AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

AIM: To compare the clinical outcomes of extended depth-of-focus intraocular lenses(EDOF IOLs)using either micromonovision implantation or mixed implantation of EDOF and diffractive bifocal IOLs.METHODS: This retrospective clinical trial included 130 patients(260 eyes), who were divided into two groups. Group RR comprised 70 patients(140 eyes)bilaterally implanted with ZXR00 IOLs(Tecnis ZXR00, where one target was -0.5 D to -0.75 D and the other was 0 to -0.25 D). Group RM comprised 60 patients(120 eyes)unilaterally implanted with both ZXR00 and ZMB00 IOLs(Tecnis ZMB00, 0 to -0.25 D). Postoperative outcomes were compared after 3 mo, including visual acuity, defocus curves, stereoacuity, modulation transfer functions(MTFs), higher-order aberrations, and Visual Function-14(VF-14)questionnaire responses.RESULTS: Group RR had superior bilateral intermediate vision, while the group RM had superior bilateral near vision(both P<0.05). Group RM also exhibited superior MTFs and reduced higher-order aberrations(both P<0.05). Stereoacuity and VF-14 questionnaire results showed no statistically significant difference between groups(P>0.05).CONCLUSION: The implantation of micromonovision has significantly improved near vision. IOLs and their collocation can be customized according to individual patient needs to achieve precise treatment and provide cataract patients with high-quality vision.

Background The widespread use of herbicides has led to environmental contamination and has implications for human health. The liver is an important organ for the detoxification of environmental pollutants; however, studies on the association between herbicide exposure and liver function are limited. Objectives To investigate the association between baseline serum herbicide levels and changes in liver enzyme levels and liver enzyme abnormalities over a 5-year period in middle-aged and older adults. Methods This study was based on a nested case-control population of type 2 diabetes established in the Dongfeng-Tongji cohort, with a total of 1388 subjects included in this study and followed up for 5 years. Epidemiological data were collected through questionnaires, and baseline serum concentrations of three herbicides (metolachlor, propham, and acetochlor) were measured by gas chromatography-triple quadrupole mass spectrometry. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were detected at baseline and follow-up visits. The associations between baseline serum herbicide levels and changes in AST and ALT over 5 years were assessed using linear regression models with herbicide levels categorized into quartiles, adjusting for age, sex, education level, smoking status, drinking status, physical activity, body mass index, and new-onset type 2 diabetes occurred during follow-up. The relationship between baseline serum herbicide levels and the risk of liver enzyme abnormalities during follow-up was further analyzed using logistic regression models. Results The positive rates of metolachlor, propham, and acetochlor were all higher than 80%, and their spiked rates of recovery ranged from 73.46% to 106.77%. The mean ± standard deviation of the age of subjects at baseline was (62.7±7.6) years, with 34.1% being male. The median serum levels of metolachlor, propham, and acetochlor at baseline were 0.05, 0.16, and 0.03 ng·mL⁻¹, respectively. There was no significant difference in baseline serum herbicide levels between the normal and abnormal liver enzyme groups at follow-up (P >0.05). The baseline liver enzyme levels and the changes in AST and ALT over 5 years in those who developed abnormal liver enzymes were significantly higher than those in the normal liver enzyme group (P <0.05). The linear regression analysis showed that the changes in AST increased progressively over 5 years in the second, third, and fourth quartiles of propham compared to the lowest quartile group (the second quartile: b=1.49, 95%CI: 0.10, 2.87; the third quartile: b=1.52, 95%CI: 0.14, 2.90; the fourth quartile: b=1.69, 95%CI: 0.31, 3.08; P <0.05). The associations of serum metolachlor and acetochlor with changes in AST were not significant. Additionally, no significant relationships were found between the three serum herbicides and the changes in ALT over 5 years or the risk of liver enzyme abnormalities. Conclusion Serum propham levels in middle-aged and older adults are positively associated with changes in liver enzyme AST, which may have an effect on liver function. More studies are needed to provide scientific evidence for the association between herbicide exposure and liver function.

