Objective: To investigate the expression and functional role of FK506 binding protein 10 (FKBP10) in oral squamous cell carcinoma (OSCC), and to provide a research basis for the estimated prognosis and targeted therapy of OSCC. Methods: A total of 284 OSCC samples and 19 normal samples were selected from the Cancer Genome Atlas (TCGA) database, and diagnostic analysis was performed to determine mRNA expression. Survival analysis for FKBP10 and OSCC was conducted on a gene expression profile interaction analysis website. Real-time fluorescence quantitative PCR and Western Blot were used to detect the mRNA and protein expression of FKBP10 in four OSCC cell lines and SAS and SCC9 cells transfected with siRNA. The cell proliferation ability of FKBP10-silenced cells was detected using the CCK8 method, and the cell cycle distribution and apoptosis were detected by flow cytometry. Cell migration and invasion ability were detected through wound healing and invasion experiments. The expression changes of total protein and phosphatidylinositol 3-kinase (PI3K)-serine/threonine kinase (AKT) after FKBP10 silencing were analyzed by proteomics and Western Blot. Results: According to the analysis of gene expression levels, the mRNA expression level of FKBP10 in OSCC was significantly higher than that in normal tissues (P < 0.001). In terms of diagnosis, the expression level of FKBP10 has unique diagnostic value for OSCC (P < 0.05). The survival analysis of FKBP10 and OSCC showed that a high expression of FKBP10 led to a decrease in patient survival and poor prognosis (P < 0.05). The expression of FKBP10 mRNA and protein in OSCC cell lines was higher than that in normal oral keratinocytes (P < 0.001). Silencing FKBP10 can reduce the proliferation, invasion, and migration ability of SAS and SCC9 (P < 0.001), and also block their cell cycle in the G0/G1 phase (P < 0.001), with a significant increase in apoptosis (P < 0.05). Protein mass spectrometry and Western blot analysis revealed that FKBP10 silencing significantly downregulated the expression of multiple proteins in the RAP1 signaling pathway, mainly RAP guanine nucleotide exchange factor 1 (RAPGEF1) (P < 0.05) and the phosphorylation of PI3K-AKT proteins (P < 0.05). Conclusion FKBP10 is highly expressed in OSCC, leading to poor prognosis for patients. Downregulated FKBP10 expression can inhibit the proliferation, migration, and invasion ability of OSCC cells, hinder cell cycle progression, and promote apoptosis via the RAP1-PI3K-AKT axis. FKBP10 is a potential therapeutic target and prognostic biomarker for OSCC.

Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To explore the effects and mechanism of Salvianolic acid B(SalB)on Parkinson's disease(PD).Methods:Forty-eight C57BL/6 male mice were randomly separated into control group(control)withoutdrugs,model group(MPTP)with intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrah-ydropyridine(MPTP),SalB control group with intraperitoneal injection of SalB,and SalB treatment group(MPTP+SalB).Construction of PD mouse model by intraperitoneal injection of MPTP,and treatment with intraperitoneal injection of SalB.Pole climbing test was applied to assess behavior differences.The time of first black stool excretion and water content of feces were measured to evaluate intestinal dysfunctions.The number of tyrosine hydroxylase(TH)positive cells in substantia nigra and the level of Toll like receptor 4(TLR4)in colon were analyzed by immunohistochemistry.The pathological changes of colonic mucosa were observed by HE staining.The levels of calprotectin(CP)and tumor necrosis factor-α(TNF-α)in colon were determined by ELISA.Western blot was used to determine the level of TH in midbrain,the protein level of TH,tight junction protein(ZO-1),and protein level of TLR4/MyD88/NF-κB signaling pathways which express in colon.Results:Com-pared with the Control group,the climbing time,T-turn time and the first black stool excretion time in MPTP group increased while the fecal water content and the number of TH positive cells in substantia nigra were decreased.Accompanied by TLR4 positive cells in colon,pathological injury score of colonic mucosa,levels of CP and TNF-α in colon increased,expression of TH in midbrain and expression of ZO-1 in colon decreased.Expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon increased.Com-pared with MPTP group,SalB treatment shortened the climbing time,T-turn time and the first black stool excretion time in SalB treat-ment group,increased the fecal water content and the number of TH positive cells in substantia nigra,lowered TLR4 positive cells in colon,enhanced expression of TH in midbrain and colon,reduced the pathological injury score of colonic mucosa,significantly decreased levels of CP and TNF-α in colon,enhanced expression of ZO-1 in colon,inhibited expressions of TLR4,MyD88,Nuclear NF-κB p65 and p-NF-κB p65 in colon.Conclusion:SalB can protect the nerves and intestines and alleviate the intestinal inflamma-tion of PD mice,which may be related to the inhibition of TLR4/MyD88/NF-κB signal pathway.

