Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

Objective To explore the mechanism of action of Neiyi Soft Extract in the treatment of endometriosis(EMS)based on network pharmacology and transcriptomics.Methods A model of SD rat with EMS was replicated by autotransplantation method.After successful modeling,the rats were randomly divided into model group,Neiyi Soft Extract low-,medium-and high-dose groups and dienogest group,with 10 rats in each group.Another sham-operated group(10 rats)was set up.After four consecutive weeks of intervention,the volume size of the endometriotic lesions was measured,and its pathological changes were detected by hematoxylin-eosin(HE)staining.RNA was extracted from the rat lesions for transcriptomic sequencing,and Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)functional enrichment analysis were performed on the differential genes among various groups.The main active ingredients and their targets of Neiyi Soft Extract were collected and screened in databases such as TCMSP,the disease targets of EMS were collected through databases such as OMIM,the intersection targets between the drug ingredient targets and the diseases were obtained by using Venn diagrams,GO enrichment analysis and KEGG pathway enrichment analysis of genes in the intersection targets of the drug ingredients and the diseases were performed by using gene enrichment analysis online tool(Metascape).The network pharmacology enrichment pathway and transcriptomics enrichment pathway were taken for intersection,the mRNA and protein expression levels of the key targets on the intersection pathway were correspondingly detected by real-time quantitative polymerase chain reaction(qPCR)and Western Blot,respectively.Results The volume of lesions in the model group was significantly increased compared with that of the sham-operated group(P<0.01);the volume of lesions in rats in the drug-administered groups was significantly reduced compared with that of the model group(P<0.05).A total of 341 active ingredients were obtained from Neiyi Soft Extract,and there were 2 178 disease-related targets of EMS,and 278 intersections between drug targets and disease targets;189 differential genes were screened in the sham-operated group and the model group;255 differential genes were screened in the model group and Neiyi Soft Extract high-dose group;and 740 differential genes were screened in the sham-operated group and the Neiyi Soft Extract high-dose group,including 390 up-regulated genes and 350 down-regulated genes.The result of intersection of KEGG enrichment pathways between the network pharmacology and transcriptomics showed that the distriution mainly included P53 signaling pathway,FOXO signaling pathway,cell cycle,etc.The qPCR and Western Blot validation results showed that Neiyi Soft Extract could inhibit the proliferation of endometrial stromal cells and up-regulated the mRNA and protein expression levels of BAX,Caspase3 in EMS rats(P<0.05 or P<0.01),and down-regulated BCL-2 mRNA and protein expression levels(P<0.05 or P<0.01).Conclusion Neiyi Soft Extract may play a therapeutic role in the treatment of EMS by regulating the P53 signaling pathway.

Background During pregnancy, negative emotions such as anxiety and depression may induce cortisol disruption. Cortisol can be transmitted to the fetus through the placental barrier, thereby affecting the neurodevelopment of the offspring. Objective To investigate the relationship between placental cortisol, maternal depression during pregnancy, and neurodevelopment of 3-month-old infants. Methods From September 2022 to September 2023, 171 pregnant women ordered routine prenatal checks at the obstetrics outpatient department of a tertiary hospital in Ningxia were selected using a prospective cohort design. After providing informed consent, these women participated in a questionnaire survey that covered general individual characteristics, prenatal depression, and sleep quality. At birth, placental samples were collected to measure cortisol levels using ELISA kits. Follow-up assessments on the neurodevelopmental of 3-month-old infants were conducted using the Warning Sign for Children Mental and Behavioral Development. LASSO regression analysis was conducted to screen the influencing factors of depression during pregnancy. Huber regression analysis was then applied to assess potential linear relationship between depression during pregnancy and placental cortisol levels. Log-binomial regression was used to analyze the linear relationships between cortisol levels and neurodevelopmental delay in 3-month-old infants. Additionally, a mediation effect model was fitted using R 4.3.3 to assess possible mediating role of cortisol in the association between prenatal depression and neurodevelopmental delay in 3-month-old infants. Results The positive rate of prenatal depression was 33.33%. Nine factors affecting prenatal depression were identified by LASSO regression, including rural residence, high school education or above, extroverted personality characteristics, moderate early pregnancy reactions, baby sex expectation, prenatal anxiety, family dysfunction, exposure to stressful life events during pregnancy, and moderate prenatal sleep quality. The Huber regression model showed a positive linear correlation between prenatal depression and placental cortisol (P<0.05). With or without controlling confounding factors, the results of log-binomial regression modeling showed that cortisol levels were associated with a reduced risk of neurodevelopmental delay in 3-month-old infants (crude model: RR=0.988, 95%CI: 0.9768, 0.9996, P＜0.05; adjusted model: RR=0.988, 95%CI: 0.9764, 0.9993, P＜0.05). A mediating effect of placental cortisol between prenatal depression and the risk of neurodevelopmental delay in 3-month-old offspring was found statistically significant (P=0.045), accounting for 67.0% of the total effect. Conclusion Prenatal depression is associated with elevated placental cortisol levels, and higher cortisol levels are found to be related to a lower risk of neurodevelopmental delay in infants. Placental cortisol mediates the relationship between prenatal depression and infant neurodevelopment.

