A novel inhibitor of N 6-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities

N 6-methyladenosine (m6A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m6A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m6A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Clinical effects of autologous follicular unit extraction transplantation in the treatment of small area secondary cicatricial alopecia after burns / 中华烧伤杂志

Objective: To explore the clinical effects of autologous follicular unit extraction (FUE) transplantation in the treatment of small area secondary cicatricial alopecia (hereinafter referred to as cicatricial alopecia) after burns. Methods: A retrospective observational study was carried out. According to the adopted treatment methods, 18 patients (12 males and 6 females, aged (29±6) years) who received autologous FUE transplantation for small area cicatricial alopecia after burns from March 2017 to November 2019 in the First Affiliated Hospital of Air Force Medical University were included in FUE transplantation group, and 18 patients (13 males and 5 females, aged (33±5) years) who were treated with expanded flap transplantation for small area cicatricial alopecia after burns by the same surgery team during the same period in the same hospital were included in expanded flap transplantation group. All the patients were followed up for more than 1 year. At the last follow-up, the follicular unit density in the transplanted area was measured by Folliscope hair detection system and the hair survival rate was calculated; the visual analogue scale (VAS) method was adopted to evaluate the treatment effect; patients were asked their satisfaction with the treatment effect and the occurrence of complications during follow-up; the hair growth and the scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area were recorded. Data were statistically analyzed with Fisher's exact probability test and independent sample t test. Results: At the last follow-up, the follicular unit density in the transplanted area of patients in FUE transplantation group was (46.8±2.0)/cm2, which was significantly higher than (42.5±4.3)/cm2 in expanded flap transplantation group (t=3.84, P<0.01); the hair survival rates of patients were similar between the two groups (P>0.05). At the last follow-up, VAS scores evaluating the treatment effect of patients were similar between the two groups (P>0.05); the satisfaction score of patients toward the treatment effect in FUE transplantation group was 8.6±1.1, which was significantly higher than 7.6±0.8 in expanded flap transplantation group (t=2.89, P<0.01). During the follow-up, no inflammation or infection occurred in patients of the two groups, but only 2 patients in expanded flap transplantation group had postoperative pain. At the last follow-up, the transplanted area of patients in the two groups was covered with new hair, and the hair growth direction was basically consistent with the surrounding normal hair; scalp thickness, pain, pruritus, pigmentation, and surface roughness of the transplanted area of patients were similar between the two groups (P>0.05). Conclusions: Autologous FUE transplantation has better long-term follicular unit density and patients' satisfaction than expanded flap transplantation in the treatment of small area cicatricial alopecia after burns, showing better postoperative effect and a good prospect of clinical application.

Application of Single-cell RNA Sequencing Technology to Exploring Cardioprotective Mechanism of Chinese Medicine After Myocardial Infarction： A Rewiew / 中国实验方剂学杂志

The pathological changes of the heart after myocardial infarction （MI） are complex， involving multiple molecular mechanisms and various cells， such as myocardial cells， endothelial cells， fibroblasts， and macrophages. With multiple targets， Chinese medicine demonstrates ideal cardioprotective effect. However， the complex mechanism of multi-component Chinese medicine formulas has not been elucidated， thus limiting the further application. The high-throughput single-cell RNA sequencing （scRNA-seq） technology offers single-cell transcriptome analysis of hundreds of drugs under different processing conditions in a single experiment and identifies the differences in the response of different cells and cell subtypes to drug treatment. scRNA-seq technology helps us to understand the exact cellular and molecular mechanisms of cardiac remodeling from acute ischemic events to chronic cardiac scarring. The application of scRNA-seq to studying the cardioprotective mechanism of Chinese medicine after MI can boost the development of Chinese medicine， help obtain richer， more accurate and comprehensive information. It can give us a clear insight into the mechanism of Chinese medicine based on complex network. In this study， we summarized the research on cardioprotective mechanism of Chinese medicine and introduced the development of scRNA-seq technology and the application to MI research. Finally， we explored the possible application prospects of scRNA-seq in the research on cardioprotective mechanism of Chinese medicine after MI， hoping to provide ideas for the modernization of Chinese medicine.

