Hypertrophic cardiomyopathy is an autosomal-dominant disease.Disease-causing mutations have been found in genes encoding structural components of the thick and thin filament systems of cardiac myocyte;it has therefore been named as a disease of sarcomere.Many approaches have been used to characterize the pathogenesis of the desease.Transgenic animal models have been created to gain further insight into the pathogenesis of this disease.Most of these models has been made in mice;however,recently a transgenic rabbit model has been created.In addition,there are several natural-occurring forms of HCM in animals.The discovery of responsible genes and the elucidation of the molecular mechanisms of pathogenesis through the use of animal models promise improved and early diagnosis and the potential for mechanism-based therapeutics.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) are easily isolated and amplified, and facilitate the exogenous gene transfer and expression. In the human medicine, it is believed that BMSCs are ideal therapeutic cells and target cells in the gene therapy.OBJECTIVE: To investigate liposome-mediated cytosine deaminase (CD) gene transfecting rabbit BMSCs and its gene expression. DESIGN: A single sample observation. SETTING: Dalian Research and Development Center for Stem Cell and Tissue Engineering; Department of Biochemistry, College of Basic Medical Science, Dalian Medical University.MATERIALS: This study was performed at in the Dalian Research and Development Center for Stem Cell and Tissue Engineering; Department of Biochemistry, College of Basic Medical Science, Dalian Medical University from March 2006 to June 2007. New Zealand big-ear white rabbits of either gender, weighing 2.0-2.5 kg, with the age of 5 months old, were included in this study. METHODS: The CD gene was obtained from E.coli JM109 DNA by polymerase chain reaction (PCR). The fragment was cloned into pMD19-T vector. After restriction enzyme BamHI/XhoI digestion analysis and DNA sequence analysis, pIRES2-AcGFP1-CD eukaryotic expression plasmid was constructed. Meanwhile, BMSCs were harvested, cultured and identified. After enzyme digestion of eukaryotic expression plasmid, the rabbit BMSCs were transfected by Lipofectamine 2000-mediated method. Twenty-four hours after transfection, expression of green fluorescent protein was observed under an inverted fluorescent microscope. MAIN OUTCOME MEASURES: Construction of eukaryotic expression plasmid and identification of CD gene-transferred BMSCs. RESULTS: CD gene was cloned and connected to eukaryotic expression plasmid with green fluorescence. Twenty-four hours after transfecting rabbit BMSCs, it was found under an inverted microscope that under the excitation of 488 nm blue light, green fluorescence appeared in the pIRES2-AcGFP1-CD and pIRES2-AcGFP1 empty-plasmid transfected BMSCs, but not in the non-transfected ones. It indicates that CD gene successfully transferred BMSCs. CONCLUSION: BMSCs are ideal vectors in the CD gene therapy.

Objective To determine the characteristics of treatment and diagnosis,surgical timing and surgical methods in severely head-injured patients with central herniation.Methods Twenty patients with central herniation caused by contusions and lacerations of the bilateral frontal lobes hospitalized from July 2010 to December 2012 were retrospectively reviewed.There were 11 males and 9 females,at mean age of 42 years (range,18-70 years).Injury was caused by traffic accidents in 15 patients,falls in 3 and fighting events in 2.Eight patients were treated immediately on admission and twelve patients underwent emergency operation.All the operations involved simultaneous bilateral craniectomy for decompression,including bilateral decompressive craniectomy in 6 patients and unilateral decompressive craniectomy in 14 patients.Glasgow Outcome Scale (GOS) and Montreal Cognitive Assessment were used to evaluated outcome evaluation and cognitive impairment respectively.Complications were recorded.Results All patients were followed up for 6-12 months (mean,8 months).According to GOS,good recovery was presented in 10 patients,moderate disability occurred in 6,severe disability in 2,vegetative state in 1,and death in 1.Eleven patients suffered severe mental disorders especially personality change and disturbance of intelligence,and restored after 12 months.Five patients were complicated by epilepsy and two hydrocephalus.Conclusions For central herniation in patients with severe head injury,an emergent surgery is necessary if there exist conscious disturbance and pupil aggravations,hematoma enlargement and significant displacement of midline structure.Timely bilateral balance decompressive craniectomy is effective to reduce the mortality and disability and improve quality of life.

When the size of a neurosphere cultured in vitro reaches a certain critical value, a necrotic core will appear inside the neurosphere because of the limitation of oxygen or other nutrients transport from medium to the cells in the neurasphere. Large necrotic core will greatly reduce the expansion of NSCs. The cellular automaton (CA) model is applied in this article to model the growth of NSCs in sphere state. The appearance and enlargement of the necrotic core in a neurosphere is calculated by coupling the CA model with the nutrient diffusion analysis in bioreactors. The calculation results indicate that the culture conditions, such as seeding density, the concentration of nutrients in medium and the mass transfer coefficient between a neurosphere and medium, have some effects on the appearance of the necrotic core. However, the necrotic core mainly depends on the inner diffusion. It will certainly appear if the size of the neurosphere is large enough even the outside mass transfer is in a good condition in bioreactors. Additionally, the appearance of the necrotic core resulting from the shortage of oxygen is earlier than that caused by the limitation of glucose. And the growth of the necrotic core is very fast after its appearance, and the whole neurosphere may become necrotic. The model developed with cellular automaton and mass transfer is a good qualitative representation of NSCs growth in bioreactors.
Bioreactors ; Cell Culture Techniques ; methods ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Computer Simulation ; Models, Biological ; Neurons ; cytology ; Spheroids, Cellular ; Stem Cells ; cytology ; Tissue Engineering ; methods

