Objective: To analyze the process of handling a pulmonary tuberculosis(TB) outbreak among senior high school students in a boarding school in Chongqing, as well as to investigate the underlying causes of the outbreak, so as to provide evidence to inform TB prevention and control strategies in school settings. Methods: From November 2023 to April 2024, an epidemiological investigation was conducted into the TB outbreak in a grade 12 class from a boarding high school. Suspected cases were screened using symptom screening, tuberculin skin test (TST), and chest X-ray examinations. Confirmed cases underwent individual epidemiological interviews and sputum culture; Cultured positive mycobacterial strains were subjected to whole genome sequencing after identification as Mycobacterium tuberculosis. Results: A total of 10 active pulmonary TB cases were identified, all from the same class, yielding a student attack rate of 16.67%. Three isolates were culture positive, as well as all strains were of L2 type，and the WGS analysis of the strains suggested a common transmission chain. Excluding the index case, four additional cases were detected through symptom driven health care visits. Notably, 70% of patients presented with "chest tightness and chest pain" symptoms, and 50% had "cough" symptoms,but none were detected during morning health checks or tracking of absences due to illness. A total of 326 contacts were identified and underwent three rounds of screening and one follow up examination. In the initial screening, 35 close contacts from the same class showed strong TST positivity, corresponding to a strong positivity rate of 55.56%, significantly higher than the 20.76% observed among casual contacts ( χ 2=29.80, P <0.01). Among the 35 strongly TST positivvity close contacts and five individuals with moderate TST positivity whose induration had increased by ≥10 mm over two years, none received timely preventive treatment initially; five of them were subsequently diagnosed with active TB within three months. Following this, 25 individuals initiated preventive therapy, resulting in a preventive treatment initiation rate of 62.50%. Among TST negative classmates who converted to strong positivity on repeat TST testing at three months, 75.00% started preventive treatment, but only 22.22% completed the full course. Conclusion Inadequate implementation of morning health checks and cause tracking for absenteeism due to illness, poorly standardized screening procedures, and delayed preventive treatment may have been key factors contributing to the spread of the outbreak.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

The brain-gut interaction theory is a multidimensional integrative concept based on the brain-gut axis， involving neural， endocrine， and immune regulatory networks as well as the gut microbiota. Zang-fu organs （脏腑） theory in traditional Chinese medicine （TCM） shows a high degree of consistency with the brain-gut interaction theory， and the core functions such as the spleen and stomach governing the ascending of the clear and descending of the turbid， the liver governing the free flow of qi， and the heart governing mental and emotional activities are closely associated with the multi-level regulatory mechanisms of the brain-gut axis. TCM therapy can modulate brain-gut interactions through multiple pathways in the treatment of spleen and stomach diseases， including the regulation of gastrointestinal hormone secretion， neurotransmitter levels， the hypothalamic-pituitary-adrenal （HPA） axis， immune homeostasis and inflammatory responses， as well as the gut microecology. However， current basic research on the brain-gut interaction theory in TCM for spleen and stomach diseases still faces several challenges， such as difficulties in integrating TCM spleen-stomach theory with modern pathophysiology， lack of innovation in research concepts， and limitations in research methodologies. It is therefore proposed that multidisciplinary collaboration， multi-omics technologies， and targeted research approaches should be adopted to provide more comprehensive methods for basic research on TCM spleen and stomach diseases， thereby promoting the in-depth development of brain-gut interaction theory.

19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

Objective To explore the syndrome characteristics of Henoch-Schonlein purpura nephritis in Shaanxi area;To provide reference for TCM clinical syndrome differentiation and treatment.Methods Clinical data on patients diagnosed with Henoch-Schonlein purpura nephritis who received outpatient or inpatient treatment at five hospitals in Shanxi area including Hospital of Shaanxi University of Chinese Medicine and Yulin Traditional Chinese Medicine Hospital etc from August 2020 to August 2022 were under retrospective collection.TCM syndrome distribution law in patients with Henoch-Schonlein purpura nephritis in Shaanxi area was concluded through frequency statistics,clustering analysis,principal component analysis,and complex network analysis.Results Totally 143 patients were included,involving 64 symptoms.3 groups of syndromes were obtained after clustering analysis,and principal component analysis was performed for each group of syndromes.Using complex network analysis and combining the results of clustering analysis and principal component analysis,classification groups for each group of main symptoms and comorbidities were formed,and their main syndrome classification was determined:qi-yin deficiency syndrome,accounting for 47.55％;spleen deficiency and dampness,accounting for 34.97％;wind-heat attacking the exterior,accounting for 17.48％.Conclusion The syndromes of Henoch-Schonlein purpura nephritis in Shaanxi area are mainly divided into three types:qi-yin deficiency,spleen deficiency and dampness and wind-heat attacking the exterior.Among them,qi-yin deficiency is the most common.

