Fungal keratitis represents a significant cause of blindness, with current therapeutic approaches yielding limited success. The disease's onset and progression are primarily driven by fungal virulence factors and the host's immune response. The innate immune system is the first to respond, with neutrophils playing a pivotal role in the antifungal defense. Although neutrophils are critical for pathogen clearance, their excessive or abnormal activation can lead to tissue damage, exacerbating the disease. Thus, elucidating the mechanisms underlying neutrophil activity in fungal keratitis is crucial for refining treatment strategies. This article aims to systematically review the principal antimicrobial mechanisms employed by neutrophils, including phagocytosis, degranulation, and the formation of neutrophil extracellular traps(NETs). Furthermore, it explores the crosstalk between neutrophils and macrophages, alongside their collective impact and underlying mechanisms in the context of fungal keratitis. Exploration of the mechanisms of fungal keratitis facilitates precise intervention and enhances the efficacy of treatment.

AIM:To explore the relationship be-tween the level of myeloid-derived suppressor cell(MDSC)infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC).METHODS:A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024.Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration,dividing the patients into high-in-filtration group(MDSC≥2)and low-infiltration group(MDSC＜2).The objective response rate(iORR),disease control rate(iDCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves,and Cox regression analysis was applied to identify factors influencing prognosis.RESULTS:Among the 92 patients,53 were in the low MDSC infiltration group,and 39 were in the high MDSC infiltration group.The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group.The objective response rate(iORR)was 77.3％in the low MDSC infiltration group,higher than the 56.4％in the high MDSC in-filtration group(P=0.033).The disease control rate(iDCR)was 94.3％,also significantly higher than the 66.7％in the high MDSC infiltration group(P=0.001).Moreover,the median progression-free sur-vival(PFS)and overall survival(OS)in the low MD-SC infiltration group were 16.9 months and 27.6 months,respectively,which were significantly lon-ger than those in the high MDSC infiltration group(PFS 12.6 months,OS 22.3 months).Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group.Cox univariate analysis showed that smoking,PD-L1 ex-pression levels,tumor stage,and MDSC infiltration level were closely associated with PFS and OS.Mul-tivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS(HR=2.678,P=0.013)and OS(HR=2.254,P=0.022).CONCLUSION:The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor com-bined with chemotherapy in NSCLC patients.High MDSC infiltration suggests reduced treatment sen-sitivity and poor prognosis.MDSC infiltration level may serve as a predictive biomarker for the effica-cy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

AIM:To explore the relationship be-tween the level of myeloid-derived suppressor cell(MDSC)infiltration in tumor tissues and the clinical efficacy and prognosis of combined PD-1 inhibitor and chemotherapy in the treatment of advanced non-small cell lung cancer(NSCLC).METHODS:A retrospective analysis was conducted on 92 NSCLC patients who received PD-1 inhibitor combined with chemotherapy at the First Affiliated Hospital of Anhui Medical University from June 2019 to June 2024.Tumor tissue samples were examined using immunohistochemistry to detect the level of MDSC infiltration,dividing the patients into high-in-filtration group(MDSC≥2)and low-infiltration group(MDSC＜2).The objective response rate(iORR),disease control rate(iDCR),progression-free survival(PFS),and overall survival(OS)were compared between the two groups.Kaplan-Meier survival analysis and Log-rank test were used to plot PFS and OS survival curves,and Cox regression analysis was applied to identify factors influencing prognosis.RESULTS:Among the 92 patients,53 were in the low MDSC infiltration group,and 39 were in the high MDSC infiltration group.The low MDSC infiltration group showed significantly better treatment responses compared to the high MDSC infiltration group.The objective response rate(iORR)was 77.3％in the low MDSC infiltration group,higher than the 56.4％in the high MDSC in-filtration group(P=0.033).The disease control rate(iDCR)was 94.3％,also significantly higher than the 66.7％in the high MDSC infiltration group(P=0.001).Moreover,the median progression-free sur-vival(PFS)and overall survival(OS)in the low MD-SC infiltration group were 16.9 months and 27.6 months,respectively,which were significantly lon-ger than those in the high MDSC infiltration group(PFS 12.6 months,OS 22.3 months).Kaplan-Meier analysis revealed that both PFS and OS in the low MDSC infiltration group were significantly longer than those in the high MDSC infiltration group.Cox univariate analysis showed that smoking,PD-L1 ex-pression levels,tumor stage,and MDSC infiltration level were closely associated with PFS and OS.Mul-tivariate Cox regression analysis further indicated that high MDSC infiltration was an independent risk factor for both PFS(HR=2.678,P=0.013)and OS(HR=2.254,P=0.022).CONCLUSION:The level of MDSC infiltration in tumor tissues is closely related to the efficacy and prognosis of PD-1 inhibitor com-bined with chemotherapy in NSCLC patients.High MDSC infiltration suggests reduced treatment sen-sitivity and poor prognosis.MDSC infiltration level may serve as a predictive biomarker for the effica-cy and prognosis of PD-1 inhibitor combined with chemotherapy in advanced NSCLC.

