Allergen immunotherapy（AIT）can alter the natural course of allergic diseases through immunomodulatory mechanisms and maintain the efficacy after completion. The induction of immune tolerance by AIT is considered to be effective treatment and the mechanism involves the participation of a variety of immune cells，including effector T cells，B cells，dendritic cells，innate lymphoid cells，mast cells and basophils. Studies have found that a variety of immune cells in peripheral blood changed during AIT treatment and the changes of some immune cells were related to the efficacy of AIT，which may provide some theoretical reference for practical clinical activities and may become potential biomarkers for predicting and evaluating the efficacy of AIT. This article reviews the changes of peripheral blood immune cells in the treatment of AIT.

Helicobacter pylori(Hp)is a common Gram-negative bacillus causing gastrointestinal infec-tions.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bacteri-cidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other disea-ses by Hp.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective To identify potential biomarkers associated with LN,with the goal of improving early diagnosis,disease monitoring,and the development of more precise treatment strategies.Methods Gene expression data were downloaded from the Gene Expression Omnibus(GEO)database for datasets GSE22221,GSE112943,GSE99967,and GSE32591.Intersecting genes were obtained through the application of weighted gene co-expression network analysis(WGCNA)and linear models for microarray data(LIMMA).Subsequently,biological function and pathway analyses were conducted on these intersecting genes using Gene Ontology(GO)and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Next,protein-protein interaction(PPI)network analysis was performed,and hub genes highly associated with LN were identified using the CytoHubba algorithm,support vector machine(SVM),and random forest(RF)methods.Receiver operating characteristic(ROC)analysis was performed,and three potential biomarkers were validated using the GSE72798 dataset.Results The green-yellow module(P=7.4e-40)and the cyan module(P=1.5e-14)were identified through WGCNA analysis.A total of 193 differentially expressed genes were identified using LIMMA,with 113 intersecting genes related to LN being identified.GO and KEGG analyses indicated that these genes were mainly enriched in viral or bacterial defense,type I interferon signaling pathway,neutrophil-mediated immunity,and Toll-like receptor signaling.MX1,IFI44,and STAT1 were identified as hub genes using CytoHubba,SVM,and RF methods,with AUC values of 0.874,0.879,and 0.833,respectively.Validation using the GSE72798 dataset demonstrated that the expression of MX1,IFI44,and STAT1 was significantly higher in LN patients compared to healthy individuals(P＜0.001 for all).Conclusion MX1,IFI44,and STAT1 play crucial roles in the pathogenesis of LN and may serve as important biomarkers and potential therapeutic targets for LN.

As the utilization of computed tomography in lung cancer screening becomes more prevalent in the post-pandemic era, the incidence of multiple primary lung cancer (MPLC) has surged in various countries and regions. Despite the continued application of advanced histologic and sequencing technologies in this research field, the differentiation between MPLC and intrapulmonary metastasis (IM) remains challenging. In recent years, the specific mechanisms of genetic and environmental factors in MPLC have gradually come to light. Lobectomy still predominates in the treatment of MPLC, but the observation that tumor-specific sublobar resection has not detrimentally impacted survival appears to be a viable option. With the evolution of paradigms, the amalgamated treatment, primarily surgical, is an emerging trend. Among these, stereotactic ablative radiotherapy (SABR) and lung ablation techniques have emerged as efficacious treatments for early unresectable tumors and control of residual lesions. Furthermore, targeted therapies for driver-positive mutations and immunotherapy have demonstrated promising outcomes in the postoperative adjuvant phase. In this manuscript, we intend to provide an overview of the management of MPLC based on the latest discoveries.
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Humans ; Lung Neoplasms/therapy* ; Early Detection of Cancer ; Lung/surgery* ; Treatment Outcome ; Radiosurgery/methods* ; Neoplasms, Multiple Primary/pathology*

