[Objective]To investigate the effect of blue light on emmetropization in guinea pigs,explore the potential mechanisms and assess its application in myopia prevention and control.[Methods]Three-week-old male guinea pigs(n=20)were randomly assigned to the white light group and the blue light group.Refraction and ocular biological parameters were measured every 2 weeks until the experiment ended at week 8.And the 4D-data-independent acquisition(4D-DIA)proteomics technology was used to analyze retina from both the blue light and white light groups,exploring protein composition,expression differences,and biological functions.[Results]After 2 weeks,Guinea pigs exposed to white light gradually tended towards emmetropia,showing a statistically significant difference in refractive error compared to the blue light group(P<0.001).From week 4,the axial length of the blue light group was significantly shorter than that of the white light group(P<0.05).Meanwhile,the vitreous chamber length in the blue light group was significantly smaller than that of the white light group from week 2(P<0.05).A total of 161 differentially expressed proteins were identified by proteomics technology in the retina,with 98 proteins upregulated and 63 proteins downregulated.These proteins were primarily enriched in biosynthetic pathways such as vesicle transport,redox reaction,niacin and nicotinamide metabolism and NAD+metabolism.[Conclusions]Guinea pigs raised under blue light exhibit hyperopic drift and slowed axial elongation,which slows the procession of emmetropization.Based on the 4D-DIA technology,the differentially expressed proteins between the blue light and white light groups are primarily involved in NAD+metabolism,niacin and nicotinamide metabolism.Especially in NAD+salvage synthesis,nicotinamide phosphoribosyl transferase(NAMPT)is upregulated,while sirtuin 2(SIRT2)is downregulated.It provides new insights into the mechanism of blue light in emmetropization and a theoretical basis for myopia prevention and control.

ObjectivesTo analyze the trends in mortality and disease burden of colorectal cancer (CRC) among the registered residents in Danyang City, Jiangsu Province, from 2013 to 2023, and to provide a scientific basis for developing CRC prevention and control strategies. MethodsMortality surveillance data on CRC among the registered residents in Danyang City from 2013 to 2023 were collected and analyzed. Crude mortality rate (CMR), age-standardized mortality rate (ASMR), years of life lost (YLL) due to premature death, and YLL rate were calculated. The annual percentage change (APC) and average annual percent change (AAPC) of CMR, ASMR and YLL rate were calculated with Joinpoint Regression Program 4.9.0.1. ResultsA total of 1 920 deaths from colorectal cancer were recorded in Danyang City during 2013‒2023, with an average annual CMR of 21.75/100 000, which showed an upward trend (APC=6.47%, 95%CI: 4.21%‒8.79%, P<0.001), with higher CMR observed in males than that in females. The overall ASMR by Chinese standard population was 12.10/100 000, with no obvious temporal trends (APC=1.37%, P=0.364). ASMR increased with age, particularly after 45 years. The total YLL due to CRC was 34 711 person-years, with an average YLL rate of 3.93‰. The YLL rate showed a significant upward trend from 2013 to 2023 (APC=4.96%, 95%CI: 4.08%‒18.16%, P<0.001) in Danyang City. ConclusionThe mortality rate of colorectal cancer in Danyang City is relatively high and has shown a rising trend, resulting in an increasing disease burden on the residents year by year. Continued efforts to strengthen CRC prevention and control are needed, particularly targeting males and the elderly population.

