AIM: To investigate the protective effect of β-sitosterol on retinal structure and function and its underlying molecular mechanism in a sodium iodate(NaIO3)-induced mouse model of dry age-related macular degeneration(ARMD).METHODS: A dry ARMD mouse model was established by NaIO3 injection. The therapeutic effect of β-sitosterol intervention was evaluated using fundus photography, histopathology(HE staining), and electroretinography(ERG). Network pharmacology was employed to screen potential targets of β-sitosterol in ARMD, and molecular docking was used to validate the binding ability between β-sitosterol and these targets. The impact of β-sitosterol on ARPE-19 cell viability and apoptosis pathways was analyzed using CCK-8 assay, Hoechst staining, and Western blotting.RESULTS: The β-sitosterol significantly alleviated structural damage in the retinas of model mice(increased retinal and outer nuclear layer thickness, reduced yellowish-white drusen-like deposits)and functional impairment(partial restoration of a-wave and b-wave amplitudes). Network pharmacology identified PON1 as a key target of β-sitosterol; molecular docking demonstrated that β-sitosterol binds to PON1 via hydrophobic interactions and hydrogen bonds. In vitro experiments showed that β-sitosterol(10 μmol/L)significantly increased ARPE-19 cell viability(P<0.01), reduced apoptosis(P<0.01), upregulated PON1 expression(P<0.01), and concurrently suppressed cleaved-Caspase3 expression(P<0.01).CONCLUSION: The β-sitosterol likely protects against oxidative stress-induced retinal damage by modulating PON1 to suppress the Caspase3-dependent apoptotic pathway. These findings provide experimental evidence supporting the development of β-sitosterol as a novel therapeutic agent for dry ARMD.

Objective: This study aims to explore the association between oral lichen planus (OLP) and Hashimoto’s thyroiditis (HT) and its anti-thyroid antibodies to provide clinical evidence for thyroid disease screening in patients with OLP. Methods: This study was approved by the institutional ethics committee. A total of 125 clinically and histopathologically confirmed patients with OLP were enrolled as the case group, and they were matched with 125 non-OLP controls based on sex and age. Demographic data (gender, age, lesion type, and disease duration) were collected from both groups. Serum levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured to analyze their associations with sex, age, lesion type, and disease duration in patients with OLP. Result: The prevalence of HT in patients with OLP was 31.20%, significantly higher than that in the control group (9.60%) (χ2=18.504, P<0.001). The prevalence of HT in female patients with OLP (39.13%) was significantly higher than that in male patients (9.09%)（χ2=10.93，P<0.001）. The positivity rate of thyroid peroxidase antibodies (TPOAb) in patients with OLP (17.6%) was significantly higher than in the control group (4.0%) (χ2=10.989, P<0.001). The TPOAb positivity rate was significantly higher in female patients (22.83%) than in male patients (3.03%) (χ2=5.210, P=0.014). There was no statistically significant difference in the positivity rate of TgAb between patients with OLP (7.2%) and the control group (3.2%) (P>0.05). Patients with erosive lesions had a significantly higher TPOAb positivity rate (25.0%, 17/68) compared to those with non-erosive lesions (8.77%, 5/57), and the difference was statistically significant (χ2=4.831, P=0.028). Logistic regression analysis revealed that female patients with OLP had an 8.935-fold higher risk of being TPOAb positive compared to males (OR=8.935, 95%CI: 1.134-70.388, P=0.038). Patients with erosive OLP lesions had a 3.199-fold higher risk of TPOAb positivity compared to those with non-erosive lesions (OR=3.199, 95%CI: 1.064-9.618, P=0.038). Conclusion The prevalence of HT is higher in patients with OLP, with higher positivity rates of anti-thyroid antibodies observed in female patients and those with erosive OLP lesions. This suggests that thyroid disease screening should be incorporated into the clinical management of patients with OLP, especially for women and patients who present with erosive lesions.

