OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

OBJECTIVE To investigate the ameliorative effects and mechanism of Sanwei ganlu on hepatic fibrosis in rats. METHODS The rats were randomly divided into normal group， model group， silibinin group （positive control， 50 mg/kg）， and Sanwei ganlu low-dose， medium-dose， and high-dose groups （80， 250， 800 mg/kg）. Except for normal group， hepatic fibrosis rat models were established by intraperitoneal injection of CCl4 in the other groups of rats. Starting from the 6th week of modeling administration， they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week experiment， liver and spleen indexes of rats were calculated； the pathological structure and fibrosis changes of liver tissue were observed by HE， Masson and Sirus Red staining. The contents of alanine transaminase （ALT）， aspartate transaminase （AST）， procollagen type Ⅲ （PC Ⅲ）， collagen type Ⅳ （COL-Ⅳ）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and IL-1β in serum， and hyaluronic acid （HA） and laminin （LN） in liver tissue were all detected. RESULTS Compared with the model group， the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group； the contents of ALT， AST， PC Ⅲ， COL-Ⅳ， IL-6， TNF-α and IL-1β in serum as well as the contents of HA and LN in liver tissue significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS Sanwei ganlu can alleviate the progression of hepatic fibrosis in rats， possibly by inhibiting the synthesis of collagen fiber， reducing transaminase content， down-regulating the levels of HA， LN， PC Ⅲ and COL-Ⅳ， and reducing the inflammatory response.

OBJECTIVE To analyze the use of children’s drugs in public medical institutions in the Inner Mongolia Autonomous Region， and provide some reference for the rational use of children’s drugs and the improvement of children’s drug list in the whole region. METHODS The generic names， specifications， and dosage forms of children’s drugs were collected from all levels of public medical institutions in the Inner Mongolia Autonomous Region in 2023. The method of defined daily dose （DDD） and ranking ratio （B/A） were used to explore the frequency of drug use， daily average cost and cost-effectiveness of children’s drugs in this region， and the dosage forms， category， and drug use convergence of children’s drugs in medical institutions in the whole region. RESULTS In 2023， 1 751 public medical and health institutions in Inner Mongolia Autonomous Region were equipped with 267 kinds of children’s drugs， including 12 drug categories. The main dosage forms were granules， oral solutions， and syrups. The drugs that were frequently used in medical institutions at all levels were mainly antipyretic， analgesic， anti-inflammatory drugs （mostly Chinese patent medicines）， and respiratory drugs. The daily average cost of children’s drugs with the highest DDDs in tertiary， secondary， and primary public medical institutions was low， and the B/A value of most drugs with higher DDDs was around 1. However， the B/A value of some drugs was high， which may lead to overuse. The drug use convergence between primary public medical institutions and secondary/tertiary public medical institutions was less than 50%. CONCLUSIONS The types of drugs involved in children’s drugs in Inner Mongolia Autonomous Region are comprehensive and the social and economic benefits are in good synchronization， but the dosage form is single and there are few special rules and dosage forms for children. The proportions of Chinese patent medicines in primary and secondary public medical institutions are high， and the risk of drug use should be paid attention. The cohesion between children’s drugs in primary public medical institutions and higher public medical institutions is slightly poor.

