ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 （FGF21） overexpression against CCl₄-induced acute liver injury （ALI） and its association with silent information regulator 1/glutathione peroxidase 4 （SIRT1/GPX4） expression and ferroptosis-related markers. MethodsFemale ICR mice （8 weeks old） were randomly divided into Control， CCl₄， adeno-associated virus （AAV）-FGF21， and AAV-FGF21 + CCl₄ groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein （GFP） labeling. ALI was induced by intraperitoneal injection of CCl₄ （0.3 mL/kg）， with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes （ACSL4， PTGS2， HJV， FPN， GPX4）， FGF21， and SIRT1. Protein expression of FGF21， SIRT1， and GPX4 were determined by Western blot. Iron content， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group， the FGF21 mRNA and protein expression elevated in CCl₄ group； serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2， the iron content and MDA levels all increased （P<0.01）. The mRNA levels of SIRT1， GPX4， HJV， and FPN， the GSH level and SOD activity all decreased （P<0.05）， and the protein levels of SIRT1 and GPX4 both decreased （P<0.05）. Compared with the CCl₄ group， the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased （P<0.01）， and the liver/body ratio of mice decreased （P<0.01）. The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2， iron content and MDA level all decreased （P<0.01）， while the mRNA levels of SIRT1， GPX4， HJV， FPN， GSH level and SOD activity all increased （P<0.05）. The protein levels of SIRT1 and GPX4 both increased （P<0.05）. ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features， thereby contributing to the alleviation of CCl₄-induced ALI.

Antibody drug conjugates (ADC) have emerged as a cutting-edge technology in anti-tumor treatment, making significant strides in recent years. ADC couple a highly active small molecule toxin payload to highly specific antibodies through a linker, enabling precise targeting of tumor cells while reducing systemic toxicity, thereby expanding the therapeutic window. However, due to the complexity of ADC molecule design, its efficacy and safety are influenced by various factors. Model-informed drug development (MIDD) is a powerful tool that utilizes various mathematical models for modeling and simulation to conduct quantitative analysis, guiding drug development and decision-making. By integrating multi-faceted data and information using mathematical models, it is possible to gain insights into the complex mechanisms, pharmacokinetics, and pharmacodynamics of ADC, providing unique perspectives for optimizing ADC development processes and clinical translation decisions. This review will introduce the basic concepts of MIDD and ADC and discuss application cases of MIDD in different stages of ADC development, aiming to provide beneficial references for the advancement of ADC.

Objective To develop a hypoxia endurance testing system for aviation physiological training of pilots.Methods The hypoxia endurance testing system comprised a low-oxygen mixed gas generator,a pressurization system for low-oxygen mixed gas and a personal breathing apparatus.The low-oxygen mixed gas generator consisted of a main unit composed of an air compressor,a filter,a buffer tank,polymer membrane,a control module,sensors and regulators,wire cables,supporting hoses,etc.;the pressurization system for low-oxygen mixed gas was made up of a protective box,a cooling fan,a motor and a driver,a control module,a solenoid valve,a convergence block,a pressure gauge,etc.;the personal breating apparatus was composed of a gas cylinder,a pressure reducer,an oxygen supply regulator,etc.Forty-eight subjects were selected for hypoxia exposure tests to verify the effectiveness of the system.Results The system developed had the functions of low-oxygen gas preparation,pressurized filling and hypoxia experiment,and the experimental results indicated the acute hypoxia exposure by the system significantly caused signs and symptoms of hypoxia and weakened physiological functions.Conclusion The system developed gains advantages in high accuracy of gas volume fraction control,safety and remarkable effect of simulated hypoxia,and can be an effective tool for acute high-altitude hypoxia testing and training of pilots.[Chinese Medical Equipment Journal,2025,46(10):23-28]

