Objective: To investigate the regulatory role of miR-6824-3p in macrophage function and its molecular mechanism in inhibiting hepatitis B virus (HBV) replication, thereby providing experimental evidence to elucidate the immune regulatory mechanisms underlying persistent HBV infection. Methods: miR-6824-3p mimic and inhibitor were transfected into human THP-1-induced macrophages. Real-time quantitative PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), neutral red uptake, reactive oxygen species (ROS) production, and fluorescent latex particle phagocytosis assays were employed to evaluate the effects of miR-6824-3p on macrophage phenotype and function. Through a combination of bioinformatics analysis, dual luciferase reporter assays, western blot, and siRNA interference techniques, we identified the target gene of miR-6824-3p and examined their effects on downstream signaling pathways. qRT-PCR and western blot analyses were performed to assess the impact of miR-6824-3p-regulated macrophages on HBV DNA, pgRNA, cccDNA, and HBV-associated antigen levels in HepAD38 cells. Key effector molecules were identified through neutralization assays. Results: miR-6824-3p mimic significantly promoted the expression and secretion of proinflammatory factors, such as TNF-α and IL-1β, in macrophages (P<0.001), while concurrently reducing ROS production and phagocytosis (P<0.05). Furthermore, miR-6824-3p downregulated NRAS expression in macrophages, which was accompanied by a reduction in MAPK signalling path-way activity (p-MEK, p-ERK). Compared to the control group, the medium of macrophages with overexpressed miR-6824-3p inhibited the expression of HBV DNA, pgRNA, cccDNA, and HBV-associated antigens HBsAg, HBeAg, and HBcAg in HepAD38 cells (P<0.01). Similar results were also observed in the co-culture system of macrophages with HepAD38 cells. The addition of TNF-α neutralizing antibodies markedly attenuated the aforementioned antiviral effects (P<0.001). Conclusion: miR-6824-3p targets NRAS to affect the downstream MAPK signaling pathway, regulating the immune function of macrophages. The TNF-α induced by miR-6824-3p is one of the key molecules that suppress HBV replication. This study provides evidence for further elucidating the molecular mechanisms by which miRNAs influence HBV replication via modulating the host immune microenvironment.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

In recent years, the incidence of dry eye disease(DED)is increasing, positioning it as one of the most prevalent diseases affecting the ocular surface. Inflammatory response is the pathological basis of DED, involving various inflammatory mediators and inflammatory signaling pathways. Consequently, anti-inflammatory treatment emerges as a fundamental strategy for preventing and managing DED. This review summarizes the classic inflammatory factors involved in the development and progression of DED, including interleukins, tumor necrosis factor, matrix metalloproteinases, chemokines, and cell adhesion molecules. It also discusses the relevant inflammatory signaling pathways: the MAPKs pathway, NF-κB pathway, Wnt pathway and TLR pathway. Additionally, this review addresses the mechanisms of action and alterations in relevant biomarkers associated with current first-line recommended anti-inflammatory therapies, including corticosteroids, immunosuppressants, nonsteroidal anti-inflammatory drugs, and traditional Chinese medicine approaches to inflammation management. This comprehensive overview aims to enhance understanding of the inflammatory mechanisms underlying DED while exploring future therapeutic prospects.

OBJECTIVE To develop the quality evaluation standard indicator system for hospital cough and wheeze pharmaceutical care clinic （CWPC） pharmacist training within the layered learning practice model （LLPM）， and apply it in clinical practice. METHODS Our teaching team established an LLPM model to train cough and wheeze pharmacists， according to the actual conditions of our college. Using qualitative interview methods， expert questionnaires were compiled with literature research； the expert correspondence methods were employed to conduct two rounds of consultation with 10 domestic respiratory medicine experts， thus constructing an evaluation index system for the teaching quality of cough and wheeze pharmacists. The experts’ positive coefficient， authority coefficient， Kendall’s harmony coefficient， and the degree of concentration of opinions were calculated. The analytic hierarchy process （AHP） was used to determine the weight of each indicator within the index system. From June 2023 to June 2024， the teaching team enrolled 21 pharmacists in the training program. The teaching team assessed and scored the trial group （LLPM） and control group （traditional teaching model） based on the benefit indicators for pharmacists and patients in the evaluation index system， and compared the results. RESULTS This study explored the establishment of a training system for cough and wheeze pharmacists under the LLPM model， and initially established an evaluation index system using the Delphi method. In two rounds of Delphi method questionnaires， the recovery rate was 100%， with an authority coefficient exceeding 0.8， Kendall’s harmony coefficient ranging from 0.235 to 0.459， and all P-values being less than 0.05. Four primary （comprising trainee feedback， learning gains， behavioral improvements， and training performance）， 12 secondary and 33 tertiary indicators were finalized. In the empirical evaluation， the results of the two groups showed a significant benefit to the pharmacists in the trial group. Specifically， the percentage of patients receiving corticosteroids for COPD or wheeze service patients per month （80.5%）， an average increase in the number of cough and wheeze team service outpatient visits per month （compared to the same period of the previous year） of 14.8 visits per month， and the patient satisfaction score （4.9） were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS The application of the LLPM in competency training for pharmacists specializing in cough and wheeze care yields multiple benefits and holds significant guiding value. The constructed training quality evaluation index system under this model is scientific and reliable.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative. Isovalerylspiramycin I (ISP I) as a major component of carrimycin applied to upper respiratory infections, was first found to possess anti-fibrotic potential. The present study aims to evaluate the functions and mechanisms of ISP I in protecting against liver fibrosis. According to our results, ISP I not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation (BDL) rats and carbon tetrachloride (CCl₄) mice. We proved that nucleotide-binding protein 2 (NUBP2) was the direct target of ISP I. ISP I through targeting NUBP2, increased the amount of vascular non-inflammatory molecule-1 (VNN1) on the cell membrane, which will inhibit oxidative stress and fibrosis. Simultaneously, the original carrimycin's protective effect on liver damage and fibrosis was verified. Therefore, our study provides potential agents for patients with liver fibrosis-related diseases, and the clear mechanism supports wide application in the clinic.

