1.Effects of Yangxin Tongmai Formula (养心通脉方) on Methylation Key Genes and the PERK/ATF4/CHOP Signaling Pathway in Myocardial Tissue of Coronary Heart Disease Model Rats with Blood Stasis Syndrome
Chun ZHANG ; Shumeng ZHANG ; Yan MAO ; Xing CHEN ; Huifang KUANG ; Yi YANG ; Lingli CHEN ; Jie LI
Journal of Traditional Chinese Medicine 2026;67(7):784-791
ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula (养心通脉方, YTF) in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group (n=12) and a modeling group (n=60). The modeling group was subjected to a high-fat diet, intragastric administration of vitamin D3, and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group, YTF low-, medium-, and high-dose groups, and the atorvastatin calcium group, with 8 rats in each group and 1 rat reserved. The YTF low-, medium-, and high-dose groups received YTF at 6, 12, and 18 g/(kg·d) by gavage, respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/(kg·d) by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/(kg·d) by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration, serum lipid levels including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), myocardial enzymes including cardiac troponin T (cTnT), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH), and inflammatory factors including interleukin-1β (IL-1β) and interleukin-10 (IL-10) were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group, model group, and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group, the model group showed increased levels of TC, TG, LDL-C, cTnT, CK-MB, LDH, and IL-1β, along with decreased levels of HDL-C and IL-10 (P<0.05 or P<0.01). Compared to the model group, all treatment groups exhibited decreased levels of TC, LDL-C, CK-MB, and LDH, along with increased IL-10 levels. Among these, the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups (P<0.05 or P<0.01). HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling, disordered arrangement, pyknosis, and disappearance of nuclei, thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group, model group, and YTF high-dose group, including 109 hypermethylated and 131 hypomethylated genes; eif2ak3 was identified as a key differentially methylated gene. Compared to the control group, the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 (eIf2ak3), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and Bax, along with a decreased level of B-cell lymphoma-2 (Bcl-2) protein (P<0.05 or P<0.01). Compared to the model group, the YTF high-dose group showed decreased protein levels of eIf2ak3, p-PERK, ATF4, CHOP, and Bax, and an increased level of Bcl-2 protein (P<0.05 or P<0.01). ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway, thereby inhibiting endoplasmic reticulum stress, reducing myocardial cell apoptosis, and exerting therapeutic effects in coronary heart disease blood stasis syndrome.
2.Risk factors for decompensated liver cirrhosis and the construction of a nomogram prediction model
Yuanyuan LIANG ; Huifang QU ; Xiyue WANG ; Yan WANG ; Hezhao ZHANG ; Jun XU
Journal of Clinical Hepatology 2026;42(6):1327-1334
ObjectiveTo investigate the independent risk factors for decompensation in patients with liver cirrhosis, to construct a nomogram-based risk assessment model, and to assess its risk assessment performance and clinical value by comparing it with Model for End-Stage Liver Disease (MELD), MELD combined with serum sodium concentration (MELD-Na), and MELD 3.0 scoring system. MethodsA retrospective analysis was performed for 514 patients with liver cirrhosis who attended The First Hospital of Shanxi Medical University from January 2020 to May 2025, and related data were collected, including demographic data and laboratory markers. According to the presence or absence of decompensation, the patients were divided into compensation group with 275 patients and decompensation group with 239 patients. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The least absolute shrinkage and selection operator regression analysis was used for screening of variables, and the multivariate logistic regression analysis was used to identify independent risk factors for decompensated liver cirrhosis and construct a nomogram model. The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to assess the discriminatory ability, calibration, and net clinical benefit of the model. ResultsThe multivariate logistic regression analysis showed that low hemoglobin (odds ratio [OR]=0.984, 95% confidence interval [CI]: 0.969 — 0.999, P<0.05), low lymphocytes (OR=0.564, 95%CI: 0.383 — 0.830, P<0.05), high international normalized ratio (OR=3.131, 95%CI: 1.242 — 7.891, P<0.05), and low serum sodium (OR=0.922, 95%CI: 0.872 — 0.975, P<0.05) were independent risk factors for decompensation events in patients with liver cirrhosis. Construct the prediction model equation: Logit(P)=intercept value-0.016×hemoglobin-0.573×lymphocytes+1.141×INR-0.081×serum sodium. The nomogram constructed based on these factors had a good discriminatory ability, with an area under the ROC curve (AUC) of 0.787, a specificity of 77.8%, and a sensitivity of 67.4%, and it had significantly better predictive performance than MELD score (AUC=0.718), MELD-Na score (AUC=0.719), and MELD 3.0 score (AUC=0.725). The calibration curve showed good consistency between the probability of risk assessed by the model and the observed probability. The decision curve analysis showed that compared with the MELD-based scores, this model provided higher net clinical benefit across a wide range of risk thresholds. ConclusionThis study successfully constructed and validated a nomogram risk assessment model incorporating hemoglobin, international normalized ratio, lymphocytes, and serum sodium. This model has good clinical practicability and can help to achieve early identification of high-risk patients with decompensated liver cirrhosis and optimize intervention strategies in clinical practice.
3.Clinical diagnostic value of MRI combined with serum CYR61 and CXCL1 for acute stroke
Juan TIAN ; Huifang WANG ; Weijing ZHANG
Chinese Journal of Radiological Health 2026;35(3):394-400
Objective To evaluate the clinical utility of combining magnetic resonance imaging (MRI) findings with serum levels of cysteine-rich protein 61 (CYR61) and C-X-C motif chemokine ligand 1 (CXCL1) for early identification of acute stroke. Methods The study was conducted 205 patients with suspected acute stroke admitted to the neurology department of our hospital between April 2021 and April 2024. Based on brain CT imaging and clinical diagnosis, 119 patients were acute stroke group and 86 to non-acute stroke group. All patients underwent MRI examination. Serum levels of CYR61 and CXCL1 were measured. Receiver operating characteristic (ROC) curves were generated to assess diagnostic value, and Kappa tests were used to performed to evaluate the consistency. Results Serum level of CYR61 and CXCL1were significantly higher in the acute stroke group than in the non-acute stroke group (P<0.05). The area under the ROC curve (AUC) for serum CYR61 in diagnosing acute stroke was 0.867 (95%CI: 0.819-0.915), with diagnostic threshold of 6.02 μg/L; for CXCL1, the AUC was 0.818 (95%CI: 0.762-0.875), with a threshold of 1.28 ng/mL. The Kappa values for agreement between MRI, serum CYR61, and CXCL1 clinical diagnosis results were 0.766, 0.586, and 0.528, respectively, the Kappa value for the consistency between the combination of the three with clinical diagnosis results was 0.920 (P<0.05). The sensitivity, negative predictive value, and accuracy of the combination of MRI, serum CYR61, and CXCL1 were obviously higher than that of the individual diagnosis, and the specificity and positive predictive value were obviously higher than that of the individual diagnosis of serum CYR61 and CXCL1 (P<0.05). Conclusion The clinical diagnostic accuracy of MRI combined with serum CYR61 and CXCL1 in the diagnosis of acute stroke is high, the combined diagnosis is obviously better than the individual diagnosis of each indicator.
