Arboviruses are transmitted by blood-sucking arthropods and infect vertebrates through insect bites. Its global prevalence and recurrence threaten human life and health. However, the pathogenic mechanism has not yet been fully elucidated. Neutrophils, as the most numerous leukocytes in the body, are the first to arrive at the site of infection after pathogen invasion, and play a role in the immune response through a variety of anti-infective mechanisms, including phagocytosis of pathogens, production of cytokines and antimicrobial substances, respiratory outbreaks, and secretion of NETs, which is an important member of the body's defence against pathogenic microorganisms. However, it is worth noting that excessive activation of neutrophils may also lead to a strong inflammatory response, which not only fails to control the infection effectively, but also causes damage to host tissues and further aggravates the severity of the infection. Previous knowledge of the role of neutrophils was mostly limited to fighting bacterial and fungal infections. However, it is only in recent years that their role in antivirus has been gradually revealed and valued. Therefore, its role and mechanism in controlling arboviral infections are not yet clear. In this paper, we present an overview of the role of neutrophils in arboviral infections and their possible effects on the host.

Objective To analyze the effects of different probiotic treatments on intestinal microecology and immune function of neonates with antibiotic-associated diarrhea. Methods 80 neonates with antibiotic-associated diarrhea treated in our hospital between January 2022 and January 2024 were collected as study subjects. It was divided into an observation group and a control group of 40 cases each according to the method of treatment. The observation group was treated with Clostridium typhimurium two-live bacterial powder, and the control group was treated with Bifidobacterium bifidum three-live bacterial powder. Compare the treatment effect, intestinal flora and immune function changes of the two groups. Results There was no difference in the comparison of gender, age, weight, vomiting, fever and the time from the start of antibiotics to the appearance of diarrhea between the two groups of children (P>0.05). The observation group had a higher overall effective rate than the control group (P<0.05). There was no difference in the counts of Lactobacillus, Lactobacillus, Bifidobacterium, and Eubacterium before treatment between the two groups (P>0.05). The counts of lactobacilli, lactobacilli, bifidobacteria, and eubacteria increased in both groups after treatment, and they were higher in the observation group than in the control group (P<0.05). There was no difference in IgA, IgG and IgM before treatment between the two groups (P>0.05). The IgA, IgG, and IgM of the children in both groups increased after treatment, and the observation group was better than the control group (P<0.05). Conclusion Different probiotics have good effect in treating newborns with antibiotic-associated diarrhea, among which Clostridium typhimurium diphtheriae has the most obvious effect on the intestinal microecology and immune function of the children.

Abstract：This study aimed to investigate the dissemination and molecular drug resistance characteristics of Mycobacterium tuberculosis complex (MTBC) among non-elderly populations (<60 years old) attending tuberculosis-designated medical institutions in Luoyang during the COVID-19 pandemic from an age-stratified perspective. Sputum specimens from 16,631 patients (9,990 in the non-elderly group) at Luoyang Infectious Disease Hospital from 2020 to 2022 were analyzed using real-time fluorescence PCR to detect the MTBC-specific insertion sequence IS6110. Melting curve technology was applied to positive specimens to assess molecular drug resistance to isoniazid (INH), rifampin (RFP), streptomycin (SM), and ethambutol (EMB). Age-stratified comparisons were conducted to further reveal the MTBC dissemination and drug resistance patterns in non-elderly populations. During 2020-2022, sputum specimens from 16,631 patients (9,990 in the non-elderly group) were subjected to real-time fluorescence PCR for detecting the MTBC-specific insertion sequence IS6110. For positive specimens, melting curve technology was used to analyze the molecular drug resistance to isoniazid (INH), rifampin (RFP), streptomycin (SM), and ethambutol (EMB). Age-stratified comparisons of the experimental results were performed to further reveal the MTBC dissemination and drug resistance characteristics in non-elderly populations. The results revealed that both MTBC detection rates (15.9% vs. 13.8%) and the overall drug resistance rate (27.1% vs. 20.9%) were significantly higher in non-elderly individuals compared to the elderly group (all P < 0.001). Subgroup analysis indicated that among non-elderly populations males, retreatment patients, and the main urban population were high-burden subgroups with MTBC and drug resistance. The epidemic patterns of multidrug-resistant tuberculosis (MDR-TB) and poly-resistant tuberculosis (PDR-TB) were predominantly characterized by MDR3 (resistance to INH + RFP + SM) and PDR2 (resistance to INH + SM), with detection rates of 4.8% (77 cases) and 2.3% (37 cases) respectively. The study showed that non-elderly populations (<60 years old) are key drivers of tuberculosis transmission and drug resistance development in this region, with males, retreatment patients, and urban residents facing particularly prominent risks. It is recommended to implement targeted tuberculosis burden monitoring for this group, optimize life-cycle prevention and control strategies based on age-stratified characteristics, and provide a scientific basis for precision tuberculosis control in the post-COVID-19 era.

