Effects of pharmacist-led interventions on glycaemic control, adherence, disease management and health-related quality of life in patients with type 2 diabetes: a protocol for a network meta-analysis.

INTRODUCTION: The increase in the number of patients with uncontrolled type 2 diabetes mellitus (T2DM) is in need of effective management interventions. However, research to date has been limited to the evaluation of the outcomes of community pharmacists alone. Therefore, the aim of the study protocol is to compare the effects of clinical pharmacist-led intervention strategies for the management of T2DM in the outpatient settings. METHOD AND ANALYSIS: The study will collect and analyse data applying standard Cochrane methodological procedures. A search for eligible studies and ongoing trials will be conducted using PubMed, Embase, Medline (via Ovid), EBSCO (via Ovid), Lippincott Williams & Wilkins (LWW) Journals (via Ovid), ProQuest Health and Medical Complete, and ClinicalTrials.gov (clinicaltrials.gov) from database inception to December 2023. Clinical and health outcomes will be measured using both glycaemic control related indicators (eg, glycated haemoglobin, fasting blood glucose, postprandial glucose) and general indicators (eg, adherence, disease management and health-related quality of life). The meta-analysis will conduct pairwise meta-analysis using random effects models and network meta-analysis (NMA) employing the Bayesian hierarchical model. The visualisation and statistical analysis will be carried out using RevMan, R Studio and ADDIS. Additionally, we will evaluate the certainty of the evidence by using Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: There will be no primary data collection from NMA participants, and there is no requirement for formal ethical review. Our aim is to present the results of this NMA in a peer-reviewed scientific journal, at conferences, and in the mainstream media. PROSPERO REGISTRATION NUMBER: CRD42022355368.

The Influence of Diagnosis Intervention Packet Policy Intervention on Medication Structure and Drug Cost of Elderly Hypertensive Inpatients in China: A Multicenter Interrupted Time-Series Analysis.

Background: DIP is a new medical insurance payment system developed in China which was implemented in Guangzhou in January 2018, but few studies have focused on its intervention effect on the drug burden of elderly hypertensive patients. Methods: Nine medical institutions in Guangzhou, China, were selected, among which, daily full medical orders of elderly hypertensive inpatients from 2016 to 2020 were randomly collected. To assess the impact of DIP policy intervention on patient drug burden, we took the data after policy implementation in January 2018, as the intervention data, and applied a segmented regression model with interrupted time series to analyze the trend and changes in average daily drug costs per month and medication structure, stratified by age, sex, and inpatient department. Results: A total of 34,276 elderly hypertensive patients' daily full medical orders were obtained. The immediate level change of drug costs after intervention was -23.884 RMB/month (P = 0.652), and the trend change was statistically significant (-15.642 RMB/month, P = 0.002). The relative cumulative effect at the end of the study was -78.860% (95% CI: -86.087% to -69.076%), and the intervention effect was more significant in surgical and male patients. The analysis of drug structure changes showed that after the implementation of the DIP policy intervention, the proportion of anti-infective drugs, anti-tumor drugs, and biological products all showed a significant downward trend (P < 0.05), while nutritional drugs showed a significant upward trend (P = 0.011), but no immediate horizontal change in slope was observed. Conclusion: The typical practice in China showed that DIP policy intervention can improve the drug burden of elderly hypertensive hospitalized patients and has a stable long-term effect, and the intervention effect is not consistent across different clinical department and populations with different characteristics, and it would also cause changes in the medication structure.

Targeting mTOR Complex 2 in Castration-Resistant Prostate Cancer with Acquired Docetaxel Resistance.

