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 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.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

Based on the results of the National Drug Sampling and Inspection Programme,we summarized the history,the standard collection,the production enterprises and the dosage form specifications,the quality standard study,the pharmacological and pharmacodynamic study,and the clinical application study of Wuwei Qingzhuo preparation of Mongolian medicine and Shiliu Jianwei preparation of Zang medicine,to provide the basis for improved quality standards for both preparations.The development of these two preparations was searched and analyzed through literature.The available information shows that there is very little research on the two preparations and insufficient pharmacological experimental and clinical experimental data.The two preparations are basically the same in prescription and efficacy.However,the quality standards are very different,which are not conducive to the quality control of the two and their related dosage forms.And it is suggested that the Chinese Pharmacopoeia should take the situation of this category into comprehensive consideration,and unify the quality standards of the two preparations.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

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.

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.

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

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