The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification / 中国药理学通报

Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.

Effects of total ginsenosides from Panax ginseng stems and leaves on gut microbiota and short-chain fatty acids metabolism in acute lung injury mice / 中国中药杂志

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.

Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS / 中国中药杂志

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 μg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice / 中国结合医学杂志

OBJECTIVE@#To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice.@*METHODS@#Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing.@*RESULTS@#Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism.@*CONCLUSION@#APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Study on the Mechanism of Multi-Drug Resistance of Agaricus Blazei Extract FA-2-b-β Mediated Wnt Signaling Pathway to Reverse Acute T Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the mechanism of drug reversing resistance of Agaricus blazei extract FA-2-b-β on T cell acute lymphoblastic leukemia (T-ALL) cell lines.@*METHODS@#Cell proliferation was detected by CCK-8 assay; the apoptosis, cell cycle mitochondrial membrane potential, and intracellular rhodamine accumulation were detected by flow cytometry, and apoptosis-related gene and protein expression were detected by qPCR and Western blot; the membrane surface protein MDR1 was observed by immunofluorescence microscopy.@*RESULTS@#Different concentrations of FA-2-b-β significantly inhibited proliferation and induced apoptosis of CCRF-CEM and CEM/C1 (P<0.05), and CCRF-CEM cell cycle were arrested at S phase, and CEM/C1 cells were arrested at G0/G1 phase. Western blot and qPCR results show that FA-2-b-β inhibited ABCB1、ABCG2、CTNNB、MYC and BCL-2 expression, but upregulated Bax expression. In addition, FA-2-b-β reversed the resistance characteristics of CEM/C1 drug-resistance cells, which decreased mitochondrial membrane potential, and significantly increased the intracellular rhodamine accumulation, and weakening of the expression of the membrane surface protein MDR1. With the Wnt/β-catenin inhibitor (ICG001), the process was further intensified.@*CONCLUSION@#Agaricus Blazei Extract FA-2-b-β inhibits cell proliferation, promotes apoptosis, regulates the cell cycle, reduces mitochondrial energy supply, and down-regulate MDR1 expression to reverse the resistance of CEM/C1, which all suggest it is through regulating the Wnt signaling pathway in T-ALL.

Cell-derived nanovesicles from mesenchymal stem cells as extracellular vesicle-mimetics in wound healing

Wound healing is a dynamic process that involves a series of molecular and cellular events aimed at replacing devitalized and missing cellular components and/or tissue layers. Recently, extracellular vesicles (EVs), naturally cell-secreted lipid membrane-bound vesicles laden with biological cargos including proteins, lipids, and nucleic acids, have drawn wide attention due to their ability to promote wound healing and tissue regeneration. However, current exploitation of EVs as therapeutic agents is limited by their low isolation yields and tedious isolation processes. To circumvent these challenges, bioinspired cell-derived nanovesicles (CDNs) that mimic EVs were obtained by shearing mesenchymal stem cells (MSCs) through membranes with different pore sizes. Physical characterisations and high-throughput proteomics confirmed that MSC-CDNs mimicked MSC-EVs. Moreover, these MSC-CDNs were efficiently uptaken by human dermal fibroblasts and demonstrated a dose-dependent activation of MAPK signalling pathway, resulting in enhancement of cell proliferation, cell migration, secretion of growth factors and extracellular matrix proteins, which all promoted tissue regeneration. Of note, MSC-CDNs enhanced angiogenesis in human dermal microvascular endothelial cells in a 3D PEG-fibrin scaffold and animal model, accelerating wound healing in vitro and in vivo. These findings suggest that MSC-CDNs could replace both whole cells and EVs in promoting wound healing and tissue regeneration.

Four-Hour Fasting for Semifluids and 2-Hour Fasting for Water Improves the Patient Experience of Esophagogastroduodenoscopy: A Randomized Controlled Trial

Background/Aims@#We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol. @*Methods@#In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting. @*Results@#One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the “4+2” protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0–5.0] vs 4.0 [4.0–5.0], p=0.266). No adverse events were observed during the study. @*Conclusions@#The “4+2” protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD.

