The protective effect of nicotinamide riboside on mitochondrial function of retinal ganglion cell / 中国药师

Objective To explore the protective effect in a model of nicotinamide riboside(NR)against carbonyl cyanide m-chlorophenylhydrazone(CCCP)-induced oxidative stress in R28 cells.Methods 4 μmol/L CCCP was used to induce oxidative stress in R28 cells,and 400 nmol/L NR was used to intervene.The cell viability was quantified by CCK-8 assay.The apoptosis was detected by Annexin-V/PI double staining and flow cytometry.Western blotting was used to examine the levels of Cytochrome C,Caspase-3,and Caspase-9 to evaluate the apoptosis.Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential(MMP),MitoSOX was used to detect the mitochondrial reactive oxygen species(mtROS)levels,and adenosine triphosphate(ATP)assay kit was used to assess ATP generation ability to evaluate mitochondrial function.Results After CCCP treatment of R28 cells,the cell viability decreased,the apoptotic protein levels and apoptosis rates increased,the MMP decreased,and the mtROS generation increased(P＜0.05).After NR pretreatment,the cell viability increased,the apoptotic protein levels and apoptosis rates decreased,the MMP increased,and the mtROS generation decreased(P＜0.05).Conclusion:NR enhances the cell viability,reduces the expression of apoptotic proteins,and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.

Efficacy and safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma / 白血病·淋巴瘤

Objective:To investigate the efficacy and safety of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of multiple myeloma (MM).Methods:The clinical data of 64 MM patients who received ASCT in the Second Affiliated Hospital of Xi'an Jiaotong University from October 2015 to March 2022 were retrospectively analyzed. The clinical characteristics, therapeutic effects and adverse reactions of the patients were summarized.Results:Of the 64 patients, 42 were male and 22 were female; the median age was 54 years old (37-69 years old). The median number of CD34 + cells collected from 46 patients in the CE (cyclophosphamide, etoposide) regimen mobilization group and 17 patients in the plerixafor mobilization group were 7.50×10 6/kg [(1.15-24.73)×10 6/kg] and 4.54×10 6/kg [(0.75-10.40)×10 6/kg], and the difference was statistically significant ( Z = 3.02, P = 0.024). Hematopoietic reconstitution was successful in all 64 patients, and the median time for white blood cell and platelet engraftment was 11 d (8-13 d) and 11 d (8-15 d), respectively. The patients' pretreatment regimens were all high-dose melphalan, the median white blood cell and platelet engraftment time of 29 patients in the oral group were 11 d (8-13 d) and 11 d (8-15 d), respectively, the median white blood cell and platelet engraftment time of 35 patients in the intravenous infusion group were 11 d (8-12 d) and 11 d (8-15 d), respectively, and there were no statistical differences (both P > 0.05). The ≥CR rate was 48.4% (31/64) before transplantation and 70.3% (45/64) three months after transplantation, and the difference was statistically significant ( χ2 = 6.35, P = 0.012). The median follow-up time of all patients was 27 months (2-67 months). The 3-year OS and PFS rates were 77.6% and 54.9%, and the median OS and PFS time were 67 and 52 months. The median hospitalization time was 20 d (15-37 d). There was no transplantation-related mortality, and the main adverse reactions were gastrointestinal reactions (100.0%, 64/64), grade 4 thrombocytopenia (98.4%, 63/64), grade 4 neutropenia, and agranulocytosis with fever (40.6%, 26/64). Conclusions:ASCT is effective for MM patients suitable for transplantation, which can further improve the remission rate and remission depth, prolong the PFS and OS time of patients, and the adverse reactions are controllable.