Objective To investigate the clinical effect and hearing loss of endolymphatic sac decompression(ESD)combined with one or two semicircular canal obstruction(SCO)in treating the patient with stage Ⅲ or stageⅣ Meniere disease.Methods Forty-three patients with stage Ⅲ or stage Ⅳ Meniere disease,who failed to respond to conventional conservative treatment and had the expectation of preserving residual hearing function,were enrolled in the study.They were divided into three groups according to the operation they underwent:ESD combined with lateral and posterior semicircular canal obstruction(ESD+LPSCO)13 cases,ESD combined with lateral semicircu-lar canal obstruction(ESD+LPSCO)14 cases,and ESD only 16 cases.Data of vertigo,ear fullness and tinnitus be-fore and after operation was collected,analyzed and compared.Hearing function before and after the operation was also evaluated.Results The number of vertigo attacks in the three groups(ESD+LPSCO,ESD+LSCO,and ESD)were all significantly reduced after operation.The vertigo control rate were 92.3％,78.6％and 62.5％re-spectively.Compared with pre-operation,the vertigo severity post-operation in the three groups were also signifi-cantly reduced.And the improvement rate of vertigo severity after ESD+LPSCO and ESD+LSCO were both 100％,which were significantly higher than that of ESD(68.8％).The discomfort of tinnitus and ear fullness in the three groups were significantly improved compared with that of pre-operation.The improvement rates of tinnitus in the three groups were 46.2％,50.0％and 43.8％respectively,with no significant difference.The improvement rate of ear fullness in the three groups were 61.5％,57.1％and 50.0％respectively,with no significant difference either.The proportion of patients with decreased hearing after operation in the three groups was 15.4％,7.1％and 18.8％,respectively,and the differences were insignificant.Conclusion ESD combined with one or two SCO can effectively control vertigo and other symptoms of patients with stage Ⅲ or Ⅳ Meniere's disease who had failure to conventional conservative treatment,and can preserve the residual hearing function in considerable extent.

Objective:To analyze the acute poison epidemic and provide evidence for developing prevention and control strategies for acute poisoning.Methods:A retrospective analysis was conducted on acute poisoning cases collected from 2016 to 2022 in a health emergency information platform for acute poisoning accidents. The cases were grouped according to the distribution of poisoning occurrence time, geographic distribution, demographic distribution, types of toxicants, poisoning causes, and outcomes. Data were organized and analyzed using Excel 2016 and R 4.2.3.Results:A total of 95 754 acute poisoning cases were included in this study. The primary toxicants were pesticides, drugs, and industrial/household chemicals, accounting for 30.4%, 22.4%, and 20.4% of the total cases, respectively. Acute poisoning occurred throughout the year, with the highest frequency from June to August, accounting for 31.9%. The seasonal distribution varied among different types of toxicants. Except for plant poisoning, which showed a bimodal distribution, the other poisonings showed an unimodal distribution. There was a strong seasonality in fungal poisoning, which peaked in July. There was an obvious seasonality in animal poisoning, with a peak in August. The proportion of biological poisonings in the southwest region was higher than in other regions, including plants, animals, and fungi. There were more females than males, and their education level was mainly junior high school and below (35.2%). The main occupation was farmers (34.2%), and the main causes of poisoning were accidents and suicides. The case fatality rate of all poisoning cases was 1.24%. Pesticide poisoning was the most common type, and chlorfenapyr (11.68%), Diquat (7.23%), and paraquat (7.05%) ranked as the top three toxicants.Conclusions:The occurrence of acute poisoning has an obvious seasonal trend, and the toxicant spectrum of different regions and populations is different. A comprehensive poisoning surveillance system can provide a better understanding of the occurrence of poisonings, and facilitate the formulation of more scientifically precise poisoning prevention and control strategies.

