The Type VII secretion system (T7SS) is the only secretion system exclusively found in Gram-positive bacteria. It closely links to bacterial growth and virulence, which plays an important role in the interaction between bacteria-bacteria, bacteria-host, and bacteria-environment. Overall, the functional diversity of T7SS is associated with its effector proteins. Therefore, the article will discuss the effector proteins secreted by T7SS, providing a comprehensive review of their structure and function, secretion mechanisms, and the regulatory modes of gene transcription, with the aim to offer new perspectives for further research into bacterial T7SS.

To understand the prevalence of rabies, Toxoplasma gondii and influenza A virus in stray cats in Qingpu, Shanghai. Serum samples from 153 stray cats collected from 40 residential community between June 2022 and August 2010 were tested for antibodies to rabies, Toxoplasma gondii and influenza A viruses by ELISA. The H3, H5, H7 and H9 serotypes of influenza A antibody positive samples were identified by HI test. Real-time PCR was used for the detection of Toxoplasma gondii RNA in whole blood samples and influenza virus RNA in throat and anal swab samples. The results showed that the positive rates of rabies, Toxoplasma gondii and influenza A were 14.38% (22/153) , 11.76% (18/153) and 3.92% (6/153) respectively. The difference of positive rate of Toxoplasma gondii antibody between spring (March-May) and summer (June-August) was very significant. The positive rate of H3 was 0.65% (1/153) . No H5, H7 and H9 antibody was detected. The results showed no Toxoplasma gondii antigen was detected in the whole blood samples ,and no influenza antigen was detected in throat swab samples and anal swab samples. The results suggest that the rabies antibody level of stray cats in Qingpu District was low, which was not enough to block the Rabies transmission. Toxoplasma gondii infection exists in stray cats, especially in summer. The presence of influenza A infection in stray cats suggests that stray cats can act as a "Mixer" for human and animal influenza viruses, posing a risk of zoonosis transmission. Therefore, it is necessary to continuously monitor the infection of rabies, Toxoplasma gondii and influenza A virus in stray cats to provide basis for scientific prevention and control.

【Abstract】Purposes Bloodstream infection (BSI) has a high mortality and disability rate, and accurate and timely pathogen diagnosis is crucial. Our aim is to evaluate the value of droplet digital PCR (ddPCR) in diagnosing bloodstream infections. Methods We conducted a prospective study, collecting 55 patients suspected of bloodstream infection and comparing droplet digital PCR detection (approximately 3 hours) with traditional blood culture (BC, at least 48 hours). Results The sensitivity and negative predictive value of ddPCR were high, and the positive rate was significantly higher than that of blood culture; It was not significantly correlated with the inflammatory factors procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) in plasma; However, in the ddPCR+/BC+ group, the number of gene copy of pathogenic bacteria detected by ddPCR showed a synchronous trend with PCT, CRP, and WBC. In addition, all the six samples with carbapenem-resistant Klebsiella pneumoniae isolates identified through antimicrobial susceptibility testing were also detected by ddPCR, with serinase (blaKPC) or metalloenzymes (blaNDM and blaIMP). The mecA gene was also detected in all the three samples with methicillin-resistant Staphylococcus isolates. Moreover, ddPCR detected antimicrobial resistance genes in other nine culture-negative samples. Conclusion Droplet digital PCR is a rapid pathogen-detecting method that can be supplementary to traditional blood culture. When combined with clinical symptoms, ddPCR can be used to quickly diagnose patients with suspected bloodstream infections. At the same time, it also has potential advantages in detecting antimicrobial resistance genes.

The purpose of the current study is to investigate the current situation of pathogenic microorganism laboratory in Shanghai disease control institutions, analyze the biosafety situation of the laboratory, and put forward countermeasures and suggestions for further strengthening and standardizing the biosafety management of laboratories in Shanghai. Investigate the biosafety status of pathogenic microorganism laboratories in 16 district level disease control institutions in the field testing. It was found that the allocation rate of biosafety cabinet, autoclave, eye washer and UV lamp reached 100%. The biosafety cabinet and UV lamp are well maintained and the qualified rate of eye washer and autoclave is 87.50%. Among them, the indicators of the management system have been completed well, and the indicators of personnel management and experimental process management need to be improved. The compliance rate of residual chlorine monitoring values in wastewater treatment is lower than 80%. The results show that the establishment of biosafety system and the implementation of laboratory responsibilities are well completed, and waste disposal, facilities and equipment management, and emergency plan system need to be further improved and improved.