Evaluation of clinical efficacy and prognostic factors in multiple myeloma patients treated with auto-HSCT: A single-center real-world study / 西安交通大学学报(医学版)

【Objective】 To evaluate the clinical efficacy and prognostic factors in multiple myeloma (MM) patients treated with autologous hematopoietic stem cell transplantation (auto-HSCT). 【Methods】 The clinical data of 155 MM patients newly diagnosed and suitable for transplantation in our hospital from 2014 to 2021 were retrospectively analyzed. They were divided into auto-HSCT group and non-auto-HSCT group according to the treatment mode. The clinical efficacy, overall survival (OS) and progression-free survival (PFS) of the two groups were compared. Furthermore, the prognostic factors of auto-HSCT group were analyzed. 【Results】 ① There were 51 patients in auto-HSCT group and 104 patients in non-auto-HSCT group. There was no statistical difference in baseline characteristics except age between the two groups. ② Hematopoietic reconstruction was achieved in all patients in auto-HSCT group, and no transplantation-related mortality was found. ③ The clinical efficacy of pre-and post-transplantation was compared in auto-HSCT group. sCR/CR rate was significantly increased after transplantation (P=0.041). The effective remission rate (≥VGPR) was also higher (P=0.05). As for the best efficacy, sCR/CR rate and effective remission rate were both significantly higher in auto-HSCT group than in non-auto-HSCT group (P=0.001). ④ In auto-HSCT group, by the end of follow-up, the median OS was not reached, the median PFS was 30.5 months, and 3-year OS and PFS was 87% and 40.3%, respectively. In non-auto-HSCT group, the median OS was 61 months, the median PFS was 21 months, and 3-year OS and PFS was 65.3% and 33.1%, respectively. It indicated that OS was significantly prolonged in auto-HSCT group (P=0.004). PFS was also prolonged but without significant difference (P=0.065). ⑤ Analysis of prognostic factors in auto-HSCT group showed that decreased PLT (P=0.038) and increased serum-adjusted calcium (P=0.017) were independent risk factors for OS, decreased PLT (P=0.005), female (P=0.018) and disease status of PR or worse before transplantation (P=0.012) were independent risk factors for PFS. 【Conclusion】 Auto-HSCT can improve the remission rate, prolong OS in MM patients, and possibly prolong PFS. Increased serum-corrected calcium and decreased PLT are independent prognostic factors for OS in patients treated with auto-HSCT. Decreased PLT, female, and disease status of PR or worse before transplantation are independent prognostic factors for PFS.

Comprehensive Treatment of Anaplastic Thyroid Cancer / 肿瘤防治研究

Anaplastic thyroid cancer (ATC) is a rare malignancy, accounting for 1%-2% of all thyroid cancers, however, ATC accounts for the majority of deaths from thyroid cancer. Currently, the main comprehensive treatments are surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy. Based on the latest American Thyroid Association guidelines and the related literatures, we summarize the most reasonable and effective therapeutic strategies to improve the survival rate of patients with ATC as well as the quality of life.

Reduction of gut microbial diversity and short chain fatty acids in BALB/c mice exposure to microcystin-LR.

Gut microbiota has been shown to play critical roles in host health. The present study was to determine the toxicological effects of microcystin-LR (MCLR) on gut microbial community and metabolites using 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS). MCLR was administered to BALB/c mice by gavage for eight weeks. Results of the microbial alpha-diversity (Sobs, Chao1, ACE and Shannon indexes) decreased in MCLR-treated group versus controls. Phylum Candidatus Saccharibacteria decreased significantly in MCLR-treated group versus controls. Correspondingly, more than thirties genera in relative abundance decreased, especially short chain fatty acid (SCFA)-producing bacteria (e.g., Alistipes and Ruminococcus). These results indicated that the gut microbial community structure was remarkably changed by MCLR. Furthermore, concentrations of SCFAs were significantly decreased after MCLR exposure (P < 0.01), where butyrate decreased as high as 4.9-fold. Consequently, sub-chronic exposure to MCLR could not only alter the microbial composition but metabolites. This study offered novel insights into the toxic mechanism of MCs from gut microbiota, and facilitated further clarification of risks to human health from MCs exposure.

The Differential Expression of Long Noncoding RNAs in Type 2 Diabetes Mellitus and Latent Autoimmune Diabetes in Adults.

