Analysis of the characteristics of intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis.

Objective: To understand the characteristics of the intestinal microbiota after oral tolerance in infants with food protein-induced proctocolitis (FPIAP) treated with amino acid formula and their differences from healthy children, aiming to provide a scientific basis for guiding the application of probiotics during treatment. Methods: FPIAP infants were prospectively enrolled, fecal specimens were obtained, and DNA was extracted for PCR amplification of the bacterial 16S rRNA gene V4 region. Library construction and sequencing were performed, and bioinformatic analysis was performed after obtaining valid data. Results: There were 36 patients in the FPIAP group: 20 males and 16 females, age 21.944 ± 13.277 months. Diarrhea with blood in the stool were the main symptom, with an average course of 14.83 ± 9.33 days. Thirty infants (83.33%) had mucus stool, 11.11% (4/36) of them experiencing vomiting, and 55.56% (20/36) of the infants displaying poor intake and weight gain, 28 (77.78%) patients with moderate eczema, 2 (5.6%) patients with chronic respiratory symptoms. The treatment time with amino acid formula was 5.51 ± 2.88 months. A control group comprising of 25 healthy infants who were full-term, natural delivery, bottle fed, and matched in terms of age (24.840 ± 12.680 months) and gender (15 males and 10 females) was selected. Anaerobic bacteria were less abundant in FPIAP infants than healthy infants (P = 4.811 × 10-5), but potentially pathogenic bacteria were more abundant (P = 0.000). The abundance of Actinobacteria was low in FPIAP infants, the abundance of Proteobacteria was high, and the abundance of Firmicutes was reduced. Bifidobacterium could be used as a bacterial genus to differentiate healthy and FPIAP infants. Both α-and ß-diversity indicators of intestinal microbiota were lower in FPIAP infants. In FPIAP infants, glucose and energy metabolism and amino acid anabolism were decreased, and inflammation-related lipopolysaccharide synthesis pathways were increased. Conclusion: Compared with healthy infants, FPIAP infants with oral tolerance after amino acid formula treatment had differences in the structure and diversity of intestinal microbiota, among which Bifidobacterium was significantly reduced. Trial Registration: This trial was registered on https://register.clinicaltrials.gov/.

Effects and mechanisms of dihydroartemisinin combined with carfilzomib on the activity, proliferation, and apoptosis of multiple myeloma cells / 国际肿瘤学杂志

Objective:To study the effects and potential mechanisms of the combination of dihydroartemisinin and carfilzomib on the activity, proliferation, and apoptosis of multiple myeloma ARD cell lines.Methods:In vitro cultivation of multiple myeloma ARD cells involved treating the cells with dihydroartemisinin at concentrations of 0, 5, 10, 20, 40, and 80 μg/ml, and with carfilzomib at concentrations of 0, 5, 10, 20, 40, and 80 nmol/L. The ARD cells were divided into a control group (no treatment) , a dihydroartemisinin group (2 μg/ml) , a carfizomib group (8 nmol/L) , and a combination group (dihydroartemisinin 2 μg/ml + carfizomib 8 nmol/L) . Cell activity and proliferation were assessed by MTT assay and EdU-488 assay; cell apoptosis was evaluated using live cell/dead cell dual staining and flow cytometry. The expression levels of apoptosis-related proteins were examined using Western blotting analysis. Results:The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 μg/ml dihydroartemisinin were (100.00±2.18) %, (50.22±3.09) %, (37.39±2.34) %, (30.42±1.79) %, (23.80±1.12) %, and (18.04±0.79) %, respectively, and there was a statistically significant difference ( F=653.30, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 nmol/L carfilzomib were (100.00±1.12) %, (83.98±2.95) %, (67.27±2.10) %, (58.24±2.02) %, (46.34±1.14) %, and (37.47±1.36) %, respectively, and there was a statistically significant difference ( F=227.40, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±2.67) %, (67.23±0.57) %, (76.23±2.83) %, and (27.06±1.09) %, respectively, and there was a statistically significant difference ( F=655.60, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The EdU-488 experiment showed that the EdU-positive rates of ARD cells in the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±8.17) %, (68.07±6.14) %, (85.04±2.78) %, and (19.62±3.83) %, respectively, and there was a statistically significant difference ( F=115.20, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.047; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The live cell/dead cell dual staining experiment showed, under bright-field observation, the cell morphology was intact in the control group. In all the drug groups, the cell morphology became irregular, reduced in size with condensed cytoplasmic, and apoptotic vesicles with irregular morphology were seen around the cells, among which the most obvious changes were seen in the combination group. Under fluorescence observation, the cells in the control group only displayed green fluorescence. In all drug-treated groups, cells with red fluorescence were observed, with the combination group having the highest percentage of cells with red fluorescence among the total cell population. The apoptosis rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (9.06±2.95) %, (29.50±1.34) %, (20.77±3.00) %, and (58.23±5.13) %, respectively, and there was a statistically significant difference ( F=115.80, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.012; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . There were statistically significant differences in the relative expression levels of P53, Cleaved-Caspase-3, Bcl-2, and Bax proteins among the control group, dihydroartemisinin group, carfilzomib group, and combination group ( F=21.76, P<0.001; F=42.87, P<0.001; F=44.27, P<0.001; F=163.50, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.05) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.05) . Conclusion:The combination of dihydroartemisinin and carfilzomib can synergistically inhibit the activity and proliferation of multiple myeloma ARD cells, and promote apoptosis, and the underlying mechanism may be associated with the mitochondrial apoptosis pathway.