This aim of this study was to distinct the physical characterization and protein components of outer membrane vesicle (OMV) secreted from Pseudomonas aeruginosa under normal culture condition and meropenem (MEM) stimulated culture by a variety of technological means including transmission electron microscopy (TEM), Liquid chromatography tandem mass spectrometry (LC-MS/MS). At the same time, mouse macrophage cell line Raw264.7 was cultured and incubated with OMV for 48 hours in vitro, the secretion level of various inflammatory cytokines in Raw264.7 cells was detected by enzyme-linked immunosorbent assay (ELISA). The results showed that, compared with normal culture samples (normal-OMV), there was no significant difference in the morphology and size of OMV derived from P. aeruginosa under pressure culture with a certain concentration of MEM (MEM-OMV). The particle concentration of MEM-OMV was significantly higher than the particle concentration of Normal-OMV (20 ± 0.53×108/mL vs 1.50 ± 0.76×108/mL). The results of proteomics analysis showed that the protein expression of the two kind of OMVs was also heterogeneous, MEM-OMV containing more MexA and MexB proteins related to efflux pumps. The results of cell experiments showed that MEM-OMV could stimulate Raw264.7 cells to produce significantly higher concentrations of IL-6, TNF-α, IL-8 and IFN-γ than Normal-OMV. In conclusion, the addition of meropenem can change the production rate of OMV secreted by P. aeruginosa, the inclusion of protein and the immune stimulation effect on macrophages.

Abstract： Objective To analyze the isolation, identification and drug sensitivity of Gordonia bronchialis in tumor patients with catheter related bloodstream infection, and provide reference for clinical treatment of infectious diseases caused by this bacteria. Method The blood culture positive sample was collected from a patient with endometrial cancer after radiotherapy, which was collected through venous catheter and peripheral vein. At the same time, the isolate was identified and analyzed by using VITEK MS fully automated microbial mass spectrometry detection system and molecular sequencing technology, and the drug sensitivity tests were conducted according to the Gram positive rod bacteria drug sensitivity test standards. Result After incubating the venous catheter blood and peripheral venous blood for 48 hours, a positive alarm was reported, and Gram positive bacteria were found on the smear. Cultivated on a blood agar plate for 24 hours, it grew non hemolytic bacterial colonies which were white,rough and dry. After 48 hours of cultivation, the white ,roug hand dry bacterial colonies transformed into orange, rough and dry bacterial colonies. The VITEK MS mass spectrometer and 16S rRNA sequencing technology both identified that this bacterium was Gordon bronchialis, and the drug sensitivity results showed that this bacterium was sensitive to vancomycin, ceftriaxone, cefepime, ciprofloxacin, imipenem, meropenem, linezolid, and compound sulfamethoxazole. Conclusion This study reports the biological characteristics and diagnosis and treatment process of Gordonia bronchialis. Although this bacterium is common in the environment, there are relatively few cases related to human diseases. Like all microbial infections, timely diagnosis and treatment should be carried out for suspected or confirmed Gordonia bronchialis's infection.

[Abstract] Polymicrobial co-colonization is associated with the occurrence, development and persistence of co-infection. Co-colonized microorganisms usually increase their antibiotic resistance and pathogenicity, making it a challenge for clinical doctors. However, the interactions between co- colonized microorganisms are very complex, and different microorganisms have different ways of influencing each other, which can change with different duration of colonization.?This article provides an overview of detection and the risk factors for co-colonization of antibiotic-resistant microorganisms and the interactions between co-colonizing microorganisms.

Abstract: Aim： To improve the understanding of rhino-orbito-cerebral mucormycosis infection after chemotherapy in children with leukemia. Methods： The clinical data of a child with acute B - lymphocytic leukemia (B - ALL) complicated with rhino-orbito-cerebral mucormycosis during induction chemotherapy were retrospectively analyzed, and the related literature was reviewed. Results： A 3- year - old girl was diagnosed with B - ALL. During induction chemotherapy, she had repeated fever, eyelid swelling, nasal bleeding, eyelid ptosis, and blurred vision. She was diagnosed with rhino-orbito-cerebral mucormycosis by nasal endoscopy and airway secretion culture and cranial enhanced MRI, and was given amphotericin B liposome IV drip, posaconazole oral administration, and amphotericin B intrathecal injection to used for fungal therapy. The infection was effectively controlled. Conclusion： Mucor is a kind of conditioned pathogenic fungi, which is more common in patients with low immunity. Mucor enters human body through nasal cavity and respiratory tract, which can invade paransal sinus and orbits, causing necrotizing inflammation and granuloma. It can also invade the brain directly or through the bloodstream, causing intracranial infection. The onset and the progression of mucormycosis is quickly, but the diagnosis is difficult, and it has a high mortality rate. Combined treatment with amphotericin B as the main drug and surgery can improve the prognosis.