Objective:To summarize the clinical features and genetic effects of cases of fetal chromosomal structural abnormalities caused by maternal complex chromosomal rearrangements (CCR).Methods:Three female CCR carriers referred to the Prenatal Diagnostic Center at Guangzhou Women and Children's Medical Center, Guangzhou Medical University between October 2023 and June 2024 were retrospectively enrolled. Genetic analyses included chromosomal karyotyping, chromosomal microarray analysis (CMA), and low-coverage whole-genome copy number variation (CNV) sequencing. Clinical features of the three cases with fetal chromosomal structural abnormalities caused by maternal CCR were systematically reviewed using descriptive statistics.Results:(1) Case 1: CNV sequencing identified an 11.95 Mb duplication at 1q43q44 region of chromosome (CNV of uncertain significance) and a 36.09 Mb deletion at 5p15.33p13.2 region of chromosome (pathogenic CNV) in the fetus (maternally inherited). Maternal karyotype was 46,XX,t(1;8;3;5)(q43;q22.1;q26.2;p13.2). The pregnancy was terminated after genetic counseling. (2) Case 2: Maternal karyotype 46,XX,t(3;20)(p25;q13.1),t(6;12)(q25.2;q21.2),ins(11;14)(q23;q24q13) was transmitted to the fetus [46,XX,ins(11;14)(q23;q24q13)mat]. CMA of the fetus showed no abnormalities and the pregnancy was continued after genetic counseling. (3) Case 3: CMA of the products of conception revealed a 71.59 Mb duplication at 2p24.3p11.2 (pathogenic CNV). Maternal karyotype was 46,XX,der(2)t(2;3)(q21;q23)ins(11;2)(p13;p24p11.2),der(3)t(2;3),der(11)ins(11;2). The abnormal chromosome 2 segment in products of conception was maternally inherited.Conclusions:All three cases of fetal/abortus chromosomal abnormalities originated from maternal CCR. Early combined cytogenetic and molecular prenatal diagnosis is critical for CCR carriers during pregnancy.

Objective:To evaluate the current situation of the protective effect of hearing protection device (HPD) worn by manufacturing workers and discuss their possible influencing factors.Methods:A total of 3634 noisy workers were surveyed and tested. The study conducted surveys of workers on the use of HPD. The 3M TM E-A-R Fit TM binaural verification system was used to measure the personal attenuation device (PAR) of workers wearing HPD. Results:The M ( Q1, Q3) of baseline PAR obtained by 3634 workers was 12 (2, 19) dB. There was a statistically significant difference in baseline PAR among the three types of HPDs ( H=336.39, P<0.01) . After pairwise comparison, it was found that the baseline PAR of workers wearing foam earplugs and earmuffs was higher than that of pre-molded earplugs ( P<0.01) . There were differences in baseline PAR among workers in different industries ( Z=359.73, P<0.01) . Education level, age of using HPD, types of HPDs, noise exposure intensity, with or without knowledge of correct methods, and comfort evaluation were the main factors affecting baseline PAR ( P<0.05) . There were 1536 workers (43.4%) failed the baseline PAR test. After the intervention, the median PAR increased significantly from 1 (0, 6) dB (baseline) to 18 (14, 22) dB (after the intervention) ( P<0.01) . The follow-up test found that the follow-up PAR of 328 workers was higher than the baseline PAR of the initial test, and the follow-up PAR was higher than the post-intervention PAR of the initial test ( P<0.01) . Conclusion:Under the conditions of this study, the protective effect of HPD was affected by factors such as incorrect understanding of wearing methods, exposure to high-intensity noise, low education level, a short period of time of HPD use and low comfort of hearing protectors. The protective effect could be improved through training, optimizing the wearing of hearing protector models, and follow-up interventions. Enterprises should use suitability verification to ensure the correct selection and wearing of noisy workers.

Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.

Liver fibrosis is a vital cause of morbidity in patients with liver diseases and developing novel anti-fibrotic drugs is imperative.Isovalerylspiramycin Ⅰ(ISP Ⅰ)as a major component of carrimycin applied to upper respiratory infections,was first found to possess anti-fibrotic potential.The present study aims to evaluate the functions and mechanisms of ISP Ⅰ in protecting against liver fibrosis.According to our results,ISP Ⅰ not only reduced the expressions of fibrogenic markers in LX-2 cells but also appeared great protective effects on liver injury and liver fibrosis in bile duct ligation(BDL)rats and carbon tetrachloride(CCl4)mice.We proved that nucleotide-binding protein 2(NUBP2)was the direct target of ISP Ⅰ.ISP Ⅰ through targeting NUBP2,increased the amount of vascular non-inflammatory molecule-1(VNN1)on the cell membrane,which will inhibit oxidative stress and fibrosis.Simultaneously,the original carri-mycin's protective effect on liver damage and fibrosis was verified.Therefore,our study provides po-tential agents for patients with liver fibrosis-related diseases,and the clear mechanism supports wide application in the clinic.

Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.