Effect of oxaliplatin on the activation of hepatic stellate cells and its mechanism / 临床肝胆病杂志

ObjectiveTo investigate the effect of oxaliplatin on the activation of hepatic stellate cells （HSCs）， as well as the association of oxaliplatin with microRNA-30a-5p and autophagy. MethodsHSC-LX2 cells were cultured and divided into groups according to the following three protocols： control group， PDGF treatment group， oxaliplatin treatment group， oxaliplatin+PDGF treatment group； control group， microRNA-30a-5p transfection group， PDGF treatment group， microRNA-30a-5p transfection+PDGF treatment group； control group， 3-MA group， microRNA-30a-5p inhibitor group， microRNA-30a-5p inhibitor+3-MA group. Western Blot was used to measure the expression of HSC activation-related proteins （Collagen-I and alpha-smooth muscle actin ［α- SMA］） and HSC autophagy-related proteins （Beclin-1， P62， and LC3B）； LysoTracker staining and immunofluorescence assay were used to measure the expression of LC3B autophagosomes； RT-PCR was used to measure the expression level of microRNA-30a-5p； bioinformatics techniques were used to predict the potential targets of microRNA-30a-5p in HSCs. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsAfter the cells were treated with oxaliplatin， RT-PCR results showed that the oxaliplatin treatment group had a significantly higher expression level of microRNA-30a-5p than the control group （P<0.01）； Western Blot showed that the oxaliplatin treatment group had significant reductions in the expression levels of the HSC activation-related proteins α-SMA and Collagen-‍Ⅰ and the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （all P<0.001）； immunofluorescence assay showed that the oxaliplatin treatment group had a significantly lower number of autophagosomes than the control group （P<0.05）. After HSC-LX2 cells were transfected with microRNA-30a-5p mimic， compared with the control group， the microRNA-30a-5p mimic group had significant reductions in the expression levels of the autophagy-related proteins Beclin 1 and LC3BⅡ/Ⅰ （P<0.05） and the HSC activation-related protein Collagen-‍‍Ⅰ （P<0.001）； after HSC-LX2 cells were transfected with microRNA-30a-5p inhibitor， Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC activation-related proteins Collagen-‍Ⅰ and α-SMA and the autophagy-related protein Beclin 1 （t=2.41， 2.32， and 4.57， all P<0.05）. Western Blot showed that compared with the control group， the microRNA-30a-5p inhibitor group had significant increases in the expression levels of the HSC autophagy-related protein Beclin 1 and the HSC activation-related protein α-SMA （both P<0.05）， and after the treatment with the autophagy inhibitor 3-MA， there were no significant differences in the expression of these proteins between the two groups （P>0.05）. The bioinformatics analysis using TargetScan， PicTar， and miRanda databases showed that the autophagy-related protein Beclin-1 might be a potential target of miRNA-30a-5p. ConclusionOxaliplatin can inhibit the activation of HSCs by upregulating the expression of microRNA-30a-5p， which provides new ideas and a new target for the treatment of liver fibrosis.

