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.

Neoantigen pulsed dendritic cell vaccine(Neo-DCVac)is a new type of tumor immunotherapy.Neoantigen is strong immunologic and tumor-specific mutated peptides expressed in a tumor.Neo-DCVac is a therapeutic modality based on the uptake and processing of neoantigens by dendritic cells and their delivery and activation of T cells to trigger the body's immune response for anti-tumor effects.The development of individualized Neo-DCVac based on high-throughput sequencing is expected to be a new direction for precision immunotherapy of tumors.In this review,we discuss construction of individualized Neo-DCVac,clinical application of combination therapy in solid tumors,suitable population for vaccination and the current limitations of Neo-DCVac,aiming to provide a theoretical reference for research on tumor immunotherapy.

ObjectiveTo simulate the microstructure and mechanical properties of tendon tissue and promote its regeneration and repair, electrospinning technology was used to prepare L-polylactic acid (PLLA) fiber membranes loaded with different nano zinc oxide contents and with oriented structures. Physical and chemical characterization and biological performance evaluation were carried out to explore their effects on tendon cell proliferation and differentiation. MethodsPreparation of PLLA fiber scaffolds and PLLA/ZnO fiber scaffolds containing different mass fractions of nano ZnO was performed using electrospinning technology. The physicochemical properties of the scaffold were characterized by scanning electron microscopy, mechanical stretching, and EDS spectroscopy. The scaffold was co-cultured with mouse tendon cells to detect its biocompatibility and regulatory effects on cell differentiation behavior. ResultsThe fiber scaffolds were arranged in an oriented manner, and zinc elements were uniformly distributed in the fibers. The tensile strength and Young’s modulus of PLLA/0.1%ZnO fiber scaffolds were significantly higher than PLLA fiber scaffolds. The number of cells on the surface of PLLA/0.1%ZnO fiber scaffold was significantly higher than that of the PLLA group, and the activity was better; mouse tendon cells exhibit directional adhesion and growth along the fiber arrangement direction. ConclusionThe oriented PLLA/0.1%ZnO fiber scaffold had excellent physicochemical properties, which can significantly promote the oriented growth, proliferation and differentiation of tendon cells. It is expected to be used for tendon tissue regeneration and repair in the future.

Objective To develop a portable medical oxygen purity analyzer capable of real-time detection of multi-compo-nent gases in medical oxygen or aviation oxygen to ensure the safety of oxygen consumption.Methods The portable medical oxygen purity analyzer with STM3F103RC as the main controller involved in a management module,an oxygen detection module,a carbon monoxide/chlorine detection module,a flow/carbon dioxide detection module and a dew point detection module as its hardware components,which had its human-machine interface programmed with DGUS supervision,control and data acquisition(SCADA)software and system program developed with C language under Keil MDK environment.The performance verification of the analyzer developed was carried out in terms of oxygen detection error and stability and errors for measuring carbon monoxide,chlorine and carbon dioxide.Results The analyzer showed high precision when used to detect oxygen with high volume fraction,with long-term stability and the absolute error restrained within±0.1％;the erros for measuring carbon monoxide,chlorine and carbon dioxide were all limited within±5％FS to meet the desired requirements.Condusion The portable medical oxygen purity analyzer developed with high precision,stability and portability can be used for detection of medical oxygen and aviation oxygen.[Chinese Medical Equipment Journal,2024,45(3):36-40]

