Incidence, characteristics, and risk factors of drug-associated muscle adverse reaction: a retrospective real-world study of inpatients.

OBJECTIVE: To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use. METHODS: We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses. RESULTS: Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs. CONCLUSION: Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

A case-control study on the clinical characteristics of granisetron-related arrhythmias and the development of a predictive nomogram.

BACKGROUND: Automatic monitoring and assessment are increasingly employed in drug safety evaluations using hospital information system data. The increasing concern about granisetron-related arrhythmias requires real-world studies to improve our understanding of its safety. AIM: This study aimed to analyze the incidence, clinical characteristics, and risk factors of granisetron-related arrhythmias in hospitalized patients using real-world data obtained from the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II) and concurrently aimed to develop and validate a nomogram to predict the occurrence of arrhythmias. METHOD: Retrospective automatic monitoring of inpatients using granisetron was conducted in a Chinese hospital from January 1, 2017, to December 31, 2021, to determine the incidence of arrhythmias using ADE-ASAS- II. Propensity score matching was used to balance confounders and analyze clinical characteristics. Based on risk factors identified through logistic regression analysis, a prediction nomogram was established and internally validated using the Bootstrap method. RESULTS: Arrhythmias occurred in 178 of 72,508 cases taking granisetron with an incidence of 0.3%. Independent risk factors for granisetron-related arrhythmias included medication duration, comorbid cardiovascular disease, concomitant use of other 5-hydroxytryptamine 3 receptor antagonists, alanine aminotransferase > 40 U/L, and blood urea nitrogen > 7.5 mmol/L. The nomogram demonstrated good differentiation and calibration, with enhanced clinical benefit observed when the risk threshold ranged from 0.10 to 0.82. CONCLUSION: The nomogram, based on the five identified independent risk factors, may be valuable in predicting the risk of granisetron-related arrhythmias in the administered population, offering significant clinical applications.

Analysis of clinical characteristics and automatic monitoring of drug-induced arrhythmias in 167,546 inpatients.

OBJECTIVE: The purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of drug-induced arrhythmias in a real-world inpatient population. METHODS: According to the inclusion and exclusion criteria as well as the ADR evaluation criteria, we retrospectively evaluated hospitalized patients in 2019 using the arrhythmia module of the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). A detailed analysis was performed on the demographic data, ADR manifestations, and medication distribution of 2097 patients with drug-induced arrhythmias and QT interval prolongation. RESULTS: Of the 167,546 hospitalized patients, there were 1809 cases of drug-induced arrhythmias, with an incidence of 1.08%. The ADRs in 45.35% of positive patients occurred within 3 days after medication administration, and 46.73% of the patients were 65 years old or older. The predominant ADRs identified in this study were extrasystole, tachycardia, and QT interval prolongation, of which the incidence was 0.20%. Levofloxacin was the most involved drug, and levofloxacin-associated rates of incidence of arrhythmia and QT interval prolongation were 1.24% and 0.44%, respectively. The risk factors for drug-induced arrhythmias were male sex, advanced age, emaciation, obesity, and underlying illnesses such as cardiovascular diseases, diabetes mellitus, cerebrovascular diseases, and hepatic and renal inadequacy (P < 0.05). CONCLUSION: The incidence of drug-induced arrhythmias was in the range of common, while QTc interval prolongation was occasional. It is necessary to pay attention to patients with risk factors.

MiR-1281 is involved in depression disorder and the antidepressant effects of Kai-Xin-San by targeting ADCY1 and DVL1.