Y-box-binding protein 1 mediates sorafenib resistance via the extracellular signal regulated-protein kinase pathway in hepatoma cells / 中华肝脏病杂志

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Experts consensus on the procedure of dental operative microscope in endodontics and operative dentistry / 国际口腔科学杂志·英文版

The dental operative microscope has been widely employed in the field of dentistry, particularly in endodontics and operative dentistry, resulting in significant advancements in the effectiveness of root canal therapy, endodontic surgery, and dental restoration. However, the improper use of this microscope continues to be common in clinical settings, primarily due to operators' insufficient understanding and proficiency in both the features and established operating procedures of this equipment. In October 2019, Professor Jingping Liang, Vice Chairman of the Society of Cariology and Endodontology, Chinese Stomatological Association, organized a consensus meeting with Chinese experts in endodontics and operative dentistry. The objective of this meeting was to establish a standard operation procedure for the dental operative microscope. Subsequently, a consensus was reached and officially issued. Over the span of about four years, the content of this consensus has been further developed and improved through practical experience.

Comparative molecular analysis of oral submucous fibrosis and other organ fibrosis based on weighted gene co-expression network analysis / 中南大学学报(医学版)

OBJECTIVES@#There is currently a lack of economic and suitable animal models that can accurately recapitulate the oral submucous fibrosis (OSF) disease state for indepth study. This is one of the primary reasons for the limited therapeutic methods available for OSF. Based on the underlying logic of pan-cancer analysis, this study systematically compares OSF and the other four types of organ fibrosis from the aspects of molecules, signaling pathways, biological processes, etc. A comprehensive analysis of the similarities and differences between OSF and other organ fibrosis is helpful for researchers to discover some general rules of fibrosis disease and may provide new ideas for studying OSF.@*METHODS@#Microarray data of the GSE64216, GSE76882, GSE171294, GSE92592, and GSE90051 datasets were downloaded from GEO. Differentially expressed mRNAs (DEmRNAs) of each type of fibrosis were identified by Limma package. Weighted gene co-expression network analysis (WGCNA) was used to identify each type of fibrosis-related module. The similarities and differences of each fibrosis-related-module genes were analyzed by function and pathway enrichment analysis.@*RESULTS@#A total of 6 057, 10 910, 27 990, 10 480, and 4 801 DEmRNAs were identified in OSF, kidney intestinal fibrosis (KIF), liver fibrosis (LF), idiopathic pulmonary fibrosis (IPF), and skin fibrosis (SF), respectively. By using WGCNA, each type of fibrosis-related module was identified. The co-expression networks for each type of fibrosis were constructed respectively. Except that KIF and LF have 5 common hub genes, other fibrotic diseases have no common hub genes with each other. The common pathways of OSF, KIF, LF, IPF, and SF mainly focus on immune-related pathways.@*CONCLUSIONS@#OSF and the other 4 types of fibrotic diseases are tissue- and organ-specific at the molecular level, but they share many common signaling pathways and biological processes, mainly in inflammation and immunity.

Influence of buccal acupuncture on analgesic effect, immune indicators, and expression of Survivin and Livin proteins in patients with advanced-stage primary liver cancer / 针灸推拿医学（英文版）