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

Abstract: Objective　To analyze the treatment outcomes of elderly patients with pulmonary tuberculosis in Chongqing, so as to provide reference for the prevention and control strategies of the epidemic of elderly pulmonary tuberculosis. Methods　The data of tuberculosis cases aged ≥65 years in Chongqing from 2015 to 2020 were collected from the National Health Insurance Information Project Disease Prevention and Control Information system. Descriptive statistical methods were used to analyze the data. Results The registration rates of elderly active pulmonary tuberculosis patients and etiological positive patients were 110.95/10-5and 32.25/10-5 in 2015 and 84.06/10-5 and 57.29/10-5 in 2020. The annual decline rate of active tuberculosis registration was 5.40%, and the annual increase rate of pathogenic-positive tuberculosis registration was 12.18%. The registration rates of active tuberculosis patients and etiological positive patients in the whole population were 70.75/10-5 and 17.63/10-5 in 2015 and 50.34/10-5 and 29.14/10-5 in 2020. The annual decline rate of active tuberculosis registration was 6.58%, and the annual increase rate of pathogenic-positive tuberculosis registration was 10.57%. From 2015 to 2020, a total of 25 931 cases of elderly pulmonary tuberculosis were registered, of which 21 374 (82.43%) cases were successfully treated and 4 010 (15.80%) cases had unfavorable outcomes. The proportion of cured and death patients showed an increasing trend year by year (χ2trend=313.853, 100.502, P<0.01). From 2015 to 2020, the average annual successful treatment rate of elderly pulmonary tuberculosis in the whole city was 82.43%, with the lowest rate in southeast Chongqing (74.23%), followed by urban areas (81.99%). The success rate of elderly pulmonary tuberculosis treatment in the whole city, west Chongqing, northeast Chongqing and southeast Chongqing showed a downward trend year by year (χ2trend=230.199, 35.278, 108.076, 112.130, all P<0.01), with annual decline rates of 2.77%, 2.26%, 3.0% and 4.12%, respectively. Among the registered elderly patients, female, 65-<75 years old, Han nationality, newly diagnosed, no complications, and negative for etiology (χ2=15.234, 255.910, 146.842, 179.998, 25.575, 131.170, P<0.01) had higher success treatment rates. Conclusions The prevalence of pulmonary tuberculosis in the elderly population in Chongqing City is declining, but the positive registration rate of etiology is increasing annually, and the success rate of treatment is decreasing. Therefore, it is necessary to strengthen the systematic management, publicity and education of elderly patients (especially those in southeast Chongqing, male, positive patients and severe patients) to effectively control the epidemic of tuberculosis in the elderly.

Objective: To explore the changes in bacterial community structure, antibiotic resistance genome, and pathogen virulence genome in river water before and after the river flowing through Haikou City and their transmission and dispersal patterns and to reveal anthropogenic disturbance's effects on microorganisms and resistance genes in the aquatic environment. Methods: The Nandu River was divided into three study areas: the front, middle and rear sections from the upstream before it flowed through Haikou City to the estuary. Three sampling sites were selected in each area, and six copies of the sample were collected in parallel at each site and mixed for 3 L per sample. Microbial community structure, antibiotic resistance, virulence factors, and mobile genetic elements were analyzed through bioinformatic data obtained by metagenomic sequencing and full-length sequencing of 16S rRNA genes. Variations in the distribution of bacterial communities between samples and correlation of transmission patterns were analyzed by principal co-ordinates analysis, procrustes analysis, and Mantel test. Results: As the river flowed through Haikou City, microbes' alpha diversity gradually decreased. Among them, Proteobacteria dominates in the bacterial community in the front, middle, and rear sections, and the relative abundance of Proteobacteria in the middle and rear sections was higher than that in the front segment. The diversity and abundance of antibiotic resistance genes, virulence factors, and mobile genetic elements were all at low levels in the front section and all increased significantly after flow through Haikou City. At the same time, horizontal transmission mediated by mobile genetic elements played a more significant role in the spread of antibiotic-resistance genes and virulence factors. Conclusions: Urbanization significantly impacts river bacteria and the resistance genes, virulence factors, and mobile genetic elements they carry. The Nandu River in Haikou flows through the city, receiving antibiotic-resistant and pathogen-associated bacteria excreted by the population. In contrast, antibiotic-resistant genes and virulence factors are enriched in bacteria, which indicates a threat to environmental health and public health. Comparison of river microbiomes and antibiotic resistance genomes before and after flow through cities is a valuable early warning indicator for monitoring the spread of antibiotic resistance.
Humans ; Rivers ; Virulence Factors/genetics* ; RNA, Ribosomal, 16S/genetics* ; Microbiota/genetics* ; Anti-Bacterial Agents ; Drug Resistance, Microbial/genetics*

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca²⁺ current. Using noise analysis of Ca²⁺ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca²⁺ channels along with Ca_V1.3 expression. All these changes could act synergistically to enhance the Ca²⁺ influx into IHCs. Inhibition of intracellular Ca²⁺ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*

The succession of microbiota is closely associated with several essential factors, including race, sex, health condition, lifestyle, postmortem interval, etc., and it has great potential application value in forensic medicine. This paper summarizes recent studies on the forensic applications of the microbiome, including individual identification, geographical feature identification, origin identification of the tissue or body fluid, and postmortem interval estimation, and introduces the current machine learning algorithms for microbiology research based on next-generation sequencing data. In addition, the current problems facing forensic microbiomics such as the extraction and preservation of samples, construction of standardization and database, ethical review and practical applicability are discussed. Future multi-omics studies are expected to explore micro ecosystems from a comprehensive and dynamic perspective, to promote the development of forensic microbiomics application.
Humans ; Forensic Medicine ; Autopsy ; Microbiota/genetics* ; Algorithms ; High-Throughput Nucleotide Sequencing ; Postmortem Changes