By comparing the differences in vaginal microbiota structure between patients with vulvovaginal candidiasis and healthy individuals, analyze the association between different dominant bacteria and vulvovaginal candidiasis. Recruiting 18 patients with vulvovaginal candidiasis (VVC group) and 27 healthy individuals (NC group). Patients in the VVC group were treated with lactobacillus vaginal capsules combined with clotrimazole, while patients in the NC group were not treated. Collect vaginal secretions from the NC group once, and from the VVC group four times (before medication and 10 days/30 days/60 days after medication). Extract total DNA from vaginal secretions samples, analyze bacterial diversity in vaginal secretions samples using [][][]high-throughput sequencing technology, discuss changes in bacterial community in vaginal secretions samples from VVC patients before and after treatment, and analyze differences from normal population samples. The vaginal microbiota in the VVC group was mainly composed of L. iners, while in the NC group, it was mainly composed of curled L. crispatus. After treatment with antifungal drugs, there was no significant difference in the composition of vaginal bacterial communities in the VVC group compared to before treatment. There is a significant difference in the composition of vaginal microbiota between the VVC group and the NC group, and antifungal drugs cannot promote the transition of vaginal bacterial community to a healthy state.

To investigate the clinical characteristics, drug resistance types and risk factors of Klebsiella pneumoniae infection in elderly patients. The clinical data from 322 elderly patients with community-acquired pneumonia (CAP) who admitted to Renhe Hospital of Baoshan District Shanghai from 2021 to 2023 were collected, and the patients were divided into a Klebsiella pneumoniae-infected group (KP group, 56 patients) and a non-Klebsiella pneumoniae-infected group (NKP group, 266 patients). Multifactorial logistic regression analysis was used to identify risk factors and the receiver operating characteristic curve (ROC) was assessed to the clinical value of indicators for Klebsiella pneumoniae infection. The results showed that Klebsiella pneumoniae exhibited high rates of resistance to ampicillin, cefuroxime, ceftazidime and piperacillin. Multifactorial analysis showed that males, respiratory failure, solid shadows in the lungs, and high fasting glucose levels were independent risk factors for Klebsiella pneumoniae infection. ROC curve showed that the area under the curve (AUC) for assessing the risk of infection for males, respiratory failure, and high fasting glucose levels exceeded 0.6, and the AUC of the combined indicator of the four independent risk factors reached 0.762. The elderly CAP population with Klebsiella pneumoniae demonstrates specific clinical characteristics and faces a high rate of drug resistance. Being male, high fasting glucose, respiratory failure and having solid shadows in the lungs were independent risk factors for infection with Klebsiella pneumoniae. Therefore, early identification and implementation of effective treatment and management strategies for these high-risk groups is essential in clinical practice.

Abstract:Antiviral treatment is a crucial tool for delaying the course of chronic hepatitis B and improving the prognosis of the illness. Chronic hepatitis B is today a significant infectious disease. Throughout the whole process, the body's immunological response is vital. The therapeutic relevance of immune factor IL-21 levels in the management of chronic hepatitis B is examined in this paper. The virologic response, HBeAg seroconversion, and viral recurrence in hepatitis B patients are all significantly influenced by serum IL-21. Variations in blood IL-21 levels are linked to recurrence after stopping nucleoside (acid) analogue treatment and can predict the virological response of individuals receiving these treatments. In clinical practice, serum IL-21 level monitoring can aid in the development of more successful individualized treatment plans. Additionally, IL-21 has demonstrated strong antiviral potential based on its immunomodulatory action, offering a novel treatment target and concept for chronic hepatitis B.

Chronic infection with the hepatitis B virus (HBV) is a significant contributor to severe liver diseases, including cirrhosis and hepatocellular carcinoma, thereby posing a substantial global health concern. This investigation employed an HBV transgenic mouse model harboring mutations in the basal core promoter (BCP) region to assess its virological characteristics and hepatic damage. The extent of liver fibrosis was determined using Sirius Red staining of liver tissue. Furthermore, whole-genome transcriptomic analysis of liver tissue was conducted. The study revealed that 12-week-old HBV transgenic mice with BCP region mutations exhibited elevated levels of HBV-DNA replication and spontaneous liver fibrosis. Differential gene expression analysis identified 729 upregulated and 325 downregulated genes within the HBV-Tg cohort, predominantly associated with the extracellular matrix, peroxisome proliferator-activated receptor (PPAR) pathway, and cytochrome P450 pathway. Protein-protein interaction (PPI) network analysis indicated that pivotal genes were implicated in collagen synthesis, inflammatory response, cell cycle regulation, and apoptosis. The pathological alterations observed in this murine model align with the progression of chronic liver disease, thereby offering a robust and effective model for elucidating the mechanisms underlying HBV infection-related hepatic pathology.

