The Potential of Clostridium butyricum to Preserve Gut Health, and to Mitigate Non-AIDS Comorbidities in People Living with HIV.

A dramatic reduction in mortality among people living with HIV (PLWH) has been achieved during the modern antiretroviral therapy (ART) era. However, ART does not restore gut barrier function even after long-term viral suppression, allowing microbial products to enter the systemic blood circulation and induce chronic immune activation. In PLWH, a chronic state of systemic inflammation exists and persists, which increases the risk of development of inflammation-associated non-AIDS comorbidities such as metabolic disorders, cardiovascular diseases, and cancer. Clostridium butyricum is a human butyrate-producing symbiont present in the gut microbiome. Convergent evidence has demonstrated favorable effects of C. butyricum for gastrointestinal health, including maintenance of the structural and functional integrity of the gut barrier, inhibition of pathogenic bacteria within the intestine, and reduction of microbial translocation. Moreover, C. butyricum supplementation has been observed to have a positive effect on various inflammation-related diseases such as diabetes, ulcerative colitis, and cancer, which are also recognized as non-AIDS comorbidities associated with epithelial gut damage. There is currently scant published research in the literature, focusing on the influence of C. butyricum in the gut of PLWH. In this hypothesis review, we speculate the use of C. butyricum as a probiotic oral supplementation may well emerge as a potential future synergistic adjunctive strategy in PLWH, in tandem with ART, to restore and consolidate intestinal barrier integrity, repair the leaky gut, prevent microbial translocation from the gut, and reduce both gut and systemic inflammation, with the ultimate objective of decreasing the risk for development of non-AIDS comorbidities in PLWH.

The inhibition of FTO attenuates the antifibrotic effect of leonurine in rat cardiac fibroblasts.

BACKGROUND: Myocardial fibrosis (MF) is a common pathological condition in cardiovascular diseases that often causes severe cardiac dysfunction. MF is characterized by changes in cardiomyocytes, cardiac fibroblasts (CFs), levels of collagen (Col) -1, -3, and overdeposition of the extracellular matrix. Our previous research showed that leonurine (LE) effectively inhibits collagen synthesis and differentiation of CFs, but the mechanism is not fully elucidated. Recent evidence indicates that fat mass and obesity-associated proteins (FTO) regulates the occurrence and development of MF. This study aimed to explore the role of FTO in the antifibrotic effects of LE. METHODS: Neonatal rat CFs were isolated, and induced using angiotensin II (Ang II) to establish a cell model of MF. Cell viability, wound healing and transwell assays were used to detect cell activity and migration ability. The protein and mRNA levels of MF-related factors were measured following stimulation with Ang II and LE under normal conditions or after FTO knockdown. The RNA methylation level was measured by dot blot assay. RESULTS: The results showed that LE (20, 40 µM) was not toxic to normal CFs. LE reduced the proliferation, migration and collagen synthesis of Ang II-induced CFs. Further investigation showed that FTO was downregulated by Ang II stimulation, whereas LE reversed this effect. FTO knockdown facilitated the migration of CFs, upregulated the protein levels of Col-3, α-SMA and Col-1 in Ang II and LE-stimulated CFs, and enhanced the fluorescence intensity of α-SMA. Furthermore, LE reduced N6-methyladenosine (m6A) RNA methylation, which was partially blocked by FTO knockdown. FTO knockdown also reduced the expression levels of p53 protein in Ang II and LE-stimulated CFs. CONCLUSIONS: Our findings suggest that the inhibition of FTO may attenuate the antifibrotic effect of LE in CFs, suggesting that FTO may serve as a key protein for anti-MF of LE.

The p53/miR-29a-3p axis mediates the antifibrotic effect of leonurine on angiotensin II-stimulated rat cardiac fibroblasts.

