Objective:To investigate the mechanism of immunomodulatory effects of umbilical cord mesenchymal stem cells(UC-MSCs)modified by miR-125b-5p on systemic lupus erythematosus(SLE).Methods:The expression level of miR-125b-5p was detected by real-time fluorescence quantitative PCR in UC-MSCs and peripheral blood mononuclear cells(PBMCs)from SLE patients and health checkers.Annexin V-FITC/PI apoptosis detection kit was used to detect the effect of miR-125b-5p on apoptosis of UC-MSCs.MRL/lpr mice in each group were injected with UC-MSCs via tail vein,and T-lymphocyte subsets in the spleen of the MRL/lpr mice were detected by flow cytometry after 5 weeks.The expression levels of interleukin(IL)-4 and IL-17A in serum of MRL/lpr mice were detected by ELISA.Hematoxylin-eosin staining was used to observe the pathological manifestations of the lungs and kidneys of the MRL/lpr mice.Results:miR-125b-5p was significantly down-regulated in PBMCs of SLE patients compared with healthy controls(P＜0.01).Compared with the UC-MSCs group,the expression of miR-125b-5p in UC-MSCs modified by miR-125b-5p group was increased(P＜0.01).The survival rate of UC-MSCs was significantly increased by miR-125b-5p(P＜0.01).Compared with the untreated group of MRL/lpr mice,the expression level of IL-4 in serum was increased(P＜0.05);the expression level of IL-17A was decreased(P＜0.05);the proportion of Th17 cells in the spleen of MRL/lpr mice was decreased(P＜0.05);the inflammatory cells infiltration and micro-thrombosis of lungs and kidneys of MRL/lpr mice were significantly reduced in the UC-MSCs modified by miR-125b-5p treatment group.Conclusion:UC-MSCs modified by miR-125b-5p have immunomodulatory effects on systemic lupus erythematosus.

OBJECTIVE：To study the relationship of polymorphism of clopidogrel absorption and metabolism related genes CYP2C19（* 2，* 3，* 17），ABCB1 C3435T and PON1 Q192R in patients with coronary heart disease in Xinjiang Uygur Autonomous Region ，and to explore the characteristics of population and combined diseases. METHODS ：A total of 1 126 patients with coronary heart disease who underwent clopidogrel absorption and metabolism related gene testing during hospitalization in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to June 2020 were included as the study subjects. The gender，age，body mass index （BMI），nationality and the proportion of combined with hypertension and diabetes were compared among different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. RESULTS ：Among 1 126 patients，1 126 had CYP2C19 * 2，* 3 and * 17 genotypes，1 109 had ABCB1 C3435T genotype and 1 123 had PON1 Q192R genotype. The distribution of each genotype was in line with Hardy-Weinberg balance （P＞0.05）. There were 66（5.86％）， com 459（40.76％），476（42.27％） and 125（11.10％）patients with CYP2C19 ultra-rapid metabolizer （UM）， extensive metabolizer（EM），intermediate metabolizer （IM）and poor metabolizer（PM），respectively. The proportion of patients with UM metabolism phenotype with BMI ＞24 was significantly higher than those of patients with IM and PM metabolism phenotypes （P＜0.05）. The proportion of Han nationality patients with UM metabolic phenotype was significantly lower than those of patients with EM ，IM and PM metabolic phenotypes （P＜0.05）；the proportion of Uygur nationality was significantly higher than that of patients with EM ，IM and PM metabolic phenotypes （P＜ 0.05）. There were 355，538 and 216 patients with ABCB1 C3435T wild-type（CC），heterozygous（CT）and mutant homozygous （TT）genotypes，respectively；the proportion of Han nationality in TT genotype patients was significantly lower than that in CC and CT genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that in CC and CT genotype patients （P＜0.05）；the proportion of TT genotype patients with diabetes was significantly higher than that of patients with CT genotype （P＜0.05）. There were 365，519 and 239 patients with PON1 Q192R wild-type（GG），heterozygous（GA）and mutant homozygous （AA），respectively；the proportion of Han nationality in AA genotype patients was significantly lower than that in GG and GA genotype patients （P＜0.05），and the proportion of Uygur nationality was significantly higher than that of GG and GA genotype patients （P＜0.05）；the proportion of Han nationality and BMI ≤24 in patients with AA genotype were significantly lower than those with GA genotype （P＜0.05），and the proportion of Uygur nationality ，BMI＞24 and hypertension were significantly higher than those in GA genotype patients （P＜0.05）. CONCLUSIONS ：There are significant nationality differences among patients with different CYP2C19 metabolic phenotypes and ABCB1 C3435T and PON1 Q192R genotypes. In addition，patients with BMI ＞24 account for high proportion among CYP2C19 UM metabolism genotype ；patients with diabetes account for high proportion among ABCB1 C3435T TT genotype ；patients with BMI ＞24 and hypertension account for high proportion among PON1 Q192R AA genotype.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.

