OBJECTIVES: To evaluate the effectiveness and safety of deucravacitinib in Chinese patients with moderate-to-severe plaque psoriasis. METHODS: This retrospective study included 41 patients with moderate-to-severe plaque psoriasis treated with deu-cravacitinib 6 mg once daily for 16 weeks at the First Affiliated Hospital of Wenzhou Medical University between January and September 2024. Effectiveness was assessed by the psoriasis area and severity index (PASI), static physician's global assessment (sPGA), palmoplantar psoriasis area and severity index (PPASI), modified nail psoriasis severity index (mNAPSI), and dermatology life quality index (DLQI) at baseline, 4, 8, 12 and 16 weeks after treatment. Adverse events during treatment were recorded. Laboratory parameters, including complete blood count, liver and kidney function, electrolytes, and lipids, were assessed at baseline, 8, 16 weeks after treatment to evaluate safety. Univariate and multivariate logistic regression analyses were performed to explore factors associated with achieving PASI75 at week 16, using baseline characteristics as independent variables. RESULTS: Significant reductions from baseline in PASI and DLQI scores were observed from week 4 through week 16 (all P<0.01). Overall response rates for PASI75, PASI90, PASI100, sPGA 0 or 1 grade, and DLQI 0 or 1 point increased progressively over the treatment period. 75, 90, and 100 refer to a score reduction of at least 75%, at least 90%, and 100%, respectively, from baseline. Response rates of PASI75, PASI90, PASI100 for the scalp, limbs, and trunk, PPASI75, PPASI90, PPASI100 for palmoplantar lesions, and mNAPSI75, mNAPSI90 for nail lesions increased progressively over time but with different trends. Scalp lesions improved most markedly from week 4, followed by the limbs, whereas improvements in trunk and palmoplantar lesions were relatively slower. Nail lesions responded more slowly, with only 20% of patients achieving marked improve-ment at week 16. Deucravacitinib demonstrated good tolerability and compatibility with concomitant medications. No severe adverse events were reported, indicating a favorable safety profile. Multivariate logistic regression analysis revealed no significant association between the achievement of PASI75 response at week 16 and patient age, body mass index, disease duration, or baseline PASI, sPGA, or DLQI scores (all P>0.05). CONCLUSIONS In this real world study of Chinese patients with moderate-to-severe plaque psoriasis, deucravacitinib demonstrated favorable effectiveness and safety over 16 weeks of treatment.
Humans ; Psoriasis/drug therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; China ; Adult ; Treatment Outcome ; Severity of Illness Index ; Quality of Life ; Aged

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective:To investigate the endorectal ultrasound findings in rectal neuroendocrine neoplasms (R-NEN) and to compare the diagnostic performance of ERUS and MRI for T staging of R-NENs.Methods:The imaging features of 77 confirmed R-NEN cases with different pathological grades in the Sixth Affiliated Hospital, Sun Yat-sen University from August 2015 to August 2021 were retrospectively analyzed and the abilities of ERUS and MRI for T staging of R-NENs were compared.Results:A total of 77 R-NEN patients underwent preoperative ERUS examinations and detected lesions in 62 patients with a detection rate of 80.52%. Among them, 30 cases underwent simultaneous MRI examinations, and detected lesions in 25 cases with a detection rate of 83.33%, without statistical difference between MRI and ERUS ( P>0.05). R-NEN exhibited hypoechoic nodules with rich blood flow in the submucosa on ERUS. Grade G1 and G2 tumors generally had sizes less than 10 mm, clear boundaries, and regular shapes, while G3 was typically large, irregular, poorly defined, and more likely to invade the musculi propria and serous layer. G3 demonstrated a more profound infiltration level, a less defined border, and a larger diameter than G1 and G2, with statistically significant differences (all P<0.05). For T staging, the accuracy of ERUS was 86.67%, and that of MRI was 94.67%, with no statistical difference ( P>0.05). Conclusions:ERUS is effective for detecting R-NEN lesions and useful for tumor grading with comparable performance to MRI, and should be recommended for preoperative evaluation of neuroendocrine tumors.

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

Allergic asthma is a complex heterogeneous disease of respiratory system.It has extensive variability at the genetic level,and has a variety of opportunities to change genetic diversity.More and more studies have shown that targeting Wnt/β-catenin signaling pathway can affect the occurrence and development of allergic asthma,but its specific immune mechanism is not clear.In this paper,we mainly introduce Wnt/β-catenin signal and its role and function in allergic asthma provide a new target for drug inter-vention in the treatment of allergic asthma.

