DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.
DNA End-Joining Repair/physiology* ; Gene Editing/methods* ; Mycobacterium/physiology* ; DNA Breaks, Double-Stranded ; Humans

OBJECTIVE To clarify the hearing improvement and tympanic membrane healing of tympanoplasty in patients with chronic suppurative otitis media in the stationary phase with soft tissue shadow of mastoid bulla on mastoid CT,and to compare its hearing improvement and tympanic membrane healing with that of canal wall up mastoidectomy+tympanoplasty.METHODS A retrospective analysis was conducted on clinical data of inpatient surgical cases diagnosed with chronic suppurative otitis media in the stationary phase with soft tissue shadow of mastoid bulla by preoperative mastoid CT at the Department of Otolaryngology Head and Neck Surgery,the First Affiliated Hospital of Nanchang University between September 2020 and April 2022.Patients were divided into two groups based on the surgical procedure:Group A,tympanoplasty,including 23 cases of type Ⅰ tympanoplasty(A1)and 26 cases of type Ⅱ tympanoplasty with ossicular chain reconstruction(A2);Group B,canal wall up mastoidectomy+tympanoplasty,including 21 cases of canal wall up mastoidectomy with type Ⅰ tympanoplasty(B1)and 20 cases of canal wall up mastoidectomy with type Ⅱ tympanoplasty and ossicular chain reconstruction(B2).Each patient was followed up for one year postoperatively,and at approximately one year after the operation,otoscopy and pure-tone audiometry(PTA)and air-bone gap(ABG)measurements at four frequencies(500,1 000,2 000,and 4 000 Hz)were performed and compared to preoperative values.RESULTS The average PTA at 1 year postoperatively for group A(A1 and A2)and group B(B1 and B2)were(36.35±16.21)dB HL[(31.96±11.78)dB HL,(40.24±18.68)dB HL]and(35.85±12.19)dB HL[(40.24±18.68)dB HL,(39.69±13.69)dB HL],respectively.Compared with preoperative PTA,the difference was statistically significant with P<0.05.The average ABG at 1 year postoperatively for group A and group B were(16.07±6.69)dB HL[(15.16±5.48)dB HL,(16.88±7.63)dB HL]and(15.21±6.40)dB HL[(13.93±5.29)dB HL,(16.56±7.28)dB HL],respectively.Compared with preoperative ABG,the difference was statistically significant with P<0.05.There was no statistically significant difference in postoperative average PTA and ABG between group A and group B.There was no statistically significant difference in effective rate between group A and group B.The results of ear endoscopy at 1 year postoperatively showed that the tympanic membrane healed well in both group A and group B.CONCLUSION There is no significant difference in hearing improvement and tympanic membrane healing between the two surgical procedures of tympanoplasty and canal wall up mastoidectomy+tympanoplasty for patients with CSOM at rest with shadowing of the mastoid sinus on mastoid CT.In clinical work,patients with CSOM at rest who have soft tissue shadow in the mastoid sinus on mastoid CT can opt for simple tympanoplasty.

Lung cancer is the malignant tumor with the highest incidence and mortality rates globally. Current treatment methods for lung cancer primarily include surgery， chemotherapy， targeted therapy， and immunotherapy. However， the main limitations of these treatments are their side effects， the drug resistance， and the economic burden they impose. As a critical cancer pathway， the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway regulates tumor occurrence and development through multiple mechanisms by influencing various downstream targets. Consequently， the JAK/STAT signaling pathway offers a promising avenue for lung cancer treatment research. Numerous studies have demonstrated that the JAK/STAT signaling pathway plays a key role in the proliferation and growth of lung cancer cells， angiogenesis， epithelial-mesenchymal transition （EMT）， metabolic alterations， remodeling of the immune microenvironment， and the development of treatment resistance. Traditional Chinese medicine （TCM） has garnered increasing attention due to its minimal side effects， low economic burden， and its potential to enhance efficacy and reduce toxicity when used in conjunction with Western medicine. In addition to traditional Chinese medicine compounds， a growing number of Chinese medicine monomers have come into the spotlight because of their more targeted effects. Numerous studies investigating the regulation of the JAK/STAT signaling pathway by TCM in the treatment of lung cancer have demonstrated that TCM can inhibit the proliferation and invasion of lung cancer cells， tumor angiogenesis， and EMT， improve the inflammatory and immunosuppressive microenvironments， and enhance treatment sensitivity by intervening in the JAK/STAT signaling pathway， thereby impeding the progression of lung cancer. In recent years， the research on the regulation of this pathway by TCM in the treatment of lung cancer has been updated rapidly. However， the summary of these studies has not been updated in time. This review summarizes and reflects on the recent research findings regarding the regulation of the JAK/STAT signaling pathway by TCM to intervene in lung cancer from three aspects， introducing the JAK/STAT pathway， elaborating the mechanism of this pathway in lung cancer， and exploring the intervention of TCM in the treatment of lung cancer through this pathway， to provide more reference for the treatment of lung cancer in the future.