Overactivation of cardiac fibroblasts (CFs) is one of the main causes of myocardial fibrosis (MF), and inhibition of CF activation is a crucial strategy for MF therapy. A previous study by our group demonstrated that leonurine (LE) effectively inhibits collagen synthesis and myofibroblast generation originated from CFs, and eventually mitigates the progression of MF (where miR-29a-3p is likely to be a vital mediator). However, the underlying mechanisms involved in this process remain unknown. Thus, the present study aimed to investigate the precise role of miR-29a-3p in LE-treated CFs, and to elucidate the pharmacological effects of LE on MF. Neonatal rat CFs were isolated and stimulated by angiotensin II (Ang II) to mimic the pathological process of MF in vitro. The results show that LE distinctly inhibits collagen synthesis, as well as the proliferation, differentiation and migration of CFs, all of which could be induced by Ang II. In addition, LE promotes apoptosis in CFs under Ang II stimulation. During this process, the down-regulated expressions of miR-29a-3p and p53 are partly restored by LE. Either knockdown of miR-29a-3p or inhibition of p53 by PFT-α (a p53 inhibitor) blocks the antifibrotic effect of LE. Notably, PFT-α suppresses miR-29a-3p levels in CFs under both normal and Ang II-treated conditions. Furthermore, ChIP analysis confirmed that p53 is bound to the promoter region of miR-29a-3p, and directly regulates its expression. Overall, our study demonstrates that LE upregulates p53 and miR-29a-3p expression, and subsequently inhibits CF overactivation, suggesting that the p53/miR-29a-3p axis may play a crucial role in mediating the antifibrotic effect of LE against MF.

Effects of 4-DAMP on allergic rhinitis in guinea pigs and its potential mechanism.

Background: Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa mainly mediated by immunoglobulin E (IgE), which seriously affects the life quality of affected patients. This study aimed to observe the effects of 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP; a selective M3 receptor antagonist) on ovalbumin (OVA)-induced AR guinea pigs, and to explore its potential mechanism of involvement. Methods: An AR model was established by inducing male guinea pigs (4-6 weeks of age) with OVA. AR guinea pigs were randomly divided into a model group, 0.6 mg/kg ipratropium bromide (IB) group, 0.12 and 0.6 mg/kg 4-DAMP group (n=18). The 0.6 mg/kg IB group, 0.12 and 0.6 mg/kg 4-DAMP group animals were treated with IB (0.6 mg/kg) and 4-DAMP (0.12 or 0.6 mg/kg) by intranasal instillation per nostril daily. Animals in the model group and normal group were treated with saline as control. The AR symptom scores were counted and nasal secretion weights were measured. Histopathological methods were used to observe nasal mucosa. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of histamine and cytokines. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expressions of mucin 5AC (MUC5AC), matrix metalloproteinase 9 (MMP9), and epidermal growth factor receptor (EGFR). Results: Compared with model group animals, the AR symptom scores and nasal secretion weights of animals treated with 4-DAMP were reduced significantly, goblet cell metaplasia was reversed, and eosinophil infiltration was visibly alleviated. The levels of histamine and cytokines in nasal lavage fluid (NLF) were decreased, and the protein and messenger RNA (mRNA) expressions of MUC5AC, MMP9, and EGFR were inhibited. Conclusions: Treatment with 4-DAMP has a certain effect on AR, especially for mucus hypersecretion, which provides a new idea for clinical treatment of AR.

Malassezia in Inflammatory Bowel Disease: Accomplice of Evoking Tumorigenesis.

