Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Hemagglutinin and neuraminidase, two important glycoproteins on the surface of influenza virus, play a considerable role in the entry and release stage of the viral life cycle, respectively. With in-depth investigation of influenza virus glycoproteins and the continuous innovation of drug discovery strategies, a new generation of glycoproteins inhibitors have been continuously discovered. From the point of view of medicinal chemistry, this review summarizes the current advances in seeking small-molecule inhibitors targeting influenza virus glycoproteins, hoping to provide valuable guidance for future development of novel antiviral drugs.

Objective:To investigate the characteristics of allergen component in dust mite（DM） -induced allergic rhinitis（AR） patients, and provide reference for the diagnosis and treatment of AR. Methods:DM-induced AR patients with or without allergic asthma（AA） who visited the Allergy Department of Tongji Hospital, Huazhong University of Science and Technology between 2021 and 2022 were enrolled. Patients'age, gender, and visual analog scale（VAS） for symptoms were recorded. sIgE and sIgG4 levels of allergen components such as Der f1, Der f2, Der p1, Der p2, Der p7, Der p10, Der p21, and Der p23 were detected using a protein chip method. The sensitization characteristics of the allergen components in the patients were observed, and the correlation between sIgE, sIgG of each component and VAS as well as the component differences between AR and AR with AA（AR&AA） were evaluated. Results:A total of 87 DM-induced AR patients were enrolled, with 42.5% of them were AR&AA, their VAS scores were significantly higher than those of AR patients（6.38±1.95 vs 5.25±1.85, P=0.009 8）. The order of sensitization rates for DM components was as follows: Der p2（82.8%）, Der f2（81.6%）, Der p1（74.7%）, Der f1（70.1%）, and Der p23（35.6%）. The order of positive rates for sIgG4 was: Der p2（21.8%）, Der f2（13.8%）, Der p21（8.0%）, and Der p7（6.9%）. There were no correlation between the sIgE, sIgG4 levels or positive numbers of components and VAS scores, but there were positive correlations between sIgE, sIgG4 concentrations of components. Compared with AR patients, AR&AA patients had higher levels of sIgE for Der p（60.5[7.2-91.1]vs 14.0[4.8-45.1], P=0.02）, Der f（49.8[15.7-81.6]vs 21.3[7.0-50.2], P=0.04）, Der p1（27.2[0.7-51.5]vs 2.6[0.2-24.9], P=0.02）, Der p2（20.0[1.4-60.6]vs 5.5[0.6-19.1], P=0.004）, and Der f2（58.9[16.0-89.2]vs 23.4[0.9-56.8], P=0.009）, and a higher proportion of AR with AA patients had sIgE levels of Der p1（70.3% vs 48.0%, P=0.038） and Der p23（27.0% vs 14.0%, P=0.039） that were ≥3 grades. Conclusion:Der p1/f1, Der p2/f3, and Der p23 are the major components of DM sensitized AR patients. Multiple component sensitization and sIgE, sIgG4 levels of each component are not correlated with the severity of AR. The sIgE levels of the Der p1/f1, Der p2/f3, and Der p23 components in AR&AA patients are higher than AR.
Animals ; Humans ; Allergens ; Pyridinolcarbamate ; Rhinitis, Allergic/therapy* ; Pyroglyphidae ; Asthma ; Antigens, Dermatophagoides

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.
Autoimmune Diseases ; Child ; Humans ; Hypersensitivity/therapy* ; Immunologic Deficiency Syndromes/therapy* ; Primary Immunodeficiency Diseases/therapy*