The interaction between microorganisms and the human host is complex. Fusobacterium nucleatum, a commensal bacterium in the human body, can lead to chronic inflammatory responses under pathological conditions, playing an important role in plaque formation and bacterial pathogenicity through its various adhesion proteins. In recent years, increasing evidence has shown a link between periodontitis and respiratory diseases, with common periodontal pathogens detected in samples from various respiratory diseases. These pathogens can promote the adhesion and invasion of respiratory pathogens, enhance inflammatory responses and apoptosis in respiratory epithelial cells, induce mucin overexpression, and disrupt the balance of the respiratory immune system, thereby influencing the occurrence and development of respiratory diseases. In this review, we examine the association between Fusobacterium nucleatum and respiratory diseases (mainly chronic obstructive pulmonary disease, lung infectious diseases, lung cancer, and bronchitis) and summarize the mechanisms and molecular changes by which Fusobacterium nucleatum promotes the progression of related diseases. This provides new insights into the pathogenesis of respiratory diseases and offers new ideas for developing treatment and prevention strategies for these conditions.

To analyze distribution characteristics of vaccination failure types among laboratory-confirmed cases of measles in Shanghai during 2009-2017, measles cases with confirmed vaccination document among the measles laboratory-confirmed cases in Shanghai from 2009 to 2017 were selected to conduct a descriptive study about their characteristics. Measles virus IgG avidity assay was used to analyse the average relative avidity index (RAI) and determined proportions of different groups with high/medium/low affinity ratio. Among the 253 laboratory-confirmed cases of measles with a clear history of immunity, the male to female ratio was 1:1.72 (160/93). Among these IgG-positive measles cases, IgG with high, low, and suspicious affinity accounted for 53.99%, 24.54%, and 21.47% respectively. The proportion of high-affinity cases across different age groups exhibits a wave-like pattern of increase and decrease. The 1-19 years age group has the highest number of cases, while the 20-29 years group shows a slight decline. Among patients aged 30-39 years, the proportion of high-affinity cases within this age group reached the highest percentage at 76.9%. 0 doses, 1 dose, ≥2 doses Measles containing vaccine, The proportions of high affinity cases with MCV) immunity history were 11.71%(41/350), 26.56% (51/192), and 60.65% (37/61) respectively.

Helicobacter pylori (Hp), as a common gastric pathogen, has a high global infection rate and is the main cause of various gastrointestinal diseases such as gastritis, gastric ulcers, and gastric cancer. The treatment of eradicating Hp infection NOt only improves the diseases related to gastric inflammation and intestinal microbiota disorders caused by it, but also reduces the risk of gastric cancer. However, with the widespread use of antibiotics, the resistance of Hp continues to rise, increasing the failure rate of treatment. Therefore, there is an urgent need to find new treatment options or adjuvant drugs. Fucoidan has attracted much attention due to its unique biological functions and wide application fields. Research has found that Fucoidan has therapeutic and preventive effects on Hp infection related gastritis and intestinal microbiota disorders. This article elaborates on the main role and related mechanisms of Fucoidan in antagonizing Hp infection, including direct inhibition, reduction of inflammatory response, enhancement of antioxidant capacity, and regulation of gut microbiota. It provides a theoretical basis for Fucoidan to become an effective drug for treating Hp infection and aims to incorporate it into the treatment plan for eradicating Hp infection.