BACKGROUND: Long noncoding RNAs (lncRNAs) were previously found to be closely related to the pathogenesis of diabetes. OBJECTIVES: To reveal the differentially expressed lncRNAs and messenger RNAs (mRNAs) involved in type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) and predict the lncRNA target genes to derive their expression profiles for the diagnosis of T2DM and LADA and their differential diagnosis. METHODS: Twelve venous blood samples were collected from T2DM patients, LADA patients, and nondiseased subjects to obtain total RNAs. After removing rRNA from total RNAs to establish the desired library for sequencing, quality control and quantification analyses were carried out. The fragments per kilobase of exon model per million reads mapped (FPKM) of lncRNAs were calculated to construct the gene expression profiles of lncRNAs and mRNAs. Fold changes (fold change: 2.0) and p values (p values (. RESULTS: Compared to nondiseased controls, 68,763 versus 28,523 lncRNAs and 133 versus 1035 mRNAs were significantly upregulated and significantly downregulated, respectively, in T2DM patients. For LADA patients, 68,748 versus 28,538 lncRNAs and 219 versus 805 mRNAs were significantly upregulated and significantly downregulated, respectively, relative to nondiseased controls. Compared to T2DM patients, 74,207 versus 23,079 lncRNAs and 349 versus 137 mRNAs were significantly upregulated and significantly downregulated, respectively, in LADA patients. Based on the correlation analysis, seven lncRNA-mRNA pairs (BTG2, A2M, HECTD4, MBTPS1, DBH, FLVCR1, and NCBP2) were significantly coexpressed, and two lncRNAs (ENST00000608916 and ENST00000436373) were newly discovered. CONCLUSION: Significant differences in lncRNA expression were discovered among the three groups. Furthermore, after predicting lncRNA expression profiles, GO/KEGG pathway analysis could deduce the target gene function.

Relationship between abdominal fat distribution and diabetic complications in patients with type 2 diabetes mellitus / 中华内分泌代谢杂志

Objective:To investigate the association of abdominal fat distribution with glycolipid metabolism and diabetic complications in patients with T2DM.Methods:Totally 357 inpatients with T2DM were collected from the Endocrinology Department of our hospital. All patients received quantitative computed tomography to measure the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and were divided into three groups depending on the tertile of VAT value: T1 group (VAT<162.0 cm 2), T2 group (162.0≤VAT<221.1 cm 2), T3 group (VAT≥221.1 cm 2). The incidences of diabetic kidney disease, diabetic retinopathy, diabetic peripheral neuropathy, peripheral atherosclerosis, and cardia-cerebrovascular disease were examined in all patients. Results:HbA 1C level in T1 group was higher than that in T3 group( P<0.05). High density lipoprotein-cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) in T1 group were higher compared with those in T2 and T3 groups ( P<0.05). Male proportion, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), 24h urinary albumin, diabetic kidney disease and peripheral atherosclerosis in T2 and T3 groups were higher than those in T1 group ( P<0.05). Fasting C- peptide (FCP) and modified homeostasis model assessment for insulin resistance (HOMA-IR) in T3 group were higher than those in T1 and T2 group ( P<0.01). VAT and SAT were positively correlated with BMI, FCP, and HOMA-IR (p<0.01). VAT was positively correlated with age, SBP, DBP, TG, 24h urinary albumin, diabetic kidney disease, peripheral atherosclerosis, and cardia-cerebrovascular disease ( P<0.05), while inversely correlated with HbA 1C, HDL-C, and eGFR ( P<0.05). SAT was positively correlated with total cholesterol and low density lipoprotein-cholesterol ( P<0.01), while negatively correlated with peripheral atherosclerosis ( P<0.01). Multivariate logistic regression analysis showed that VAT was still a risk factor for diabetic kidney disease after adjusted by age, BMI, SBP and fasting plasma glucose( P=0.013). Conclusion:VAT and SAT are associated with blood lipids and insulin resistance, while VAT seems to be a risk factor for diabetic kidney disease.