Objective:To investigate the level of urinary serine protease(Corin) in early diabetic kidney disease(DKD) and its correlation with clinical stage.Methods:One hundred and seventy-three patients with type 2 diabetes mellitus(DM) from two tertiary A hospitals in Henan, diagnosed between April 2023 and December 2023 were selected as the research group, and 120 healthy subjects were selected as the control group. Basic clinical information and laboratory data were collected, and urinary Corin level was detected. DM patients were classified into G1-G5 stages based on estimated glomerular filtration rate(eGFR), and those in the early DKD stages(G1-G3) were further divided into A1-A3 subgroups based on urinary albumin/creatinine ratio(ACR). Spearman correlation analysis was performed to assess relationships between urinary Corin and other indicators, linear regression analysis identified factors influencing urinary Corin in early DKD patients, logistic regression analysis evaluated the risk factors for early DKD, and receiver operating characteristic(ROC) curve analysis determined the diagnostic value of urinary Corin in early DKD. Results:Urinary Corin levels were significantly higher in early DKD patients compared to healthy controls, with levels increasing as ACR rose( P<0.05). Urinary Corin was positively associated with serum creatinine( r=0.570), urea( r=0.458), cystatin C( r=0.693), ACR( r=0.616), urinary transferrin( r=0.448), urinary α1 microglobulin( r=0.507), urinary n-acetyl-β-D-glucosaminase( r=0.388) and A subgroup( r=0.692) while was negatively correlated with eGFR( r=-0.647), albumin( r=-0.312)(all P<0.05). eGFR was the only independent factor affecting urinary Corin. After adjusting for confounding factors in logistic regression analysis, urinary Corin was still an independent influencing factor for early DKD. ROC curve analysis indicated that urinary Corin had a diagnostic AUC of 0.842(95% CI 0.791-0.892, P<0.001), with a cut-off value of 2 226.04 pg/mL, sensitivity of 0.712, and specificity of 0.858 for early DKD diagnosis. Conclusions:Urinary Corin was elevated in early DKD patients and correlated with clinical stage. Urinary Corin is an independent factor of early DKD, and a reliable predictor of early DKD diagnosis.

Objective:To investigate the level of urinary serine protease(Corin) in early diabetic kidney disease(DKD) and its correlation with clinical stage.Methods:One hundred and seventy-three patients with type 2 diabetes mellitus(DM) from two tertiary A hospitals in Henan, diagnosed between April 2023 and December 2023 were selected as the research group, and 120 healthy subjects were selected as the control group. Basic clinical information and laboratory data were collected, and urinary Corin level was detected. DM patients were classified into G1-G5 stages based on estimated glomerular filtration rate(eGFR), and those in the early DKD stages(G1-G3) were further divided into A1-A3 subgroups based on urinary albumin/creatinine ratio(ACR). Spearman correlation analysis was performed to assess relationships between urinary Corin and other indicators, linear regression analysis identified factors influencing urinary Corin in early DKD patients, logistic regression analysis evaluated the risk factors for early DKD, and receiver operating characteristic(ROC) curve analysis determined the diagnostic value of urinary Corin in early DKD. Results:Urinary Corin levels were significantly higher in early DKD patients compared to healthy controls, with levels increasing as ACR rose( P<0.05). Urinary Corin was positively associated with serum creatinine( r=0.570), urea( r=0.458), cystatin C( r=0.693), ACR( r=0.616), urinary transferrin( r=0.448), urinary α1 microglobulin( r=0.507), urinary n-acetyl-β-D-glucosaminase( r=0.388) and A subgroup( r=0.692) while was negatively correlated with eGFR( r=-0.647), albumin( r=-0.312)(all P<0.05). eGFR was the only independent factor affecting urinary Corin. After adjusting for confounding factors in logistic regression analysis, urinary Corin was still an independent influencing factor for early DKD. ROC curve analysis indicated that urinary Corin had a diagnostic AUC of 0.842(95% CI 0.791-0.892, P<0.001), with a cut-off value of 2 226.04 pg/mL, sensitivity of 0.712, and specificity of 0.858 for early DKD diagnosis. Conclusions:Urinary Corin was elevated in early DKD patients and correlated with clinical stage. Urinary Corin is an independent factor of early DKD, and a reliable predictor of early DKD diagnosis.

