[Guidelines for economic evaluation of post-marketing Chinese patent medicine].

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.

Photosynthetic-Membrane-Like Ion Translocation in Visible-Light-Harvesting Nanofluidic Channels.

The selective uphill and downhill movement of protons in and out of photosynthetic membrane enabled by ion pumps and ion channels is key to photosynthesis. Reproducing the functions of photosynthetic membranes in artificial systems has been a persistent goal. Here, a visible-light-harvesting nanofluidic channels is reported which experimentally demonstrates the ion translocation functions of photosynthetic membranes. A molecular junction consisting of photosensitive ruthenium complexes linked to TiO2 electron acceptors forms the reaction centers in the nanofluidic channels. The visible-light-triggered vectorial electron injection into TiO2 establishes a difference in transmembrane potential across the channels, which enables uphill transport of ions against a 5-fold concentration gradient. In addition, the asymmetric charge distribution across the channels enables the unidirectional downhill movement of ions, demonstrating an ion rectification effect with a ratio of 18:1. This work, for the first time, mimics both the uphill and downhill ion translocation functions of photosynthetic membranes, which lays a foundation for nanofluidic energy conversion.

Protective human antibodies against a conserved epitope in pre- and postfusion influenza hemagglutinin.

Phylogenetically and antigenically distinct influenza A and B viruses (IAV and IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved in both IAV and IBV hemagglutinins (HAs) could protect against disease by diverse virus subtypes. Only one reported HA Ab, isolated from a combinatorial display library, protects against both IAV and IBV. Thus, there has been so far no information on the likelihood of finding naturally occurring human Abs that bind HAs of diverse IAV subtypes and IBV lineages. We have now recovered from several unrelated human donors five clonal Abs that bind a conserved epitope preferentially exposed in the postfusion conformation of IAV and IVB HA2. These Abs lack neutralizing activity in vitro but in mice provide strong, IgG subtype-dependent protection against lethal IAV and IBV infections. Strategies to elicit similar Abs routinely might contribute to more effective influenza vaccines.

Roles and regulation of Aquaporin-3 in maintaining the gut health: an updated review.

Aquaporin-3 (AQP3) is a predominant water channel protein expressed in the intestine, and plays important roles in the gut physiology and pathophysiology due to its permeability to water, glycerol and hydrogen peroxide. In this review, we systematically summarized the current understanding of the expression of AQP3 in the intestine of different species, and focused on the potential roles of AQP3 in water transport, different types of diarrhea and constipation, intestinal inflammation, intestinal barrier function, oxidative stress, and autophagy. These updated findings have supported that AQP3 may function as an important target in maintaining gut health of human and animals.

Efficacy, safety, and cost-effectiveness of therapeutic drug monitoring (TDM) for TNF inhibitor therapy in rheumatic disease: A systematic review and meta-analysis.

OBJECTIVE: The benefits of TDM-guided TNFi therapy in patients with rheumatic disease was still controversial. This systematic review and meta-analysis was conducted to explore if the TDM-guided TNFi therapy is superior to empirical-guided therapy. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956). RESULTS: A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I2=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I2=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I2=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I2=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I2=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost. CONCLUSION: TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.

The Impact of Prescribing Monitoring Policy on Drug Use and Expenditures in China: A Multi-center Interrupted Time Series Study.

BACKGROUND: A prescribing monitoring policy (PMP) was implemented in November 2015 in Anhui province, China, the first province to pilot this policy to manage the use and costs of select drugs based on their large prescription volumes and/ or costs in hospitals. This study evaluated the impact of PMP on the use and expenditures of different drugs in three tertiary hospitals in Anhui. METHODS: We obtained monthly drug use and expenditures data from three tertiary hospitals in Anhui (November 2014 through September 2017). An interrupted time series (ITS) design was used to estimate changes in defined daily doses (DDDs per month) and drug expenditures (dollars per month) of policy-targeted and non-targeted drugs after PMP implementation. Drugs were grouped based on whether they were recommended (recommended drugs) by any clinical guidelines or not (non-recommended drugs), or if they were potentially over-used (proton pump inhibitors, PPIs). RESULTS: After PMP, DDDs and costs of the targeted PPIs (omeprazole) declined while use of non-targeted PPIs increased correspondingly with overall sustained declines in total PPIs. The policy impact on recommended drugs varied based on whether the targeted drugs have appropriate alternatives. The DDDs and costs of recommended drugs that have readily accessible appropriate alternatives (atorvastatin) declined, which offset increases in its alternative non-target drugs (rosuvastatin), while there was no significant change in those recommended drugs that did not have appropriate alternative drugs (clopidogrel and ticagrelor). Finally, the DDDs and costs of non-recommended drugs decreased significantly. CONCLUSION: PMP policy impact was not the same across different drug groups. PMP did help contain the use and costs of potentially over-used drugs and non-recommended drugs. PMP did not seem to reduce the use of first-line therapeutic drugs recommended by clinical treatment guidelines, especially those lacking alternatives; such drugs are unlikely appropriate candidates for PMP.