Molecular Mechanism Analysis of Jiangtang Xiaozhi Tablets in Treatment of NAFLD / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of Jiangtang Xiaozhi tablets （JTXZT） in the treatment of non-alcoholic fatty liver disease （NAFLD） by means of network pharmacology and molecular docking. Method:With the help of traditional Chinese medicine （TCM） Systems Pharmacology Database and Analysis Platform （TCMSP）， TCMs Integrated Database （TCMID）， Encyclopedia of TCM （ETCM） and Bioinformatics Analysis Tool for Molecular Mechanism of TCM （BATMAN-TCM）， the chemical compositions of medicinal materials in JTXZT were obtained， the compound targets were predicted in SwissTargetPrediction database and STITCH database. The targets of NAFLD were searched by The Human Gene Database （GeneCards）， Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD） and DisGeNET， and intersection analysis was performed with the targets of the active ingredients to obtain the targets of JTXZT for treatment of NAFLD. Based on STRING 11.0 database， the protein-protein interaction （PPI） network of therapeutic targets was constructed， and the enrichment analysis of therapeutic targets was carried out by DAVID 6.8. Finally， the interaction characteristics of key components and core therapeutic targets of JTXZT for treatment of NAFLD were verified based on molecular docking. Result:The key components of JTXZT for treatment of NAFLD were quercetin， luteolin， kaempferol， berberine， isorhamnetin， betulinic acid， oleanolic acid， ursolic acid. formononetin and hexitol， and the core targets of JTXZT for treatment of NAFLD were mitogen-activated protein kinase 1 （MAPK1）， Jun proto-oncogene， activator protein-1 （AP-1） transcription factor subunit （JUN）， MAPK3， protein kinase B1 （AKT1 or Akt1）， tumor protein p53 （TP53）， E1A binding protein p300 （EP300）， Fos proto-oncogene， AP-1 transcription factor subunit （FOS）， tumor necrosis factor （TNF），amyloid beta precursor protein （APP） and cytochrome P450 family 2 subfamily E member 1 （CYP2E1）. Biological function and pathway enrichment analysis showed that JTXZT mainly through xenobiotic metabolic process， oxidation-reduction process， cholesterol metabolic process and other biological processes， regulating phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， MAPK signaling pathway， NAFLD and insulin signaling pathway to play a role in the treatment of NAFLD. The results of molecular docking showed that the active components of JTXZT had a good affinity with the core targets of JTXZT for the treatment of NAFLD. Conclusion:JTXZT treats NAFLD through multiple active components， multiple key targets and multiple action pathways.

Clinical observation of Ranibizumab on retinopathy of prematurity with or without preretinal hemorrhage / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To compare the therapeutic effect of Ranibizumab on retinopathy of prematurity(ROP)with or without preretinal hemorrhage(PRH). <p>METHODS: From April 2017 to January 2018, a retrospective study was carried out on the diagnosed and treated ROP cases 66 eyes of 34 in the Affiliated Eye Hospital of Nanchang University. All the infants were divided into two groups according to PRH or not. All patients were treated with intravitreal Ranibizumab under tropical anesthesia. The infants were followed up, and the cure and retreatment rate between the two groups after initial treatment were compared. <p>RESULTS: After the initial treatment of intravitreal Ranibizumab, the cure rate was 65%(17)and 98%(39), and the retreatment rate was 35%(9)and 2%(1)in bleeding and non-bleeding group, respectively. 9 eyes with PRH needed retreatment; however, only 1 eye retreatment in the non-bleeding group. Notably, all the retreatment cases were cured by once more intravitreal Ranibizumab. The cure rate between two groups was statistically significant. <p>CONCLUSION: The curative effect with initial treatment of ROP with PRH was significantly lower than that without PRH. The retreatment cases were attenuated by repeated intravitreal Ranibizumab treatment.