Purpose: Mammalian Target of rapamycin (mTOR) plays a central role in regulating cell growth, proliferation, and cell cycle. The key component of mTORC2 is highly expressed in docetaxel-resistant prostate cells. However, the underlying molecular effects on prostate cells remain unclear. Methods: A docetaxel-resistant human prostate cell line (PC-3/DTX) was constructed to investigate the role of mTORC2 in docetaxel resistance. The lentivirus was transfected into cells to knock down the expression of Rictor, and cell viability was measured by Cell Counting Kit 8 (CCK-8). Flow cytometry was used to analyze the cell cycle, and the changes in related signal cascades were assessed by immunohistochemistry (IHC) staining and Western blot. Results: Docetaxel showed the lowest IC50 (50% inhibitory concentration) in PC-3/DTX cells with sh-RNA. Decreased Rictor expression resulted in a larger proportion of arrested cells in the G0/G1 phase in PC-3/DTX cells. The IC50 values of the AZD8055 group were lower than in the Rapamycin group when treated with docetaxel again. Furthermore, a larger proportion of PC-3/DTX cells were arrested in the G0/G1 phase in the AZD8055 group compared to the Rapamycin group. The IHC results of the prostate cancer tissues from a CRPC patient revealed the over expression of Rictor only, while Raptor expression was unaffected. Conclusion: We investigated the role of mTORC2 signaling on the acquired docetaxel -resistant PC-3 cells to identify potential methods for clinical treatment. MTORC2 expression is essential for docetaxel drug resistance of PC-3 cells. The mTORC1/2 inhibitor AZD8055 caused more significant disruption of mTORC2 kinase activity than the mTORC1 inhibitor Rapamycin, which lead to decreased docetaxel-mediated resistance. Therefore, reversing docetaxel resistance, may become a therapeutic option in the treatment of mCRPC patients.

TPGS-based and S-thanatin functionalized nanorods for overcoming drug resistance in Klebsiella pneumonia.

Tigecycline is regarded as the last line of defense to combat multidrug-resistant Klebsiella pneumoniae. However, increasing utilization has led to rising drug resistance and treatment failure. Here, we design a D-alpha tocopheryl polyethylene glycol succinate-modified and S-thanatin peptide-functionalized nanorods based on calcium phosphate nanoparticles for tigecycline delivery and pneumonia therapy caused by tigecycline-resistant Klebsiella pneumoniae. After incubation with bacteria, the fabricated nanorods can enhance tigecycline accumulation in bacteria via the inhibitory effect on efflux pumps exerted by D-alpha tocopheryl polyethylene glycol succinate and the targeting capacity of S-thanatin to bacteria. The synergistic antibacterial capacity between S-thanatin and tigecycline further enhances the antibacterial activity of nanorods, thus overcoming the tigecycline resistance of Klebsiella pneumoniae. After intravenous injection, nanorods significantly reduces the counts of white blood cells and neutrophils, decreases bacterial colonies, and ameliorates neutrophil infiltration events, thereby largely increasing the survival rate of mice with pneumonia. These findings may provide a therapeutic strategy for infections caused by drug-resistant bacteria.

Risk Perception, Self-efficacy, Lay Theories of Health, and Engagement in Health-Protective Behaviors Among Hospital Pharmacists During the COVID-19 Pandemic.

BACKGROUND: Risk perception is an important predictor of health-protective behaviors during pandemics. However, the underlying mechanism connecting risk perception and health-protective behaviors is not well understood. The current study investigates how risk perception predicts hospital pharmacists' engagement in health-protective behaviors during the peak period of COVID-19 pandemic in China and the mediating effects of lay theories of health and self-efficacy. METHOD: A cross-sectional study on risk perception and engagement in health-protective behaviors was conducted among hospital pharmacists during the COVID-19 pandemic in China. A total of 4121 hospital pharmacists completed the study. RESULTS: Risk perception, self-efficacy, and lay theories of health were significant predictors of health-protective behaviors among pharmacists. Lay (entity) theories of health and self-efficacy mediated the relationship between risk perception and engagement in health-protective behaviors among hospital pharmacists. CONCLUSION: Risk perception, self-efficacy, and lay theories (entity versus incremental) of health significantly predicted hospital pharmacists' engagement in health-protective behaviors during the COVID-19 pandemic in China.

Platinum-Induced Peripheral Neuropathy (PIPN): ROS-Related Mechanism, Therapeutic Agents, and Nanosystems.

