Connexin 43 gap junction affects survival and drug resistance of multiple myeloma side population cells.

Drug resistance remains a major challenge for multiple myeloma (MM) treatment, and side population (SP) cells may play a key role in this resistance. The function of connexin 43 (Cx43)-mediated gap junction intercellular communication (GJ-IC) in MM cells is poorly understood. Bone marrow mesenchymal stem cells (BMSCs) from different sources were isolated and cultured. SP cells of MM cell line RPMI 8266 were separated by flow cytometry. Real-time reverse transcriptase-polymerase chain reaction and Western blot were used to detect Cx43 mRNA and protein expression in BMSCs, RPMI 8266 and SP cells from different sources. The effects of BMSCs from different sources on SP cell cycle, in vitro colony formation ability, stem cell-related gene expression and drug resistance, and the addition of 18α glycyrrhetinic acid (18αGA) as a pathway inhibitor were observed. Here, we demonstrate that MM cells expressed Cx43 and contained a high percentage of SP cells. We observed an increase in the survival and proliferative capacity of SP cells compared with RPMI 8226 cells, but treatment with 18αGA decreased SP cell survival and proliferation (all P<0.05). MM cells were sensitive to dexamethasone- and bortezomib-induced apoptosis; however, this sensitivity was significantly decreased when MM cells were co-cultured with BMSCs, and 18αGA partly recovered this cytotoxicity (all P<0.05). Collectively, our data suggest that GJ-IC between BMSCs and MM cells is one of the important regulatory mechanisms underlying MM cells survival, proliferation, and drug sensitivity.

Contrast-enhanced magnetic resonance angiography in the identification of prostatic arterial anatomy in patients with benign prostatic hyperplasia: prospective comparison with digital subtraction angiography.

AIM: To evaluate the utility of contrast-enhanced magnetic resonance angiography (CE-MRA) for identifying prostatic artery (PA) anatomy in patients with benign prostatic hyperplasia (BPH) before PA embolisation (PAE), using digital subtraction angiography (DSA) as the reference standard. MATERIALS AND METHODS: A total of 176 patients underwent pelvic CE-MRA at 3 T. DSA was performed within the following 7 days. Two interventional radiologists compared the CE-MRA findings with DSA findings to assess the anatomy of the PAs. The rates of correct identification of the origins and collaterals of the PAs by CE-MRA were calculated. The utility for predicting the optimal X-ray tube angle obliquity for visualising the origins of the PAs by CE-MRA was evaluated. An exact McNemar's test was used to compare the detection rates of the PAs and the collaterals with DSA versus CE-MRA. A two-sided p-value of <0.05 was considered statistically significant. RESULTS: Of the 376 PAs identified by DSA, CE-MRA correctly identified the origins of 369 vessels (98.1%), with a 1.9% false-negative rate and no false-positive results. Of the 57 total collaterals identified by DSA, CE-MRA identified 50 vessels correctly (87.7%), with a 12.3% false-negative rate and no false-positive results. No significant differences were observed between CE-MRA and DSA in the identification of the PA origins (p=0.824) and the collaterals (p=0.327). The optimal degree for an oblique projection to visualise the origins of the PAs could be predicted accurately (100%) by pre-procedural CE-MRA. CONCLUSION: CE-MRA before PAE can reliably predict the PA anatomy and facilitate procedural planning.

[Bendamustine monotherapy for Chinese patient treatment with relapsed or refractory B cell non-Hodgkin lymphoma: a phase â ¡, prospective, multicenter, single-arm study].

Objective: To evaluate the efficacy and safety of bendamustine monotherapy in Chinese patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) . Methods: This prospective, multicenter, open label, single-arm, phase Ⅱ study investigated bendamustine's efficacy and safety in Chinese patients with R/R B-NHL. A total of 78 patients with B-NHL in 11 hospitals in China from March 2012 to December 2016 were included, and their clinical characteristics, efficacy, and survival were analyzed. Results: The median age of all patients was 58 (range, 24-76) years old, and 69 (88.4% ) patients had stage Ⅲ/Ⅳ disease. 61 (78.2% ) patients were refractory to previous treatments. Patients received a median of 4 (range, 1-10) cycles of bendamustine treatment. The overall response rate was 61.5 (95% CI 49.8-72.3) % , the median response duration was 8.3 (95% CI 5.5-14.0) months, and the complete remission (CR) rate was 5.1 (95% CI 1.4-12.6) % . In the full analysis set, median progression-free survival (PFS) and median OS were 8.7 (95% CI 6.7-13.2) months and 25.5 months (95% CI 14.2 months to not reached) , respectively, after a median follow-up of 33.6 (95% CI 17.4-38.8) months. Lymphopenia (74.4% ) , neutropenia (52.6% ) , and leukopenia (39.7% ) , thrombocytopenia (29.5% ) and anemia (15.4% ) were the most common grade 3-4 hematologic adverse events (AE) . The most frequent non-hematologic AEs included nausea (43.6% ) , vomiting (33.3% ) , and anorexia (29.5% ) . Univariate and multivariate analysis showed that <4 cycles of bendamustine treatment was a poor prognostic factor for PFS (P=0.003) , and failure to accept fludarabine containing regimen was a poor prognostic factor for OS (P=0.009) . Conclusion: Bendamustine monotherapy has good efficacy and safety in the treatment of patient with R/R B-NHL.

