Objective To study the effect and mechanisms of chloride channel blocker 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) on thansforming growth factor β1 (TGF-β1) induced human conjunctival fibroblasts (HConF) fibrosis.Methods Cell counting kit (CCK-8) was used to screen out the optimal TGF-β1 treatment time and the optimal NPPB concentration.The cells were divided into control group,TGF-β1 treatment group and TGF-β1+NPPB group.Cell proliferation and cell cycle were detected by CCK-8 and flow cytometer,respectively.Cell migration ability were observed by scratch and transwell migration assays.Western blot and Real time-PCR were used to detect the expression of collagen Ⅰ (COL-Ⅰ),fibronectin (FN) and α-smooth muscle actin (α-SMA).The phosphorylation level of PI3K and Akt were measured by Western blot.Results TGF-β1 promotes cell proliferation in a time-dependent manner.There was no statistically significant difference in A values between 48 hours and 72 hours after TGF-β1 treatment (P =0.064).Forty-eight hours was selected as the most appropriate time for TGF-β1 treatment.NPPB inhibited HConF cell proliferation in a concentration-dependent manner.Compared with the control group,the proliferation A values of cells in the 50 mol/L and 100 mol/L NPPB groups were significantly reduced (P =0.020,0.000),and 100 mol/L was selected as the optimal concentration of NPPB.The cell proliferation A value,migration area and migration cell number of TGF-β1 +NPPB group were significantly lower than those of TGF-β1 treatment group (all at P＜0.05).Compared with the control group and TGF-β1 +NPPB group,the proportion of G1 phase cells in the TGF-β1 treatment group was reduced,and the proportion of cells in the S phase and G2/M phase were increased,with statistically significant differences between them (all at P ＜ 0.05).The protein and mRNA expression of α-SMA,COL-Ⅰ and FN in the TGF-β1 treatment group were higher than those in the control group and TGF-β1+NPPB group,with statistically significant differences between them(all at P＜0.05);the ratios of p-PI3K/PI3K and p-Akt/Akt in the TGF-β1 treatment group were significantly higher than those in the control group and TGF-β1 +NPPB group,with statistically significant differences between them (all at P＜0.05).Conclusions NPPB may inhibit TGF-β1 induced HConF fibrosis process by inhibiting phosphorylation of PI3K and Akt.

Objective To investigate the effects of visfatin gene overexpressian on insulin sensitivity and plasma fibroblast growth factor 21 (FGF-21) level in rats. Methods The recombinant visfatin plasmid was constructed and transfected into normal rats. The euglyeemic-hyperinsulinemie clamp experiments were performed to evaluate the change of insulin sensitivity before and after administration of the plasmid, and plasma FGF-21 level was determined by radioimmunoassay. Results Plasma visfatin levels and glucose infusion rates (GIR) were significantly increased [(1.49±0.06 vs 0.99±0.04) and (35.3±1.4 vs 27.6±1.7) mg·kg-1·min-1,respectively, all P<0.01]. Fasting insulin level was significantly decreased [(14.5±3.7 vs 24.4±6.2) mU/L,P<0.05], total cholesterol and high-density lipoprotein cholesterol were significantly decreased [(1.31±0.10 vs1.76±0.22) mmol/L and (0.59±0.04 vs 0.95±0.15) mmol/L, respectively, all P<0.05], and plasma FGF-21 level was also decreased [(2.25±0.19 vs 2.59±0.23)μg/L, P<0.05] after plasmid being injected 3 days compared with that before injection, but there were no significant differences in fasting glucose and adiponectin levels before and after administration. Conclusion The transfection of visfatin plasmid increases plasma visfatin level, decreases FGF-21 levels and improves insulin sensitivity in normal rats.