Objective:To compare the efficacy, dosage, and safety of dupilumab combined with minocycline or with minocycline and systemic glucocorticoids (sGC) versus minocycline alone or in combination with sGC in patients with bullous pemphigoid (BP) .Methods:A retrospective cohort study was conducted on BP patients who visited the Department of Dermatology, Peking University First Hospital from March 2021 to June 2022 and were treated with one of the following two therapeutic regimens: minocycline alone or in combination with sGC (M-MG group), and dupilumab combined with minocycline or with minocycline and sGC (MD-MGD group). Disease control rates, time to disease control, complete remission rates, time to complete remission, BP disease area index (BPDAI) scores, drug usage, time to pruritus relief, relapse rates, and occurrence rates of adverse reactions were compared between the two groups. Survival analysis was performed using Kaplan-Meier (KM) curves and Log-rank test. Confounders were controlled by 1∶1 matching on the propensity score in the two groups.Results:A total of 164 patients were collected, including 110 in the M-MG group (62 males and 48 females, aged 74.6 ± 12.8 years) and 54 in the MD-MGD group (33 males and 21 females, aged 74.6 ± 13.3 years). After two-week follow-up, there was no significant difference in the disease control rate between the two groups ( P = 0.341); however, the minocycline dose, proportion of patients using sGC, sGC dose, and cumulative sGC dose were all significantly higher in the M-MG group than in the MD-MGD group (all P < 0.05). A total of 152 patients (92.7%) achieved disease control in the two groups during the follow-up, while the disease control rate and time to disease control did not differ between the two groups (both P > 0.05); 52 patients (31.7%) achieved complete remission, there was no significant difference in the complete remission rate between the MD-MGD group (16/54, 29.6%) and M-MG group (36/110, 32.7%; χ2 = 0.16, P = 0.689), but the time to complete remission ( M[ Q1, Q3]) was significantly shorter in the MD-MGD group (98.5[78.0, 185.2] days) than in the M-MG group (223.5 [175.2, 277.0] days, P = 0.001). KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.024). A total of 73 patients (44.5%) recorded the time to pruritus relief during the follow-up, and the MD-MGD group showed significantly shorter time to pruritus relief (54 patients, 14.0 [3.0, 14.0] days) compared with the M-MG group (19 patients, 14.0 [7.0, 19.0] days; P = 0.015). After propensity score matching, each group included 42 patients; during the follow-up, there was no significant difference in the complete remission rate between the M-MG group and MD-MGD group ( P > 0.05), but the time to complete remission was significantly longer in the M-MG group than in the MD-MGD group ( P = 0.019); KM survival curve analysis showed that the cumulative complete remission rate was significantly higher in the MD-MGD group than in the M-MG group ( P = 0.041). Among the 164 patients, adverse reactions occurred in 58 (35.4%), grade 3 or more severe adverse reactions occurred in 11 (6.70%), but no dupilumab-related adverse reactions were reported. Conclusions:Compared with minocycline alone or in combination with sGC in the treatment of BP, the dupilumab combination therapy could relieve pruritus and result in complete remission in a shorter time. Additionally, dupilumab could help to accelerate the reduction in dosages of sGC and minocycline, with few adverse reactions and favorable safety.

Objective To study the relationship between ubiquitin carboxyl terminal hydrolase L1(UCH-L1),peroxiredox protein 1(PRDX1),and the therapeutic effect of ateplase in patients with acute ischemic stroke(AIS).Methods A total of 198 AIS patients admitted to the First Hospital of Jiaxing from June 2020 to June 2022 were selected as the study group,and 100 healthy individuals who underwent physical examinations during the same period were selected as the healthy group.The serum levels of UCH-L1 and PRDX1 were detected using enzyme linked immunosorbent assay(ELISA).AIS patients were all treated with intravenous thrombolysis with ateplase.After 10 days of treatment,the clinical efficacy was evaluated.Clinical data of patients with different therapeutic effects and differences in serum UCH-L1 and PRDX1 levels were compared,and the relationship between UCH-L1,PRDX1 and the therapeutic effect of ateplase was analyzed.Results The UCH-L1 and PRDX1 of patients in the study group were higher than those in the healthy group(P<0.05).The levels of UCH-L1 and PRDX1 in severe AIS patients were higher than those in moderate and mild AIS patients(P<0.05).UCH-L1 and PRDX1 in complete anterior circulation infarction type AIS patients were higher than those in lacunar infarction,posterior circulation infarction,and partial anterior circulation infarction types(P<0.05).After treatment with ateplase,the levels of UCH-L1 and PRDX1 in AIS patients were lower than before treatment,and the worse the treatment effect of ateplase,the higher the levels of UCH-L1 and PRDX1(P<0.05).The combined prediction of UCH-L1 and PRDX1 for the efficacy of ateplase therapy in AIS patients was better than a single prediction(P<0.05).Age,severity of disease,National Institute of Health stroke scale score at admission,UCH-L1,PRDX1 are risk factors that affect the recovery of AIS patients after ateplase treatment(P<0.05).Conclusion The elevated levels of UCH-L1 and PRDX1 in the serum of AIS patients are related to the severity of the disease and stroke classification,and are risk factors affecting the efficacy of ateplase treatment in AIS patients.They can be used for early prediction of the efficacy of ateplase treatment.