Accumulating evidence indicates that patients with inflammatory bowel disease (IBD) have a significantly higher risk of developing different cancers, while the exact mechanism involved is not yet fully understood. Malassezia is a lipid-dependent opportunistic yeast, which colonizes on mammalian skin and internal organs. Also, dysbiosis in fungal communities accompanied by high level of Malassezia are fairly common in inflammatory diseases such as IBD and various cancers. In cancer patients, higher levels of Malassezia are associated with worse prognosis. Once it is ablated in tumor-bearing mice, their prognostic conditions will be improved. Moreover, Malassezia manifests multiple proinflammatory biological properties, such as destruction of epithelial barrier, enrichment of inflammatory factors, and degradation of extracellular matrix (ECM), all of which have been reported to contribute to tumor initiation and malignant progression. Based on these facts, we hypothesize that high levels of Malassezia together with mycobiome dysbiosis in patients with IBD, would aggravate the microecological imbalance, worsen the inflammatory response, and further promote tumorigenesis and deterioration. Herein, we will discuss the detrimental properties of Malassezia and explore the key role of this fungus in the correlation between IBD and cancer, in order to take early surveillance and intervention to minimize the cancer risk in individuals with IBD.

Preventing dispensing errors through the utilization of lean six sigma and failure model and effect analysis: A prospective exploratory study in China.

AIMS: To utilize lean six sigma (LSS) and failure model and effect analysis (FMEA) to prevent dispensing errors in a Chinese teaching hospital. METHODS: Medication errors (MEs) reported to the China Core Group of the international network for the rational use of drugs (INRUD) by pharmacists at the hospital were collected. Following LSS methodology, the data analysis was structured according to define, measure, analyse, improve, and control (DMAIC) phases, and typical LSS tools (Pareto diagrams, brainstorming sessions) were used to determine the risk factors leading to dispensing errors. FMEA was applied to generate the risk priority numbers (RPNs) of MEs events, and key medications targeted for error prevention strategies were identified through quantitative analysis of the impacts of failure. Finally, corrective measures to prevent MEs were implemented and monitored for efficacy. RESULTS: Before the implementation of this programme, a total of 603 cases of dispensing errors were reported from the Year 1 to Year 6, reaching an average rate of incidence of 0.33 cases per 10 000 medication orders delivered, and no difference was found between these years (P = .9424). There was also no difference as location, error type, contributing factors, cause classification were considered. We then determined the real cause behind dispensing errors, and a total of 67 medications were targeted for specific error prevention strategies. One year after intervention, progress had been achieved in the following aspects: the incidence rate of dispensing errors was significantly decreased compared with the previous years (0.19, P = .007). Simultaneously, the incidence rate of dispensing errors occurred in outpatient pharmacy (0.04, P = .0008), with junior pharmacists (0.15, P = .0258), with LASA medications (0.06, P = .0319), as well as with memory-based errors were significantly decreased (0.03, P = .0191). CONCLUSION: The combination of LSS and the FMEA tool can be an efficient approach for helping reduce MEs in pharmacy dispensing.

Leonurine Attenuates Myocardial Fibrosis Through Upregulation of miR-29a-3p in Mice Post-myocardial Infarction.

ABSTRACT: Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for inhibiting fibrosis in many preclinical experiments. However, whether LE protects against MF after MI through modifying miR-29 remains unclear. The present study aimed to investigate the therapeutic effects of LE on MF, and to elucidate the underlying mechanisms involved. A mouse model of MI was established, followed by administration of LE for 4 weeks. We found that LE effectively improved cardiac function, and attenuated fibrosis and cardiac remodeling in mice post-MI. In vitro, LE simultaneously inhibited proliferation and migration of neonatal mouse cardiac fibroblasts (CFs) exposed to angiotensin II (Ang II), and the activation of collagen synthesis and myofibroblast generation was markedly suppressed by LE. Notably, we found that all mature miR-29 family members were downregulated in the myocardial tissues of mice post-MI, whereas LE significantly upregulated miR-29a-3p expression, and such upregulation was also detected in LE-treated CFs under Ang II stimulation. Knockdown of miR-29a-3p by a specific miRNA inhibitor upregulated the protein levels of TGF-ß, collagen III, and collagen I in CFs, and completely reversed the antifibrotic effects of LE on CFs. Our study suggests that LE exerts cardioprotective effects against MF, possibly through the upregulation of miR-29a-3p.

Short-Chain Fatty Acids: A Soldier Fighting Against Inflammation and Protecting From Tumorigenesis in People With Diabetes.

