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The geological model plays an important role in geophysics and engineering geology. The data source of geological modeling comes from interpretation data, borehole data, and outcrop data. Due to economic and technical limitations, it is impossible to obtain highly accurate and high-density data sources. The sparsity and inaccuracy of data sources lead to the uncertainty in geological models. Unlike the problem of probability, there is not enough samples for a geological model. Spatial diffusion model and merging model are introduced, which are more satisfied with the cognition of uncertainty than the existing methods. And then, using conditional information entropy, a quantification method of geological uncertainty, is proposed. Compared with the approaches of information entropy, this method took full account of the constraints of geological laws. Based on the uncertainty models and conditional information entropy, a framework of uncertainty assessment in geological models is established. It is not necessary in our framework to create multiple geological models, which is a time-consuming and laborious task. The application of Hashan survey located at north of China shows that the method and framework of this study are reasonable and effective.

Aims Atherosclerosis (AS) is a leading cause of cardiovascular morbidity and mortality. Atherosclerotic lesions show increased levels of proteins associated with the fibroblast growth factor receptor (FGFR) pathway. However, the functional significance and mechanisms governed by FGFR signalling in AS are not known. In the present study, we investigated fibroblast growth factor receptor 1 (FGFR1) signalling in AS development and progression. Methods and results Examination of human atherosclerotic lesions and aortas of Apoe−/− mice fed a high-fat diet (HFD) showed increased levels of FGFR1 in macrophages. We deleted myeloid-expressed Fgfr1 in Apoe−/− mice and showed that Fgfr1 deficiency reduces atherosclerotic lesions and lipid accumulations in both male and female mice upon HFD feeding. These protective effects of myeloid Fgfr1 deficiency were also observed when mice with intact FGFR1 were treated with FGFR inhibitor AZD4547. To understand the mechanistic basis of this protection, we harvested macrophages from mice and show that FGFR1 is required for macrophage inflammatory responses and uptake of oxidized LDL. RNA sequencing showed that FGFR1 activity is mediated through phospholipase-C-gamma (PLCγ) and the activation of nuclear factor-κB (NF-κB) but is independent of FGFR substrate 2. Conclusion Our study provides evidence of a new FGFR1–PLCγ–NF-κB axis in macrophages in inflammatory AS, supporting FGFR1 as a potentially therapeutic target for AS-related diseases. [ABSTRACT FROM AUTHOR]

Artificial nanofluidic channels that achieve light-driven ion transport in biological systems based on photoelectric effect have attracted significant attention for signal transduction and light energy conversion. However, the light-responsive performance is limited by the charge separation efficiency on the surface of the channels. Herein, we introduce semiconductor p–n junctions into nanofluidic channels to enhance their light-driven ion transport. The p–n junction is formed by an n-type titanium dioxide (TiO2) nanoparticles layer on an electrochemically fabricated p-type polypyrrole (PPy) membrane. The light-induced charge separation at p–n junctions increases the surface charge density of the positively charged PPy membrane. Consequently, the light-driven ion current through the nanofluidic channels is enhanced from 79.6 to 111.9 nA by 40.6% when compared with a single-component p-type PPy membrane. The proof-of-concept demonstration of enhanced light-driven ion transport by semiconductor p–n junctions provides a route toward high-performance light-responsive nanofluidic channels, which demonstrates potential applications for light-controlled mass transport, signal transduction, and energy conversion. [ABSTRACT FROM AUTHOR]

This study aimed to identify factors that affect physicians' generic prescribing behavior based on the theory of planned behaviors (TPB). Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions. Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the "Consistency Evaluation of Quality and Efficacy of Generic Drugs" (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively. Conclusion: Physicians' attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians' prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians' prescribing practice is likely affected by perceived strong control over prescribing generic drugs. [ABSTRACT FROM AUTHOR]

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 β-adrenergic receptor (β-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 β-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, β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