In this study, a strain of Getah virus (GETV, GenBank:OM363683) was successfully rescued using a reverse genetics approach. First, the optimized viral sequence was cloned into the low-copy plasmid pFK containing either the T7 or CMV promoter, named T7-GETV and CMV-GETV, respectively. Viral RNA was synthesized via in vitro transcription (IVT) using T7-GETV as a template, followed by RNA transfection into BHK-21 cells via liposome-mediated transfection. The viral titer was determined using 50% tissue culture infectious dose (TCID50) method and the expression of viral protein E1 was detected through Western blot (WB), validating the successful rescue of GETV. Further, the cytopathic effect (CPE) was observed via light microscope, and the growth characteristics of GETV were systematically analyzed using the TCID50 assay, real-time quantitative polymerase chain reaction (RT-qPCR), and WB. Additionally, based on the structure of GETV replicon, two replicative expression vectors were constructed using CMV-GETV as a template by retaining the non-structural protein genes and replacing the structural protein genes with the reporter gene mCherry or Renilla luciferase (Rluc), named pFK-GETV-mCherry and pFK-GETV-Rluc, respectively. Two control plasmids were also constructed by inserting only the reporter gene mCherry or Rluc downstream of the CMV promoter in the pFK plasmid, named pFK-mCherry and pFK-Rluc, respectively. Analysis with Image J software revealed that the average fluorescence intensity per cell of cells transfected with pFK-GETV-mCherry was approximately 5 times higher than that of cells transfected with pFK-mCherry. RT-qPCR results indicated that mCherry gene transcription level in cells transfected with pFK-GETV-mCherry was also about 5 times higher than that in cells transfected with pFK-mCherry, and both results were highly consistent. WB results indicated that mCherry protein expression level in cells transfected with pFK-GETV-mCherry was also higher than that in cells transfected with pFK-mCherry at the same time point. Renilla luciferase assay showed that Rluc expression efficiency in cells transfected with pFK-GETV-Rluc was about three orders of magnitude greater than that in cells transfected with pFK-Rluc. This study provides a robust reverse genetics tool for GETV research and demonstrates the ability of the GETV replicative expression vector to enhance exogenous gene expression, establishing a foundation for the development of replicative DNA vaccines.

This article introduces an innovative Individually Ventilated Cage (IVC) system, incorporating remote locking and position detection features to enhance efficiency and safety in laboratory animal management. As life science research advances, the demand for experimental animals increases, posing challenges for traditional IVC systems due to issues like cage misplacement from improper handling. The new IVC system, integrated with software, employs clear lighting cues and system alarms to effectively differentiate cage statuses in complex operational contexts, providing instant feedback and significantly reducing the likelihood of mishandling. Its reservation management and locking capabilities prevent mishaps when multiple groups share the IVC system, further boosting efficiency and safety in laboratory management. This IVC system, with its remote locking and position detection capabilities, not only improves operational accuracy and efficiency but also brings heightened security and reliability to laboratory animal management, offering crucial support for life science research and biosafety laboratory management.

Shroom2 is an actin-binding protein involved in the regulation of cell motility and actin cytoskeleton remodeling. Schistosome eggs can induce granuloma formation, leading to organized immune aggregates around the eggs. We unexpectedly observed that Shroom2-deficient mice exhibited a significantly higher mortality rate after infection with Schistosoma japonicum compared to wild-type mice. This study aims to investigate the disease progression in Shroom2 knockout mice after infection with Schistosoma japonicum, revealing the potential role of the Shroom2 gene in the immune response to schistosome infection and granuloma formation around the eggs. We used CRISPR/Cas9 technology to generate Shroom2 knockout (KO) mice. Both C57BL/6 wild-type (WT) and Shroom2 KO mice were infected with Schistosoma japonicum, with each mouse receiving an infection of approximately 30±2 cercariae via abdominal skin exposure. The mice were monitored daily, and the number of deaths was recorded. At 5 and 7 weeks post-infection, mice were sacrificed for blood routine analysis and liver histopathology with hematoxylin-eosin (HE) staining. Shroom2 knockout mice showed a significant increase in mortality during the acute phase of schistosome infection, accompanied by severe liver pathology and abnormal blood parameters. These findings suggest that the Shroom2 gene plays a critical role in regulating the host immune response, and its deficiency may increase susceptibility to pathogens, accelerating disease progression.

