Association of physical activity pattern and risk of Parkinson's disease.

Increasing evidence suggests an association between exercise duration and Parkinson's disease. However, no high-quality prospective evidence exists confirming whether differences exist between the two modes of exercise, weekend warrior and equal distribution of exercise duration, and Parkinson's risk. Hence, this study aimed to explore the association between different exercise patterns and Parkinson's risk using exercise data from the UK Biobank. The study analyzed data from 89,400 UK Biobank participants without Parkinson's disease. Exercise data were collected using the Axivity AX3 wrist-worn triaxial accelerometer. Participants were categorized into three groups: inactive, regularly active, and engaged in the weekend warrior (WW) pattern. The relationship between these exercise patterns and Parkinson's risk was assessed using a multifactorial Cox model. During a mean follow-up of 12.32 years, 329 individuals developed Parkinson's disease. In a multifactorial Cox model, using the World Health Organization-recommended threshold of 150 min of moderate-to-vigorous physical activity per week, both the active WW group [hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.43-0.78; P < 0.001] and the active regular group (HR = 0.44; 95% CI = 0.34-0.57; P < 0.001) exhibited a lower risk of developing Parkinson's disease compared with the inactive group. Further, no statistically significant difference was observed between the active WW and the active regular groups (HR = 0.77; 95% CI = 0.56-1.05; P = 0.099). In conclusion, in this cohort study, both the WW exercise pattern and an equal distribution of exercise hours were equally effective in reducing Parkinson's risk.

Cleavage of gasdermin by apoptotic caspases triggers pyroptosis restricting bacterial colonization in Hydra.

Gasdermin (GSDM) proteins, as the direct executors of pyroptosis, are structurally and functionally conserved among vertebrates and play crucial roles in host defense against infection, inflammation, and cancer. However, the origin of functional GSDMs remains elusive in the animal kingdom. Here, we found that functional GSDME homologs first appeared in the cnidarian. Moreover, these animal GSDME homologs share evolutionarily conserved apoptotic caspase cleavage sites. Thus, we verified the functional conservation of apoptotic caspase-GSDME cascade in Hydra, a representative species of cnidarian. Unlike vertebrate GSDME homologs, HyGSDME could be cleaved by four Hydra caspase homologs with caspase-3 activity at two sites. Furthermore, in vivo activation of Hydra caspases resulted in HyGSDME cleavage to induce pyroptosis, exacerbating injury and restricting bacterial burden, which protects Hydra from pathogen invasion. In conclusion, these results suggest that GSDME-dependent pyroptosis may be an ancient and conserved host defense mechanism, which may contribute to better understanding on the origin and evolution of GSDMs.

Population Pharmacokinetics of Isavuconazole in Adult: A Systematic Review.

Isavuconazole (ISA) is a second generation broad-spectrum triazole antifungal drug derived from voriconazole structure, and its oral capsules is currently the only oral preparation approved for invasive mucormycosis. In recent years, population pharmacokinetic studies of ISA have been reported continuously. This paper aims to summarize the characteristics of population pharmacokinetic models of ISA in adults, and provide theoretical basis for individualized administration of ISA. We systematically searched PubMed, Embase, CNKI, Wanfang, VIP and other databases to collect population pharmacokinetic models published from the establishment of the database to March 2023. A total of 6 studies were included in this review, including healthy men and women, invasive fungal infections with malignant tumors or neutropenia, solid organ transplantation. The dose of ISA was 40-400mg for single-dose. The multiple-dose of ISA was 200mg every 8 hours for the first 48 hours and then 200mg once daily. All studies used a two-compartment model, first-order elimination. For oral formulations, except for one study that used first-order absorption, the others used Weibull absorption. Body mass index (BMI) was the most common covariable, followed by total body weight, lean body mass, race, sex, population type (healthy volunteers/patients), and creatinine clearance. These studies included several covariates, and the clearance rate (CL) was similar among populations. In the future, external validation and population pharmacokinetic studies in special populations such as patients with severe liver disease and ECMO support are needed.

GPNMB Ameliorates Neuroinflammation Via the Modulation of AMPK/NFκB Signaling Pathway After SAH in Mice.