Kai-Xin-San (KXS) is a Chinese medicine formulation that is commonly used to treat depression caused by dual deficiencies in the heart and spleen. Recent studies indicated that miRNAs were involved in the pathophysiology of depression. However, there have been few studies on the mechanism underlying the miRNAs directly mediating antidepressant at clinical level, especially in nature drugs and TCM compound. In this study, we identified circulating miRNAs defferentially expressed among the depression patients (DPs), DPs who underwent 8weeks of KXS treatment and health controls (HCs). A total of 45 miRNAs (17 were up-regulated and 28 were down-regulated) were significantly differentially expressed among three groups. Subsequently, qRT-PCR was used to verify 10 differentially expressed candidate miRNAs in more serum samples, and the results showed that 6 miRNAs (miR-1281, miR-365a-3p, miR-2861, miR-16-5p, miR-1202 and miR-451a) were consistent with the results of microarray. Among them, miR-1281, was the novel dynamically altered and appeared to be specifically related to depression and antidepressant effects of KXS. MicroRNA-gene-pathway-net analysis showed that miR-1281-regulated genes are mostly key nodes in the classical signaling pathway related to depression. Additionally, our data suggest that ADCY1 and DVL1 were the targets of miR-1281. Thus, based on the discovery of miRNA expression profiles in vivo, our findings suggest a new role for miR-1281 related to depression and demonstrated in vitro that KXS may activate cAMP/PKA/ERK/CREB and Wnt/ß-catenin signal transduction pathways by down-regulating miR-1281 that targets ADCY1 and DVL1 to achieve its role in neuronal cell protection.

A Clinical Practice Guideline for the Emergency Management of Anaphylaxis (2020).

Background: For anaphylaxis, a life-threatening allergic reaction, the incidence rate was presented to have increased from the beginning of the 21st century. Underdiagnosis and undertreatment of anaphylaxis are public health concerns. Objective: This guideline aimed to provide high-quality and evidence-based recommendations for the emergency management of anaphylaxis. Method: The panel of health professionals from fifteen medical areas selected twenty-five clinical questions and formulated the recommendations with the supervision of four methodologists. We collected evidence by conducting systematic literature retrieval and using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This guideline made twenty-five recommendations that covered the diagnosis, preparation, emergency treatment, and post-emergency management of anaphylaxis. We recommended the use of a set of adapted diagnostic criteria from the American National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network (NIAID/FAAN), and developed a severity grading system that classified anaphylaxis into four grades. We recommended epinephrine as the first-line treatment, with specific doses and routes of administration for different severity of anaphylaxis or different conditions. Proper dosage is critical in the administration of epinephrine, and the monitor is important in the IV administration. Though there was only very low or low-quality evidence supported the use of glucocorticoids and H1 antagonists, we still weakly recommended them as second-line medications. We could not make a well-directed recommendation regarding premedication for preventing anaphylaxis since it is difficult to weigh the concerns and potential effects. Conclusion: For the emergency management of anaphylaxis we conclude that: • NIAID/FAAN diagnostic criteria and the four-tier grading system should be used for the diagnosis • Prompt and proper administration of epinephrine is critical.

A Risk-Prediction Nomogram for Neutropenia or Febrile Neutropenia after Etoposide-Based Chemotherapy in Cancer Patients: A Retrospective Cohort Study.

INTRODUCTION: This study was conducted to develop and validate a nomogram for predicting the risk of neutropenia or febrile neutropenia (FN) in tumor patients in the first cycle of etoposide-based chemotherapy. METHODS: This retrospective cohort study used an information system to monitor patients with non-Hodgkin's lymphoma or solid tumors receiving an etoposide regimen in the first chemotherapy cycle in our hospital from 2009 to 2020. Binary logistic regression analysis was used to identify the influencing factors of patients with neutropenia or FN. Those factors were then used to develop a nomogram. RESULTS: A total of 1,554 patients were divided into the development group (n = 1,072) and validation group (n = 482). Variables used to predict neutropenia or FN were Karnofsky performance status (odds ratio [OR] = 0.85, 95% confidence interval [CI] = 0.81-0.89, p < 0.01), metastatic sites ≥3 (OR = 6.33, 95% CI = 2.66-15.11, p < 0.01), comorbidity of heart disease (OR = 4.88, 95% CI = 1.74-13.67, p < 0.01), recent surgery (OR = 7.96, 95% CI = 1.96-32.36, p < 0.01), administration of alkylating agents (OR = 4.50, 95% CI = 1.10-18.48, p < 0.01), total bilirubin ≥25 µmol/L (OR = 11.42, 95% CI = 4.00-32.61, p < 0.01), and lymphocyte count <0.7 × 109/L (OR = 4.22, 95% CI = 2.00-9.75, p < 0.01). CONCLUSION: This model can aid the early identification and screening of the potential risk of neutropenia or FN in the first cycle of treatment for patients using etoposide-based chemotherapy.