Objective: To investigate the effects of buccal acupuncture on analgesia, immune indicators, and expression levels of Survivin and Livin proteins in patients with advanced-stage primary liver cancer. Methods: Eighty patients with advanced-stage primary liver cancer were selected and divided into control and treatment groups according to the difference in treatment modalities, with 40 patients in each group. The control group received transcatheter arterial chemoembolization (TACE), and the treatment group received buccal acupuncture in addition to TACE. The recent efficacy, analgesic effect, liver function, serum tumor markers, Survivin and Livin protein expression levels in liver cancer tissue, and immune indexes were analyzed and compared between the two groups. Results: The objective response rate (ORR) and disease control rate (DCR) of the treatment group were 37.5％ and 77.5％, respectively, which were significantly higher than those of the control group (22.5％ and 52.5％), and the recent efficacy of the treatment group was significantly better than that of the control group (P<0.05). The onset of analgesia in the treatment group was significantly faster than that in the control group (P<0.05), the duration of analgesia was significantly longer than that in the control group (P<0.05), and the numeric rating scale (NRS) score of pain after treatment was significantly lower than that in the control group (P<0.05). In the treatment group, the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin/globulin (A/G) were significantly lower than those in the control group (P<0.05), and the serum levels of alpha-fetoprotein (AFP), alpha-L-fucosidase (AFU), and carcinoembryonic antigen (CEA) were significantly lower than those in the control group (P<0.05), and the expression levels of Survivin and Livin in liver cancer tissue were significantly lower than those in the control group (P<0.05); CD4+ and CD4+/CD8+ in the treatment group were significantly higher than those in the control group, and CD8+ was significantly lower than that in the control group after treatment (P<0.05). Conclusion: Buccal acupuncture can reduce the degree of pain and liver function damage in patients with advanced- stage primary liver cancer and lower the serum tumor marker levels, and its mechanism of action may be related to the down-regulation of Survivin and Livin protein expression levels in the liver cancer tissue and the regulation of the immune function.

Value of a microRNA risk score model in predicting the prognosis of hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo screen out the microRNAs (miRNAs) associated with the prognosis of hepatocellular carcinoma (HCC) through data mining of miRNA transcriptome data of HCC downloaded from The Cancer Genome Atlas (TCGA) database, to establish a miRNA risk score model, and to investigate its value in predicting the prognosis of HCC. MethodsThe miRNA expression data and clinical data of HCC samples were downloaded from TCGA database and R language was used to screen out differentially expressed miRNAs between HCC tissue and adjacent tissue, which were randomly divided into training set and testing set after being integrated into clinical data. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed for the training set to screen out the miRNAs associated with the prognosis of HCC, and then a miRNA risk score model was established. The Kaplan-Meier method was used to evaluate the robustness of the model and whether it could predict the prognosis of patients in the same clinical stage. Finally, the receiver operating characteristic (ROC) curve was plotted and the area under the ROC curve (AUC) was calculated to compare the predictive accuracy of the model versus TNM staging in the training set, the testing set, and the entire set. ResultsA total of 300 differentially expressed miRNAs were screened out and the LASSO Cox regression analysis revealed that hsa-miR-139-5p, hsa-miR-1180-3p, hsa-miR-1269b, hsa-miR-3680-3p, hsa-miR-509-3-5p, and hsa-miR-31-5p were associated with the prognosis of HCC. The risk score was calculated for each sample according to the established miRNA risk score model, and the samples were divided into high-risk group and low-risk group according to the median risk score. The Kaplan-Meier curve showed that in both training and testing sets, the high-risk group had a significantly lower survival rate than the low-risk group (P＜0.05). The ROC curve was used to evaluate the prediction efficiency of this model, and the results showed that in the training set, the testing set, and the entire set, the miRNA model had an AUC of 0.817, 0.808, and 0.814, respectively, while TNM staging had an AUC of 0.667, 0.665, and 0.663, respectively. The results of independent prognostic analysis also showed that this miRNA score model could be used as an independent prognostic factor for HCC (P＜0.05). ConclusionHsa-miR-139-5p, hsa-miR-1180-3p, hsa-miR-1269b, hsa-miR-3680-3p, hsa-miR-509-3-5p, and hsa-miR-31-5p are associated with the prognosis of HCC, and the miRNA risk score model has a better prediction accuracy than TNM staging in the training set, the testing set, and the entire set. The stratified analysis also shows that the model can predict the prognosis of patients within the same TNM stage, and therefore, it has a certain reference value in clinical practice and can be used as an independent model for predicting the prognosis of HCC patients.