Effectiveness and safety of anti-BCMA chimeric antigen receptor T-cell treatment in relapsed/refractory multiple myeloma: a comprehensive review and meta-analysis of prospective clinical trials.

Background: Chimeric antigen receptor T cells treatment targeting B cell maturation antigen (BCMA) is an emerging treatment option for relapsed/refractory multiple myeloma (RRMM) and has demonstrated outstanding outcomes in clinical studies. Objective: The aim of this comprehensive review and meta-analysis was to summarize the effectiveness and safety of anti-BCMA CAR-T treatment for patients with relapsed/refractory multiple myeloma (RRMM). Our research identifies variables influencing outcome measures to provide additional evidence for CAR-T product updates, clinical trial design, and clinical treatment guidance. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard was followed for conducting this comprehensive review and meta-analysis, which was submitted to PROSPERO (CRD42023390037). From the inception of the study until 10 September 2022, PubMed, Web of Science, EMBASE, the Cochrane Library, CNKI, and WanFang databases were searched for eligible studies. Stata software (version 16.0) was used to assess effectiveness and safety outcomes. Results: Out of 875 papers, we found 21 relevant trials with 761 patients diagnosed as RRMM and were given anti-BCMA CAR-T treatment. The overall response rate (ORR) for the entire sample was 87% (95% CI: 80-93%) complete response rate (CRR) was 44% (95% CI: 34-54%). The minimal residual disease (MRD) negativity rate within responders was 78% (95% CI: 65-89%). The combined incidence of cytokine release syndrome was 82% (95% CI: 72-91%) and neurotoxicity was 10% (95% CI: 5%-17%). The median progression-free survival (PFS) was 8.77 months (95% CI: 7.48-10.06), the median overall survival (OS) was 18.87 months (95% CI: 17.20-20.54) and the median duration of response (DOR) was 10.32 months (95% CI: 9.34-11.31). Conclusion: According to this meta-analysis, RRMM patients who received anti-BCMA CAR-T treatment have demonstrated both effectiveness and safety. Subgroup analysis confirmed the anticipated inter-study heterogeneity and pinpointed potential factors contributing to safety and efficacy, which may help with the development of CAR-T cell studies and lead to optimized BCMA CAR-T-cell products. Systematic Review Registration: Clinicaltrials.gov, PROSPERO, CRD42023390037.

Traditional Chinese medicine for frozen shoulder: An evidence-based guideline.

BACKGROUND: Frozen shoulder is a common disorder that can lead to long-lasting impairment in shoulder-related daily activities. Traditional Chinese medicine (TCM) has played an important role in the effort to manage frozen shoulder. PURPOSE: We aimed to develop an evidence-based guideline for treating frozen shoulder with traditional Chinese medicine. STUDY DESIGN: Evidence-based guideline. METHODS: We developed this guideline based on internationally recognized and accepted guideline standards. The guideline development group used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the certainty of evidence and the strength of recommendations. The benefits and harms, resources, accessibility, and other factors were fully taken into account, and the GRADE grid method was used to reach consensus on all recommendations. RESULTS: We established a multidisciplinary guideline development panel. Based on a systematic literature search and a face-to-face meeting, nine clinical questions were identified. Finally, twelve recommendations were reached by consensus, comprehensively considering the balance of benefits and harms, certainty of evidence, costs, clinical feasibility, accessibility, and clinical acceptability. CONCLUSION: This guideline panel made twelve recommendations, which covered the use of manual therapy, acupuncture, needle knife, Cheezheng Xiaotong plaster, Gutong plaster, exercise therapy and integrated TCM and Western medicine, such as combined modalities and corticosteroid injections. Most of them were weakly recommended or consensus based. The users of this guideline are most likely to be clinicians and health administrators.