Background With economic development and globalization, shift work has become prevalent across industries. Its relationship with type 2 diabetes mellitus (T2DM) attracts increasing attention. Objective To thoroughly explore the relationship between shift work and T2DM, and analyze the impacts of specific shift patterns on T2DM, so as to provide a basis for formulating reasonable shift schedules. Methods We conducted a 1:2 matched case-control study among adults (20-60 years) who ordered occupational health examinations at the Wuxi No.8 People's Hospital from November to December 2023. The case group comprised 200 T2DM patients, while the controls were 400 age-stratified matched non-diabetic individuals. General demographic characteristics, behavioral habits, medical history, and shift work exposure data (including shift patterns, frequency, and length of service) 5 years prior to diagnosis were collected through standardized questionnaires. Logistic regression adjusted for selected confounders was employed to evaluate the association between shift work and T2DM. Results The logistic regression analysis demonstrated that shift work was associated with an increased risk of T2DM. After adjusting for confounding factors, shift workers had a 3.55 times higher risk of being diagnosed T2DM compared to non-shift workers (OR=3.55, 95%CI: 1.026, 12.263). The risk varied across different shift patterns, and the three-shift two-rotation system showed the highest risk (OR=4.17, 95%CI: 1.921, 9.035), followed by the two-shift system (OR=2.94, 95%CI: 2.016, 4.281) and four-shift three-rotation system (OR=2.66, 95%CI: 1.611, 6.093). Workers with more than 3 monthly shift days had a 2.74-fold increased risk (95%CI: 1.658, 4.512) compared to non-shift workers. Additionally, working more than 8 h daily (OR=1.74, 95%CI: 1.185, 2.562) and having more than 20 years of service (OR=2.51, 95%CI: 1.581, 3.976) were both significantly associated with a higher T2DM risk. The trend tests revealed that each incremental increase in monthly shift days and length of service elevated T2DM risk by 2.61 times (95%CI: 1.813, 3.765) and 1.49 times (95%CI: 1.147, 1.931), respectively (P<0.05). Conclusion Shift work is an independent risk factor for T2DM, with three-shift two-rotation system posing the highest risk. Shift frequency, daily working hours, and length of service are all significant factors affecting the risk of T2DM. These findings support industry-specific shift policy reform and targeted glucose monitoring and health interventions are recommended for workers engaged in high-risk shift patterns (e.g., three-shift two-rotation system, frequent shifts) and those with prolonged shift work history (>20 years).

Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Objective To differentiate disguised visual acuity,(VA)by analyzing discrepancies across diversified visual acuity tests.Methods Volunteers were recruited,and VA(V,and V2)was measured before and after the experiment.Volunteers independently selected an experimental VA(Vt)and were assigned to either the disguised group or the control group.A specially designed heterogeneous optotype chart and a single-optotype chart with variable test distances were used to measure VA(t1,t2,t3),while a standard logarithmic VA chart was used to measure VA(t4).Based on the maximum VA discrepancy(△t),t4 was classified as"real"(≤ 1 line),"disguised"(≥ 2 lines),or"suspicious"(＞1 and＜2 lines with anomaly).Results A total of 126 valid cases were collected,including 30 in the control group and 96 in the disguised group,with VA ranging from 0.2～1.5.All 88 opinions classified as"disguised"were from the disguised group,and all 29 classified as"real"were from the control group.Of the 7 cases deemed"suspicious,"6 were from the disguised group.The sensitivity,specificity,and overall diagnostic accuracy were 91.7％,96.7％(P＜0.0001),and 92.9％(P＜0.0001),respectively.In the disguised group,38 cases exhibited unexplained identifying anomalies.Conclusion A VA discrepancy of ≥ 2 lines is a reliable indicator for detecting disguised visual acuity.Identifying anomalies may serve as a novel and sensitive marker for recognizing visual disguise.

Objective To differentiate disguised visual acuity,(VA)by analyzing discrepancies across diversified visual acuity tests.Methods Volunteers were recruited,and VA(V,and V2)was measured before and after the experiment.Volunteers independently selected an experimental VA(Vt)and were assigned to either the disguised group or the control group.A specially designed heterogeneous optotype chart and a single-optotype chart with variable test distances were used to measure VA(t1,t2,t3),while a standard logarithmic VA chart was used to measure VA(t4).Based on the maximum VA discrepancy(△t),t4 was classified as"real"(≤ 1 line),"disguised"(≥ 2 lines),or"suspicious"(＞1 and＜2 lines with anomaly).Results A total of 126 valid cases were collected,including 30 in the control group and 96 in the disguised group,with VA ranging from 0.2～1.5.All 88 opinions classified as"disguised"were from the disguised group,and all 29 classified as"real"were from the control group.Of the 7 cases deemed"suspicious,"6 were from the disguised group.The sensitivity,specificity,and overall diagnostic accuracy were 91.7％,96.7％(P＜0.0001),and 92.9％(P＜0.0001),respectively.In the disguised group,38 cases exhibited unexplained identifying anomalies.Conclusion A VA discrepancy of ≥ 2 lines is a reliable indicator for detecting disguised visual acuity.Identifying anomalies may serve as a novel and sensitive marker for recognizing visual disguise.

Objective To establish a lipid differentiation model of primary rat bone marrow mesenchymal stem cells(rBMSCs)in vitro using homocysteine(Hcy),and analyze the specific effects of Hcy on lipid and bone differentiation of BMSCs;to comprehensively explore the effects of mangiferin on lipid and bone differentiation of BMSCs,and further reveal the potential mechanism of mangiferin in the treatment of osteoporosis through the inter-vention of Hcy-induced BMSCs by different concentrations of mangiferin.Methods First,rBMSCs were extracted and isolated.The rBMSCs that were well-cultured to a certain generation were placed in culture medium containing different concentrations of Hcy(0.125,0.250,0.5,1,2,4 mmol/L)to establish lipid differentiation model of rBMSCs.Then,different concentrations of mangiferin(37.5,75,150 μmol/L)were applied to the experimental cells for intervention.After culture for a certain period of time,the cells were collected for the following tests:The accumulation of lipids in the cells was detected by semi-quantitative method of oil red 0 dye solution to evaluate the degree of lipid differentiation;The activity of alkaline phosphatase(ALP)was measured by pNPP method;The expression of bone morphogenetic protein-2(BMP-2)and type Ⅰ collagen(Col Ⅰ)were detected by western blot assay to evaluate the degree of bone differentiation.Results Mangiferin could significantly up-regulate the expression of BMP-2 and Col Ⅰ in vitro,increase the level of ALP,and promote bone differentiation of rBMSCs.Hcy promoted lipid differentiation of rBMSCs by increasing lipid accumulation,and down-regulated the expression of BMP-2 and Col Ⅰ,reduced the intracellular ALP level,thereby inhibiting bone differentiation of rBMSCs.How-ever,the above Hcy-related effects could be successfully reversed by mangiferin.Conclusion Mangiferin can sig-nificantly promote bone differentiation of rBMSCs in vitro,while Hcy can inhibit bone differentiation of rBMSCs and promote its lipid differentiation.Mangiferin has the ability to reverse this effect,indicating that mangiferin has certain potential in the treatment of osteoporosis-related diseases.