Converging evidences showed that people with diabetes mellitus (DM) have significantly higher risk for different cancers, of which the exact mechanism underlying the association has not been fully realized. Short-chain fatty acids (SCFAs), the fermentation products of the intestinal microbiota, are an essential source for energy supply in gut epithelial cells. They have been reported to improve intestinal barrier integrity, prevent microbial translocation, and further dampen inflammation. Gut dysbiosis and reduction in SCFA-producing bacteria as well as SCFAs production in the intestine are commonly seen in metabolic disorders including DM and obesity. Moreover, inflammation can contribute to tumor initiation and progression through multiple pathways, such as enhancing DNA damage, accumulating mutations in tumor suppressor genes Tp53, and activating nuclear factor-kappa B (NF-κB) signaling pathways. Based on these facts, we hypothesize that lower levels of microbial SCFAs resulted from gut dysbiosis in diabetic individuals, enhance microbial translocation, and increase the inflammatory responses, inducing tumorigenesis ulteriorly. To this end, we will discuss protective properties of microbial SCFAs and explore the pivotal roles SCFAs played in the link of DM with cancer, so as to take early precautions to reduce the risk of cancer in patients with DM.

Ipragliflozin as an add-on therapy in type 2 diabetes mellitus patients: An evidence-based pharmacoeconomics evaluation.

AIM: To evaluate the efficacy, safety and cost-effectiveness of ipragliflozin as an add-on therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, the Cochrane Library, Web of Science and four Chinese databases, as well as the ClinicalTrials.gov website were searched from their inception through Jan 2019. Methodological quality was assessed using the Cochrane risk of bias, and meta-analysis was performed using RevMan5.3. RESULTS: A total of 11 randomized controlled trials with 1766 patients were included. Ipragliflozin administered (50 mg) once daily as an add-on therapy to other glucose-lowering medications (metformin, pioglitazone, sulfonylurea, α-glucosidase inhibitor, sitagliptin, insulin) was associated with reductions in hemoglobin A1c (HbA1c) of -0.74% (95% confidence interval (CI) -1.00 to -0.48), fasting plasma glucose (WMD -25.03 mg/dL; 95% CI -32.89 to -17.16), weight, waist circumference, blood pressure, and triglycerides levels. Neither the incidence of treatment-emergent adverse events (TEAEs) (RR 1.08; 95% CI 1.00 to 1.16) nor drug-related TEAEs (RR 1.19; 95% CI 0.93 to 1.54) was significantly increased. However, it was associated with an increased risk of hypoglycemia when added to insulin (RR 1.71; 95% CI 1.13 to 2.61). Compared with the pioglitazone group and the sitagliptin + metformin group, the incremental cost-effectiveness ratio of ipragliflozin add-on therapy group was $4976.89, $2089.76 per percentage of qualified HbA1c, respectively. CONCLUSION: Ipragliflozin as an add-on therapy is well tolerated and effective. Ipragliflozin as an add-on therapy do not appear cost-effective compared with metformin alone, but may be competitive against pioglitazone group and the sitagliptin + metformin group.

Leonurine alleviates LPS-induced myocarditis through suppressing the NF-кB signaling pathway.