Development and Validation of a Nomogram for Predicting Drug-Induced Acute Kidney Injury in Hospitalized Patients: A Case-Control Study Based on Propensity-Score Matching.

Background: Drug-induced acute kidney injury (D-AKI) is associated with increased mortality and longer hospital stays. This study aims to establish a nomogram to predict the occurrence of D-AKI in hospitalized patients in a multi-drug environment. Methods: A single center retrospective study among adult hospitalized patients was conducted from July 2019 to September 2019 based on the Adverse Drug Events Active Surveillance and Assessment System-2 developed by our hospital. According to the propensity score matching algorithm, four controls per case were matched to eliminate the confounding bias caused by individual baseline variables. The predictors for D-AKI were obtained by logistic regression equation and used to establish the nomogram. Results: Among 51,772 hospitalized patients, 332 were diagnosed with D-AKI. After matching, 288 pairs and 1,440 patients were included in the study, including 1,005 cases in the development group and 435 cases in the validation group. Six variables were independent predictors for D-AKI: alcohol abuse, the concurrent use of nonsteroidal anti-inflammatory drugs or diuretics, chronic kidney disease, lower baseline red blood cell count and neutrophil count ≥7 × 109/L. The area under the curve (AUC) of the prediction model in the development group and validation group were 0.787 (95%CI, 0.752-0.823) and 0.788 (95%CI, 0.736-0.840), respectively. The GiViTI calibration belts showed that the model had a good prediction accuracy for the occurrence of D-AKI (p > 0.05). Conclusion: This nomogram can help identify patients at high risk of D-AKI, which was useful in preventing the progression of D-AKI and treating it in the early stages.

Incidence, characteristics and risk factors for drug-induced liver injury in hospitalized patients: A matched case-control study.

AIMS: The diagnosis of drug-induced liver injury (DILI) is relatively complex and involves a wide variety of drugs. The purpose of this study was to use algorithms to quickly screen DILI patients, determine its incidence and identify risk factors. METHODS: The Adverse Drug Events Active Surveillance and Assessment System-2 was used to extract the data of patients hospitalized in 2019 according to the set standards and the Roussel Uclaf Causality Assessment Method was used to evaluate patients who met the standards. A retrospective case-control study was conducted according to suspected drugs, length of hospital stay and height- and weight-matched controls, and logistic regression was used to identify risk factors. RESULTS: Among the 156 570 hospitalized patients, 480 patients (499 cases) with DILI were confirmed and the incidence of DILI was 0.32%. Anti-infective agents, antineoplastic agents and nonsteroidal anti-inflammatory drugs were the major categories of drugs causing DILI, and the highest incidence of DILI was due to voriconazole. The latency period and hospital stay of patients with cholestasis were both relatively long. Patients with hyperlipidaemia (adjusted odds ratio [AOR] 1.884), cardiovascular disease (AOR 1.465), pre-existing liver disease (AOR 1.827) and surgical history (AOR 1.312) were at higher risk for DILI. CONCLUSIONS: The incidence of DILI in hospitalized patients was uncommon (0.32%) and its pathogenic drugs were widely distributed. The incidence of DILI for many drugs has been seriously underestimated. It is recommended to focus on patients with hyperlipidaemia, cardiovascular disease, pre-existing liver disease and surgical history.

Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

BACKGROUND: Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS: Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS: We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS: We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.

Clinical Characteristics of Hospitalized Patients with Drug-Induced Acute Kidney Injury and Associated Risk Factors: A Case-Control Study.