Ceruloplasmin(Cp)is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body,thereby maintaining copper homeostasis.Additionally,Cp functions as a significant enzyme known as ferroxidase,which is involved in iron metabolism within the body.Numerous studies have suggested a close relationship between Cp and metabolic disorders,such as diabetes and cardiovascular diseases.Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism.The various activities associated with lipid metabolism,including lipid synthesis,adipose hydrolysis,fatty acid oxidation,lipid transport,and absorption,collectively contribute to maintaining lipid homeostasis.Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications.Cp regulates lipid metabolism through two main mechanisms.Firstly,Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction.Secondly,copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism,lipoprotein metabolism,and fatty acid synthesis.As a result,the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways.Although the correlation between Cp and lipid metabolism has been identified,an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted.This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research,with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

AIM:To observe the anti-scarring effects and safety of triamcinolone acetonide(TA)-loaded hydrogel sustained-release sheeting on stab incision glaucoma surgery(SIGS)with “one-step tunnel method” in rabbit eyes.METHODS:A total of 48 healthy New Zealand white rabbits were randomly selected and divided into 4 groups(12 rabbits in each group), trabeculectomy(Trab)group, SIGS group, polyvinyl alcohol hydrogel(PVAH)sheeting was implanted under the conjunctiva flap during SIGS(PVAH group), and hydrogel sustained-release sheeting loaded with TA was implanted under the conjunctiva flap during SIGS(TA/PVAH group). On the 1, 2, 3, and 4 wk after surgery, the intraocular pressure, filtering bubble morphology, anterior chamber reaction, and other complications were observed and recorded in each group. Then animals were euthanized, and the surgery area tissues of right eye were taken for pathological tissue paraffin section. Masson staining, picric acid-Sirius rose red staining, as well as α-smooth muscle actin(α-SMA)and fibroblast growth factor 2(FGF2)immunohistochemistry staining was performed on every section. The infiltration of inflammatory cells, proliferation of fibroblasts and synthesis of type I and type III collagen fibers in local tissues were observed. The average positive area ratio of α-SMA and FGF2 antibody immunohistochemical staining in each group was calculated and compared.RESULTS: The TA/PVAH group maintained diffuse and elevated functional filtering blebs, while flat filtering blebs appeared in Trab, SIGS and PVAH groups at 2 wk after surgery. Functional filtering blebs were present in 1 eye(33%), 2 eyes(67%)in the PVAH and TA/PVAH group at 4 wk after surgery, respectively, while the other filtering blebs were flattened. Masson staining showed that the hydrogels in PVAH and TA/PVAH groups did not degrade at 4 wk after surgery. Compared with the Trab and SIGS groups, the filtration passages were more obvious, with less collagen fiber proliferation. Sirius red staining showed that the expression of type I collagen and type III collagen in the TA/PVAH group was less than that in the Trab group, SIGS group and PVAH group at 4 wk after surgery. Immunohistochemical staining showed that the α-SMA expression in the TA/PVAH group was significantly lower than that in the Trab and SIGS groups at 1 wk after surgery(P<0.01). The α-SMA expression was the highest in the Trab and SIGS groups at 2 wk after surgery, while the α-SMA expression in the PHAP and TA/PVAH groups was significantly lower than that in the first two groups(P<0.01). Compared with the Trab group, the expression of FGF2 in the PVAH and TA/PVAH group was significantly increased at 1, 2, 3 and 4 wk after surgery(P<0.05). Compared with the SIGS group, FGF2 expression in the TA/PVAH group was significantly increased at 4 wk after surgery(P<0.05).CONCLUSION:In SIGS surgery of rabbit eyes, implanting hydrogel sustained-release sheeting loaded with TA under conjunctival flap can effectively inhibit the scarring of the filtering bleb, which may be the interaction of the anti-scar effect of TA and the stent function of hydrogel.