4.Effects of the Bushen Zhuyun Formula(补肾助孕方)on JAK2/STAT3 Signaling Pathway and Macrophage Polarization in Uterine Tissues of Mice with Embryo Implantation Failure
Yunan LIU ; Huifang ZHOU ; Chen WANG ; Mengwen ZHANG ; Ping CHEN
Journal of Traditional Chinese Medicine 2026;67(16):1767-1774
ObjectiveTo explore the effect of Bushen Zhuyun Formula(补肾助孕方, BZF) on macrophage pola-rization in mouse uterine tissue with embryo implantation failure based on the janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) signaling pathway. MethodsFifty female and 25 male C57BL/6 mice were randomly divided into five groups including blank group, model group, low- and high-dose BZF groups, and dydrogesterone group, with 10 female and 5 male mice in each group. Except for the blank group, female mice in the estrous phase were subjected to superovulation induction. At 18:00 on the same day, female mice were co-housed with male mice at a ratio of 2∶1. The presence of sperm in vaginal exfoliated cells was examined on the following day, which was designated as gestational day 1 (GD1). On GD4, an oil-based mifepristone solution was subcutaneously injected into the neck region of female mice to establish an embryo implantation dysfunction model. Beginning on GD1, mice in the low- and high-dose BZF groups were given 11.18 and 22.36 g/kg of the BZF solution by gavage, respectively. The dydrogesterone group was given 2.6 mg/kg of dydrogesterone solution by gavage. The blank group and the model group were given 10 g/kg of normal saline by gavage once daily. Interventions were administered once a day until GD4. On GD5, uterine tissues were collected, and HE staining was performed to evaluate endometrial morphology, endometrial thickness, and glandular number in female mice. The proportions of M1 and M2 macrophages in uterine tissues were detected by flow cytometry, and the levels of transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) in uterine tissue were measured by ELISA. The protein expression levels of Janus kinase 2 (JAK2), phosphorylated JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated STAT3 (p-STAT3) in uterine tissue were detected by western blotting, and the mRNA expressions of JAK2, STAT3, IL-10, and TGF-β1 in uterine tissue was detected by real-time quantitative PCR. ResultsCompared to the blank group, the model group exhibited smaller and straighter endometrial glands, denser stroma, and fewer blood vessels, with reduced endometrial thickness and decreased glandular numbers. The proportion of M1 macrophages in uterine tissue increased, while the proportion of M2 macrophages and the levels of IL-10 and TGF-β1 decreased. The protein expression levels of JAK2, p-JAK2, STAT3, and p-STAT3, as well as the p-JAK2/JAK2 and p-STAT3/STAT3 ratios, were reduced. The mRNA expressions of JAK2, STAT3, IL-10, and TGF-β1 also decreased (P<0.05). Compared to the model group, the above indicators were improved in the low- and high-dose BZF groups, while some indicators were improved in the dydrogesterone group (P<0.05). Compared to the dydrogesterone group and the low-dose BZF group, the high-dose BZF group showed superior effects in improving endometrial morphology, endometrial thickness, glandular number, the proportion of M1 macrophages in uterine tissues, TGF-β1 levels, JAK2, p-JAK2, and p-STAT3 protein expression levels, the p-STAT3/STAT3 and p-JAK2/JAK2 ratios, as well as JAK2, IL-10, and TGF-β1 mRNA expressions (P<0.05). ConclusionBZF can improve the morphology of the endometrium during implantation in mice with embryo implantation failure, which may be related to specific regulation of the JAK2/STAT3 signaling pathway, modulation of macrophage polarization, and promotion of anti-inflammatory cytokine expression.
5.Effects of coal mine dust on lung function in rats
LIU Yang ; LI Meng ; LU Liyuan ; WANG Ru ; YANG He ; ZHANG Huifang
Journal of Preventive Medicine 2025;37(1):96-101
Objective:
To explore the impacts of coal mine dust on lung function in rats, so as to provide the basis for the early prevention and treatment of coal worker's pneumoconiosis.