Platinum (Pt) drugs (e.g., oxaliplatin, cisplatin) are applied in the clinic worldwide for the treatment of various cancers. However, platinum-induced peripheral neuropathy (PIPN) caused by the accumulation of Pt in the peripheral nervous system limits the clinical application, whose prevention and treatment are still a huge challenge. To date, Pt-induced reactive oxygen species (ROS) generation has been studied as one of the primary mechanisms of PIPN, whose downregulation would be feasible to relieve PIPN. This review will discuss ROS-related PIPN mechanisms including Pt accumulation in the dorsal root ganglia (DRG), ROS generation, and cellular regulation. Based on them, some antioxidant therapeutic drugs will be summarized in detail to alleviate the Pt-induced ROS overproduction. More importantly, we focus on the cutting-edge nanotechnology in view of ROS-related PIPN mechanisms and will discuss the rational fabrication of tailor-made nanosystems for efficiently preventing and treating PIPN. Last, the future prospects and potential breakthroughs of these anti-ROS agents and nanosystems will be briefly discussed.

A Retrospective Study of 158 Cases on the Risk Factors for Recurrence in Ameloblastoma.

Background: Ameloblastoma is an odontogenic tumor occurring in jaws, with local aggressiveness and postoperative recurrence. This study was aim to investigate the clinical and radiographic risk factors for recurrence in ameloblastoma. Methods: Patients diagnosed with ameloblastoma between March 2009 and March 2019 were retrospectively analyzed. Clinical and Radiological data and follow-up records were collected. Survival analyses were performed by Kaplan-Meier and log-rank tests, as well as Cox proportional hazards model. Results: One hundred and fifty-eight patients (104 males and 54 females were enrolled. The overall recurrence rate for ameloblastoma was 13.29%, and 10.76% recurred within 5 years. Most of the tumors were located in mandible (86.71%), while the rest 21 cases were in maxilla (13.29%). More than half cases (55.06%) showed multilocular radiolucency, 61 cases (38.61%) showed unilocular radiolucency. Significant differences were found with amelobastoma recurrence rate related to treatment modality, impacted tooth and root resorption (P =0.002, 0.022 and 0.007 respectively). Conclusions: Treatment modality, impacted tooth and root resorption all showed statistically significant associations with the recurrence rate in ameloblastoma. However, due to the limitation of this study, further studies are needed to reveal the true mechanism of ameloblastoma recurrence.

The molecular and cellular insight into the toxicology of bortezomib-induced peripheral neuropathy.

The proteasome inhibitor bortezomib (BTZ) is a first-line antitumor drug, mainly used for multiple myeloma treatment. However, BTZ shows prominent toxicity in the peripheral nervous system, termed BTZ-induced peripheral neuropathy (BIPN). BIPN is characterized by neuropathic pain, resulting in a dose reduction or even treatment withdrawal. To date, the pathological mechanism of BIPN has not been elucidated. There is still no effective strategy to prevent or treat BIPN. This review summarizes the pathological mechanisms of BIPN, which involves the pathological changes of Schwann cells, neurons, astrocytes and macrophages. A better knowledge of the pathological mechanisms of BIPN would provide new ideas for therapeutic interventions of BIPN patients.

Co-transfection with BMP2 and FGF2 via chitosan nanoparticles potentiates osteogenesis in human adipose-derived stromal cells in vitro.

OBJECTIVE: To investigate if co-transfection of human bone morphogenetic protein 2 (BMP-2, BMP2) and human fibroblast growth factor 2 (FGF2, FGF2) via chitosan nanoparticles promotes osteogenesis in human adipose tissue-derived stem cells (ADSCs) in vitro. MATERIALS AND METHODS: Recombinant BMP2 and/or FGF2 expression vectors were constructed and packaged into chitosan nanoparticles. The chitosan nanoparticles were characterized by atomic force microscopy. Gene and protein expression levels of BMP-2 and FGF2 in ADSCs in vitro were evaluated by real-time polymerase chain reaction (PCR), western blot, and enzyme-linked immunosorbent assay. Osteocalcin (OCN) and bone sialoprotein (BSP) gene expression were also evaluated by real-time PCR to assess osteogenesis. RESULTS: The prepared chitosan nanoparticles were spherical with a relatively homogenous size distribution. The BMP2 and FGF2 vectors were successfully transfected into ADSCs. BMP-2 and FGF2 mRNA and protein levels were significantly up-regulated in the co-transfection group compared with the control group. OCN and BSP mRNA levels were also significantly increased in the co-transfection group compared with cells transfected with BMP2 or FGF2 alone, suggesting that co-transfection significantly enhanced osteogenesis. CONCLUSIONS: Co-transfection of human ADSCs with BMP2/FGF2 via chitosan nanoparticles efficiently promotes the osteogenic properties of ADSCs in vitro.