(1) Background: Uptake of pharmacogenomic testing in routine clinical practices is currently slow in China. Pharmacists might play an important role in leveraging care through applying pharmacogenomics, therefore, it is important to better understand clinical pharmacists' knowledge of and attitudes toward pharmacogenomic testing, which has not been well-studied. (2) Methods: A self-administered survey was developed based on previous knowledge of pharmacogenomic testing and its uptake in China. Participants were recruited through the Committee of Pharmaceutical Affairs Management under the Chinese Hospital Association. (3) Results: A total of 1005 clinical pharmacists completed the questionnaire, among whom 996 (99.10%) had heard of pharmacogenomic testing before participation. More than half of respondents (60.0%, n = 597) rated their knowledge of pharmacogenomic testing as "average", while 25% rated it "good" or "excellent". "Guidelines, consensus and treatment paths for disease diagnosis and treatment" (78.7%) were the most preferred sources of information about pharmacogenomic testing. Most respondents (77.0%) believed that pharmacogenomics could "help to improve efficacy and reduce the incidence of adverse reactions". Our participants also believed that patients would benefit most from pharmacogenomic testing through better prediction of individual drug responses and thus informed treatment decisions. The top challenge for the uptake of pharmacogenomic testing was its high cost or lack of insurance coverage (76.7%). (4) Conclusions: Most Chinese clinical pharmacists who participated in our study had a positive attitude toward pharmacogenomic testing, while the knowledge of pharmacogenomic testing was generally self-assessed as average. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plasma Antioxidant Capacity and Antioxidant Gene Expression in the Muscle As shown in Figure 1, dietary supplementation with compound antioxidants of 200 mg/kg vitamin E, 0.3 mg/kg selenium-enriched yeast, and 20 mg/kg soy isoflavones significantly decreased the plasma MDA concentration, and increased the plasma GSH/GSSG ratio ( I p i < 0.05). However, further studies by techniques such as fecal microbiota transplantation would be needed to elucidate the interactions between these antioxidant compounds with dynamic changes in gut microbiota as well as the role and potential mechanism of gut microbiota in enhanced antioxidant capacity and meat quality by dietary compound antioxidants. Keywords: compound antioxidants; finishing pigs; carcass traits; gut microbiota; meat quality; vitamin E; selenium-enriched yeast; soy isoflavones EN compound antioxidants finishing pigs carcass traits gut microbiota meat quality vitamin E selenium-enriched yeast soy isoflavones N.PAG N.PAG 18 08/29/22 20220801 NES 220801 1. [Extracted from the article]

Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to explore the safety, tolerance, pharmacokinetics, pharmacodynamics, and immunogenicity of LY06006, a recombinant humanized monoclonal antibody to RANKL, when administrated subcutaneously in Chinese healthy adults. Research design and methods: This was a randomized, double-blinded, placebo-controlled, single ascending dose study performed in 32 healthy Chinese adults, who were randomly assigned to receive a single injection dose of 18, 60, 120 mg study drug or placebo with a follow-up of 140–252 days. Results: No deaths or drug-related serious adverse events occurred. LY06006 was rapidly absorbed in the 60 mg group with a Tmax range of 120–480 h and serum LY06006 concentrations decreased slowly 11–13 days after dosing with a long mean (SD) half-life of 389.58 (63.44) h. The most frequent AEs were elevated serum parathyroid hormone (PTH) level (83.3%), hypocalcemia (54.2%), and hypophosphatemia (45.8%). None of the 32 subjects tested positive for anti-drug antibody during the trial. Conclusion: Single-dose subcutaneous administration of LY06006 was safe and well-tolerated in healthy Chinese adults. Cmax showed linear pharmacokinetic characteristics in the dose range of 18–120 mg based on dose-exposure proportionality analysis. [ABSTRACT FROM AUTHOR]

The article discusses the prevalence of antidepressant medication use in China based on the National Health Insurance database and identifies the most commonly used medications. The study found that the most commonly used antidepressants were selective serotonin reuptake inhibitors, and the most commonly prescribed drugs by generic name were paroxetine, escitalopram, and sertraline.v.

The simulation of the ion pumping against a proton gradient energized by light in photosynthesis is of significant importance for the energy conversion in a non‐biological environment. Herein, we report light‐powered ion pumping in a polystyrene sulfonate anion (PSS) doped polypyrrole (PPy) conducting polymer membrane (PSS‐PPy) with a symmetric geometry. This PSS‐PPy conducting polymer membrane exhibits a cationic selectivity and a light‐responsive surface‐charge‐governed ion transport attributed to the negatively charged PSS groups. An asymmetric visible irradiation on one side of the PSS‐PPy membrane induces a built‐in electric field across the membrane due to the intrinsic photoelectronic property of PPy, which drives the cationic transport against the concentration gradient, demonstrating an ion‐pumping effect. This work is a prototype that uses a geometry‐symmetric conducting polymer membrane as a light‐powered artificial ion pump for active ion transport, which exhibits potential applications in nanofluidic energy conversion. [ABSTRACT FROM AUTHOR]