BACKGROUND: Drug-induced acute kidney injury (D-AKI) is increasingly common and can extend the hospital length of stay and increase mortality. This study is aimed at analyzing the clinical characteristics of hospitalized patients with D-AKI and the associated risk factors in a multidrug environment. METHODS: A retrospective study among hospitalized patients was conducted in July 2019 based on the Adverse Drug Events Active Surveillance and Assessment System-2 developed by the authors. Four controls were matched with each case according to the matching criteria. The risk factors for D-AKI were identified by binary multivariate logistic regression. RESULTS: A total of 23,073 patients were hospitalized in July 2019, 21,131 of whom satisfied the inclusion criteria. The independent risk factors for D-AKI consisted of alcohol abuse (odds ratio (OR), 2.05; 95% confidence interval (CI), 1.04-4.07), nonsteroidal anti-inflammatory drug (NSAID) use (OR, 2.39; 95% CI, 1.25-4.58), diuretic use (OR, 2.64; 95% CI, 1.42-4.92), prior anemia (OR, 4.10; 95% CI, 1.94-8.67), and prior chronic kidney disease (OR, 2.33; 95% CI, 1.07-5.08). CONCLUSIONS: The occurrence of D-AKI in hospitalized patients had significant associations with alcohol abuse, combination therapy with NSAIDs or diuretics, and prior anemia or chronic kidney disease. Clinicians should meticulously follow patients with the above characteristics.

Development of a Computer-Assisted Adverse Drug Events Alarm and Assessment System for Hospital Inpatients in China.

BACKGROUND: Computerized detection is a promising method for monitoring adverse drug events (ADEs); however, this method is currently in its infancy and is a new area of exploration in China. This study aimed to develop a computerized ADE alarm and assessment system to help pharmacists effectively detect, assess, and analyze possible ADEs in patients in China. METHODS: Based on the clinical characteristics of these adverse drug events, we designed combined multiparameters as ADE alert rules to be assembled into detection configurations. We also developed system function modules by extracting data from the People's Liberation Army (PLA) general hospital information system (electronic medical records). Positive predictive values were calculated for the alert. RESULTS: Five function modules were created in this platform: automatic screening, assisted evaluation, risk characteristic analysis, report generation into SRS (spontaneous reporting system), and a dictionary database. Four ADE alert configurations were set in our ADE alarm and assessment system: drug-related thrombocytopenia, anemia, liver injury, and kidney injury. The positive predictive values of the 4 monitored ADEs were approximately 44.4% to 95.8%. CONCLUSIONS: An automatic ADE screening system was established for hospitalized patients in Chinese medical institutions. Compared with previous studies, combined drug-event alerts and a system-assisted assessment interface performed better than alerts based only on laboratory values. Furthermore, this platform's assisted-layered evaluation and risk factor analysis functions could save considerable time for professionals and improve early prevention of potentially serious ADEs. To date, this system has been applied in 10 large-scale medical institutions.

Comparison of Different Liver Test Thresholds for Drug-Induced Liver Injury: Updated RUCAM versus Other Methods.

According to the updated Roussel Uclaf Causality Assessment Method (RUCAM), drug-induced liver injury (DILI) is currently defined based on thresholds of alanine aminotransferase (ALT) levels above 5 × the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) levels greater than 2 × the ULN. However, many parameters with different thresholds are also currently used in the clinic. We therefore performed a comparative analysis to evaluate which set of criteria was the most appropriate to detect DILI. We enrolled hospitalized patients who received fluoroquinolones to treat or prevent infections. Three liver test criteria were used to diagnose DILI in these patients. RUCAM criteria were defined as the gold standard, and the other two criteria were as follows: 1) ALT or aspartate aminotransferase (AST) levels greater than 5 × the ULN on two consecutive occasions and/or ALP levels greater than 2 × the ULN on two consecutive occasions [issued by DILI Network (DILIN)]; 2) ALT levels greater than 1 × the ULN on two consecutive occasions or ALT levels greater than 2 × the ULN [issued by the National Medical Products Administration (NMPA) of China]. We found that the RUCAM criteria resulted in 657 warnings, DILIN criteria resulted in 358, NMPA criteria resulted in 1,377, and the positive predictive value (PPV) were 9.74%, 10.89%, and 9.73% (P = 0.80), respectively. The levels of agreement of the DILIN and NMPA criteria with the RUCAM criteria were moderate, but the agreement between the DILIN criteria and NMPA criteria was poor. In conclusion, the NMPA criteria with relatively lax thresholds for the parameters require much more labor to determine the diagnosis, making them unsuitable for clinical practice. Conversely, the DILIN criteria employing stricter thresholds for the parameters were more effective but would miss some positive cases, and the cases it identified were usually quite serious, which is not conductive to early intervention. Therefore, we still recommend the use of the RUCAM criteria in clinical practice.

