[Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes].

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 µg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 µg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor ß1 (TGF-ß1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-ß1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-ß1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-ß1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-ß1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

[Clinical features of 19 patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia].

Objective: To assess the clinical characteristics and prognosis of patients with SIL-TAL1-positive T-cell acute lymphoblastic leukemia (T-ALL) . Methods: The clinical data of 19 SIL-TAL1-positive T-ALL patients admitted to the First Affiliated Hospital of Soochow University between January 2014 and February 2022 were retrospectively computed and contrasted with SIL-TAL1-negative T-ALL patients. Results: The median age of the 19 SIL-TAL1-positive T-ALL patients was 15 (7 to 41 years) , including 16 males (84.2%) . SIL-TAL1-positive T-ALL patients had younger age, higher WBC, and hemoglobin compared with SIL-TAL1-negative T-ALL patients. There was no discrepancy in gender distribution, PLT, chromosome abnormality distribution, immunophenotyping, and complete remission (CR) rate. The 3-year overall survival (OS) was 60.9% and 74.4%, respectively (HR=2.070, P=0.071) . The 3-year relapse-free survival (RFS) was 49.2% and 70.6%, respectively (HR=2.275, P=0.040) . The 3-year RFS rate of SIL-TAL1-positive T-ALL patients was considerably lower than SIL-TAL1-negative T-ALL patients. Conclusion: SIL-TAL1-positive T-ALL patients were connected to younger age, higher WBC, higher HGB, and poor outcome.

Hypoxia Modulates Melanoma Cells Proliferation and Apoptosis via miRNA-210/ISCU/ROS Signaling.

In this study, luciferase reporter assay was used to establish the relationship between miR-210 and ISCU. This research was performed on both cell lines (A2058, G361, and 293T) and tissue samples. We found that miR-210 was upregulated in hypoxia and was elevated in melanoma in comparison with adjacent normal tissues. Expression of ISCU protein was decreased in melanoma tissues, and ISCU gene is a direct target of miR-210. ISCU knockdown with miR-210 enhanced ROS production. The results of our study showed that miR-210/ISCU/ROS axis can serve as a novel therapeutic target in melanoma.

S-Adenosylmethionine Rescues Cognitive Deficits in the rTg4510 Animal Model by Stabilizing Protein Phosphatase 2A and Reducing Phosphorylated Tau.

BACKGROUND: Alterations in the methionine cycle and abnormal tau phosphorylation are implicated in many neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia. rTg4510 mice express mutant human P301L tau and are a model of tau hyperphosphorylation. The cognitive deficit seen in these animals correlates with a burden of hyperphosphorylated tau and is a model to test therapies aimed at lowering phosphorylated tau. OBJECTIVE: This study aimed to increase protein phosphatase 2A activity through supplementation of S-adenosylmethionine and analyze the effect on spatial memory and tau in treated animals. METHODS: 6-month-old rTg4510 mice were treated with 100 mg/kg S-adenosylmethionine by oral gavage for 3 weeks. Spatial recognition memory was tested in the Y-maze. Alterations to phosphorylated tau and protein phosphatase 2A were explored using immunohistochemistry, western blot, and enzyme-linked immunosorbent assays. RESULTS: Treatment with S-adenosylmethionine increased the Y-maze novel arm exploration time and increased both the expression and activity of protein phosphatase 2A. Furthermore, treatment reduced the number of AT8 positive neurons and reduced the expression of phosphorylated tau (Ser202/Thr205). S-adenosylmethionine contributes to multiple pathways in neuronal homeostasis and neurodegeneration. CONCLUSION: This study shows that supplementation with S-adenosylmethionine stabilizes the heterotrimeric form of PP2A resulting in an increase the enzymatic activity, a reduced level of pathological tau, and improved cognition.

[Identification and functional study of the Schistosoma japonicum epidermal growth factor receptor gene].

OBJECTIVE: To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum. METHODS: Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy. RESULTS: The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production. CONCLUSIONS: Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.

[Children's non-carcinogenic health risk assessment of heavy metals exposure to residential indoor dust around an e-waste dismantling area in South China].