Cryptococcus is an opportunistic pathogen that causes cryptococcal meningitis in immunocompromised patients. Cryptococcus mainly causes subacute or chronic infection, the acute course is rare, this article introduces a case of progressive exacerbation of meningitis caused by acute infection of Cryptococcus neoformans in a diabetic patient, and to understand the development process affecting the occurrence and development of cryptococcal meningitis.

OBJECTIVE This meta-analysis aims to clarify the microbial distribution of periprosthetic joint infection (PJI) and explore therapeutic strategies for specific pathogens associated with PJI.Methods PubMed, CNKI (China National Knowledge Infrastructure), and Wanfang Database were searched for relevant literature up to November 8, 2022. Studies reporting on the distribution of PJI pathogens and their antimicrobial susceptibility were included. Data on pathogen distribution and antibiotic resistance profiles were collected. Studies meeting the criteria underwent quality assessment using the Joanna Briggs Institute (JBI) critical appraisal tool for analytical cross-sectional studies. Meta-analysis was conducted using STATA 17 software.Results A total of 25 studies were included, consisting of 22 retrospective studies and 3 randomized controlled trials. Among the 25 studies, the overall prevalence of Gram-positive bacteria was 76% (95% CI: 0.72-0.80, P < 0.01), Gram-negative bacteria was 18% (95% CI: 0.15-0.21, P < 0.01), fungi was 3% (95% CI: 0.02-0.04, P < 0.01), and mycobacteria was 2% (95% CI: 0.01-0.02, P < 0.01).Conclusion Coagulase-negative Staphylococci and Staphylococcus aureus are the two main pathogens contributing to periprosthetic joint infections. Clinical practices should explore more effective utilization of existing drugs, mitigate the development of bacterial resistance, and seek new drug targets, in order to provide a wider range of antibiotic options for periprosthetic joint infections.

Ubiquitination plays an important role in many biological processes, including viral infections, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies have found that DUBs inhibits or enhances viral infection through various mechanisms, the role of DUBs in viral regulation is still unknown and needs to be further explored. Ubiquitin specific protease (USP) belongs to cysteine protease and is one of the important members of Deubiquitination enzyme family. USP family molecules affect viral replication through positive or negative regulatory mechanisms in a variety of ways. For example, USP4, USP8, USP13, USP15 and USP49 have antiviral effects, while USP1, USP7, USP17 and UL36USP negatively regulate the antiviral immune response of the body. This review aims to comprehensively review the regulatory mechanisms and research progress of USP family members in antiviral immune response, which not only reveals the complex role of these proteases in virus-host interactions, but also provides valuable molecular targets and theoretical basis for the development of novel antiviral strategies. With the deepening of research, the multifaceted nature of USPs in virus infection and prevention and control will gradually become clear, contributing new solutions to global public health challenges.

There are few reports on bloodstream infections caused by Aeromonas dhakensis. This article presents a case report of a patient with liver cirrhosis who developed Aeromonas dhakensis bloodstream infection. The disease progressed rapidly with a poor prognosis. During the species identification process, methods such as the bioMerieux VITEK 2 Compact, Bruker mass spectrometer, and 16S rRNA sequencing were unable to provide accurate identification. However, gyrB sequencing and metagenomic next-generation sequencing (mNGS) were able to yield definitive species results. Through the comprehensive application of multiple methods, we provided a clear identification result for clinical diagnosis.

Objective We aimed to identify the differences in the diversity and composition of intestinal fungal flora between the plaque psoriatic patients and the healthy individuals. Methods We obtained the fresh fecal samples from the psoriatic patients and the healthy controls, collected from January 2021 to December 2021 in the dermatology clinic, the Fourth Hospital of Hebei Medical University. Fecal samples were processed and ITS was sequenced using the Illumina NovaSeq PE250 platform by UPARSE software. Results 1. Although a slight elevation was found in the richness and diversity of the intestinal fungi for the psoriasis group, there was no statistical difference between the two groups by the alpha diversity analysis (P>0.05)；2. A significant separation was detected between P and C groups with the analysis of PLS-DA；3.There were more than 10 species in the richness were significant different between two groups by the species diversity analysis. Phaffomycetaceae, Psathyrellaceae, Wickerhamomyces, Papiliotrema_flavescens in group P, and Saccharomycopsis, Saccharomycopsis fibuliger, Cutaneotrichosporon_cyanovorans, Cutaneotrichosporon, Aspergillus_conicus, Penicillium sumatraense, Mrakia blollopis, Hyphopichia, Talaromyces_duclauxii in the group C, were found increased, respectively. Conclusion The composition of intestinal fungal flora in the plaque psoriatic patients was significantly different compared with the healthy controls.