Ischemic stroke （IS） is the most common type of stroke that can lead to severe neurological dysfunction while effective diagnostic and therapeutic methods are currently limited. Exosomes are natural vesicles that can play a key role in intercellular communication by delivering proteins， lipids， and nucleic acids. Notably，IS could cause changes in the level and content of exosome， which can serve as a potential biomarker to assist the diagnosis and treatment of IS. This article reviews the potential diagnostic value of exosomes，discusses their repair effects， and explores the potential application as drug carriers in IS. We also provide a concise summary of the current clinical research status based on exosomes.
Exosomes ; Diagnosis

ObjectiveTo investigate the effect of Danggui Shaoyaosan （DSS） on the morphology and function of mitochondria in rats model of Alzheimer's disease （AD） and its possible mechanism. MethodRats model of AD was established by injection of streptozocin （STZ） into bilateral ventricles of SD rats. The 40 rats were randomly divided into sham group， model group， low， medium and high dosages of Danggui Shaoyaosan （12，24，36 g·kg^-1·d^-1） groups，observed the morphological changes of mitochondria in hippocampus of rats by electron microscopy after 14 days of continuous gavage. In situ end labeling（TUNEL） staining used to detect apoptosis and immunofluorescencereactive used to observe the expression of reactive oxygen species （ROS） and peroxisome proliferators-activated receptor γ coactivator lalpha （PGC-1α），quantitative Real-time polymerase chain reaction（Real-time PCR）detected the mRNA expression of dynamin-related protein 1 （Drp1），mitochondrial fusion protein 2 （MFN2） ，cytochrome C oxidase subunit Ⅳ （COX Ⅳ） and PGC-1α. Western blot detected the protein expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK），phosphorylation（p）-AMPK，recombinant Sirtuin 1 （SIRT1） and PGC-1α. ResultCompared with the sham group，the results of model group showed that the damage of mitochondria in hippocampus was more obvious，accelerated the ROS production and apoptosis rate （P<0.01），decreased the mRNA level of MFN2，COX Ⅳ，PGC-1α，increased the mRNA level of Drp1，and descended the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.05，P<0.01）.Compared with the model group，the medium and high dose of DSS group notably improved the damage of mitochondria，reduced the production of ROS and apoptosis rate （P<0.01），promoted the mRNA expression of MFN2，COX Ⅳ，PGC-1α，inhibited the mRNA expression of Drp1，and up-regulated the protein of p-AMPK/AMPK，SIRT1，PGC-1α （P<0.01）. ResultDSS can significantly ameliorate the mitochondrial homeostasis imbalance in AD rats.

Objective:To analyze the pathogens distribution, drug resistance and risk factors of bacterial infection in patients undergoing liver transplantation for liver failure.Methods:The retrospective case-control study was conducted. The clinical data of 88 patients with liver failure who underwent liver transplantation in The First Affiliated Hospital of Xi′an Jiaotong University from July 2020 to June 2023 were collected. There were 57 males and 31 females, aged (44±9)years. Observation indicators:(1) incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure; (2) drug resistance of bacteria; (3) risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers and percentages. Univariate analysis was conducted using the chi-square test or Fisher exact probability. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Incidence and pathogens distribution of bacterial infection in patients undergoing liver transplantation for liver failure. Of 88 patients, 40 cases had bacterial infection after liver transplantation, with the incidence as 45.45% and occurrence time as postoperative 18(range, 1-57)days. Of the 40 cases with bacterial infection after liver transplantation, 9 cases had single strain infection and 31 cases had mixed bacterial infection. A total of 135 strains of different pathogenic bacteria were isolated from 40 patients, 106 of which were Gram-negative bacteria, 29 were Gram-positive bacteria. Of the Gram-negative bacteria, the top 4 pathogenic bacteria were 37 strains of Acinetobacter baumannii, 35 strains of Klebsiella pneumoniae, 11 strains of Pseudomonas aeruginosa, 9 strains of Stenotrophomonas maltophilia. Of the Gram-positive bacteria, there were 22 strains of Enterococcus faecium, 3 strains of Staphylococcus aureus, 3 strains of Staphylococcus epidermidis, 1 strain of Staphylococcus haemolyticus. Of the 135 strains of pathogenic bacteria, 64 strains were isolated from respiratory tract, 26 strains were from abdomen, 23 strains were from biliary tract, 16 strains were from blood, 6 strains were from other sites. (2) Drug resistance of bacteria. Of the Gram-negative bacteria, Acinetobacter baumannii had a resistance rate of lower than 30.0% to colistin, tigacyclinei, minocycline, a resistance rate of 30.0%-50.0% to amikacin and tobramycin, a resistance rate of over 70.0% to cefotetan, ceftazidime, cefepime, cefoperazone/sulbactam, piperacillin/tazobactam, meropenem, imipenem, ciprofloxacin, cotrimoxazole, levofloxacin. Klebsiella pneumoniae showed a resistance rate of lower than 30.0% to ceftazidime/avibactam, colistin, tigacyclinei and a resistance rate of more than 70.0% to other tested antibiotics. Pseudomonas aeruginosa showed a resistance rate of more than 50.0% to meropenem, imipenem, levofloxacin and a resistance rate of lower than 50.0% to other tested antibiotics. Stenotrophomonas maltophilia showed a resistance rate of lower than 30.0% to cotrimoxazole, levofloxacin, minocycline. Klebsiella oxytoca showed a resistance rate of more than 50.0% to piperacillin/tazobactam, cefoperazone/sulbactam and a resistance rate of lower than 50.0% to other tested antibiotics. The resistance rate of Escherichia coli to amikacin, tobramycin, ceftazidime/avibactam, colistin, and tigecycline was less than 30.0%, and the resistance rate to other tested antibiotics was more than 50.0%. Of the Gram-positive bacteria, Staphylococcus aureus showed a resistance rate of 0 to tigacyclinei, vancomycin, teicoplanin, linezolid, a resistance rate of lower than 50.0% to gentamicin and ciprofloxacin, and a resistance rate of more than 50.0% to erythromycin, penicillin G, ampicillin, tetracycline, levofloxacin. Staphylococcus showed a resistance rate of more than 50.0% to erythromycin, penicillin G, oxacillin, and a resistance rate of 0 to other tested antibiotics. (3) Risk factors of bacterial infection in patients undergoing liver transplantation for liver failure. Results of multivariate analysis showed that preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure ( odds ratio=6.440, 95% confidence interval as 2.155-19.248, P<0.05). Conclusions:The incidence of bacterial infection in patients undergoing liver transplantation for liver failure is high, with the most common sites of respiratory tract and abdomen. The pathogenic bacteria are mainly Gram-negative bacteria, which show an extensive and high drug resistance. Preoperative model for end-stage liver disease score ≥30 was an independent risk factor for bacterial infection in patients undergoing liver transplantation for liver failure.