Objective:To investigate the effect of low density lipoprotein cholesterol (LDL-C) on the progression of retinal arteriosclerosis by using a deep learning model.Methods:A cohort study was performed.Data of 1 928 individuals who underwent the medical examination at Beijing Yijiandian Clinic between January 2016 and August 2023 were reviewed, including baseline demographics, physical examination, serological test and fundus photography.Retinal arteriosclerosis was identified using a deep learning model.Five groups were divided according to LDL-C levels, including 389 subjects in group 1 (0.64-1.90 mmol/L), 387 subjects in group 2 (1.91-2.26 mmol/L), 384 subjects in group 3 (2.27-2.57 mmol/L), 385 subjects in group 4 (2.58-2.95 mmol/L), and 383 subjects in group 5 (2.96-6.06 mmol/L).The association between LDL-C levels and progression of retinal arteriosclerosis and the dose-response relationship were analyzed by logistic regression analysis and restricted cubic spline (RCS) regression model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2021PHB058-001).Written informed consent was obtained from each subject.Results:The incidence of retinal arteriosclerosis progression was 22.10% (426/1 928) during the mean follow-up (66.84±6.58) months.The proportions of fundus progression in groups 1, 2, 3, 4, and 5 were 15.68%(61/389), 21.71%(84/387), 21.35%(82/384), 25.71%(99/385), and 26.11%(100/383), respectively, with statistical significant differences among them ( χ2=15.97, P=0.003).Using group 1 as a reference, LDL-C 2.58-2.95 mmol/L was an independent risk factor for progression of retinal arteriosclerosis ( OR=1.52, 95% CI: 1.04-2.22), and RCS analysis showed an " L" shaped association.The effect of LDL-C on retinal arteriosclerosis showed a threshold effect, with the risk of retinal arteriosclerosis progression increasing with increasing LDL-C when LDL-C was <2.34 mmol/L ( OR=1.97, 95% CI: 1.10-3.62), and stabilizing when LDL-C was ≥2.34 mmol/L. Conclusions:LDL-C has a threshold effect on the impact of retinal arteriosclerosis progression, and the threshold is 2.34 mmol/L.

Objective:To investigate the effect of S100A10 macrophage-mediated inflammation and migration.Methods:C57BL/6J mouse model of S100A10-KO,and RAW264.7 cell line of S100A10-KO were established.Taking mice's peritoneal macro-phages(PMs)and bone marrow macrophages(BMDMs),resuscitating RAW264.7 cell lines,and collecting cells.qRT-PCR was used to detect the effect of S100A10 knockout on the secretion of inflammatory factors in macrophages;wound healing assay and Transwell assay were used to detect the effect of S100A10 knockout on macrophage migration;CCK8 kit was used to detect the effect of S100A10 knockout on the proliferation of RAW264.7 cells;qRT-PCR and Western blot were used to detect the expressions of matrix metallopro-teinase 9(MMP9)and non-muscle myosin heavy chain 9(MYH9).Results:After S100A10 knockout,the inflammatory factors IL-6,IL-1β and MCP-1 levels(P<0.05)secreted by RAW264.7,PMs and BMDMs were excreted decreased;cell scratches and Transwell showed that S100A10 knockout inhibited macrophage migration;CCK8 experiments showed that the proliferation capacity of macro-phages weakened after S100A10 knockout;qRT-PCR and Western blot experiments showed that the migration-related proteins MMP9 and MYH9 decreased after S100A10 knockout.Conclusion:S100A10 knockout decreases the secretion of inflammatory factors by macrophages and attenuated the migration and proliferation of macrophages.

Objective:To estimate and analyze the levels of occupational exposure of aircrews in China, and to provide scientific basis for strengthening occupational health management.Methods:Through the FlightAware website, the flight data were collected of a total of 104 routes flying between airports with large passenger volume in China. Four kinds of cosmic radiation dose estimation programs CARI, SIEVERT, PCAIRE, and JISCARD-EX were compared and analyzed from the aspects of covering the number of airports in China, program user experience and example calculation of airline effective dose. Based on route logs, CARI-7A was applied to estimate the levels of occupational exposure of Chinese aircrews to cosmic radiation.Results:The difference in the effective doses calculated by use of these four cosmic radiation dose estimation programs for the routes with different solar activity levels was statistically significant ( M=7.52-180.98, P<0.05). The annual effective dose estimated by PCAIRE for 68 routes from 2014 to 2021 was significantly higher than that estimated by CARI-7A ( Z=2.52, P<0.05). Based on CARI-7A, the annual effective doses from cosmic radiation to aircrews in China from 2014 to 2021 were estimated, being 1.26 (0.57-2.35) mSv for flight attendants and 1.03 (0.47-1.92) mSv for pilots. The effective dose from cosmic radiation to aircrews on a single flight on some high-frequency routes in China ranged from 0.57 to 6.88 μSv. Conclusions:The level of occupational exposure of Chinese aircrews to cosmic radiation meets the requirements of national standards, but is higher than that of occupational exposure from medical and industrial applications of radiation, so it is still necessary to further strengthen the mamagememt of occupational exposure and occupational health of aircrews.

