Clinical characteristics and genetic analysis of two children with neonatal severe hyperparathyroidism / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic variants in two children with neonatal severe hyperparathyroidism (NSHPT).@*METHODS@#Two children who were diagnosed with NSHPT at the Children's Hospital Affiliated to Xi'an Jiaotong University respectively in August 2019 and April 2022 were selected as the study subjects. Clinical data were collected, and both children were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing.@*RESULTS@#The main clinical features of the two children have included growth delay, hypotonia, hypercalcemia, hypophosphatemia, hyperparathyroid hormonemia, and renal calcium deposition. WES results showed that child 1 has harbored a homozygous c.1378_1G>A splicing variant of the CASR gene, which was unreported previously, whilst child 2 has harbored a homozygous c.2038C>T missense variant of the CASR gene, which was known to be likely pathogenic. Sanger sequencing confirmed that the parents of both children were heterozygous carriers.@*CONCLUSION@#The homozygous c.1378_1G>A and c.2038C>T variants of the CASR gene probably underlay the NSHPT in the two children. Discovery of the c.1378_1G>A variant has enriched the mutational spectrum of the CASR gene.

Noninvasive assessment of liver fibrosis staging with MR elastography versus ultrasound real-time shear wave elastography in a rabbit model / 中华放射学杂志

Objective:To explore the value of MR elastography (MRE) and shear wave elastography (SWE) for staging liver fibrosis in a rabbit model.Methods:From March to November 2020, 200 healthy New Zealand white rabbits were randomly divided into control group ( n=40) and liver fibrosis group ( n=160) by random number table method. The volume ratio of CCl 4 and olive oil was 1∶1 to prepare 50% CCl 4 oil solution, and the experimental rabbits in the liver fibrosis group were subcutaneously injected with 50% CCl 4 olive oil solution. It was injected once a week at the dose of 0.1 ml/kg in the first to third weeks, once a week at the dose of 0.2 ml/kg in the 4th to 6th weeks. The dose of 0.1 ml/kg was injected twice a week from week 7 to 16. The control group were subcutaneously injected with an equal dose of normal saline. At the end of the 4th, 8th, 12th, and 16th week, 40 and 10 animals in the liver fibrosis group and the control group were randomly selected by random number table method for MRE and SWE, respectively, to obtain the liver elastic stiffness (LS), which were recorded as LS MRE and LS SWE. After the examination, the experimental rabbits were sacrificed and liver tissue of rabbits were taken for histopathological Scheuer staging, and they were divided into F0-F4 groups. One-way ANOVA was used to evaluate the differences of LS MRE and LS SWE in different stages of liver fibrosis. Spearman correlation was used to analyze the correlation between LS and pathological stages. The receiver operating characteristic curve was used to evaluate the efficacy of LS MRE and LS SWE in diagnosing liver fibrosis staging, and the area under the curve (AUC) was compared using the Z test. Results:Totally 162 rabbits were included, which covered F0 ( n=38), F1 ( n=33), F2 ( n=35), F3 ( n=31) and F4 ( n=25). Significant differences of LS MRE and LS SWE values were found among different stages of liver fibrosis ( F=295.29, 102.40, both P<0.001). LS MRE, LS SWE were both positively correlated with liver fibrosis stage ( r=0.93, 0.81, both P<0.001). The AUC of LS MRE for diagnosing liver fibrosis stages ≥F1, ≥F2, ≥F3, and ≥F4 were 0.955, 0.967, 0.996, and 0.980, respectively; the AUC of LS SWE were 0.856, 0.880, 0.974, and 0.953, respectively. The AUC of liver fibrosis stage ≥ F1, ≥ F2 for LS MRE value were greater than LS SWE value ( Z=2.93, 3.29, P=0.003, 0.001), and the AUC of ≥F3, ≥F4 had no significant differences ( Z=1.58, 1.68, P=0.115, 0.093). Conclusion:Both MRE and SWE can accurately predict the stage of liver fibrosis in experimental rabbits, and MRE is better than SWE in diagnosing early liver fibrosis.