Glycoprotein non-metastatic melanoma protein B (GPNMB) got its name from the first discovery in a cell line of non-metastatic melanoma. Later studies found that GPNMB is widely expressed in various tissues and cells of the human body, most abundant in neural tissue, epithelial tissue, bone tissue, and monocyte-macrophage system. GPNMB has been shown to have anti-inflammatory effects in a variety of neurological diseases, however, it has not been reported in subarachnoid hemorrhage (SAH). Male CD-1 mice were used and intra-arterial puncture method was applied to establish the SAH model. Exogenous recombinant GPNMB (rGPNMB) was injected intracerebroventricularly 1 h after SAH. SAH grading, brain edema and blood-brain barrier (BBB) integrity were quantified, and neurobehavioral tests were performed to evaluate the effect of GPNMB on the outcome. Dorsomorphin, the selective inhibitor on AMPK was introduced to study the downstream signaling through which the GPNMB works. Furthermore, western blot, immunofluorescence staining and ELISA were utilized to confirm the signaling. After SAH, GPNMB expression increased significantly as a result of the inflammatory response. GPNMB was expressed extensively in mouse microglia, astrocytes and neurons. The administration of rGPNMB could alleviate brain edema, restore BBB integrity and improve the neurological outcome of mice with SAH. GPNMB treatment significantly magnified the expression of p-AMPK while p-NFκB, IL-1ß, IL-6 and TNF-α were suppressed; in the meantime, the combined administration of GPNMB and AMPK inhibitor could decrease the intensity of p-AMPK and reverse the quantity of p-NFκB and the above inflammatory cytokines. GPNMB has the potential of ameliorating the brain edema and neuroinflammation, protecting the BBB and improving the neurological outcome, possibly via the AMPK/NFκB signaling pathway.

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.

Efficacy and safety of ceftazidime-avibactam versus polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infection: a systematic review and meta-analysis.

OBJECTIVES: Carbapenem-resistant Enterobacteriaceae is increasingly recognised as a significant public health concern. Ceftazidime-avibactam (CAZ-AVI) and polymyxins are considered as the last therapeutic options worldwide. This is the first meta-analysis of recently published data to compare the clinical efficacy and safety of CAZ-AVI with polymyxins in the treatment of carbapenem-resistant Enterobacteriaceae infections. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase and the Cochrane Library were systematically searched, for publications in any language, from database inception to February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies comparing the clinical efficacy and safety of CAZ-AVI with polymyxins were included. Mortality, clinical success, microbiological eradication and nephrotoxicity were assessed as the main outcomes. DATA EXTRACTION AND SYNTHESIS: Literature screening, data extraction and the quality evaluation of studies were conducted by two researchers independently, with disagreements resolved by another researcher. The Newcastle-Ottawa Scale was used to assess the bias risk for the included studies. Review Manager V.5.3 was employed for the meta-analysis. RESULTS: The meta-analysis included seven retrospective and four prospective cohort studies with 1111 patients enrolled. The CAZ-AVI groups demonstrated a lower 30-day mortality (risk ratio (RR)=0.48, 95% CI of 0.37 to 0.63, I2=10%, p<0.0001) in nine studies with 766 patients; higher clinical success (RR=1.71, 95% CI 1.33 to 2.20, I2=35%, p<0.0001) in four studies with 463 patients; and lower nephrotoxicity in seven studies with 696 patients (RR=0.42, 95% CI 0.23 to 0.77, I2=35%, p<0.05). However, no significant difference in microbiological eradication rates was observed in 249 patients from two studies (RR=1.16, 95% CI 0.97 to 1.39, I2=0, p>0.05). CONCLUSION: Available evidence suggested that CAZ-AVI treatment held a dominant position with respect to efficacy and safety compared with polymyxins in carbapenem-resistant Enterobacteriaceae infections. However, the analysis included only observational studies, and high-quality, large-scale, multicentre, double-blind randomised controlled trials are needed to confirm the advantage of CAZ-AVI.

Recent advances of cell membrane-coated nanoparticles for therapy of bacterial infection.

The rapid evolution of antibiotic resistance and the complicated bacterial infection microenvironments are serious obstacles to traditional antibiotic therapy. Developing novel antibacterial agents or strategy to prevent the occurrence of antibiotic resistance and enhance antibacterial efficiency is of the utmost importance. Cell membrane-coated nanoparticles (CM-NPs) combine the characteristics of the naturally occurring membranes with those of the synthetic core materials. CM-NPs have shown considerable promise in neutralizing toxins, evading clearance by the immune system, targeting specific bacteria, delivering antibiotics, achieving responsive antibiotic released to the microenvironments, and eradicating biofilms. Additionally, CM-NPs can be utilized in conjunction with photodynamic, sonodynamic, and photothermal therapies. In this review, the process for preparing CM-NPs is briefly described. We focus on the functions and the recent advances in applications of several types of CM-NPs in bacterial infection, including CM-NPs derived from red blood cells, white blood cells, platelet, bacteria. CM-NPs derived from other cells, such as dendritic cells, genetically engineered cells, gastric epithelial cells and plant-derived extracellular vesicles are introduced as well. Finally, we place a novel perspective on CM-NPs' applications in bacterial infection, and list the challenges encountered in this field from the preparation and application standpoint. We believe that advances in this technology will reduce threats posed by bacteria resistance and save lives from infectious diseases in the future.