Myocarditis is a serious hazard to human life and is difficult to treat due to the proliferation of inflammatory lesions in the myocardium. Leonurine (LE) is a plant phenolic alkaloid extracted from Herba leonuri that has demonstrated cardioprotective effects in many preclinical experiments. However, whether LE can be used for myocarditis therapy has not been reported. We aimed to investigate the cardioprotective effects of LE on lipopolysaccharide (LPS)-induced myocarditis in vivo and vitro. The possible mechanism involved was also further elucidated. In vivo, C57BL/6 mice were exposed to LPS with or without LE. We found out that LE effectively improved cardiac function and attenuated cardiomyocyte apoptosis in mice with myocarditis. In addition, LPS-induced inflammatory and oxidative injuries in the myocardium were also reduced by LE administration. In vitro, LPS simultaneously induced apoptosis and reduced the H9c2 cells viability, followed by elevation of intracellular reactive oxygen species (ROS) generation. However, the abnormalities mentioned were preventable by LE pretreatment in a dose-dependent manner. Both in vivo and in vitro, LPS activated the nuclear factor kappa B (NF-кB) signaling pathway in myocarditis, and LE inhibited the increased expression of phosphorylated iκBα and p65 (p-iκBα, p-p65). Furthermore, the nuclear translocalization and nuclear protein expression of p65 in LPS-injured H9c2 cells were also suppressed by LE. Our results demonstrated that LE exerts potent cardioprotective effects against myocarditis via anti-inflammatory and antioxidative mechanisms, possibly through blocking the activation of NF-кB pathway.

Effects of Sodium-glucose Cotransporter 2 Inhibitor Monotherapy on Weight Changes in Patients With Type 2 Diabetes Mellitus: a Bayesian Network Meta-analysis.

PURPOSE: The aim of this study was to systematically evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor monotherapy on the weight of patients with type 2 diabetes mellitus (T2DM) and to compare different SGLT2 inhibitors with other oral glucose-lowering medications. METHODS: PubMed, EMBASE, Cochrane Library, and the ClinicalTrials.gov Web site were searched for relevant randomized controlled trials. Patients with T2DM in the included studies were administered SGLT2 inhibitor monotherapy for at least 12 weeks. The primary outcome was the change in weight from baseline; the secondary outcome was the proportion of patients achieving a weight reduction ≥5%. A pairwise meta-analysis using the DerSimonian-Laird random effects model and a network meta-analysis with Bayesian Markov chain Monte Carlo random effects models were performed. FINDINGS: A total of 29 randomized controlled trials (11,999 patients) with a low risk of bias were identified. The results showed that the mean weight loss ranged from -2.26 kg (95% credible interval [CrI], -2.71 to -1.76) with canagliflozin 300 mg to -0.79 kg (95% CrI, -1.54 to -0.05) with ipragliflozin 25 mg compared with metformin. Compared with linagliptin and sitagliptin, the mean weight loss ranged from -3.17 kg (95% CrI, -3.67 to -2.57) with canagliflozin 300 mg to -0.93 kg (95% CrI, -1.92 to 0.05) with ipragliflozin 25 mg. Canagliflozin 300 mg reduced weight to a greater extent than the other SGLT2 inhibitors, with a probability of 99.44%. SGLT2 inhibitors also improved the proportions of patients achieving ≥5% weight loss. The effect of SGLT2 inhibitors on weight reduction was associated with dosage. IMPLICATIONS: Available evidence from randomized controlled trials suggests that SGLT2 inhibitor monotherapy exerts more beneficial effects on weight reduction than both metformin and dipeptidyl peptidase 4 inhibitors. The weight reduction effect of 300 mg canagliflozin is greater than that of most other SGLT2 inhibitors. More types of SGLT2 inhibitors in a head-to-head trial, as well as a comparison between SGLT2 inhibitors and glucagon-like peptide 1 receptor agonists, will be involved in our further research. International Prospective Register of Systematic Reviews: CRD42018089761.

Sepsis as an important risk factor for gastrointestinal bleeding in acute coronary syndrome patients: Two case reports.