Research Note: Dietary resveratrol supplementation improves the hepatic antioxidant capacity and attenuates lipopolysaccharide-induced inflammation in yellow-feathered broilers.

This experiment investigated the protective effect of resveratrol (RES) on the hepatic antioxidant status and systemic inflammation in yellow-feathered broilers challenged with lipopolysaccharide (LPS). A total of 240 healthy 1-day-old yellow-feathered broilers were randomly divided into 4 groups (control, LPS, RES, and RES+LPS), with 5 replicates of 12 chickens per replicate. The experiment lasted 21 d. The broilers were fed with either the basal diet or the basal diet supplemented with 400 mg/kg RES followed by intraperitoneal challenge with LPS (1 mg/kg body weight) or the same amount of saline at d 16, 18, and 20. The results showed that dietary RES supplementation could improve the activities of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in the liver of yellow-feathered broilers challenged with LPS (P < 0.05). Furthermore, LPS challenge increased the plasma interleukin-17 (IL-17) concentration, the hepatic interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) concentrations, as well as the concentrations of tumor necrosis factor (TNF-α), IL-6, and IL-1ß in the spleen (P < 0.05), and decreased the transforming growth factor-ß (TGF-ß) concentrations in the plasma, liver, and spleen (P < 0.05). However, dietary RES supplementation could reduce the increased TNF-α levels in the plasma, liver, and spleen induced by LPS, and increased TGF-ß level in the liver and spleen (P < 0.05). Collectively, these results suggest that dietary RES supplementation could effectively improve the hepatic antioxidant capacity and attenuate LPS-induced inflammation in yellow-feathered broilers during the starter stage.

Dietary dibutyryl cAMP supplementation regulates the fat deposition in adipose tissues of finishing pigs via cAMP/PKA pathway.

This study investigated potential mechanism of dibutyryl-cAMP (db-cAMP) on porcine fat deposition. (1) Exp.1, 72 finishing pigs were allotted to 3 treatments (0, 10 or 20 mg/kg dbcAMP) with 6 replicates. dbcAMP increased the hormone sensitive lipase (HSL) activity and expression of ß-adrenergic receptor (ß-AR) and growth hormone receptor (GHR), but decreased expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) and adipocyte fatty acid binding protein (A-FABP) in back fat. dbcAMP upregulated expression of ß-AR, GHR, PPAR-γ2 and A-FABP, but decreased insulin receptor (INSR) expression in abdominal fat. Dietary dbcAMP increased HSL activity and expression of G protein-coupled receptor (GPCR), cAMP-response element-binding protein (CREB) and insulin-like growth factor-1 (IGF-1), but decreased fatty acid synthase (FAS) and lipoprotein lipase (LPL) activities, and expression of INSR, cAMP-response element-binding protein (C/EBP-α) and A-FABP in perirenal fat. (2) Exp. 2, dbcAMP suppressed the proliferation and differentiation of porcine preadipocytes in a time- and dose-dependent manner, which might be associated with increased activities of cAMP and protein kinase A (PKA), and expression of GPCR, ß-AR, GHR and CREB via inhibiting C/EBP-α and PPAR-γ2 expression. Collectively, dbcAMP treatment may reduce fat deposition by regulating gene expression related to adipocyte differentiation and fat metabolism partially via cAMP-PKA pathway.

Physicians' Knowledge, Attitude, and Experience of Pharmacogenomic Testing in China.