Management of cytokine release syndrome related to CAR-T cell therapy / 医学前沿

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

Partial lipodystrophy type 2 : One case report and literature review / 中华内分泌代谢杂志

Familial partial lipodystrophy type 2 (FPLD2) is an autosomal dominant disorder caused by mutations in LMNA gene,which is characterized by adolescent onset selective subcutaneous fat loss with metabolic abnormalities such as insulin resistance.Severe insulin resistance can cause acanthosis nigricans,pseudoacromegaly,ovarian dysfunction,glucose,and lipid metabolism disorders.Therefore,it is often misdiagnosed as metabolic syndrome,type 2 diabetes,polycystic ovary syndrome,acromegaly,and Cushing's syndrome.Through the analysis of the diagnosis and treatment of a case of FPLD2 with acromegaly,and the importance of tracing the origin of the disease is emphasized and also does the role of genetic testing in diagnosis.It suggests that clinicians should pay attention to the fat distribution of those similar patients,and make diagnosis and treatment timely.

Characteristics of abdominal fat distribution in patients with primary aldosteronism / 中华内分泌代谢杂志

Objective To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance. Methods Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients accepted quantitative computed tomography to measure the total abdominal fat area ( TFA), visceral fat area ( VFA), and subcutaneous fat area ( SFA) when accepted adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated. Results TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P＜0.01), and there were without statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index ( P＜0. 01), TFA was positively correlated with triglycerides ( TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P＜0.05). Conclusion Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA.

Characteristics of abdominal fat distribution in patients with primary aldosteronism / 中华内分泌代谢杂志

Objective@#To compare the abdominal fat distribution in patients with primary aldosteronism (PA) and essential hypertension (EH), and to analyze the correlation between abdominal fat area and indexes such as glycolipid metabolism and insulin resistance.@*Methods@#Forty-five PA and 55 EH patients were collected from inpatients in the First Affiliated Hospital of Zhengzhou University for suspicious secondary hypertension, from September 2016 to February 2019. All patients received quantitative computed tomography to measure the total abdominal fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) when receiving adrenal CT detection. Visceral obesity was defined as VFA≥130 cm2. The percentage of visceral fat area in total abdominal fat area (V%=VFA/TFA), the ratio of visceral fat area to subcutaneous fat area (V/S=VFA/SFA) and the percentage of visceral obesity were calculated.@*Results@#TFA and VFA in EH group were higher than those in PA group matched by age, gender, and body mass index (BMI, all P<0.01), and there were no statistically significant differences in SFA, V%, V/S, and the percentage of visceral obesity between the two groups. In PA group, TFA and VFA were positively correlated with homeostasis model assessment of insulin resistance index (P<0.01), TFA was positively correlated with triglycerides (TG) and low density lipoprotein-cholesterol, while SFA was positively correlated with TG (all P<0.05).@*Conclusion@#Compared with EH patients matched by age, gender, and BMI, TFA and VFA in PA patients are lower. Abdominal fat area is associated with insulin resistance and blood lipids in PA patients, while VFA exerts a greater effect on insulin resistance than that of TFA and SFA.

Screening and identification of RNA interference sequence for human acute monocytic leukemia related antigen 22 / 白血病·淋巴瘤

Objective To screen the optimal RNA interference sequence of acute monocytic leukemia associated antigen 22 (MLAA-22) gene in order to study gene function of it. Methods MLAA-22 coding sequence (CDS) was cloned by reverse transcription polymerase chain reaction (RT-PCR) and the CDS was inserted in to pEGFP-N1-3FLAG vector to construct eukaryotic expression vector of MLAA-22. At the same time, four RNA interference sequences were designed and cloned to the vector. Expression vector and RNA interference vector were co-transfected into 293T cells, and the optimal RNA interference sequence was screened by fluorescence and Western blot analyses. Results MLAA-22 eukaryotic expression vector pEGFP-N1-3FLAG and four RNA interference vectors were successfully constructed. After co-transfected 293T cells, KD2 was selected as the optimal interference sequence of MLAA-22. Conclusion KD2 is an optimal interference sequence for targeting MLAA-22 antigen gene.