Objective:To examine the roles played by peer attachment and cognitive fusion in the association between negative life events and depression,as well as the differences in these relationships of variables among pri-mary and secondary school students.Methods:A total of 2 767 students(1 950 elementary school students and 817 middle school students)were selected.The Adolescent Life Events Scale,the Experiences in Close Relationships-Relationship Structures Questionnaire,the Cognitive Fusion Questionnaire,and the Patient Health Questionnaire were used to measure negative life events,peer attachment,cognitive fusion,and depression,respectively.Results:Negative life events,peer attachment,cognitive fusion and depression were positively correlated with each other(r=0.36-0.75,Ps＜0.001);the mediation effects of peer attachment and cognitive fusion and their chain mediation effects were 0.04,0.30,and 0.04,respectively,accounting for 6.7％,50％,and 6.7％of the total effect.There were significant differences in the chain mediation model between primary and secondary school students(△x2=47.12,△df=6,P＜0.001),and significant gender differences in the chain mediation effect among primary school students(△x2=43.72,△df=6,P＜0.001).Conclusion:Negative life events influence depression in primary and secondary school students both directly and indirectly through peer attachment and cognitive fusion.Negative life e-vents have greater impact on primary school students'(particularly girls)peer attachment.Peer attachment has grea-ter impact on secondary school students' cognitive fusion.Cognitive fusion has greater impact on primary school students' depression.Peer attachment has greater impact on primary school boys' depression.

Purpose To analyse the expression of aldo-keto reductase AKR1C3 in the tumour tissues of oral squa-mous carcinoma(OSCC)and the correlation of clinical prognosis of patients.Methods Immunohistochemical(IHC)staining was performed to analyze the expression characteristics of AKR1C3 in 86 cases of OSCC tumor tissues and paired paratumor normal tissue.The correlation between AKR1C3 expression and clinical prognosis was evaluated.Ka-plan-Meier survival analysis was conducted to assess the survival outcomes of OSCC patients.Univariate and multivari-ate Cox regression analyses were employed to identify prognostic factors.The findings were further validated by compar-ison with the Cancer Genome Atlas(TCGA)database.Results The expression of AKR1C3 was significantly higher in OSCC tumor tissues than in paratumor normal tissue,with higher expression observed at the invasive front relative to the tumor centers.Immunohistochemical analysis revealed high expression in both tumor cells and tumor-associated fibro-blasts,while no expression was detected in tumor-infiltrating immunocytes.The x2 test was used to compare the rela-tionship between different expression levels of AKR1C3 and clinicopathological features in OSCC,the results showed that high expression of AKR1C3 was strongly associated with higher tumour stage(P=0.001),lymph node metastasis(P=0.023),differentiation(P=0.018),worst pattern of invasion(P=0.024)and depth of invasion(P=0.012).Kaplan-Meier survival curve analysis showed high expression of AKR1C3 was associated with overall survival(P=0.004),disease-free survival(P=0.019),and metastasis-free survival(P=0.05)in OSCC patients.Cox re-gression model was performed for prognostic analysis.Univariate analysis showed that high expression of AKR1C3 in tumour cells was a high-risk factor for patients' tumour stage(P＜0.001),lymph node metastasis(P＜0.001),dif-ferentiation(P＜0.001),worst pattern of invasion(P＜0.001),depth of invasion(P＜0.001).Multivariate analy-sis further showed that high expression of AKR1C3 in tumour cells was an independent prognostic factor in OSCC pa-tients(P=0.025).Conclusion The AKR1C3 expression is closely related to the prognosis of OSCC patients,and patients with high AKR1C3 expression have a poor prognosis,suggesting that AKR1C3 plays an important role in the occurrence and development of OSCC.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective To investigate the clinical value of endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy.Methods The clinical data of 6 patients with esophageal stricture lesions with EUS-FNA that cannot be clearly diagnosed by endoscopic general biopsy from January 2021 to Jun 2023 were retrospectively analyzed,and the accuracy of EUS-FNA was analyzed for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy,while the results of surgery pathology or final follow-up results was taken as the diagnostic criteria.Results All the patients underwent EUS-FNA.The puncture clearly diagnosed 5 cases of malignancy and 1 case of chronic inflammation.Among them,5 patients underwent surgical operations,and the postoperative pathological findings were consistent with the puncture pathology.One patient was followed up for a long time and had repeated gastroscopy.There was no evidence of malignant tumor in the clinical manifestations and routine gastroscopic findings,so it was still considered to be an inflammatory change,which was consistent with the puncture pathological result.All patients had no complications,including abdominal pain,bleeding,perforation,and infection.Conclusion EUS-FNA is an effective and safe method for esophageal stricture lesions that cannot be diagnosed by endoscopic general biopsy and has high clinical application value.