Objective:This study aims to evaluate the clinical utility of total IgE （tIgE） and specific IgE （sIgE） levels in nasal secretions for diagnosing allergic rhinitis. The investigation is enhanced through an improved method of nasal secretion collection and advanced quantum dot immunofluorescence detection technology. Methods:A total of 88 subjects were enrolled in this study, and demographic data and clinical characteristics were collected through standardized questionnaires. Anterior rhinoscope was used to check the local condition of the nasal cavity. Each participant underwent skin prick test（SPT）. The total IgE（tIgE） and sIgE in nasal secretions were quantitatively analyzed by improved nasal secretion collection strategy and quantum dot immunofluorescence method, and the correlation between them and clinical symptoms and signs was discussed. The receiver operating characteristic curve（ROC） was used to calculate the optimum threshold and detection efficiency of total IgE and sIgE in nasal secretions. Results:The improved method successfully collected nasal secretions from all subjects. Based on SPT results, participants were categorized into three groups: normal control （20 cases）, non-allergic rhinitis （22 cases）, and allergic rhinitis （46 cases）. Analysis showed that both tIgE and sIgE levels in nasal secretions correlated with nasal symptoms and signs. A tIgE level of ≥9.42 IU/mL was identified as a cut-off for allergic rhinitis diagnosis, demonstrating an 85.37% agreement with SPT results. Furthermore, cut-off values for house dust mite sIgE （≥0.34 IU/mL） and dermatophagoides Farinae sIgE （≥0.41 IU/mL） yielded a diagnostic agreement of 97.56% with SPT. Notably, two patients in the non-allergic rhinitis group tested negative for SPT but positive for dust mite sIgE in nasal secretions and exhibited positive results in the nasal provocation test, indicating potential local allergic rhinitis. Conclusion:The assessment of tIgE and mite-specific IgE levels in nasal secretions presents a rapid, reliable, and non-invasive approach for diagnosing allergic rhinitis, particularly in cases of local allergic rhinitis.
Humans ; Immunoglobulin E/analysis* ; Quantum Dots ; Male ; Female ; Adult ; Young Adult ; Middle Aged ; Rhinitis, Allergic/immunology* ; Adolescent ; Fluorescent Antibody Technique/methods* ; Case-Control Studies ; Nasal Mucosa/immunology*

OBJECTIVES: To explore the effect of A. muciniphila gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND). METHODS: Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or A.muciniphila gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice. RESULTS: Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of Akkermansia genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. A.muciniphila gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by A.muciniphila gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice. CONCLUSIONS The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced Akkermansia abundance with distinct DGBIs-related indexes, and A. muciniphila gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.
Animals ; Mice, Transgenic ; Gastrointestinal Microbiome ; Mice ; Brain ; HIV Envelope Protein gp120/genetics* ; Akkermansia ; Disease Models, Animal

OBJECTIVES: To develop an E-selectin-targeting nanomedicine delivery system that competitively inhibits E-selectin-neutrophil ligand binding to block neutrophil adhesion to vessels and suppress their recruitment to the lesion sites. METHODS: Doxorubicin hydrochloride (DOX)-loaded liposomes (IEL-Lip/DOX) conjugated with E-selectin-affinity peptide IELLQARC were developed using a post-insertion method. Two formulations [2-1P: Mol(PC): Mol(DPI)=100:1; 2-3P: 100:3] were prepared and their modification density and in vitro release characteristics were determined. Their targeting efficacy was assessed in a cell model of LPS-induced inflammation, a mouse model of acute lung injury (ALI), a rat femoral artery model of physical injury-induced inflammation, and a zebrafish model of local inflammation. RESULTS: The prepared IEL-Lip/DOX 2-1P and 2-3P had peptide modification densities of 4.76 and 7.57 pmoL/cm², respectively. Compared with unmodified liposomes, IEL-Lip/DOX exhibited significantly reduced 48-h cumulative release rates at pH 5.5. In the inflammation cell model, IEL-Lip/DOX showed increased uptake by activated inflammatory endothelial cells, and 2-1P exhibited a higher trans-endothelial ability. In ALI mice, the fluorescence intensity of IEL-Lip/Cy5.5 increased significantly in lung tissues by 53.71% [Z-(2-1P)] and 93.41% [Z-(2-3P)], and 2-1P had an increased distribution by 24.19% in the inflammatory lung tissue compared to normal mouse lung tissue. In rat femoral artery models, 2-1P had greater injured/normal vessel fluorescence intensity contrast. In the zebrafish models, both 2-1P and 2-3P showed increased aggregation at the site of inflammation. CONCLUSIONS This E-selectin-targeting nanomedicine delivery system efficiently targets activated inflammatory endothelial cells to increase drug concentration at the inflammatory site, which sheds light on new strategies for treating neutrophil-mediated inflammatory diseases and practicing the concept of "one drug for multiple diseases".
Animals ; Liposomes ; Rats ; Nanomedicine ; E-Selectin ; Drug Delivery Systems ; Inflammation/drug therapy* ; Mice ; Doxorubicin/analogs & derivatives* ; Zebrafish ; Acute Lung Injury/drug therapy*