OBJECTIVE: Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19. This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio (NLPR) with the severity and prognosis of COVID-19, and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states. METHODS: This was a retrospective study conducted at Wuhan Union Hospital in China. COVID-19 patients admitted between November 1, 2022 and February 1, 2023 were included. In predicting prognosis for individuals with COVID-19, new inflammatory indicators were used, and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves. Furthermore, a calculation was made to determine the cutoff value for NLPR. Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff. RESULTS: This research included 455 participants with COVID-19, with a mean age of 72 years. Several inflammatory indicators were found to be strongly correlated with prognosis, and NLPR shows the greatest predictive power. Patients with NLPR > 3.29 exhibited a mortality rate of 17.3%, which was 6.2 times higher than in patients with NLPR ≤ 3.29. Importantly, providing Xuebijing injection to patients with NLPR > 3.29 was associated with a lower risk of 60-day all-cause mortality. However, there was no discernible improvement in survival among patients with NLPR ≤ 3.29 who received Xuebijing injection. CONCLUSION NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19, and can accurately identify individuals who may benefit from Xuebijing injection. Please cite this article as: Liao M, Zhang LT, Bai LJ, Wang RY, Liu Y, Han J, Liu LH, Qi BL. Xuebijing injection reduces COVID-19 patients mortality as influenced by the neutrophil to lymphocyte platelet ratio. J Integr Med. 2025; 23(3): 282-288.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Female ; Retrospective Studies ; Aged ; Neutrophils ; COVID-19 Drug Treatment ; COVID-19/blood* ; Middle Aged ; Prognosis ; Lymphocytes ; Blood Platelets ; Platelet Count ; SARS-CoV-2 ; Aged, 80 and over ; Adult

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective To investigate the adverse pregnancy outcomes of fetuses with increased nuchal translucency(NT).Methods A total of 376 pregnant women at the Third Affiliated Hospital of Zhengzhou University from May 2023 to January 2024 were selected as research subjects,who had a diagnosis of fetal NT ≥ the 95th percentile and complete pregnancy outcomes for singleton pregnancies.The fetuses were divided into simple thickening group(n=320)and thickening with structural abnormalities group(n=56)based on NT ultrasound results.The interventional prenatal diagnosis outcomes and pregnancy outcomes of two groups were compared.Results The rate of chromosomal abnormalities and the incidence of adverse pregnancy outcomes were higher in thickening with structural abnormalities group compared to simple thickening group with statistically significant differences(P＜0.05).The overall incidence of adverse pregnancy outcomes in NT thickened fetuses was 31.65％,but after excluding chromosomal abnormalities and structural malformations,the good pregnancy outcome rate in NT thickened fetuses was 98.09％.Conclusion NT thickening is associated with adverse pregnancy outcomes in fetuses,and the risk of poor fetal outcome is further increased when NT thickening combined with structural abnormalities in early pregnancy,but the pregnancy outcome is better in fetuses with NT thickening after excluding chromosomal abnormalities and structural malformations.

In 2024, a total of 27 309 cases of medication error (ME) from 484 hospitals in 27 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. Among them, 279 (1.02%) were classified as grade A, 22 081 (80.86%) as grade B, 4 268 (15.63%) as grade C, 472 (1.73%) as grade D, 96 (0.35%) as grade E, 105 (0.38%) as grade F, 6 (0.02%) as grade H, and 2 (<0.01%) as grade I; no MEs of grade G occurred. Among the 27 030 patients involved in MEs of grade B to I, 15 124 (55.95%) were male and 11 906 (44.05%) were female; their ages were from 1 day to 104 years; 3 369 (12.46%) were children (<18 years old), 12 113 (44.81%) were young and middle-aged adults (≥18 to <60 years old), and 11 548 (42.72%) were elderly (≥60 years old). The top 3 contents of ME were wrong drug class (5 347 cases, 19.13%), wrong dosage (4 913 cases, 17.58%), and wrong administration frequency (3 429 cases, 12.27%). Among the 27 030 grade B-I MEs, the main person who triggered the event were physicians (18 703 cases, 69.19%) and pharmacists (6 343 cases, 23.47%). These MEs mainly occurred in clinics (11 009 cases, 40.73%), in hospital wards (7 393 cases, 27.35%), and in pharmacies (6 219 cases, 23.27%). The main persons who discovered the MEs were pharmacists (21 021 cases, 74.14%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8 716 cases, 26.49%), tiredness (5 755 cases, 17.49%), and inexperienced skills (4 505 cases, 13.69%). A total of 209 patients were involved in severe MEs (grade E-I), including 133 (63.64%) males and 76 (36.36%) females, aged from 21 months to 94 years, of which 42 (20.10%) were children, 75 (35.88%) were young and middle-aged adults, and 92 (44.02%) were elderly. The top 3 diseases diagnosed in severe MEs were drug poisoning (41 cases, 19.62%), diabetes (34 cases, 16.27%), and hypertension (14 cases, 6.70%); the main person who triggered the MEs were patients and their families (135 cases, 64.59%); the MEs occurred mainly in patients′ houses (116 cases, 55.50%). Drug poisoning was mainly related to accidental ingestion by children, and MEs in patients with diabetes and hypertension were often related to issues on patient compliance. Based on the data of MEs in 2024, it was proposed to establish a better medication safety culture and improve the ME reporting situation in China, pay attention to the risks of misusing external drugs for internal use, children′s accidental ingestion and insulin-related MEs, strengthen the prevention of MEs related to look-alike sound-alike drugs, pay attention to the post administration management and the compliance education of home care for patients with chronic diseases, so as to improve the medication safety of patients in China.