Application prospects of single-cell transcriptome sequencing in traditional Chinese medicine research / 中国中药杂志

Single-cell transcriptome sequencing(scRNA-seq) can be used to analyze the expression characteristics of the transcriptome at the level of individual cell, and discover the heterogeneity of gene expression in individual cell that is "diluted" or averaged in study of group organization. The scRNA-seq, with the characteristics of standardization, high-throughput, and high integration, can greatly simplify the experimental operation and significantly reduce the consumption of reagents. At the same time, a variety of cells are screened and the gene expression patterns are analyzed at the single-cell level to provide a more efficient detection technique and more rich and accurate information for drug research. In the field of traditional Chinese medicine(TCM), the scRNA-seq is still a new technology, but the individual and precision concepts embodied by scRNA-seq and the theory of TCM syndrome differentiation and treatment have reached the same effect between the micro and macro aspects. This study tried to broaden the thinking for the modernization of TCM by introducing the development of scRNA-seq technology and its application in modern drug research and discussing the application prospects of scRNA-seq in TCM research.

Diffusion kurtosis imaging: correlation analysis of quantitative model parameters with molecular features in advanced lung adenocarcinoma / 中华医学杂志(英文版)

BACKGROUND@#Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.@*METHODS@#Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the Kapp and Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, Kapp, Dapp) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.@*RESULTS@#Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The Kapp values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm/ms vs. 4.20 ± 0.83 μm/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm/ms vs. 3.59 ± 0.77 μm/ms, t = 3.12, P = 0.002). The differences in mean Dapp (3.73 ± 1.26 μm/ms vs. 3.26 ± 0.68 μm/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10 mm/s vs. [1.33 ± 0.41] × 10 mm/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10 mm/s vs. [1.50 ± 0.53] × 10 mm/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10 mm/s vs. [1.67 ± 0.77] × 10 mm/s, t = 2.88, P = 0.005). Kapp was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = -0.772, P = 0.001). Dapp was moderately correlated with EGFR mutations (r = -0.650, P = 0.024) or Ki-67 PI (r = -0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = -0.679, P = 0.033).@*CONCLUSIONS@#The Kapp value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

Anti-VEGF therapy in retinopathy of prematurity / 国际眼科杂志(Guoji Yanke Zazhi)

@#Retinopathy of prematurity(ROP)is an immature proliferative retinal vascular disease that may lead to permanent blindness in preterm infant. Retinal laser photocoagulation is used for ablation of peripheral retina and treatment of ROP, however, it is destructive. Especially for the cases with lesions in Zone I region, retinal laser photocoagulation may cause severe complications. Recently, studies have demonstrated that vascular endothelial growth factor(VEGF)plays a causal role in the pathogenesis of ROP, and intravitreal injection of anti-VEGF agents can not only effectively impede ROP progression, but also gain timing for revascularization of a vascular retinal region. This article reviews the treatment indications, drug selection, injection site, dosage recommendation, follow-up of efficacy and complications of intravitreal injection of anti-VEGF agents in the treatment of ROP.

Comparison of Three CNN Models Applied in Bone Age Assessment of Pelvic Radiographs of Adolescents / 法医学杂志

Objective To compare the performance of three deep-learning models （VGG19, Inception-V3 and Inception-ResNet-V2） in automatic bone age assessment based on pelvic X-ray radiographs. Methods A total of 962 pelvic X ray radiographs taken from adolescents （481 males, 481 females） aged from 11.0 to 21.0 years in five provinces and cities of China were collected, preprocessed and used as objects of study. Eighty percent of these X ray radiographs were divided into training set and validation set with random sampling method and used for model fitting and hyper-parameters adjustment. Twenty percent were used as test sets, to evaluate the ability of model generalization. The performances of the three models were assessed by comparing the root mean square error （RMSE）, mean absolute error （MAE） and Bland-Altman plots between the model estimates and the chronological ages. Results The mean RMSE and MAE between bone age estimates of the VGG19 model and the chronological ages were 1.29 and 1.02 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-V3 model and the chronological ages were 1.17 and 0.82 years, respectively. The mean RMSE and MAE between bone age estimates of the Inception-ResNet-V2 model and the chronological ages were 1.11 and 0.84 years, respectively. The Bland-Altman plots showed that the mean value of differences between bone age estimates of Inception-ResNet-V2 model and the chronological ages was the lowest. Conclusion In the automatic bone age assessment of adolescent pelvis, the Inception-ResNet-V2 model performs the best while the Inception-V3 model achieves a similar accuracy as VGG19 model.