(1) Background: As prescribers, physicians play a decisive role in applying and promoting pharmacogenomic (PGx) testing in clinical practices. So far, little is known about physicians' perspectives on PGx testing in China. The aim of this study was to assess physicians' knowledge of, attitude towards, and experience of PGx testing in China. (2) Methods: A 39-question online survey was developed. Participants were physicians recruited through two platforms, MEDLINKER and "Dazhuanjia". (3) Results: A total of 450 respondents completed the survey and 366 questionnaires were eligible for analysis based on the inclusion criteria. Among all included physicians, 275 (75.1%) had heard of PGx testing before. More than half rated their knowledge of PGx testing as "Fair" (61.5%) while 20.0% chose "Excellent" or "Good" and 18.6% chose "Poor" or "Terrible". "Guidelines, consensus, and treatment paths for disease diagnosis and treatment" (72.7%) were the most preferred sources of information about PGx testing. Respondents were confident in their personal capacity to conduct PGx, with an average score of 3.30 ± 0.09 (out of 5.00). Most respondents (75.6%) believed that PGx could "help to improve efficacy and reduce the incidence of adverse reactions". Targeted cancer therapy (score 78.95 ± 1.26 out of 100) was considered the field where PGx testing had its highest value. Lack of professionals and knowledge (n = 186, 67.6%), high costs of testing (n = 170, 61.8%), and lack of hospitals to offer PGx testing (n = 166, 60.4%) were identified as the primary obstacles to increasing the uptake of PGx testing in China. Academic conference (n = 213, 72.4%) was considered the most efficient way for physicians to obtain information about PGx testing. (4) Conclusions: Physicians in China have poor knowledge about PGx testing; nonetheless, they generally had confidence in their capacity to order PGx testing and positive attitudes towards the use of PGx testing in routine clinical practices. Future efforts to promote the uptake of PGx testing should focus on foundational education and practical training.

Cardiovascular adverse events in chronic myeloid leukemia patients treated with nilotinib or imatinib: A systematic review, meta-analysis and integrative bioinformatics analysis.

Objective: The aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis. Materials and methods: Three databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets. Results: Patients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77-4.25]), CAD (OR = 5.30 [95% CI 3.85-7.29]), ACS (OR 2.7 [95% CI 1.60-4.54]), CVA (OR 5.76 [95% CI 2.84-11.28]), PAOD (OR 5.57 [95% CI 3.26-9.50]) and arrhythmia (OR 2.34 [1.17,4.67]) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42-4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity,mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above. Conclusion: CML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.

Trends in the utilization of psychotropic medications in China from 2018 to 2021.

Background: Monitoring psychotropic medicine consumption trends can provide information on the extent of pharmacological interventions for mental disorders and availability of psychotropic medicines. Objectives: This study aimed to illustrate the trends in psychotropic drug utilization in China's hospitals. Methods: We retrospectively analyzed the aggregated monthly psychotropic procurement records of 1009 hospitals from 31 provinces in China from January 2018 to September 2021. Total psychotropic medicine consumption included the sales of antipsychotics, antidepressants, anxiolytics, mood stabilizers, and sedatives or hypnotics. Information, including generic name, procurement amount, dosage form, strength, purchase time, and geographical data, was collected. Population-weighted psychotropic utilization was expressed in defined daily dose per 1000 inhabitants per day (DDD/1000/day). Results: Psychotropic medicine sales increased from 4.5 DDD/1000/day in Q1 2018 to 6.4 DDD/1000/day in Q3 2021; total utilization in China's hospitals increased by 42.2%. The use of each class of psychotropics showed a gradually increasing trend. Antidepressants were the most consumed psychotropics, accounting for 48.4% of the total psychotropic utilization (3.1/6.4 DDD/1000/day), followed by sedatives or hypnotics (31.3%; 2.0/6.4 DDD/1000/day) and antipsychotics (15.6%; 1.0/6.7 DDD/1000/day). Among all sub-classes of psychotropics, a most significant growth in DDD per 1000 inhabitants per day was seen for selective serotonin reuptake inhibitors (1.2-1.9 DDD/1000/day), whereas the consumption of typical antipsychotics (from 0.1 to 0.09 DDD/1000/day) and tricyclic antidepressants (from 0.05 to 0.03 DDD/1000/day) decreased during the study period. Psychotropic utilization substantially increased between Q1 2018 and Q3 2021 in regions with different economic levels. In Q3 2021, total psychotropic utilization in secondary and tertiary hospitals was 9.4 DDD/1000/day and 6.0 DDD/1000/day, respectively. Sedatives or hypnotics in secondary hospitals accounted for the largest proportion of utilized psychotropics (43.6%; 4.1/9.4 DDD/1000/day), whereas antidepressants were the most commonly used psychotropic in tertiary hospitals (50.0%, 3.0/6.0 DDD/1000/day). Conclusion: This study showed that despite increases in psychotropic medication use, the consumption of medicines is still much lower than in other countries and regions internationally. With reference to the estimated prevalence of corresponding mental disorders, our study illustrates that a large treatment gap for mental health problems exists in China. In addition, the wide use of psychotropics with weak clinical evidence raises serious concerns regarding rational use. Greater efforts are needed to increase the availability of psychotropic medicines and to facilitate proper psychotropic use.

