OBJECTIVE To analyze the clinical characteristics and influential factors of drug-induced liver injury （DILI） in children caused by intravenous azithromycin. METHODS Clinical data of 157 DILI pediatric cases caused by intravenous azithromycin， reported by the Hengshui Adverse Drug Reaction Monitoring Center from January 2015 to January 2025， were collected as the observation group. Clinical data of pediatric patients who received intravenous azithromycin but did not develop DILI during the same period at Hengshui People’s Hospital were collected in a 1∶1 ratio to serve as the control group. The clinical classification， severity and prognosis of DILI in pediatric patients from the observation group were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for DILI in children caused by intravenous azithromycin. RESULTS Among 157 DILI cases， 92 cases （58.60%） had hepatocellular injury-type， 51 cases （32.48%） had cholestatic-type， and 14 cases （8.92%） had mixed-type. DILI severity was grade 1 in 117 cases （74.52%）， grade 2 in 33 cases （21.02%）， and grade 3 in 7 cases （4.46%）. Liver function had all recovered after stopping medication and symptomatic treatment. Combined with acetaminophen [OR＝3.769， 95%CI （1.615， 8.235）， P＝0.021]， daily dose of azithromycin＞10 mg/kg [OR＝ 2.237， 95%CI （1.075， 4.655）， P＝0.034] were independent risk factors for DILI in children caused by intravenous azithromycin. CONCLUSIONS Hepatocellular injury-type and cholestatic-type are relatively common in children with DILI caused by intravenous azithromycin， with mild severity being predominant and showing a favorable prognosis. Combination with acetaminophen and daily dose＞10 mg/kg are independent risk factors for azithromycin-induced DILI in children.

Objective:To evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective To study the effect of diltiazem on coronary microcirculation and vascular endothelial function in patients with acute coronary syndrome(ACS)before surgery.Methods A total of 96 ACS patients admitted to Fengfeng General Hospital of North China Medical and Health Group between October 2023 and October 2024 were selected as subjects.The patients were divided into experimental group(n=48)and control group(n=48)by using a random number table method.The experimental group received slow intravenous infusion of diltiazem dilution before surgery and continued intravenous diltiazem during the procedure,while the control group received normal saline both preoperatively and intraoperatively.During the operation,coronary microcirculation parameters[coronary angiography,myocardial perfusion grading(TIMI),microcirculatory resistance index,intraoperative slow blood flow,and no-reflux status]were monitored.Vascular endothelial indexes(endothelin-1,vascular endothelial growth factor)were detected before and one week after surgery.Cardiovascular adverse events were also observed within six months postoperative.Results Postoperative TIMI myocardial perfusion grading in experimental group was superior to than that in control group,and the incidence of slow blood flow and no reflux during surgery in experimental group were lower than those in control group.The levels of endothelin-1 and vascular endothelial growth factor in experimental group were lower than those in control group,and the incidence of cardiovascular adverse events in experimental group were lower than those in control group,with statistically significant differences(P＜0.05).Conclusion The use of diltiazem before percutaneous coronary intervention in patients with ACS can effectively increase coronary blood flow,improve coronary microcirculation,and protect vascular endothelial function.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

Objective:To investigate the treatment and management of patients with endemic fluorosis (referred to as fluorosis) in Ankang City, Shaanxi Province, and to provide a scientific basis for adjusting and optimizing treatment and management strategies for fluorosis patients.Methods:A retrospective analysis was conducted on patient information collected from county-level disease prevention and control centers in Ankang City from 2019 to 2023. Data included demographic information, clinical treatment, chronic disease management, treatment records, work reports, and summaries. The study aimed to learn about the treatment willingness, methods, and effects of patients with fluorosis, and to evaluate the disease management situation of patients with fluorosis.Results:From 2019 to 2023, the proportion of fluorosis patients who were willing to receive treatment in Ankang City had increased from 76.80% (1 089/1 418) in 2019 to 100% (1 408/1 408) in 2023, showing an upward trend year by year (χ 2trend = 971.15, P < 0.001). A total of 6 876 patients received treatment, with a treatment rate of 100%. The majority of patients received drug treatment (99.64%, 6 851/6 876), with an effective rate of 94.90% (6 525/6 876). The effective rate of treatment for patients with fluorosis had increased from 88.71% (966/1 418) in 2019 to 94.67% (1 333/1 408) in 2023, showing an upward trend (χ 2trend = 1 002.92, P < 0.001). The adverse reaction rate of drug treatment was 0.36% (25/6 876). The combination of oral medication and local treatment had the highest effective rate (97.62%, 3 566/3 653). The management rate and contracted service rate of fluorosis patients were 100% each year, and the standardized management rate was above 99%. Conclusions:Fluorosis patients in Ankang City have a high willingness to receive treatment, with good treatment outcomes. The contracted services and management of patients are well implemented. In the future, continuous efforts should be made to improve the prevention, management, and health education of fluorosis patients.

