Intravenous transplantation of bone marrow-derived mesenchymal stem cells improved behavioral deficits and altered fecal microbiota composition of BTBR mice.

AIMS: It is recognized that autism spectrum disorder (ASD) is a highly complex neurodevelopmental disorder with communication deficits as well as multiple social barriers. The core symptoms of ASD are not treatable with current therapeutics. Therefore, finding new treatment strategies for ASD is urgently needed. Mesenchymal stem cells (MSC) have been shown to be a promising therapeutic approach in previous studies. However, the underlying mechanisms of MSC treatment for ASD through gut microbiota remain unclear and require further investigation. MAIN METHODS: BTBR mice were used as ASD model and then randomly assigned to the human bone marrow-derived mesenchymal stem cell (hBMMSC) intravenous treatment group or vehicle treatment group. C57BL/6J (C57) mice served as control. Multiple social behavioral tests were performed during the 6-week period and fecal samples were collected at different time points for 16 s rRNA sequencing analysis. KEY FINDINGS: The administration of hBMMSC improved social deficits of BTBR mice in the open field test (OFT), light-dark box test (LBT), novel object recognition (NOR), and free social test (FST), while also significantly reducing stereotypic behaviors. Additionally, hBMMSC administration notably reversed the alterations of microbiota abundance in BTBR mice, particularly the Firmicutes/Bacteroidetes ratio. Several specific differential taxa were further selected and showed a correlation with the prognosis and behavioral scores of ASD. SIGNIFICANCE: Overall, intravenous treatment with hBMMSC had a beneficial impact on ASD by ameliorating social deficits and modifying microbiota compositions. This outcome indicates that hBMMSC intravenous transplantation could be a promising therapeutic strategy for enhancing ASD symptoms improvements.

LncRNA PVT1 mediates the progression of liver necroptosis via ZBP1 promoter methylation under nonylphenol exposure.

Nonylphenol (NP) is one of the most toxic and ubiquitously present endocrine disrupting compounds. Numerous studies have shown that NP exposure induces liver injury, but the interactions between epigenetic factors and necroptosis in this context have not been examined. In this study, rats received daily NP administration (15, 45, and 135 mg/kg/day) via oral gavage over a 28-day period. The upregulation of lncRNA PVT1 was associated with the elevated expression of necroptosis-related proteins (ZBP1, RIPK3, MLKL, and p-MLKL). Moreover, similar effects were also observed after NP exposure in BRL-3A cells. LncRNA PVT1 was predominantly expressed in the nucleus, and ASO was chosen to knock down lncRNA PVT1 in BRL-3A cells. Experimental techniques such as RNA immunoprecipitation, chromatin immunoprecipitation, and co-immunoprecipitation were used to verify direct binding interactions among lncRNA PVT1, EZH2, DNMT1, and ZBP1. The evidence obtained indicated that lncRNA PVT1 could bind to DNMT1 via EZH2 and increase methylation at the ZBP1 promoter, thereby promoting necroptosis. Meanwhile, the demethylation of the highly expressed gene TET1 also promoted ZBP1 upregulation, inducing necroptosis. Taken together, these findings provide valuable insights into the potential molecular mechanisms underlying liver injury in response to NP exposure. Hence, they lay a mechanistic foundation for the evaluation of NP biosafety.

Significance and status of human milk bank development in mainland China / 中国实用护理杂志

This article aims to summarize the significance of the establishment of human milk banks, the status of human milk banks in mainland China, analyze the relevant factors that affect the development of human milk banks, and propose corresponding countermeasures to provide a reference for improving the status of human milk banks in mainland China and promoting sustainable development.

The expression and clinical value of CHI3L1 in hepatocellular carcinoma / 中华检验医学杂志