Background Previous studies have shown that bisphenol A exposure is associated with the risk of hypertension; however, most of them are cross-sectional and the conclusions are not consistent. Objective To evaluate the association between bisphenol A exposure and the incident risk of hypertension. Methods Based on a nested case-control design involving 1990 subjects derived from the Dongfeng-Tongji cohort, a total of 1080 subjects were included in this study after excluding 887 hypertensive cases at baseline and 23 subjects with missing blood pressure data in follow-up visits. Epidemiological information was collected through questionnaire survey, and serum bisphenol A concentration was detected by high performance liquid chromatography tandem mass spectrometry. Logistic regression model was used to analyze the potential association between serum bisphenol A level and the risk of hypertension incidence, and linear regression model was used to analyze the association between serum bisphenol A level and blood pressure changes between baseline and follow-up. Results The average age of the 1 080 participants was (62.03±7.45) years, of which 41.1% were male. During the follow-up period, a total of 477 (44.2%) developed hypertension. The median serum concentration of bisphenol A in the total population was 3.15 μg·L⁻¹, and the baseline bisphenol A concentration in the new case group (3.24 μg·L⁻¹) was higher than that in the control group (2.98 μg·L⁻¹) (P<0.05). After adjustment for selected covariates, the risk of hypertension increased by 12% (OR=1.12, 95%CI: 1.02, 1.22) for each unit increase in naturally log-transformed bisphenol A; the systolic blood pressure and diastolic blood pressure increased by 1.88 (95%CI: 1.08, 2.69) mmHg and 1.14 (95%CI: 0.68, 1.61) mmHg, respectively. Compared with the low bisphenol A tertile group, the risk of hypertension in the middle tertile and high tertile groups increased by 39% (OR=1.39, 95%CI: 1.01, 1.91) and 40% (OR=1.40, 95%CI: 1.02, 1.93) respectively; the systolic blood pressure increased by 5.91 (95%CI: 3.06, 8.76) mmHg and 5.71 (95%CI: 2.82, 8.59) mmHg, and the diastolic blood pressure increased by 3.09 (95%CI: 3.06, 8.59) mmHg and 2.89 (95%CI: 1.22, 4.57) mmHg, respectively (P_trend<0.001). A positive association between serum bisphenol A level and hypertension was found among those who were female, never/former smokers, never/former drinkers, without family history of hypertension, with physical exercise, and with prehypertension at baseline (P_trend<0.05). There was no interaction between selected stratified variables and bisphenol A levels on hypertension (P_interaction>0.05). Conclusion Bisphenol A exposure is positively associated with the risk of hypertension.

AIM: To investigate the effect of different lens combinations on visual acuity, visual quality and patient satisfaction by comparing mixed implantation of Tecnis Symfony ZXR00(ZXR00)and Tecnis ZMB00(ZMB00)lenses, bilateral implantation of ZMB00 lenses, and bilateral implantation of ZXR00 lenses.METHODS:This retrospective case-control study included 117 patients with cataracts(234 eyes)who underwent phacoemulsification combined with intraocular lens(IOLs)implantation from August 2020 to December 2021. The 3 groups included 36 patients(72 eyes)who underwent bilateral implantation of ZXR00(RR group), 37 patients(74 eyes)who underwent bilateral implantation of ZMB00(MM group), and 44 patients(88 eyes)who underwent implantation with a combination of ZXR00 and ZMB00(MR group). The uncorrected distance visual acuity(UDVA, 5 m), uncorrected intermediate visual acuity(UIVA, 80 cm), uncorrected near visual acuity(UNVA, 40 cm), corrected distance visual acuity(CDVA), defocus curve, stereopsis and VF-14 and QoV visual quality scale of the patients in the three groups were assessed at 3-month follow-up.RESULTS:Bilateral UNVA in the MM and MR group were significantly better than that in the RR group(P<0.05). Bilateral UIVA was the best in the RR group. There were no significant differences in bilateral UDVA, CDVA and stereopsis among the groups(P>0.05). Values for near-stereoscopic acuity at 40 cm were 107.27±80.53, 105.67±83.79, and 108.69±97.66(20-400)arcsec in the MR, MM, and RR groups, respectively(P>0.05). Satisfaction rates exceeded 90% in all groups.CONCLUSION:All groups achieved good distance, intermediate, and near visual acuity and near-stereoscopic vision postoperatively. Mixed implantation with ZXR00 and ZMB00 lenses achieved excellent full-range vision and resulted in high satisfaction. These results may aid in developing individualized clinical treatment plans.