Objective To analyze the impact of the National Centralized Drug Procurement Policy(hereinafter referred to as the"centralized procurement policy")on the utilization of breast cancer treatment drugs in a specialized cancer hospital.Methods The defined daily dose(DDD)method was used to compare the daily drug cost(DDC),drug utilization frequency(DDDs),and affordability of letrozole,anastrozole,and capecitabine before and after the implementation of the centralized pro-curement policy in a tertiary specialized cancer hospital in Guangzhou.Results and Conclusion After the policy implementa-tion,the DDC of all three drugs decreased.The out-of-pocket DDC for the selected drugs remained stable or decreased,while the out-of-pocket DDC for both originator drugs and generic drugs increased,with a more pronounced increase for originator drugs.The proportion of DDDs for the selected drugs increased post-policy.The centralized procurement policy not only reduced the prices of selected drugs but also drove down the prices of generic and originator drugs.It is recommended to further expand the scope of centralized procurement for anticancer drugs and the types of cancers covered,as well as to establish a transitional mech-anism for medical insurance payment standards.

Objective:To evaluate the effect of Bu-Zhong-Yi-Qi-Tang (BZYQT) combined with low molecular weight heparin (LMWH) on lower limb deep vein thrombosis (DVT) after fracture fixation in aged rabbits.Methods:Thirty-two elderly New Zealand rabbits of either sex, aged 36 months, weighing 3.5-4.0 kg, were divided into 4 groups ( n=8 each) using the random number table method: control group (C group), fracture fixation group (F group), low molecular weight heparin group (L group) and BZYQT combined with LMWH group (BL group). A model of fixation surgery for right femoral shaft fracture was established in anesthetized rabbits in F, L and BL groups. Starting from postoperative day 1, BL group received BZYQT at 3.6 ml/kg via gavage, F and L groups received normal saline at 3.6 ml/kg via gavage, L and BL groups received subcutaneous injection of LMWH at 200 IU/kg, and all the administrations were performed daily at 08: 00 for 7 consecutive days. On postoperative day 7, ultrasound examination was performed to assess lower limb DVT. Blood samples were collected from the marginal ear vein for determination of the serum concentrations of cortisol (COR), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and endothelin-1 (ET-1) by enzyme-linked immunosorbent assay. Femoral vein specimens were obtained under anesthesia for microscopic examination of the pathological changes of the femoral vein lumen and endothelial tissues (by HE staining) and of the morphology of vascular endothelial cells (by the transmission electron microscopy). Results:Compared with C group, the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly increased in F, L and BL groups, and the incidence of lower limb DVT within 7 days after surgery was significantly increased in F and L groups ( P<0.05). Compared with F group, the incidence of lower limb DVT within 7 days after surgery was significantly decreased in L and BL groups, and the concentrations of serum COR, TNF-α, IL-6 and ET-1 were significantly decreased ( P<0.05), and the pathological damage was significantly reduced in BL group. Compared with L group, the incidence of lower limb DVT and concentration of IL-6 were significantly decreased ( P<0.05), and pathological damage was significantly alleviated in BL group. Conclusions:BZYQT combined with LMWH can prevent the occurrence of lower limb DVT after fracture fixation in aged rabbits.

Objective:To investigate the treatment and management of patients with endemic fluorosis (referred to as fluorosis) in Ankang City, Shaanxi Province, and to provide a scientific basis for adjusting and optimizing treatment and management strategies for fluorosis patients.Methods:A retrospective analysis was conducted on patient information collected from county-level disease prevention and control centers in Ankang City from 2019 to 2023. Data included demographic information, clinical treatment, chronic disease management, treatment records, work reports, and summaries. The study aimed to learn about the treatment willingness, methods, and effects of patients with fluorosis, and to evaluate the disease management situation of patients with fluorosis.Results:From 2019 to 2023, the proportion of fluorosis patients who were willing to receive treatment in Ankang City had increased from 76.80% (1 089/1 418) in 2019 to 100% (1 408/1 408) in 2023, showing an upward trend year by year (χ 2trend = 971.15, P < 0.001). A total of 6 876 patients received treatment, with a treatment rate of 100%. The majority of patients received drug treatment (99.64%, 6 851/6 876), with an effective rate of 94.90% (6 525/6 876). The effective rate of treatment for patients with fluorosis had increased from 88.71% (966/1 418) in 2019 to 94.67% (1 333/1 408) in 2023, showing an upward trend (χ 2trend = 1 002.92, P < 0.001). The adverse reaction rate of drug treatment was 0.36% (25/6 876). The combination of oral medication and local treatment had the highest effective rate (97.62%, 3 566/3 653). The management rate and contracted service rate of fluorosis patients were 100% each year, and the standardized management rate was above 99%. Conclusions:Fluorosis patients in Ankang City have a high willingness to receive treatment, with good treatment outcomes. The contracted services and management of patients are well implemented. In the future, continuous efforts should be made to improve the prevention, management, and health education of fluorosis patients.

