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.

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.

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.

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.

[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.

Inhibition of the JAK/STAT pathway with ruxolitinib overcomes cisplatin resistance in non-small-cell lung cancer NSCLC.

This study was aimed to elucidate the roles of inhibition of related JAK/STAT pathways in regulating cytotoxicity induced by cisplatin in non-small-cell lung cancer (NSCLC) cell. We treated five non-small-cell lung cancer cell lines with cisplatin alone or with cisplatin and Jak2 inhibitor (ruxolitinib) and assessed cell viability, expression of Jak2 and STAT3 and cell apoptosis. We also investigated the effect of combination treatment inhibited tumor xenograft growth in two human NSCLC xenograft models bearing the cisplatin resistant (H1299) and sensitive (A549) cells. Different cell lines with different genetic background showed half-maximal inhibitory concentrations (IC50) of cisplatin from 4.66 to 68.28 µmol/L. They could be divided into cisplatin intrinsic resistant and cisplatin sensitive cell lines. In cisplatin-resistant cells with higher Jak2 and STAT3 expression, cisplatin and ruxolitinib combination dramatically suppressed the cell growth, down-regulated the expression of phosphorylated STAT3 and induced cleaved caspase-3 expression. Moreover combination with cisplatin and ruxolitinib also significantly inhibited the growth of resistant cell H1299, A549/DDP and H2347 in soft agar model. Finally, combination group significant inhibited the tumor growth and induced the caspase-3 expression compared with either single agent alone (P < 0.05) on the resistant cell xenografts model. The present study indicates that further study is warranted to determine the effectiveness of combination treatment with cisplatin and Jak2/stat3 pathway inhibitor for platinum-resistant NSCLC.

Antitumor activity of triterpenoid saponin-rich Adisia gigantifolia extract on human breast adenocarcinoma cells in vitro and in vivo.

The aim of this study was to explore whether the ethanolic extract of Ardisia gigantifolia rhizomes (AGB-5), a traditional herbal medicine from China, could affect the proliferation of human breast adenocarcinoma (MCF-7) cells in vitro and to explore the antitumor effects of AGB-5 in BALB/c mice engrafted with MCF-7 cells. The results showed that AGB-5 markedly inhibited the proliferation of MCF-7 cells with an IC50 value of 11.89±1.12 µg/mL, increased the S phase and decreased the G2/M phase without influence on G1 phase. MCF-7 cells treated with AGB-5 presented a dose-dependent increase of apoptosis compared with the control group. AGB-5 also significantly increased the activity of caspase-3 and -9 in a dose-dependent manner in MCF-7 cells. Furthermore, in an in vivo model, AGB-5 reduced tumor volume, brought back the red blood cell (RBC) and white blood cell (WBC) count near to normal value, enhanced superoxide dismutase and catalase level of MCF-7 bearing mice. This is the first study to verify the antitumor activity of A. gigantifolia in vivo. The results suggest that AGB-5 may have potential beneficial effects against human breast adenocarcinoma.

In vitro evaluation of the effects of various additives and polymers on nerve growth factor microspheres.

OBJECTIVE: To evaluate the effects of various additives or polymers on the in vitro characteristics of nerve growth factor (NGF) microspheres. MATERIALS AND METHODS: NGF microspheres were fabricated using polyethylene glycol (PEG), ovalbumin (OVA), bovine serum albumin (BSA) or glucose as protein protectors, and poly(lactide-co-glycolide) (PLGA) or poly(lactic acid) (PLA)/PLGA blends as encapsulation materials. RESULTS: Encapsulation efficiencies of the NGF microspheres with various additives or polymers were not more than 30%. A comparative study revealed that OVA was somewhat superior over others, and was thus chosen as the protective additive in subsequent experiments. Polymer analysis showed that NGF release from 1:1 PLA (η = 0.8):PLGA (75/25, η = 0.45) microspheres lasted for 90 d with a burst release rate of 12.7%. About 40% of the original bioactivity was retained on the 28th day, while 10% was left on the 90th day. DISCUSSION AND CONCLUSION: The combination of OVA as an additive and the PLA/PLGA blend as the coating matrix is suitable for encapsulation of NGF in microspheres for extended release.

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.

Development and internal validation of a model for predicting cefoperazone/sulbactam-associated coagulation disorders in Chinese inpatients.