Role of Y-box binding protein-1 in the development and progression of chronic liver diseases / 临床肝胆病杂志

Chronic liver diseases have various etiologies and often have poor long-term prognosis in clinical practice. Y-box binding protein-1 (YB-1) is a multifunctional protein, and in-depth studies in recent studies have found that it plays a key role in the development and progression of chronic liver diseases such as liver fibrosis and hepatocellular carcinoma (HCC). This article summarizes the role of YB-1 in chronic liver diseases such as liver fibrosis, HCC (proliferation, apoptosis, metastasis, prognosis, and drug resistance), and liver failure, so as to provide a theoretical basis for the diagnosis and treatment of chronic liver diseases.

Research advances in the regulation of epithelial-mesenchymal transition and targeted therapy for liver fibrosis / 临床肝胆病杂志

The pathological basis of liver fibrosis is the deposition of extracellular matrix (ECM), and myofibroblasts are the main source of ECM. Epithelial-mesenchymal transition (EMT) is one of production mechanisms of myofibroblasts. At present, a large number of studies have shown that intervention of key EMT molecules and signaling pathways as targets can reduce liver fibrosis. Based on literature review, this article summarizes the signaling pathways associated with EMT, important regulatory molecules, and drugs targeting EMT in the treatment of liver fibrosis, so as to provide new ideas for the treatment of liver fibrosis.

Prediction of prognosis of gastric cancer by a five-microRNA risk score model / 中华消化杂志

Objective:To analyze and screen microRNA (miRNA) related to the prognosis of gastric cancer(GC) by bioinformatics analysis, and to construct and validate a risk score model.Methods:The human genome miRNA sequencing data and corresponding clinicopathological data of the 491 samples (446 GC tissue samples and 45 normal gastric tissue samples) were downloaded from the cancer genome atlas (TCGA) database. The differentially expressed microRNA (DEM) was analyzed with edgeR package of R 4.0.2 software and the obtained DEM’s profile was randomly divided into training set and test set according to the ratio of 1∶1. The miRNA related to prognosis were analyzed and screened with univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox regression analysis was further performed to analyze the screened prognostic-related miRNA and then the prognostic risk score model was constructed. Kaplan-Meier curve, receiver operating characteristic curve (ROC), and dynamic area under the ROC were drawn to evaluate the predictive power of the model.Results:A total of 175 DEM in GC tissues were screened out based on the cut-off criteria of |log2 Fold Change|>1.5 and P<0.01. Six DEMs related to the overall survival rate of patients with GC were screened out by univariate Cox regression and LASSO regression analysis, and then a five-miRNA risk score model was successfully constructed by multivariate Cox regression. The risk score=0.183×hsa-miRNA-184+ 0.086×hsa-miRNA-675-0.231×hsa-miRNA-2115+ 0.548×hsa-miRNA-3943-1.455×hsa-miRNA-1246. In the training set, test set and overall data set, the cumulative survival rates of the patients with higher risk score were lower than those of the patients with lower risk score, respectively, and the differences were statistically significant ( χ2=18.90, 9.50 and 26.70, all P<0.05). The prediction power of the model was better than that of TNM stage. And the results of stratified analysis showed the predictive ability of the model in patients with early GC. The results of univariate Cox regression and multivariate Cox regression demonstrated that the risk score of the model, gae and M stage were independent risk factors for poor prognosis in patients with GC (hazard ratio(95% confidence interval)1.19(1.07 to 1.32), 1.20(1.06 to 1.40), 1.50(1.01 to 2.23), 1.90(1.28 to 2.90), 1.34(1.15 to 1.57), 2.10(1.05 to 4.40); all P<0.05). Conclusion:The 5-miRNA risk score model based on 5 miRNAs which was an independent prognostic factor had high accuracy in predicting the prognosis of patients with GC.