With the increasing severity of global aging, aging-related issues have become the hotspot in the field of health. In recent years, animal aging models have been widely developed and applied, which is of great significance in the study of aging mechanism. Animals with short life span, such as Caenorhabditis Elegans and Drosophila Melanogaster, have natural advantages in the study of aging. Various rat and mouse aging models have been used in aging studies. In recent years, new animal aging models have been developed, such as the African turquoise killifish. The authors reviewed main animal models used in the study of aging, and analyzed the establishment methods, evaluation indexes, advantages and disadvantages of each model in order to provide reference for related research.

Objective:To explore the clinical application value of frozen-thawed single blastocyst derived from nonpronuclear (0PN) zygotes, monopronuclear (1PN) zygotes and two-pronuclei (2PN) discarded embryos.Methods:A retrospective cohort analysis of the data of patients who underwent frozen-thawed single blastocyst transfer at the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from March 2014 to November 2020. According to the different sources of transplanted blastocysts, they were divided into 4 groups including group A derived from 2PN available embryos (2PN embryos with morphological rating Ⅰ-Ⅲ), group B derived from 0PN embryos, group C derived from 1PN embryos, group D derived from 2PN discarded embryos (2PN embryos with morphological rating Ⅳ). The basic data of the four groups were analyzed,and group A was used as the reference group to compare the clinical pregnancy outcomes of groups B, C and D, respectively. The neonatal situation was compared at the cycle of singleton live birth. Logistic regression was used to correct for confounding factors and calculate the adjusted odds ratio (a OR) and 95% confidence interval ( CI). Results:After correcting for confounding factors by logistic regression, the live birth rate in group B was significantly lower than that in group A (a OR=0.701, 95% CI: 0.534-0.920, P=0.011). The clinical pregnancy rate and the live birth rate in group D were significantly lower than those in group A (a OR=0.595, 95% CI: 0.456-0.777, P<0.001; a OR=0.600, 95% CI: 0.449-0.800, P=0.001). The differences in miscarriage rate, pregnancy complications and multiple pregnancy rate were not statistically significant compared with group A (all P>0.05). The differences in all the above indicators in group C were not statistically significant compared with group A ( P>0.05). The risk of occurrence of macrosomia (group B: a OR=2.367, 95% CI: 1.299-4.315, P=0.005; group D: a OR=2.711, 95% CI: 1.463-5.026, P=0.002), large for gestational age (group B: a OR=1.930, 95% CI: 1.158-3.217, P=0.012; group D: a OR=2.039, 95% CI: 1.174-3.543, P=0.011) were significantly higher in groups B and D than in group A. The differences in the risk of occurrence of low birth weight, small for gestational age and preterm birth were not statistically significant in groups B and D compared with group A ( P>0.05), and the difference in the risk of occurrence of the above indicators was not statistically significant in group C compared with group A ( P>0.05). Conclusion:When 2PN embryos are not available, abandoned 0PN, 1PN, and 2PN embryos can be transferred after blastocyst culture, but attention should be paid to the increased risk of macrosomia and large for gestational age in offspring.