Link between sterile inflammation and cardiovascular diseases: Focus on cGAS-STING pathway in the pathogenesis and therapeutic prospect.

Sterile inflammation characterized by unresolved chronic inflammation is well established to promote the progression of multiple autoimmune diseases, metabolic disorders, neurodegenerative diseases, and cardiovascular diseases, collectively termed as sterile inflammatory diseases. In recent years, substantial evidence has revealed that the inflammatory response is closely related to cardiovascular diseases. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) pathway which is activated by cytoplasmic DNA promotes the activation of interferon regulatory factor 3 (IRF3) or nuclear factor-κB (NF-κB), thus leading to upregulation of the levels of inflammatory factors and interferons (IFNs). Therefore, studying the role of inflammation caused by cGAS-STING pathway in cardiovascular diseases could provide a new therapeutic target for cardiovascular diseases. This review focuses on that cGAS-STING-mediated inflammatory response in the progression of cardiovascular diseases and the prospects of cGAS or STING inhibitors for treatment of cardiovascular diseases.

Effect of dietary resveratrol supplementation on growth performance, antioxidant capacity, intestinal immunity and gut microbiota in yellow-feathered broilers challenged with lipopolysaccharide.

Resveratrol (RES) displays strong antioxidant and anti-inflammatory properties in protecting the animals from various stressors and inflammatory injuries, but its interrelationship with the gut microbiota remained largely unclear. This study was carried out to investigate the effects of dietary RES supplementation on growth performance, antioxidant capacity, intestinal immunity and gut microbiota in yellow-feathered broilers challenged by lipopolysaccharide (LPS). A total of 240 yellow-feathered broilers were randomly assigned to four treatment groups in a 2 × 2 factorial design. The broilers were fed with the control diet or control diet supplemented with 400 mg/kg RES, followed by challenge with LPS or the same amount of saline. Dietary RES supplementation significantly alleviated the decreases in the final body weight (BW), average daily gain (ADG), and ADFI induced by LPS (P < 0.05). LPS challenge significantly increased plasma concentrations of triglyceride, high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and cortisol levels, but decreased triiodothyronine (T3) and insulin levels (P < 0.05). Dietary supplementation with RES significantly reversed the elevated creatinine concentrations and the decreased concentrations of T3 and insulin caused by LPS (P < 0.05). Moreover, dietary RES supplementation significantly increased plasma total antioxidant capacity (T-AOC) and catalase (CAT) activities and superoxide dismutase (SOD) and T-AOC activities in jejunal mucosa and reduced malondialdehyde (MDA) concentration in the plasma (P < 0.05). The reduction in the villus height to crypt depth ratio in duodenum, jejunum and ileum and the shortening of villus height in jejunum and ileum caused by LPS were also alleviated by RES treatment (P < 0.05). Furthermore, the increased concentrations of intestinal tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1ß caused by LPS were significantly decreased by RES treatment (P < 0.05). Dietary RES treatment increased the mRNA expression of claudin-1, claudin-5, occludin, and zonula occludens-1 (ZO-1), and decreased mRNA expression of IL-1ß, IL-8, IL-17, and TNF-α after LPS challenge (P < 0.05). Dietary RES treatments significantly decreased the dominance of cecal microbiota, and increased the Pieiou-e and Simpson index. Moreover, dietary RES supplementation increased relative abundance of UCG_ 009, Erysipelotrichaceae, Christensenellaceae_R-7_group, Anaerotruncus, RF39, and Ruminococcus while decreasing the abundance of Alistipes at genus level. Spearman correlation analysis revealed that the microbes at the order and genus levels significantly correlated with indicators of growth performance, antioxidant capacity, and intestinal health. Collectively, dietary supplementation with 400 mg/kg RES could improve growth performance and antioxidant capacity, and modulate intestinal immunity in yellow-feathered broilers challenged by LPS at early stage, which might be closely associated with the regulation of gut microbiota community composition.

The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies.