Acute kidney injury(AKI)is a syn-drome characterized by rapid decline in renal excre-tory function.Its pathogenesis is still unclear.Stud-ies have shown that macrophages are major play-ers in AKI inflammation,regulating tissue damage and regeneration repair.During AKI inflammation,macrophages can be activated into different func-tional phenotypes through molecular and signaling pathways,regulate different molecules and signal-ing pathways,and determine the progression of AKI.In this paper,the activation of macrophages and the molecular signaling pathways involved in the regulation of AKI in the past five years are re-viewed,and the mechanism of action of macro-phages in AKI is determined,which provides ideas for the study of macrophages as therapeutic tar-gets.

Objective:To observe the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) at different frequencies on cognitive impairment due to high-altitude hypoxia.Methods:Sixty officers and soldiers displaying cognitive impairment in a hypoxic high-altitude environment were randomly divided into 15Hz, 20Hz and 25Hz groups, each of 20. They were given rTMS at those frequencies for 30 days. Before the stimulation and after 15 and 30 days, event-related potentials, latencies of mismatched negativity (MMN) and P300 signals were recorded. The participants′ cognition was also evaluated using the Montreal Cognitive Assessment Scale (MoCA). Correlation between the electrophysiological indexes and the MoCA scores was computed.Results:After 15 days, all had shorter MMN latencies, higher total MoCA scores and better memory scores. The only significant difference among the three groups was in the average memory scores. After 15 days, MMN latency was significantly negatively correlated with the memory scores in all three groups ( r=0.44 to -0.54). Conclusions:rTMS at frequencies above 15Hz can effectively relieve cognitive impairment, especially memory dysfunction, resulting from high-altitude hypoxia.

Objective:To study the results of detection of pulmonary nodules among military flying personnel and analyze the contributors to pulmonary nodules so as to provide data for early prevention and interventions.Methods:The physical examination data of 1 465 military flying personnel was retrospectively analyzed who had received the annual health checkup and undergone chest CT examinations at Lintong Rehabilitation and Recuperation Center. They were grouped by age (<40 years and ≥40 years), flying hour (<1 000 h and ≥1 000 h) and type of personnel [pilots and air support (technical) personnel]. The detection rates of pulmonary nodules among flying personnel were compared across groups, and a multivariate Logistic regression analysis was conducted to analyze the contributing factors to pulmonary nodules.Results:Among the 1 465 military flying personnel, 212 cases (14.47%) with pulmonary nodules were detected. A total of 230 pulmonary nodules were detected, including 35 pulmonary nodules (15.22%) in the left upper lung, 42 pulmonary nodules (18.26%) in the left lower lung, 52 pulmonary nodules (22.61%) in the right upper lung, 47 pulmonary nodules (20.43%) in the right middle lung, and 54 pulmonary nodules (23.48%) in the right lower lung. The detection rate of pulmonary nodules among military flying personnel in the ≥1 000 h group was higher than in the <1 000 h group, and the difference was statistically significant ( χ2=4.14, P=0.042). More pulmonary nodules were detected among military flying personnel who smoked than among those who did not, and the difference was statistically significant ( χ2=9.34, P=0.002). Age, types of personnel, body mass index, and complications with other lung diseases made no significant difference in the detection rate of pulmonary nodules (all P>0.05). Multivariate Logistic regression analysis showed that smoking was a risk factor for pulmonary nodules ( OR=1.692, 95% CI: 1.217-2.351). Conclusions:Among military flying personnel, pulmonary nodules are more likely to occur in the right lung. Smoking is an independent risk factor for pulmonary nodules, suggesting that routine chest CT screening should be carried out during the annual physical examinations of military flying personnel in order to exercise early interventions.