BACKGROUND AND AIM: The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. METHODS: A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn't develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. RESULTS: 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8%. A final population of 252 cases and 252 controls was included for model development and validation. Malnutrition (OR = 2.41 (1.56-3.77)), history of recent bleeding (OR = 1.95 (1.32-2.90)), treatment duration (OR = 1.10 (1.07-1.14)), combination with carbapenems (OR = 4.43 (1.85-11.88)), and serum creatinine (OR = 1.01 (1.00-1.01)) were identified as final predictors. The model showed good discrimination, calibration, and clinical practicality, with the validated area under the receiver operating characteristic curve being 0.723 (0.683-0.770). CONCLUSIONS: The model with good performance quantifies the risk for CPZ/SAM-associated coagulation disorders, and may support individual assessment and interventions to mitigate the risk after external validation.

Methanolysis of triterpenoid saponin from Ardisia gigantifolia stapf. and structure-activity relationship study against cancer cells.

Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia gigantifolia stapf. and one potential anti-tumor saponin was methanolysised by H2SO4 to afford four new compounds. The seventeen compounds were evaluated for their anti-proliferative activity on A549, HCT-8 and Bel-7402 cells. The structure-activity relationship analysis indicated that the incorporation of =O group at C-16, L-rhamnose at R(5) and acetyl group at OH-6 of the D-glucose lead to a significant increase of the cytotoxic activity on A549 and HCT-8 but significant reduction of the cytotoxic activity on Bel-7402 cells. The synthesized saponins losing 13,28-epoxy and CHO at C-30, losed their cytotoxicities on A549 and HCT-8 cells, suggesting that the two moieties play an essential role for activity. 3ß-O-α-L-rhamnopyranosyl-(1→3)-[ß-D-xylopyranosyl-(1→2)]-ß-D-glucopyranosyl-(1→4)-[ß-D-glucopyranosyl-(1→2)]-α-l-arabinopyranoside-16α-hydroxy-13,28-epoxy-oleanane (2) showed better inhibitory activity to Bel-7402 (IC50 0.86 µM) than that of 5-FU (IC50 8.30 µM), which indicate that five saccharide and methyl moiety at C-30 are important for anti-proliferative activity. The activities of saponins 15>14, 17>16, suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather than 30(S) on Bel-7402 cells. Further molecular mechanism studies of saponins 1 and 2 were carried out on the cell cycle distribution of Bel-7402 cells.

A new triterpenoid saponin from Ardisia gigantifolia.

A new triterpenoid saponin, named 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl-(1 â†’ 2)-[α-l-rhamnopyranosyl-(1 â†’ 3)]-ß-d-glucopyranosyl-(1 â†’ 4)-[ß-d-glucopyranosyl-(1 â†’ 2)]-α-l-arabinopyranosyl-3ß,16α,28,30-tetrahydroxy-olean-12-ene (1), along with four known triterpenoids (2-5), was isolated from the rhizomes of Ardisia gigantifolia. Their structures were elucidated by spectroscopic methods. Compounds 1-4 showed cytotoxic activity against Hela, EJ, BCG, and HepG-2 cell lines. The percentage of early apoptotic cells after treatment with 1 was significantly increased compared with control cells (p < 0.05).

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.

Protection of SH-SY5Y neuronal cells from glutamate-induced apoptosis by 3,6'-disinapoyl sucrose, a bioactive compound isolated from Radix Polygala.

The neuroprotective effects of 3,6'-disinapoyl sucrose (DISS) from Radix Polygala against glutamate-induced SH-SY5Y neuronal cells injury were evaluated in the present study. SH-SY5Y neuronal cells were pretreated with glutamate (8 mM) for 30 min followed by cotreatment with DISS for 12 h. Cell viability was determined by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide (MTT) assay, and apoptosis was confirmed by cell morphology and flow cytometry assay, evaluated with propidium iodide dye. Treatment with DISS (0.6, 6, and 60 µmol/L) increased cell viability dose dependently, inhibited LDH release, and attenuated apoptosis. The mechanisms by which DISS protected neuron cells from glutamate-induced excitotoxicity included the downregulation of proapoptotic gene Bax and the upregulation of antiapoptotic gene Bcl-2. The present findings indicated that DISS exerts neuroprotective effects against glutamate toxicity, which might be of importance and contribute to its clinical efficacy for the treatment of neurodegenerative diseases.

Synthesis and inhibitory effect of piperine derivates on monoamine oxidase.

