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In this study, we performed RNA sequencing of Prx II+/+ and Prx II−/− dermal mesenchymal stem cells (DMSCs) to identify differentially expressed genes (DEGs). To explore the role of Prx II in DMSCs, we performed Gene Ontology analysis of the DEGs. The results showed that the DEGs were mainly involved in the biological processes of cell migration, intercellular adhesion, and coordination of the regulation of stem cell homing. Through the construction of protein–protein interaction network, four hub genes Cd274, Ccl5, Il1b, and Stat1 involved in cell adhesion and cell homing were screened. Quantitative reverse transcription PCR analysis showed that Cd274, Ccl5, Il1b, and Stat1 were down regulated in Prx II−/− DMSCs. miRwalk and Starbase databases were further used to screen the upstream molecules miRNA and lncRNA regulating hub gene. Prx II was found to be involved in the regulation of stem cell homing via the Tctn2/miR-351/Stat1/Il1b axis. Thus, we demonstrated that Prx II is a key molecule in the regulation of the homing ability of DMSCs. Our results provide a theoretical foundation for improving the homing ability of DMSCs by targeting Prx II.

The incidence of liver diseases has been increasing steadily. However, it has some shortcomings, such as high cost and organ donor scarcity. The application of stem cell research has brought new ideas for the treatment of liver diseases. Therefore, it is particularly important to clarify the molecular and regulatory mechanisms of differentiation of bone marrow-derived stem cells (BMSCs) into liver cells. Herein, we screened differentially expressed genes between hepatocytes and untreated BMSCs to identify the genes responsible for the differentiation of BMSCs into hepatocytes. GSE30419 gene microarray data of BMSCs and GSE72088 gene microarray data of primary hepatocytes were obtained from the Gene Expression Omnibus database. Transcriptome Analysis Console software showed that 1896 genes were upregulated and 2506 were downregulated in hepatocytes as compared with BMSCs. Hub genes were analyzed using the STRING and Cytoscape v 3.8.2, revealing that twenty-four hub genes, play a pivotal role in the differentiation of BMSCs into hepatocytes. The expression of the hub genes in the BMSCs and hepatocytes was verified by reverse transcription-quantitative PCR (RT-qPCR). Next, the target miRNAs of hub genes were predicted, and then the lncRNAs regulating miRNAs was discovered, thus forming the lncRNA-miRNA-mRNA interaction chain. The results indicate that the lncRNA-miRNA-mRNA interaction chain may play an important role in the differentiation of BMSCs into hepatocytes, which provides a new therapeutic target for liver disease treatment.

Background According to the latest American Joint Committee on Cancer and Union for International Cancer Control manuals, cystic duct cancer (CC) is categorized as a type of gallbladder cancer (GC), which has the worst prognosis among all types of biliary cancers. We hypothesized that this categorization could be verified by using taxonomic methods. Aim To investigate the categorization of CC based on population-level data. Methods Cases of biliary cancers were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Together with routinely used statistical methods, three taxonomic methods, including Fisher's discriminant, binary logistics and artificial neuron network (ANN) models, were used to clarify the categorizing problem of CC. Results The T staging system of perihilar cholangiocarcinoma [a type of extrahepatic cholangiocarcinoma (EC)] better discriminated CC prognosis than that of GC. After adjusting other covariates, the hazard ratio of CC tended to be closer to that of EC, although not reaching statistical significance. To differentiate EC from GC, three taxonomic models were built and all showed good accuracies. The ANN model had an area under the receiver operating characteristic curve of 0.902. Using the three models, the majority (75.0%-77.8%) of CC cases were categorized as EC. Conclusion Our study suggested that CC should be categorized as a type of EC, not GC. Aggressive surgical attitude might be considered in CC cases, to see whether long-term prognosis could be immensely improved like the situation in EC.