【Abstract】 Objective: By using high-throughput culture and high-throughput sequencing to detect the composition of vaginal microbiota in healthy women and patients with bacterial vaginosis, compare the differences in detection results between the two methods to provide evidence for the role of culturomics in vaginal microecology research and clinical disease diagnosis and treatment. Method: Collect vaginal secretions from 10 healthy women and 10 women with bacterial vaginosis, and use 7 different culture media for high-throughput culture of vaginal secretions. Use Clin-ToF time-of-flight mass spectrometry for identification. Simultaneously, high-throughput sequencing of the 16S rRNA V1V2 variable domain was performed directly on all samples. Result: 1. After culturing 20 vaginal secretion samples using culture omics, 35 bacterial genera were identified, with 98 bacterial species at the species level. A total of 17 Lactobacilli were cultured in all samples, of which 9 were detected in both groups. The top three detected strains in the healthy group were Lactobacillus crispatus, Lactobacillus jensenii, and Lactobacillus iners. And in the 5 samples, both Lactobacillus crispatus and Lactobacillus jensenii were cultured simultaneously. The top three detected in the BV group were Lactobacillus iners, Lactobacillus jensenii, and Lactobacillus psittaci. 2. Using the V1V2 domain of the 16S rRNA gene, high-throughput sequencing was performed on the 20 vaginal microbial samples mentioned above, a total of 18 genera were detected in all samples, of which Lactobacillus genus was detectable in all samples, and the relative abundance of Lactobacillus genus exceeded 50% in 12 samples. 3. Among the 20 vaginal microbiota samples, only 9 bacterial genera were identified simultaneously through culture and high-throughput sequencing. Conclusion: By using high-throughput culturomics and high-throughput sequencing methods to simultaneously detect the vaginal microbiota of all samples, the results showed significant differences. High throughput culture has a higher detection rate of bacterial genera and species, and can cultivate lactobacilli with low or undetectable high-throughput sequencing content. Therefore, the use of high-throughput culture groups will have higher application value in the diagnosis and treatment of bacterial vaginosis and the study of vaginal microbiota.

Objective To explore the clinical significance of detecting neutrophil elastase (NE) in patients with acute exacerbation of bronchiectasis complicated with Pseudomonas aeruginosa (PA) infection. Methods Ninety patients with acute exacerbation of bronchiectasis admitted to our hospital from August 2022 to December 2023 were regarded as the trail group. Based on sputum culture results, patients with concomitant PA infection but with other bacterial infections were identified as the combined group (n=36), while patients without concomitant PA infection were selected as the non-combined group (n=54). In addition, 90 patients who underwent stable bronchodilation outpatient visits in our hospital were regarded as the control group and divided into PA colonization group (n=42) and non-PA colonization group (n=48). The expression levels of serum NE, procalcitonin (PCT) and C-reactive protein (CRP) were detected. Pearson method was applied to analyze the correlation between serum NE level and inflammatory markers in patients with acute exacerbation of bronchiectasis. ROC curve was applied to evaluate the predictive efficacy of serum NE and PCT levels for PA infection in patients with acute exacerbation of bronchiectasis. Results The expression levels of serum NE, PCT, and CRP in the trail group were greatly higher than those in the control group (P<0.05).There were no significant differences in the expression levels of serum NE, PCT and CRP between the PA group and the non-PA group (P>0.05). The serum NE, PCT, and CRP levels in the combined group were greatly higher than those in the non-combined group (P<0.05). The serum NE level in patients with acute exacerbation of tracheal dilation was positively correlated with PCT and CRP levels (P<0.05). The area under the curve (AUC) of serum NE, PCT, CRP, and their combination in predicting PA infection in patients with acute exacerbation of bronchiectasis was 0.856, 0.756, 0.702, and 0.962, respectively. The combination of the three was better than their individual predictions (Z combination - NE=2.399, Z combination - PCT=3.741, Z combination - CRP=4.499, P=0.017, P=0.000, P=0.000), with sensitivity and specificity of 80.56% and 96.30%, respectively. Conclusion Serum NE level is greatly elevated in patients with acute exacerbation of bronchiectasis, and is closely related to inflammatory markers PCT and CRP. The combination of the three has a high predictive power for patients with acute exacerbation of bronchiectasis complicated with PA infection.