Effect of hepatic fibrosis on proton density fat fraction based on histogram analysis in evaluating hepatic steatosis: an experimental study / 中华放射学杂志

Objective:To explore the value of proton density fat fraction(PDFF) based on histogram analysis for quantification hepatic steatosis and fibrosis in rabbit model and the interference of hepatic fibrosis to the evaluation of hepatic steatosis with PDFF.Methods:From March to November 2020, 135 New Zealand white rabbits were randomly divided into control group ( n=30) and experimental group ( n=105) using a random number table. The volume ratio of CCl 4 and olive oil was 1∶1 to prepare 50% CCl 4 oil solution, and experimental rabbits were subcutaneously injected with the oil solution. An equal dose of normal saline was subcutaneously injected for control group rabbits. At the end of the 4 th, 8 th, and 12 th week, 35 in the experimental group and 10 rabbits in the control group were randomly selected to conduct the mDixon-Quant scanning, and histogram analysis of PDFF was analyzed including volume, mean, median, standard deviation, 25 th, 50 th, 75 th, 90 th quantile, skewness, kurtosis, entropy and inhomogeneity. After the examination, the rabbits were sacrificed and the liver percentage of steatosis (PSH) and fibrosis (POF) were recorded by semi-quantitative analysis. Spearman correlation analysis was used to correlate PDFF with PSH and POF. Multiple linear regression analysis was used to determine independent PDFF histogram parameters for evaluating PSH and POF. A receiver operator characteristic (ROC) curve was used to assess the diagnostic accuracy of PDFF for discriminating mild from moderate-severe hepatic steatosis and mild from moderate-severe hepatic fibrosis with median of PSH or POF for dichotomy, and DeLong test was used to compare the area under the curve (AUC). With the correction of hepatic fibrosis, correlation coefficient and AUC were compared of PDFF for discrimination mild from moderate-severe hepatic steatosis. Results:The PDFF mean, median, standard deviation, 75 th, 90 th showed correlation with PSH ( r=0.558, 0.522, 0.319, 0.723, 0.646, -0.589, all P<0.05). The entropy and 75 th were independent parameters for evaluating PSH (β=2.347, -5.960, P=0.018, 0.001). The PDFF 75 th was the optimal parameter for discriminating mild from moderate-severe hepatic steatosis with AUC=0.915 ( P=0.001). The PDFF volume, mean, median, standard deviation, 75 th, 90 th, entropy showed correlation with POF ( r=0.355, 0.393, 0.376, 0.298, 0.485, 0.426, -0.681, all P<0.05). The entropy, standard deviation and volume (β=-11.041, 1.356, 0.190, P=0.001, 0.026, 0.016) were independent parameters for evaluation of hepatic fibrosis, and the entropy was the optimal parameter for hepatic fibrosis (AUC=0.771, P=0.001). The correlation between PSH and PDFF 75 th was less pronounced when fibrosis was present ( r=0.512, P=0.001) than when fibrosis was absent ( r=0.751, P=0.002). The PDFF 75 th showed a significant difference in discriminating mild hepatic steatosis from moderate-severe hepatic steatosis after correction of POF (AUC=0.895, 0.950, Z=2.970, P=0.025). Conclusions:PDFF based on histogram analysis provided a noninvasive, accurate estimation of quantification for hepatic steatosis and fibrosis. Hepatic fibrosis reduced the correlation between hepatic steatosis and PDFF and the presence of hepatic fibrosis can confound the quantification of hepatic steatosis with PDFF.

Up-regulated miR-452-5p suppressed the expression of RORα and promoted the proliferation and migration of HCC cells / 中国药科大学学报