Objective: To evaluate the non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) in residential indoor dust for young children around an e-waste dismantling area in South China. Methods: A village around an e-waste dismantling area in South China was selected as a research site in October 2016. Convenience sampling method was used to select 36 houses in the village and 36 dust samples were collected by vacuum cleaner. The concentrations of heavy metals (Cd, Cr, Cu, Mn, Pb and Zn) in each sample were determined and expressed by the average value. Non-carcinogenic health risk assessment was conducted using the US Environmental Protection Agency (EPA) Health Risk Assessment (HRA) model, the American Toxicology and Disease Registry (ATSDR) Target-organ Toxicity Dose (TTD) approach and the ATSDR Binary Weight-of-Evidence (BINWOE) model. Results: The mean ± SD of concentrations of As, Cd, Cr, Cu, Mn, Pb and Zn were (48.90±33.91), (5.95±3.89), (173.57±580.37), (412.71±1 190.00), (612.82±540.70), (297.41±293.22) and (1 052.81±1 156.48) mg/kg, respectively. The HI value of TTD (2.670) and BINWOE (2.933) were higher than the safety threshold of EPA recommended non-carcinogenic health risk. The HI value of TTD and BINWOE were 1.93 and 2.12 times higher than the HI value of HRA (1.386). Conclusion: There was non-carcinogenic health risk of heavy metals (As, Cd, Cr, Cu, Mn, Pb and Zn) via residential indoor dust around the e-waste dismantling area for local children.

[Application of multi-slice spiral CT to assess vascular volume for the diagnosis and treatment of gastric varices].

Objective: To differentiate the inflow and outflow channels of gastric varices in cirrhotic portal hypertension patients using multi-slice spiral CT (MSCT), and to assess the relationship between calculable CT volume of gastric varices and the amount of tissue adhesive. Methods: 97 cases with cirrhotic gastric varices who were admitted from November 2013 to August 2017 were selected. The type and shape of gastric varices were observed before tissue glue injection treatment by MSCT. The correlation between CT volume of gastric varices and the amount of tissue adhesive was evaluated by Spearman rank correlation coefficient and Univariate linear regression analysis. Results: MSCT showed that Le, g type had the highest proportion (54.6%), followed by Le, g, Lg (20.6%). Le, Lg and Lgf type accounted for 17.5%, and 5.2%, respectively, while Lgf+b accounted for 2.1%. On MSCT, varices of the gastric fundus were in the direction from bottom to top, and 75% of the fundus had a large curved side varices combined with gastric and renal shunt. Under the gastroscopy, varices in the small curved side of the gastric fundus from near to far were formless. In addition, varices in the large curved side of the gastric fundus when observed from different angles to the direction of blood flow (reverse gastroscope) were 72.7% (near and far) or 20.5 % (far and near). There was a positive correlation between CT volume (R = 0.97, P < 0.001) and the amount of tissue adhesive (Y(1) = 0.35 + 0.65X1, Univariate linear regression equation; ρ = 0.89, P < 0.001, Spearman correlation analysis). Conclusion: MSCT can recognize the vascular shape and inflow and outflow channels of gastric varices. A positive correlation between CT volume and the amount of tissue adhesive, suggested that the CT volume measurement before treatment could be used as one of the method to predict the amount of tissue adhesive.

[Study on apoptosis mechanism of H9c2 cardiomyocytes induced by N, N-dimethylformamide].

Objective: To observe the change levels of nuclear factor-kappa B (NF-κB) p65 protein in cytoplasm and nuclear, phosphorylation of inhibitor of kappa B (p-IκB) protein and cytochrome C (Cyt-c) , cleaved cysteinyl aspartate specific proteinase-3 (Cleaved caspase-3) , B-cell lymphoma/leukemia-2 (Bcl-2) in cytoplasm in the process of N, N-dimethylformamide (DMF) -induced apoptosis in H9c2 cardiomyocytes, and explore the tentative mechanism of apoptosis. Methods: H9c2 cardiomyocytes were exposed to 200 mmol/L DMF. Western blotting was used to detect the protein expression levels of p65 in cytoplasm and nuclear, p-IκB after exposure for 0, 2, 4, 6, 8, 12 h, and the protein expression levels of Cyt-c, Cleaved caspase-3, Bcl-2 in cytoplasm after exposure for 0, 2, 4, 8, 12, 24 h. Immunofluorescencecytochemistry (IFC) was used to observe the location of Cyt-c after 200 mmol/L DMF exposure for different times. Results: The levels of p65 in cytoplasm and nuclear and p-IκB among groups were statistically significant (F were 7.79, 33.11, 90.25, respectively, all P<0.01) . Compared with the control group, the levels of p65 in cytoplasm of 2, 4, 6 h group were significantly decreased (all P<0.01) ; the levels of p65 in nuclear of 2, 4, 6, 8 h were significantly increased (all P<0.01) ; the levels of p-IκB of 2, 4, 6 h group were significantly increased (all P<0.01) . The levels of Cyt-c, Cleaved caspase-3 and Bcl-2 among groups were statistically significant (F were 51.42, 503.68, 73.37, respectively, all P<0.01) . Compared with the control group, the levels of Cyt-c of 8, 12 h group were significantly increased (both P<0.01) ; the levels of Cleaved caspase-3 of 2, 4, 8, 12, 24 h were significantly increased (all P<0.01) ; the levels of Bcl-2 of 2, 4, 8, 12, 24 h group were significantly decreased (all P<0.01) . IFC showed that Cyt-c was released from the mitochondria to the cytoplasm gradually as the extension of the exposure time. Conclusion: NF-κB signaling pathway and mitochondrial pathway are involved in the mechanism of DMF-induced apoptosis in H9c2 cardiomyocytes.