Chlamydia trachomatis (CT) is a Gram-negative, obligate intracellular parasite that can infect mucosal epithelial cells such as the urethra, vagina, and nasopharynx, as well as the conjunctiva, causing diseases such as trachoma, urethritis, cervicitis, and neonatal conjunctivitis. Among them, L2 CT can cause sexually transmitted lymphogranuloma, which is more invasive than other serotypes and requires long-term treatment, receiving widespread attention. Research has shown that the production of erythropoietin producing hepatocyte receptor A2 (EphA2) on the cell surface can mediate the adhesion and invasion of CT L2, and interfering with their interaction can significantly reduce the infection of CT L2. This study conducted bioinformatics analysis on human cervical epithelial cells infected with CT L2 and found that EphA2 expression was significantly upregulated in the infected group. This study successfully constructed, expressed, and purified a bivalent antibody targeting EphA2, named as EphA2-scFv-Fc. Through ELISA experiments, it was confirmed that there is a dose-dependent specific binding between EphA2-scFv-Fc and EphA2 receptors on the surface of CT L2 susceptible cells HUVEC. This study not only revealed the crucial role of EphA2 in the process of CT infection, but also successfully developed bivalent antibodies that can specifically target EphA2, providing an important foundation for the treatment of CT L2 infection.

At present, there are few studies on co-infection with Influenza A virus and Cryptococcus. This paper reports a case of a patient who developed cryptococcal (Cryptococcus gattii) infection secondary to Influenza A and subsequently suffered from meningoencephalitis, in order to enhance clinical understanding of this disease. The patient, a 58-year-old male, was diagnosed with Influenza A and experienced recurrent dizziness and headache for over a month. Later, he developed fever, episodic bilateral lower limb weakness, and intermittent consciousness disorders. Chest CT, head MRI, and cerebrospinal fluid examination after lumbar puncture were performed and Cryptococcus gattii was detected through the pathogen culture of cerebrospinal fluid. Thus the patient was diagnosed with cryptococcal meningoencephalitis. The patient was treated with liposomal amphotericin B and fluconazole for induction therapy, along with treatment reducing intracranial pressure and resisting bacterial infection. Four weeks later, the patient's consciousness improved, and the protein level of cerebrospinal fluid returned to normal. However, the intracranial pressure remained higher than 400 mmH2O. The patient was then transferred to another hospital for further treatment. Compared to Cryptococcus neoformans, Cryptococcus gattii is more commonly found in individuals with normal immune function. In this case, the patient's immune function was normal, but the influenza virus-induced pneumonia might have increased the risk of cryptococcal infection by altering the microenvironment of the lungs. Besides, Influenza A Virus can exacerbate the severity of Cryptococcus gattii infection through multiple mechanisms. Clinicians need to pay attention to the risk of secondary cryptococcal infection in influenza patients and explore comprehensive treatment strategies that combine antiviral, antifungal, immunomodulatory and prognosis-improving measures.

This study aims to construct a pseudovirus mutation library of the SARS-CoV-2 spike (S) protein based on the vesicular stomatitis virus (VSV) vector system, in order to screen potential immune escape variants and identify critical mutation sites, thereby providing scientific evidence for vaccine development and epidemic prevention and control. A random mutagenesis kit was employed to introduce random mutations into the receptor-binding domain (RBD) of the Wuhan strain S protein, followed by the construction of a pseudovirus plasmid library and subsequent virus rescue using the VSV vector system. Immune escape variants were screened through serum pressure and limited dilution methods, with their mutation sites validated by sequencing. Results demonstrated the successful construction of the SARS-CoV-2 pseudovirus plasmid library, achieving a positive rate of 98%. Immune escape variants carrying single mutations such as E484K, F486I, G339S, and S477R, as well as double mutations including E484K+K444Q and E484K+K462R, were identified. Some escape variants exhibited significant resistance to neutralizing sera, with a marked reduction in neutralizing titers observed for the E484K single mutant and E484K-related double mutants. This study confirms the feasibility of screening immune escape variants through the construction of a SARS-CoV-2 pseudovirus mutation library and elucidates their potential escape mechanisms and epidemic characteristics. These findings provide important insights into understanding the evolutionary trends of SARS-CoV-2 and offer scientific support for optimizing vaccine development and epidemic prevention strategies.