Discussion on the Industry Development Status of Blumea balsamifera Based on Patent Analysis / 中国药房

OBJECTIVE：To understand the current situation and existing problems of Blumea balsamifera industry in China ， and to provide reference for its sustainable development . METHODS ：With the keywords of “B. balsamifera ”“Ai Pian ”“Ai Fen ”， etc.，through the patent platform of SooPat and Baiten ，the patent data of B. balsamifera that had been published from Jan. 1989 to Dec. 2019 were collected. The International Patent Classification （IPC）was used to sort out and count the patent information of B. balsamifera，to understand the development status of B. balsamifera industry in technology and research field ，to analyze the existing problems and to explore the development trend of B. balsamifera industry in China so as to put forward corresponding suggestions. RESULTS & CONCLUSIONS：A total of 690 patents related to B. balsamifera were collected ，mainly invention patents，of which the authorization rate was 27.39％，the effective rate was 17.97％，and the failure rate was 55.22％. Top 10 applicants with the largest number of applications had a total of 165 applications，accounting for 23.91％ of the total number of applications. Top 10 applicants were 4 enterprises，3 natural persons and 3 colleges and universities. The patents of B. balsamifera were mainly distributed in Guizhou ，Shandong，Anhui，Guangdong，Guangxi and Hainan ，accounting for 81.01％ of the total patent applications of B. balsamifera . The patent technology field of B. balsamifera had expanded from traditional Chinese medicine to daily chemical products ，health care and physiotherapy and other daily consumer good fields. From the perspective of patent intensity，the number and quality of patent applications were not coordinated ，and there were many meaningless patent applications，and the conversion rate was low. It is suggested that China should strengthen the research on B. balsamifera and its more compatible medicinal materials ，promote the innovation ，development，transformation and upgrading of B. balsamifera industry；strengthen the systematic and in-depth research on B. balsamifera，improve the quality and conversion rate of patent xiexiaoli13@126.com technology，and revitalize the development of B. balsamifera industry； expand multi-party cooperation ， strengthen the E-mail：fulai.yu@163.com research on patent core technology ，build the strategic alliance of intellectual property rights of B. balsamifera industry，and realize the high quality development of B. balsamifera industry.

Programmed management in prenatal diagnosed pyriform sinus fistula: analysis of eight cases / 中华围产医学杂志

Objective:To evaluate the clinical effect of applying the programmed management procedure in the prenatal diagnosis of pyriform sinus fistula(PSF).Methods:This study retrospectively enrolled eight fetuses with PSF who were managed according to the programmed management procedure for prenatal diagnosis of PSF, which was established in January 2016, in Guangzhou Women's and Children's Medical Center from January 2016 to October 2020. The procedure consisted of the detection of fetal neck cysts by prenatal ultrasound followed by further confirmation by MRI, evaluation of the degree of airway compression, indwelling gastric tube after birth, no oral feeding, complement of CT/MRI, and surgical treatment within a limited time after necessary preoperative examination. The prenatal diagnosis, postnatal treatment, and follow-up were summarized using descriptive analysis.Results:(1) Prenatal: The gestational age at the first detection of cervical cysts by prenatal ultrasound was (27.1±4.1) weeks and all the cysts were located on the left side. Prenatal MRI indicated that the largest cysts was (32.0±12.2) mm in diameter, and the tracheal transit index was (10.9±2.8) mm. (2) After birth: Among the eight children, five were males and three were females, with the gestational age of (38.0±0.9) weeks and birth weight of (3 020±459) g. One case was intubated during labor due to a intrauterine tracheal transposition index of 17.4 mm. All infants were not allowed for oral feeding. The median age at CT/MRI examination was 2.5 d (1-8 d), which revealed that the maximum diameter of the cysts was (40.6±6.9) mm and visible air bubbles in all cysts. The infection index before operation was not high and the age at operation was (8.6±2.3) d. All cysts were completely removed and the PSFs were ligated at a higher position, with the average operative duration of (95.0±19.6) min, and the postoperative duration of mechanical ventilation and hospitalization of 5 h (3-71 h) and (8.8±1.0) d, respectively. No complications such as hoarseness were reported. During the follow-up of 4 to 58 months through outpatient clinic and telephone, no recurrence were observed.Conclusions:The programmed management procedure can provide guidance for postnatal treatment of patients with a prenatal diagnosis of PSF, and help to achieve a successful treatment result.