Background: Due to the lack of comprehensive evidence based on prospective studies, the efficacy and safety of Janus Kinase (JAK) inhibitors (including tofacitinib, ruxolitinib, baricitinib, ritlecitinib and brepocitinib) for alopecia areata (AA) are yet to be proved. Methods: The systematic review and meta-analysis was performed pursuant to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline and registered on PROSPERO (CRD42022303007). Results: Fourteen prospective studies (5 RCTs and 9 non-RCTs), enrolling a total of 1845 patients with AA, were included for quantitative analysis. In RCTs, oral JAK inhibitors resulted in higher good response rate compared with control (RR: 6.86, 95% CI: 2.91-16.16); topical JAK inhibitors did not show any difference compared with control (RR: 1.00, 95% CI: 0.31-3.18). In non-RCTs, the pooled rate of good response to oral, topical and sublingual JAK inhibitors were 63% (95% CI: 44%-80%), 28% (95% CI: 1%-72%) and 11% (95% CI: 1%-29%), respectively. The pooled recurrence rate in patients treated with JAK inhibitors was 54% (95% CI: 39%-69%), mainly due to the withdrawal of JAK inhibitors. In RCTs, no difference was found in the risk of experiencing most kind of adverse events; in non-RCTs, the reported adverse events with high incidence rate were mostly mild and manageable. Conclusion: JAK inhibitors are efficacious and generally well-tolerated in treating AA with oral administration, whereas topical or sublingual administration lacks efficacy. Subgroup analyses indicate that baricitinib, ritlecitinib and brepocitinib seem to have equal efficacy for AA in RCTs; ruxolitinib (vs. tofacitinib) and AA (vs. AT/AU) are associated with better efficacy outcomes in non-RCT. Due to the high recurrence rate after withdrawal of JAK inhibitors, continuous treatment should be considered to maintain efficacy. Systematic Review Registration: PROSPERO: CRD 42022303007.

Cation-Selective Oxide Semiconductor Mesoporous Membranes for Biomimetic Ion Rectification and Light-Powered Ion Pumping.

Artificial membranes precisely imitating the biological functions of ion channels and ion pumps have attracted significant attention to explore nanofluidic energy conversion. Herein, inspired by the cyclic ion transport for the photosynthesis in purple bacteria, a bilayer inorganic membrane (TiO2 /AAO) composed of oxide semiconductor (TiO2 ) mesopores on anodic alumina (AAO) macropores is we developed. This inorganic membrane achieves the functions of ion channels and ion pumps, including the ion rectification and light-powered ion pumping. The asymmetric charge distribution across the bilayer membrane contributes to the cationic selectivity and ion rectification characteristics. The electrons induced by ultraviolet irradiation introduce a built-in electric field across TiO2 /AAO membrane, which pumps the active ion transport from a low to a high concentration. This work integrates the functions of biological ion channels and ion pumps within an artificial membrane for the first time, which paves the way to explore multifunctional membranes analogous to its biological counterpart.

Clinical Pharmacists' Involvement in Pharmacogenomics Testing and Related Services in China.

Background: Pharmacogenomics (PGx) testing is increasingly used in clinical practice to optimize drug therapies. This study aims to understand the involvement of clinical pharmacists in PGx testing at tertiary hospitals in China and their self-assessed capacity to deliver such services. Methods: We developed a questionnaire exploring clinical pharmacists' involvement and self-assessed level of capacity of performing PGx tests. A random sample was obtained from the Pharmaceutical Affairs Management Professional Committee of the Chinese Hospital Association. Results: A total of 1005 clinical pharmacists completed the survey. Of these, 996 (99.1%) had heard of PGx tests and 588 (59.0%) had been involved in PGx testing and related services. Some clinical pharmacists (28.9%) provided PGx services at the rate of "1−5 cases/year" while 21.9% of clinical pharmacists provided PGx services at the rate of ">30 cases/year". Clinical pharmacists most frequently provided PGx testing for cardiovascular diseases. "Consult relevant guidelines/literature" (90.1%) was the most frequently used method to familiarize oneself with PGx testing. About 60% of the pharmacists considered themselves to have poor or fair capacity to provide PGx testing and related services. Conclusions: More than half of the pharmacists had been involved in PGx testing and related services. However, pharmacists generally had little confidence in their knowledge level of and capacity to provide PGx-related services.