Methods:
Seventy-two SPF-grade 8-week-old male Sprague-Dawley rats were randomly divided into the coal dust group, the coal-silica dust group, the silica dust group and the control group. The rats in the first three groups of rats were administered 1 mL corresponding dust suspension into the lungs using non-exposure tracheal instillation, while the rats in the control group were administered 1 mL normal saline. Respiratory rate (f), forced vital capacity (FVC), peak expiratory flow (PEF) and dynamic pulmonary compliance (Cdyn) were measured at 1, 3 and 6 months after dust exposure. Lung tissues were collected to measure reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels using corresponding ELISA kits and ATP assay kits, respectively. The relative mRNA expressions of peroxisome proliferators-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (TFAM) were detected using real-time fluorescent quantitative polymerase chain reaction assay. The relative protein expressions of PGC-1α and TFAM were detected using Western blotting.
Results:
There was no interaction between dust type and exposure duration on f (P>0.05), but there were interactions on FVC, PEF and Cdyn (all P<0.05). Compared with the control group at 6 months after dust exposure, the f of the rats in the silica dust group were increased, while the FVC and PEF of the rats in the coal-silica dust and silica dust groups were decreased, and Cdyn of the rats in the coal dust, coal-silica dust and silica dust groups were decreased (all P<0.05). There were interactions between dust type and exposure duration on ROS and ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM (all P<0.05). Compared with the control group at 3 and 6 months after dust exposure, the ROS levels in the rats in the coal dust, coal-silica dust and silica dust groups were increased, while the ATP levels, the relative mRNA and protein expressions of PGC-1α and TFAM were decreased (all P<0.05).
Conclusion
The lung function impairment in rats caused by different types of coal mine dust is related to PGC-1α-mediated mitochondrial biogenesis dysfunction, which leads to increased ROS levels, decreased ATP and TFAM levels.
6.Expert consensus on clinical treatment of acute radiation syndrome from external irradiation
Li LIANG ; Long YUAN ; Changlin YU ; Qingjie LIU ; Yulong LIU ; Wenfeng YANG ; Jin WANG ; Weixu HUANG ; Ying LIU ; Cuiping LEI ; Huifang CHEN ; Ximing FU ; Baoshan CAO ; Mopei WANG ; Zhaohui ZHANG ; Yu XIAO ; Yamei CHEN ; Quanfu SUN
Chinese Journal of Radiological Medicine and Protection 2025;45(9):827-839
China emerges as a major country in nuclear energy development and the application of nuclear and radiologic technology. The diagnosis and treatment of acute radiation syndrom (ARS) caused by external irradiation represent a core function in the country′s medical rescue of nuclear and radiological emergencies. Clinically, ARS manifests hematopoietic, gastrointestinal, cutaneous, and central nervous system syndromes, with specific clinical manifestations, signs, severity, and prognosis strongly correlated with radiation dose. China has established a number of national and provincial centers for treating radiation-induced damage. Nevertheless, most medical staff have limited experience in ARS treatment. This consensus presents a summary of recent experience in treating ARS of China. In combination with recommendations from international organizations such as the World Health Organization (WHO), this consensus proposes key evidence of critical clinical issues of ARS, covering all links in the rescue of external irradiation-induced ARS. Initially, clinical diagnosis, syndromes, and severe degrees should be determined based on clinical symptoms and dose estimates. It is necessary to normalize clinical treatment measures for hematopoietic recovery, gastrointestinal injury treatment, infection control, symptomatic treatment, and multi-organ function preservation. To this end, this consensus offers cautions. This consensus provides principles of treatment with traditional Chinese medicine, psychological intervention, and follow-up. Additionally, it highlights multidisciplinary collaboration. It is recommended that this consensus be applied in relevant treatment centers.
