This study assessed the effects of leukemia-related protein 16 (LRP16) on the regulation of pancreatic functions in mouse insulinoma (MIN6) cells. Cells with down-regulated expression of LRP16 were obtained by a shRNA interference strategy. Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay. Western blotting was applied to detect protein expression. Glucose-stimulated sub-cellular localization of PDX-1 was immunocytochemically determined. Cell proliferation and apoptosis were detected by flow cytometry. Our results showed that LRP16 regulated insulin content in MIN6 cells by controlling expression of insulin and insulin transcription factors. LRP16 gene silence in MIN6 cells led to reduced cell proliferation and increased apoptosis. The observation of phosphorylation of serine-473 Akt and the localization of PDX-1 to the nucleus under glucose-stimulation exhibited that LRP16 was a component mediating Akt signaling in MIN6 cells. These results suggest that LRP16 plays a key role in maintaining pancreatic β-cell functions and may help us to understand the protective effects of estrogen on the functions of pancreatic β-cells.

A technique of diffusive gradients in thin films (DGT) was developed for the in situ measurement of reactive phosphorus species in natural waters, sediments and potentially soils. Polyacrylamide / basic magnesium carbonate was used as the novel binding phase of DGT. Various factors, such as initial concentration, deployment time, pH and ionic strength, which may affect the adsorption of phosphate to the DGT were investigated. H2 SO4(0. 25 mol/ L, 10 mL) was used for elution of phosphate from the binding gel, and an elution efficiency of 85±5% was obtained. The DGT measurement was independent of ionic strength (0. 001-0. 05 mol/ L) and pH (4. 10-9. 15). The results indicated that the maximum adsorption capacities of DGT were limited to 20. 4 μg per disc ( T = 25℃, pH = 7. 00, [ P] = 2 mg / L). Good agreement was obtained between the measurement results of DGT method and molybdenum blue method in the P concentration from 0. 001 to 20 mg / L. The method detection limit (MDL) was 102. 4 ng / L. Field performances of DGT in synthetic seawater, the coastal seawater of Xiamen, Lake Yihai, Lake Chaohu and Nanfei River indicated that the basic magnesium carbonate-DGT method was more reliable than the commonly used ferrihydrite-DGT method.

This study assessed the effects of leukemia-related protein 16 (LRP16) on the regulation of pancreatic functions in mouse insulinoma (MIN6) cells.Cells with down-regulated expression of LRP16 were obtained by a shRNA interference strategy.Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay.Western blotting was applied to detect protein expression.Glucose-stimulated sub-cellular localization of PDX-1 was immunocytochemically determined.Cell proliferation and apoptosis were detected by flow cytometry.Our results showed that LRP16 regulated insulin content in MIN6 cells by controlling expression of insulin and insulin transcription factors.LRP16 gene silence in MIN6 cells led to reduced cell proliferation and increased apoptosis.The observation of phosphorylation of serine-473 Akt and the localization of PDX-1 to the nucleus under glucose-stimulation exhibited that LRP16 was a component mediating Akt signaling in MIN6 cells.These results suggest that LRP16 plays a key role in maintaining pancreatic β-cell functions and may help us to understand the protective effects of estrogen on the functions of pancreatic β-cells.

