Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

ObjectiveTo analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Zhangjiakou City, Hebei Province from 2013 to 2022, so as to provide a basis for HFMD prevention, control, and evaluation of intervention effectiveness. MethodsHFMD data of Zhangjiakou City from 2013 to 2022 were collected. Descriptive statistics and the Joinpoint regression model were used to analyze the trend of the epidemic. ResultsThe incidence of HFMD in Zhangjiakou was predicted to decrease with APC=-14.86% in 2013‒2022. The top five regions with the highest incidence showed varying trends: Qiaodong District (APC=-26.21%), Qiaoxi District (APC=-18.29%), Xuanhua District (APC=-14.28%), Chicheng District (APC=-18.68%), and Zhuolu County (APC=51.43% in 2013‒2016, APC=-14.27% in 2016‒2022), indicating a downward trend. Three age groups showed an upward trend in incidence: the 0-year-old group (APC=-42.82% in 2013‒2016, APC=16.54% in 2016‒2022), the 7-year-old group (AAPC=9.60%), and the 9-year-old group (AAPC=12.76%). HFMD cases occurred throughout the year, peaking from June to August, with July being the most significant month. The male-to-female ratio was1.40∶1, with no statistical difference (χ²=5.932, P>0.05). A high incidence was in children under 5 years old, with those aged 1‒4 years being the main affected group. In terms of occupation, scattered children (6 245 cases, 57.65%) and preschool children (3 653 cases, 33.72%) were the most affected. A total of 504 laboratory-confirmed cases were reported, with a detection rate of 4.65% (504/10 832). The composition of confirmed cases included CoxA 16 (193 cases, 38.29%), EV71 (75 cases, 14.88%), and other enteroviruses (236 cases, 46.83%). ConclusionFrom 2013 to 2022, HFMD in Zhangjiakou City showed a downward trend with clear seasonal, regional, and occupational distributions. It is suggested that epidemic monitoring should be strengthened, etiological detection should be enhanced, and education efforts in key areas should be improved. High-incidence counties should analyze data and conduct risk assessments effectively.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

To investigate the dynamic homing process and characteristics of macrophages in different organs of immune-mediated aplastic anemia (AA) model mice. Macrophages in donor lymph nodes were sorted by magnetic beads and labeled with PKH67. After modeling according to the preparation method of the AA model, peripheral blood rountine analysis, bone marrow biopsy and HE staining results were analyzed to verify the modeling effect. On days 4, 8, and 12 of modeling, the bone marrow, spleen, and lymph node mononuclear cells were collected, and dynamic changes of PKH67-labeled macrophages in donor mice were analyzed by flow cytometry. In this study, dynamic changes in PKH67-labeled macrophages in the pathogenesis of AA model mice were explored. Macrophages in donor mice homed to the lymph nodes, expanding and differentiating in the lymph nodes, and finally transported to the bone marrow and spleen. Through proteomics mass spectrometry analysis, the related immune inflammatory response pathway of macrophages involved in the activation of the AA bone marrow microenvironment was preliminarily revealed, which provides a basis for the pathological macrophages involved in the pathogenesis of AA model mice.

Objective To establish a scoring model for predicting the prognosis and drug sensitivity of colorectal cancer(CRC)based on the expression of disulfidptosis-related genes by bioinformatics analyses combined with the validation with CRC patient-derived organoids(CRC-PDOs).Methods NMF(non-negative Matrix Factorization)algorithm,Cox and LASSO regression analyses were used to identify disulfidptosis-related genes with predictive value for CRC prognosis,and disulfidptosis-related risk scoring formula was constructed.The differential genes and enrichment pathways among different clusters were analyzed by GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes).The sensitivity of the high/low-risk clusters of CRC patients to chemotherapy drugs was predicted using the GDSC database and validated using CRC-PDOs.Results The results of NMF algorithm showed that CRC patients could be grouped into two clusters based on the disulfidptosis-related genes.COX regression analysis demonstrated that LRPPRC and SLC7A11 were the only two genes with significance to predict the prognosis of CRC patients(P=0.047,0.033).Low expression of SLC7A11 or high expression of LRPPRC in tumors of CRC patients was significantly correlated with overall survival(OS)(P=0.004,0.003).Based on LASSO regression analysis,the mortality risk scoring formula for disulfidptosis was as follows:Risk score=LRPPRC×(-0.670 5)+SLC7A11×0.311 2,and the GSE161158 dataset could be re-grouped into high-risk and low-risk clusters accordingly.There were 125 differentially expressed genes(DEGs)between the two clusters.According to the GO and KEGG results,the up-regulated genes in high-risk cluster were mainly enriched in immune regulation,such as leukocyte chemotaxis,granulocyte migration and toll-like receptor binding.Low-risk cluster was characterized by pathways associated with sulfide metabolism,such as sulfur compound transmembrane transporter activity.Based on the GDSC database,the expression level of SLC7A11 and LRPPRC could predict chemotherapy drug sensitivity.As a representative,the efficacy of chemotherapy drug(irinotecan)on inhibiting the growth of CRC-PDOs was shown to be linearly correlated with the relative gene expression levels of SLC7A11 and LRPPRC in CRC tissues of patients(P=0.007,0.040).Conclusion According to the results based on the bioinformatics analyses and drug sensitivity testing on CRC-PDOs,disulfidptosis risk score could predict the prognosis and drug sensitivity of CRC patients,with potential clinical application prospect.

