Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective:To screening differentially expressed genes (DEGs) in proliferative diabetic retinopathy (DR) patients to provide new biological therapeutic targets for proliferative DR (PDR) therapy.Methods:A basic research. A total of 3 PDR patients (group PDR) and 3 non-diabetic patients (control group) were enrolled in the study in Tianjin Medical University Eye Hospital in October 2020. In addition, 40 cases of PDR and non-diabetic patients were selected and divided into PDR validation group and control validation group. Peripheral blood validation test was performed in PDR validation group and control validation group; RNA sequencing was performed in PDR group and control group. Transcriptomics (RNAseq) sequencing technology was used to screen DEG in PDR group and control group. The selected DEGs were analyzed by gene ontology (GO) function enrichment analysis, signal pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI). The gene expression database was used to find the high-throughput data related to PDR, and multi queue comparison analysis was carried out. The target genes of differentially expressed miRNAs were predicted through targetscan platform, so as to clearly screen the correlation between DEG and PDR. Reverse transcription polymerase chain reaction and Western blot were used to verify the expression of DEG mRNA and protein related to PDR. The relative expression of PDR related DEG mRNA and protein between PDR validation group and control validation group were compared by paired t-test. Results:A total of 1 337 DEGs were screened by RNAseq sequencing in the peripheral blood of patients with PDR, of which 419 genes were up-regulated and 918 down-regulated. Among them, direct inhibitor of apoptosis protein-binding protein with low isoelectric point ( DIABLO), zinc finger and BTB domain containing 10 ( ZBTB10), polo-like kinases 3 ( PLK3), regulatory subunit 1 ( PIK3R1) and B cell translocation gene 3 (BTG3) were differentially expressed in PDR patients. The function of GO was enriched from the analysis of molecular function, biological process and cellular composition. The results showed that DIABLO, ZBTB10, PLK3, PIK3R1, BTG3 were involved in the pathological process related to PDR. KEGG enrichment analysis showed that glucose metabolic pathways such as extracellular matrix receptors, cytokine regulatory pathway, p53 signal pathway and galactose metabolism may be involved in the process of differential genes. The analysis of PPI protein interaction network showed that the larger the DEG-associated protein node, the greater the number of associated nodes. Among them, DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 played significant roles in the formation of the action network. By comparing and analyzing the existing high-throughput data related to diabetic retinopathy in Gene Expression Omnibus database and predicting by Targetscan platform, it was found that some significant differences in miRNA reported in aqueous humor, vitreous fluid and plasma of DR patients can be regulated by the differential genes found in this study. Compared with the control verification group, the relative expressions of DIABLO, ZBTB10, PLK3, PIK3R1 mRNA and protein in peripheral blood of the PDR verification group were up-regulated, and the relative expression of BTG3 mRNA and protein was down-regulated. Conclusion:DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 are DEGs in patients with PDR, and they can participate in the disease process by regulating the biological processes of cell proliferation, fibrosis and oxidative stress.

Objective To discuss the clinical characteristics of adrenal metastases,and summarize the experience of diagnosis and treatment.Methods From January 2008 to June 2018,the clinical data of 55 patients with adrenal metastases treated in our hospital were analyzed retrospectively.This study included 34 male patients and 21 female patients and the median age was 60 years old (ranged 55 to 84 years old).The median value of maximum diameter of adrenal metastases was 3 cm (ranged 1.9 to 10.3 cm);with 35 cases on the left side,13 cases right and 7 cases bilateral.The primary sites of malignant tumors were pancreas (18 cases,32.7％),lung (12 cases,21.8％),liver (6 cases,10.9％) and colorectum (6 cases,10.9％),respectively.Thirty-four cases were confirmed by pathology after adrenalectomy and 21 cases were confirmed by needle biopsy.Thirty cases were diagnosed synchronously with the primary tumor and 25 cases were metachronous.The median time from diagnosis of primary tumors was 13.3 months (ranged 2.0 to 97.4 months).42 cases of these 55 cases were diagnosed within one year.Treatment options for adrenal metastatic lesions included single adrenalectomy in 18 cases,adrenalectomy combined with radiotherapy 16 cases,single intravenous chemotherapy 10 cases,intravenous chemotherapy combined with non-operative treatment 10 cases and single radiotherapy 1 case.Results The main pathological types were adenocarcinoma (19 cases,34.5％),ductal adenocarcinoma (10 cases,18.2％),hepatocellular carcinoma (6 cases,10.9％) and clear cell carcinoma (4 cases,7.3％).Two cases were lost follow-up and the follow-up rate was 96％,the median follow-up time was 8 months (ranged 1 to 135 months).The median overall survival (OS) time of 55 patients was 5.3 months (ranged 1 to 134 months).The one-year survival rate was 23.6％ (13/55),the two-year survival rate was 12.7％ (7/55),the three-year survival rate was 9.1％ (5/55) and the five-year survival rate was 1.8％ (1/55).Conclusions Pancreatic cancer was the most common type of malignant tumor for adrenal metastases in our hospital.Most primary tumors and adrenal metastases were diagnosed synchronously or within one year.Comprehensive treatment with retroperitoneal adrenalectomy may improve the OS,however the overall prognosis is poor.