Objective:To establish a new model for the prediction of severe outcomes of COVID-19 patients and provide more comprehensive, accurate and timely indicators for the early identification of severe COVID-19 patients.Methods:Based on the patients’ admission detection indicators, mild or severe status of COVID-19, and dynamic changes in admission indicators (the differences between indicators of two measurements) and other input variables, XGBoost method was applied to establish a prediction model to evaluate the risk of severe outcomes of the COVID-19 patients after admission. Follow up was done for the selected patients from admission to discharge, and their outcomes were observed to evaluate the predicted results of this model.Results:In the training set of 100 COVID-19 patients, six predictors with higher scores were screened and a prediction model was established. The high-risk range of the predictor variables was calculated as: blood oxygen saturation <94 %, peripheral white blood cells count >8.0×10 9, change in systolic blood pressure <-2.5 mmHg, heart rate >90 beats/min, multiple small patchy shadows, age >30 years, and change in heart rate <12.5 beats/min. The prediction sensitivity of the model based on the training set was 61.7 %, and the missed diagnosis rate was 38.3 %. The prediction sensitivity of the model based on the test set was 75.0 %, and the missed diagnosis rate was 25.0 %. Conclusions:Compared with the traditional prediction (i.e. using indicators from the first test at admission and the critical admission conditions to assess whether patients are in mild or severe status), the new model’s prediction additionally takes into account of the baseline physiological indicators and dynamic changes of COVID-19 patients, so it can predict the risk of severe outcomes in COVID-19 patients more comprehensively and accurately to reduce the missed diagnosis of severe COVID-19.

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.

Objective To observe the clinical efficacy of surgical operation combined with photodynamic therapy for plantar warts.Methods From July 2017 to June 2018,16 patients with plantar warts were enrolled in the Department of Dermatology,the Fifth People's Hospital of Suzhou City.The enrolled patients aged 10 to 42 years,including 12 males and 4 females,with a course of 4 to 15 month,and a total of 47 plantar warts.The plantar warts was removed by surgical operation and bipolar coagulation,followed by the photodynamic treatment with 5-aminolevulinic acid for 3 to 4 times with an interval of 7-10 days.Results Eleven patients showed complete clearance after operation and three times photodynamic treatments,and the other 5 patients underwent 2 operations and four times photodynamic treatments.47 plantar warts in 16 patients were disappeared completely during 6-month post-treatment follow up.The plantar warts clearance rate was 100％,and the skin texture still presented.In addition to local mild erythematous,pain and burning sensation presented after surgery,but no adverse reactions such as infection,ulcers and obvious scars occurred.Conclusions Surgery combined with 5-aminolevulinic acid photodynamic therapy is a favorable treatment for plantar warts.

Objective To observe the expression levels of serum osteopontin (OPN),adenosine kinase 1 (TK1) and secretory protein Dikkopf 1 (DKK1) in patients with lung cancer and their clinical significances.Methods Lung cancer patients treated in the First Affiliated Hospital of Xi'an Medical University from February 2017 to April 2018 were selected as the lung cancer group (60 cases),and 60 healthy adults who received physical examination in the same period were selected as the control group.The differences of serum OPN,TK1 and DKK1 levels between the lung cancer group and the control group and lung cancer patients with different characteristics were compared.Measurement data were compared by using t test.Results The levels of serum OPN,TK1 and DKK1 in lung cancer patients were (38.56±3.18) μg/L,(4.69±1.03) pmol/L and (3.76±0.89) ng/ml,respectively,which were higher than those in the control group [(15.98±2.06) μg/L,(1.01±0.22)pmol/L,(1.21±0.24) ng/ml;t =-46.162,-27.064,-21.428,all P ＜ 0.01].The levels of serum OPN,TK1 and DKK1 in lung cancer patients of different ages and gender had no statistical differences (all P ＞ 0.05).The levels of serum OPN,TK 1 and DKK1 in stage Ⅲ-Ⅳ lung cancer patients were (57.18 ±3.12) μg/L,(6.26±1.28) pmol/L and (4.98±1.03) ng/ml,respectively,which were higher than those in stage Ⅰ-Ⅱ lung cancer patients [(30.35±2.96) μg/L,(3.49±0.67) pmol/L,(3.01±0.96) ng/ml;t =-34.156,-10.690,-7.665,all P ＜ 0.01].The levels of serum OPN,TK 1 and DKK1 in non-small cell lung cancer (NSCLC) patients were (55.13±5.02) μg/L,(5.96±1.11) pmol/L and (5.02±1.32) ng/ml,respectively,which were higher than those in small cell lung cancer (SCLC) patients [(29.68±3.16) μg/L,(3.13±0.98) pmol/L,(2.86±0.56) ng/ml;t =-22.353,-10.213,-7.688,all P ＜ 0.01].Conclusion The levels of serum OPN,TK1 and DKK1 in patients with lung cancer are higher,which are related to the type and stage of lung cancer.