The purpose of this article is to analyze the clinical characteristics of confirmed cases of brucellosis in Yunnan region, and compare these cases with reported cases in the literature, in order to provide theoretical basis for the early diagnosis and treatment of brucellosis in the region. The clinical data of 36 patients with brucella infection confirmed by positive blood culture admitted during Jan. 2018 and Dec. 2022 were retrospectively analyzed; based on the clinical characteristics and diagnosis, they were divided into classic fever of unknown origin and non classic fever of unknown origin, and the epidemiological and clinical characteristics of the two groups were analyzed. The results demonstrated that, 91.67% patients lived mainly in rural areas; the acute stage is mainly , accounting for 88.89% , fever is one of the most common clinical symptoms, accounting for 94.44%, and 80.56% were complicated with liver injury. Comparing the epidemiological characteristics, clinical features, laboratory test results, and clinical outcomes of the two groups of patients, the non-UFO group had a significantly higher misdiagnosis rate than the UFO group (94.74% vs 64.71%, P=0.023); the proportion of fever accompanied by chills in the UFO group was significantly higher than that in the non-UFO group (77.78% vs 22.22%, P=0.000). There was no statistical difference between the two groups in the remaining data (P>0.05). It was concluded that, brucellosis have a high misdiagnosis rate, and patients with non-UFO are more likely to be misdiagnosed as other diseases. Incidents of Brucella infection in the Honghe of Yunnan are sporadic throughout the year, and doctors need to attach great importance to inquiring about epidemiological history and relevant laboratory tests to reduce the missed diagnosis and misdiagnosis rate of the disease.

Elizabethkingia meningoseptica (EM) can cause meningitis, sepsis, lung infection, eye infection, catheter-related bloodstream infection and surgical site infection, and is one of the important pathogens of nosocomial infection. The infection mechanism of EM includes invasion of host cells, production of proteases, biofilms, etc, and EM can produce related virulence factors to damage the immune system. In addition, EM carries multiple drug resistance genes and is resistant to commonly used antibiotics in clinical practice. This article reviews the infection types, clinical features and infection mechanisms of EM to provide a reference for the detection and treatment of EM infection.

Tuberculosis remains a chronic infectious disease that poses a serious risk to human health and the work to control tuberculosis remains very challenging. Host-directed therapy may be a new anti-tuberculosis treatment method worthy of attention and exploration. The purpose of this study was to investigate the regulatory role of GPR84, a member of the G protein-coupled receptors (GPCRs) family, in mycobacterium bovis Bacillus Calmette-Guerin (BCG) infection. In this study, wild-type C57BL/6 mice (WT Group) and Gpr84 gene-deficient mice (Gpr84-/- group) were used as controls to establish a high-dose BCG infection mouse model, the differences in the amount of bacteria in lungs, spleen, liver, kidney and other organs and the severity of lung pathological damage between Gpr84 gene-deficient mice and wild-type mice were evaluated by CFU experiment, lung tissue HE staining and acid-fast staining, the changes of body weight and general condition of mice in the two groups were observed. The results showed that the body weight of Gpr84 gene-deficient mice infected with BCG was significantly lower than that of uninfected mice. The CFU results and antacid staining showed that bacterial load in lung tissues of Gpr84-/- group was higher than that of WT group, and the differences of bacterial load in spleen and liver were consistent with those in lung. HE staining showed that the normal alveolar structure of lung tissues of Gpr84-/- group was significantly more damaged than that of WT group after BCG infection, and the number of lesions was more than that of WT group. Flow cytometric analysis of lung cells of mice showed that in the absence of infection, the knockout of Gpr84 had no significant effect on the number of resident alveolar macrophages (AMs) and interstitial macrophages (IMs) in the lungs, and in acute infection, the proportion of AMs in the lungs of mice in Gpr84-/- group was significantly higher than in WT group, while the proportion of IMs was significantly lower than in WT group, the proportion of mononuclear phagocytes (MNPs) Ly6Chi subpopulation was increased, the number of Ly6Clo subpopulation was decreased, and neutrophils (Neuts) infiltration was increased. The results revealed that the aggravated bacterial load and pathological damage after Gpr84 knockout may be related to the reduction of the relative ratio of IMs/AMs and the increase of the Ly6Chi MNPs subgroup, affecting its transformation to the Ly6Clo subgroup and increasing the infiltration of Neuts. Therefore, Gpr84 has the potential to be one of the candidate targets for host-directed therapy of tuberculosis by regulating immune function.