Objective:To investigate the clinical management value of chitinase 3-like 1 protein(CHI3L1) in hepatocellular carcinoma (HCC) by studying the expression of CHI3L1 in peripheral blood, liver cancer and paired adjacent non-tumor tissues.Methods:Retrospective study. From 2013 to 2017, 405 patients with HCC in Third Affiliated Hospital of Naval Medical University were enrolled into the study. Meanwhile, 112 patients with liver cirrhosis (LC), 114 health subjects were included as disease and health controls. CHI3L1 in peripheral blood was detected by ELISA kit. Tissues array was made by collecting 90 pairs of tumor tissues and matched paracancer tissues, from HCC patients who were conformed by pathology. The expression of CHI3L1 in HCC tissues was analyzed by immunohistochemistry. Differences between independent groups were tested by Mann-Whitney U test or Kruskal Wallis H test, Pearson correlation analysis was used for analyzing the relationship between two subjects, and matched rank sum test was used for cancer tissue and adjacent tissue comparison. Results:The median (quartile) of CHI3L1 protein in LC group, HCC group and NC group was 195.8 (103.3,330.4) μg/L,118.2 (74.9,201.0) μg/L,46.8 (30.7,66.4) μg/L independently. The protein level of CHI3L1 in LC group was significantly higher than that in HCC group and health control group ( Z=5.186,12.928, P<0.001). HCC group was significantly higher than that in health control group ( Z=10.788, P<0.001). The level of CHI3L1 in HCC group was not related to whether liver cirrhosis was accompanied ( Z=-0.286, P=0.775). The level of serum CHI3L1 was positively correlated with noninvasive fibrosis markers (HA, PⅢNP, Ⅳ-C, FIB-4 index) ( r=0.202,0.159,0.299 and 0.221, P<0.05) and negatively correlated with ALB( r=-0.326, P<0.05) while positively correlated with AST and PT( r=0.138, 0.160, P<0.05). Positively correlation was observed between CHI3L1 and tumor size ( r=0.284, P<0.001). CNLC stage [CHI3L1 level in advanced group125.2(81.9,228.5)μg/L was higher than that in early group112.0(70.2,169.2)μg/L ( Z=-2.326, P=0.018)], but no correlation with microvascular invasion( Z=-1.531) and tumor capsule(χ 2=0.818, P>0.05). In 73 cases of HCC tissues, the positive rate of CHI3L1 was 78% (57/73) in cancer tissues and 83%(61/73) in paired adjacent non-tumor tissues. The staining intensity score of paracancer tissue 1.5(1.5,2.5) was higher than that of cancer tissue 1.5(1.5,2.0)( Z=-2.053, P=0.040). Conclusions:The tissue source of CHI3L1 protein in HCC includes cancer tissue and paracancerous tissue. The detection of serum CHI3L1 level is helpful to evaluate tumor load assessment and disease stratification management in HCC.

Clinical characteristics and risk factors of multiple myeloma patients with renal impairment / 中华肾脏病杂志

Objective:To explore the clinical and cytogenetic characteristics and risk factors of multiple myeloma (MM) patients with renal impairment (RI).Methods:A total of 113 newly diagnosed patients with MM in the department of nephrology and hematology in Zhongnan Hospital of Wuhan University from January 2013 to December 2017 were enrolled. The patients were divided into RI group and non-renal impairment (NRI) group according to whether serum creatinine (Scr) at the time of diagnosis was higher than 177 μmol/L. The clinical and laboratory data of two groups were compared. The risk factors of RI in MM patients were analyzed by binary logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors.Results:The incidence of RI in 113 MM patients was 34.5%. Compared with NRI group, levels of white blood cells, serum uric acid, blood urea nitrogen, neutrophil-to-lymphocyte ratio (NLR), cystatin C, β 2-microglobulin (β 2-MG), blood phosphorus, urine light chain, bone-marrow plasma cell percentage, International Staging System (ISS) stage III percentage, light chain type percentage, positive urinary Bence-Jones protein percentage and positive urinary protein percentage were higher in RI group, while levels of estimated glomerular filtration rate (eGFR), serum bicarbonate concentration and globulin were lower in RI group (all P<0.05). There were no significant differences in other clinical variables between the two groups (all P>0.05). Fluorescence in situ hybridization (FISH) was applied to 42 MM patients to detect the following five genetic abnormalities: IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion and P53 deletion. Among them, 29 (69.0%) patients were abnormal. The incidence of RB1 deletion in RI group was higher than NRI group ( P<0.05), and there were no significant differences in the incidences of other genetic abnormalities (all P>0.05). Further logistic regression analysis showed that increase of NLR ( OR=1.589, 95% CI 1.115-2.266, P=0.010), bone-marrow plasma cell percentage ( OR=1.053, 95% CI 1.008-1.101, P=0.021) and β 2-MG ( OR=22.166, 95% CI 2.146-228.927, P=0.009), light chain type ( OR=15.399, 95% CI 1.002-236.880, P=0.049), and hyperuricemia ( OR=11.707, 95% CI 1.580-86.717, P=0.016) were the independent risk factors for RI in MM patients. The comparison of area under the ROC ( AUC) among these risk factors showed the AUC of β 2-MG was larger than that of NLR or uric acid (both P<0.05), while there were no significant differences in the rest of pairwise comparison (all P>0.05). The AUC of β 2-MG predicting RI was the largest ( AUC=0.907, 95% CI 0.853-0.962, P<0.001). Conclusions:MM patients have high morbidity of RI, and there are more RI patients with RB1 deletion in RI patients. Light chain type, hyperuricemia, high level of NLR, high bone-marrow plasma cell percentage and increased β 2-MG are the independent risk factors for RI in MM patients. Among them, β 2-MG is the best predictor for RI, and NLR plays an important role in predicting RI as a convenient and effective inflammatory marker.

