival time and disease-free survival time of patients with high expression of Mina53 (28.5 months and 22.7 months, respectively) were shorter than those with low expression (33.0 months and 31.8 months, respectively) ( P < 0.05) in HCC. Cox multivariate regression analysis showed that Mina53 and multiple tumors were independent prognostic factors affecting the overall postoperative survival time and disease-free survival time of HCC patients ( P < 0.05). Conclusion:Mina53 may play an important role in the occurrence of HCC and participate in the process of tumor growth as well as invasion and metastasis. The high expression of Mina53 signifies that the patient has a poor prognosis and thus can be used as a potential marker for judging the prognosis of HCC patients.

Objective: To understand the epidemic trend of tobacco use among junior middle school students in Shunyi District of Beijing in recent 5 years, and to provide scientific basis for formulating adolescent tobacco control strategies and intervention measures. Methods: The two stage sampling method was used to survey 3 junior middle school schools randomly selected from Shunyi District, Beijing, in November 2013, December 2015 and November 2017. The number of students surveyed each year was 1 520, 1 404 and 1 467 respectively. Results: A total of 4 500 questionnaires were distributed and 4 391 questionnaires were valid, with an effective rate of 97.6%. The current smoking rate and the attempting smoking rate in Shunyi District junior high school students increased substantially, the difference was statistically significant(χ2=9.15, 11.54, P<0.01). The exposure rate of second-hand smoke among junior high school students in Shunyi District is increasing year by year. The current smoking rate and the attempting smoking rate of second-hand smoke at home and in public places were higher than those of non-exposed ones. The differences in the current smoking rates of junior high school students (χ2=25.86, 37.61, P<0.01) and the attempting smoking rate (χ2=49.51, 63-86, P<0.01) were statistically significant. The influence of Shunyi District junior high school students through different tobacco information access channels on the current smoking rate of junior high school students increased year by year. Different tobacco information access channels have significant difference in the influence of the junior middle school students’ attempting smoking rate(P<0.05). Conclusion The overall tobacco use of junior high school students in Shunyi District of Beijing is increasing by year. The exposure of second-hand smoke is not optimistic, and the supervision of tobacco information acquisition channels is urgent to be strengthened.

This article reviews studies on the heredity of personality disorders and family environment factors from the population-based studies, and summarizes the interaction between genetic factors and environmental factors. Studies have shown that there is a genetic basis for personality disorders, including family studies, twin studies, and neurophysiological studies. In addition, environmental factors, including social psychological factors, also play an important role in the development of personality disorder. In sum, the occurrence of personality disorder is the result of interactions between genetic factors and environmental factors. This paper snmmarizes sresearch on personality disorders, and investigates the role of interaction between genetic and environmental factors in the development of personality disorders. Such evidence has implications for effective prevention and intervention of personality disorders.