Objective To investigate the expression of metastasis associated gene-1 (mag-1) and mammalian target of rapamycin (mTOR) in rectal cancer, and its correlation with clinical pathology. Methods The expressions of mag-1 and mTOR in 60 rectal cancer tissue, 30 adenoma tissues and 10 normal rectal tissues were detected by immunohistochemical method, and the correlation between the expression levels and rectal cancer clinical pathologic characteristics was discussed. Results The positive expression rates of mag-1 and mTOR in rectal cancer tissue were significantly higher than those in normal rectal tissue and adenoma tissue:55%(33/60) vs. 1/10 and 27%(8/30), 58%(35/60) vs. 2/10 and 30% (9/30), and there were statistical differences (P<0.05). The expression levels of mag-1 and mTOR in rectal cancer tissue were correlated with carcinoembryonic antigen on admission, degree of cell differentiation, TNM stage, lymph node metastasis and distant metastasis (P<0.01 or<0.05), but had no correlation with age, gender, neoplasm location and neoplasm appearance (P > 0.05). The correlation analysis result showed that the expressions of mag-1 and mTOR were positively correlated in rectal cancer tissue (r=0.730, P<0.01). Conclusions The mag-1 and mTOR may correlate with invasion and metastasis in rectal cancer, and monitoring mag-1 and mTOR expression has a certain value for determining biological behavior of rectal cancer.

Proteomics is a powerful subject focusing on large-scale study of protein structures and functions. A complete enzymatic digestion of protein complexes is the key step in modern high-resolution and high-throughput mass spectrometry (MS)-based identification and quantification. To achieve MS analysis, both peptide sample pretreatment and data acquisition are prerequisite in proteomic studies. In this paper, we summarized both the enzymatic proprieties of three common proteolytic enzymes, Trypsin, Lys-C and Glu-C, the optimization of multi-enzyme combination and an advanced sample pretreatment in proteomics research.
Enzymes ; chemistry ; Mass Spectrometry ; Proteins ; chemistry ; Proteomics ; methods ; Trypsin ; chemistry

OBJECTIVEwe aimed to investigate the mutation and expression of BRAF gene in mature T/NK cell lymphoma tissues and cell lines, explore the correlation between gene alterations and clinicopathological features and clinical outcomes of mature T/NK cell lymphoma.

METHODSFirstly, we detected common mutant sites of BRAF (locus 1 799 mutation in exon 15 and loci 463, 465 and 468 mutation in exon 11) in lymphoma Jurkat, Hut-78 and YTS cell lines, normal peripheral blood lymphocytes, different types of mature T/NK cell lymphoma and reactive hyperplasia lymph nodes by direct sequencing. Then we measured the expression of BRAF in Jurkat, Hut-78, YTS cells and normal peripheral blood lymphocytes by real time-PCR and Western-blot detection. We also used immunohistochemistry (IHC) to detect the expression of BRAF in mature T/NK cell lymphoma tissues and reactive hyperplasia lymph nodes, and to analyze the correlation between the expression of BRAF and clinocopathological features and clinical outcomes.

RESULTSWe did not find common BRAF mutation in mature T/NK cell lymphoma tissues and cell lines, and the relatively expression of BRAF gene mRNA in normal peripheral blood lymphocytes, YTS, Hut-78 and Jurkat cells were 1.000, 5.207±0.013, 8.412±0.615 and 36.720±1.797, respectively, and protein expressions were 0.051±0.003, 0.102±0.013, 0.113±0.017 and 0.304±0.010, respectively, and the expression of BRAF in peripheral T cell lymphoma Jurkat cells was significantly higher than that of Hut-78, YTS cells and normal lymphocytes (P<0.05). Only 6 of 58 peripheral T cell lymphomas (10.3%) had positive BRAF expression, and were the subgroups of peripheral T cell lymphoma-unspecified type. The statistical data did not show any correlation between positive expression of BRAF and gender, age, clinical stage, location, lactate dehydrogenase in the 21 cases of peripheral T cell lymphoma-unspecified type (P<0.05), but the positive rate of BRAF in the effective treatment group (8.3%) was significantly lower than that of the invalid group (55.6%, P<0.05).

CONCLUSIONThe expression of BRAF gene may become a marker of malignant biological characteristics and clinical therapeutic target of peripheral T cell lymphoma.

Exons ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; Lymphoma, T-Cell, Peripheral ; genetics ; metabolism ; pathology ; Proto-Oncogene Proteins B-raf ; genetics ; metabolism ; Pseudolymphoma ; genetics ; metabolism ; RNA, Messenger ; metabolism