@#To study the prognosis-related regulation mechanism of miR-452-5p and its influence on the proliferation and migration of hepatocellular carcinoma (HCC) cells, liver hepatocellular carcinoma (LIHC) dataset in The Cancer Genome Atlas (TCGA) was used to validate the differential expression of miR-452-5p and perform the Kaplan-Meier analysis of overall survival (OS).Target genes of miR-452-5p from TargetscanHuman and miRDB databases were predictived; and differentially expressed genes(DEGs) and weighted gene co-expression network analysis (WCGNA) were completed with GSE14520.Lipofectmine-2000 was used to transfect miR-452-5p mimics, mimics negative control, miR-452-5p inhibitor and inhibitor negative control into Huh7 cells,respectively.The mRNA and protein expression level of RORα in 4 groups were determined by RT-qPCR and Western blot.CCK-8 assay and Transwell assay were conducted to testify the capabilities of proliferation and migration.The regulation between miR-452-5p and RORα was confirmed by the dual luciferase reporter assay.After analysis in the TCGA-LIHC dataset, miR-452-5p had higher expression in HCC tissue than that in normal tissue, which was also associated with a shorter OS.RORα and LAMC1 were discriminated by intersecting of DEGs, WGCNA module genes, and predictive target genes.Survival analysis exhibited that dysregulation of RORα was significantly related to the OS.Overexpression of miR-452-5p in HCC cells suppressed the expression of RORα both in mRNA and protein, and also enhanced the viability and migration of HCC cells.The results of the dual luciferase reporter assay showed that miR-452-5p targeted 3′UTR of RORα.Up-regulated miR-452-5p inhibited the expression of RORα, facilitated the proliferation and migration of HCC cells, and promoted the progression and poor prognosis of HCC.

Analysis on epidemic situation and spatiotemporal changes of COVID-19 in Anhui / 中华预防医学杂志

We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.

Neonatal tuberous sclerosis complex / 国际儿科学杂志

Tuberous sclerosis complex is an autosomal dominant genetic disease,which has an incidence of 1/6 000 to 1/10 000.Clinical manifestations in TSC present age-dependency and the features of newborn are often untypical,which easily cause missed diagnosis and misdiagnosis.The magnetic resonance appearances of neurological lesions in neonates differ from those in older children and adults,and the imaging feature is very important for TSC diagnosis in neonatal period.This article reviews the clinical and imaging features and the progress of diagnosis and treatment of neonatal TSC.

Serum/glucocorticoid regulated kinase 1 promotes adventitial fibroblasts phenotypic transformation / 中华老年心脑血管病杂志

Objective To study whether SGK1 is involved in the phenotypic transformation in adventitial fibroblasts (AF).Methods Vascular AF were separated from the thoracic aortas of SD rats.The AF not stimulated with TGF-β1 were divided into blank group,control group 1 and control group 2.The AF induced with 2.5,5.0,10.0 and 15.0 ng/ml TGF-β1 were divided into groups A-D.The AF pretreated with 50 μmol/1 EMD638683 and SB203580 were divided into inhibitor group 1 and inhibitor group 2.The AF stimulated with 5 ng/ml TGF-β1 were divided into stimulation group 1 and stimulation group 2.The expression of SGK1,α-SMA and collagen Ⅰ was detected by Western blot.Results The expression of SGK1 was significantly higher in groups AC than in blank group.The expression of α-SMA was significantly higher in groups B-D than in controlgroup (P＜0.05).The α-SMA and collage Ⅰ expression levels were significantly higher in stimulation group 1 than in control group 1,and were significantly lower in inhibitor group 1 than in stimulation group 1 (P＜0.05).The SGK1 expression level was significantly higher in stimulation group 2 than in control group 2 and was significantly lower in inhibitor group 2 than in stimulation group 2 (P＜0.05).Conclusion SGK1 participates in TGF-β1-induced phenotypic transformation via p38 MAPK and is thus involved in vascular remodeling.

Progress of the anti-tumor mechanisms of Smac mimics / 国际生物医学工程杂志

The tolerance of tumor cells to treatment factors is the main reason to limit the therapeutic effect.The high expression of inhibitor of apoptosis proteins (IAPs) is an important factor in the development of therapeutic resistance in tumor cells.As an effective pro-apoptotic protein,the second mitochondria-derived activator of caspase (Smac) can significantly enhance the sensitivity of tumor cells to chemoradiotherapy and promote the apoptosis of tumor cells.However,exogenous Smac protein and its active groups can not enter the tumor cells and play their functions.Therefore,the researches on Smac mimics and their functional mechanism have become the focus of attention of researchers.In this paper,the research progress of Smac mimics and their anti-tumor mechanisms were reviewed.

Biomaterials as carrier, barrier and reactor for cell-based regenerative medicine

Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy. Emerging clinical applications of biomaterial assisted cell therapies further highlight their great promise in regenerative therapy and even cure for complex diseases, which have been failed to realize by conventional therapeutic approaches.