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Simultaneous determination of 17 kinds of free amino acid concentrations in cell culture medium by UPLC / 药学学报

To establish an ultra high performance liquid chromatography coupled with pre-column derivatization method for simultaneous determination of 17 kinds of free amino acid concentrations in CHO cell which expressed high levels of programmed death protein-1 (PD-1) antibody, and its amino acid metabolism was analyzed by this method. Using 6-aminoquinoline-N-hydroxysuccinimidyl carbamate (AQC) as a derivatization reagent, the free amino acids in different concentrations of amino acid standards or cell lines were transformed into stable UV-absorbent compounds, which were separated by gradient elution through ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm) column. The flow rate was set at 0.7 mL·min-1, the column temperature at 55 ℃, the loading amount of sample at 1 µL, the UV detection wavelength at 260 nm, and then the free amino acid concentration in cell lines which expressed PD-1 antibody was determined by external standard method. According to the changes of amino acids concentration during the process of cell culture, the amino acid metabolism was analyzed. The results showed that pre-column derivatization high performance liquid chromatography could completely separate 17 kinds of amino acids within 11 minutes, has good linear relationship (R2 ≥ 0.999 3) in the range of 0.75-500 μmol·L-1, the limits of detection was 0.1-0.3 μmol·L-1, the limits of quantitative was 0.5-1 μmol·L-1. The established method is quickly and reproducibility. Amino acid metabolism revealed that methionine, isoleucine and leucine may be the restrictive factors of expression for cell line. This method can be used for detection changes of free amino acid concentration in cell line.

The influence of homogeneous medical concept combined with focused nursing on the body function of postoperative colostomy patients with colorectal cancer and nursing evaluation / 中国实用护理杂志

Objective:To explore effect of homogeneous medical concept nursing mode combined with focused solution mode on self-efficacy and immunity function and nursing satisfaction analysis of patients with postoperative enterostomy of colorectal cancer.Methods:A total of 102 patients with colorectal cancer undergoing postoperative enterostomy admitted to Suining Central Hospital from December 2019 to December 2020 were selected and divided into control group and observation group according to random number table method, with 52 cases in observation group and 50 cases in control group. The control group received homogeneous medical concept nursing mode, and the observation group combined with the focused solution mode nursing intervention on this basis. The self-efficacy, immune function and nursing satisfaction of the two groups were compared.Results:The general self-efficacy of the observation group was higher than that of the control group ( χ2=2.61, P<0.05). After nursing, the stomato-related self-efficacy score of the observation group was 102.69 ± 12.37, which was higher than that of the control group (90.13±11.22). There was significant difference between the two groups ( t= 5.37, P<0.05). There was no significant difference in peripheral blood CD3+, CD4+ and CD4+/CD8+ and NK levels between 2 groups one day after surgery ( P>0.05). The levels of CD3+, CD4+ and CD4+/CD8+ and NK in peripheral blood of the observation group after nursing care were (67.21 ± 6.21)%, (67.22 ± 8.76)%, (2.65 ± 0.45)% and (19.50 ± 2.05)%, respectively, which were higher than those of the control group (60.32 ± 5.45)%, (60.21 ± 8.25)%, (2.41 ± 0.32)% and (15.62 ± 1.81)%. The differences were statistically significant ( t=5.95, 4.21, 3.11, all P<0.05). The total satisfaction rate of nursing in the observation group was 98.08% (51/52), which was higher than 84.00% (42/50) in the control group, and the difference was statistically significant ( χ2= 2.63, P<0.05). Conclusions:The application of homogenous medical concept nursing mode combined with focused solution mode in colorectal cancer postoperative enterostomy patients is helpful to improve patients' self-efficacy, enhance patients ′ immune function, and improve nursing satisfaction degree, which is worthy of further promotion in clinical practice.