Objective:To develop and validate a liquid chromatography-tandem mass spectrometry method for determining levofloxacin in plasma sample from pediatric patients.Method:This is a prospective, observational study. The clinical residual plasma samples from healthy individuals for physical examination in Children's Hospital Affiliated to Zhengzhou University were collected as blank matrix. Plasma samples from five pediatric patients who did not receive levofloxacin or ciprofloxacin in the department of Respiration were collected for methodological evaluation. In addition, 34 clinical plasma samples from 22 pediatric patients (9 males and 13 females; mean age (8.1±3.7) years) using levofloxacin was collected, and their plasma concentrations were determined. Using ciprofloxacin as the internal standard, levofloxacin in plasma samples was quantified by liquid chromatography-tandem mass spectrometry following protein precipitation using acetonitrile. A C18 column (Shim-pac GIST-HP C18, 2.1 mm×100 mm, 3 μm) and mobile phase composed of water (containing 0.1% formic acid) and acetonitrile (containing 0.1% formic acid) with gradient elution at a flow rate of 0.4 ml/min were used to separate levofloxacin. The column temperature was 40 ℃, injection volume was 1 μl and the total analysis time was 9 min. Levofloxacin and ciprofloxacin were ionized with an ESI source in positive ion mode and detected in multiple reaction monitoring (MRM) mode. The detected ions of levofloxacin and ciprofloxacin were m/z 362.10→318.1 and 332.15→231.05, respectively. The method′s specificity, sensitivity, linearity, precision, accuracy, recovery rate, stability, matrix effect, and carry-over were validated. All statistical analyses were performed with SPSS statistical software (version 17.0). The normality of the data was detected by the K-S test. A P<0.05 was considered statistically significant for two tailed tests. Results:The LC-MS/MS method showed a good linearity within the range of 0.062 5-20 mg/L, with the lower detection limit of levofloxacin of 0.062 5 mg/L. The calibration curve for levofloxacin was Y=0.093X+0.010 ( R2>0.99). Under different quality control levels, the accuracy ranged from 92.57% to 104.39%, and the intra-day and inter-day imprecision ranged from 2.32% to 9.35%. These values were not affected by the normal matrix, 5% hemolysis matrix and 15% hyperlipidemia matrix. Furthermore, the levofloxacin plasma samples were stable in the short term. A total of 34 plasma samples from 22 patients were collected and analyzed. Only 2 plasma samples were below the lower limit of quantification, while the other plasma concentrations of levofloxacin were ranged from 0.091 to 6.755 mg/L. Cmax was (5.52 ± 1.09) mg/L. Conclusion:The LC-MS/MS method meets the requirements of the reference method and requires a small sample size (50 μl), making it suitable for the determination of levofloxacin in plasma from pediatric patients.