Objective:To investigate the effect of recombinant lipoproteins of Brucella outer membrane protein 16, 19 (L16 and L19) on the expression of immune regulatory factors in human monocytic leukemia cell line (THP-1 cells). Methods:THP-1 cells activated with phorbol ester (PMA) were used as an in vitro experimental cell model, and a group design was used to co-culture L16, L19 and THP-1 cells (L16 stimulated group, L19 stimulated group), respectively. THP-1 cells activated with PMA were used as the control group. When co-cultured for 4 hours, immunofluorescence staining (IFS) and Western blotting were used to detect whether L16 and L19 entered the cells, respectively; when co-cultured for 12, 24 hours, real-time fluorescent quantitative PCR was used to measure the mRNA expression levels of interferon regulatory factor 1 (IRF-1) and trans activator protein of major histocompatibility complex class Ⅱ (CⅡTA); Western blotting was used to detect the protein expression levels of T cell immunoglobulin mucin-3 (Tim-3) and γ interferon receptor 1 (IFNGR1). Results:When co-cultured for 4 hours, L16 and L19 were observed entering THP-1 cells in the L16 stimulated group and L19 stimulated group, respectively. When co-cultured for 12 hours, the expression level of IRF-1 mRNA in the L16 stimulated group (0.16 ± 0.15) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 24 hours, the expression level of CⅡTA mRNA in the L16 stimulated group (0.17 ± 0.10) was significantly lower than that in the control group (1.00 ± 0.00, P < 0.05). When co-cultured for 12 and 24 hours, there were no statistically significant differences in the expression levels of IRF-1 and CⅡTA mRNA between the L19 stimulated group and the control group ( P > 0.05). Western blotting results showed that there were statistically significant differences in the expression levels of INFGR1 and Tim-3 protein among the control group, L16 stimulated group, and L19 stimulated group after co-cultured for 12 and 24 hours ( F = 50.92, 6.80, 148.73, 156.57, P < 0.05). Among them, when co-cultured for 12 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were significantly lower than that in the control group, and the L19 stimulated group was higher than the L16 stimulated group ( P < 0.05), and the expression level of Tim-3 protein in the L19 stimulation group was higher than that in the control group ( P < 0.05). When co-cultured for 24 hours, the expression level of INFGR1 protein in the L16 and L19 stimulated groups were lower than that in the control group, and the L19 stimulated group was higher than that in the L16 stimulated group ( P < 0.05); and the expression level of Tim-3 protein in the L16 stimulated group was higher than that in the control group and L19 stimulated group ( P < 0.05). Conclusions:Brucella L16 can downregulate the expression levels of IRF-1 and CⅡTA mRNA in THP-1 cells. Both L16 and L19 can downregulate IFNGR1 and upregulate Tim-3 protein expression levels.