RATIONALE: Sepsis is a common stressor that may decrease microcirculation in the gastrointestinal tract in patients and increase the gastrointestinal bleeding risk of stress-related mucosal disease. However, the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) bleeding risk score, recommended by authoritative guidelines for acute coronary syndrome (ACS), does not include sepsis as a bleeding risk factor. PATIENT CONCERNS: The 2 cases were about ACS with hemorrhagic complications. The first patient was an 88-year-old man with hypertension, gallstones, hepatic cysts, and chest pain; the second one was a 79-year-old man with chest pain and hypertension. These 2 ACS patients had no bleeding on admission; however, both patients suffered apparent gastrointestinal bleeding immediately after the development of sepsis or severe sepsis. DIAGNOSES: Both patients were diagnosed as ACS with sepsis. INTERVENTIONS: The first ACS patient had no use of proton pump inhibitors (PPIs) for prophylaxis prior to the diagnosis of sepsis. The second one was administered PPIs at standard oral doses. OUTCOMES: The first patient suffered from gastrointestinal bleeding immediately after the onset of sepsis. And oral PPIs failed to prevent upper gastrointestinal bleeding for the second patient, when severe sepsis developed. However, the second patient's gastrointestinal hemorrhage gradually stopped immediately after high doses of PPIs were administered intravenously, rather than orally. When sepsis developed again, the second patient also had no recurrent gastrointestinal bleeding under the protection of PPIs at standard oral doses. LESSONS: Our report suggests that sepsis may be an important bleeding risk factor for ACS patients, and the reasonable use of PPIs to prevent gastrointestinal bleeding could be vital for ACS patients complicated with sepsis.

Effects of Ginsenoside Rg3 on fatigue resistance and SIRT1 in aged rats.

BACKGROUND: Ginsenoside Rg3 (Rg3) is one of the key components of a frequently used herbal tonic panax ginseng for fatigue treatment. However, the molecular mechanisms of Rg3 on anti-fatigue effects have not been completely understood yet. METHODS AND MATERIALS: We built a postoperative fatigue syndrome (POFS) model and tried to elucidate the molecular mechanisms responsible for anti-fatigue effects of Rg3. 160 aged male rats were randomly divided into four groups (n = 40/group): normal group, Rg3-treated normal group (Rg3 group), postoperative fatigue syndrome model group (POFS group) and Rg3-treated postoperative fatigue syndrome model group (POFS + Rg3 group). The open field test (OFT) was used to assess general activity and exploratory behavior of rats in different groups. We then analyzed total cholesterol (TC), serum triglyceride (TG) and lactate dehydrogenase (LDH) in the blood, as well as superoxide dismutase (SOD), malondialdehyde (MDA), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in skeletal muscles of rats. We also detected the influence of Rg3 on silent information regulator of transcription 1 (sirtuin1, SIRT1) activity and protein 53 (p53) transcriptional activity in vitro. RESULTS: Rg3 significantly increased the journey distance and rearing frequency, while slowed down the rest time. The serum concentrations of TC, TG and LDH were all up-regulated by Rg3. Meanwhile, Rg3 increased concentrations of SOD, but also decreased MDA release out of skeletal muscles. The mRNA expressions of PGC-1α and PEPCK were also enhanced by Rg3. Besides, Rg3 could activate SIRT1 and suppress p53 transcriptional activity in the biological process. DISCUSSION AND CONCLUSION: Rg3 could improve exercise performance and resist fatigue possibly through elevating SIRT1 deacetylase activity.

Medication-related risk factors associated with health-related quality of life among community-dwelling elderly in China.

BACKGROUND: Previous studies have demonstrated that medication adherence has an impact on health-related quality of life (HRQoL). However, other medication-related factors that may influence HRQoL have not been extensively studied, especially factors based on the Medication-Risk Questionnaire (MRQ), and such studies are mostly done in Western countries. Our objective was to explore risk factors associated with HRQoL among community-dwelling elderly with chronic diseases in mainland China, especially the medication-related risk factors regarding MRQ. METHODS: The study was conducted in a community health service center through surveys to eligible patients. The main outcomes of HRQoL were assessed by the EuroQol-5D (EQ-5D) scale and EQ-visual analog scale (EQ-VAS). Medication-related risk factors according to MRQ associated with HRQoL were identified using a multiple linear regression. RESULTS: A total of 311 patients were analyzed, averaging 71.19±5.33 years, and 68.8% were female. The mean EQ-5D index was 0.72±0.09, and the mean EQ-VAS score was 71.37±11.97. The most prevalent problem was pain/discomfort, and 90.0% believed that they could take care of themselves without any problems. Sex, age, educational level, frailty, function status, and certain medication-related factors regarding MRQ were found to be significant factors impacting the HRQoL. A multivariate analysis showed that MRQ factors of polypharmacy, multimorbidity, feeling difficultly with taking medicines as prescribed, and taking medicines with narrow therapeutic index had negative impacts on the quality of life. CONCLUSION: Patient's internal characteristics and medication-related risk factors according to MRQ were associated with quality of life. The results of the MRQ is an indicator of quality of life that can identify patients who need interventions.