Objective:To investigate the timing of the first frozen-thawed embryo transfer (FET) on clinical and perinatal outcomes in whole embryo freezing patients, who used the medroxyprogesterone acetate (MPA) in progestin primed ovarian stimulation (PPOS).Methods:A retrospective cohort study was conducted to analyze the clinical data of patients with the first FET after ovulation induction by PPOS protocol in Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2015 to November 2021. According to the time interval between the day of oocytes retrieved and the day of the first FET in the ovulation induction cycle, they were divided into two groups. Group A: transplantation was performed during the first menstrual cycle after oocyte retrieval (time interval ≥24 d and <45 d, n=80), group B: transplantation was performed at least one month apart after oocytes retrieved (time interval ≥45 d, n=1 040). After propensity score matching (PSM), the general data, clinical excretion promotion, embryo laboratory indicators, indicators related to the first FET cycle, clinical and perinatal outcomes were compared between the two groups. Results:Before PSM, the age of group A was significantly higher than that of group B [38 (35, 41) years vs. 37 (32, 40) years, P=0.020]. After PSM, there were no significant differences in general data, ovulation induction cycle data, embryo laboratory indicators, clinical pregnancy rate, live birth rate and perinatal outcomes between the two groups (all P>0.05). Conclusion:Compared with FET at least one month after oocytes retrieval, FET during the first menstrual cycle after PPOS does not affect clinical or perinatal outcomes. FET can be performed as early as possible after oocytes retrieval according to the condition of patients to shorten the time to reach their first live birth.

Objective:To explore the clinical application value of frozen-thawed single blastocyst derived from nonpronuclear (0PN) zygotes, monopronuclear (1PN) zygotes and two-pronuclei (2PN) discarded embryos.Methods:A retrospective cohort analysis of the data of patients who underwent frozen-thawed single blastocyst transfer at the Reproduction Center of the Third Affiliated Hospital of Zhengzhou University from March 2014 to November 2020. According to the different sources of transplanted blastocysts, they were divided into 4 groups including group A derived from 2PN available embryos (2PN embryos with morphological rating Ⅰ-Ⅲ), group B derived from 0PN embryos, group C derived from 1PN embryos, group D derived from 2PN discarded embryos (2PN embryos with morphological rating Ⅳ). The basic data of the four groups were analyzed,and group A was used as the reference group to compare the clinical pregnancy outcomes of groups B, C and D, respectively. The neonatal situation was compared at the cycle of singleton live birth. Logistic regression was used to correct for confounding factors and calculate the adjusted odds ratio (a OR) and 95% confidence interval ( CI). Results:After correcting for confounding factors by logistic regression, the live birth rate in group B was significantly lower than that in group A (a OR=0.701, 95% CI: 0.534-0.920, P=0.011). The clinical pregnancy rate and the live birth rate in group D were significantly lower than those in group A (a OR=0.595, 95% CI: 0.456-0.777, P<0.001; a OR=0.600, 95% CI: 0.449-0.800, P=0.001). The differences in miscarriage rate, pregnancy complications and multiple pregnancy rate were not statistically significant compared with group A (all P>0.05). The differences in all the above indicators in group C were not statistically significant compared with group A ( P>0.05). The risk of occurrence of macrosomia (group B: a OR=2.367, 95% CI: 1.299-4.315, P=0.005; group D: a OR=2.711, 95% CI: 1.463-5.026, P=0.002), large for gestational age (group B: a OR=1.930, 95% CI: 1.158-3.217, P=0.012; group D: a OR=2.039, 95% CI: 1.174-3.543, P=0.011) were significantly higher in groups B and D than in group A. The differences in the risk of occurrence of low birth weight, small for gestational age and preterm birth were not statistically significant in groups B and D compared with group A ( P>0.05), and the difference in the risk of occurrence of the above indicators was not statistically significant in group C compared with group A ( P>0.05). Conclusion:When 2PN embryos are not available, abandoned 0PN, 1PN, and 2PN embryos can be transferred after blastocyst culture, but attention should be paid to the increased risk of macrosomia and large for gestational age in offspring.