Objective To observe RNA-Seq analysis ofgene expression profiling in retinal vascular endothelial cells after anti-vascular endothecial growth factor (VEGF) treatment.Methods Retinal vascular endothelial cells were cultured in vitro,and the logarithmic growth phase cells were used for experiments.The cells were divided into the control group and high glucose group.The cells of two groups were cultured for 5 hours with 5,25 mmol/L glucose,respectively.And then,whole transcriptome sequencing approach was applied to the above two groups of cells through RNA-Seq.Now with biological big data obtained as a basis,to analyze the differentially expressed genes (DEGs).And through enrichment analysis to explain the differential functions of DEGs and their signal pathways.Results The gene expression profiles of the two groups of cells were obtained.Through analysis,449 DEGs were found,including 297 upregulated and 152 downregulated ones.The functions of DEGs were influenced by regulations over molecular biological process,cellular energy metabolism and protein synthesis,etc.Among these genes,ITGB 1BP2,NCF 1 and UNC5C were related to production of inflammation;AKR1C4,ATP 1A3,CHST5,LCTL were related to energy metabolism of cells;DAB 1 and PRSS55 were related to protein synthesis;SMAD9 and BMP4 were related to the metabolism of extracellular matrix.GO enrichment analysis showed that DEGs mainly act in three ways:regulating biological behavior,organizing cellular component and performing molecular function,which were mainly concentrated in the system generation of biological process part and regulation of multicellular organisms.Pathway enrichment analysis showed that gene expressions of the two cell groups were differentiated in transforming growth factor-β (TGF-β) signaling pathway,complement pathway and amino acid metabolism-related pathways have also been affected,such as tryptophan,serine and cyanide.Among them,leukocyte inhibitory factor 9 and bone morphogenetic protein 4 play a role through the TGF-β signaling pathway.Conclusions High glucose affects the function of retinal vascular endothelial cells by destroying transmembrane conduction of retinal vascular endothelial cells,metabolism of extracellular matrix,and transcription and translation of proteins.

Objective To observe the synergistic effect of metformin and anti-vascular endothelial growth factor (VEGF) in the treatment of diabetic retinopathy.Methods This study was composed of clinical data review and in vitro cell experiment.Ten patients (12 eyes) with diabetic macular edema treated with antiVEGF drugs were included in the study.Patients were randomly divided into the VEGF group (anti-VEGF drug therapy) and the combined treatment group (anti-VEGF drug combined with metformin).The changes of visual acuity and central retinal thickness (CRT) were compared between the two groups.As far as the in vitro experiment was concerned,vascular endothelial cells were divided into the control group (normal cells),the VEGF group (50 ng/ml VEGF),the anti-VEGF group (50 ng/ml VEGF+2.5 μg/ml of conbercept),and the combined group (50 ng/ml VEGF +2.5 μg/ml of conbercept +2.0 mmol/L of metforrnin).And then MTT cell viability assay,scratch assay and real-time quantitative polymerase chain reaction assay were performed to analyze the cell viability,cell migration and mRNA level of VEGFR2,protein kinase C (PKC)-α and PKC-β successively.Results Review of clinical trial shows that the CRT recovery rates in the combined treatment group were much higher than that in the VEGF group at 3 month after the operation,while the difference was statistically significant (t=-2.462,P＜0.05).In vitro cell experiment results showed that VEGF induction upregulated the viability and mobility of vascular endothelial cells obviously compared with control group,at the same time,the use of anti VEGF drugs can effectively reverse the trend,in contrast,combination of metformin and anti-VEGF showed a more superior effect to some extent (P＜0.05).In the VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-[β were significantly increased compared with the control group (P＜ 0.01);while the mRNA expression of VEGFR2,PKC-αand PKC-β in the combination group decreased significantly compared with the VEGF group and the control group (P＜0.05).However,in the anti-VEGF group,the mRNA expression of VEGFR2,PKC-αand PKC-β were decreased,but has failed to reach the level of statistical learn the difference.Conclusions The combination ofmetformin and anti-VEGF drugs can reduce the CRT of diabetic retinopathy patients and inhibit the proliferation and migration of retinal vascular endothelial cells which induced by VEGF.The synergistic mechanism may be related to the inhibitory effect of metformin on the expression of VEGFR and PKC.