Improvement in Hypertension Management with Pharmacological and Non- Pharmacological Approaches: Current Perspectives.

PURPOSE: Improving hypertension management is still one of the biggest challenges in public health worldwide. Existing guidelines do not reach a consensus on the optimal Blood Pressure (BP) target. Therefore, how to effectively manage hypertension based on individual characteristics of patients, combined with the pharmacological and non-pharmacological approach, has become a problem to be urgently considered. METHODS: Reports published in PubMed that covered Pharmacological and Non-Pharmacological Approaches in subjects taking hypertension management were reviewed by the group independently and collectively. Practical recommendations for hypertension management were established by the panel. RESULTS: Pharmacological mechanism, action characteristics, and main adverse reactions varied across different pharmacological agents, and patients with hypertension often require a combination of antihypertensive medications to achieve the target BP range. Non-pharmacological treatment provides an additional effective method for improving therapy adherence and long-term BP control, thus reducing the risk of cardiovascular diseases, and slowing down the progression of the disease. CONCLUSION: This review summarizes the available literature on the most convincing guideline principles, pharmacological treatment, biotechnology interference, interventional surgical treatment, managing hypertension with technical means of big data, Artificial Intelligence and Behavioral Intervention, as well as providing future directions, for facilitating Current and Developing knowledge into clinical implementation.

Cost-effectiveness of rivaroxaban versus warfarin in non-valvular atrial fibrillation patients with chronic kidney disease in China.

WHAT IS KNOWN AND OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients with chronic kidney disease (CKD), rivaroxaban was not inferior to warfarin in preventing stroke and systemic embolism. However, a comparative evaluation of the cost-effectiveness of rivaroxaban and warfarin therapies for NVAF patients at different renal function levels has not yet been reported, and this study aimed to estimate the cost-effectiveness of rivaroxaban compared with warfarin in Chinese NVAF patients with CKD. METHODS: A Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs associated with the use of rivaroxaban relative to warfarin in patients with NVAF at different estimated glomerular filtration rate (eGFR) levels as follows: 30 to <50, 50 to <80 and ≥80 mL/min. Input parameters were sourced from the clinical literature. Probabilistic sensitivity analyses were performed to assess model uncertainty. RESULTS AND DISCUSSION: The incrementalQALYs with rivaroxaban was slightly increased by approximately 0.3 QALY as compared with that with warfarin in all the subgroups, resulting in an ICER of $9,736/QALY (eGFR, 30 to <50 mL/min), $9,758/QALY (50 to <80 mL/min) and $9,969/QALY (≥80 mL/min). The probabilistic sensitivity analysis suggested a chance of >80% that the ICER would be lower than the willingness-to-pay threshold of three times the GDP of China in 2019 in all the subgroups. Results were consistent even under the assumption of anticoagulant discontinuation after major bleeding events. The model was most sensitive to event-free-related utility and survival rates. WHAT IS NEW AND CONCLUSION: The existing evidence supports the cost-effectiveness of rivaroxaban therapy as an alternative anticoagulant to warfarin for patients with NVAF at different renal function levels.

Assessment of the Potential Adverse Events Related to Ribavirin-Interferon Combination for Novel Coronavirus Therapy.

PURPOSE: We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). METHODS: Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. RESULTS: A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. CONCLUSION: The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.

Cost-effectiveness analysis of cinacalcet for haemodialysis patients with moderate-to-severe secondary hyperparathyroidism in China: evaluation based on the EVOLVE trial.