Research Progress and Prospect of Machine Learning in Bone Age Assessment / 法医学杂志

Bone age assessment has always been one of the key issues and difficulties in forensic science. With the gradual development of machine learning in many industries, it has been widely introduced to imageology, genomics, oncology, pathology, surgery and other medical research fields in recent years. The reason why the above research fields can be closely combined with machine learning, is because the research subjects of the above branches of medicine belong to the computer vision category. Machine learning provides unique advantages for computer vision research and has made breakthroughs in medical image recognition. Based on the advantages of machine learning in image recognition, it was combined with bone age assessment research, in order to construct a recognition model suitable for forensic skeletal images. This paper reviews the research progress in bone age assessment made by scholars at home and abroad using machine learning technology in recent years.

Changing trend regarding the burden on cerebrovascular diseases between 1990 and 2016 in China / 中华流行病学杂志

Objectives@#To analyze the status quo and trends on the burden of cerebrovascular diseases between 1990 and 2016 in China.@*Methods@#Morbidity mortality, years of life lost (YLL), years of lived with disability (YLD) and disability-adjusted life year (DALY) related to cerebrovascular diseases between 1990 and 2016, were collated and analyzed, according to the results of the Global Burden of Diseases Study 2016 (GBD 2016). Numbers on incidence and morbidity were used to assess the incidence of diseases, while the numbers of death and mortality were used to assess the death of diseases. Years of life lost due to premature death (YLL), years lost due to disability (YLD) and disability-adjusted life year (DALY) were used to assess the burden of diseases. Changing trend on the burden of cerebrovascular disease from 1990 to 2016 was also analyzed.@*Results@#In 2016 and 1990, the numbers of new cases/morbidity and the number of deaths/mortality on cerebrovascular diseases in the country showed an upward trend. Rates regarding YLL and DALY on cerebrovascular diseases remained stable from 1990 to 2016, however, the YLD rate showed a slow upward trend. The changing rate of DALY was mainly influenced by YLL. Both DALY and YLL crude rates in males showed a slow upward trend, with the highest DALY rate appearing in the ≥70 age group. Disease burden on males was heavier than that of the females and in the 50-60 age group, which taking the largest proportion. As for the composition in DALY, YLL appearing much larger than YLD and slowly increasing. Analysis on the subtypes of diseases, proportions of YLL and DALY in hemorrhagic stroke were greater than that in ischemic stroke while the proportion of YLD in ischemic stroke was in the opposite.@*Conclusions@#The burden of disease on cerebrovascular diseases remained heavy and the differences appeared in age, gender and subtypes of diseases. Our findings called for the adoption of measures including screening, intervention and rehabilitation to be taken on target populations, in order to reduce the burden on both individuals and the society.

Comparison of parameters for diffusion-weighted intravoxel incoherent motion imaging in lung cancer patients with different histopathological subtypes / 中华肿瘤杂志

Objective@#To explore the intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) model in lung cancer patients with different histopathological subtypes.@*Methods@#A total of 105 patients were recruited, including 68 cases of adenocarcinoma, 22 cases of squamous carcinoma and 15 cases of small cell carcinoma. All patients underwent magnetic resonance examination consisting of axial IVIM-DWI sequence on a 3.0 T whole body scanner, then the standard ADC (sADC), diffusion coefficient (D), pseudo-diffusion coefficient(D*), perfusion fraction (f), distributed diffusion coefficient (DDC) and water diffusion heterogeneity index (α) were calculated for each lesion within the IVIM-DWI model.@*Results@#Mean sADC values were (1.45±0.26) ×10-3mm2/s, (1.36±0.48) ×10-3mm2/s and (1.35±0.40) ×10-3mm2/s for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean f values were (59.75±16.37) %, (47.41±18.69) % and (48.96±19.88) % for adenocarcinoma, squamous carcinoma and small cell carcinoma, respectively. Mean α values were 0.72±0.13 for adenocarcinoma, 0.62±0.12 for squamous carcinoma, and 0.63±0.11 for small cell carcinoma, respectively. Statistical analyses indicated that the sADC, f and α values among different histopathological subtypes were significantly different (P<0.05), while there was no significant difference in D, D* and DDC values (P>0.05). Furthermore, the comparison showed that the sADC, f and α values of patients with adenocarcinoma were significantly higher than those with squamous carcinoma or small cell carcinoma (P<0.05), whereas there was no significant difference between squamous carcinoma group and small cell carcinoma group (P>0.05).@*Conclusions@#The sADC, f and α values derived from the IVIM-DWI model can be used for comprehensive non-invasive evaluation of diffusion, perfusion and heterogeneity of microenvironment in lung cancer patients. And the IVIM-DWI model may be a promising tool for predicting histopathological subtypes of lung cancer.