During the process of dairy farming,various factors such as physical injury and bacterial infection act upon body tissues or organs,leading to the disruption of skin or mucous tissue integ-rity and subsequent tissue injury and trauma.The healing of these injuries is a complex process that necessitates the coordinated efforts of different cells and involvement of diverse cytokines.A-mong them,the interaction between macrophages and myofibroblasts is indispensable for efficient tissue repair.Nod-like receptor protein 3(NLRP3),a pattern recognition receptor in the innate im-mune system,may play a regulatory role in modulating this intricate process.In this study,cow myofibroblasts and M1 type bone marrow-derived macrophages were cultured in vitro,followed by collection of cell culture supernatant for co-culture analysis.Both cytokine secretion levels in M1 type bone marrow-derived macrophages as well as expression patterns levels of myofibroblast growth factor protein and mRNA were detected.The regulatory mechanism underlying NLRP3 in-volvement in mediating interactions between these two cell types was investigated using NLRP3 inhibitor MCC950.The results showed that an effective method for culturing cow muscle fibroblasts in vitro was successfully established and myofibroblast conditioned medium(MFbCM)could regulate M1 macrophage secretion profiles.Moreover,M1 macrophage conditioned medium(M1?CM)was found to influence myofibroblast growth factor expression levels.Our findings sug-gest that NLRP3 plays a significant regulatory role during crosstalk between myofibroblasts and M1-type pro-inflammatory macrophages.

Objective To investigate the changes and clinical significance of γδT cells and their major functional subsets γδT1 and γδT17 cells in the peripheral blood of patients with systemic lupus erythematosus (SLE). Methods Ratios and absolute numbers of γδT cells, γδT1 cells and γδT17 cells in peripheral blood were detected by flow cytometry in 21 SLE patients (SLE) group and 16 healthy controls (HC group). Correlations of γδT cells, γδT1 cells and γδT17 cells in the peripheral blood with clinical indicators were analyzed by Pearson correlation analysis. Results In SLE patients, the percentage of γδT cells to lymphocytes in the peripheral blood was (2.30±1.10)%, which was significantly lower than (3.30±1.51)% in the HC group (P < 0.05); the percentage of γδT1 cells to lymphocytes in peripheral blood was (0.93±0.67)%, which was significantly lower than (2.09±1.21)% in the HC group (P < 0.001); the ratio of γδT17 cells to lymphocytes in the peripheral blood was (1.53±2.82)‰, which showed an increasing trend when compared to (0.18±0.12)‰ in the HC group (P>0.05). The absolute number of γδT cells in the peripheral blood in SLE patients was (2.88±2.18)×10⁴/mL, which was significantly lower than (7.96±3.96)×10⁴/mL in the HC group (P < 0.000 1); the absolute number of γδT1 cells in the peripheral blood in SLE patients was (1.20±1.17)×10⁴/mL, which was significantly lower than (5.05±3.04)×10⁴/mL in the HC group (P < 0.000 1); the absolute number of γδT17 cells in the peripheral blood in SLE patients was (1.03±1.08)×10³/mL, which was significantly higher than (0.40±0.24)×10³/mL in the HC group (P < 0.05). The proportion of γδT17 cells in the peripheral blood of SLE patients was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (r=0.59, P < 0.01) and erythrocyte sedimentation rate (r=0.65, P < 0.01), while the absolute number of γδT17 cells was positively correlated with the SLEDAI score (r=0.59, P < 0.01) and negatively correlated with the complement C3 level (r=-0.53, P < 0.05). Conclusion The significant decrease in the number of γδT cells in the peripheral blood of SLE patients is mainly due to the reduction of its γδT1 cell subset; γδT17 cells play an important role in the pathogenesis and activity of SLE.

Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.

Objective:To investigate the associations between small diffusion-weighted imaging (DWI) hyperintensities lesions and total cerebral small vessel disease (cSVD) burden and the influence on prognosis in patients with acute intracerebral hemorrhage (ICH).Methods:Consecutive patients with acute spontaneous ICH from January 2018 to June 2021 were recruited in the Stroke Center of Zhengzhou People′s Hospital. Magnetic resonance imaging was performed to quantify DWI hyperintensities lesions and cSVD imaging markers, including white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds, which were calculated for the total cSVD burden (0-4 points). The prognosis was assessed with the modified Rankin Scale (mRS) at discharge and 90-day. Multivariable Logistic regression models were adopted to explore the associations between DWI lesions and total cSVD burden and clinical outcome.Results:Of 283 included patients, 59 (20.8%) had small DWI lesions, 32 (11.3%) had multiple lesions. They were mostly punctate, mainly located in the cortical and subcortical regions, and scattered in multiple vascular territories. With the increase of cSVD burden, the number of DWI lesions gradually increased. Spearman correlation analysis showed that the total cSVD burden was positively correlated with the number of DWI lesions ( r=0.21, P<0.001). In multivariable regression analyses, the total cSVD burden was independently associated with DWI lesions ( OR=1.63, 95% CI 1.23-2.15, P=0.001). The 90-day poor outcome (mRS scores≥4) in patients with DWI lesions was significantly higher than those without DWI lesions (39.3% vs 16.3%, χ 2=14.38, P<0.001), while there was no statistically significant difference in the poor outcome of discharge between the two groups (26.5% vs 17.7%, χ 2=3.06, P=0.080). With the increase in the number of DWI lesions, the 90-day poor outcome increased significantly (trend chi-squared test χ 2=11.50, P=0.001). Multivariable analyses showed that DWI lesions ( OR=4.39, 95% CI 1.92-10.03, P<0.001) and their number ( OR=1.42, 95% CI 1.06-1.90, P=0.018) were independently associated with the 90-day poor outcome. Conclusions:Higher total cSVD burden is an independent risk factor for small DWI lesions in patients with ICH. Small DWI lesions were independently associated with the 90-day poor outcome, but not with the discharge outcome.

Objective:To identify the morphological alterations in the Golgi apparatus of skin fibroblasts in spinocerebellar ataxia type 3 (SCA3) patients.Methods:In this study, 3 SCA3 patients and 3 healthy volunteers were obtained in the First Affiliated Hospital of Zhengzhou University from 2016 to 2020. The cytosine, adenine, and guanine repeats of 3 SCA3 patients were 14/76, 20/80 and 21/82, respectively. Tissue mass culture was used to amplify skin fibroblasts derived from SCA3 patients and healthy volunteers. Cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry, respectively. Western blotting and immunofluorescence assay were used to detect the protein expression of ataxin-3, Golgi reassembly stacking protein 2 (GORASP2), and Golgi matrix protein 130 (GM130) in the skin fibroblasts. The morphology of the Golgi apparatus in skin fibroblasts was detected using transmission electron microscopy.Results:Tissue culture of skin fibroblasts of both SCA3 patients and healthy volunteers was successfully established. The patient-derived dermal fibroblasts expressing mutant ataxin-3 protein exhibited reduced cell viability ( t=5.06,P=0.007), increased apoptosis ( t=3.77, P=0.020), fragmentation of the Golgi apparatus, increased expression of GM130 ( t=5.23, P=0.006), and decreased expression of GORASP2 ( t=4.35, P=0.012). Transmission electron microscopy revealed that the Golgi apparatus was disorganized in skin fibroblasts. Conclusion:Fragmentation of the Golgi apparatus occurs in the skin fibroblasts of SCA3 patients, and abnormal morphology and structure of the Golgi apparatus may be involved in the pathogenesis of SCA3.