Flow diverters in the treatment of unruptured vertebral artery dissecting aneurysm: A single-center experience.

Objective: To evaluate the efficacy and safety of flow diverters (FD) in the treatment of vertebral artery dissecting aneurysm (VADA). Methods: A total of 16 patients with 17 unruptured VADAs treated with FD from January 2017 to May 2021 were included. Data of clinical outcomes and radiographic examination were collected and assessed by the modified Rankin Scale (mRS) and O'Kelly-Marotta (OKM) grading scale. Results: All patients were treated with a single FD. No perioperative complications occurred. The mean age was 55.1 years old. The mean size of the aneurysm was 10.4 mm. All patients had a favorable occlusion (OKM D + C3) result and the complete occlusion rate in the 6th month was 66.7% (OKM D). The mean clinical follow-up time was 7.8 months, and all patients had a good clinical outcome (mRS = 0). No procedure-related complication occurred at the last follow-up time. Conclusion: FD is an effective and safe tool for treating unruptured VADA. Long-term prospective studies with a large sample are still needed to confirm these findings in the future.

Evidence-based guideline for the prevention and management of perioperative infection.

BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

Risk factors of tigecycline-associated fibrinogen reduction in patients with renal transplantation: a case-control study.

Background: Hypofibrinogenemia is a serious adverse reaction related to tigecycline administered against multidrug-resistant (MDR) bacteria and can lead to therapy termination. High dose and prolonged tigecycline therapy, renal failure, and base level of fibrinogen (FIB) were reported risk factors of tigecycline-associated FIB reduction. But results are unknown in patients with renal transplantation. Methods: A single-center and a case-control study involving renal transplantation patients was conducted. From January, 2017 to January, 2020, patients with a tigecycline course more than 2 days and a baseline FIB level greater than 2 g/L were enrolled. Hypofibrinogenemia was defined as plasma FIB <2.0 g/L. The extent of FIB reduction was calculated based on the baseline of FIB level before tigecycline administration. FIBRO was defined as the extent of FIB reduction over 50%, and FIBRB referred to the extent of FIB reduction below 50%. Univariate and multivariate analyses were performed by logistic regression models to identify independent risk factors of tigecycline-associated FIB reduction. Results: In total, 120 patients were enrolled. A total of 114 patients (95.00%) developed with hypofibrinogenaemia. Hypofibrinogenemia mainly occurred 3 days after tigecycline administration. Of them, 79 (65.83%) developed FIBRO with a median occurrence of 3 [2-4] days after initiation of tigecycline. Multivariable regression analysis demonstrated that the FIB level before tigecycline use [odds ratio (OR): 3.225, 95% confidence interval (CI): 1.801-5.772] and total tigecycline dose (OR: 4.930, 95% CI: 1.433-16.959) were risk factors for FIBRO. Conclusions: The FIB level before tigecycline use and total tigecycline dose were significantly associated with FIBRO, suggesting that FIB level and coagulation-related indicators should be closely monitored during tigecycline treatment to avoid life-threatening bleeding events.

Roles of Micro Ribonucleic Acids in Astrocytes After Cerebral Stroke.

Cerebral stroke is one of the highest-ranking causes of death and the leading cause of disability globally, particularly with an increasing incidence and prevalence in developing countries. Steadily more evidence has indicated that micro ribonucleic acids (miRNAs) have important regulatory functions in gene transcription and translation in the course of cerebral stroke. It is beyond arduous to understand the pathophysiology of cerebral stroke, due in part to the perplexity of influencing the network of the inflammatory response, brain edema, autophagy and neuronal apoptosis. The recent research shows miRNA plays a key role in regulating aquaporin 4 (AQP4), and many essential pathological processes after cerebral stroke. This article reviews the recent knowledge on how miRNA influences the inflammatory response, brain edema, infarction size, and neuronal injury after cerebral stroke. In addition, some miRNAs may serve as potential biomarkers in stroke diagnosis and therapy since the expression of some miRNAs in the blood is stable after cerebral stroke.