Flagella are the main motility structure of Clostridioides difficile that affects the adhesion, colonization, and virulence of C. difficile in the human gastrointestinal tract. The FliL protein is a single transmembrane protein bound to the flagellar matrix. This study aimed to investigate the effect of the FliL encoding gene flagellar basal body-associated FliL family protein (fliL) on the phenotype of C. difficile. The fliL gene deletion mutant (ΔfliL) and its corresponding complementary strains (: : fliL) were constructed using allele-coupled exchange (ACE) and the standard molecular clone method. The differences in physiological properties such as growth profile, antibiotic sensitivity, pH resistance, motility, and spore production ability between the mutant and wild-type strains (CD630) were investigated. The ΔfliL mutant and the : : fliL complementary strain were successfully constructed. After comparing the phenotypes of strains CD630, ΔfliL, and : : fliL, the results showed that the growth rate and maximum biomass of ΔfliL mutant decreased than that of CD630. The ΔfliL mutant showed increased sensitivity to amoxicillin, ampicillin, and norfloxacin. Its sensitivity to kanamycin and tetracycline antibiotics decreased, and the antibiotic sensitivity partially returned to the level of CD630 strain in the : : fliL strain. Moreover, the motility was significantly reduced in the ΔfliL mutant. Interestingly, the motility of the : : fliL strain significantly increased even when compared to that of the CD630 strain. Furthermore, the pH tolerance of the ΔfliL mutant significantly increased or decreased at pH 5 or 9, respectively. Finally, the sporulation ability of ΔfliL mutant reduced considerably compared to the CD630 strain and recovered in the : : fliL strain. We conclude that the deletion of the fliL gene significantly reduced the swimming motility of C. difficile, suggesting that the fliL gene is essential for the motility of C. difficile. The fliL gene deletion significantly reduced spore production, cell growth rate, tolerance to different antibiotics, acidity, and alkalinity environments of C. difficile. These physiological characteristics are closely related to the survival advantage in the host intestine, which is correlated with its pathogenicity. Thus, we suggested that the function of the fliL gene is closely related to its motility, colonization, environmental tolerance, and spore production ability, which consequently affects the pathogenicity of C. difficile.
Humans ; Clostridioides/metabolism* ; Clostridioides difficile/metabolism* ; Bacterial Proteins/metabolism* ; Virulence ; Anti-Bacterial Agents/metabolism*

Objective:To investigate the clinical significance of graft-versus host disease (GVHD)accompanied with new T-cell receptor (TCR) genes clonal rearrangement after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The clinical data of 2 patients admitted to People's Hospital of Henan University from December 2018 to March 2020 who developed GVHD after allo-HSCT accompanied with TCR genes clonal rearrangement were retrospectively analyzed, and the related literatures were reviewed.Results:Patient 1 was diagnosed with peripheral T-cell lymphoma non-specific type (PTCL-NOS), and then developed severe acute GVHD (aGVHD) after identical sibling allo-HSCT, and gradually developed liver chronic GVHD (cGVHD), skin cGVHD and new TCR genes clonal rearrangement. Patient 2 was diagnosed with acute myeloid leukemia (AML)-M 4, and severe aGVHD, hepatic cGVHD, and clonal rearrangement of TCR genes were gradually detected after identical sibling allo-HSCT. Conclusions:The TCR genes clonal rearrangement after allo-HSCT is not necessarily suggestive of tumors, and it may be related to lymphocyte development disorder caused by GVHD, so the comprehensive judgement should be carefully made.

Objective To overview the methodological quality,report quality and evidence quality of the Meta-Analyses/Systematic Reviews(MAs/SRs)of acupuncture for post-stroke cognitive impairment(PSCI).Methods A search was conducted for MAs/SRs on PSCI using English or Chinese from inception to 20 February 2022 published in four Chinese databases:CNKI,Wanfang,VIP,CBM;and three English databases:PubMed,Embase and Cochrane Library.The MAs/SRs were evaluated for methodological quality using AMSTAR 2 and for reporting quality using PRISMA,and the quality of evidence was assessed using the GRADE system.Results A total of 18 MAs/SRs were included in this study,of which 89%showed the effectiveness and safety of acupuncture for PSCI.According to AMSTAR 2,1 study was of low methodological quality and 17 studies were of critically low quality;according to PRISMA,1 study was of high quality,16 studies were of moderate quality and 1 study was of poor quality;GRADE showed that of the 71 outcomes included,however,there was no evidence of high quality outcomes,with 10 of moderate quality,17 of low quality,and 44 of very low quality.Conclusion Acupuncture may be effective and safe in the treatment of PSCI,but in current acupuncture for PSCI is generally of low quality and should be interpreted with caution.