Drug-related problems among community-dwelling older adults in mainland China.

Background Little is known about the extent of drug-related problems (DRPs) in community-dwelling older adult patients with chronic diseases in mainland China. Setting A medication therapy review service at a community health center in Chongqing, China. Objective To identify and categorize DRPs along with pharmacists' recommendations in addressing the DRPs identified. Method The study was conducted between May 2015 and July 2016. A total of 102 community-dwelling older adults were included. MTR was carried out by clinical pharmacists. DRPs and pharmacotherapy recommendations were recorded and analyzed. Main outcome measure The number of drug-related problems and main problem categories. Results The average age of patients was 69.4 years. Patients took an average of 6.3 medications. A total of 489 DRPs were identified (mean of 4.8 per patient). The most common category was under-treated (27.8%) followed by over- or under-dose (18.8%) and monitoring (17.8%). The number of medications taken was the significant associated factor for DRPs. Pharmacists made 526 recommendations to address the DRPs (mean of 1.1 recommendations per DRP). Primary care providers accepted 68.1% of these recommendations, and implemented 60.9% of them. Conclusion The prevalence of DRPs among studied patient population was high. Pharmacists may play a vital role in addressing the DRPs and optimize pharmacotherapy through MTR service located in community health centers.

Efficacy and feasibility of a collaborative multidisciplinary program for antibiotic prophylaxis in clean wound surgery.

Background Despite national and international guidelines and recommendations, inappropriate prophylactic antibiotic use for clean wound surgery remains a common phenomenon in many Chinese hospitals, causing higher medical costs and bacterial resistance. Objective To improve the prescribing behavior for antibiotic prophylaxis and decrease antibiotic abuse and/or misuse in clean wound surgery. Setting The teaching hospital of a medical university in Southwest China. Methods A collaborative multidisciplinary program involving educational, technical, and administrative strategies was undertaken. It was characterized by a monthly evaluation by clinical pharmacists for randomly selected cases of clean wound surgery, as well as a group discussion attended by correlative personnel, consisting of the administrative staff, experts from the Rational Drug Use Committee, clinical pharmacists and surgeons. Main outcome measure The overall incidence of antibiotic prophylaxis, appropriate antibiotics selection, appropriate initial dosage timing, proper drug combination and the duration of antibiotic prophylaxis were measured. Results from 2009 to 2014, the rate of antibiotic prophylaxis for clean wound surgery declined from nearly 100% to 20-30%. Improvements were also observed in drug selection, timing of the first dose, and dosage and duration for antibiotic prophylaxis. Broad-spectrum antibiotics and enzyme inhibitors have seldom been used after 2011. The medical cost for antibiotics also decreased. Conclusion A collaborative multidisciplinary program, together with a group discussion, is efficient for improving rational antibiotic prophylaxis for clean wound surgery. This study indicates that clinical pharmacists can play a pivotal role in providing the professional evaluation of medical cases, education, and intervention.

Electronic medication reconciliation in hospitals: a systematic review and meta-analysis.