AIM: To investigate the relationship between vascular smooth muscle cell (VSMC) injury, organelle stress response and autophagic cell death (autophagy) and ferroptosis induced by the chemical hypoxia inducer cobalt chloride (CoCl2) through the bioinformatics analysis and in vitro cell experimentation. METHODS: The dataset GSE119226 of VSMC treated with cobalt chloride was acquired from the gene expression database (GEO). The R language was used to investigate the relationship between CoCl2 treatment and organelle stress response (Golgi stress, endoplasmic reticulum stress) and two forms of cell death (ferroptosis and autophagic cell death). With primary cultured rat VSMC (rVSMC) and CoCl2-induced anoxia model, the changes in cell viability were detected by CCK-8 method, and reactive oxygen species (ROS) levels were measured using DCFH-DA method. The expression levels of HIF-1α (a key molecule in hypoxia), Golgi stress markers GM130 and p115, endoplasmic reticulum stress markers GRP78 and CHOP, autophagy markers LC3-II / LC3-I and Beclin1, and ferroptosis markers GPx4 and xCT were detected by Western blot. The effect of inducing or inhibiting organelle stress and cell death on the CoCl2-induced cell damage was also observed. RESULTS: Differentially expressed genes analysis of GSE119226 dataset showed that CoCl2 treatment of VSMCs had significant effects on organelle function and stress response, autophagy and ferroptosis-related genes, in which endoplasmic reticulum stress, protein processing in endoplasmic reticulum, regulation of Golgi to plasma membrane protein transport, autophagy / autophagic cell death, and ferroptosis pathways were remarkably enriched. The results of in vitro experiment showed that compared with normal rVSMC, cell viability was significantly decreased after CoCl2 treatment, as well as HIF-1α protein expression and ROS levels in rVSMCs were increased. In rVSMC treated with Co-Cl2, the expression levels of Golgi structural proteins GM130 and p115 (reflecting the occurrence of Golgi stress) were decreased, while the markers GRP78 and CHOP (reflecting the occurrence of endoplasmic reticulum stress) were increased. At the same time, CoCl2 treatment also reduced the expression of autophagy markers LC3-II/LC3-I and Beclin1 (indicating the decrease levels of autophagy), while the expression of ferroptosis markers GPx4 and xCT were decreased (indicating the occurrence of ferroptosis). Compared with CoCl2 treatment group, induced Golgi stress, endoplasmic reticulum stress, or ferroptosis could further reduce cell viability, while inhibition of these processes could improve cell viability. On the other hand, increasing the level of autophagy can improve the cell viability. CONCLUSION: Hypoxia induced by cobalt chloride can lead to VSMC injury. Golgi stress, endoplasmic reticulum stress, ferroptosis, and the reduction of autophagy level play an important role in it. Inhibition of organelle stress response and ferroptosis, or increase of autophagy level can improve VSMC injury caused by cobalt chloride.

Fungal infections of the digestive tract in children can be caused by a variety of fungi, the most common of which are Candida and Aspergillus.Occurrence of invasive fungal infections is dependent on numerous factors including geographic location and routes of exposure, and host factors, such as predisposing conditions, high-risk medications, or underlying medical comorbidities that modulate overall immune function.However, advances in DNA and ribosomal RNA sequencing and serologic testing have led to shifts in how gut fungal microbiota are identified and in diagnosing opportunistic infections.This article will briefly expound the common pathogens, risk factors, clinical manifestations, diagnosis, and treatment of gastrointestinal fungal infections in children.

Objective To assess the tear film stability and morphological characteristics of the tarsal gland in myopic children.Methods In this prospective descriptive study,myopic children who performed refractive examinations in the Pediatric Ophthalmology & Refraction Clinic,Jinan Mingshui Eye Hospital from November 2021 to November 2022 were in-cluded.An Ocular Surface Disease Index(OSDI)questionnaire survey was carried out;tear meniscus height(TMH),non-invasive first breakup time(NIf-BUT)and images of the tarsal glands were obtained by OCULUS Keratograph 5M compre-hensive ocular surface analyzer.In addition,the atrophy and tortuosity of tarsal glands were scored to analyze the tear film stability and clinical characteristics of tarsal glands in myopic children.Results A total of 48 myopic children(91 eyes)aged from 7 to 16(10.25±2.23)years were recruited,including 27 males(56.25％)and 21 females(43.75％).The aver-age TMH was(0.19±0.04)mm(95％CI:0.18-0.19)and the average NIf-BUT was(5.40±2.62)s(95％CI:4.90-5.94);the TMH was positively correlated with NIf-BUT(r=0.223,P=0.034).The tarsal gland atrophy score was 1(0,1).The tortuosity score of the upper and lower tarsal gland was 0(0,1)and 0(0,0),respectively,with a statistically significant difference(Z=3.692,P＜0.001).In all subjects,49 eyes(53.85％)had tarsal gland atrophy,and 37 eyes(40.66％)had tarsal gland tortuosity.There were significant differences in TMH and NIf-BUT between children aged＜12 years and children aged ≥12 years(both P＜0.05).There was a significant difference in TMH between children with an OSDI score＜13 and children with an OSDI score ≥ 13(t=2.305,P=0.026).There was a significant difference in NIf-BUT between mild and moderate myopia children(t=2.300,P=0.024);the spherical equivalent was positively correlated with NIf-BUT(r=0.283,P=0.023).Conclusion Children with mild to moderate myopia show low tear film stability and a certain proportion of abnormal morphology in tarsal glands.In addition to the refractive status of children,attention should also be paid to ocular surface health in the refraction clinic.

Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

Objective To investigate the correlation between serum Irisin,long pentraxin 3(PTX3),human metas-tasis-associated lung adenocarcinoma transcript 1(MALAT1)levels and the severity of diabetic retinopathy(DR)and the value of combined diagnosis.Methods Eighty-five patients with type 2 diabetes mellitus(T2DM)combined with DR at Cangzhou Central Hospital from April 2022 to April 2023 were selected as the DR group,85 patients with T2DM alone were selected as the non-DR group,and 85 healthy volunteers were selected as the control group during the same period.Pa-tients in the DR group were further divided into the proliferative DR(PDR)group(38 patients)and the non-PDR group(47 patients)based on whether DR was in the proliferative phase.Clinical data of patients in the DR group were collected,including gender,diastolic pressure,age,systolic pressure,disease course,fasting plasma glucose(FPG),body mass in-dex,hemoglobin A1c(HbA1c),smoking history,triglyceride(TG),drinking history,peak systolic velocity(PSV),peak end-diastolic velocity(PEDV),resistance index(RI),fasting insulin(FINS),family history of diabetes,total cholesterol(TC),and homa-insulin resistance(HOMA-IR).Enzyme-linked immunosorbent assay was used to detect serum levels of Irisin and PTX3 in each group of patients,and real-time quantitative polymerase chain reaction was used to detect the ser-um level of MALAT1.The correlations between serum levels of Irisin,PTX3 and MALAT1 and the severity of DR were ana-lyzed using the Pearson correlation coefficient.The influencing factors of the DR severity were identified using the Logistic regression.The value of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR alone was analyzed using the receiver operating characteristic(ROC)curve.The value of regimens containing and not containing serum Irisin,PTX3,and MAL-AT1 levels in diagnosing DR was analyzed using the ROC curve,net reclassification index(NRI),and integrated discrimina-tion improvement(IDI)index.Results The serum levels of Irisin,PTX3,and MALAT1 were compared among the three groups of patients,and the differences were statistically significant(all P＜0.001).The disease course of patients in the PDR group was longer than that in the non-PDR group,the PSV,PEDV and serum Irisin level were lower than those in the non-PDR group,while the RI,FPG,HbA1c,TG,FINS,HOMA-IR,and serum PTX3 and MALAT1 levels were higher than those in the non-PDR group(all P＜0.05).The serum Irisin level in DR patients was negatively correlated with the severity of DR(r=-0.512,P＜0.001),while the PTX3 and MALAT1 levels were positively correlated with the severity of DR(r=0.497,0.573,both P＜0.05).The Logistic regression analysis showed that the disease course,FPG,HbA1c,TG,FINS,HOMA-IR,PSV,PEDV,RI,and serum levels of Irisin,PTX3 and MALAT1 were influencing factors for the DR progression(allP＜0.05).The area under the curve(AUC)of serum Irisin,PTX3,and MALAT1 levels in diagnosing DR was 0.743,0.811,and 0.773,respectively.Compared with conventional diagnostic protocols,the AUC of the new diagnostic protocol containing serum levels of Irisin,PTX3,and MALAT1 significantly increased(Z=2.708,P=0.007),and the NRI and IDI were 0.039(95％CI:0.022-0.069)and 0.026(95％CI:0.014-0.047),respectively(all P＜0.05).Conclusion The serum Irisin level in DR patients decreases,while the serum PTX3 and MALAT1 levels increase,which are closely related to the severity of DR.Diagnostic plans containing serum Irisin,PTX3,and MALAT1 indicators have high diagnostic value.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objective To study Chinese medicine consultation strategies to achieve rapid capture of key information about patients'conditions and to advance the development of objectification in Chinese medicine consultation.Methods A symptom questioning model based on frequent pattern mining algorithm in correlation analysis was used,and a cross-merging method was used to establish a TCM symptom questioning strategy between single-system symptom questioning and multi-system integrated symptom questioning in TCM,to achieve the shortest time and highest efficiency in capturing key information about the patient's condition.Results A breakthrough from single-system questioning to five-system integrated questioning was achieved,and the process of efficiently obtaining information about the patient's condition was achieved through both single-system and five-system symptom questioning modes,and the system was able to obtain 92%of the patient's symptom information with at most 65%fewer questions than the traditional scale questioning method,greatly improving the efficiency of obtaining information about the patient's symptoms.Conclusion With the two different symptom questioning modes,the traditional TCM questioning mode of asking patients based on scales is broken,the time to obtain symptoms from patients is shortened,the questioning process is simplified,and discrepancies due to inexperience or human subjectivity are reduced,which can be used in clinical aids to diagnosis in TCM.