Objective To investigate the genetic polymorphisms and populational diversity of one SNP site on vitamine D receptor gene exon 2 in Northern China Han nationality, Uygur, Tibetan, and Kazark populations. Methods The DNA samples from 271 unrelated individuals were typed by using PCR-RFLP and DNA sequencing analysis. Results ACG was the commonest allele with frequencies ranging from 0.57 to 0.72. The frequencies of genotype ACG/ATG was beyond 0.5 in both Tibetan and Uygur. The frequencies of both genotypes ACG/ATG and ACG/ACG were 0.3976 in Han nationality. In Kazak population, the frequency of genotype ACG/ACG was 0.5769. Both DP and EPP of the SNP site were beyond 0.56 and 0.16 respectively in these four populations. The genotype distribution was accord with Hardy-Weinberg equilibrium. There was some difference of the frequency distribution between these four groups. Comclusion SNP site on vitamine D receptor gene exon 2 is one with high polymorphism and certain popu-lational diversity.

【Objective】 To study the technology of separating and purifying C1 esterase inhibitor (C1-INH) by using the waste washing liquid as raw materia during the preparation of human prothrombin complex (PCC) l. 【Methods】 C1-INH was isolated and purified by a two-step method of polyethylene glycol (PEG) 4000 precipitation and cation chromatography. The pH of raw materials and the concentration of PEG4000 were adjusted to investigate the optimal conditions of PEG4000 precipitation method. After PEG was precipitated and centrifuged, the supernatant is treated as the loading solution for cation exchange chromatography, using Fractogel EMD SE HiCap(M) gel and CM Sepharose FF gel for ion exchange chromatography. The most suitable gel and separation conditions were selected by comparing the C1-INH antigen yield, activity yield and specific activity. 【Results】 Under the condition of pH 6.1, when the mass fraction of PEG4000 was 14%, the recovery rate of C1 esterase inhibitor was close to 70%, and the removal rate of ceruloplasmin was more than 95% after stirring for 10 minutes. As fractogel EMD SE HiCap(M) gel was used for cation exchange chromatography, when the eluent salt concentration was 0.25 M sodium chloride, the activity yield of C1 esterase inhibitor was greater than 80%, and the specific activity was greater than 5 IU/mg. 【Conclusions】 Using the waste washing liquid as the raw material during the preparation of PCC, the C1 esterase inhibitor with high specific activity can be prepared through PEG precipitation and purification by Fractogel EMD SE HiCap(M) ion exchange chromatography.

The percutaneous transhepatic portal approach is the most commonly used technique for islet transplantation, largely owing to its safety and minimally invasive characteristic. Bleeding complications after islet transplantation are rare. A case of type 1 diabetes mellitus (T1DM) was treated in Tianjin First Center Hospital, who had a massive intra-abdominal hemorrhage after percutaneous transhepatic portal vein catheterization for islet transplantation. Through the review of the overall development of the case, we aim to improve the awareness of the complications of islet transplantation, to reduce the incidence of complications after percutaneous transhepatic portal vein transplantation, and to provide experience.

Objective To investigate the expressions of ABCG2 and V-ATPase in NSCLC and their expression rates in pathological classification, TNM stages and pathological grades and the expression correlation between ABCG2 and V-ATPase. Methods Expressions of ABCG2 and V-ATPase were accessed with EnVinsion immunohistochemistry in tumor samples from 92 NSCLC patients. The corresponding data was analyzed statistically. Results Expressions of ABCG2 and V -ATPase were found both in the lung adenocarcinoma and lung squamous cell cancer, and the difference between these two kinds of tumors was significant (P =0.003,0.000). ABCG2 expression was significantly different among TNM stages of lung adenocarcinoma (P=0.004) as well as among pathological grades of lung adenocarcinoma (P =0.028) and squamous cell carcinoma (P =0.000), while no significant difference was found among TNM stages of squamous cell lung carcinoma. The level of V-ATPase expression was associated with TNM stages of lung adenocarcinoma (P =0.026) and pathological grades of lung squamous cell carcinoma (P =0.002), however, among TNM stages of lung squamous cell carcinoma and pathological grades of lung adenocarcinoma, the difference was not significant. Additionally, the significant correlation was found between expression of ABCG2 and V-ATPase in all samples, adenocarcinoma and squamous cell carcinoma (P<0.001). Conclusion The significant correlation is found between expression of ABCG2 and V-ATPase, which indicate that they may co-work to participate in the mechanism of anticancer drug resistance.