Yersinia pestis, the cause of plague, is transmitted by flea bite. Y. pestis forms a biofilm in the proventriculus of its flea vector to enhance transmission. Biofilm formation in Y. pestis is positively regulated by the intracellular levels of the second messenger cyclic diguanylate (c-di-GMP). The c-di-GMP in Y. pestis is synthesized by two diguanylate cyclases (DGC), HmsT and HmsD, and degraded by phosphodiesterase (PDE), HmsP. Here we summarized the regulators that modulate c-di-GMP metabolism and biofilm formation in Y. pestis and discussed their regulatory mechanism.

Objective:To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy. Meth-ods:HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were de-tected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression. Results:In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expres-sion of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentra-tions of 100 nmol by 10.7%and 200 nmol by 38.9%(P<0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9%(P<0.05) in the 5μmol/L group but not in the 1μmol/L group. SAHA significantly affected the pri-mary cells at a concentration of 1μmol/L and reduced the cells at 87.1%at a concentration of 5μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors. Conclusion: HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.

Objective To understand the various HPV types and the factors influencing their distribution among women with normal cervical cytology in the Shanghai area, to provide basic data for cervical cancer prevention and vaccine use.Methods A questionnaire-based survey was conducted among 3 372 married women in the Shanghai area. A PCR reverse dot blot (PCR-RDB) method was adopted for HPV genotyping of cervical exfoliated cell samples from 3 206 women. Odds ratio (OR) for HPV infection were analyzed using logistic regression. Results Of the 3 206 women investigated, 669 (20.87%) were positive for HPV infection. The highest incidence of HPV infections was seen in the age groups of 55-59 years, 50-54 years and 45-49 years, with the rates of positive detection being 27.67%, 21.65%, and 21.55%, respectively. While 70.4% of the positive cases had a single infection, 29.6% showed multiple infections. In cases with multiple infections, double infection was predominant (20.63%). The top five high-risk gene types were HPV52(3.65%),HPV53(2.71%),HPV51(2.03%),HPV58(1.87%),and HPV16 (1.40%). The top three low-risk gene types were HPV81 (2.03%), HPV42 (1.43%), and HPV55 (1.31%). Among the women with HPV infections,there were 483 having medium-high-risk HPV infection.There were significant differences in the age,the age at first sexual activity,sexual activities per week,education,and alcohol consumption between HPV positive and HPV negative patients. Age stratification showed that the infection rates in the 55-59 years old group were significantly higher than that in the other age groups(χ2=15.349, P=0.000). Both single factor and multivariate non-conditional logistic regression analyses showed that higher education and the start of sexual activity at a later age were protective factors for medium-high-risk HPV infection,with regression coefficients of-0.165 and-0.08,respectively (P<0.01) in the multivariate analysis. The risk factors included age between 55- 59 years, menstrual status (menopause), sexual activity (≥3 times per week) and alcohol consumption. High-risk HPV infections also had the same risk factors,and the odds ratios were 1.558,1.275,and 1.678,respectively(P<0.01).However, 55-59 years of age and alcohol consumption are independent risk factors for medium-high risk HPV infection. Conclusions High-risk HPV in women of Shanghai is commonly caused by HPV52, HPV53, HPV51,HPV58,and HPV16.The high-risk group includes women who are 55-59 years old.While drinking is an independent risk factor for medium-high risk HPV infection, a moderate sex life and delayed age at first sex can reduce the risk of high-risk HPV infections.