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.

Quantification of Venetoclax for Therapeutic Drug Monitoring in Chinese Acute Myeloid Leukemia Patients by a Validated UPLC-MS/MS Method.

Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25−8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (Cmax) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (Cmin) was 1018.0 ± 729.4 ng/mL. Additionally, Cmax and Cmin showed a positive correlation with AST levels. Furthermore, Cmax was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.

Poor Compliance Causes Acute Rejection in Kidney Transplant Recipients During COVID-19 Pandemic: 2 Cases Report.

The COVID-19 pandemic has lasted for more than one year, which caused much trouble to the health management of kidney transplant recipients. Numerous patients cancelled their review appointment or even lost connection with doctors because of the great pressure medical system undergoing, strict travel restrictions, and the worries about COVID-19 infection risk. Herein, we introduce two kidney transplant recipients, a 33-year-old man and a 32-year-old man, who did not take the immunosuppressant drugs and did not go back to the hospital to do the renal function examination as the doctor's request. When they paid their first return visit several months after the pandemic outbreak, they were both diagnosed with acute rejection and admitted to the hospital. After receiving pulse steroid therapy, they were in remission but failed to reverse the rejection. The level of serum creatinine did not recover to the one before pandemic outbreak. These cases suggest that it is necessary to ensure that kidney transplant recipients follow the doctor's advice to take drugs and follow-up regularly to examine their renal function over pandemic period. Additionally, typical pulse steroid therapy may not that effective toward these patients.

Recent advances in ferroptosis and therapeutic strategies for glioblastoma.

Ferroptosis is an emerging form of cell death characterized by the over-accumulation of iron-dependent lipid peroxidation. Ferroptosis directly or indirectly disturbs glutathione peroxidases cycle through diverse pathways, impacting the cellular antioxidant capacities, aggravating accumulation of reactive oxygen species in lipid, and it finally causes oxidative overload and cell death. Ferroptosis plays a significant role in the pathophysiological processes of many diseases. Glioblastoma is one of the most common primary malignant brain tumors in the central nervous system in adults. Although there are many treatment plans for it, such as surgical resection, radiotherapy, and chemotherapy, they are currently ineffective and the recurrent rate is almost up to 100%. The therapies abovementioned have a strong relationship with ferroptosis at the cellular and molecular level according to the results reported by numerous researchers. The regulation of ferroptosis can significantly determine the outcome of the cells of glioblastoma. Thus ferroptosis, as a regulated form of programed cell death, has the possibility for treating glioblastoma.

Pharmacist-led quality control circle in sustained reduction of carbapenem-resistance at a Chinese tertiary teaching hospital.

BACKGROUND: The spread of carbapenem-resistant Gram-negative bacteria poses a substantial threat to morbidity and mortality worldwide, which is mainly attributed to the overuse of carbapenem. This study aimed to evaluate the use of a quality control circle (QCC) in controlling the overuse of carbapenems and improving the state of carbapenem resistance at a Chinese tertiary teaching hospital. METHODS: A pharmacist-led multidisciplinary QCC project was carried out and the plan-do-check-act (PDCA) method was applied for 12 months. The data on carbapenem consumption, bacterial identification, and antibacterial susceptibility testing were collected to evaluate the effect of this project. RESULTS: The antibiotics use density (AUD) of carbapenems exhibited a decreasing trend over time (P<0.001), and the AUD of meropenem, imipenem, and biapenem decreased by 30.20%, 42.45%, and 78.05% after the intervention, respectively. The total AUD of carbapenems decreased from 7.37 to 3.96, which included the decrease in the irrational use of carbapenems by 1.61, accounting for 47.21% of the total. Moreover, the positive correlations were discovered between the resistance rate of carbapenem-resistant Klebsiella pneumonia (CRKP)/Acinetobacter baumannii (CRAB) and the AUD of carbapenems (P<0.05). The resistance rate of CRKP and CRAB decreased from 51.93% and 89.21% to 32.94% and 60.66%, respectively, following QCC project implementation. CONCLUSIONS: This is the first study to highlight the success of a multifaceted intervention QCC project and PDCA method, which led to a significant reduction in the AUD and resistance rate of carbapenems. QCC is a feasible and effective management tool for improving the quality of carbapenem use in medical institutions.