Application of improved chromosome short-term culture method in the chromosome karyotype analysis of leukemia patients / 西安交通大学学报(医学版)

Objective To make the chromosome karyotype analysis of 130 patients with leukemia by using the improved chromosome short-term culture method.Methods We optimized the main factors with a single factor gradient experiment in short-term culture of bone marrow chromosome, including colchicines concentration, duration of action of colchicines,and hypotonic time.On this basis,we conducted the three-factors and three-level orthogonal experiment to achieve improved bone marrow chromosome preparation system,which was later applied in 130 patients with leukemia in our hospital.Results The orthogonal experiment results showed that the optimum conditions were colchicines concentration of 0.07 μg/mL,colchicines action time of 80 min,and hypotonic time of 35 min during the preparation of the bone marrow chromosome.Using this method,the chromosome preparation success rate reached 97.69% and the detection rate of abnormal karyotype reached 82.3% in the chromosome karyotype analysis.Conclusion Bone marrow chromosome preparation system with colchicines concentration of 0.07 μg/mL and colchicines action time of 80 min,and hypotonic time of 35 min is worthy of clinical promotion.

Modified Glasgow prognostic score as a prognostic factor in castrate-resistant prostate cancer treated with docetaxel-based chemotherapy and clinical analysis / 中华泌尿外科杂志

Objective To explore the prognostic value of modified Glasgow prognostic score (mGPS) and risk factors in predicting overall survival (OS) in the castrate-resistant prostate cancer (CRPC) treated with docetaxel-based chemotherapy.Methods We retrospectively analyzed the data of 48 consecutive Chinese patients with CRPC received docetaxel-based chemotherapy in our institution from January 2008 to January 2012.Patients were divided into three groups according to the mGPS:0,1 and 2 score groups,and compare the OS among the three groups.Variables that were influenced the efficacy of chemotherapy were included in the univariate analysis and multivariate model.Survival analysis was performed using Kaplan-Meier curves,and the differences in overall survival rates were assessed using the Logrank test.Results The follow-up was performed until April 2014.There were 48 CRPC patients including mGPS 0 score group 30 cases,mGPS 1 score group 11 cases and mGPS 2 score 7 cases.The median OS was 22,11,9 months,respectively,P＜0.01.Univariate analysis showed that:prechemotherapy baseline total prostate-specific antigen (tPSA),Eastern Cooperative Oncology Group (ECOG) score,the number of chemotherapy cycle,visceral metastasis and PSA response were associated with poor prognosis (P＜0.05).Multivariate analysis showed that:prechemotherapy mGPS 1-2 score,baseline tPSA＞60 μg/L,the number of cycles of chemotherapy≤5,with visceral metastasis and PSA response in patients with CRPC were independent risk factors for prognosis in the CRPC treated with docetaxel-based chemotherapy.Conclusion mGPS is an independent risk factor for prognosis in the CRPC patients treated with docetaxel-based chemotherapy.

Research of detecting the development of mechanical variation in necrotic femoral head in daily activities by finite ele-ment method / 中华骨科杂志

Objective To propose an optimal therapeutic scheme, finite element analysis was used to evaluate the biome?chanical status of femoral head under daily activities. Methods Non?necrotic femoral head volunteers (11 people) and necrotic femoral head patients (7 cases) were included in this study. All these participants were divided into two groups:control group and abnormal group. The DICOM imaging files of each participant were imported into ScanIP software to form a mask showing the prox?imal femurs. Then the finite element models of proximal femurs were progressively reconstructed. The generated models were im?ported into Abaqus, and the forces were added on these models to simulate daily activities, including standing, sitting, upstairs, and squatting etc. The loads and boundary conditions of digital daily activities simulation were collected from Orthoload database. All of the femoral finite element models were progressed in Abaqus under above activity conditions. After the models were pro?cessed, stress concentrating region was defined in each models respectively, which expressed the main bearing structure in each model based on the result of finite element analysis. At last, the elastic modulus (E?modulus) and strain of the stress concentrating region in each femoral model were extracted and calculated. Results There was no significant difference in age, weight, and height between these two groups. In control group, no significant differences of E?modulus (7 125±745 MPa on left, and 7 112±751 MPa on right) and strain (micro?strain:952 on left, and 954 on right)were found between their bilateral proximal femurs;however in abnormal group, the patients' E?modulus (5 798±1036 MPa on normal side, and 6 667±888 MPa on necrotic side) and strain (mi?cro?strain:1 261 on normal side, and 987 on necrotic side) of necrotic side were significantly lower than normal side. As to all the daily activities which were considered in this study, in abnormal group, the E?modulus among each postures of abnormal side were significantly lower than the E?modules of healthy side;the micro?strain in downstairs was also significantly lower than other pos?tures. Conclusion Daily activities with different intensity could generate different mechanical effects on femoral head, espe?cially on necrotic femoral head. The higher intensity of posture, the greater damage would be found in necrotic femoral head.