7.Application of EAERI support strategy in the recovery of patient safety incidents by the second victim
Huifang QIU ; Liyan WANG ; Yanhua LIU ; Xiaohong ZHANG ; Jiaqi CHEN ; Rongxin DU
Chinese Journal of Practical Nursing 2025;41(1):28-34
Objective:To explore the effect of EAERI (E: environment; A: accompany; E: emotion; R: respect; I: information) support strategies in the application of nurse second victims in restoring the passage of a patient safety incident, and to provide support to nurse second victims experiencing a safety incident in restoring the incident and mitigating secondary victimization from the incident.Methods:The method of historical comparison was adopted. A convenience sampling method was used to select nurses who experienced patient safety events in Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2023 to February 2024 as the study subjects, which were divided into observation group and control group by the historical control grouping method. The observation group used the EAERI support strategy for patient safety incident reduction, and the control group used the conventional reduction method. The second victims of the nurses in both groups were assessed for their level of harm and support in the patient safety incident using the Second Victim Experience and Support Tool before and after the event reduction, respectively.Results:A total of 124 second victims completed the study. There were 63 cases in the control group, including 13 males and 50 females, with an age of (30.24 ± 4.91) years old. There were 20 males and 41 females in the observation group, with an age of (30.85 ± 5.50) years old. Before the restoration event, there was no significant differences in the total scores of victim experience and support, the degree of injury and the degree of support between the two groups (all P>0.05). The total scores of victim experience and support, the degree of injury and the degree of support were (89.35 ± 10.69), (44.57 ± 6.19), (44.78 ± 9.40) points in the control group, and (64.13 ± 9.36), (33.56 ± 8.84), (30.56 ± 3.17) points in the observation group. The differences were significant between the two groups ( t=14.02, 8.07, 11.29, all P<0.01). Conclusions:The EAERI support strategy is feasible and effective. The implementation of the EAERI support strategy can reduce the degree of injury when the second victim of the nurse restores the safety incident and improve the degree of support.
8.Meta-integration of real disease experience in young and middle-aged patients with end-stage renal disease
Qitao MA ; Hongyi LI ; Xiangyun LI ; Wei ZHANG ; Xiaoyuan ZHANG ; Huifang ZHANG
Chinese Journal of Practical Nursing 2025;41(15):1183-1191
Objective:To systematically evaluate the disease experience and inner needs of young and middle-aged patients with end-stage renal disease, so as to provide evidence for medical personnel to pay more attention to the mental health of this population and give personalized care.Methods:The qualitative studies on the real experience, psychological feeling and experience of young and middle-aged patients with end-stage renal disease were searched by PsycInfo, PubMed, Embase, CINAHL, Web of Science, China National Knowledge Network, Wanfang, VIP and China Biomedical Literature Database. The retrieval period was from the establishment of the database to April 20, 2024. Joanna Briggs Institute Evidence-based Health Care Center Evaluation criteria (2016 edition) were used to evaluate the literature quality, and the results were summarized and integrated by aggregative meta-integration method.Results:A total of 10 studies were included, and 47 clear findings were extracted and classified into 10 new categories, which were combined into 4 integrated results: the phased changes of patients′ real experience at all levels of body, mind and society, impairment of their own and family role functions, desire for support and lack of autonomy in decision-making, and reconstruction of positive attitude and future outlook in the face of disease.Conclusions:Nursing staff should pay attention to and understand the psychosocial conditions of young and middle-aged patients with end-stage renal disease, timely provide targeted psychological support and help to enhance their confidence in treatment, better return to work and society, and improve their quality of life.
