Dry eye disease(DED)is a common ocular surface disorder worldwide, primarily characterized by a loss of homeostasis of the tear film, and frequently associated with meibomian gland dysfunction(MGD), decreased tear film stability, ocular discomfort, and visual impairment. In recent years, factors such as the widespread use of digital devices,the aging population, and environmental changes have contributed to a significant increase in its global prevalence, making it a major public health concern. Red light therapy(RLT), also known as low-level laser therapy(LLLT)or photobiomodulation(PBM), is a non-invasive treatment that utilizes low-energy red or near-infrared light to irradiate tissues. It exerts photobiomodulatory effects to promote cellular repair and functional recovery. This therapy has demonstrated considerable potential in treating various ocular conditions. Its broader clinical application could improve therapeutic outcomes, alleviate patient discomfort and financial burden, and reduce the consumption of healthcare resources, thereby yielding significant socio-economic benefits. This paper systematically reviews the multifaceted mechanisms and application prospects of RLT in managing DED, including its anti-inflammatory effects, improvement of meibomian gland function, promotion of conjunctival goblet cell repair, and alleviation of visual fatigue, aiming to provide a theoretical foundation and practical reference for its clinical adoption.

OBJECTIVE To observe the expressions of micro ribonucleic acid-129-5p(miR-129-5p),interleukin-6(IL-6)/signal transducer and activator of transcription 3 gene(STAT3)/helper T cell 17(Th17)signaling path-ways in peripheral blood of the sepsis children complicated with pulmonary infection and analyze the clinical signif-icance.METHODS A total of 123 sepsis children who were complicated with pulmonary infection and were treated in the 971st Hospital of the Navy of The Chinese People's Liberation Army,the 904 Hospital of the Joint Logis-tics Support Force of the People's Liberation Army and Qingdao Women's and Children's Hospital from Jan.2020 to Dec.2023 were assigned as the sepsis complicated with pulmonary infection group,meanwhile,55 sepsis children who were not complicated with pulmonary infection were chosen as the simple sepsis group.The expres-sion levels of miR-129-5p,IL-6 mRNA,STAT3 mRNA and Th17 mRNA in peripheral blood mononuclear cells(PBMCs)were statistically analyzed.Receiver operating characteristics(ROC)curves were drawn to analyze the efficiencies of miR-129-5p and IL-6/STAT3/Th17 pathways in prediction of poor prognosis of the sepsis children with pulmonary infection.RESULTS The miR-129-5p level of the sepsis complicated with pulmonary infection group was lower than that of the simple sepsis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the sepsis complicated with pulmonary infection group were higher than those of the simple sepsis group(all P＜0.05).With the aggravation of illness condition,the miR-129-5p level was reduced,and the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA were elevated(all P＜0.05).The miR-129-5p level of the poor prog-nosis group was lower than that of the favorable prognosis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the poor prognosis group was higher than those of the favorable prognosis group(all P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of miR-129-5p was the largest(0.887)in prediction of the poor prognosis of the sepsis children complicated with pulmonary infection(P＜0.05).CONCLUSION The sepsis children complicated with pulmonary infection show the decline of expression level of peripheral blood miR-129-5p and enhancement of activation degree of IL-6/STAT3/Th17 pathways,which can be used as the indexes for assessment of illness condition and as auxiliary indexes for assessment of prognosis.