Peroxiredoxin II (Prx II) is involved in proliferation, differentiation, and aging in various cell types. However, Prx II-mediated stem cell regulation is poorly understood. Here, dermal mesenchymal stem cells (DMSCs), cell-growth factor-rich conditioned medium from DMSCs (DMSC-CM), and DMSC-derived exosomes (DMSC-Exos) were used to explore the regulatory role of Prx II in DMSC wound healing. Following treatment, wound healing was significantly decelerated in Prx II-/- DMSCs than in Prx II+/+ DMSCs. In vitro stimulation with 10 μM H2O2 significantly increased apoptosis in Prx II-/- DMSCs compared with Prx II+/+ DMSCs. The mRNA expression levels of EGF, b-FGF, PDGF-B, and VEGF did not significantly differ between Prx II-/- and Prx II+/+ DMSCs. Fibroblasts proliferated comparably when treated with Prx II+/+ DMSC-CM or Prx II-/- DMSC-CM. Wound healing was significantly higher in the Prx II-/- DMSC-Exos-treated group than in the Prx II+/+ DMSCs-Exos-treated group. Moreover, microRNA (miR)-21-5p expression levels were lower and miR-221 levels were higher in Prx II-/- DMSCs than in Prx II+/+ DMSCs. Therefore, our results indicate that Prx II accelerated wound healing by protecting DMSCs from reactive oxygen species-induced apoptosis; however, Prx II did not regulate cell/growth factor secretion. Prx II potentially regulates exosome functions via miR-21-5p and miR-221.

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation.

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.

OBJECTIVE: To study the clinical features and treatment outcome of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGAD). METHODS: A retrospective analysis was performed for the clinical data of 28 children with MOGAD (with 38 demyelinating episodes). RESULTS: Among the disease spectrums of 28 children with MOGAD, optic neuritis was the most common (12 cases, 43%), followed by acute disseminated encephalomyelitis (9 cases, 32%). Among the 38 demyelinating episodes in the 28 children, there were 29 cases (76%) of lesions in the acute stage on head magnetic resonance imaging (MRI), and most of these lesions were extensive or isolated subcortical white matter lesions. A total of 24 cases of spinal MRI results in the acute stage were recorded, among which there were 11 cases (46%) of spinal lesions. MRI abnormalities of the optic nerve were found in 18 cases of optic neuritis in the acute stage. Of the 28 children, 20 (71%) had an increase in white blood cell count in cerebrospinal fluid, with lymphocytes as the most common type of cells, and 3 children had an increase in protein. The titer of serum MOG antibody was 1:10-1:320 in the 28 children. All 28 children were administered with glucocorticoids, along with immunoglobulin in 18 children. The symptoms of 26 children (93%) were alleviated during follow-up, and only 2 children had neurological sequela of the optic function. CONCLUSIONS: The clinical manifestations are diverse in children with MOGAD. Immunotherapy is effective and most children have a good prognosis.

Introduction: Systematic reviews need constantly updating as new evidence emerges. The aim of this comprehensive systematic review/meta-analysis focused on trials that provided acupuncture during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) which were compared with routine care for a range of outcomes - implantation rate, biochemical pregnancies (presence of a positive urinary pregnancy test or a positive serum human chorionic gonadotrophin test), clinical pregnancies, ongoing pregnancies, and rates of miscarriage and live birth. Methods: A systematic search of MEDLINE and EMBASE databases for randomized controlled trials (RCTs) on acupuncture treatment during IVF or ICSI was carried out from database inception until July 31, 2017. Study selection, data extraction, quality assessment and bias assessment were carried out by 2 researchers independently, with adjudication by the third researcher when necessary. A meta-analysis was performed to compare outcomes between women receiving acupuncture and those receiving routine care, and pooled relative risks (RR) were calculated. Results: Statistically significant differences were observed in rates of clinical pregnancy (RR = 1.19, 95% confidence intervals (CI): 1.06–1.34 p=0.002), live birth (RR = 1.36, 95% CI: 1.09–1.69 p=0.006), and implantation rate (RR = 1.31, 95% CI: 1.08–1.59 p=0.006) between the acupuncture and the control groups. No significant differences were found for biochemical pregnancies (RR = 1.12, 95% CI: 0.92–1.35 p=0.268), ongoing pregnancies (RR = 1.21, 95% CI: 0.95–1.55 p=0.130), or miscarriage (RR = 0.89, 95% CI: 0.67–1.20 p=0.447) between the two groups. Adverse events were described in 4 studies. Conclusions: Acupuncture may have an impact on the outcome rates of implantation, clinical pregnancy, and live birth; however, well-designed RCTs are warranted to further validate its effects.