Objective:To explore the clinical characteristics and risk factors of sarcopenia in elderly patients with chronic kidney disease (CKD) stage 3-4.Methods:It was a single-center, retrospective observational study. CKD stage 3-4 patients aged ≥60 years old from March 2019 to March 2022 in the Geriatrics Department of the First Affiliated Hospital of Zhengzhou University were enrolled in the study. General data of the patients were collected, and laboratory indicators, muscle strength, physical function and appendicular muscle mass index (ASMI) were measured. According to the diagnostic criteria of sarcopenia, the patients were divided into no sarcopenia CKD group and sarcopenia CKD group. Baseline data between these two groups were compared. Logistic regression analysis was used to analyze the related factors of sarcopenia in elderly CKD stage 3-4 patients.Results:A total of 162 CKD stage 3-4 patients were enrolled in this study, with 89 males (54.9%) and a median age of 75 (69, 82) years. Sarcopenia was diagnosed in 40 cases, and the prevalence was 24.7% (95% CI 18.1%-31.3%). Compared with no sarcopenia CKD group, age, proportion of dementia, cystatin C, urea nitrogen, C-reactive protein (CRP) and ratio of urine protein to creatinine were higher (all P<0.05), while body mass index (BMI), hemoglobin, carbon dioxide combining power, estimated glomerular filtration rate (eGFR), serum albumin and the proportion of regular exercise and using α-ketones were lower in sarcopenia CKD group (all P<0.05). Meanwhile, grip strength, walking speed, short physical performance battery score and ASMI were lower in sarcopenia CKD group (all P<0.05). Multivariable logistic regression analysis results showed that low eGFR ( OR=0.824, 95% CI 0.687-0.987, P=0.036), low BMI ( OR=0.463, 95% CI 0.304-0.704, P<0.001), low serum albumin ( OR=0.459, 95% CI 0.263-0.802, P=0.006) and high CRP ( OR=2.754, 95% CI 1.708-4.439, P<0.001) were the independent related factors of sarcopenia in elderly CKD patients. Conclusions:The prevalence of sarcopenia in elderly CKD stage 3-4 patients is high. Low eGFR, low BMI, low serum albumin and high CRP are the independent risk factors for sarcopenia in elderly CKD stage 3-4 patients.

OBJECTIVE To establish the fingerprint and multi-component content determination method of Crataegus pinnatifida leaves from different producing areas， and to evaluate the quality of C. pinnatifida leaves and screen the differential markers. METHODS Seventy-eight batches of C. pinnatifida leaves were collected from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province. High-performance liquid chromatography （HPLC） and Similarity Evaluation System for Traditional Chinese Medicine Chromatographic Fingerprints （2012 edition） were used to draw the fingerprints and conduct similarity evaluation. Grey correlation analysis， cluster analysis （CA）， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed by using SPSS 19.0， MetaboAnalyst 5.0 and SIMCA 14.1 software. The differential markers affecting the quality of C. pinnatifida leaves were screened with variable importance in the projection （VIP） value greater than 1 and the error line not exceeding the origin as the criterion. Using vitexin rhamnoside as an internal reference， the contents of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin in 78 batches of C. pinnatifida leaves were determined by the same HPLC combined with quantitative analysis of multi- components by single-marker （QAMS）， and the results were compared with external standard method. RESULTS Eight common peaks were calibrated in the fingerprints for 78 batches of C. pinnatifida leaves from 4 producing areas. Five known components were identified， including chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， vitexin rhamnoside （peak 4）， hypericin （peak 7） and isoquercetin （peak 8）； their similarities ranged from 0.871 to 0.998. Average relative correlations of samples from Chengde of Hebei Province， Huludao of Liaoning Province， Yuncheng of Shanxi Province and Linyi of Shandong Province were 0.538， 0.528， 0.462 and 0.435， respectively. CA and PCA showed that the samples from Chengde of Hebei Province and Huludao of Liaoning Province were roughly classified into one category， while the samples from Linyi of Shandong Province and Yuncheng of Shanxi Province were roughly classified into one category； VIP values of peak 1， 2， 3 and 5 were all greater than 1. By QAMS， the relative correction factors of chlorogenic acid， glucosylvitexin， hypericin and isoquercetin were 0.401， 0.993， 1.670 and 1.615 （RSD＜2%）. Compared with external standard method， except for isoquercetin in the two batches of samples （S39 and S41）， there was no significant difference in the content of each component in other batches of samples （the relative deviations≤ 5%）. CONCLUSIONS The established fingerprint and QAMS method are simple to operate and can be used to evaluate the quality of C. pinnatifida leaves. The sample from Chengde of Hebei Province is relatively good in quality. Chlorogenic acid （peak 1）， glucosylvitexin （peak 3）， and the corresponding components of peaks 2 and 5 may be differential markers affecting the quality of C. pinnatifida leaves.