9.Diagnosis and Treatment Strategies for Sj?gren's Syndrome Based on the Theory of"Spleen as the Mother of the Five Organs"
Keying ZHU ; Ximeng LI ; Songwei LI ; Huan LI ; Xueqin ZHOU ; Pin LI ; Xinyan ZHANG ; Shuyue ZHANG ; Huifang HE ; Huijun GUO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(10):2975-2985
Sj?gren's syndrome(SS)is one of the common rheumatic diseases in clinical practice.Modern medicine commonly uses drugs such as artificial tears,saliva,glucocorticoids,immunosuppressants,and biologics to control the condition.Clinical practice has shown that in addition to modern medical basic treatment,the use of traditional Chinese medicine(TCM)can help improve the clinical efficacy of SS.According to the symptoms and signs of Sj?gren's syndrome in TCM,it is classified as"dryness and obstruction",and the core pathogenesis of the disease is spleen deficiency and deficiency of body fluids.Subsequently,toxic and pathogenic factors gather,leading to the decline of internal organs.The initial causes are spleen damage,unstable barrier,and invasion of pathogenic factors.The core link is spleen dysfunction,insufficient body fluid,and dryness arising from it.Spleen deficiency generates evil,obstruction of qi,and lack of body fluids are the root causes of illness.The main treatment method is the"spleen strengthening method",which treats spleen deficiency,dampness and stagnation,and the body fluid is not distributed.The treatment focuses on strengthening the spleen and qi,supplementing the lungs and generating fluids.Spleen deficiency leads to loss of vitality,blood stasis obstructs blood vessels,and the treatment is to strengthen the spleen,soothe the liver,remove blood stasis,and unblock the orifices.The spleen yang is not vigorous,and qi transformation is impaired.The treatment is to invigorate the spleen and warm the stomach,promote yang circulation,and promote diuresis.
10.Individualized administration of vancomycin in obese patients guided by trough concentration or AUC24h/MIC
Huifang ZHANG ; Yaxin FAN ; Fangqing ZHOU ; Zelin CUI ; Guanhua ZHU ; Mengting CHEN ; Jing ZHANG ; Ruilan WANG
Chinese Journal of Infection and Chemotherapy 2025;25(1):7-14
Objective To compare the safety and efficacy of vancomycin in obese patients guided by trough concentration and AUC24h/MIC,and to provide data for individualized administration of vancomycin in obese patients.Methods We retrospectively collected the data of obese adult patients(BMI 30 kg/m2)who had severe infection caused by gram-positive cocci and treated with vancomycin intravenously in two Grade A tertiary hospitals in Shanghai from 2012 to 2024.The patients were assigned to trough concentration monitoring group or AUC24h/MIC monitoring group according to the therapeutic drug monitoring(TDM)method at the time of admission.Nephrotoxicity and efficacy were compared between the two groups of patients.Results A total of 22 obese patients were included in this study,including 12 in the trough concentration monitoring group and 10 in the AUC24h/MIC monitoring group.No significant difference was found between the two groups in gender,age,BMI,creatinine clearance before treatment,underlying disease,site of infection,pathogen type,or concomitant medications.The proportion of ICU admission was higher in AUC24h/MIC monitoring group.The length of ICU stay,vancomycin treatment duration,bacterial clearance rate and comprehensive efficacy rate did not show significant difference between the two groups.The average daily dose of vancomycin in trough concentration monitoring group was significantly lower than that in A UC24h/MIC monitoring group[(1.63±0.59)g vs(2.29±0.72)g,P=0.026].The average treatment duration was not significantly different between the two groups[(15.33±10.28)d vs(14.90±6.92)d,P=0.911].Compared with the trough concentration monitoring group,the initial peak concentration[(30.99±16.22)mg/L vs(19.41±5.42)mg/L,P=0.025]and overall peak concentration[(33.67±16.53)mg/L vs(22.08±3.96)mg/L,P=0.045]of vancomycin were lower in theAUC24h/MIC monitoring group,but the initial trough concentration[(11.03±8.66)mg/L vs(6.33±4.45)mg/L,P=0.139]and overall trough concentration[(13.75±9.74)mg/L vs(9.74±4.24)mg/L,P=0.218]were similar in the two groups.Vancomycin-associated nephrotoxicity did not occur in any group,but 41.7%of the patients in the trough concentration monitoring group reached the threshold of renal toxicity,i.e.trough concentration ≥15 mg/L.Conclusions Vancomycin treatment with conventional dosing regimen still have good clinical efficacy in obese adult patients.Vancomycin therapy guided by A UC24h/MIC can achieve the target value at lower concentration or exposure,which is promising for reducing vancomycin-associated nephrotoxicity.


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