Objective To investigate the in vitro effects of bone marrow mesenchymal stem cells (BM MSCs) on the replication of HBV with the participation of lymphocytes and to analyze the possible mechanism.Methods The HBV genomic DNA transfected HepG2.2.15 cell line was used to evaluate the HBV replication.Bone marrow and spleen samples were collected from BN rats for the isolation of BM MSCs and T lymphocyte cells, respectively.Five groups of co-culturing with different cells were designed in this study.The cellular activities of lymphocytes and HepG2.2.15 cells were detected at the time of 24 h, 48 h and 72 h after co-culturing by using MTT method.The levels of HBV DNA and HBV cccDNA were detected by real-time polymerase chain reaction ( PCR) .T cell subsets in co-culture were measured by using fluores-cence labeled antibodies and flow cytometry analysis.ELISA was used to detect the levels of cytokines in the supernatant of cultured cells.Results Compared with HepG2.2.15 cells group, BM MSCs+HepG2.2.15 cells and splenic lymphocytes+HepG2.2.15 cells co-culture groups, the levels of HBV DNA and HBV cccDNA were significantly decreased in splenic lymphocytes+BM MSCs+HepG2.2.15 cells co-culture group after 48 h of culture [ HBV DNA: ( 181.000 ±14.731 ) IU/ml vs ( 6270.000 ±300.450 ) IU/ml, (2564.000±231.058) IU/ml, (2433.300±302.379) IU/ml;HBV cccDNA: (4.330×105 ±0.464×105 ) IU/ml vs (11.100×105±0.375×105) IU/ml, (8.930×105±0.778×105) IU/ml, (9.850×105±0.810× 105) IU/ml;P<0.01].The secretion of IFN-γin the supernatant of co-cultured cells was negatively corre-lated with HBV DNA level, but the levels of IL-10 and IL-22 were positively correlated with HBV DNA.The ratio of CD4+/CD8+cells was increased in splenic lymphocytes+BM MSCs+HepG2.2.15 cells co-culture group.The percentage of CD8+cells showed a positive correlation with HBV DNA.Conclusion BM MSCs could inhibit the expression of HBV DNA to enhance the clearance of HBV strains.It might be possibly due to rebalancing of Tc1/Tc2 cells and regulating the expression of autocrine agents and cytokines.

Objective:To study the clinical pathological features of patients with relapsed diffuse large B-celllymphoma (DLBCL) and to provide evidence for early clinical screening of recurrent cases.Methods:The clinical and pathological data of the 20 patients, who had relapsed DLBCL (relapsed group) and were admitted to the First Affiliated Hospital of Nanjing Medical University from January 2015 to December 2019, were included. Meanwhile, other 34 patients with DLBCL who had achieved complete response (CR) for 36 months or more (CR group) were used as controls.Statistical methods were used to retrospectively analyze the differences in general conditions, clinical characteristics, lab resultsand pathological features between the two groups.Results:Clinically, there were 6 males and 14 females with a median age of 55.5 (33-85) years in the relapsed group and 14 males and 20 females with a median age of 53 (15-89) years in the CR group. The relapsed and CR groups had significant difference in Ann Arbor stage ( P=0.001), International Prognostic Index score ( P=0.006), primary lesions ( P=0.003), extranodal involvement ( P=0.002), and hepatitis B viral infection ( P=0.046), β2-MG level ( P=0.029), LDH level ( P=0.005) and CRP level ( P=0.006), while the age ( P=0.732), gender ( P=0.416), ECOG score ( P=0.248), B symptoms ( P=0.511), the presence of hypoalbuminemia ( P=0.279), anemia ( P=0.983) and A/G( P=0.416) showed no statistical difference.Pathologically, compared with the CR group, the relapsed group was mostly non-GCB type (85% vs. 59%, P=0.048), with a higher CD5 positive rate (25% vs.3%, P=0.014) and a lower bcl-6　positive rate (60% vs. 88%, P=0.017), while the expression of Ki-67, CD10, bcl-2, MUM1, CD20 and PAX5 was not different between the two groups. Conclusion:Most of the patients with relapsed DLBCL are non-GCB type. The patients with CD5 positivity, stage III-IV, International Prognostic Index score 3-5, nodal origin, often involving>1 extranodal organ, abnormally elevated LDH, CRP and β2-MG level, and HBV infection are more likely to relapse.