Fungal keratitis is a serious blinding eye disease. The development of fungal infections depends primarily on the interaction of fungal virulence with host immune defense factors. The cornea is considered an immune-privileged organ, and resident macrophages are the main immune cells that respond to the heterogeneity exhibited by the microenvironment with their polarization. In the early stage of infection, macrophages polarize towards M1, which promotes inflammation and facilitates fungal clearance but produces a cellular storm that exacerbates immune damage; in the late stage of infection, macrophages polarize towards M2, which suppresses the inflammatory response and facilitates tissue repair, but may be immunosuppressed or even immune escape to the detriment of pathogen clearance. The balance between pro-inflammatory and anti-inflammatory responses is key to maintaining the functional integrity of the cornea. Current antifungal drug therapy is limited, so it is particularly important to find a therapeutic target for the inflammatory response triggered by the immune response in addition to antifungal therapy. In this review, the functional and phenotypic characterization of macrophage subsets associated with fungal keratitis was reviewed, more in-depth research is needed to explore the specific mechanisms by which macrophage polarization and their impact on fungal keratitis. Targeted regulation of macrophage differentiation based on their phenotype and function could be an effective approach to treat and manage fungal keratitis in the future.

To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 μmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.
Cell Hypoxia ; Chemotaxis ; Cytokines ; Epithelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Macrophages

Objective To compare the clinical characteristics of chronic bronchitis ( CB),emphysema (EM ), asthma - chronic obstructive pulmonary disease overlapping syndrome ( ACOS ) with frequent exacerbations ( FE ) or infrequent exacerbations ( iFE ) and induced sputum inflammatory cells and the heterogeneity of the transmitter. Methods Ninety-one cases of chronic obstructive pulmonary disease( COPD) with acute exacerbation were divided into CB,EM or ACOS phenotype,among which 44 were frequent,and 47 were non frequent. The clinical data,induced sputum inflammatory cells,interferon-γ(IFN-γ),tumor necrosis factor-α ( TNF-α ), interleukin ( IL )-4, IL-13 were analyzed. Results The FEV1% was ( 47 ± 13. 1 )%, significantly lower than that of non frequent episodes (( 56. 2 ± 10. 2)%),and the difference was statistically significant(P＝0.049).The FEV1/FVC% was (54.3±9.3)%,significantly lower than that of non frequent episodes (60. 1±7. 3)%,and there was a significant difference between them ( P＝0. 001) . The proportion of patients with GOLD III and IV,the percentage of neutrophils in induced sputum,tumor necrosis factor -α(TNF-α) and interferon-γin the patients with frequent episodes were significantly higher than those with non frequent episodes (P＜0. 05). Among them,FEV1/FVC% and TNF-αwere independent risk factors for COPD patients (P＝0. 032, 0. 021) . The FEV1% of patients with CB phenotypic frequent episodes were ( 47. 9 ± 14. 9 )%, significantly lower than that of non frequent episodes ((57. 2±10. 9)%)(P＝0. 000),and FEV1/FVC% was (53. 4± 9. 5)% in patients with CB frequent episodes,significantly lower than that of non frequent episodes ((60. 3±6. 9)%),and the difference was statistically significant (P＝0. 022),while the level of N%,TNF-α in induced sputum were significantly higher in CB phenotype subjects with FE than those in subjects with iFE(P＜0. 01). Patients with frequent episodes of emphysema had longer duration of disease (P＜0. 05),lower FEV1%and FEV1/FVC%(P＜0. 05),the proportion of GOLD III patients and the induced sputum TNF-αwere higher, but there was no significant difference in the number and proportion of phlegm inflammatory cells,interferon-γ, interleukin 4 and interleukin 3. The level of GOLD III and the IL-13 level of induced sputum in patients with frequent ACOS phenotype were significantly higher than those in patients with non frequent episodes (P＜0. 05) . Conclusion The lung function,the severity of the disease,the course of the disease,and the percentage of sputum neutrophils,tumor necrosis factor-α,or interleukin 13 are helpful in diagnosing patients with high risk of frequent episodes.