The design of an electrode surface is critical to the oxygen evolution reaction (OER) during electrochemical water splitting since the catalytic activity depends strongly on surface characteristics, such as the coating uniformity of the catalysts, electrolyte wetting, and the gas‐bubble release ability. Here, nonprecious‐metal electrocatalysts (MnO nanowires) are electrochemically deposited on the surface of a porous gold microgrid. The discontinuous solid–liquid contact lines, which are formed by the microgrids during the liquid‐phase electrochemical reaction, generate MnO nanowires with high coating uniformity. The micro/nanostructure of the electrode induces a superhydrophilic surface, which facilitates the wetting of the alkaline electrolyte and increases the electrochemical active surface area. Simultaneously, the underwater superaerophobicity of the electrode promotes the release of the oxygen products, thus reducing the occupation of the catalytic sites by the gas bubbles. The synergistic effect of electrolyte wetting and gas release ensures that this superhydrophilic/superaerophobic electrode exhibits a current density of 10 mA cm−2 for the OER at an overpotential of 530 mV in 0.1 m KOH, placing the catalyst among the best MnO catalysts for OER. This work avails a new basis for synergistically optimizing the synthesis methods (electrolyte wetting and gas‐bubble release) toward high‐performance OER electrodes. [ABSTRACT FROM AUTHOR]

Cardiovascular complications are a well-documented limitation of conventional cancer chemotherapy. As a notable side effect of cisplatin, cardiotoxicity represents a major obstacle to the treatment of cancer. Recently, it has been reported that cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway was associated with the occurrence and development of cardiovascular diseases. However, the effect of STING on cardiac damage caused by cisplatin remains unclear. In this study, cisplatin was shown to activate the cGAS-STING signaling pathway, and deficiency of STING attenuated cisplatin-induced cardiotoxicity in vivo and in vitro. Mechanistically, the STING-TNF-α-AP-1 axis contributed to cisplatin-induced cardiotoxicity by triggering cardiomyocyte apoptosis. In conclusion, our results indicated that STING might be a critical regulator of cisplatin-induced cardiotoxicity and be considered as a potential therapeutic target for preventing the progression of chemotherapy-associated cardiovascular complications. [ABSTRACT FROM AUTHOR]

The characteristics of electrolyte wetting and gas release are of vital importance for the electrocatalytic activity of a hydrogen evolution electrode (HEE). Herein, we reported a strategy to synergistically optimize the electrolyte wetting and gas release of a HEE to enhance its electrocatalytic activity. In our work, Pt nanosheets arrays were electrochemically deposited on a conductive substrate of Au microgrid to form a HEE. The micropores of Au grids induced discontinuous solid/liquid two‐phase contact lines in microscale, which facilitated the wetting of proton‐contained electrolyte. Simultaneously, the superaerophobicity of HEE promoted the release of hydrogen gas products. The joint improvement on electrolyte wetting and gas release enhanced the current density of hydrogen evolution reaction at a high overpotential by ∼300 % when compared with Pt nanosheets arrays on a flat Au substrate. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate potentially inappropriate medications (PIMs) prevalence and predictors in community healthcare institutions (CHIs) for the elderly. Methods: We conducted a retrospective observational study, deriving data of patients aged ≥60 from 66 CHIs in Beijing, 2014‐2018. The system of Criteria of PIM for Older Adults in China was applied to identify PIMs. The primary outcome was the prevalence of visits with at least one PIM; secondary outcomes were the frequency and rate per thousand visits of specific PIMs. We used descriptive analysis and generalized linear models to analyzed PIMs and the predictors, and marginal effects methods were applied to estimate the mean adjusted PIMs prevalence. Results: Overall, 4 528 884 elderly patient visits from 2014 to 2018 were eligible for inclusion. A total of 719 757 PIMs were detected, with 14.1% of the visits contained at least one PIM. PIM prevalence was significantly correlated with age, number of prescribed medications and number of diagnoses. Overall, 6.0 per thousand elderly patients in CHIs were exposed to at least one high‐risk PIM, while 117.5 per thousand were exposed to at least one low‐risk PIM. In 2018, 20% of GPs were responsible for more than half of overall PIM visits. Conclusion: Prescribing of PIMs for older adults is common in CHIs in China, especially for patients who are aged, having multiple medications and diagnostic diseases. Strategies should be developed to enhance prescribing quality for geriatric patients, with special targeting of doctors responsible for a high number of PIMs. [ABSTRACT FROM AUTHOR]