Objective:To investigate the relationship between clinicopathologic features and prognosis of pancreatic ductal adenocarcinoma located in the head of pancreas.Methods:A retrospective study was performed on 169 patients undergoing radical resection for pancreatic head cancer collected in the First Affiliated Hospital with Nanjing Medical University from January 2018 to April 2019. Univariate analysis and multivariate analysis were performed.Results:Patient′s age, tumor differentiation, tumor maximum diameter, resection margin (several resection margins including portal vein groove resection margin, posterior resection margin, and uncinate resection margin), number of positive lymph nodes, number of regional lymph node dissected, and some preoperative and postoperative indicators were associated with prognosis ( P<0.05). Direct tumor invasion of organs and surrounding tissues, perineural and vascular invasion, pathologic variants etc. had no statistical significance for survival time. Patient′s age, maximum tumor diameter, degree of differentiation, uncinate incision margin, number of regional lymph nodes dissected, and preoperative CA19-9 were independent factors affecting prognosis. Patients older than 74 years of age, with tumors larger than 3 cm in diameter, poorly differentiated, less than 7 regional lymph node dissected, positive uncinate margin, and preoperative CA19-9 higher than 1.5×10 5 U/L were independent risk factors in patients with pancreatic head cancer. Conclusions:Old age, tumor lager than 3 cm, poor differentiation, low examined lymph nodes, direct uncinate margin involvement and (or) with preoperative CA19-9 higher than 1.5×10 5 U/L are related to poor prognosis of head pancreatic cancer.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma, and its etiology and molecular mechanism has not been fully elucidated. Recently, increasing evidence has indicated that long non-coding RNA (LncRNA) participates in the occurrence, development, invasion and metastasis of DLBCL. This article reviews lncRNA-related genes and signaling pathways as well as the molecular mechanism of DLBCL.

The growing demand for new therapeutic strategies in the medical and pharmaceutic fields has resulted in a pressing need for novel druggable targets. Paradoxically, however, the targets of certain drugs that are already widely used in clinical practice have largely not been annotated. Because the pharmacologic effects of a drug can only be appreciated when its interactions with cellular components are clearly delineated, an integrated deconvolution of drug-target interactions for each drug is necessary. The emerging field of chemical proteomics represents a powerful mass spectrometry (MS)-based affinity chromatography approach for identifying proteome-wide small molecule-protein interactions and mapping these interactions to signaling and metabolic pathways. This technique could comprehensively characterize drug targets, profile the toxicity of known drugs, and identify possible off-target activities. With the use of this technique, candidate drug molecules could be optimized, and predictable side effects might consequently be avoided. Herein, we provide a holistic overview of the major chemical proteomic approaches and highlight recent advances in this area as well as its potential applications in drug discovery.
Chromatography, Affinity ; Drug Delivery Systems ; methods ; Drug Design ; Drug Discovery ; methods ; Humans ; Mass Spectrometry ; Proteome ; chemistry ; Proteomics ; methods ; Small Molecule Libraries ; chemistry

Objective: To analyze the current status of anticoagulant therapy for in-hospital patients with acute coronary syndromes (ACS) at county hospitals of China and to explore the relationship between anticoagulant therapy and clinical outcomes in real medical environment. Methods: 99 county hospitals from15 provinces of China were selected for this prospective registry study and 12373 eligible ACS patients without interventional therapy admitted from 2011-09 to 2014-06 were enrolled. The basic condition, previous history, initial assessment, anticoagulants (unfractionated heparin/low molecular weight heparin) application, severe bleeding events and in-hospital mortality were collected in all patients. Multiple logistic regression analysis was conducted to explore the relationship between anticoagulant therapy and clinical outcomes including in-hospital mortality, severe bleeding events and combined endpoints; meanwhile, possible confounders were adjusted. Results: A total of 9985/12373 ACS patients received anticoagulant therapy and 2388 did not. Anticoagulant therapy was conducted in 92.7% (4237/4570) patients with ST-segment elevation myocardial infarction (STEMI), 90.8% (1639/1805) with non-ST-segment elevation myocardial infarction (NSTEMI) and 68.5% (4109/5998) with unstable angina (UA); there were differences by regions and genders,P<0.01and no difference by age. Multivariable analysis indicated that anticoagulant therapy decreased the risk of in-hospital mortality in ACS patients at 53% (OR= 0.47, 95% CI 0.36-0.62), such reduction in STEMI patients was at 55% (OR=0.45, 95% CI 0.32-0.64), in NSTEMI patients was at 58% (OR=0.42, 95% CI 0.24-0.75); while it had no real effect in UA patients,P>0.05. Meanwhile, it did not increase the risk of severe bleeding events in ACS patients,P>0.05. Conclusion: Anticoagulant therapy has been widely used in STEMI and NSTEMI patients at county hospitals of China and obviously decreased the in-hospital mortality; while the application rate was relatively low in UA patients. The general safety of anticoagulant therapy has been good in ACS patients.