Cardiovascular risk factors among dermatomyositis patients with positive anti-Jo-1 antibody / 中国免疫学杂志

Objective:To assess the association between anti-Jo-1 antibody and cardiovascular risk factors among patients with dermatomyositis (DM).Methods:87 patients with DM were included from 2006 to 2013.Serum anti-Jo-1 antibody was measured by ELISA,and cardiovascular risk factors were evaluated.Multiple linear regression was used to assess the association between anti-Jo-1 antibody and cardiovascular risk factors in these patients.Results:The prevalence of hypertension,diabetes,hyperuricemia,and dyslipidemia were 16.09%,22.99%,10.34% and 67.82%,respectively.16.09% of DM patients had a positive anti-Jo-1 antibody and these patients had higher frequency of arthralgia/Raynaud's phenomenon/interstitial lung disease,and higher level of leukocyte and C reactive protein,while had lower level of serum uric acid (P<0.05).Multiple linear regression demonstrated that anti-Jo-1 antibody was closely associated with the level of C reactive protein and serum uric acid.Conclusion:Positive anti-Jo-1 antibody is associated with inflammation marker;however,the detailed mechanism remains further research.

Clinical features of 59 patients with scrub typhus in Kunming City / 中华地方病学杂志

Objective To study the clinical features of patients with scrub typhus and provide scientific basis for clinical diagnosis and treatment. Methods Clinical data of patients with scrub typhus in the First Affiliated Hospital of Kunming Medical University from January 2016 to December 2016 were collected. Epidemiological data, clinical manifestations, laboratory findings, image examination results, treatment and outcome were retrospectively analyzed. Results The clinical manifestations included 59 cases (100.0％) with fever, 44 cases (74.6％) with headache, 39 cases (66.1％) with chills, 34 cases (57.6％) with muscle and joint pain, 29 cases (49.2％) with prostration, 49 cases (83.1％) with eschar or ulcer, 42 cases (71.2％) with lymphadenectasis, 23 cases (39.0％) with hepatosplenomegaly. Laboratory test results: 51 cases (86.4％) had normal or elevated white blood cell count, 50 cases of eosinophil reduced (84.7％), 27 cases of blood platelet (PLT) reduced (45.8％), 33 cases of albumin reduced (55.9％), 50 cases of alanine aminotransferase (ALT) increased (84.7％), 48 cases of aspartate aminotransferase (AST) increased (81.4％), and 56.1％ (23/41) of the patients with triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3) and free thyroxine (FT4) levels significantly lowered, with predominantly free FT3 reduction (82.6％,19/23); C reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR) and ferritin were increased in 93.9％(46/49), 35.4％ (17/48), 64.9％ (24/37), and 83.8％ (31/37) of the patients, and 95.6％(43/45) was accompanied with chest radiographic abnormalities. Tetracycline, doxycycline and azithromycin treatment were all effective. Conclusions The clinical manifestations of patients with scrub typhus, involving multisystem, are diverse and thyroid hormones decrease is observed. Early diagnosis and treatment is the key to improve the prognosis of patients with scrub typhus.