OBJECTIVE: As the cost-effectiveness evaluation of cinacalcet and conventional therapy in China has not been reported, the objective of this study was to make a pharmacoeconomic evaluation of cinacalcet specific to the Chinese healthcare setting in patients with moderate-to-severe secondary hyperparathyroidism (SHPT) undergoing dialysis. DESIGNS: Data from Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events trial were used for this analysis. A semi-Markov model was constructed to estimate quality-adjusted life years (QALYs) and lifetime costs in cinacalcet plus conventional therapy (cinacalcet strategy) compared with conventional therapy (standard strategy), in patients with moderate-to-severe SHPT undergoing dialysis. Treatment effect estimates from the unadjusted intent-to-treat (ITT) analysis and covariate-adjusted ITT analysis were used as the main analyses. Model sensitivity to variations in individual inputs and overall decision uncertainty were assessed through probabilistic sensitivity analyses. PRIMARY AND SECONDARY OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) as measured by cost per QALY gained. RESULTS: The ICER for cinacalcet strategy was US$44 400 per QALY gained using the covariate-adjusted ITT analysis. Probabilistic sensitivity analysis suggested a 46.2% chance of the ICER being below a willingness-to-pay threshold of US$26 508. Treatment effects from unadjusted ITT analysis yielded an ICER of US$87 210 per QALY. The model was most sensitive to the treatment effect on mortality. CONCLUSIONS: Existing evidence does not support the cost-effectiveness of cinacalcet strategy in patients with moderate-to-severe SHPT undergoing dialysis when applying a willingness-to-pay threshold of US$26 508 per QALY, whether it is using the treatment effect from covariate-adjusted ITT analysis or unadjusted ITT analysis.

Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05-1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44-9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3-5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0-4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.

[Management of a colon cancer patient complicated with COVID-19].

OBJECTIVE: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). METHODS: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. RESULTS: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. CONCLUSIONS: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

[Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data].

OBJECTIVE: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. METHODS: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). RESULTS: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. CONCLUSIONS: In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

Development and Validation of a Medication Selection Model Under Clinical Application of Renin-Angiotensin Inhibitor Combined with Calcium Channel Blocker for Hypertension Patients.

BACKGROUND This study evaluated the impact of clinical features and concomitant conditions on the clinical selection of different renin-angiotensin system (RAS) inhibitors in patients with hypertension, and built a renin-angiotensin inhibitors selection model (RAISM) to provide a reference for clinical decision making. MATERIAL AND METHODS We included 213 hypertensive patients in the study cohort; patients were divided into two groups: the angiotensin-converting enzyme inhibitor (ACEI) combined with calcium channel blocker (CCB) group (ACEI+CCB group) and the angiotensin receptor antagonist (ARB) combined with CCB group (ARB+CCB group). Basic demographic characteristics and concomitant conditions of the patients were compared. Single-factor and multi-factor analysis was performed by adopting logistic regression model. The RAISM was established by utilizing the nomograph technology. C-index and calibration curve were used to evaluate the model's efficacy. RESULTS In the study, 34.27% of the patients used ACEI+CCB and 65.73% of patients used ARB+CCB. The difference in age, body mass index (BMI), elderly patient, diabetes, renal dysfunction, and hyperlipidemia between the 2 groups determined medication selection. To be specific, compared to the group using ARB+CCB, the odds ratios and 95% confidence interval (CI) of the aforementioned factors for the ACEI+CCB group were 0.476 (0.319-0.711), 1.274 (1.001-1.622), 0.365 (0.180-0.743), 0.471 (0.203-1.092), 0.542 (0.268-1.094), and 0.270 (0.100-0.728), respectively; The C-index of RAISM acquired from the model construction parameters was 0.699, and the correction curve demonstrated that the model has good discriminative ability. CONCLUSIONS The outcome of our study suggests that independent discriminating factors that influence the clinical selection of different RAS inhibitors were elderly patient, renal insufficiency, and hyperlipidemia; and the RAISM constructed in this study has good predictability and clinical benefit.

Protective effects of Corbrin Capsule against permanent cerebral ischemia in mice.