Objective:To investigate the recognition of the post competency index system among rural general practice assistant physicians and its influencing factors.Methods:This study was a cross-sectional survey. A questionnaire survey on the recognition of post competency index system was conducted from October 2020 to September 2021 among rural general practice assistant physicians from 10 provinces/municipalities selected by stratified cluster sampling method. The recognition of rural general practice assistant physicians at all levels of indexs and the factors influencing recognition were analyzed.Results:A total of 1 123 questionnaires were distributed and 1 024 valid ones were collected with a recovery rate of 91.18%. Of the 1 024 respondents, 529 were male(51.7%) and 435 were aged 40-49 years(42.5%), which was the highest proportion by age group. The average overall recognition score of the index system was 4.41, and the scores of the primary indexes were 4.32-4.45. Three primary indexes had the highest recognition scores: professional competence, basic health care services, and interpersonal communication and teamwork. The recognition scores on the second level index were 4.18-4.61, and the proportion of recognition scores greater than 4 was over 80%. There were significant differences in the recognition scores of the index system among assistant physicians with different working years, educational background, professional title and work unit ( F/H=6.41, 14.83, 12.45, 7.53, P<0.01). Educational background(associate degree: B=0.091, P=0.015; bachelor degree and above: B=0.196, P<0.001) and professional title(intermediate professional title and above: B=-0.234, P<0.001) were the independent factors influencing the recognition degree of the index system for rural general practice assistant physicians. Conclusions:The post competency index system is generally recognized by rural general practice assistant physician, and academic qualifications and professional title status may influence its recognition.

Objective:To evaluate the application feasibility of the post competency index system of rural general practice assistant physicians, and to analyze and compare the post competency of rural general practice assistant physicians with different characteristics through a survey among rural general practice assistant physicians in China.Methods:This study was a cross-sectional study. A questionnaire survey was conducted among rural general practice assistant physicians in 10 provinces/municipalities selected by stratified cluster sampling method from October 2020 to September 2021. The post competency scores were self-evaluated based on the post competency index system of rural general practice assistant physicians. The results of the survey were analyzed and the application feasibility of the index system was evaluated.Results:A total of 1 123 questionnaires were distributed and 1 024 valid questionnaires were returned with a recovery rate of 91.2%. Of the 1 024 respondents, 529 were males (51.7%), 435 were aged 40-49 years (42.5%), 434 had a secondary school education or less (42.4%), and 531 were junior practitioners (51.9%). The Cronbach′s α coefficient of the overall questionnaire was 0.987, and the Cronbach′s α coefficient of the first level index ranged from 0.897 to 0.974. The cumulative variance contribution rate of exploratory factor analysis was 72.012%. The confirmatory factor analysis showed χ2/ df=3.926, RMSEA=0.076, CFI=0.858, IFI=0.859, indicating that the model fit was basically good. The average self-evaluation scores of the first level index ranged from 3.95 to 4.25, and the average self-evaluation scores of the second level index ranged from 3.74 to 4.36. There were significant differences in self-evaluation scores of post competency among rural general practice assistant physicians with different working years, professional titles, working units and economic regions( F=4.67, 10.54, 22.16 and 20.90,all P<0.05). People with low self-evaluation scores of post competency had the following characteristics: working 10-19 years, intermediate or above titles, working in community health service centers, located in the eastern region.People with high self-evaluation scores of post competency had the following characteristics: primary professional title, working in the village clinic. Conclusion:The competency index system of rural general practice assistant physicians has good application feasibility,and it can be used to evaluate post competency for the education and training of rural general practice assistant physicians.

Atherosclerosis(AS)is a common cardiovascular disease,and its treatment and prevention have been the focus of medical research.AS an emerging technology,nanotechnology has unique advantages and plays an important role in the prevention,diagnosis and treatment of AS.This paper reviews the latest research on the application of nanotechnology in AS diseases,systematically discusses the role of nanotechnology in the diag-nosis and treatment of AS,and comprehensively analyzes the effects of nano-drug carriers based on different sur-face trimmers,loading diagnostic and therapeutic drugs so as to monitordisease progression of AS and its targeted treatment.The aim is to provide new thought for the clinical treatment of AS.