This paper reports a case of pulmonary infection caused by Corynebacterium striatum in an elderly patient. The patient, male, 93 years old, was treated with piperacillin-tazobactam, imipenem-cilastatin and levofloxacin due to "aspiration pneumonia" 2 months ago. The patient's pulmonary infection was difficult to control, and meropenem was upgraded for anti-infection, but the effect was not good. After empiric antifungal treatment with fluconazole, the pulmonary infection continued to persist and the symptoms worsened. Sputum culture result showed Corynebacterium striatum (++++) with a large diameter inhibitory zone against linezolid. Considering that the above treatment plan was not satisfactory, fluconazole was discontinued and meropenem combined with linezolid was adjusted for anti-infection. After the antibiotic adjustment, the patient's cough and sputum symptoms gradually improved within 10 days. Meropenem was then downgraded to levofloxacin, and levofloxacin was combined with linezolid for further anti-infection. After 2 days of downgraded treatment, the lung infection improved, antibiotics were discontinued, and the lung infection was successfully treated.

Hepatitis B virus (HBV) infection is one of the major global public health problems, with nearly 887,000 deaths from HBV-associated disease each year[1] . Due to the persistence of covalently closed circular DNA (cccDNA) in the nucleus of hepatocytes within the liver, which leads to chronicity of HBV infection and even relapse after treatment, increasing the risk of cirrhosis as well as hepatocellular carcinoma, close attention to cccDNA during treatment plays an important role in monitoring the disease in patients with slow hepatitis B. In contrast, cccDNA testing requires invasive liver puncture to obtain, which is difficult to be widely performed in clinical work.Existing studies Serum HBV RNA can reflect the level of cccDNA in patients, and the following is a review of the progress of the application of serum HBV RNA testing in the treatment of HBV.

The purpose of this paper is to analyze the clinical characteristics of severe pneumonia caused by Whipple's disability infection in children and to improve the understanding and diagnosis of this disease among pediatricians.The clinical data of 2 children with severe Whipple's pneumonia who were admitted to our hospital from 2020 to 2021 were retrospectively analyzed, and relevant domestic and foreign literatures were reviewed.One case (case 1) was a female, 3 years and 5 months old, and the other (case 2) was a male, 5 months old. The clinical manifestations were mainly fever, cough, and shortness of breath, and there was no epidemic medical history. In case 1, the number of leukocytes increased, mainly neutrophils, and in case 2, the number of leukocytes decreased; in 2 cases, C-reactive protein and procalcitonin were both higher than normal values, and lung CT showed different degrees of plaques Shadow, air bronchus sign. In case 1, Staphylococcus aureus (sequence number 202869) and Tropheryma whipple (sequence number 98984) were detected by metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid; Tropheryma whipple (sequence number 30020)and Acinetobacter Baumannii(sequence number 15020) were detected in case 2 by mNGS. Both cases were given ventilator-assisted breathing, and both were given meropenem combined with vancomycin and compound sulfamethoxazole for anti-infective treatment. Both cases improved and were discharged from hospital.The results indicate that severe pneumonia caused by Tropheryma whipple infection in children is rare, and the main clinical manifestations are fever, cough, and shortness of breath, and other pathogenic bacteria can be combined. Early metagenomic next-generation sequencing should be carried out to confirm the diagnosis as soon as possible and targeted anti-infective treatment should be given in time.

In order to understand the T cell immune status of active tuberculosis (ATB) patients，the study compared the expression levels of T cell immune molecules and the proportion of T cell functional subsets between ATB patients and healthy controls (HC). 21 ATB patients and 10 HC were enrolled from December 2020 to May 2021. Peripheral blood samples were collected from the participants, and flow cytometry was performed for surface and intracellular staining to investigate the proportion and functional status of peripheral blood T cells. Fisher's exact probability test and Non- parametric Mann-Whitney U test were used to analyze the data. The result showed that the proportion of Tfh in CD4+ T cells was significantly lower in ATB patients than that in HC, and the proportions of naive T cells, progenitor exhausted T cells in CD8+ T cells were lower in ATB patients compared to HC, while terminal exhausted T cells were higher (P<0.05). The expression of CD62L on CD4+ T cells was significantly lower in the ATB group (P=0.01). The expression of TIM-3 and CD127 on CD8+ T cells as well as T-bet and TCF1 in CD8+ T cells in the ATB group were also significantly lower than those in the HC, while KLRG1, PD1, TIGIT, and CD69 were higher (P<0.05). The conclusion could be drawed that T cells from patients with active tuberculosis exhibit a unique immune phenotype, with decreased pro-inflammatory capacity and increased anti-inflammatory capacity, as well as an exacerbated differentiation towards an exhausted phenotype of CD8+ T cells.