Nanofluidic diodes mimicking biological ion channels are emerging as desirable materials for controllable ion transport in artificial nanochannels due to their rectification properties. However, the precise control of the chemical composition, geometric structure, surface charges and subsequent rectification of nanofluidic diodes is still challenging. Herein, bottom-up self-assembly is used to fabricate nanofluidic diodes with building blocks of an alumina nanoporous membrane and ion-selective polystyrene opals. Through changing the sphere sizes of opals, the surface charges of opals and the assembly sequence of the building blocks, the chemical composition, geometric structure and surface charges of nanofluidic diodes are tailored on demand, which results in precise control of the rectification. The ion rectification of these assembled diodes is theoretically investigated by a model calculation based on Poisson–Nernst–Planck equations. The bottom-up assembled diodes are applied in conversion of osmotic energy into electricity, which demonstrates a high conversion performance. [ABSTRACT FROM AUTHOR]

Inspired by the formation mechanism of a biological membrane potential, we described the generation of an artificial membrane potential through redox-regulating anion distribution on the two sides of a polypyrrole film. The polarity of the membrane potential could be regulated by the redox reaction. [ABSTRACT FROM AUTHOR]

Although several case reports and small clinical trials have reported promising outcomes with Janus kinase (JAK) inhibitors for vitiligo, high-quality evidence and guidelines are lacking. We evaluated the efficacy and safety of JAK inhibitors for the treatment of vitiligo using a meta-analysis of randomized controlled trials (RCTs). We searched the PubMed, Embase, and Cochrane Library databases up to August 2023, with additional studies from ClinicalTrials.gov and company websites. We assessed outcomes, including percentage improvement in total vitiligo area score index (TVASI) and facial vitiligo area score index (FVASI); the proportion of patients achieving 50% improvement in TVASI (TVASI50) and 50% and 75% improvement in FVASI (FVASI50 and FVASI75); the risk of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infections, and skin-related adverse events (AEs). Five studies with 1,550 participants were included. JAK inhibitors were associated with a higher proportion of TVASI50 (relative risk [RR] 2.67, 95% confidence interval [CI] 1.24-5.78) and FVASI75 (RR 3.97, 95%CI 2.62-6.02) responders than placebo. JAK inhibitors significantly increased the risk of skin-related AEs (RR 1.96, 95% CI 1.29-2.98) compared with placebo. However, the risk of TEAEs, SAEs, and infections was not significantly different between the JAK inhibitor and placebo groups. Subgroup analysis showed that JAK1 and JAK1/2 inhibitors were more effective than JAK3 inhibitors. However, there was insufficient evidence to suggest that the route of administration affects the efficacy and safety of JAK inhibitors in vitiligo. These findings indicate that JAK inhibitors are effective in repigmentation and well tolerated in patients with vitiligo., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

This study mainly investigated the effects of berberine (BBR) on the bile acid metabolism in gut-liver axis and the microbial community in large intestine of weaned piglets challenged with enterotoxigenic Escherichia coli (ETEC) by microbiome and metabolome analyses. Sixty-four piglets were randomly assigned to four groups including Control group, BBR group, ETEC group, and BBR + ETEC group. Dietary BBR supplementation upregulated the colonic mRNA expression of Occludin , Claudin-5 , trefoil factor 3 ( TFF3 ), and interleukin ( IL ) -10 , and downregulated colonic IL-1β and IL-8 mRNA expression in piglets challenged with ETEC K88 ( p  < 0.05). The hepatic non-targeted metabolome results showed that dietary BBR supplementation enriched the metabolic pathways of primary bile acid biosynthesis, tricarboxylic acid cycle, and taurine metabolism. The hepatic targeted metabolome analyses showed that BBR treatment increased the hepatic concentrations of taurocholic acid (TCA) and taurochenodeoxycholic acid (TDCA), but decreased the hepatic cholic acid (CA) concentration ( p  < 0.05). Further intestinal targeted metabolome analyses indicated that the deoxycholic acid (DCA), hyocholic acid (HCA), 7-ketodeoxycholic acid (7-KDCA), and the unconjugated bile acid concentrations in ileal mucosa was decreased by dietary BBR treatment ( p  < 0.05). Additionally, BBR treatment significantly upregulated the hepatic holesterol 7 α-hydroxylase ( CYP7A1 ) and sterol 27-hydroxylase ( CYP27A1 ) mRNA expression, and upregulated the ileal mRNA expression of farnesoid X receptor ( FXR ) and apical sodium-dependent bile acid transporter ( ASBT ) as well as the colonic mRNA expression of FXR , fibroblast growth factor19 ( FGF19 ), takeda G protein-coupled receptor 5 ( TGR5 ) and organic solute transporters beta ( OST-β ) in piglets ( p  < 0.05). Moreover, the microbiome analysis showed that BBR significantly altered the composition and diversity of colonic and cecal microbiota community, with the abundances of Firmicutes (phylum), and Lactobacillus and Megasphaera (genus) significantly increased in the large intestine of piglets ( p  < 0.05). Spearman correlation analysis showed that the relative abundances of Megasphaera (genus) were positively correlated with Claudin-5 , Occludin , TFF3 , and hepatic TCDCA concentration, but negatively correlated with hepatic CA and glycocholic acid (GCA) concentration ( p  < 0.05). Moreover, the relative abundances of Firmicute (phylum) and Lactobacillus (genus) were positively correlated with hepatic TCDCA concentration ( p  < 0.05). Collectively, dietary BBR supplementation could regulate the gut microbiota and bile acid metabolism through modulation of gut-liver axis, and attenuate the decreased intestinal tight junction expression caused by ETEC, which might help maintain intestinal homeostasis in weaned piglets., Competing Interests: YB was employed by Shanwei Xinsheng Leisure Agriculture Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nie, Lu, Yin, He, Bai and Zhu.)