Risk factors of necrotizing enterocolitis after surgery for intestinal atresia / 中国新生儿科杂志

Objective:To study the risk factors of necrotizing enterocolitis (NEC) after surgery for intestinal atresia.Method:From August 2013 to June 2020, children with intestinal atresia receiving surgery in our hospital were retrospectively reviewed. The patients were assigned into NEC group and non-NEC group according to the occurrence of postoperative NEC. Demographic data and clinical characteristics were summarized and the risk factors for postoperative NEC were analyzed using Logistic regression analysis method.Result:A total of 96 infants were enrolled and NEC occurred in 13 patients (13.5%) after surgery for intestinal atresia. Compared with the non-NEC group, the NEC group were diagnosed of intestinal atresia [4.0(1.5,6.0)d vs. 1.4(0,2.0)d, P<0.001] and received surgery [4.8(2.0,7.0)d vs. 3.1(1.0,4.0)d, P=0.034] at later ages. The incidences of complex intestinal atresia [76.9%(10/13) vs. 44.6%(37/83), P=0.030] and blood transfusion [46.2%(6/13) vs. 13.3%(11/83), P=0.007] in the NEC group were higher than the non-NEC group. Logistic regression analysis showed that the age of initial diagnosis of intestinal atresia ( OR=3.346, 95% CI 1.493~7.500, P=0.003), complex intestinal atresia ( OR=9.052, 95% CI 1.119~73.209, P=0.039) and blood transfusion ( OR=6.835, 95% CI 1.399~33.380, P=0.018) were independent risk factors for postoperative NEC. Conclusion:Patients with delayed diagnosis of intestinal atresia, complex intestinal atresia and blood transfusion within 48 hours after surgery should be monitored for the occurrence of postoperative NEC.

Progress of congenital sodium diarrhea in children / 国际儿科学杂志

Congenital sodium diarrhea(CSD)refers to a rare and intractable secretory diarrhea of intrauterine onset with high fecal sodium loss which is caused by abnormal intestinal sodium absorption.Congenital sodium diarrhea is a disease with clinical and genetical heterogeneity.It can be classified as non-syndromic congenital sodium diarrhea(non-sCSD)and syndromic congenital sodium diarrhea(sCSD)according to the clinical features.The diagnosis of CSD is made based on the manifestation and genetic analysis.The mutations of CSD include SLC9A3 gene、GUCY2C gene and SPINT2 gene.The main treatment of CSD is symptomatic treatment and some of these patients will develop inflammatory bowel disease(IBD). Lifelong clinical and biological follow-up of patients is necessary.

The effects of multi-disciplinary team management on the outcome in neonates with omphalocele / 中国新生儿科杂志

Objective To study the effect of multi-disciplinary team (MDT) management on the outcome in neonates with omphalocele.Method A retrospective non-randomized controlled clinical study was conducted.Neonates who were diagnosed as omphalocele and admitted to the surgical neonatal intensive care unit of the Guangzhou Women and Children Medical Center from December 2010 to December 2017 were collected.Because MDT was established in December 2014,infants were assigned into non-MDT group and MDT group according to their dates of admission.The characteristics and outcomes between non-MDT group and MDT group were compared using x2,t-test or rank-sum test.Multivariate analysis was performed by Logistic regression.Result A total of 91 neonates were included in the study,50 were in non-MDT group and 41 were in MDT group.The mortality in MDT group (2.4％,1/41) was lower than that in non-MDT group (18.0％,9/50),the difference was statistically significant (P ＜ 0.05).The median time of mechanical ventilation of giant omphalocele in non-MDT group (18.3 hours) was longer than that in MDT group (41.7 hours),the difference was also statistically significant (P ＜ 0.05).After adjusting for the associated confounding risk factors,the risk of death in non-MDT group was 54 times higher than that in MDTgroup (OR=54.19,95％CI2.64 ～1 113.49,P＜0.05).Conclusion There was significant association between the MDT management and the decreased risk of death of omphalocele.

Detection of chromosomal abnormalities in abortic tissues derived from patients with recurrent abortions using BoBs technique / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of BACs-on-Beads (BoBs) technique for the detection of chromosomal abnormalities in abortus tissues from recurrent pregnancy loss.@*METHODS@#A total of 109 abortus samples were collected and analyzed with the BoBs technique. The incidence and types of chromosomal abnormalities for different age groups and gestational weeks were compared.@*RESULTS@#The BoBs assay has succeeded in all cases, with an incidence for chromosomal abnormalities reaching 62.39% (68/109). The major findings included trisomy 16 (12/68), trisomy 22 (9/68), trisomy 13 (9/68) and trisomy 21 (8/68). The abnormal rate was significantly higher in those above 35-year-old compared with that of the 0.05). The aberration rates were similar for samples derived from second, third and fourth time abortions (P>0.05).@*CONCLUSION@#BoBs technique can detect chromosomal aberrations in miscarriages and may be routinely used for the analysis of early spontaneous abortions.