LncRNA OIP5-AS1 induces epithelial-to-mesenchymal transition and renal fibrosis in diabetic nephropathy via binding to miR-30c-5p.

NIn recent years, the incidence of diabetic nephropathy (DN) is rising, and is one of the most important complications of diabetic patients. In this study, the role and regulatory mechanism of lncRNA OIP5-AS1 in the regulation of DN were investigated. Here, the expressions of lncRNA OIP5-AS1 and miR-30c-5p were detected by RT-qPCR. Western blot analysis was used to detect the protein expression of E-cadherin, N-cadherin, TGF-ß1, α-SMA. The relationship between OIP5-AS1 and miR-30c-5p was confirmed by dual luciferase reporter assay. The results showed that the expression of lncRNA OIP5-AS1 was increased in db/db DN mice kidney tissue and high glucose-stimulated HK2 cells. lncRNA OIP5-AS1 promoted epithelial-to-mesenchymal transition (EMT) and renal fibrosis in high glucose-stimulated HK2 cells. In addition, lncRNA OIP5-AS1 directly targets miR-30c-5p, and lncRNA OIP5-AS1 negatively regulated miR-30c-5p expression in high glucose-stimulated HK2 cells. More importantly, overexpression of miR-30c-5p attenuated the promoting effect of OIP5-AS1 on EMT and renal fibrosis in high glucose-stimulated HK2 cells. In conclusion, lncRNA OIP5-AS1 induces EMT and renal fibrosis in DN via binding to miR-30c-5p.

[Value of lenvatinib for the treatment of advanced hepatocellular carcinoma].

Objective: To observe the safety and efficacy of lenvatinib for the treatment of medium-advanced hepatocellular carcinoma. Methods: A total of 36 patients with medium-advanced hepatocellular carcinoma from the First Medical Center of the Chinese PLA General Hospital were retrospectively analyzed from January 2018 to May 2019. All patients had shown tumor progression after at least 2 sessions of TACE. The patients were consisted of 30 males and 6 females with age range of 35 to 76 (54±10) years. Patients received orally administered lenvatinib at a dose of 12 mg once daily for patients ≥ 60 kg and 8 mg once daily for patients<60 kg. According to modified RECIST criteria the tumor response, disease control rate, overall survival and progression free survival were evaluated once every 6-8 weeks. The adverse events were recorded. Results: No patient was in complete response, 2 cases (5.7%) in partial response, and 5 cases (14.3%) in stable disease, respectively. Disease control rate was 20.0% (7/35), the overall survival was 11.5 months, and the progression free survival was 5.3 months. The overall incidence of adverse events was 66.7% (24/36). The most frequent adverse events were hypertension, proteinuria, hand-foot skin reaction and abdominal distension. Conclusion: Lenvatinib can extend the overall survival in a percentage of medium-advanced hepatocellular carcinoma patients who were unresectable and refractory to TACE. Although the incidence of adverse events is high, most of them are mild and reversible.

Associations among menopausal status, menopausal symptoms, and depressive symptoms in midlife women in Hunan Province, China.

Objective: This study aimed to determine the associations among menopausal status, menopausal symptoms, and depressive symptoms in midlife women in Hunan, China.Methods: A secondary analysis involving 3199 women aged 40-55 years was performed based on data from the Women Health Needs Survey 2018 in Hunan Province, central south China. The depressive symptoms were determined using the 9-item Patient Health Questionnaire. The menopausal symptoms were assessed using the Kupperman Menopausal Index. Demographic characteristics and menopausal status were measured using self-administered questionnaires.Results: The prevalence of depressive symptoms was 19.3%. The three most common menopausal symptoms were insomnia (48.0%), fatigue (42.7%), and mood swing (39.8%). The increase in depressive symptoms was significantly associated with menopausal status and menopausal symptoms. After controlling for demographic variables, multivariate logistic regression showed that menopausal transition (odds ratio [OR] = 1.14, 95% confidence interval [95% CI] = 1.12-1.86), postmenopause (OR =1.52, 95% CI = 1.09-2.11), and four menopausal symptoms including mood swing (OR = 1.32, 95% CI = 1.03-1.70), depressive mood (OR = 2.28, 95% CI = 1.79-2.91), palpitations (OR = 1.37, 95% CI = 1.06-1.77), and urinary tract infection (OR = 1.49, 95% CI = 1.16-1.92) were associated with depressive symptoms.Conclusions: Independent of demographic variables, menopausal transition, postmenopause, and four menopausal symptoms (mood swing, depressive mood, palpitations, and urinary tract infection) increase the risk of depressive symptoms.