Corbrin Capsule is a traditional Chinese patent medicine with the main component of fermentative cordyceps fungus powder (Cs-C-Q80). The indications of Corbrin Capsule include chronic renal insufficiency, chronic obstructive pulmonary (COPD), pulmonary fibrosis, and chronic bronchitis. However, the effects of Corbrin Capsule on acute cerebral ischemia are still unclear. The objective of this study was to explore the preventive effect of Corbrin Capsule in permanent and transient middle cerebral artery occlusion (MACO) mice model. Male C57BL/6 mice were given Corbrin of 0.04, 0.2 and 1 mg/kg by gavage once a day for 3, 7 or 14 days and then subjected to pMCAO or tMCAO. Infarct volumes, neurological deficit score, ATP concentration, SOD activity and MDA content were assessed. Results showed that prolonged pretreatment with Corbrin (1.0 mg/kg) to 7 days or more effectively ameliorated brain infarct and neurological scores in pMCAO mice. Shorter (3 days) or without pretreatment of Corbrin was invalid, suggesting a pretreatment time window. The ATP concentration was significantly increased with effective Corbrin pretreatments in ischemic brains, while the content of MDA sharply decreased in Corbrin groups. In tMCAO mice, Corbrin showed no neuroprotection even with pretreatment. In conclusion, long-term pre-administration of Corbrin Capsule is necessary for its anti-cerebral ischemic effects, and the underlying mechanisms might be associated with increase of ATP concentration and the anti-inflammatory effects in ischemic brain tissue.

Aromatase inhibitors and risk of cardiovascular events in breast cancer patients: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular events (CVEs) was considered as one of the primary cause to reduce the quality of life in breast cancer patients with aromatase inhibitors (AIs) treatment, which has not been sufficiently addressed. The aim of this study was to assess the correlation between risk of CVEs and AIs in patients with breast cancer. METHODS: Included studies were obtained from the databases of Embase, Pubmed, Cochrane Library, Clinical Trials.gov, and reference lists. The main outcome measures were overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Furthermore, the association and the risk differences among different tumor types, AIs,ages,or treatment regimens were conducted. Fixed-effect or random-effect models were applied in the statistical analyses according to the heterogeneity. Our analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Seventeen studies, which included 44,411 subjects, were included in our analyses. The overall incidence of CVEs in AIs group was 13.02% (95% CI: 8.15-20.17%) and almost all of the high-grade CVEs occurred in patients treated with AIs. The pooled ORs of CVEs was 0.9940 (95% CI: 0.8545-1.1562). Under sub-group analysis, the incidence of CVEs related to exemestane was higher than that of controls (OR = 1.1564, 95% CI: 1.0656-1.2549), but no statistical differences in risk of CVEs were found in other sub-group analysis. No evidence of publication bias was found for incidence of CVEs in our meta-analysis by a funnel plot. CONCLUSIONS: These results suggest that patients with breast cancer treated with AIs do not have a significant risk of developing CVEs in comparison with the controls, and exemestane might not be considered as the alternative AI to the breast cancer patients from the perspective of CVEs. Further studies are recommended to investigate this association and the risk differences among different tumor types, AIs or treatment regimens.

Incidence of menopausal symptoms in postmenopausal breast cancer patients treated with aromatase inhibitors.

Aromatase inhibitors (AIs) are the standard of care for postmenopausal women with estrogen receptor-positive breast cancer. Here, we performed a meta-analysis to evaluate the occurrence of menopausal symptoms in breast cancer patients receiving the AI therapy. Patients treated with AIs had an increased risk of all-grade arthralgia (1.63 [95% CI: 1.34-1.98]) and insomnia (1.24 [95% CI: 1.14-1.34]). The overall incidence of hot flashes, fatigue, arthralgia, sweating, and insomnia in patients receiving AIs was 30.47% (95% CI: 25.51%-35.93%), 17.16% (95% CI: 14%-20.85%), 17.91% (95% CI: 11.29%-27.22%), 14.64% (95% CI: 11.46%-18.52%), and 16.52% (95% CI: 12.45%-21.6 %), respectively. Both arthralgia (RR = 0.34, 95% CI: 0.16-0.75) and sweating (RR = 11.02, 95% CI: 4.11-29.57) differed between patients with early- and advanced-stage breast cancer. Our findings indicates that AIs are associated with a significant risk of developing arthralgia and insomnia in breast cancer patients. Effective early detection and management of menopausal symptoms would likely lead to safer use of AIs in breast cancer patients.