The role of specific carbohydrate diet in pediatric inflammatory bowel disease / 中华实用儿科临床杂志

Nutrition treatment plays an important role in the treatment and follow - up management of pediatric inflammatory bowel disease (IBD). The theory of specific carbohydrate diet(SCD),first presented in 1951,is a strict diet limitation focused on the sorts of carbohydrate:monosaccharide is the only kind of carbohydrate that is permitted, disaccharide and most complex carbohydrate like polysaccharide and starch are eliminated,intake of protein and fat is not limited,and processed meat and other processed food are cut down appropriately. Currently,mechanism of SCD diet′s treatment efficacy on IBD is not elucidated clearly. The hypothesis of this theory is:(1)Bowel inflammation of IBD patients leads to the decline of disaccharidase′s function,thus glucose,galactose and fructose are the only kinds of car-bohydrate that can be absorbed. (2)Occurrence of IBD is related to the disorder of bowel bacteria. The change of diet may regulate the bowel bacteria,which may be helpful to the symptoms of IBD. Retrospective case studies and case re-ports preliminarily indicated the efficacy of SCD in improving pediatric IBD symptoms and maintenance of clinical re-mission. However,high level evidence is still required to support the hypothesis. The limitation of carbohydrate by SCD would be the clue for the diet of pediatric IBD patients. However,the menu should be formulated according to the eating habits and the available food,as well as the requirement of the growth and development in children.

Nutritional risk screening of inpatient children with singer-center gastroenterological diseases in Sichuan province / 中华实用儿科临床杂志

Objective To evaluate the application of clinical Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP),and to investigate the nutritional risks of inpatient children with gastroenterological diseases in Sichuan province and their associated clinical characteristics and the features of hygiene economics.Methods STAMP was utilized for nutrition screening of inpatient children with gastroenterological diseases in Chengdu Women and Children's Central Hospital from January 2015 to March 2017.All the enrolled children were divided into 3 groups according to the STAMP scores:low risk group (LR group),moderate risk group (MR group) and high risk group (HR group).Clinical and economic data were compared among 3 groups.Results A total of 3 672 assessments were accomplished,including 2 372 times for males and 1 300 times for females (＜ 2 years old:2 021 times,2-5 years old:803 times,＞5 years old:848 times).Among them,147 children were identified as LR(4.00％),2 296 children as MR (62.53％),and 1 229 children as HR (33.47％).Statistically significant differences were observed among 3 groups in average length of hospital stay (P ＜0.001),the total cost at hospital (P ＜0.001),drug cost (P ＜ 0.001),antibiotic use (x2 =21.66,P ＜ 0.001),parenteral nutrition administration (x2 =46.43,P ＜ 0.001),blood products use (x2 =45.00,P ＜ 0.001),while there was no significant difference in re-admissions for over 3 times (P ＞ 0.05).Malnutrition rate was 4.08％ (6/147 cases) in LR group,2.05％ (47/2 296 cases) in MR group and 31.90％ (392/1 229 cases) in HR group,respectively,and among them 146 patients were diagnosed as severe malnutrition.Digestive tract infections were the most common diseases in MR group(66.33％,1 523/2 296 cases) and HR group(68.27％,839/1 229 cases).Moreover,children with stomatitis,gastrointestinal postoperation,acute pancreatitis,inflammatory bowel disease,esophageal diseases,digestive malformations,cyclic vomiting,malnutrition,and acute intestinal obstruction were all in HR group.Conclusions Nutritional risk is likely to raise the burden of disease.STAMP is applicabile clinically when it is utilized for nutrition risk screening of inpatient children with gastroenterological diseases in Sichuan province and provides evidence for nutrition support treatment.