Transarterial embolisation with bleomycin and N-butyl-2-cyanoacrylate -Lipiodol mixture for symptomatic polycystic liver disease: preliminary experience.

AIMS: To evaluate the therapeutic effect and safety of transarterial embolisation using a bleomycin-Lipiodol mixture and N-butyl-2-cyanoacrylate (NBCA)-Lipiodol mixture (BNL) for the treatment of polycystic liver disease (PLD). MATERIALS AND METHODS: From June 2012 to July 2018, a total of consecutive 14 symptomatic patients (13 women and 1 man; mean age, 49.3±9.9 years) with PLD were referred and underwent transcatheter arterial embolisation (TAE) with BNL. RESULTS: Technical success was achieved in all cases. PLD-related severe symptoms were improved remarkably in 13 of the treated patients. The mean maximum abdominal circumference decreased significantly from 100.6±9.4 to 94.9±9.1 cm (p<0.01). The total liver volume decreased significantly compared with pre-TAE in 13 patients at 6-12 months after TAE. It decreased from 9,776±2,219 to 8,303±2,009 cm3 (p<0.01). There were no major complications associated with the procedure. CONCLUSION: TAE with the bleomycin-Lipiodol mixture and NBCA-Lipiodol mixture may be an effective method for treating symptomatic PLD patients, with improvement of symptoms and shrinkage of cyst volume.

[Advances in the research of transcatheter arterial thrombolysis for severe frostbite therapy].

Severe frostbite (grade Ⅲ to Ⅳ) is a common disease accompanied with high disability rate in cold regions, especially for military training and disaster events in cold regions. The treatment of severe frostbite mainly includes rapid rewarming in the early stage and amputation in the later stage; while the damage of vascular endothelial cells, microvascular thrombosis, and decreased tissue perfusion secondary to severe frostbite are important factors affecting prognosis. Transcatheter arterial thrombolysis is a new technique for the treatment of severe frostbite. It has the advantages of minimally invasive, high safety, and significantly reduced amputation rate. We reviewed the advances in the research of transcatheter arterial thrombolysis for the treatment of severe frostbite.

[Transarterial chemoembolization with bleomycin treatment for moderate-advenced hepatocellular carcinoma].

Objective: To investigate the safety and efficacy of transarterial chemoembolization (TACE) using bleomycin for the treatment of medium-advanced hepatocellular carcinoma (HCC). Methods: Between December 2015 and December 2017, a total of 160 patients from the Chinese PLA General Hospital with moderate-advanced HCC whose diagnoses were confirmed by pathology or clinical imaging and were in accord with the Barcelona Clinic Liver Cancer (BCLC) staging criteria were prospectively analyzed.All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE.All patients included 135 males and 25 females , age 35-74 (57±8)years, were randomly divided into two groups, the treatment group: TACE procedures consisted of bleomycin+ pirarubicin+ oxaliplatin+ fluorouracil, the control group: pirarubicin+ oxaliplatin+ fluorouracil, and according to modified RECIST criteria the tumor response was evaluated once every 4-6 weeks, survival analysis was performed, overall survival and progression free survival were evaluated.the adverse events were recorded. Results: Response rate of the treatment group was 27.5%(22/80), the median progression free survival(mPFS)was 5.8 months, and the median overall survival (mOS) was 8.1 months.Response rate of the control group was 7.5%(6/80), mPFS of 2.9 months, and mOS of 4 months.The differences in mPFS and in mOS between the two groups were statistically significant (P=0.009, 0.002 respectively), and no serious adverse occurred. Conclusion: It is suggested that transarterial chemoembolization with bleomycin is safe and effective for medium-advenced HCC.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis.

We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.

Identification of single nucleotide polymorphisms in the ASB15 gene and their associations with chicken growth and carcass traits.

ASB15 is a member of the ankyrin repeat and suppressor of cytokine signaling box family, and is predominantly expressed in skeletal muscle. In the present study, an F2 resource population of Gushi chickens crossed with Anka broilers was used to investigate the genetic effects of the chicken ASB15 gene. Two single nucleotide polymorphisms (SNPs) (rs315759231 A>G and rs312619270 T>C) were identified in exon 7 of the ASB15 gene using forced chain reaction-restriction fragment length polymorphism and DNA sequencing. One was a missense SNP (rs315759231 A>G) and the other was a synonymous SNP (rs312619270 T>C). The rs315759231 A>G polymorphism was significantly associated with body weight at birth, 12-week body slanting length, semi-evisceration weight, evisceration weight, leg muscle weight, and carcass weight (P < 0.05). The rs312619270 T>C polymorphism was significantly associated with body weight at birth, 4, 8, and 12-week body weight, 8-week shank length, 12-week breast bone length, 8 and 12-week body slanting length, breast muscle weight, and carcass weight (P < 0.05). Our results suggest that the ASB15 gene profoundly affects chicken growth and carcass traits.