Objective This study was designed to verify the cross-cultural psychometric properties of the Functional Remission of General Schizophrenia (FROGS) scale and the four-item version (mini-FROGS) in Chinese schizophrenic individuals. Methods Item clustering analysis was used to show the clustering relationship among items. Confirmatory factor analysis (CFA) was used to test the structural validity of the scale. The Global Assessment of Functioning (GAF) was used as a criterion to test convergent validity. The receiver operating characteristic curve (ROC) and the area under the ROC curve (ROC-AUC) were calculated to test the sensitivity and specificity of FROGS and mini-FROGS for functional assessment. Fifty participants were randomly selected for retest at two-month intervals. Results A total of 228 schizophrenia individuals were enrolled in our study. The results of the item clustering analysis and CFA supported the 3-factor structure of the original scale, and all items, except for the item “absence of antisocial or violent”, showed good psychometric characteristics. The correlated coefficients between FROGS and mini-FROGS with the GAF were excellent (FROGS: r = 0.74, p＜0.01; mini-FROGS: r = 0.65, p＜0.01). The retest showed that the scale had good stability and validity over time (ICC = 0.856; 95% CI = 0.701∼0.941). Both mini-FROGS and FROGS had good sensitivity and specificity for the measurement of social function (mini-FROGS: ROC-AUC = 84.3% (76.9%–91.6%), and FROGS: ROC-AUC = 89.2% (83.0%–95.4%)), and there was no difference between the two versions of ROC-AUC (P = 0.154). Conclusion The results of our study showed that the Chinese version of FROGS and mini-FROGS had good psychometric properties for assessing the social function of people with schizophrenia in China. In particular, the mini-FROGS version was better used in the clinical setting because of its convenience and efficiency.

To evaluate the safety of intravenous thrombolysis (IVT) in cerebral microbleeds (CMBs) patients with prior antiplatelet therapy.Four hundred and forty nine patients with acute ischemic stroke aged (66.8 ± 12.9) years, including 298 males and 151 females, underwent susceptibility-weighted imaging (SWI) examination and MRI-guided IVT therapy between June 2009 and June 2015. The presence of CMBs, previous antiplatelet therapy, HT subtypes according to ECASS II criteria and functional outcome based on modified Rankin scale (mRS) at 3 months were analyzed in logistic regression model.Total 934 CMBs were detected in 172 (38.3%) patients, among whom 63 (14.0%) previously received antiplatelet therapy. All patients received intravenous recombinant tissue-plasminogen activator (rt-PA) for thrombolysis with the onset-to needle time of (229.0 ± 103.7) min. The pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 10 (IQR 5-15). Logistic regression analysis indicated that prior antiplatelet use increased neither risk of parenchymal hematoma (PH) (OR=0.809,95% CI:0.201-3.262, P=0.766) nor adverse functional outcome (OR=1.517, 95% CI:0.504-4.568, P=0.459) in patients with CMBs; while in patients with multiple CMBs (≥ 3) prior antiplatelet use increased risk of hemorrhagic transformation (OR=9.737, 95% CI: 1.364-69.494, P=0.023), but not adverse functional outcome (OR=1.697, 95% CI:0.275-10.487, P=0.569).The study indicates that in patients with CMBs, thrombolytic therapy should not be excluded due to the prior use of antiplatelet; however, the larger prospective studies are needed in future for patients with multiple CMBs.