Objective To explore the dynamic change and clinical signiticance of plasma D-damer level in patients with cerebral hemorrhage and acute craniocerebral injury.Methods 50 patients with cerebral hemorrhage and 40 patients with acute craniocerebral injury were selected,The enzyme-linked immunosorbent assay (ELISA) was used to measure plasma D-dimer level in two groups of patients after onset,and the results were compared with 40 healthy controls.Results The levels of plasma D-dimer in the patients with cerebral hemorrhage were 1.59mg/L,2.10mg/L,1.03 mg/L,0.82mg/L at 3 h,6h,12h,2d after onset,which in the patients with acute craniocerebral injury were 1.61mg/L,2.02mg/L,1.01mg/L and 0.67mg/L,respectively.And the plasma D-dimer levels were 0.50mg/L,0.49mg/L,0.47mg/L,0.48mg/L in the control group at 3h,6h,12h and 2d after onset.The levels of plasma D-dimer in the patients with acute craniocerebral injury were significantly higher than those in the control group,and the differences were statistically significant (t =9.35,12.17,4.03,3.05,all P ＜ O.05).At 7d after onset,the D-dimer levels in the cerebral hemorrhage group and acute craniocerebral injury group were 0.53mg/L,0.55mg/L,respectively,which of the control group was 0.47mg/L,there was no statistically significant difference among the three groups(P ＞ 0.05).Conclusion Cerebral hemorrhage patients and acute craniocerebral injury patients have high coagulation and fibrinolytic activity in brief increase trend,dynamic observation of plasma D-dimer level in patients with cerebral hemorrhage and acute craniocerebral injury is helpful to determine courses,condition and evaluate prognosis.

Objective To introduce the application of the network training on clinicians'knowledge of malaria diagnosis and treatment in Yunnan Province,and evaluate its effect. Methods Through the platform Yiboshi(www.yiboshi.com),the medi-cal and health personnel at the units of provincial,prefectural,county levels and 25 townships of 25 border counties were trained on the knowledge of malaria diagnosis,treatment,prevention and control,and the effects were evaluated by examina-tions,questionnaires and interviews. Results Totally 7152 participants were trained,the average participation,completion and pass rates of the training were 95.26%,98.55% and 97.30%,respectively. The trainees mainly learned malaria control knowledge from 3 aspects,namely policy of malaria elimination,malaria epidemiology,malaria diagnosis and treatment. The questionnaires showed that 95.94%of the participants considered that their theoretical and technical levels improved,97.30%were interested in the training content,93.24% recognized the arrangement of the training time was reasonable,and 91.89%were satisfied with the service of the platform. Conclusions The network training on knowledge of malaria diagnosis and treat-ment in Yunnan Province has achieved good effect. The network training meets the need of training a large number of clinicians in the malaria elimination and post-elimination stage.

AIM:To investigate the regulatory role of hypoxia mimic reagent cobalt chloride ( CoCl2 ) on cave-olin-1 (Cav-1) generation and the influence of Cav-1 on the abilities of migration and invasion of human lung adenocarcino-ma A549 cells.METHODS:The concentrations of Cav-1 and hypoxia-inducible factor ( HIF)-1αin pleural effusion of the patients with lung cancer ( MPE) or tuberculous pleurisy ( TBPE) were detected, and the correlation was also compared. A549 cells were treated with CoCl2 at different concentrations and time in the presence or absence of HIF-1αinhibitor YC-1.The concentrations of Cav-1 and HIF-1αin the cell supernatants were measured by ELISA.The effects of Cav-1 induced by CoCl2 on the migration and invasion of A549 cells were determined by scratch test and Transwell invasion trial, respec-tively.RESULTS:The levels of Cav-1 and HIF-1αin MPE were significantly higher than those in TBPE.There was a highly positive correlation between Cav-1 and HIF-1αlevels in the pleural effusion.CoCl2 induced the generation of Cav-1 and HIF-1αin A549 cells in a concentration-and time-dependent manner, the peak occurred at 200 μmol/L or 24 h, while the concentration over 200 μmol/L or after treated over 24 h, a concentration-or time-dependent inhibition was ob-served.HIF-1αinhibitor YC-1 concentration-dependently inhibited the generation of HIF-1αand Cav-1 induced by CoCl2 in A549 cells.CoCl2 enhanced A549 cells migration and invasion, with 200 μmol/L played the strongest role, which were down-regulated significantly in the presence of YC-1.CONCLUSION:The alteration of hypoxia-induced Cav-1 generation might be involved in the migration and invasion of A549 cells.A possible role for HIF-1αis indicated in Cav-1 generation.