In this study, we constructed a full-length infectious clone of the Tick-borne encephalitis virus (TBEV), providing an essential tool for a deeper understanding of TBEV replication and pathogenesis. Initially, we predicted prokaryotic promoters within the full-length sequence of TBEV and introduced synonymous mutations to these promoters to abrogate their activity, thereby reducing the bacterial toxicity of the cDNA. Subsequently, considering sequence complexity and cloning efficiency, the TBEV cDNA sequence was divided into two segments for synthesis and cloned into the pFK vector using homologous recombination technology. Thereafter, we obtained viral RNA through in vitro transcription and transfected the RNA into cells. Using RT-qPCR with specific primers for the E protein of TBEV, we successfully detected viral RNA replication. Concurrently, Western blot analysis with specific antibodies against the TBEV NS1 protein enabled us to successfully detect the expression of viral proteins. TCID50 assays demonstrated a significant increase in viral titer after 48 hours, confirming the successful rescue of the virus. Finally, through plaque assays, we verified the infectivity of the second-generation virus in BHK-21 cells after 96 hours of observation. The results showed a significant increase in plaque numbers with decreasing dilution of the viral solution, and an increase in relative viral RNA expression and protein expression over time, indicating that the second-generation viral solution possesses infectivity and the ability to replicate within cells. These findings provide new tools and strategies for TBEV research.

Objective：Decreasing pathogen levels on surfaces reduces the potential for exposure and minimizes disease risks. As a result, evaluation of surface disinfectants in different usage scenario matters. Methods：The suspension quantitative bactericidal test was used to examine the germicidal effects on smooth and porous surfaces with different killing time expense for four kinds of disinfectants, including 5% ethanol, 1% hydrogen peroxide and 500 mg/L chlorine-containing disinfectant. Results：The experimental results exhibit that the 1% hydrogen peroxide disinfectant is more efficient for smooth scene and the killing pair value sustained more than 5 among different functioning time (1-5 min). On the other hand, the chlorine-containing disinfectants showed higher kill pair value (≥4) for different pathogens on porous surfaces. Conclusion：In general, chlorine-containing disinfectant presents broader microbicidal spectrum, faster disinfectant efficiency and is more suitable to meet various clinical disinfectant needs. However, it is not friendly to the environment. When choosing a rapid disinfectant, a comprehensive assessment needs to be made based on the degree of environmental harmfulness.

Tuberculous meningitis (TBM) is the most common and severe type of central nervous system tuberculosis. It is associated with high mortality and morbidity, but is difficult to diagnose and treat, posing a serious threat to human health [1][2]. Clinically, high mortality and disability rates are often caused by factors such as atypical TBM symptoms, lack of early rapid, sensitive and specific diagnostic detection technology, misdiagnosis due to co-infection with other pathogens, multidrug-resistant tuberculosis, and anti-tuberculosis drugs being restricted by the blood-brain barrier. This article summarizes a case of tuberculous meningitis diagnosed by COVID-19 screening, aiming to remind clinicians that when treating patients with fever, they should also conduct comprehensive pathogen examinations. At the same time, before more sensitive early diagnostic technology is available, direct acid-fast smear of cerebrospinal fluid is crucial for the early diagnosis of tuberculous meningitis.

To analyze the distribution and drug sensitivity of pathogenic bacteria of bloodstream infections in patients hospitalized in Xinchang County Hospital of Traditional Chinese Medicine to provide a basis for the diagnosis and treatment of clinical bloodstream infections. All blood culture samples from Xinchang County Hospital of Traditional Chinese Medicine were collected from January 2019 to December 2021, and The pathogen species and drug sensitivity in vitro were analyzed statistically. 10,879 blood culture samples were collected, of which 787 were culture-positive (7.23%), mainly from the intensive care unit. The pathogens detected included 760 aerobic (96.57%), 5 anaerobic (0.64%) and 22 fungal (2.80%) strains; the gram-negative bacteria (40.03%) were mainly Escherichia coli, Klebsiella pneumoniae and Aspergillus chimaerae, and the gram-positive bacteria (55.78%) were mainly Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus hominis. Drug sensitivity results showed that Escherichia coli and Klebsiella pneumoniae were more than 80% resistant to ampicillin and more than 80% sensitive to cephalosporins; Staphylococcus epidermidis, Staphylococcus aureus and Staphylococcus hominis were more than 70% resistant to penicillin and more sensitive to antimicrobial drugs such as linezolid and tigecycline (greater than 90%). Blood culture positive samples are mainly from immunocompromised patients' wards, and the pathogenic bacteria are mainly Escherichia coli, Klebsiella pneumoniae, Staphylococcus epidermidis and Staphylococcus aureus which are sensitive to some antibacterial drugs, but with the application of antibiotics in treatment, drug resistance will change, and the clinic should strengthen the detection of pathogenic bacteria and drug susceptibility of bloodstream infections to provide a basis for the diagnosis and treatment of bloodstream infections.