Influence of Wnt/beta-catenin signal transduction pathway on the differentiation of umbilical cord mesenchymal stem cells into hepatocyte-like cells / 中国组织工程研究

BACKGROUND:Umbilical cord mesenchymal stem cells can be induced to differentiate into hepatocyte-like cells in vitro and in vivo.However,the exact mechanism is still unknown. Existing studies have shown that the Wnt/β-catenin signaling pathway is closely related to this process. OBJECTIVE: To explore the effect of Wnt/β-catenin signaling pathway on the differentiation of umbilical cord mesenchymal stem cells into hepatocyte-like cells and its potential molecular mechanism. METHODS: Human umbilical cord mesenchymal stem cells were extracted from the neonatal umbilical cord by tissue adherent method. After being cultured and purified, the umbilical cord mesenchymal stem cells at passages 4-6 were divided into four groups: control group (DMEM culture group), hepatocyte-like differentiation group, activator Wnt3a group (adding 20 μg/L Wnt3a, an activator of Wnt/β-catenin signaling pathway, under the differentiation condition), and inhibitor Dkk-1 group (adding 20 μg/L Dkk-1, an inhibitor of Wnt/β-catenin signaling pathway, under the differentiation condition). Induced cells were collected respectively on days 7, 14, 21, 28. Their mRNA and protein expressions of α-fetoprotein (AFP), albumin (ALB), hepatocyte nuclear factor 4α (HNF4α) and Cytokeratin-19 (CK-19) in the cells were detected by real-time quantitative PCR and western blot respectively. Meanwhile, Periodic Acid-Schiff staining, low-density lipoprotein uptake test and indocyanine green absorption test were applied to detect the function of hepatocyte-like cells. RESULTS AND CONCLUSION: Compared with the control group, expressions of AFP and HNF4α mRNA and protein as well as ALB mRNA were significantly up-regulated in the hepatocyte-like differentiation group, activator Wnt3a group and inhibitor Dkk-1 group (P < 0.05). Whereas, there was a decrease in the CK-19 expression at mRNA and protein levels (P < 0.01) in these three groups. Compared with the hepatocyte-like differentiation group, the mRNA and protein expressions of AFP and HNF4α, and the mRNA expression of ALB were significantly down-regulated in the activator Wnt3a group (P < 0.05). Compared with hepatocyte-like differentiation group and activator Wnt3a group, the inhibitor Dkk-1 group had higher expression of AFP, HNF4α mRNA and their proteins as well as the mRNA expression of ALB (P <0.05). Findings from the Periodic Acid-Schiff staining, low-density lipoprotein uptake test and indocyanine green absorption test showed more positive cells in the inhibitor Dkk-1 group than in the hepatocyte-like differentiation group and least positive cells in the activator Wnt3a group. Overall, these findings suggest that the inhibition of Wnt/β-catenin signaling pathway promotes the differentiation of umbilical cord mesenchymal stem cells into hepatocyte-like cells;conversely,the cell differentiation can be inhibited via the Wnt/β-catenin pathway.

Surgical nursing of rare giant neurofibroma resection and reconstruction / 中国实用护理杂志

Objective To report the surgical nursing strategy of a patient undergoing resection of a rare giant neurofibroma.Methods Through the preoperative comprehensive assessment of patients,multidisciplinary joint consultation and proposed possible surgical risks and countermeasures,specialist to formulate surgical plans,surgical care and nursing key points,difficulties and countermeasures.Results The psychological nursing,detailed and perfect the preoperative preparation work,the personnel allocation was sufficient,the division of labor was clear,the disease changes were actively observed in the operation,the venous pathway was strictly managed,the accurate record,the risk that might occur in the active prevention operation and the treatment plan,the postoperative closely monitors the condition.Good observation and nursing in the operation area to prevent infection.Conclusions In view of difficult and complicated operation,through the comprehensive formulation of surgical nursing measures and strict execution in surgery,it is the guarantee for the smooth completion of the operation,the operation process is smooth,the successful implementation of tumor resection,the effect is satisfactory,the patient is returned to the ward,and there is no special discomfort.