A series of piperine derivates (1-19) have been designed, synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. It is worth noting that most of the small amine moieties substituted on the piperidine ring proved to be potent and selective inhibitors of MAO-B rather than of MAO-A. 5-(3,4-methylenedioxyphenyl)-2E,4E-pentadienoic acid n-propyl amide (3) showed the greatest MAO-B inhibitory activity (IC(50)(MAO-B)=0.045 µM) and good selectivity (IC(50)(MAO-A)=3.66 µM). The conjugated double bond and carbonyl group of piperine are proved to be an essential feature for piperine and related alkylamides to exhibit MAO-inhibitory activity. Binding mode of the titled compounds was predicted using FlexX algorithm. The design and optimization of novel small molecule monoamine oxidase inhibitors will be guided by the results of this report.

Risk factors for thrombocytopenia in adult chinese patients receiving linezolid therapy.

BACKGROUND: Linezolid (LZD), an oxazolidinone antibiotic agent, has excellent activity and bioavailability against most methicillin-sensitive and methicillin-resistant gram-positive bacteria. Although LZD is generally well tolerated, several studies have found adverse hematologic effects, of which thrombocytopenia is of most concern. OBJECTIVE: To investigate the risk factors for thrombocytopenia in patients who received oral or parenteral LZD therapy between February 1 and November 30, 2010. METHODS: Data were extracted retrospectively from the electronic medical records in our hospital information system. Thrombocytopenia was defined as either a final platelet count of <100 × 10(9)/L (criterion 1) or a 25% reduction from the baseline platelet count (criterion 2). Risk factors were determined using logistic regression analysis, and clinical features were predicted using receiver operating characteristic curves. RESULTS: The study included 254 patients, with mean (SD) age of 59 (17.66) years. The duration of LZD therapy was 9.43 (5.63) days. Thrombocytopenia developed in 69 patients (27.2%), as defined by criterion 1, and in 127 patients (50%), as defined by criterion 2. At univariate analysis, age, weight, creatinine clearance, serum albumin concentration, baseline platelet count, daily dosage, and concomitant use of caspofungin, levofloxacin, and meropenem were significant risk factors for thrombocytopenia. At multivariate analysis and using ROC curves, daily dose ≥18.75 mg/kg, baseline platelet count ≤181 × 10(9)/L, duration of LZD therapy ≥10 days, and concomitant use of caspofungin and levofloxacin were independent risk factors for thrombocytopenia as defined by criterion 1, whereas creatinine clearance ≤88.39 mL/min/1.73 m(2), serum albumin concentration ≤33.5 g/L, daily dose ≥18.46 mg/kg, and caspofungin were independent risk factors for thrombocytopenia as defined by criterion 2. CONCLUSIONS: The incidence of LZD-related thrombocytopenia in the Chinese population is much higher than that suggested by the drug instructions. Low pretreatment platelet count, low body weight, low serum albumin concentration, long-term drug administration, advanced age, renal insufficiency, and concomitant use of caspofungin, levofloxacin, and meropenem have been identified as risk factors. Although predictors have been proposed for use in clinical practice to screen for patients at high risk who require intensified monitoring, further research on the dosage-based pharmacokinetics and pharmacodynamics of LZD are urgently needed.

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.

Protective role of tea polyphenols in combination against radiation-induced haematopoietic and biochemical alterations in mice.

The purpose of this study was to investigate the radioprotective effects of tea polyphenols (TPs) in various combinations against radiation-induced damage in mice. Mice were divided into different groups: non-irradiated control, irradiated control, amifostine (43.6 mg/kg, i.v. 30 min before irradiation; positive control) and various combinations of tea polyphenols in different doses. The radioprotective effect on the haematopoietic system, serum cytokines and endogenous antioxidant enzymes were studied. TP50, containing approximately 50% of (-)-epigallochatechin-3-gallate in addition to other catechins, showed the greatest radioprotective effect against radiation-induced changes in haematological parameters (red blood cell count, white blood cell count and haemoglobin), and maintained the spleen and thymus indices unchanged (spleen or thymus weight/body weight × 1000). Tea polyphenols also significantly decreased radiation-induced lipid peroxidation (malondialdehyde levels), elevated endogenous antioxidant enzymes (superoxide dismutase) and reduced the serum cytokines which were elevated in radiation-induced toxicity. This evidence shows the potential of tea polyphenols, particularly in the combination found in TP50, as radioprotectors in mice, especially regarding recovery of the haematopoietic system, antioxidant potential activity and reduction of inflammatory cytokines.