Incidence, clinical features, and risk factors of fluoroquinolone-induced acute liver injury: a case-control study.

BACKGROUND: Fluoroquinolone-related hepatotoxicity is rare but serious and is attracting increasing attention. We explored the incidence, clinical features and risk factors of acute liver injury associated with fluoroquinolone use. MATERIALS AND METHODS: Based on the Adverse Drug Events Active Surveillance and Assessment System that we developed, we carried out a case-control study by enrolling patients who were hospitalized and received fluoroquinolones to treat or prevent infections at the Chinese People's Liberation Army General Hospital from Jan 2016 to Dec 2017. The incidence of fluoroquinolone-induced acute liver injury was estimated, and logistic regression was used to reveal the risk factors of this adverse reaction. RESULTS: We found that 17,822 patients received fluoroquinolones, and 13,678 of them met the inclusion criteria. A total of 91 patients developed acute liver injury after receiving the medication, and 369 controls were matched to these patients. The overall incidence of fluoroquinolone-induced acute liver injury in the Chinese population is approximately 6-7 cases per 1,000 individuals annually. Multivariate logistic regression analysis showed that older age slightly decreased the risk of hepatotoxicity (OR, 0.98; 95% CI, 0.96-0.99). The male sex (OR, 2.19; 95% CI, 1.07-4.48), alcohol abuse (OR, 2.91; 95% CI, 1.39-6.11) and hepatitis B carrier status (OR, 2.38; 95% CI, 1.04-5.48) increased the risk of liver injury. Concurrent use of cephalosporins or carbapenems was also associated with an increased risk. CONCLUSION: Increased risk of fluoroquinolone-related hepatotoxicity may be associated with youth, the male sex, alcohol abuse, hepatitis B carrier status and the concurrent use of cephalosporins or carbapenems.

Efficacy of tea polyphenols (TP 50) against radiation-induced hematopoietic and biochemical alterations in beagle dogs.

OBJECTIVE: To investigate the radioprotective effect of tea polyphenols (TP 50) against radiation-induced organ and tissue damage. METHODS: Beagle dogs were exposed to a single acute dose of whole-body γ-radiation (3 Gy) and orally administered TP 50 (80 or 240 mg·kg－1·d－1) for 28 consecutive days. A hemogram was obtained from experimental dogs every other day for 42 d. At the end of the experiment, enzyme activities of the antioxidants superoxide-dismutase andglutathione peroxidase, serum levels of inflamma- tory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), colony-forming units of bone marrow hematopoietic progenitor cells, andorgan coefficients were measured. RESULTS: Dogs exposed to γ-radiation alone exhibited typical hematopoietic syndrome. In contrast, irradiated dogs that received TP 50 exhibited an improved blood profile with reduced leucopenia, thrombocytopenia (platelet counts), and reticulocyte levels. TP 50 also significantly elevated levels of the endogenous antioxidant enzyme superoxide-dismutase, reduced the increased levels of serum cytokine in response to radiation-induced toxicity, and increased colony-forming units of bone marrow hematopoietic progenitor cells. In addition, TP 50 repaired radiation-induced organ damage. CONCLUSION: The current findings suggest that oral administration of TP 50 to beagle dogs effectively alleviated hematopoietic bone marrow dam- age induced by γ-radiation.