The effect of the shape of nanorod arrays on the nanocarpet effect.

The bundling of densely packed free-standing nanorods/nanotubes in a liquid environment, or the 'nanocarpet effect', has a direct impact on the stability of nanostructures used for chemical and biological sensors. Using glancing angle deposition, we prepared four different structures: vertically aligned, tilted, zigzag, and square spring Si nanorod arrays, and compared their stabilities after water treatment. We found that although the tilted nanorods were bent in the nanorod tilting direction, they did not form nanorod bundles, and this structure was the most stable one. The larger the tilting angle, i.e., the more inclined the nanorod was to the surface, the more stable the structure. We also found that the quasi-vertical nanorod structures, the zigzag and square spring structures, showed improved stabilities compared to vertically aligned nanorods. Furthermore, by properly depositing a capping layer on top of the vertically aligned nanorods, the structure became mechanically very stable while the high porosity nature of the nanorod array was maintained. This work is helpful for designing stable nanostructures used in a liquid environment.

[Effects of recombinant human macrophage colony stimulating factor (rhM-CSF) on stromal cell derived during the time of mice colony formation unit-spleen (CFU-S) and its role on CD34+ cells expansion in vitro].

OBJECTIVE: To investigate the effects of stromal cell derived from mice spleen during in vitro expansion of CD34+ hematopoietic stem cells from umbilical cord blood. METHODS: Irradiated and non-irradiated mice at day 10, 12 and 14 were sacrificed and their spleens were taken for collecting spleen cells. The cells were stimulated with recombinant human macrophage colony stimulating factor(rhM-CSF) for collecting adherent spleen derived stroma cells. The effects of spleen derived stromal cells which treated with mitomycin served as a feeder layer, combined with different cytokines on in vitro expansion of purified cord blood CD34+ were assayed. Clonogenic assay and flow cytometry were employed to analyze phenotype of expanded cells and their ability to form different colony in vitro. RESULTS: 1) rhM-CSF efficiently stimulated spleen derived stromal cells to proliferate; 2) The mice stromal cells obtained during the time of colony formation-unit spleen (CFU-S) promoted the CD34+ cells to form colony in semisolid medium and, combined with cytokines, thereby efficiently expanded the hematopoietic cells from cord blood. After two weeks incubation, CD34 positive cells were 100 times more than original cells cultured and expanded cells still have the ability to form multi-lineage colony in vitro. CONCLUSION: rhM-CSF can stimulate the stromal cells derived from CFU-S to proliferate and support the survival and expansion of CD34+ cells separated from cord blood.

[Effects of SDF-1 alpha and its receptor on regulation of hematopoiesis].

Hematopoietic stem/progenitor cell transplantation is one of main choices for treating patients with malignant tumor or heredity diseases in recently year. The homing of hematopoietic stem cells(HSC) is a committed step to ensure the bone marrow hematopoiesis reconstitution. Recent studies have showed that stromal cell derived factor-1 (SDF-1) and its receptor has important effects on proliferation, differentiation, homing of HSC to bone marrow and hematopoiesis reconstitution. The purpose of this review is to give a recent update informations on mechanism of hematopoiesis regulation mediated by SDF-1 and its receptor.

[Measurement of MEFV in 66 cases of asthma in the convalescent stage and after treatment with Chinese herbs].

This paper reported the measurement of maximal expiratory flow-volume curve (MEFV) for 66 cases of asthmatics in the convalescent stage. Among which the data of FEV, PEF, V75, V50, V25 in 35 cases (53.03% of the total) gave different abnormal as compared with healthy persons. It showed that in the convalescent stage, most of the asthmatics still possessed obstruction of airways and chiefly of small airways. 35 cases of asthmatics in the convalescent stage was given the Chinese herbal decoction of chiefly invigorating Kidney (Viscum coloratum 15g, Psoralea corylifolia 15g, Eucommia ulmoides 15g, Lycium chinense 9g, Tussilago farfara 15g, Artemisia capillaris 9g, and Pogostemon cablin 9g as daily dosage) for treatment of 10 weeks and measuring MEFV curves to observe their changes before and after treatment. The results showed that different parameters of MEFV was improved in some extent which suggested that the airway obstruction of asthmatics in the convalescent stage was reversible. In discussion, the authors indicated that the prompt treatment for asthmatics in the convalescent stage was conductive early to prevent emphysema and confirmed that the treatment with Chinese herbs of chiefly invigorating Kidney deserved to be propagated.