Research advances in signaling pathways involved in the development of hepatic fibrosis / 临床肝胆病杂志

Liver fibrosis is a pathological process for the liver to repair various chronic liver injuries and may eventually progress to liver cirrhosis,liver failure,or even liver cancer.Therefore,early intervention arid treatment of liver fibrosis is of particular importance.This article summarizes the latest research advances in the roles of TGF-β/Smad signaling pathway,Notch signaling pathway,Wnt signaling pathway,Hedgehog signaling pathway,and integrin signaling pathway in the pathogenesis of liver fibrosis and points out that these signaling pathways play an extremely important role in the development and progression of liver fibrosis and may provide new directions for the treatment of liver fibrosis.

Analysis of the risk factors of bleeding after endoscopic resection of colorectal polyps / 中国内镜杂志

Objective To analyze the risk factors of bleeding after endoscopic resection of colorectal polyps.Methods 342 cases of colorectal polyps treated by endoscopic surgery in our hospital were taken as the research objects. The incidence of bleeding after endoscopic surgery was statistically studied. All the patients were divided into bleeding group and no hemorrhage group, with postoperative bleeding as the dependent variable, and related factors which may be induced postoperative bleeding (gender, age, diabetes mellitus, with hypertension and hyperlipidemia history, drinking history, polyp occurrence location, polyp pathology type, polyp size, morphology of colonic polyps, polyp number) as the independent variable to make advanced single factor regression analysis. Then using the logistic regression analysis tool for multivariate analysis.Results The incidence of postoperative bleeding was 7.60% (26/342) in 342 patients. Single factor analysis showed that the bleeding in the proportion of patients with hypertension was higher than that of without complication (P 2.0 percentage higher than that without complication (P 2.0 cm, and polyps were the risk factors of postoperative hemorrhage (P 2.0 cm, polyp morphology of pedicle polyps.

Efficiency and safety of daclatasvir in treatment of chronic hepatitis C: A meta-analysis / 解放军医学杂志

Objective To evaluate the efficacy and safety of daclatasvir in treatment of chronic hepatitis C (CHC). Methods Articles regarding treatment and safety of CHC were retrieved from PubMed, EMBASE, The Cochrane Central Register of Controlled Trials, Chinese Journals Full-text Database (CNKI, China National Knowledge Infrastructure), and WanFang Digital Journal Full-text Database to collect clinical RCTs (randomized controlled trials) for CHC treated by daclatasvir. Meta-analysis was performed by using Review Manager 5.3. Results A total of six RCTs including 1100 patients met the inclusion criteria. Metaanalysis results were as follows. 1) The overall RVR (rapid virological response), cEVR (complete early virological response) and SVR24 (sustained virological response at post-treatment week 24) rates were significantly higher in daclatasvir group than in control group. 2) The RVR, cEVR, and SVR24 rates were significantly higher in daclatasvir (60mg/d) group than in control group. 3) The RVR and cEVR rates were significantly higher in daclatasvir (10mg/d) group than in control group, but no significant difference existed between the two groups in the SVR24 rate. 4) No significant differences were found in nonspecific adverse events, liver function, hematologic system or skin between daclatasvir and control groups. Conclusion Daclatasvir is effective and safe in treatment of CHC, and daclatasvir 60mg/d is a better choice as compared with daclatasvir 10mg/d.

Chemical Constituents from Leaves of Acanthopanax henryi (II)

Nineteen compounds, including one organic acid (1), one anthraquinone (2), one amide (3), and sixteen triterpenoid saponins (4 - 19) were isolated from the leaves of Acanthopanax henryi (Oliv.) Harms (Araliaceae). Their structures were determined on the basis of physicochemical properties and spectral analyses (HR-MS and NMR). Among them, compounds 2, 3, 7, 12 and 19 were new within Araliaceae. Compounds 4, 5, 9 - 11, 13, 14, 16 and 18 were reported for the first time from the Acanthopanax genus. Except for compounds 4 and 9, other compounds were isolated from A. henryi (Oliv.) Harms for the first time. The rare anthraquinone, compound 2, significantly decreased the production of NO and the levels of other inflammatory factors, such as TNF-alpha and IL-6, in lipopolysaccharide (LPS)-stimulated macrophages in a dose-dependent manner. This is the first time to report anti-inflammatory effect of this compound.