Clinic research on the treatment for humeral shaft fracture with minimal invasive plate osteosynthesis: a retrospective study of 128 cases.

INTRODUCTION: Minimal invasive plate osteosynthesis (MIPO) is one of the most important techniques in the treatment for humeral shaft fractures. This study was performed to evaluate the efficacy of MIPO technique for the treatment for humeral shaft fractures. MATERIALS AND METHODS: We retrospectively evaluated 128 cases with humeral shaft fractures that were treated with MIPO technique from March 2005 to August 2008. All the patients were followed up by routine radiological imaging and clinical examinations. Constant-Murley score and HSS elbow joint score were used to evaluate the treatment outcome. RESULTS: The average duration of the surgery was 60 min (range 40-95 min) without blood transfusion. All fractures healed without infection. All cases recovered carrying angle except four cases with 10°-15° cubitus varus. After the average follow-up of 23 (13-38) months, satisfactory function was achieved according to Constant-Murley score and HSS elbow joint score. Constant-Murley score was 80 on average (range 68-91). According to HSS elbow joint score, there were 123 cases of excellent clinical outcome and five cases of effective outcome. CONCLUSION: It seems to be a safe and effective method for managing humeral shaft fractures with MIPO technique.

[Intervention study of compassion fatigue of oncology nurses in Balint group activities].

Objective: To explore the effectiveness of Balint group on compassion fatigue among oncology nurses. Methods: From January to December 2016, 35 oncology nurses from one general hospital were enrolled. 18 cases were allocated in the observation group and 17 cases in the control group by computer randomization. Nurses in the observation group were received a total of 8 times Balint Group activities, with 2 times a month and 1.5 hours each time, which is aiming to discuss difficult cases encountered in the clinic to help nurses have a deeper experience and a better understanding of the emotions and behaviors, fantasies and needs between nurse-patient interaction. Nurses in the control group without intervention. All the Participants were requested to complete the survey of the Professional Quality of Life (ProQOL) , the Jefferson Scale of Empathy-Health Professionals (JSE-HP) , and the General Health Questionnaire (GHQ) at pre and post intervention. Results: Before intervention, two group of nurses in age, working years, marriage, and education were not statistically significant (P>0.05). There was no difference in the scores of empathy, compassion satisfaction, secondary traumatic stress, and General health (P>0.05). After intervention, the scores of JSE-HP and its three dimensions of perspective taking, emotional care, and trans-positional consideration in the observation group had significantly higher than the control group (P<0.05). The level of compassion satisfaction in the observation group was higher, and the general health status was lower (P<0.05). There was no statistically difference in the level of burnout and secondary traumatic stress between two groups (P>0.05) . Conclusion: Balint group has a positive role in promoting nurses'empathetic skills, compassion satisfaction and mental health.

Association between the resistin gene-420 C>G polymorphism and obesity: an updated meta-analysis.