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., Competing Interests: Competing interests statement:J.F., S.C.H., and G.K. filed a provisional patent application regarding use of recombinant post-fusion HA2 for influenza vaccination.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Nie, Lu, Bai and Jiang.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Chen, Yan, Dong, Chen, Niu, Wang, Zhang, Nie and Fang.)

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., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, He, Zhang, Cai, Liu, Nie and Shi.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Hu, Zhao, Lu, Nie and Shi.)

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-1β 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-1 β, 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&#95; 009 , Erysipelotrichaceae , Christensenellaceae&#95;R-7&#95;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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Li, Xiong, Nie, Zhang and Zhu.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yan, Fan, Chen, Xia, Wang, Dong, Wang, Niu, Rao, Chen, Nie and Fang.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Zhang, Nie, Qi, Shi, Han, Zhou, He and Wang.)

Objective: We aimed to compare the efficacy, acceptability, and tolerability of vortioxetine in the treatment of Major Depressive Disorder (MDD) in adults., Method: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), and www.ClinicalTrials.gov for randomized controlled trials that examined vortioxetine vs. placebo or other antidepressants for the treatment of MDD from database inception to August 30, 2021, using keywords Vortioxetine, Brintellix, Trintellix, LuAA21004, major depressive disorder, mood disorder, affective disorder, and MDD. We identified 789 publications after removing duplicates. After screening, 20 eligible randomized controlled trials were identified, of which 19 were included in the final meta-analysis. We included adults (aged 18 years and older) with a primary diagnosis of MDD. Two review authors independently selected the studies and extracted data. We extracted data on study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability, and tolerability. Analyses were performed using random-effects models, and outcomes were pooled as risk ratios (RRs) and standardized mean differences (SMDs)., Results: In total, 20 studies (8,547 participants) met the inclusion criteria. Vortioxetine outperformed the placebo in efficacy outcomes, including response (RR 1.35, 95% CI 1.23-1.48; P < 0.001), remission (RR 1.33, 95% CI 1.17-1.52; P < 0.001), and cognitive function (SMD 0.34, 95% CI 0.16-0.52; P = 0.0003). Compared with the serotonin noradrenaline reuptake inhibitors (SNRIs), vortioxetine had better tolerability (RR 0.90, 95% CI 0.86-0.94; P < 0.001) but no significant difference in response (RR 0.91, 95%CI 0.82-1.00; P = 0.06) or remission (RR: 0.99, 95% CI 0.81-1.20, P = 0.88). Vortioxetine had no difference in response (RR 1.08, 95% CI 0.88-1.32; P = 0.46), remission (RR 1.00, 95% CI 0.41-2.44; P = 1.00) comparing with selective serotonin reuptake inhibitors (SSRIs)., Conclusions: Vortioxetine is more advantageous over placebo in treating MDD among adults, but no significant difference compared to SNRIs and SSRIs in general., Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display&#95;record.php?ID=CRD42021278355, identifier: CRD42021278355., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Cai, Hu, Lu, Nie and Shi.)