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.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like blaTEM, blaSHV, and blaCTX-M. The isolates were highly pathogenic to mice, as evidenced by the diseased organs of the deceased mice observed on autopsy. [Conclusion] The three strains of hvKp isolated in this study carried multiple drug-resistant genes and were highly pathogenic, which suggests that in laboratories and clinical practices it is imperative to promptly identify and adopt necessary disposal strategies to prevent further spread of hvKp.

Computed tomography (CT) examination is the major measure for detecting and diagnosis of foreign bodies in human body. Although CT has high sensitivity in diagnosis of foreign body, some interference factors may still lead to missed diagnosis or misdiagnosis. Here we report a rare case that a bamboo stick accidentally pierced into the left chest of a young man who was drunk and unware of this hurt. The patient experienced cough, chest pain, fever, hemoptysis, and was misdiagnosed as primary and secondary tuberculosis based on chest CT examinations at a local hospital, although no tubercular bacillus detected by sputum smear. He subsequently received anti-tuberculous treatments in the following three years, but no improvement of his symptoms was observed. Until one month before his death, the bamboo stick was detected by spiral CT examination as well as three-dimensional image reconstruction at another hospital. Postmortem examination revealed pneumonia, pulmonary infarction, and abscess as the causes of his death. We analyze the potential reasons of misdiagnosis in this case, aiming to provide reference for the diagnosis and treatment of pulmonary inflammation associated with foreign body in the future.
Abscess ; Diagnostic Errors ; Humans ; Male ; Pneumonia ; Pulmonary Infarction ; Tuberculosis, Pulmonary

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective The paper aimed to discuss the influence of case teaching of forensic pathology based on network platform on the critical thinking ability of forensic students.Methods Students majoring in forensic were randomly divided into the experimental group and the control group with 20 students per group. According to heterogeneity classification, the experimental group was divided into 4 subgroups. The subgroups participated in network cases learning whereas the control group received traditional case teaching. Participants were required to fill in California Critical Thinking Disposition Inventory-Chinese Version (CCTDI-CV) before and after learning. CCTDI-CV scores, the scores of final exam and the number of students who had improved in CCTDI-CV scores were compared between the two groups. Results For the experimental group, the total score of CCTDI-CVand the scores of items including looking for the truth, systematized ability, self-confidence, thirst for knowledge were significantly improved after learning. The performance of the experimental group was better than that of the control group at the end of teaching (P＜0.05) . The scores of final exam were higher in the experimental group compared to the control group (P＜0.05) .Conclusion Forensic pathology cases teaching based on network platform is an effective way to stimulate students'critical thinking ability and to improve the study ability.

OBJECTIVES: To study the epidemiological and pathological features of sudden death （SD） in Yunnan Province and to provide scientific evidence for prevention and forensic identification of sudden death. METHODS: Totally 363 SD cases were collected from the autopsies between 2009 and 2017 in the Forensic Centre of Kunming Medical University. The related factors such as etiology, age, inducing factor, time interval between the onset of disease and death, morbidity season and pathological change were retrospectively analysed. RESULTS: The incidence of SD in males was significantly higher than that of females. The peak age was ≥35-55 years. The mortality rate was relatively high within 6 h after the onset of disease. The season order with descending number of deaths was spring, summer, winter and autumn. The top ten causes of SD were coronary heart disease, sudden unexplained death （SUD）, cerebral hemorrhage, acute hemorrhagic necrotic pancreatitis, aortic dissection rupture, cardiomyopathy, pneumonia, pulmonary thromboembolism, amniotic fluid embolism and allergy. Exercise, infusion, surgery, medication and minor injury were the most common predisposing factors of sudden coronary death. Consciousness disorder or coma, chest pain or chest tightness, and abdominal pain were the most common premortem symptoms of sudden coronary death. CONCLUSIONS The SD is more common in middle-aged males, which is the key population for the prevention of SD. For the forensic identification and prevention of SD, the attention on SUD should be paid.
Adult ; Aortic Rupture ; Autopsy ; Cause of Death ; China/epidemiology* ; Death, Sudden/pathology* ; Death, Sudden, Cardiac/pathology* ; Female ; Forensic Pathology ; Humans ; Incidence ; Male ; Middle Aged ; Pulmonary Embolism ; Retrospective Studies ; Seasons

Objective To evaluate the pharmacokinetics and safety of single micro dose in travenous temozolomidein Chinese health male volunteers or standard treatment in glioma patients.Methods 14 healthy subjects of phase 0 research were assigned to take a single microdose of 2 mg · m-2 intravenous temozolomide.24 glioma patients of phase Ⅰ research were assigned to take 150 mg · m-2 intravenous temozolomide.These rumconcentrations of temozolomide were assayed with LC-MS/MS.Results Fourteen healthy subjects pharmacokinetic parameters wereCmax (0.14 ± 0.03) μg · mL-1,tmax (80.40 ± 12.60) min,t1/2 (114.00±6.00) min,AUC0-24h (25.80 ±4.72) μg · mL-1 · min,AUC0-x (26.20 ±4.79) μg · mL-1 · min.Twenty-one glioma patients were included in the pharmacokinetic analysis,pharmacokinetic parameters were Cmax (7.92 ± 1.50) μg · mL-1,tmax (87.90 ± 5.38) min,t1/2 (108.00 ± 5.25) min,AUC0-24h (1530.00 ±270.00) μg · mL-1 · min,AUC0-∞ (1550.00 ±273.00) μg · mL-1 · min.All the 14 healthy volunteers and 24 glioma patients were included in the safety analysis.No adverse events were detected in health volunteers.6 gliomapatients experienced 7 adverse events related to temozolomide.There were no serious adverse events in two early clinical reseach.Conclusion Pharmacokinetic parameters of phase 0 research of intravenous temozolomide reflected the characteristics of the drug distribution and elimination in some extent.It is significative to follow-up clinical trials.

Objective To evaluated the pharmacokinetics and safety of single microdose imatinib mesylate in Chinese health volunteers.Methods Eight subjects were randomly assigned to take orally a single microdose of 4 mg imatinib mesylate.The serum concentrations of ima-tinib were assayed with LC-MS/MS.Results The following pharmaco-kinetic parameters were calculated by WinNolin 6.3 software.Cmax (12.70 ±6.61 ) ng · mL-1, tmax ( 1.94 ±0.94 ) h, AUC0-24 h (90.10 ±37.70)ng· mL-1· h, t1/2 ( 10.40 ± 5.01 ) h, CL/F (47.20 ±33.40)L· h-1, V/F ( 541.00 ± 128.00 ) L, MRT (7.21 ±1.30)h.No adverse events and serious adverse events were detected.Conclusion Pharm-acokinetic parameters of phase 0 research of imatinib mesylate reflected the characteristics of the drug distribution and elimination in some extent.It was significant to protect subjects in phase 0 research by taking microdose imatinib mesylate.

Humans ; Nasal Cavity ; pathology ; Nasal Obstruction ; diagnosis ; Nasal Polyps ; diagnosis ; Turbinates