Peritoneal dialysis is a recognized renal replacement therapy. Long term peritoneal dialysis will lead to changes in the morphology and function of the peritoneum, that is, peritoneal fibrosis, which is a known cause of the loss of peritoneal ultrafiltration capacity. Pyroptosis is a special type of soluble programmed cell death, characterized by cell swelling, rupture, secretion of cell contents and significant proinflammatory effect. The pyroptosis can be divided into typical and atypical pathways, and the inflammatory body of NOD like receptor heat protein domain related protein 3 (NLRP3) is the most important initiator. Current evidence shows that high glucose peritoneal dialysis fluid can induce peritoneal Mesothelium to scorch, and the inflammation and cell damage caused by it can aggravate the progress of peritoneal fibrosis. Different signal pathways have been proved to regulate the occurrence of pyroptosis. The latest research has proved that some potential targeted methods to inhibit pyroptosis can effectively inhibit the inflammation of peritoneal mesothelium and alleviate peritoneal fibrosis. This article mainly discusses the molecular mechanism of pyroptosis and the relationship between pyroptosis and peritoneal fibrosis.

BACKGROUND AND OBJECTIVES: The International Society for Cellular Therapy (ISCT) proposed a set of minimal markers for identifying human mesenchymal stromal cells (hMSCs) in 2007. Since then, with the growing interest of better characterising hMSCs, various additional surface markers have been proposed. However, the impact of how culture conditions, in particular, the culture surface, vary the expression of hMSC markers was overlooked. METHODS AND RESULTS: In this study, we utilized the RNA sequencing data on hMSCs cultured on different surfaces to investigate the variation of the proposed hMSC biomarkers. One of the three ISCT proposed positive biomarker, CD90 was found to be significantly down regulated on hMSCs culture on fibrous surfaces when compared to flat surfaces. The detected gene expression values for 177 hMSCs biomarkers compiled from the literature are reported here. Correlation and cluster analysis revealed the existence of different biomarker communities that displayed a similar expression profile. We found a list of hMSCs biomarkers which are the least sensitive to a change in surface properties and another list of biomarkers which are found to have high sensitivity to a change in surface properties. CONCLUSIONS: This study demonstrated that substrate properties have paramount effect on altering the expressions of hMSCs biomarkers and the proposed list of substrate-stable and substrate-sensitive biomarkers would better assist in the population characterisation. However, proteomic level analysis would be essential to confirm the observations noted.
Biomarkers ; Chemistry ; Gene Expression ; Humans ; Mesenchymal Stromal Cells ; Quality Control ; Regenerative Medicine ; Sequence Analysis, RNA ; Surface Properties ; Transcriptome

Objective To analyze the positive features of cytomegalovirus antibodies in children aged 0-12 years in Shandong.Methods 1 429 inpatients and outpatiens w ho came to Shandong Provincial Hospital Affil-iated to Shandong University from January 2014 to December 2016 were enrolled in the study.Cytomegalovir-us IgG and IgM antibodies were detected by chemiluminescence.SPSS21.0 software was used for statistical a-nalysis.Results The positive rate of IgG and IgM antibody of cytomegalovirus was 89.36% and 16.59% re-spectively,and the positive rate of IgG antibody of cytomegalovirus in male was 88.04%,which was signifi-cantly lower than 91.32% in female (P<0.05).The positive rate of cytomegalovirus IgM antibody in male was 14.07%,which was significantly lower than 20.31% in female (P<0.05).The positive rate of IgG anti-body of cytomegalovirus was the lowest in 6-12 months age group ( 73.68%),the highest in 0-<6 months age group (92.73%);cytomegalovirus IgM antibody positive rate was the lowest in 4-12 year-old age group (10.26%),and the highest in 1-3 year-old age group (21.57%).The positive rate of IgM antibody of cyto-megalovirus was the highest in winter (22.92%) and the lowest in autumn (11.11%),and the differences of positive rate between the four seasons were statistically significant (P<0.05).A total of 4 cytomegalovirus antibody combination patterns were detected,with the most common type of cytomegalovirus IgG antibody positive and cytomegalovirus IgM antibody double negative,accounting for 73.27%.Conclusion There were differences in sex,age and season in the positive rates of CMV antibody in Shandong area.Prevention and con-trol of cytomegalovirus infection in children should be strengthened.