OBJECTIVE: The aim of this study was to assess the relationship of the resistin gene (RETN)-420 C>G polymorphism and obesity susceptibility by conducting an updated meta-analysis. MATERIALS AND METHODS: The electronic databases including PubMed, Medline, Embase, China National Knowledge Infrastructure, Chinese Wanfang Database, and Chinese VIP database were searched for relevant studies published before December 2013. The fixed effect model or random effects model was used based on the heterogeneity test results. The sensitivity analysis was performed in the allelic model and the dominant genetic model, respectively. Publication bias was assessed via funnel plot. The meta-analysis was performed using the software of RevMan 5.2. RESULTS: Data were obtained from 10 included studies, involving 5,069 cases and 6,673 controls. The overall odds ratios (ORs) with its 95% confidence interval (CI) showed no association between RETN-420 C>G polymorphism and obesity in the allelic model (p = 0.09; OR = 1.10; 95% CI = 0.991.24), the dominant model (p = 0.09; OR = 1.16; 95% CI = 0.98-1.36), and the recessive model (p = 0.71; OR = 1.02; 95% CI = 0.90-1.16). Sensitivity analysis showed statistical differences of association analysis within the allelic model (p = 0.04; OR = 1.14; 95% CI = 1.01-1.28) and the dominant genetic model (p = 0.04; OR = 1.21; 95% CI = 1.01-1.45), when 1 study was omitted. No publication bias was observed. CONCLUSIONS: The RETN-420 C>G polymorphism may be related to obesity with G allele as a risk factor.

Rab1 in cell signaling, cancer and other diseases.

The endoplasmic reticulum (ER) and Golgi membrane system have major roles in cell signaling and regulation of the biosynthesis/transport of proteins and lipids in response to environmental cues such as amino acid and cholesterol levels. Rab1 is the founding member of the Rab small GTPase family, which is known to mediate dynamic membrane trafficking between ER and Golgi. Growing evidence indicate that Rab1 proteins have important functions beyond their classical vesicular transport functions, including nutrient sensing and signaling, cell migration and presentation of cell-surface receptors. Moreover, deregulation of RAB1 expression has been linked to a myriad of human diseases such as cancer, cardiomyopathy and Parkinson's disease. Further investigating these new physiological and pathological functions of Rab1 should provide new opportunities for better understanding of the disease processes and may lead to more effective therapeutic interventions.

The transcriptional modulator BCL6 as a molecular target for breast cancer therapy.

Inappropriate expression or activation of transcription factors can drive patterns of gene expression, leading to the malignant behavior of breast cancer cells. We have found that the transcriptional repressor BCL6 is highly expressed in breast cancer cell lines, and its locus is amplified in about half of primary breast cancers. To understand how BCL6 regulates gene expression in breast cancer cells, we used chromatin immunoprecipitation followed by deep sequencing to identify the BCL6 binding sites on a genomic scale. This revealed that BCL6 regulates a unique cohort of genes in breast cancer cell lines compared with B-cell lymphomas. Furthermore, BCL6 expression promotes the survival of breast cancer cells, and targeting BCL6 with a peptidomimetic inhibitor leads to apoptosis of these cells. Finally, combining a BCL6 inhibitor and a signal transducer and activator of transcription3 inhibitor provided enhanced cell killing in triple-negative breast cancer cell lines, suggesting that combination therapy may be particularly useful. Thus, targeting BCL6 alone or in conjunction with other signaling pathways may be a useful therapeutic strategy for treating breast cancer.

Clinicopathological characteristics and outcome of patients with small cell neuroendocrine carcinoma of the uterine cervix: case series and literature review.

OBJECTIVE: To analyze the clinicopathological data of 13 cases of small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix who received treatment at this medical institutions over the past five years with patient survival as the primary endpoint. MATERIALS AND METHODS: The clinicopathologic data of 13 cases were reviewed. Immunohistochemistry was performed using antibodies against synaptophysin and chromogranin A and Ki-67. Survival was analyzed using the Kaplan-Meier method and log-rank tests. RESULTS: The median age of these patients was 37 years (range 21-62). Immunohistochemistry showed that the positive rate of synaptophysin and chromogranin A was 100% (13/13) and 69.23% (9/13), respectively. The median survival of patients with early-Stage I-II SCNEC of the uterine cervix (17.5 months) was significantly higher than that of patients with advanced stage SCNEC of the uterine cervix (four months) (p < 0.05). There was no local recurrence in all 13 patients. Five patients died of distant metastasis in less than six months. CONCLUSION: SCNEC of the uterine cervix is a highly-malignant disease and early-stage patients showed significantly longer survival compared to late-stage patients. Early diagnosis and prompt combination treatment may improve the outcome of patients with SCNEC of the uterine cervix.