Objective:To analyze the distribution of clinically isolated fungal strains and their resistance to common antifungal drugs in Shandong province.Methods:Through the Shandong Children’s Bacterial & Fungal Drug Resistance Surveillance and Research Collaborative Network, a total of 1 030 fungi were collected in 46 hospitals of Shandong province from January 1 to December 31, 2018. The source and type of strains were analyzed, and antifungal drug sensitivity tests were performed by using the micro-dilution method. Whonet 5.6 and SPSS 22.0 were applied to analyze the data.Results:The overall main strains were Candida albicans (38.74%, 399/1 030), Candida tropicalis (16.99%, 175/1 030) and Candida parapsilosis (16.41%, 169/1 030); the main fungi strains in child patients were C. albicans (52.50%, 63/120), C. parapsilosis (12.50%, 15/120) and C. tropicalis (9.17%, 11/120); the main fungi strains in adult patients were C. albicans (36.37%, 331/910), C. tropicalis (17.03%, 155/910) and C. parapsilosis (15.27%, 139/910). The isolation rate of main Candida strains from January to March and August to December was much higher than that of other months. The drug resistance rates of C. albicans to fluconazole and voriconazole were 7.14% and 7.43%, respectively, and the drug resistance rates to itraconazole were 50.44%. The resistance rates of C. tropicalis to fluconazole, voriconazole and itraconazole were 29.05%, 23.29% and 48.65%, respectively. The sensitivity rates of C. parapsilosi to fluconazole, voriconazole and itraconazole were 93.06%, 93.75% and 94.44%, respectively. Candida glabrata showed a dose-dependent sensitivity rate of 2.33% to fluconazole. Analysis of 244 blood fungi strains showed that non-candida albicans bacteremia accounted for 70.08%. In the pathogen spectrum covering 92.22%, fluconazole was sensitive to 64.65% of the pathogens, voriconazole was 68.88%, and amphotericin B was 88.75%. After quantification, the effective rates of fluconazole, voriconazole and amphotericin B in the clinical treatment of fungal bacteremia were 70.10%, 74.69% and 96.23%, respectively. Among them, the sensitivity rate of voriconazole to C. tropicalis was lower than that of fluconazole. Conclusions:Candida is the main clinical fungus isolates in hospitals of Shandong province. The resistance rate of C. tropicalis to azole antifungal drugs is on the rise, and the sensitivity of other Candida species to clinically used antifungal drugs is basically stable.

Purpose: Sedentary behavior attributes to the increased risk of some cancers and all-cause mortality. The evidence is limited for the association between television (TV) viewing time, a major sedentary behavior, and risk of colorectal cancer death. We aimed to examine this association in Japanese population. Materials and Methods: A prospective cohort study encompassed of 90,834 men and women aged 40-79 years with no prior history of colorectal cancer who completed a self-administered food frequency questionnaire, and provided their TV viewing information. The participants were followed-up from 1988-1990 to the end of 2009. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression for risk of colorectal cancer mortality according to TV viewing time. Results: During the median 19.1-year follow-up period, we documented 749 (385 men and 364 women) colorectal cancer deaths. The multivariable-adjusted HRs for mortality from colorectal cancer were 1.11 (0.88-1.41) for 1.5 to < 3 hr/day, 1.14 (0.91-1.42) for 3 to < 4.5 hr/day and 1.33 (1.02-1.73) for ≥ 4.5 hr/day in comparison to < 1.5 hr/day TV watching; p-trend=0.038, and that for 1-hour increment in TV viewing time was 1.06 (1.01-1.11). Moreover, the multivariable-adjusted HR (95%CI) of colon cancer for 1-hour increment in TV viewing time was 1.07 (1.02-1.13). Age, body mass index, and level of leisure-physical activity did not show significant effect modifications on the observed associations. Conclusion TV viewing time is associated with the increased risk of colorectal cancer mortality among Japanese population, more specifically colon rather than rectal cancer.

Purpose: Sedentary behavior attributes to the increased risk of some cancers and all-cause mortality. The evidence is limited for the association between television (TV) viewing time, a major sedentary behavior, and risk of colorectal cancer death. We aimed to examine this association in Japanese population. Materials and Methods: A prospective cohort study encompassed of 90,834 men and women aged 40-79 years with no prior history of colorectal cancer who completed a self-administered food frequency questionnaire, and provided their TV viewing information. The participants were followed-up from 1988-1990 to the end of 2009. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazard regression for risk of colorectal cancer mortality according to TV viewing time. Results: During the median 19.1-year follow-up period, we documented 749 (385 men and 364 women) colorectal cancer deaths. The multivariable-adjusted HRs for mortality from colorectal cancer were 1.11 (0.88-1.41) for 1.5 to < 3 hr/day, 1.14 (0.91-1.42) for 3 to < 4.5 hr/day and 1.33 (1.02-1.73) for ≥ 4.5 hr/day in comparison to < 1.5 hr/day TV watching; p-trend=0.038, and that for 1-hour increment in TV viewing time was 1.06 (1.01-1.11). Moreover, the multivariable-adjusted HR (95%CI) of colon cancer for 1-hour increment in TV viewing time was 1.07 (1.02-1.13). Age, body mass index, and level of leisure-physical activity did not show significant effect modifications on the observed associations. Conclusion TV viewing time is associated with the increased risk of colorectal cancer mortality among Japanese population, more specifically colon rather than rectal cancer.