Objective To study the effects and mechanisms of tetramethylpyrazine(TMP)on tumor necrosis factor-α(TNF-α)-induced inflammatory injury in human coronary artery endothelial cells(HCAEC).Methods HCAEC were randomly divided into four groups:the control group(no treatment),the model group(treated with TNF-α,50 ng/mL for 24 hours),the TMP group(pre-treated with TMP,80 μg/mL for 12 hours followed by TNF-α treatment for 24 hours),and the SIRT1 inhibitor group(pre-treated with TMP and the specific SIRT1 inhibitor EX527 for 12 hours followed by TNF-α treatment for 24 hours).Cell viability was assessed using the CCK-8 method,lactate dehydrogenase(LDH)activity was measured using an LDH assay kit,reactive oxygen species(ROS)levels were observed using DCFH-DA staining,expression of pyroptosis-related proteins was detected by Western blot,and SIRT1 expression was analyzed using immunofluorescence staining.Results Compared to the control group,the model group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Compared to the model group,the TMP group exhibited increased cell viability,decreased LDH activity,ROS level and expression of pyroptosis-related proteins,and increased SIRT1 expression(P<0.05).In comparison to the TMP group,the SIRT1 inhibitor group showed decreased cell viability,increased LDH activity,ROS level and expression of pyroptosis-related proteins,and decreased SIRT1 expression(P<0.05).Conclusions TMP may attenuate TNF-α-induced inflammatory injury in HCAEC,which is associated with the inhibition of pyroptosis and activation of the SIRT1 signaling pathway.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G⁺) or Gram-negative bacteria (G^-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G⁺ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G⁺ bacteria. Additionally, depletion of SCFAs-producing G⁺ bacteria rather than G^- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G⁺ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G⁺ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

[Abstract] Objective To elucidate the important role of Nogo-A in climacteric neurodegeneration such as memory impairment by observing memory function and the expression of Nogo-A in hippocampus and striatum of rats under low estrogen condition. Methods Fouthy-five female SD rats were divided into sham operation group, ovariectomized group and ovariectomized estrogen treatment group with 15 rats in each group. Medication was given 2 weeks after ovariectomized. Estrogen treatment group was subcutaneously injected in groin with estrogen [25 μg/ (kg.d)] dissolved in sterile sesame oil. The sham operation group and the ovariectomized group were given the same amount of aseptic sesame oil. Samples were collected after 6 weeks of drug treatment. The difference of memory function of rats in three groups was observed by conditioned fear training experiment, and the expression of Nogo-A in hippocampus and striatum was observed by immunohistochemistry and Western blotting. Results Compared with the sham and estrogen treatment group, memory function in ovariectomized group decreased significantly and the number of Nogo-A positive neurons in hippocampus and striatum of ovariectomized rats was significantly higher than that of sham operation group (P < 0. 05). There was no difference between the estrogen treatment group and the sham operation group with the memory function and the Nogo-A expression (P > 0. 05). The result of immunoblotting was consistent with the above-mentioned immunohistochemical result. Conclusion The increased expression of Nogo-A in hippocampus and striatum under low estrogen condition may be one of the key reasons for memory impairment in climacteric women.