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Objective:To study the clinical features of intrahepatic biliary cystadenoma (BCA), with the aim to improve its treatment results.Methods:The clinical data and follow-up results of 86 patients with BCA treated at our department from March 2010 to January 2021 were retrospectively analyzed. Of 86 patients, there were 15 males and 71 females, with age of (48.4±13.1) years old. According to the surgical procedures carried out, 44 patients were divided into the minimally invasive group and 42 into the open group. Clinical data including imaging data, blood biochemistry, and tumor markers were collected. The follow-up data of these patients was collected in outpatient clinics or by telephone review.Results:Of 86 patients, 19(22.1%) patients had a monocystic lesion while 67(77.9%) patients had a multicystic lesion, 64 patients (74.4%) had intracapsular segregation, and 12(14.0%) patients had solid structures. Eighty-six patients with BCA were misdiagnosed as hepatic cysts in 9 patients (10.4%), hepatic echinococcosis in 2 patients (2.3%), biliary hamartoma in 1 patient (1.2%), and hepatic hemangioma in 1 patient (1.2%) before surgery. The tumor size [(6.5±3.2) vs. (9.0±4.0) cm], operative time [115(88, 185) vs. 195(160, 254) min], intraoperative blood loss [50(20, 162) vs. 300(200, 600) ml], and postoperative hospital stay [4(3, 6) vs. 8(7, 10) d] were significantly lower in the minimally invasive group than the open group. The differences were statistically significant ( P<0.05). In the 73 patients with complete follow-up, (median follow-up 63.5 months), 4 patients had developed tumor recurrence. Conclusion:Intrahepatic bile duct cystadenoma lacks specific clinical manifestations, and has a high rate of misdiagnosis and mistreatment. Early radical hepatectomy improved clinical outcomes.

Aim To investigate the effects of Angelica dahurica extract and imperatorin on gouty arthritis induced by monosodium urate(MSU)crystal.Methods The model of gouty arthritis was established by injecting MSU crystals into the left ankle of rats.The degree of ankle swelling was measured at 0-24 h in rats.The histopathological changes of synovial tissues were observed.Meanwhile the mRNA and protein expression levels of Nod-like receptor protein 3(NLRP3), interleukin-1β(IL-1β), cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1 receptor type 1(IL-1R1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)were detected by Western blot and RT-PCR in synovial tissues.Results Angelica dahurica extract and imperatorin significantly reduced MSU induced left ankle swelling in rats, and improved inflammatory infiltration in synovial tissues.The expression of NLRP3, IL-1β, caspase-1, IL-1R1, IL-6, TNF-α protein or mRNA in synovial tissues decreased significantly.Conclusion Angelica dahurica extract and its active component imperatorin could ameliorate gouty arthritis, which supplys basic data support for its clinical application.

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

OBJECTIVES: To identify the differentially expressed genes (DEGs) during the pathogenesis of periodontitis by bioinformatics analysis. METHODS: GEO2R was used to screen DEGs in GSE10334 and GSE16134. Then, the overlapped DEGs were used for further analysis. g:Profiler was used to perform Gene Ontology analysis and pathway analysis for upregulated and downregulated DEGs. The STRING database was used to construct the protein-protein interaction (PPI) network, which was further visua-lized and analyzed by Cytoscape software. Hub genes and key modules were identified by cytoHubba and MCODE plug-ins, respectively. Finally, transcription factors were predicted via iRegulon plug-in. RESULTS: A total of 196 DEGs were identified, including 139 upregulated and 57 downregulated DEGs. Functional enrichment analysis showed that the upregulated DEGs were mainly enriched in immune-related pathways including immune system, viral protein interaction with cytokine and cytokine receptor, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, and chemokine receptors bind chemokines. On the contrary, the downregulated DEGs were mainly related to the formation of the cornified envelope and keratinization. The identified hub genes in the PPI network were CXCL8, CXCL1, CXCR4, SEL, CD19, and IKZF1. The top three modules were involved in chemokine response, B cell receptor signaling pathway, and interleukin response, respectively. iRegulon analysis revealed that IRF4 scored the highest. CONCLUSIONS The pathogenesis of periodontitis was closely associated with the expression levels of the identified hub genes including CXCL8, CXCL1, CXCR4, SELL, CD19, and IKZF1. IRF4, the predicted transcription factor, might serve as a dominant upstream regulator.
Computational Biology ; Gene Expression Profiling ; Humans ; Microarray Analysis ; Periodontitis ; Protein Interaction Maps