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.

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: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 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.

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.

Objective:To investigate the effect of nuclear factor E2-related factor 2 (Nrf2) on the cellular tight junction protein Claudin-18 in endotoxin-induced acute lung injury (ALI).Methods:Eighteen healthy male C57BL/6 mice were divided into control group, endotoxin-induced ALI model group (ALI group) and Nrf2 activator tert-butylhydroquinone (tBHQ) pretreatment group (tBHQ+ALI group) according to random number table method, with 6 mice in each group. Mice endotoxin-induced ALI model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 15 mg/kg), and the mice in the control group was injected with an equal amount of phosphate buffer solution (PBS). The mice in the tBHQ+ALI group received three intraperitoneal injections of tBHQ (a total of 50 mg/kg) at an interval of 1 hour before molding. The last injection of tBHQ was accompanied by LPS of 15 mg/kg. The mice in the control group and model group were given equal amounts of PBS, and PBS or LPS was given at the last injection. The mice were sacrificed at 12 hours after LPS injection to take lung tissues. After the lung tissue was stained with hematoxylin-eosin (HE) staining, the pathological changes were observed under light microscopy, and the lung injury score was calculated. The lung wet/dry ratio (W/D) was determined. Nrf2 protein expression in the lung tissue was detected by Western blotting. Positive expression of Claudin-18 in the lung tissue was determined by immunohistochemistry.Results:The lung tissue showed normal structure, without significant pathological change in the control group. Compared with the control group, the alveolar septum widened accompanied by inflammatory cell infiltration, capillary hyperemia and tissue edema in the ALI group, the lung injury score and lung W/D ratio were significantly increased (lung injury score: 6.50±1.05 vs. 1.83±0.75, lung W/D ratio: 3.79±0.22 vs. 3.20±0.14, both P < 0.01), and the Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly lowered [Nrf2 protein (Nrf2/β-actin): 0.41±0.33 vs. 1.22±0.33, Claudin-18 ( A value): 0.28±0.07 vs. 0.44±0.10, both P < 0.05]. After tBHQ pretreatment, the degree of lung histopathological injury was significantly reduced compared with the ALI group, the alveolar space slightly abnormal, inflammatory cell infiltration and tissue edema reduced, the lung injury score and lung W/D ratio were significantly decreased (lung injury score: 3.00±0.89 vs. 6.50±1.05, lung W/D ratio: 3.28±0.19 vs. 3.79±0.22, both P < 0.01), and Nrf2 protein expression and Claudin-18 positive expression in the lung tissue were significantly increased [Nrf2 protein (Nrf2/β-actin): 1.26±0.09 vs. 0.41±0.33, Claudin-18 ( A valure): 0.45±0.04 vs. 0.28±0.07, both P < 0.05]. Conclusion:Nrf2 alleviated pulmonary edema and improved endotoxin-induced ALI by up-regulating Claudin-18 expression.

In this report,we described a case of a clinical practice,in which the clinical pharmacists was involved in the treatment of a soft tissue sarcoma patient,who was diagnosed with mental disorders induced by regorafenib.The patient was complicated with hypoproteinemia,hepatic insufficiency,leukoencephalopathy and other diseases.Before the treatment,the patient's mental was normal.After continuous administration of regorafenib(40 mg,po,qd)for 5 days,the patient has a sudden loss of consciousness.Clinical pharmacists excluded the possibility of mental disorders caused by tumor brain metastases,exacerbation of leucoencephalopathy or hepatic encephalopathy and the drugs used together.They determined that mental disorders were likely to be related to the use of regorafenib through the association evaluation of adverse reactions.It was considered to be an adverse reaction induced by regorafenib.Therefore,regorafenib treatment was temporarily suspended and symptomatic treatment was given.After 5 days,the patient's mental state improved.In addition,clinical pharmacists monitored the patient for symptomatic treatment,and provided appropriate antitumor drug treatment recommendations based on evidence-based evidence.This case suggests that the clinical use of regorafenib should be vigilant against mental disorders adverse reactions,do a good job of pharmaceutical care,and timely drug analysis and symptomatic treatment after adverse reactions.