Direct intercellular communications dominate the interaction between adipose-derived MSCs and myofibroblasts against cardiac fibrosis

The onset of cardiac fibrosis post myocardial infarction greatly impairs the function of heart. Recent advances of cell transplantation showed great benefits to restore myocardial function, among which the mesenchymal stem cells (MSCs) has gained much attention. However, the underlying cellular mechanisms of MSC therapy are still not fully understood. Although paracrine effects of MSCs on residual cardiomyocytes have been discussed, the amelioration of fibrosis was rarely studied as the hostile environment cannot support the survival of most cell populations and impairs the diffusion of soluble factors. Here in order to decipher the potential mechanism of MSC therapy for cardiac fibrosis, we investigated the interplay between MSCs and cardiac myofibroblasts (mFBs) using interactive co-culture method, with comparison to paracrine approaches, namely treatment by MSC conditioned medium and gap co-culture method. Various fibrotic features of mFBs were analyzed and the most prominent anti-fibrosis effects were always obtained using direct co-culture that allowed cell-to-cell contacts. Hepatocyte growth factor (HGF), a well-known anti-fibrosis factor, was demonstrated to be a major contributor for MSCs' anti-fibrosis function. Moreover, physical contacts and tube-like structures between MSCs and mFBs were observed by live cell imaging and TEM which demonstrate the direct cellular interactions.

Directed assembly of cell-laden microgels for building porous three-dimensional tissue constructs.

The organization of cells within a well-defined microenvironment is important in generating the resulting tissue function. However, the cellular organization within biodegradable scaffolds often does not resemble those of native tissues. In this study, we present directed assembly of microgels to organize cells for building porous 3D tissue constructs. Cell-laden microgels were generated by molding photocrosslinkable polyethylene glycol diacrylate within a poly(dimethyl siloxane) stencil. The resulting microgels were subsequently packed as individual layers (1 mm in height) on a glass substrate by removing the excess prepolymer solution around the microgels. These clusters were crosslinked and stacked on one another to fabricate thick 3D constructs that were greater than 1 cm in width and 3 mm in thickness. To generate pores within the engineered structures, sodium alginate microgels were integrated in the engineered constructs and used as a sacrificial template. These pores may be potentially useful for fabricating a vascular network to supply oxygen and nutrients to the engineered tissue constructs. This simple and versatile building approach may be a useful tool for various 3D tissue culture and engineering applications.

Treatment strategy of pyogenic brain abscesses:a report of 45 cases / 解放军医学杂志

Objective To explore the best treatment strategy of pyogenic brain abscesses.Methods Clinical data of 45 patients(34 males and 11 females,ages ranged from 7 to 76 years,averaged 42.6 years) with brain abscess treated from January 1999 to March 2008 were retrospectively analyzed.Among the 45 patients,there were 40 with single brain abscess and 5 with multiple brain abscess;43 with unilocular abscess and 2 with multilocular abscess.19 patients accepted the conservative treatment with the third generation cephalosporin,16 were treated with stereotactic puncture of abscess,8 treated with stereotactic puncture and drainage,and microsurgical excision was performed in 5 patients.Results Of the 19 patients treated with conservative method,16 were cured,no recurrence was found during the follow-up period(from 6 months to 5 years) in 13 patients,and another 3 were deteriorated and accepted stereotactic operation.All the stereotactic operations were carried successfully out in 24 patients(including 3 cases after expectant treatment failure) and only one patient needed another stereotactic aspiration two weeks later because of abscess recurrence after the initial operation.Epileptic seizure was found in one patient at the end of stereotactic procedure.Total removal of brain abscess was performed by microsurgical craniotomy in 5 patients.At the time of discharge,clinical symptoms disappeared or were improved remarkably,and CT or MRI re-examination disclosed the disappearance or obviously diminution of abscess in all patients.No abscess recurred during the follow-up period(from 4 months to 3 years,average 14 months) in 22 patients.Conclusion A set of treatment strategy of pyogenic brain abscesses has been proposed and stereotactic operation seems to be the most appropriate surgical choice.