Objective To explore the changes of the thickness of myometrium(MT),apparent diffusion coefficient value of myometrium(ADCM),thickness of junctional zone(JZT)and apparent diffusion coefficient value of junctional zone(ADCJz)in patients with endometrial fibrosis.Methods A total of 59 patients with endometrial fibrosis and 34 healthy women(volunteer)of childbearing age were prospectively included.The JZT,ADCJz,MT and ADCM were measured.Independent samples t-test was used to compare the differences in JZT,ADCJZ,MT,and ADCM between the two groups.A combined prediction model was established using binary logistic regression analysis(combining mean JZT,mean ADCJZ,and mean MT).The efficiency of each parameter's mean value and the combined prediction model in diagnosing endometrial fibrosis was evaluated using the receiver operating characteristic(ROC)curve.Results JZT(anterior wall,posterior wall,fundus and mean;P=0.007,0.035,0.001 and＜0.001,respectively),ADCJZ(anterior wall,posterior wall,fundus and mean;all P＜0.001)and MT(anterior wall,posterior wall and mean;P=0.003,＜0.001 and 0.003,respectively)were significantly larger in patients with endometrial fibrosis compared to volunteer.Mean ADCJZ[area under the curve(AUC)=0.872]and the combined prediction model(AUC=0.953)had high value for diagnosing endometrial fibrosis.Conclusion MRI can be used for noninvasively assessing the changes of myometrium and JZ in patients with endometrial fibrosis.

Objective:To construct a risk prediction and column chart model for venous thromboembolism (VTE) in patients with nephrotic syndrome and provide reference for VTE prevention.Methods:To use the retrospective cohort study design, the nephrotic syndrome patients who were hospitalized in Peking University Third Hospital from January 2018 to December 2022 were selected as the study subjects by convenient sampling method. Using univariate and multivariate Logistic regression analysis to analyze the risk factors for VTE in patients with nephrotic syndrome, establish a risk prediction model, and draw a column chart. The receiver operating characteristic (ROC) working curve and Hosmer Lemeshow test were used to verify the predictive performance of the model.Results:Among the 279 collected patients,187 males and 92 females, aged (54.25 ± 16.29) years, 43 cases developed thrombosis, with an incidence rate of 15.4%. The results of univariate analysis showed that different genders, ages, activity ability, alcohol consumption history, use of diuretics, albumin, hematocrit, fibrinolytic products, activated partial thromboplastin, D-dimer quantification and glomerular filtration rate showed differences in the occurrence of VTE in patients with nephrotic syndrome ( χ2=4.22, 4.62, 12.30, Z values were -5.73 to 6.07, t=-2.07,all P<0.05). The results of multivariate Logistic regression analysis showed that age, whether diuretics were used, activated partial thromboplastin, D-dimer and glomerular filtration rate were independent influencing factors for VTE ( OR values were 0.913- 3.285, all P<0.05). The above factors were five independent variables to construct a column chart. The area under the ROC curve of the model was 0.810, and the maximum value of the Jordan index was 0.518, the sensitivity was 66.67% and the specificity was 85.15%. The Hosmer-Lemeshow goodness-of-fit test showed that the model fit well ( χ2=12.00, P=0.151). Conclusions:The constructed column chart can personalized predict the risk of thrombosis in patients with nephrotic syndrome and help nursing staff in quickly identifying high-risk patients for thrombosis and taking corresponding intervention measures in a timely manner.

Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

A rapid analytical method for determination of paraquat and diquat in tea samples was established by improving the QuEChERS pre-treatment method combined with ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry(UPLC-MS/MS).Four kinds of tea powder were extracted by using acetonitrile-0.1％formic acid solution(3∶7,V/V)and ultrasonic treatment,and the supernatant was purified with 400 mg C18 and 400 mg PSA and separated on hydrophilic HILIC(100 mm×2.1 mm,1.8 μm)column by using 0.1％formic acid aqueous solution(Containing 5 mmol/L ammonium formate)and acetonitrile as mobile phases.In the electrospray ion source positive ion mode(ESI+),multiple reaction monitoring scanning technology(MRM)was used for determination,and the matrix-matched standard solution external standard method was used for quantitative analysis.The results showed that paraquat obtained good linear relationship in the content range of 0.18-200 μg/kg and diquat obtained good linear relationship in the content range of 0.36-200 μg/kg,and the correlation coefficients(R2)were 0.9939-0.9976 and 0.9959-0.9987,respectively.The limits of detection(LODs)were 0.06 and 0.12 μg/kg,and the limits of quantitation(LOQs)were 0.18 and 0.36 μg/kg,respectively.The average spiked recoveries for tea samples varied from 84.4％to 128.8％,with the relative standard deviations(RSDs)from 0.6％to 13.5％.The method was simple and efficient,with accurate quantification ability and low detection limit,which could realize efficient determination of paraquat and diquat in tea samples.

Objective:To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa.Methods:A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c. 997C>T (p.Q333X) and c. 3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. Conclusion:The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.