Clinical characteristics and risk factors of multiple myeloma patients with renal impairment / 中华肾脏病杂志

Objective@#To explore the clinical and cytogenetic characteristics and risk factors of multiple myeloma (MM) patients with renal impairment (RI).@*Methods@#A total of 113 newly diagnosed patients with MM in the department of nephrology and hematology in Zhongnan Hospital of Wuhan University from January 2013 to December 2017 were enrolled. The patients were divided into RI group and non-renal impairment (NRI) group according to whether serum creatinine (Scr) at the time of diagnosis was higher than 177 μmol/L. The clinical and laboratory data of two groups were compared. The risk factors of RI in MM patients were analyzed by binary logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors.@*Results@#The incidence of RI in 113 MM patients was 34.5%. Compared with NRI group, levels of white blood cells, serum uric acid, blood urea nitrogen, neutrophil-to-lymphocyte ratio (NLR), cystatin C, β2-microglobulin (β2-MG), blood phosphorus, urine light chain, bone-marrow plasma cell percentage, International Staging System (ISS) stage III percentage, light chain type percentage, positive urinary Bence-Jones protein percentage and positive urinary protein percentage were higher in RI group, while levels of estimated glomerular filtration rate (eGFR), serum bicarbonate concentration and globulin were lower in RI group (all P<0.05). There were no significant differences in other clinical variables between the two groups (all P>0.05). Fluorescence in situ hybridization (FISH) was applied to 42 MM patients to detect the following five genetic abnormalities: IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion and P53 deletion. Among them, 29 (69.0%) patients were abnormal. The incidence of RB1 deletion in RI group was higher than NRI group (P<0.05), and there were no significant differences in the incidences of other genetic abnormalities (all P>0.05). Further logistic regression analysis showed that increase of NLR (OR=1.589, 95%CI 1.115-2.266, P=0.010), bone-marrow plasma cell percentage (OR=1.053, 95%CI 1.008-1.101, P=0.021) and β2-MG (OR=22.166, 95%CI 2.146-228.927, P=0.009), light chain type (OR=15.399, 95%CI 1.002-236.880, P=0.049), and hyperuricemia (OR=11.707, 95%CI 1.580-86.717, P=0.016) were the independent risk factors for RI in MM patients. The comparison of area under the ROC (AUC) among these risk factors showed the AUC of β2-MG was larger than that of NLR or uric acid (both P<0.05), while there were no significant differences in the rest of pairwise comparison (all P>0.05). The AUC of β2-MG predicting RI was the largest (AUC=0.907, 95%CI 0.853-0.962, P<0.001).@*Conclusions@#MM patients have high morbidity of RI, and there are more RI patients with RB1 deletion in RI patients. Light chain type, hyperuricemia, high level of NLR, high bone-marrow plasma cell percentage and increased β2-MG are the independent risk factors for RI in MM patients. Among them, β2-MG is the best predictor for RI, and NLR plays an important role in predicting RI as a convenient and effective inflammatory marker.

Effect of estrogen on proliferation of astrocytes in hippocampus of mice following middle cerebral artery occlusion / 中华老年心脑血管病杂志

Objective To study the effect of estrogen on proliferation of astrocytes in hippocampus of mice following middle cerebral artery occlusion(MCAO).Methods One hundred and eight Kunming mice were randomly divided into estrogen group(n=54)and saline group(n=54).The animals in two groups underwent right MCAO with tissue samples taken at 3,6,12,24,48and 72h after MCAO.The ischemic site was detected and the ischemic size was measured with TTC staining,the damage of neurons in hippocampus was assayed with HE staining,the expression of GFAP in hippocampal astrocytes was detected with immunohistochemical staining.Results The cerebral infarction size was significantly smaller in estrogen group than in saline group at different time points after MCAO(P＜0.05,P＜0.01)especially at 12hafter MCAO(31.50％±3.36％vs 54.50％±5.68％,P=0.019).The damage of hippocampal neurons aggregated with the prolonged ischemia time in two groups and was milder in estrogen group than in saline group at the same time points.The expression level of GFAP positive cells in bilateral hippocampal areas was higher when the ischemia time was prolonged and was significantly higher in ischemic hippocampus of estrogen group than in that of control group except at 6hin CA3ischemic area(P＜0.05).Conclusion Estrogen can protect mice against focal cerebral ischemia,stimulate the genesis of astrocyte synapses,alleviate neuronal damage after ischemia,and can thus reduce the size of cerebral infarction.