Protective Effect of JXT Ethanol Extract on Radiation-Induced Hematopoietic Alteration and Oxidative Stress in the Liver.

This study aims at investigating the radioprotective effect of ethanol extract from Ji-Xue-Teng (JXT, Spatholobus suberectus) on radiation-induced hematopoietic alteration and oxidative stress in the liver. Mice were exposed to a single acute γ-radiation for the whole body at the dose of 6.0 Gy, then subjected to administration of amifostine (45 mg/kg) or JXT (40 g crude drug/kg) once a day for 28 consecutive days, respectively. Bone marrow cells and hemogram including white cells, red cells, platelet counts, and hemoglobin level were examined. The protein expression levels of pJAK2/JAK2, pSTAT5a/STAT5a, pSTAT5b/STAT5b, and Bcl-2 in bone marrow tissue; levels of reactive oxygen species (ROS); and the activity of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum and liver tissue were determined. At the end of the experiment, the effect of JXT on cell viability and G-CSF and G-CSFR levels in NFS-60 cells were tested by CCK-8 assay, ELISA, and flow cytometry. The results showed that the mice exposed to γ-radiation alone exhibited a typical hematopoietic syndrome. In contrast, at the end of the 28-day experiment, irradiated mice subjected to oral administration of JXT showed an obvious improvement on blood profile with reduced leucopenia, thrombocytopenia (platelet counts), RBC, and hemoglobin levels, as well as bone marrow cells. The expression of pJAK2/JAK2, pSTAT5a/STAT5a, and Bcl-2 in bone marrow tissue was increased after JXT treatment. The elevation of ROS was due to radiation-induced toxicity, but JXT significantly reduced the ROS level in serum and liver tissue, elevated endogenous SOD and GSH-PX levels, and reduced the MDA level in the liver. JXT could also increase cell viability and G-CSFR level in NFS-60 cells, which was similar to exogenous G-CSF. Our findings suggested that oral administration of JXT effectively facilitated the recovery of hematopoietic bone marrow damage and oxidative stress of the mice induced by γ-radiation.

Effect of JYTK on Antioxidant Status and Inflammation in Patients With Type 2 Diabetes: A Randomized Double-Blind Clinical Trial.

BACKGROUND: Diabetes is a metabolic disorder caused by oxidative stress and inflammation. JianYuTangKang (JYTK), as a potential Chinese integrative medicine, is an antioxidant used in Chinese medicine with potential anti-inflammatory properties. OBJECTIVES: The present randomized clinical trial was carried out to evaluate the effects of JYTK on oxidative stress and inflammation in patients with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: The parallel, randomized, double-blinded, placebo-controlled clinical trial included 150 newly diagnosed T2DM patients receiving metformin treatment (1.5 g/day), some of whom also received JYTK (4.5 g/day) in tablet form. The control group received 4.5 g/day placebo plus 1.5 g/day metformin. Body mass index (BMI), fasting plasma glucose, urinary albumin-to-creatinine ratio, and complete blood count as well as antioxidant and inflammation indices such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, superoxide dismutase (SOD), malonaldehyde (MDA), glutathione peroxidase (GPX), and high sensitivity C-reactive protein (hs-CRP) levels were assessed at baseline and at different time points during the treatment. RESULTS: All 112 patients, including 59 in the treatment group (JYTK + metformin) and 52 controls (metformin only) completed the 26-week clinical trial. JYKT plus metformin treatment increased IL-6 (36.4 ± 11.5 ng/L; P < 0.05), TNF-α (17.5 ± 11.3 vs. 22.5 ± 12.9 ng/L; P < 0.05), and MDA (1.9 ± 0.9; P < 0.05) levels compared to the control (2.2 ± 0.6 mM/mL), whereas total SOD level decreased (98.1 ± 30.4 vs. 78.5 ± 29.3 U/mL; P < 0.05). There were no changes in GPX and hs-CRP levels. There were no adverse effects associated with JYTK treatment. CONCLUSIONS: JYTK combined with metformin improves some antioxidant indices (SOD and MDA), and decreases inflammation in patients with T2DM, suggesting that it can reduce the risk of diabetic complications.