Objective:To observe the therapeutic effect of intraocular lens (IOL) protected phacoemulsification (PHACO) in patients with hard nucleus cataract.Methods:A randomized controlled clinical study was conducted.A total of consecutive 120 patients (120 eyes) with hard nucleus cataract of Emery grade Ⅳ or Ⅴ were enrolled from January 2019 to May 2022.The patients were randomly divided into PHACO group receiving routine PHACO, IOL protected PHACO group receiving PHACO under IOL protection, and extracapsular cataract extraction (ECCE) group receiving ECCE, with 40 cases (40 eyes) in each group.Finally, 99 patients completed the follow-up, including 30 cases (30 eyes) in PHACO group, 35 cases (35 eyes) in IOL protected PHACO group, and 34 cases (34 eyes) in ECCE group.The total operation time, intraoperative PHACO time and cumulative energy release of each patient were recorded.The corneal endothelial cell density (ECD), coefficient of variation in endothelial cell area (CV), hexagonal endothelial cell ratio (6A), corneal astigmatism and the number of eyes with different grades of uncorrected visual acuity were measured and compared after 3-month follow-up.The intraoperative and postoperative complications were recorded.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Yanbian University Hospital (NO.2023002).Patients were informed of study content and purpose and signed a consent form before treatment.Results:There was no significant difference in ultrasonic energy and time between PHACO group and IOL protected PHACO group ( P=0.691, 0.982).The total operation time was (38.81±2.73) and (36.45±3.45) minutes in PHACO group and IOL protected PHACO group, significantly shorter than (69.60±4.35) minutes in ECCE group (both at P<0.001).There was no significant difference in age, sex, lens nucleus hardness and other baseline data among the three groups before operation (all at P>0.05).Three months after operation, the number of patients with higher uncorrected visual acuity in PHACO group and IOL protected PHACO group was larger than that in ECCE group ( P=0.006, 0.007).The ECD and 6A in IOL protected PHACO group were (2 155.57±177.88)/mm 2 and (41.31±5.18)%, respectively, which were significantly higher than (1 912.64±224.11)/mm 2 and (36.18±3.27)% in PHACO group, and the CV in IOL protected PHACO group was (50.34±5.90)%, which was lower than (55.67±3.30)% in PHACO group, showing statistically significant differences ( P=0.007, 0.003, 0.005).At 1 week and 3 months after the operation, the corneal astigmatism was significantly lower in IOL-protected PHACO group than in ECCE group, but higher than in PHACO group, and the difference were statistically significant (all at P<0.05). Conclusions:Compared with conventional PHACO, IOL-protected PHACO can effectively reduce the damage of corneal endothelium caused by ultrasonic energy, shorten the operation time and reduce postoperative inflammatory reaction compared with ECCE, and does not significantly increase postoperative corneal astigmatism.IOL-protected PHACO is an effective improved surgical method for patients with hard nucleus cataract.

The nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome is an inflammatory protein complex, and can participate into the inflammatory response. Upon activation, these inflammasomes can lead to Caspase-1 activation, thereby inducing a cascade of inflammatory factor activation and further cell pyroptosis. Excessive activation of inflammasomes will induce the overexpression of inflammatory factors, persistently triggering immune dysregulation and inflammatory chain reactions, even causing severe damage. The recent studies have confirmed a close association between retinal diseases, such as diabetic retinopathy(DR), retinal ischemia-reperfusion injury(RIRI), and proliferative vitreoretinopathy(PVR)with immune dysregulation and inflammatory responses, which is serving as crucial factors in the progression of retinal diseases. This article reviews the NLRP3 inflammasome signaling pathway and its role in the occurrence and development of retinal diseases, in order to provide new ideas for the pathogenesis and prevention of retinal diseases.