Objective:To investigate the relationship between triglyceride glucos (TyG), C-reaction protein/albumin (CRP/Alb), 25-hydroxy vitamin D[25(OH)D] and the prognosis of patients with continous ambulatory peritoneal dialysis (CAPD).Methods:A total of 220 CAPD patients in the Affiliated Hospital of Jining Medical University from January 2017 to March 2020 were prospectively selected and divided into death group and survival group according to the 6-month prognosis. The peritoneal urea clearance index (Kt/V urea), TyG, CRP/Alb, 25(OH)D were compared between the two groups. Logistic regression was used to analyze the prognostic factors of CAPD patients. The predictive value of TyG, CRP/Alb and 25(OH)D on the prognosis of CAPD patients was analyzed by receiver operating characteristic (ROC) curve. Results:After 3 months and 6 months of dialysis, the peritoneal Kt/V urea in the death group [(1.21±0.18)ml/(s·1.73 m 2), (1.02±0.14)ml/(s·1.73 m 2)] was significantly lower than that in the survival group [(1.57±0.40)ml/(s·1.73 m 2), (1.49±0.42)ml/(s·1.73 m 2)] (all P<0.05). After 3 months and 6 months of dialysis, the TyG [(8.79±0.86), (9.24±1.03)] and CRP/Alb [(4.98±0.94)×10 -4, (5.14±1.39)×10 -4] in the death group were higher than those in the survival group [(8.03±0.60), (7.26±0.93), (3.57±1.19)×10 -4, (3.07±0.88)×10 -4], while the 25(OH)D [(19.14±2.29)ng/ml, (17.79±3.17)ng/ml] was lower than that of survival group [(22.67±3.03)ng/ml, (24.31±2.51)ng/ml] (all P<0.05). TyG and CRP/Alb at 3 months and 6 months of dialysis were negatively correlated with Kt/V urea, while the 25(OH)D was positively correlated with Kt/V urea (all P<0.05). Logistic regression analysis showed that Kt/Vurea, TyG, CRP/Alb and 25(OH)D were associated with prognosis in the two groups after 3 and 6 months of dialysis (all P<0.05). The AUC of TyG, CRP/Alb and 25(OH)D at 6 months of dialysis combined to predict the prognosis of CAPD patients was the highest, which was 0.911. Conclusions:TyG, CRP/Alb and 25(OH)D are associated with all-cause mortality in CAPD patients. High TyG and CRP/Alb and low 25(OH)D suggest a higher risk of all-cause mortality. Combined detection of all indicators can effectively predict the prognosis of CAPD, which is convenient for early clinical intervention.

Objective:To investigate the relationship between serum osteopontin (OPN), bone morphogenetic protein 2 (BMP2), retinol binding protein 4 (RBP4) and renal function and bone mineral density in patients with diabetes nephropathy (DN).Methods:A total of 120 patients with DN diagnosed in the Affiliated Hospital of Jining Medical University from January 2020 to December 2021 were selected as the DN group, 60 patients with simple diabetes as the type 2 diabetes mellitus (T2DM) group, and 60 subjects with normal glucose tolerance test as the control group. The serum OPN, BMP2, RBP4, low bone mineral density (LBMD), femoral neck bone density (FNBMD) and renal function indicators of the three groups were compared. According to the urinary albumin excretion rate (UAER) of DN patients, the patients were divided into microalbuminuria DN group (71 cases) and massive albuminuria DN group (49 cases), and stratified comparison was made. The simple linear correlation analysis was used to analyze the OPN of DN patients. BMP2, RBP4, renal function and bone mineral density.Results:The fasting blood glucose (FPG), glycated hemoglobin (HbA 1c), serum creatinine (Scr), UAER, and cystatin (CysC) levels of DN group patients were significantly higher than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The FPG and HbA 1c in the T2DM group were higher than those in the control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of DN group patients were higher than those of T2DM group and control group, while the RBP4, LBMD, FNBMD of DN group were lower than those of T2DM group and control group, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of the T2DM group were higher than those of the control group, while RBP4 was lower than that of the control group, and the differences were statistically significant (all P<0.05); The levels of FPG, HbA 1c, Scr, UAER, and CysC in patients with macroalbuminuria DN were significantly higher than those in patients with microalbuminuria DN, and the differences were statistically significant (all P<0.05); The OPN and BMP2 of patients in the large albuminuria DN group were higher than those in the microalbuminuria DN group, while the RBP4, LBMD, and FNBMD of patients in the large albuminuria DN group were lower than those in the microalbuminuria DN group, and the differences were statistically significant (all P<0.05). The OPN of DN group patients was positively correlated with Scr, UAER, and CysC (all P<0.05), while BMP2 was positively correlated with UAER and CysC (all P<0.05); The OPN and BMP2 of DN group patients were negatively correlated with LBMD and FNBMD (all P<0.05), while RBP4 was positively correlated with LBMD and FNBMD (all P<0.05). Conclusions:OPN, BMP2, RBP4 are closely related to the degree of renal function impairment and bone loss in DN patients, and can to some extent reflect the degree of bone metabolism and osteoporosis in T2DM patients.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.