To investigate the cerebral lesions of diffusion weighted imaging (DWI) hyperintensity in patients with subacute stroke with intravoxel incoherent motion (IVIM) technique.The clinical data of 20 patients with ischemic stroke (3 to 7 d after onset) who underwent DWI and IVIM scanning between June 2014 and July 2015, were retrospectively analyzed. The parameters from IVIM including slow diffusion coefficient (D), fast diffusion coefficient (D(*)) and perfusion fraction (f) were processed. DWI hyperintensity was segmented by its signal intensity greater than the mean+2 standard deviations of the value in the homologous contralateral region. Then, DWI hyperintensity was classified into two regions of interest (ROIs): infarction core and peri-core with the ADC threshold of 0.55 × 10⁻³ mm²/s. The mirrored ROIs of infarction core and peri-core were also obtained. Then, we measured the values of ADC and D, D(*) and f in these ROIs. The ratios of ADC (rADC), D (rD), D(*) (rD(*)) and f (rf) were also calculated (e.g., rADC=ADCinfarction core/ADCmirrored region).Compared with mirrored region, ADC, D and f in the infarction core region decreased by 45% (P0.001), 42% (P0.001) and 32% (P0.001), respectively; while ADC, D and f in the peri-core region decreased by 22% (P0.001), 32% (P0.001) and 8% (P=0.009), respectively. The values of rADC, rD, rD(*) and rf in the infarction core region were significantly lower than those in the peri-core region (all P0.001). Pearson analysis showed that rADC was positively correlated with rf in the peri-core region (r=0.467, P=0.038).During subacute stage of stroke, compared to the infarction core region within DWI hyperintensity, D and f increase in the peri-core region of DWI hyperintensity, reflecting the increased water diffusion in microstructure and perfusion volume in microvasculature. This result shows that the potential reason for the heterogeneous ADC signal is associated with the disappearance of cellular edema and microvascular compensatory with increased blood volume.

The effect of additives including yeast extract, precursor amino acids and ATP on the production of glutathione (GSH) by recombinant E. coli was investigated. The addition of precursor amino acids (glutamate, cysteine and glycine) and ATP improved intracellular GSH accumulation. When 2.0 g/l ATP and 9 mmol/l precursor amino acids were added at the beginning and after 12 h of fermentation, respectively, cell concentration and intracellular GSH content was 24% and 1.4 times higher than that of culture without additions. Growth inhibition was observed while the initial glucose concentration was above 20 g/l. Based on the analysis of the batch culture process, different fed-batch cultures in jar fermenters were carried out in which three kind of simple feeding strategies were applied. An exponential feeding strategy increased cell density, productivity and biomass yield. Using this strategy, cell density and total GSH quantity in broth reached 80 g(DCW)/l and 880 mg/l at 25 h without pure oxygen, respectively.

In order to improve the level of service of a public transport (PT) system and solve the problem of transfer inconvenience, a novel planning method for multi-hierarchy PT network and transfer terminals location is presented based on the following ideas, defined below: transfer terminals by classification, service for the districts, PT network by hierarchy, planning layer by layer, optimizing dynamically for PT network and multimodal terminals planning. Most methods described in the literature for bus route network planning, bus rapid transit (BRT) route location and transfer hub location ignore the dynamic relationship between PT route network planning and transfer hub location. The objective of this paper is to present a methodology to simultaneously optimize PT route network and transfer terminal location planning. The transfer terminal location is based on the analysis of the transfer terminals importance indicator. The objective functions, constraints and location optimization methods are different for every level of the PT network hierarchy. By using the trip assignment volume result of the route network scheme, the importance indicators are recalculated and the multimodal terminals are relocated. According to the current transfer terminal locations, the multi-hierarchy PT network is redesigned. The PT network and transfer terminal locations are iteratively adjusted until the assessment results meet the equilibrium objectives. This proposed method provides a reference for future PT network and multimodal terminal location planning.

Two indole alkaloids were isolated from the culture of Aspergillus fumigatus (strain No. CY018), an endophytic fungus harboring inside the elder leaf of Cynodon dactylon. These two chemicals were identified as fumigaclavine C and fumitremorgin C. In screening the bioactivity of these two indole alkaloids, their vasorelaxant effects on isolated rat thoracic aortic rings were observed. The results showed that fumigaclavine C exhibited potent concentration-dependent vasorelaxant actions in isolated rat aortic rings pre-contracted by high K+ or phenylephrine (with EC50 values of 5.62 micromol/L and 1.58 micromol/L, respectively) whereas fumitremorgin C displayed a weaker vasorelaxation. A detailed investigation was therefore performed with fumigaclavine C. The vasorelaxing action of fumigaclavine C is independent of the presence of endothelium, suggesting its effect of vasorelaxation was not related to endothelial mediators. Blockage of L-type voltage-dependent calcium channels, activation of ATP-sensitive potassium channels and inhibition of Ca2+ release from intracellular Ca2+ stores may be involved in fumigaclavine C induced relaxation of rat isolated aortic rings. These results demonstrate that fumigaclavine C from the endophytic fungus has a potential capacity in vascular protection and thus may have therapeutic use in protection against cardiovascular disease.