A comparison study of metformin only therapy and metformin combined with Chinese medicine jianyutangkang therapy in patients with type 2 diabetes: A randomized placebo-controlled double-blind study.

The aim of this 26-week, double-blind, controlled clinical trial, was to compare the efficacy of monotherapy (metformin only) with combination therapy (Chinese medicine prescription JianYuTangKang [JYTK] plus metformin) on type 2 diabetes. All patients on metformin were randomized to receive authenticated JYTK (59 patients) or placebo JYTK (53 patients), 4.5g daily, for 26 weeks. Patients also received information regarding diet and exercise. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C) level, and a lipid profile were measured before, during, and after the treatment. The results of the treatment group (JYTK plus metformin) were noninferior to those of the control group (metformin plus placebo) at 8 and 18 weeks. After 26 weeks of treatment, FPG levels decreased to 6.1±1.0mmol/L in the treatment group and 7.0±1.5mmol/L in the control group (p<0.01). HbA1C levels after 26 weeks were also significantly decreased in the treatment group compared with the control group (p<0.01). In addition, lipid profiles were also significantly different between the two groups. Integrated traditional Chinese and Western medicine therapy (JYTK plus metformin) for patients with type 2 diabetes mellitus may not only help improve glycemia and insulin sensitivity, but also help to modify the diabetes related lipid equilibrium. And thereby provides a basis for a novel, effective, and safe approach, to treat type 2 diabetic patients.

Thrombocytopenia in Patients Receiving Prolonged Linezolid May be Caused by Oxidative Stress.

BACKGROUND AND OBJECTIVES: Oxidative stress in drug-induced thrombocytopenia (TP) has been discussed. This study was carried out to assess the oxidative stress in patients with normal platelet count (NPC) and TP after linezolid (LZD) treatment and to evaluate if TP caused by LZD is associated with a reduction in antioxidation ability and an increase in lipid peroxidative product in platelets. METHODS: After LZD treatment for 20 days, 44 patients with TP and 73 patients with NPC were included in this study. Blood samples were collected on the day before medicine treatment and day 7, 14, and 20 after LZD therapy. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and cholesterol as well as the activities of antioxidative enzyme were estimated. In addition, we identified 37 patients with TP caused by low-dose methotrexate (7.5-25 mg/week) therapy as a positive control group. RESULTS: In total, 37.60% of cases presented with TP on the 20th day of LZD administration. Individuals with TP had significantly elevated levels of ROS and MDA, low levels of superoxide dismutase (SOD) and catalase (CAT), significantly decreased high-density lipoprotein-cholesterol, low-density lipoprotein (LDL)-cholesterol levels, and increased oxidized-LDL levels in comparison to individuals with NPC. However, no significant changes in the levels of glutathione-peroxidase were found in the course of time. In all cases with LZD, significant increases in levels of ROS, MDA, and ox-LDL were found in the 20-day samples compared with their respective samples before LZD treatment. Correlation analysis revealed a positive association between platelet count and levels of SOD on day 20 and CAT on days 14 and 20 in plasma, a negative association between platelet count and level of MDA and ROS on days 14 and 20 in patients with LZD-induced TP. CONCLUSIONS: The oxidative stress markers were increased in LZD-induced TP, suggesting that oxidative damage might be the underlying mechanism.

[Anti-radiation effect and mechanism studies of ethanol extracts from Spatholobus suberectus and its active component catechin].