Objective To investigate the predictive factors for death within 30 days after admission in patients with decompensated liver cirrhosis and acute kidney injury(AKI),and to establish and validate a nomogram prediction model.Methods The Joint Medical Record Management System of The First Affiliated Hospital of Nanchang University was used to obtain the patients with decompensated liver cirrhosis who were hospitalized in Department of Gastroenterology and Department of Infectious Diseases from January 2015 to December 2020,among whom 330 patients who met the 2015 International Club of Ascites diagnostic criteria for AKI were enrolled and divided into training group with 193 patients and validation group with 137 patients.A Cox regression analysis was used to investigate the predictive factors for death,and then a nomogram prediction model for the risk of death within 30 days after admission was established and validated.The independent-samples t-test was used for comparison of normally distributed continuous data between two groups,and a one-way analysis of variance was used for comparison between multiple groups,while the least significant difference t-test was used for further comparison between two groups;The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups,while the Kruskal-Wallis H test was used for comparison between multiple groups.The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results The prevalence rate of AKI was 16.5%in patients with decompensated liver cirrhosis.The 330 patients included in the study had a mean age of 53.6±12.4 years,and male patients accounted for 79.1%.The mortality rate was 50.0%within 30 days after admission,with a mortality rate of 46.6%in the training group and 54.7%in the validation group.The presence of acute-on-chronic liver failure(ACLF)on admission was an independent risk factor for the progression of AKI into stage 1(odds ratio=2.571,95%confidence interval:1.143-5.780,P=0.022).The nomogram based on white blood cell count,international normalized ratio,presence or absence of hepatic encephalopathy,and AKI stage on admission could well predict the risk of death with 30 days after admission,with a C-index of 0.680 in the training group and 0.683 in the validation group,and it was not inferior to CTP score and MELD score.Conclusion ACLF is an independent risk factor for the progression of AKI into stage 1.The nomogram prediction model established in this study can effectively predict the risk of death within 30 days after admission and thus has important guiding significance for the early identification and management of patients with decompensated liver cirrhosis and AKI.

Objective To investigate arterial endothelial dysfunction in stable chronic obstructive pulmonary disease (COPD) patients and the correlation between the degree of endothelial dysfunction and the severity of COPD.Methods Forty stable COPD patients were enrolled in a COPD group and 30 non-COPD individuals in a control group.The endothelium-dependent flow-mediated vasodilatation (FMD) of the brachial artery and serum eNO value were measured in both groups.Forced expiratory volume in 1 second (FEV1)/prediction of FEV1 was determined and expressed as FEV1 (％ pred).Results The mean FMD was significantly lower in the COPD group (11.21±5.19) ％ than in the control group (19.86±5.24)％ (t=6.090,P=0.001).The Pearson's correlation analysis showed FMD was positively correlated with FEV1 (％pred) in COPD patients (r=0.440,P＜0.05).The mean serum eNO level in the COPD group (108.58 ± 42.22) μmol/L was significantly lower than in the control group (151.17 ± 97.40)μmol/L (t =2.242,P =0.039).Conclusions The endothelium-dependent flow-mediated vasodilatation is significantly impaired in stable COPD patients,and the degree of impairment is proportional to the FEV1 (％ prediction of FEV1) in COPD patients.

Objective By a sequencing panel consisting of 50 targeted genes, aiming at depicting the molecular landscape of ET, PV, and PMF, which are three major subtypes of MPN, to provide valuable information in the diagnosis and prognosis of MPN.Methods A retrospective study was conducted of 53 patients from Huashan hospital and Changhai hospital. All patients were diagnosed in accordance with the 2016 WHO diagnostic criteria for MPN, including 31 cases of ET(11 males, 20 females, median age 55 years), 17 cases of PV(12 males, 5 females, median age 65 years), and 5 cases of PMF(4 males, 1 females, median age 67 years), and underwent next-generation of DNA sequencing of their bone marrow or blood samples. The genetic analyses were performed on bone marrow or peripheral blood. Referring to COSMIC, dbSNP, Clinvar and other public databases, we analyzed the sequencing data, and elucidated the mutation profile of MPN patients, combining with their clinic information. Results In addition to the typical JAK2, CALR, and MPL mutations, pathogenic mutations in other 11 genes were detected, as well as 4 SNPs that confer individual susceptibility to MPNs (rs4858647, rs9376092, rs58270997, rs621940). The average rate of mutated genes was 2.3 genes per patient. In all patients (53 cases), the mutated genes detected were TET2, EZH2, ASXL1, MIR662, SF3B1, BARD1, DNMT3A, KIT, RUNX1, TP53, NRAS according to their mutational frequency. Conclusions Applying next-generation sequencing technology, multi-gene sequencing of a bunch of typical BCR-ABL-negative MPN patients can be performed at one time within 2 working days, and pathogenic mutations other than JAK2, CALR, MPL can be found, which has a bright prospection in clinic.