Pituitary crisis in a multiple myeloma patient during treatment / 中国肿瘤临床

Multiple myeloma is common in the older population and is treated mainly with chemotherapy. However, chemotherapy-related side effects imitate the clinical manifestations of Sheehan's syndrome, which leads to misdiagnosis and missed diagnosis, particularly for older patients without a clear history of postpartum hemorrhage. Therefore, when older women with malignant myelomas show refractory hyponatremia and gastrointestinal disorders while under chemotherapy, a diagnosis of Sheehan's syndrome should be considered. The early detection of the disorder will guarantee timely individualized treatment.

Allogeneic peripheral blood stem cell transplantation using a low toxicity conditioning regimen with fludarabine and busulfan for 13 patients with hematological malignancies / 白血病·淋巴瘤

[Objective]To discuss the clinical effect of fludarabine and busulfan (Bu+Flu) as a low toxicity myeloablative conditioning regimen for allogeneic peripheral blood stem cell transplantation (allo-HSCT)in leukemia patients.[Methods]Clinical data of 13 patients with hematological malignancies receiving conditioning regimen with Bu+Flu for allo-HSCT were analyzed retrospectively.Conditioning regimen was Bu+Flu,compalriot mismatched and unrelated transplantation combined with rabbit anti-human thymocytes immune globulin (ATG).CsA+short course of methotrexate or CsA + mycophenolate mofetil were used to prevent graft-versus-host disease (GVHD).DNA sequencing of short tandem repeat (STR)polymorphism analysis method was performed for identification of donor stem cells implantation.[Results]13 patients all tolerated with this conditioning regimen well,no serious complications occurred.Neutrophil engraftment was at 9-15 days (median 11 days),platelet engraftment at 8-25 days (median 13 days).10 patients achieved hematopoiesis reconstitution with their full donor chimerisms confirmed by STR-DNA analysis.Acute GVHD occurred in 5 cases,accounting for 38.5％.Chronic GVHD occurred in 4 cases of 10 patients could be assessed,accounting for 40.0％.Severe GVHD more than Ⅱ degree did not happen.1-39 months (median time 11 months)of follow-up revealed the overall survival rate of 76.9％(10/13),disease-free survival of 61.5％ (8/13).The causes for death were relapse in all.[Conclusion]The conditioning regimen with Bu+Flu has low toxicity,well tolerance and better effect.

Endoplasmic reticulum stress-related apoptosis pathway is involved in unilateral ureteral obstruction-induced renal interstitial fibrosis in rats / 中华肾脏病杂志