Objective To study the prognostic factors of survival in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib.Methods From May 2008 to Dec 2012,the clinical data of 82 cases with mRCC adminstered by sunitinib were reviewed retrospectively.The study included 60 male patients and 22 female patients,whose age ranged from 29 to 82 years [mean (56.1±11.3) years].Among them,52 cases presented hematuria,flank pain and palpable mass.The size of renal tumor ranged from 2.0 to 18.0 cm [mean (8.0±3.0) cm].The location of tumor included 41 in left kidney,37 in right kidney and 4 in bilateral kidney.The pathological tissue obtained from the operation in 69 cases and from biopsy in 13 cases.The pathological results demonstrated renal cell carcinoma in 75 cases,papillary cell carcinoma in 2 cases,chromophobe cell carcinoma in 2 cases,sarcomatoid carcinoma in 2 cases,collecting duct carcinoma in one case.The site of metastasis included lung in 50 cases,liver in 11 cases,bone in 14 cases,pancrease in 3 cases,retroperitoneal lymph node in 31 cases.In 52 cases,the ECOG scores ranged from 1 to 2.The others scores were more than 3.The average level of hemoglobin,AKP,LDH and leukocyte were (132±24)g/L,(90±65) U/L,(168±114) U/L and (6.4±2.0)×109/L,respectively.Before treatment,the abnormal cases in those parameters were 59,9,6 and 2,respectively.According to the MSKCC risk model,14 cases were classified into the high risk group and 68 cases into medium risk group.74 cases were accepted the sunitinb therapy within one year after diagnosis and 8 cases were accepted same therapy until one year after diagnosis.The overall survival (OS) rates were calculated by Kaplan-Meier method and Cox regression model was used to analyze the relationship between the influencing factors and the prognosis.Results The average OS was (21.6± 14.1) months (ranged 2.8 to 64.1 months).The survival rate at 1 st,2nd and 3rd year were 71％,64％ and 58％,respectively.Single factor analysis showed that significant prognostic factors were as follows:ECOG performance status ≥ 2 (P =0.005),clinical symptom during first clinic visiting (P =0.031),without nephrectomy (P =0.012),the number of metastatic sites ≥ 2 (P =0.015),hemoglobin before treatment (P=0.005),serum AKP level before treatment (＞126 U/L) (P=0.007),MSKCC score≥ 3 (P =0.000),the presence of liver metastases (P =0.000) and bone metastases (P =0.000) and relative dose intensity in the first month (1M-RDI) of sunitinib ≥ 50％ (P=0.000).Cox regression model showed that the beneficial predictive factors were ECOG performance status＜2 (P=0.136),no symptom during the first clinic visiting (P=0.801),serum AKP ＜126 U/L (P=0.618) before treatment,the absence of bone (P =0.068) and pancreas metastases (P =0.265).Sunitinib 1M-RDI ≥ 50％ was the independent predictive factor (P=0.000).Conclusions In targeted therapy era,there is some change in the prognostic factors for mRCC and target drug play an important role in the prognosis of mRCC.Sunitinib 1M-RDI ≥50％ is the independent predictive factor for the prognosis of renal carcinoma.

Objective To investigate the clinical features , diagnosis and key technique points of laparoscopic partial adrenalectomy for small adrenal pheochromocytoma . Methods From Oct.2006 to Jun. 2011, clinical data of 32 cases with small adrenal pheochromocytoma (≤3.0 cm) were collected and retro-spectively analyzed .Hypertension was observed in 12 patients, whereas 20 patients presented with adrenal incidentaloma .Thirteen patients had a left adrenal neoplasm , eighteen patients had a right adrenal tumor , while one patients had bilateral tumors .The positive rate of plasma-free metanephrines ( MNs) and 24-hours urinary catecholamine (CA) in diagnosing small renal pheochromocytomas was 92.6%(25/27) and 81.3%(26/32) respectively.The main localization diagnosis included ultrasonography , 131I-MIBG, and CT or MRI, with positive rates of 71.9%(23/32), 93.8%(15/16) and 96.9%(31/32) respectively.All the laparoscopic adrenalectomies were performed retroperitoneally .During the surgery , the internal part of the adrenal gland closing to the retroperitoneum was dissected first , and the whole adrenal gland was resected completely. Results Partial adrenalectomy was performed for 30 cases and radical adrenalectomy for 2 ca-ses.All operations were successful without perioperative or postoperative complications .The maximum diame-ter of tumor was 1.7±0.2 (1.0-3.0) cm.Histopathological results showed that all the cases were benign pheochromocytoma.The operative time was 82 (40-210) min.The estimated blood loss was 57 (20-180) ml.No patient required blood transfusion . Conclusions Plasma-free MNs, 24-hours urinary CA and VMA are important qualitative examinations in detection of adrenal pheochromocytoma .Ultrasonography , CT,MRI, and 131 I-MIBG are important in the localization of adrenal tumors .Retroperitoneal laparascopic partial adrenalectomy is the preferred choice in the management of small adrenal pheochromocytoma .Dissecting the internal part of the adrenal gland closing to the retroperitoneum first and exploring the whole adrenal tissue are the key technique points during the operations .