Incidence of venous thromboembolism and hemorrhage in Chinese patients after pulmonary lobectomy: mechanical prophylaxis or mechanical prophylaxis combined with pharmacological prophylaxis: a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) and postoperative bleeding are important complications of lung resection surgery. We investigated the preventive effect of mechanical prophylaxis versus pharmacological prophylaxis after lobectomy, and evaluated the effect of both on the incidence of hemorrhagic events. METHODS: A prospective study of 424 lobectomies with moderate to high risk of VTE (Caprini risk score <5) in a single center was performed from April 2020 to March 2021. Patients were 1:1 randomly allocated to mechanical prophylaxis or to the low-molecular-weight heparin (LMWH)-combination-prophylaxis. The incidence of postoperative thrombotic and bleeding events and relevant factors of the two groups were analyzed. RESULTS: A total of 410 participants, with 202 and 208 in the mechanical prophylaxis and LMWH-combination-prophylaxis groups respectively, were selected for analysis. Both groups had similar baseline and clinical characteristics. There were no cases of VTE or major bleeding during the study, but the incidence rate of minor bleeding in the LMWH-combination-prophylaxis group was significantly higher than mechanical prophylaxis group [odds ratio (OR) 0.035, 95% confidence interval (CI): 0.011-0.113]. CONCLUSIONS: A case-by-case risk assessment of VTE and hemorrhage remains necessary to determine the most appropriate method of thrombosis prophylaxis for patients undergoing pulmonary surgery. Mechanical prophylaxis may be preferable for lung cancer patients with moderate to high risk of VTE (Caprini risk score <5) undergoing lobectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051073.

Guideline for the evaluation of prescription appropriateness.

Evaluation of prescriptions is a necessary process of evaluating the appropriateness of clinical drug usage, discovering existing problems, and formulating solutions. There are challenges for professionals within hospital medical departments and for clinicians and pharmacists who have clinical questions relating to inappropriate or abnormal prescriptions as identified by the electronic evaluation system of prescription. Medications are usually used correctly according to the drug instructions or guidelines. At present, there are no relevant domestic or international guidelines, or principles or standards for identifying inappropriate or abnormal prescriptions. To develop the guideline for evaluation of prescriptions appropriateness in clinical practice, the Pharmaceutical Affairs Commission of the Chinese Hospital Association formed the guideline working group consisting of multidisciplinary experts. The guideline working group summarized clinical questions in the evaluation of prescriptions, searched for supporting evidence, and reached a consensus for recommendations. The guideline contains 6 recommendations for evaluating prescription appropriateness, and the general principle of these recommendations is that clinicians should provide drug instructions, guidelines, or moderate evidence supporting the prescription, and the evaluators will then judge the prescription to be either appropriate or irrational. The recommendations resolve common clinical questions, using supporting examples, explanations and a flow chart. The evaluation of prescription appropriateness could be made more systematic and transparent based on this guideline's conclusions.

Oral delivery of infliximab using nano-in-microparticles for the treatment of inflammatory bowel disease.

The anti-tumor necrosis factor-α (anti-TNF-α) blocker, has shown great efficacy for the treatment of inflammatory bowel disease (IBD). However, systemic exposure to it can cause considerable safety problems due to reduced suppression of the systemic immune response and loss of response to the production of anti-drug antibodies. Thus, we try to devise a targeted vehicle system for oral administration of anti-TNF-α antibodies for the treatment of IBD. In the present study, we developed an oral Infliximab (IFX) loaded nano-in-microparticles, based on chitosan (CS)/carboxymethyl chitosan (CMC) and alginate (Alg), which could protect IFX from the harsh environment of the gastrointestinal tract and produce targeted drug delivery to the inflamed intestine. In vivo studies demonstrated that the IFX loaded nano-in-micro vehicle can alleviate colitis by ameliorating inflammation and maintaining the intestinal epithelial barrier.

Research Progress on the Mechanism of Mitochondrial Autophagy in Cerebral Stroke.

Mitochondrial autophagy is an early defense and protection process that selectively clears dysfunctional or excessive mitochondria through a distinctive mechanism to maintain intracellular homeostasis. Mitochondrial dysfunction during cerebral stroke involves metabolic disbalance, oxidative stress, apoptosis, endoplasmic reticulum stress, and abnormal mitochondrial autophagy. This article reviews the research progress on the mechanism of mitochondrial autophagy in ischemic stroke to provide a theoretical basis for further research on mitochondrial autophagy and the treatment of ischemic stroke.