Objective:To explore the effect of family doctor system on the risk stratification of community hypertensive population by application of Markov modelMethods:Retrospective investigation was conducted on hypertensive patients under continuing management from 13 community health service centers in Shanghai Xuhui District from January 2014 to December 2016. Among 98 996 subjects, 50 920 (51.45%) were contracted to family doctors (contracted group) and 48 046 (48.55%) did not contracted to family doctors (non-contracted group). According to the risk stratification of hypertension, the four-state Markov model (low-risk, medium-risk, high-risk, and extremely high-risk) was established. The prediction effect of the model was validated, and the changes in the risk stratification status of hypertension in the study subjects from 2017 to 2020 was predicted by using the Markov model.Results:Among all subjects the number of medium-risk and extremely high-risk accounted for the majority(>80%). Compared with 2014, in 2016 the number of low-risk patients with hypertension was decreased from 9 042 cases (17.76%) to 6 851 cases (13.45%) in contracted group; and from 9 971 cases (20.75%) to 7 906 cases (16.46%) in non-contracted group; the number of people at extremely high risk of hypertension was increased from 15 609 cases (30.65%) to 17 639 cases (34.64%) in the contracted group; from 13 847 cases (28.82%) to 15 641 cases (32.55%) in the non-contracted group. According to the Markov model one year after the risk stratification, the risk status of most subjects remained in the original one. There was not transform from extremely high-risk to low-risk state (0%), but there was transform from low-risk to extremely high-risk state in some extend, and the degree of transform in non-contracted group [2.06%(205/9 971)] was higher than the contracted group [1.85%(167/9 042)]. Predicted by the Markov model, between 2017 and 2020 the number and proportion of the medium-risk>extremely high-risk>low-risk>high-risk in both contracted group and non-contracted group. With the extension of time, low-risk proportion is gradually reduces, and the rate of reduction of the contracted group was lower than that of the non-contracted group, while proportion of medium-risk, high-risk and extremely high-risk is gradually increased.Conclusions:The constructed Markov model is accruable and stable, which can be used in the study of hypertension prognosis. The study indicates that the contracted services of family doctor have positive effects on the management of community hypertensive patients.

Objective:To identify new prognostic markers and therapeutic targets for gastric adenocarcinoma.Methods:The public datasets of gastric adenocarcinoma collected from GEO database (GSE33335 and GSE63089) were downloaded for analysis. There were 70 GC tissues and paired normal tissues in the two profile datasets. Differentially expressed genes (DEGs) between GC tissues and normal stomach tissues were selected by the R software. Protein-protein interaction (PPI) of these DEGs were visualized by the Search Tool for the Retrieval of Interacting Genes (STRING). The key gene sets were analyzed by Cytoscape and Molecular Complex Detection (MCODE). The mRNA and protein expression levels of prognosis related genes identified by public database were confirmed by using GC tissues and paired normal tissues collected from July 2019 to September 2019 in Affiliated Hospital of Nantong University.Results:DEGs were identified in the two datasets by using R software. A total of 128 DEGs were detected, including 85 up-regulated genes ( log2FC>1.2 and FDR<0.01) and 43 down-regulated genes ( log2FC<-1.2 and FDR<0.01) in the GC tissues. PPI network model and MCODE model were established by using the Online String tool and Cytoscape software, and 27 key genes were obtained, including 25 genes related with prognosis of GC patients ( P<0.05). We identified 14 significant DEGs in GC tissues, including cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) and pituitary-tumor transforming gene (PTTG1), which were significantly enriched in the cell cycle pathway through KEGG pathway enrichment analysis. The positive expression rate of PTTG1 in GC tissues was 68.8% (22/32), significantly higher than 18.8% (6/32) in normal gastric tissues ( P<0.05). Conclusions:The expression of PTTG1 is different in GC and gastric tissues, implicates it is the key gene in gastric carcinogenesis. The prognoses of GC patients with higher PTTG1 expression are worse. PTTG1 might participate in the development of gastric adenocarcinoma by regulating cell cycle.