The effect of agglomerant thickness on the stress distribution of all ceramic crown of central incisor / 实用口腔医学杂志

Objective: To study the effect of the stress distribution with three dimensional(3-D) finite element analysis technique between zirconia all-ceramic crown of maxillary central incisors and agglomerant with different thickness. Methods: A 3-D finite element model of all-ceramic crown (core layer and the veneer layer), agglomerant, tooth, tooth root and alveolar bone was established from CBCT data. The agglomerant thickness was designe as 50, 100 and 150 μm respectively. After a load simulating occlusion was imposed on to the model the stress distribution of agglomerant layer, the equivalent of veneer layer and the maximum principal stress were analysed. Results: With the increase of agglomerant thickness and the change of occlusion, the maximum principal stress of all ceramic crowns gradually increased, the equivalent stress increased first and then decreased, the equivalent stress and the maximum principal stress of agglomerant layer showed a downward trend. Conclusion: The use of agglomerant layer with the thickness of 50 μm is feasible for the bond of all ceramic crowns and may reduce the risk of veneer chipping.

Early physical growth and disease analysis among children born delivered by HBsAg-positive mothers / 中华预防医学杂志

Objective@#To estimate the early physical growth and disease in children born to HBsAg-positive mothers.@*Methods@#This was a retrospective cohort study. Three areas as Xihu in Hangzhou, Lanxi in Jinhua, and Haiyan in Jiaxing in Zhejiang province were selected by cluster sampling. The growth outcomes of children born to HBsAg-positive mothers (exposure group) and matched 1∶1 women uninfected with HBV (control group) in 2014 were investigated and compared at birth, 6, 9, 12, and 18 months, respectively. There were totally 342 children in each group.@*Results@#The incidences of low birth weight (LBW) for children born to exposure and control group were 1.8% (6/342), and 2.6% (9/342), respectively (P=0.433); and, rates of preterm birth were 2.3% (8/342), and 2.0% (7/342), respectively (P=0.794). The mean birth weight of children born to mothers without HBV infection (3.4±0.4) kg was dramatically higher than children in exposure group (3.3±0.4) kg (P=0.019). At 18 months, the average head circumference was significantly greater among children in control group (47.3±1.3) cm than children in exposure group (47.0±2.0) cm (P=0.038). Additional, mean birth weeks, height, weight, increases in height/weight/head circumference each month, weight/height/head circumference for age Z scores, proportion of growth retardation and low weight, disease prevalence were not observed statistically differences between two groups (P>0.05). All children born to HBsAg-positive mothers were received three-dose HBV vaccination. The rate of hepatitis B immunoglobulin for births born to HBsAg-positive was 98.8% (338/342). Mother to children transmission of HBV at 18 months was 1.0% (1/97).@*Conclusion@#No significant differences in growth development and disease prevalence were found among children born to HBsAg-positive women and women without HBV infection.

[Influencing factors of renal function in hypertensive patients with obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To investigate the related factors of renal functions in hypertensive patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: A total of 438 hypertensive patients with complain of snoring at night were enrolled in the study from the First teaching Hospital of Xinjiang Medical University during March 2011 and March 2014. The diagnosis of OSAHS was confirmed with polysomnography examination, and the patients were divided into 4 groups according to the apnea hypoventilation index (AHI): hypertensive group (AHI<10/h, n=102), mild OSAHS group (AHI 10-<15/h, n=97), moderate OSAHS group (AHI 15-<30/h, n=149), and severe OSAHS group (AHI≥30/h, n=90). The blood urea, creatinine, eGFR, 24h-urinary total protein (24h UTP), 24h-urinary microalbumin, cystatin C (Cyst C) were measured and compared among groups, and the influencing factors of renal function were analyzed. RESULTS: There were no significant differences in age, gender, body mass index(BMI), 24-hour systolic blood pressure (24hSBP), fasting blood-glucose, high-density lipoprotein cholesterol (HDL-C) among the groups (P<0.05). 24h-UTP and 24h-urinary microalbumin in the severe OSAHS group were higher than those in other groups (P<0.05); and all patients with OSAHS had higher Cyst C levels than those without OSAHS (all P<0.05). Logistic regression analysis showed that BMI (OR=1.486, 95% CI 1.022-2.160) and severe OSAHS (OR=7.138, 95% CI 1.835-27.769) were influencing factors of 24h-UTP; blood pressure (OR=2.368, 95% CI 1.324-4.234) and BMI (OR=1.678, 95% CI 1.263-2.230) were influencing factors of 24h-urinary microalbumin; age (OR=1.998, 95% CI 1.325-3.013), blood pressure (OR=3.202, 95% CI 1.319-7.773) and severe OSAHS (OR=5.462, 95% CI 1.103-27.041) were influencing factors of Cyst C. CONCLUSION: OSAHS is a risk factor for early renal damage in patients with hypertension. Age, BMI, blood pressure and severe OSAHS may be influencing factors for renal function in hypertensive patients with OSAHS.