Objective To investigate the distribution and drug resistance of pathogenic bacteria isolated and cultured from valve vegetations in infective endocarditis, and to provide evidence for diagnosis and treatment of infective endocarditis in this area. Methods A total of 185 patients with infective endocarditis and cardiac surgery admitted to our hospital from March 2016 to December 2022 were selected to collect clinical data. Pathogens were isolated from the culture of valvular vegetations, and drug susceptibility tests were performed on common pathogens. Results The positive rate of valvular vegetation culture was 53.5% (99/185), and the pathogenic bacteria isolated from valvular vegetation culture included 70 strains of Streptococcus spp. (70.7%, 70/99) and 17 strains of Staphylococcus spp. (17.2%, 17/99), 5 strains of nutritionally variant Streptococci (5.0%, 5/99), 2 strains of Enterococcus spp. (2.0%, 2/99), 2 strains of HACEK organisms (2.0%, 2/99), 1 strain of Brucella ovis (1.0%, 1/99), 1 strain of Gemella haemolysans (1.0%, 1/99) and 1 strain of Pseudomonas (1.0%, 1/99). Streptococci spp. was completely sensitive to penicillin, cefotaxime, cefepime, vancomycin, meropenem, daptomycin and linezolid, while was partially resistant to tetracycline (47.1%, 33/70), erythromycin (38.6% , 27/70), clindamycin (27.1%, 19/70), levofloxacin (7.1%, 5/70) and chloramphenicol (1.4%, 1/70). Staphylococci spp. was completely sensitive to vancomycin, teicolanin, dattomycin, minocycline, chloramphenicol and linezolid, with resistance rates of 100%, 76.5%, 41.2% and 35.3% to penicillin, methicillin, erythromycin and clindamycin, respectively, and 10% to 20% to other commonly used drugs. Conclusions The main pathogens of infective endocarditis were Streptococcus spp. and Staphylococcus. spp. Positive valvular vegetation culture is valuable in supplementing and confirming blood culture. Penicillin remains the recommended treatment for streptococcal IE, and vancomycin can be a viable option for severe infections of Streptococcus spp. and Staphylococcus spp.

Objective To discuss the serotype distribution and drug resistance of nontyphoidal salmonellosis (NTS) infection in children in Tangshan City from 2022 to 2024. Methods: From January 2022 to December 2024, 235 children diagnosed with NTS infection in our hospital were served as subjects. The basic characteristics of the children were statistically explored, and the cultured NTS were subjected to serotype and drug sensitivity tests to analyze the drug resistance of NTS detected in different years. Results In 2022, 2023, and 2024, 79, 84, and 72 cases of NTS infection were detected in the Tangshan area, respectively, with no conspicuous difference in the proportions of male and female cases (P>0.05). Among 235 children with NTS infection, those < 1 year old accounted for the highest proportion (45.53%), while those aged 1-2 years (excluding 2 years) accounted for 29.79%. From 2022 to 2024, the NTS infection rate among children in the Tangshan area was highest in summer and lowest in winter. The serotype test showed that a total of 17 serotypes were detected in 235 children with NTS infection, of which 51.91% were Salmonella typhimurium and 15.32% were Salmonella enteritis. The drug sensitivity test revealed that 235 NTS strains had the highest resistance rate to ampicillin (average value was 77.02%), a relatively high resistance rate to compound sulfamethoxazole (average value was 48.09%), and a relatively low resistance rate to antibiotics such as ceftriaxone (average value was 16.60%) and ceftazidime (average value was 22.55%). There was no conspicuous difference (P>0.05) in the resistance rates of Salmonella typhimurium and Salmonella enteritis to eight antibiotics, including ampicillin. Conclusion: The serotypes of NTS infected children in Tangshan city are mainly Salmonella typhimurium and Salmonella enteritis. NTS strains have a high resistance rate to ampicillin and compound sulfamethoxazole. In clinical practice, antibiotics should be selected reasonably based on the serotype and resistance of NTS infected children to avoid overuse of antibiotics.

Little was known regarding the differences in the gut microbiomes of brucellosis patients and healthy subjects (HCs). To explore the characteristics of the gut microbiota in brucellosis patients, 16s rRNA sequencing data from 40 Chinese HCs, 16 acute and 3 post-treatment brucellosis were analyzed. Acute and post-treatment brucellosis were lower in community richness and microbial diversity compared to HCs (P<0.05). Actinobacteria and subordinate genera, Bifidobacterium and Collinsella, were higher in acute brucellosis. Antibiotic treatment further reduced microbial diversity and enriched Gram-positive bacteria such as Enterococcus, Corynebactereraceae and Lactobacillales. PICRUSt2 analysis identified significant differences in 18 KEGG pathways, among which 10/13 (76.9%) metabolism pathway increased in brucellosis groups compared to HCs, indicating metabolic enhancement after Brucella infection. In conclusion, our cohort study detected altered microbiota and decreased microbial diversity in the brucellosis patients, marked by a significant overgrowth of disease-related microbes from Actinobacteria, which was a new perspective for the pathogenesis of brucellosis.