OBJECTIVE: Medication reconciliation (MedRec) is recognised as a multiprofessional process for the prevention of medication discrepancies. The goal of this study is to evaluate the available electronic medication reconciliation (eMedRec) tools and their effect on unintended discrepancies that occur in hospital institutions. METHOD: PubMed, EMBASE, the Cochrane Library, Web of Science, the ClinicalTrials.gov website and four other Chinese databases were searched for relevant studies starting from their inception through October 2017. Methodological quality was assessed using the nine standard criteria of Cochrane Effective Practice and Organisation of Care Review Group (EPOC) and meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 13 studies (three randomised controlled trials and 10 non-randomised controlled trials) were identified. Meta-analysis results demonstrated a reduced number of medications with unintended discrepancies (relative risk (RR)=1.85, 95% confidence interval (CI) 1.55 to 2.21), while no statistically significant differences were observed in the number of patients with unintended medication discrepancies (RR=2.74, 95% CI 0.59 to 12.73). Common discrepancies included medication omission, dose discrepancy, and frequency discrepancy. We found that the clinical impact of medication discrepancy was mild. A total of 12 electronic tools were reported and were mostly integrated into the hospital's information system. However, the usability, user adherence, and user satisfaction were found to lack sufficient evidence. CONCLUSION: eMedRec was shown to reduce the incidence of medication with unintended discrepancies and improve medication safety. However, the electronic tools are diversified and the effects on other outcomes still require a comprehensive evaluation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017067528.

Current strategies to improve the safety of chimeric antigen receptor (CAR) modified T cells.

Adoptive immunotherapy adopting chimeric antigen receptor (CAR) modified T cells has arisen attention as a hard-hitting therapy for numerous cancers. CARs are genetically engineered receptors that could stimulate tumor cytotoxicity once binding to the specific tumor epitopes. In spite of current noteworthy achievements in hematologic malignancies, the safety problems have aroused public awareness. In this review, we will focus on recent potential strategies to improve the security of CAR modified T cells.

ß-Caryophyllene/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway.

This work was conducted to prepare ß-caryophyllene-hydroxypropyl-ß-cyclodextrin inclusion complex (HPßCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HPßCD/BCP was prepared, optimized, characterized, and evaluated. HPßCD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HPßCD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HPßCD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HPßCD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HPßCD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HPßCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPßCD/BCP in the therapy of vascular dementia in the future.

An epirubicin-peptide conjugate with anticancer activity is dependent upon the expression level of the surface transferrin receptor.

Epirubicin (EPI) is one of the most widely used anticarcinogens; however, serious side effects, including cardiomyopathy and congestive heart failure, limit its long­term administration. To overcome this problem, the HAIYPRH peptide ligand was used with EPI in the synthesis of a HAIYPRH­EPI conjugate. The anticancer activity and cellular uptake of the conjugate were measured and evaluated. The results of the present study indicated that the cytotoxicity of HAIYPRH­EPI was correlated with the expression of the cell surface transferrin receptor (TfR). The conjugate exerted high cytotoxicity and proapoptotic function when in an LN229 glioma cell line, which overexpresses surface TfR. It was hypothesized that transferrin (Tf) can promote cytotoxicity. Conversely, the conjugate exhibited very low cytotoxicity and proapoptotic function in a U87 glioma cell line, in which surface TfR expression was undetectable. In addition, fluorescence microscopy and flow cytometry methods were used to evaluate cellular uptake, and the results of these methods were consistent with the present hypotheses. The conjugate cellular uptake of the conjugate in LN229 cells was markedly higher compared with that in U87 cells, and it was hypothesized that Tf can enhance the uptake in LN229 cells. The cytotoxicity of HAIYPRH­EPI was dependent upon the expression of surface TfR. Considering that the majority of cancer cells have high rates of iron uptake and surface TfR is generally overexpressed on cancer cells, it was speculated by the authors that HAIYPRH­EPI may form part of an effective strategy for increasing the selectivity of EPI for cancer cells, as well as reducing its systemic toxicity. To confirm the hypothesis, the effects of HAIYPRH­EPI on non­cancerous cell lines were investigated. A future study will examine the side effects of HAIYPRH­EPI, using a suitable delivery system in an animal model.