To study the anti-radiation effect and mechanism of ethanol extracts from Spatholobus suberectus and its active component catechin, ICR mice were exposed to 6Gy irradiation and randomly divided into normal group, model group, positive control group (amifostine, 43.6 mg•kg⁻¹, iv 30 min before irradiation), SSD group (10, 20, 40 g•kg⁻¹) and catechin group (50, 100, 200 mg•kg⁻¹). The mice were administered the appropriate drugs once a day after irradiation for 28 consecutive days. Blood samples were collected from the tail end and the number of peripheral blood cells was counted before irradiation and on day 1, 3, 7, 14, 21 and 28 using a microcell counter. Changes of thymus and spleen index of mice on day 7 were observed. The serum SOD, GSH-Px activity and MDA level were detected by the colorimetric method. The colony forming ability of bone marrow hematopoietic progenitor cells on day 7 was detected by semi solid culture method. The HE staining was adopted to observe the pathological changes. The apoptosis of bone marrow cells was detected by flow cytometry. The expression of cleaved caspase-3 and Bax of bone marrow cells were measured separately by western-blotting and immunohistochemistry method. SSD and catechin can both significantly revert the irradiated-induced decline in hematological parameters (RBC, WBC, PLT, Hb), improve thymus and spleen index, significantly enhance serum SOD and GSH-Px activity and decrease the MDA level. The proliferation and differentiation of hematopoietic progenitor cells in bone marrow were promoted, the apoptosis of bone marrow cells was significantly up-regulated and the expression of cleaved caspase-3 and Bax was significantly reduced in SSD and catechin group. SSD and catechin have significant anti-radiation effect and its mechanism may be related to hematopoietic promoting, antioxidant and anti-apoptotic effects.

AG4, a compound isolated from Radix Ardisiae Gigantifoliae, induces apoptosis in human nasopharyngeal cancer CNE cells through intrinsic and extrinsic apoptosis pathways.

3ß-O-{α-L-Pyran rhamnose-(1→3)-[ß-D-xylopyranose-(1→2)]-ß-D-glucopyranose-(1→4)-[ß-D-lucopyranose-(1→2)]-α-L-pyran arabinose}-cyclamiretin A (AG4) is a saponin component obtained from the Giantleaf Ardisia Rhizome (Rhizoma Ardisiae Gigantifoliae). The present study aimed to investigate the antitumor potential of AG4 and its possible mechanisms in human nasopharyngeal carcinoma cells (CNE). We exposed tumor cells to AG4 to investigate which cell line was the most sensitive to AG4. Cell viability was assessed using the MTT reduction assay, and the effects of AG4 on apoptosis, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and cell cycle were detected using a flow cytometer; the glutathione, superoxide dismutase and malondialdehyde activities were measured using colorimetric methods. The relative expressions of Bax, Bad, Bid, Bcl-2, and Fas mRNA were calculated using the (Equation is included in full-text article.)comparative method by real-time PCR studies and protein was detected by western blotting. AG4 markedly inhibited the growth of CNE cells by decreasing cell proliferation, inducing apoptosis, and blocking the cell cycle in the S phase. The release of caspase-3, caspase-8, and caspase-9 was stimulated by AG4 in CNE, and the decreased proliferation induced by AG4 was blocked by the inhibitor of pan caspase (Z-VAD-FMK). Moreover, the MMP was decreased in AG4-treated cells, and AG4-induced cell apoptosis was accompanied by a rapid and lasting increase in ROS, which was abolished by N-acetyl-L-cysteine (NAC); glutathione, superoxide dismutase, and malondialdehyde were regulated by AG4. AG4 inhibited Bcl-2 mRNA and protein expression and stimulated Bax, Bad, Bid, Fas mRNA, and protein expression in CNE cultures, suggesting an effect at the transcriptional and protein level. In addition, both the FasL inhibitor (AF-016) and the Bcl-2 family inhibitor (GX15-070) could prevent the cell apoptosis induced by AG4. The findings suggested that AG4-induced apoptosis in CNE cells involved a death receptor pathway and a Bcl-2 family-mediated mitochondrial signaling pathway by decreasing the MMPs in an ROS-dependent manner and regulating genes and proteins relative to apoptosis; also, regulation of cell cycles may also play a role in the antitumor mechanism of AG4.