Objective To investigate the effect of endoplasmic reticulum stress (ERS)-associated apoptosis on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) in rats. Methods Eighteen healthy male Wistar rats undergoing UUO were sacrificed at 3,7,14 days after operation. Additional seven rats underwent sham operation. Histological changes were observed by HE and Masson staining. Immunohistochemistry was performed on renal tissue for α-smooth muscle actin (α-SMA). Chromatometry was used to detect the content of hydroxyproline. Apoptosis cells were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and the electrophoresis analysis of genome DNA. The mRNA expression of glucose-regulated protein 78 (GRP78), which are important markers of ERS, were detected by RT-PCR. Western blotting was used to assess the protein level of GRP78 and cysteinyl aspartate specific proteinase-3 (caspase-3). Results Compared with sham operation group, the degree of renal interstitial and the level of hydroxyproline content of UUO group increased significantly (P<0.05). Immunohistochemistry staining indicated that a-SMA extensively expressed in renal tubular and interstitial cells. The apoptotic cells in the renal tubular and interstitium were continuously increased from day 3 to the end of experiment of UUO group. As early as 3 days after surgery, the mRNA level of GRP78 in UUO group increased compared with sham operation group (P<0.01), while the protein expression increased on day 7 after surgery (P<0.01). Prolonged ERS triggered apoptosis, the protein expression of caspase-3 increased significantly on day 3 after surgery (P< 0.05), and the expression sustained high level during the experiment afterwards. There was a positive correlation between GRP78 protein expression and hydroxyproline content (r =0.657, P< 0.01) as well as caspase-3 protein expression (r=0.714, P<0.01). Conclusions UUO induces a significant up-regulation in endoplasmic reticulum molecular chaperones at early stage, indicating that ERS response is activated in the rat kidney. Prolonged ERS can lead to renal tubular and interstitial cell apoptosis, and caspase-3-mediated ERS associated apoptosis may contribute to the fibrosis.

Neuroform self-expanding stent for treatment of symptomatic intracranial vertebrobasilar arterial stenosis / 中国组织工程研究

OBJECTIVE:To study the safety and efficacy of Neuroform self-expanding stent for symptomatic intracranial artery stenosis.METHODS:A total of 37 patients with symptomatic intracranial artery stenosis received treatment at the Department of Neurosurgery,Affiliated Hospital of Behua University and Xuanwu Hospital were selected,who were ineffective to anticoagulation and antiplatelet treatment,including 24 males and 13 females,aged from 49 to 72 years,mean aged 64 years.All patients were received Neuroform self-expanding stent following angiography.RESULTS:All patients underwent PTAS with mean preoperative stenosis were reduced from 64% to 24% after percutaneous transluminal angioplasty (PTAS).The technically successful rate was 100%.All the patients were received a 6-22 month follow-up (average 13 months).The average artery stents was retrieved by 50%-90% after stent deployment.There was no arterial dissection,acute occlusion of the target artery or symptomatic distal emboli.Within the follow-up period,1 patient endured asymptomatical artery full occlusion.Two stents were implanted simultaneously in 3 patients,1 of them suffered bilateral vertebral artery stenosis,and 2 had right vertebral arterial and basilar artery stenosis.One patient suffered acute in-stent thrombosis and recovered after thrombolytic therapy.No pathogenetic condition was aggravated in the follow-up.CONCLUSION:The application of Neuroform self-expanding stent can alleviate the ischemic symptoms of patients with vertebrobasilar stenosis and elevate the operative safety and effectiveness.However,further study is needed to evaluate the long-term therapeutic effect.

Effects of oxidative stress on expressions of TGF-?1 and TGF-?RⅠ in rat kidney after unilateral ureteral obstruction / 吉林大学学报(医学版)

Objective To investigate the effects of oxidative stress on the expressions of transforming growth factor-?1(TGF-?1) and transforming growth factor-? receptor Ⅰ(TGF-?RⅠ) in rat unilateral ureteral obstruction(UUO) models.Methods Thirfty Wistar rats were randomly assigned into three groups:SOR group(sham-operated group,n=7);UUO group(operation group,n=11);US group(spironolactone 50 mg?kg-1?d-1 by daily gastric gavage after UUO,n=12).All the rats were killed 14 d after surgery.Renal fibrosis was assessed by the determination of tissue hydroxyproline(HYP) content.Malondialdehyde(MDA),superoxide dismutase(SOD) as well as aldosterone(ALD) content were measured.Histological changes were observed by HE and Masson staining.Immunohistochemistry was performed to detect the expressions of TGF-?1 and TGF-?RⅠ.Western blotting was used the determine the expression of TGF?RⅠ protein.Results Compared with sham group,the ALD contents in plasma and kidney tissues in UUO group significantly increased(P