Objective To study the effect of diltiazem on coronary microcirculation and vascular endothelial function in patients with acute coronary syndrome(ACS)before surgery.Methods A total of 96 ACS patients admitted to Fengfeng General Hospital of North China Medical and Health Group between October 2023 and October 2024 were selected as subjects.The patients were divided into experimental group(n=48)and control group(n=48)by using a random number table method.The experimental group received slow intravenous infusion of diltiazem dilution before surgery and continued intravenous diltiazem during the procedure,while the control group received normal saline both preoperatively and intraoperatively.During the operation,coronary microcirculation parameters[coronary angiography,myocardial perfusion grading(TIMI),microcirculatory resistance index,intraoperative slow blood flow,and no-reflux status]were monitored.Vascular endothelial indexes(endothelin-1,vascular endothelial growth factor)were detected before and one week after surgery.Cardiovascular adverse events were also observed within six months postoperative.Results Postoperative TIMI myocardial perfusion grading in experimental group was superior to than that in control group,and the incidence of slow blood flow and no reflux during surgery in experimental group were lower than those in control group.The levels of endothelin-1 and vascular endothelial growth factor in experimental group were lower than those in control group,and the incidence of cardiovascular adverse events in experimental group were lower than those in control group,with statistically significant differences(P＜0.05).Conclusion The use of diltiazem before percutaneous coronary intervention in patients with ACS can effectively increase coronary blood flow,improve coronary microcirculation,and protect vascular endothelial function.

Objective:To investigate the clinical features of nontuberculous mycobacteria (NTM) disease patients with positive anti-interferon γ (IFN-γ) autoantibody.Methods:Forty-three adult human immunodeficiency virus-uninfected patients with NTM disease hospitalized in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University from July 2021 to August 2023 were included. Clinical data and NTM strain information of the patients were collected. The plasma levels of anti-IFN-γ autoantibodies were detected by enzyme-linked immunosorbent assay, and the patients were divided into antibody positive group and antibody negative group. The clinical characteristics and laboratory examination results between the two groups were compared. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was used to determine the correlation factors of positive anti-IFN-γ autoantibodies. Results:Among the 43 patients, 13 cases (30.2%) were positive for anti-IFN-γ autoantibodies and 30 cases (69.8%) were negative. The proportions of patients with NTM disseminated infection (9/13 vs 30.0%(9/30))and combined bacterial infection (5/13 vs 6.7%(2/30)) in antibody positive group were both higher than those in antibody negative group, and the differences were both statistically significant ( χ2=5.74 and 6.73, respectively, both P<0.05). The white blood cell count, platelet count, the proportion of platelet count >350×10 9/L of antibody positive patients were all higher than those of antibody negative group, while the white sphere ratio was lower than that of antibody negative group, with statistical significance ( t=2.42, 3.02, χ2=9.77 and t=3.66, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, procalcitonin, globulin, immunoglobulin G, immunoglobulin A and immunoglobulin M in antibody positive patients were all higher than those in antibody negative group, and the differences were all statistically significant ( U=99.50, 112.00, 115.50, 61.50, 76.50, 99.00 and 83.00, respectively, all P<0.05). Mycobacterium abscessus complex (seven cases and 11 cases, respectively) and Mycobacterium avium complex (five cases and 13 cases, respectively) were the main isolated strains in antibody positive and antibody negative patients. Multivariate logistic regression analysis showed that combined with bacterial infection (odds ratio ( OR)=21.83, 95% confidence interval ( CI) 1.94 to 245.71), NTM disseminated infection ( OR=7.64, 95% CI 1.10 to 53.26), platelet count>350×10 9/L ( OR=14.31, 95% CI 1.91 to 107.04) were risk factors for anti-IFN-γ autoantibodies positive (all P<0.05). Conclusions:Patients with positive anti-IFN-γ autoantibodies have higher probability of having elevated levels of systemic inflammation. Anti-IFN-γ autoantibody test is recommended for patients with NTM disease who present with co-bacterial infection, NTM disseminated infection, or elevated platelet count (>350×10 9/L).