Objective: To explore the regulatory effects of ginkgo biloba extract on airway inflammatory injury and Toll⁃like receptor 4(TLR4)/nucleotide⁃binding oligomerization domain⁃containing 3(NLRP3) pathway in rats with vided into four groups : the normal control group , Methods: Thirty⁃six male SD rats were selected and randomly divided into four groups : the normal control group , the model group , the prednisone treatment group , and the ginkgo biloba extract treatment group , with 9 rats in each group. Except for the normal control group , the COPD rat mod⁃els in the other groups was constructed by intratracheal instillation of lipopolysaccharide (LPS) combined with ciga⁃rette smoke exposure. After successful modeling , the rats were continuously administered drugs for 12 weeks , fol⁃lowed by sampling. The general conditions and respiratory symptoms of the rats were observed. The pathological changes of lung tissues were observed by hematoxylin⁃eosin (HE) staining technique ; the mRNA and protein ex⁃pression levels of TLR4 , tumor necrosis factor⁃α (TNF⁃α ) , interleukin⁃1β (IL⁃1β) and NLRP3 in rat lung tissueswere detected by real⁃time quantitative polymerase chain reaction (RT⁃qPCR) and Western blot. Results: Com⁃pared with the normal control group , the lung tissues of rats in the model group were significantly damaged , and the protein and mRNA expression of TLR4 , TNF⁃α , IL⁃1β , and NLRP3 increased ( P < 0. 05 ) . Compared with the model group , lung tissue damage was reduced in the prednisone group and the ginkgo biloba extract group , and TLR4 , TNF⁃α , IL⁃1β , NLRP3 protein and mRNA expression decreased (P < 0. 05) . Conclusion Ginkgo biloba airway inflammatory response by inhibiting the TLR4/NLRP3 signaling pathway.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

OBJECTIVE To observe the expressions of micro ribonucleic acid-129-5p(miR-129-5p),interleukin-6(IL-6)/signal transducer and activator of transcription 3 gene(STAT3)/helper T cell 17(Th17)signaling path-ways in peripheral blood of the sepsis children complicated with pulmonary infection and analyze the clinical signif-icance.METHODS A total of 123 sepsis children who were complicated with pulmonary infection and were treated in the 971st Hospital of the Navy of The Chinese People's Liberation Army,the 904 Hospital of the Joint Logis-tics Support Force of the People's Liberation Army and Qingdao Women's and Children's Hospital from Jan.2020 to Dec.2023 were assigned as the sepsis complicated with pulmonary infection group,meanwhile,55 sepsis children who were not complicated with pulmonary infection were chosen as the simple sepsis group.The expres-sion levels of miR-129-5p,IL-6 mRNA,STAT3 mRNA and Th17 mRNA in peripheral blood mononuclear cells(PBMCs)were statistically analyzed.Receiver operating characteristics(ROC)curves were drawn to analyze the efficiencies of miR-129-5p and IL-6/STAT3/Th17 pathways in prediction of poor prognosis of the sepsis children with pulmonary infection.RESULTS The miR-129-5p level of the sepsis complicated with pulmonary infection group was lower than that of the simple sepsis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the sepsis complicated with pulmonary infection group were higher than those of the simple sepsis group(all P＜0.05).With the aggravation of illness condition,the miR-129-5p level was reduced,and the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA were elevated(all P＜0.05).The miR-129-5p level of the poor prog-nosis group was lower than that of the favorable prognosis group,while the levels of IL-6 mRNA,STAT3 mRNA and Th17 mRNA of the poor prognosis group was higher than those of the favorable prognosis group(all P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of miR-129-5p was the largest(0.887)in prediction of the poor prognosis of the sepsis children complicated with pulmonary infection(P＜0.05).CONCLUSION The sepsis children complicated with pulmonary infection show the decline of expression level of peripheral blood miR-129-5p and enhancement of activation degree of IL-6/STAT3/Th17 pathways,which can be used as the indexes for assessment of illness condition and as auxiliary indexes for assessment of prognosis.

Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure(CHF).METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery.Modeled rats were divided into model group,Qiangxin decoction low-dose and high-dose groups(12.25,24.50 g/kg,calculated by crude drug),and chemical medicine group(Sacubitril valsartan sodium tablets,10.42 mg/kg),with 10 rats in each group;control group was set up without treatment.Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days.After the last medication,the contents of N-terminal pro-brain natriuretic peptide(NT-proBNP)and adenosine triphosphate(ATP)in serum and phosphatidic acid(PA)and cardiolipin(CL)in myocardial tissue were all detected;the pathological damage and collagen fibrosis of rat myocardial tissue were observed;the apoptosis of myocardial cells was determined;the ultrastructure of myocardial tissue was observed;the protein expressions of mitofusin 1(Mfn1),Mfn2,optic atrophy protein 1(OPA1)and dynamin-related protein 1(Drp1)were all detected in myocardial tissue.RESULTS Compared with control group,the serum content of NT-proBNP,apoptotic rate of myocardial cells,and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly;serum content of ATP,contents of PA and CL,and relative expressions of Mfn1,Mfn2 and L-OPA1 proteins were all significantly reduced(P＜0.05).There were abnormal membrane tissue structure in various layers of myocardial tissue,degeneration and necrosis of myocardial cells,and severe fibrosis;the mitochondria were swollen,with reduced or absent cristae,and uneven matrix density.After intervention with Qiangxin decoction,the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats(excluding CL content in the Qiangxin decoction low-dose group)were significantly reversed(P＜0.05);the pathological damage of myocardial tissue had significantly improved,fibrosis had significantly reduced,mitochondrial morphology tended to be normal,cristae had increased,and matrix density was uniform.CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats,thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis,the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)pre-sents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2％dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2％ DSS-induced Rag1-/-mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage indepen-dently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned me-dium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Objective:To investigate the clinical efficacy and safety of amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension.Methods:A total of 280 patients with primary hypertension who were treated at Shougang Shuigang Hospital between June 2022 and June 2023 were selected as study subjects. A clinical case-control study was conducted, and the RAND function method was utilized to randomly allocate the subjects into four groups, each receiving a different treatment: amlodipine besylate group (Group A, n = 70), benazepril hydrochloride group (Group B, n = 70), compound formulation amlodipine besylate and benazepril hydrochloride tablets group (Group C, n = 71), and amlodipine besylate plus benazepril hydrochloride group (Group D, n = 69). Relevant therapeutic indicators (blood pressure compliance rate, changes in blood pressure values) and safety indicators (adverse reactions, medication adherence) were observed. Results:The blood pressure compliance rates of Group C and Group D were 91.5% (65/71) and 89.9% (62/69), respectively. There was no statistically significant difference between the two groups ( χ2 = 1.24, P = 0.143), but both were higher than the rates of 77.1% (54/70) and 74.3% (52/70) in Group A and Group B, respectively ( χ2 = 5.68, 4.86, P = 0.004, 0.012). Before treatment, there was no statistically significant difference in systolic and diastolic blood pressure among the four groups of patients (all P > 0.05). After treatment, there was a statistically significant decrease in both systolic and diastolic blood pressure among the four groups compared with their pre-treatment levels (all P < 0.05). Specifically, Group C and Group D exhibited significant reductions in blood pressure following treatment ( t = 4.35, 5.12, 7.25, 5.86, all P < 0.05). Meanwhile, there was no statistically significant difference in systolic blood pressure between Group C and Group D after treatment ( P > 0.05), while diastolic blood pressure was lower in Group C than Group D after treatment ( t = 6.01, P < 0.05). There was a significant downward trend observed in total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels (all P < 0.05). Notably, Group B and Group D reported higher incidences of dry cough, with 15 and 10 cases, respectively, compared with Group A and Group C, which had 1 and 3 cases, respectively. These differences were statistically significant ( χ2 = 4.25, 5.04, both P < 0.05). Furthermore, the treatment compliance rates for Group A, Group B, and Group C were 72.9% (51/70), 71.4% (50/70), and 74.6% (53/71), respectively, all exceeding the 46.4% (32/69) compliance rate of Group D. These differences were also statistically significant ( χ2 = 4.68, 5.24, 4.98, all P < 0.05). Conclusion:The clinical efficacy and safety of the compound formulation amlodipine besylate and benazepril hydrochloride tablets (II) in the treatment of primary hypertension are superior to those of single tablets and combination therapy.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.