Objective:To explore the potential clinical value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT muscle imaging in the diagnosis of cervical dystonia (CD). Methods:From January 2021 to April 2022, 50 patients with CD (14 males, 36 females; age (45.8±12.5) years) who were treated in Second Affiliated Hospital of Soochow University were prospectively included. The 99Tc m-MIBI SPECT/CT muscle imaging results of 400 pieces of muscle (bilateral sternocleidomastoid, musculus scapulae, splenius capitis and musculus trapezius; each of 100 pieces) in 50 patients were analyzed and divided into the dystonic muscle group and normal muscle group according to the electromyography (EMG). Toronto western spasmodic torticollis rating scale (TWSTRS) score, SUV max and target-to-background ratio (TBR) of single superficial cervical muscle and total cervical muscle, and EMG diagnosis results were obtained before botulinum toxin injection. ROC curves of SUV max and TBR of dystonic muscles were constructed to determine AUCs and the difference was compared by Delong test. Differences of SUV max and TBR between 2 groups were analyzed by Mann-Whitney U test. Spearman rank correlation analysis was used to analyze the correlation of SUV max, TBR and TWSTRS scores of total cervical muscle. Results:There were 205 pieces of muscle in dystonic muscle group and 195 pieces of muscle in normal muscle group. The uptake of 99Tc m-MIBI in dystonic muscle was significantly increased in CD patients, and the non-whole uptake of 99Tc m-MIBI was increased in some dystonic muscles, which was manifested as uneven uptake of the whole muscle. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of visual analysis were 95.12%(195/205), 75.90%(148/195), 85.75%(343/400), 85.58%(195/242) and 93.67%(148/158), respectively. There were significant differences of SUV max (1.74(1.42, 2.12) vs 0.92(0.81, 0.99)) and TBR (2.55(1.92, 3.27) vs 1.44(1.22, 1.73)) between the dystonic muscle group and the normal muscle group ( z value: -15.29, -12.69, both P<0.001). The diagnostic efficiency of SUV max in dystonic muscle was better than TBR (AUC: 0.942 vs 0.867; z=5.03, P<0.001). SUV max, TBR and TWSTRS score in the neck muscles of patients with CD showed positive correlation ( rs values: 0.44, 0.45, both P<0.001). Conclusion:99Tc m -MIBI SPECT/CT muscle imaging is a good diagnostic method for dystonic muscle in patients with CD.

Background: Stage at diagnosis and molecular subtype are important clinical factors associated with breast cancer patient survival. However, subgroup survival data from a large study sample are limited in China. To estimate the survival differences among patients with different stages and various subtypes of breast cancer, we conducted a hospital-based multi-center study on breast cancer in Beijing, China. Methods: All resident patients diagnosed with primary, invasive breast cancer between January 1, 2006 and Decem-ber 31, 2010 from four selected hospitals in Beijing were included and followed up until December 31, 2015. Hospital-based data of stage at diagnosis, hormone receptor status, and selected clinical characteristics, including body mass index (BMI), menopausal status, histological grade, and histological type, were collected from the medical records of the study subjects. Overall survival (OS) and cancer-specific survival (CSS) were estimated. Cox proportional hazards models were employed to evaluate the associations of stage at diagnosis and molecular subtype with patient survival. Results: The 5-year OS and CSS rates for all patients were 89.4％ and 90.3％. Survival varied by stage and molecu-lar subtype. The 5-year OS rates for patients with stage Ⅰ, Ⅱ, Ⅲ, and IV diseases were 96.5％, 91.6％, 74.8％, and 40.7％, respectively, and the corresponding estimates of 5-year CSS rates were 97.1％, 92.6％, 75.6％, and 42.7％, respectively. The 5-year OS rates for patients with luminal A, luminal B, HER2, and triple-negative subtypes of breast cancer were 92.6％, 88.4％, 83.6％, and 82.9％, respectively, and the corresponding estimates of 5-year CSS rates were 93.2％, 89.1％, 85.4％, and 83.5％, respectively. Multivariate analysis showed that stage at diagnosis and molecular subtype were important prognostic factors for breast cancer. Conclusions: Survival of breast cancer patients varied significantly by stage and molecular subtype. Cancer screen-ing is encouraged for the early detection and early diagnosis of breast cancer. More advanced therapies and health care policies are needed on HER2 and triple-negative subtypes.