Clinical, Endoscopic and Pathological Characteristics of Crawling - type Early Gastric Adenocarcinoma / 胃肠病学

Background: Crawling-type gastric adenocarcinoma is a rare subtype of gastric cancer, however, the understanding on this special entity of gastric cancer is still lacking. Aims: To investigate the clinical, endoscopic and pathological characteristics of crawling-type early gastric adenocarcinoma. Methods: Patients diagnosed as crawling-type early gastric adenocarcinoma in Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were recruited consecutively in a retrospective study. The clinical data were reviewed, the pathological specimens were collected for immunohistochemical staining, and a telephone follow-up was conducted for prognosis analysis. Results: Fourteen patients with crawling-type early gastric adenocarcinoma and fulfilling the inclusion criteria were enrolled in the study, of them, 9 were male, 5 were female, and the mean age was 65.9 years old. No family history of gastric cancer was reported. The clinical manifestations were not specific. All patients were positive for Helicobacter pylori (Hp) infection. Tumors were more likely to occur in the middle and lower thirds of the stomach, with marked atrophic background mucosa. Macroscopically, 11 lesions were superficial-depressed (0-IIc) and 3 were superficial-flat type (0-IIb+ IIc). The color of the lesions was red. Lesions with indistinct border were observed endoscopically in 10 cases. Complete resection was achieved in all 14 patients after endoscopic submucosal dissection n=10 or surgical treatment n=4. Three submucosal and 11 intramucosal infiltration were observed pathologically. Immunohistochemical results of gastric (MUC5AC and MUC6) and intestinal (MUC2, CD10 and CDX-2) markers showed that most of the patients were mixed immunophenotype; the Ki-67 index ranged mostly between 30% and 70%. In a mean follow-up time of 38 months, all 14 patients were survived. Two patients with heterochronous early gastric cancer were found by follow-up endoscopy. Conclusions: When a superficial-depressed or superficial-flat type tumor with reddish color change and atrophic background mucosa is observed endoscopically in an Hp-positive patient, the possibility of crawling-type early gastric adenocarcinoma should be considered. Adequate preoperative evaluation should be carried out to judge the extent and depth of tumor invasion, which may guide the decision of treatment strategy. Postoperative endoscopic surveillance is recommended.

Analysis of m / 中国生物化学与分子生物学报

In this study, we performed high-throughput sequencing technology methylated RNA immunoprecipitation sequencing (MeRIP-seq), transcriptome sequencing (RNA-seq) and bioinformatics to analyze the differentially m6A-methylated and differentially expressed profile of circular RNA (circRNA) in middle cerebral artery occlusion/reperfusion (MCAO/R) model, which provided some scientific evidences for revealing the relationship between RNA epigenetic modification and cerebral ischemia reperfusion injury. The neurological deficit scores of mice were evaluated by the Longa score standard. TTC staining was used to detect cerebral infarction volumes, and dot blot was used for the quantification of m

Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma / 中国医学科学院学报

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

Analysis of clinical pathological characteristics of high-level squamous endotausal lesions in the postmenopausal cervix / 中国综合临床

Objective:To investigate the clinical pathologic features of high-grade squamous intraepithelial lesions (HSIL) in postmenopausal women.Methods:The clinical data of hospital patients with HSIL admitted to the Department of Gynecology of The First People's Hospital of Lianyungang, Jiangsu Province from January 2019 to December 2020 were retrospectively analyzed. Patients undergoing liquid-based thin-layer cytology, high-risk human papillomavirus (HR-HPV), colposcopy, cervical biopsy and Endocervical curettage (ECC), pathological diagnosis of HSIL, followed by cold knife conization (CKC). The diagnosis and treatment process conformed to the cervical cancer diagnosis and treatment norms, and there were a total of 594 patients with no previous cervical surgery history,including 463 cases in the premenopausal group and 131 cases in the menopausal group, and the age, contact bleeding, gynecological examination, HR-HPV, liquid-based thin layer cytology, colposcopy and biopsy results, and post-cervical cone surgery pathological results were compared and analyzed, and multivariate Logistic regression analysis was carried out for statistically different factors to identify the clinical pathological characteristics of postmenopausal HSIL patients. T-test was used for the comparison between measurement data groups with normal distribution, and rank sum test was used for the comparison between measurement data groups with non normal distribution. Counting data use χ 2 test or Fisher exact probability method. Logistic regression analysis was used in multivariate analysis. Results:There was no significant difference in the positive rate of contact bleeding (12.98%(17/131)) and HR-HPV (77.86%(102/131)) between postmenopausal group and non postmenopausal group (11.45%(53/463) and 80.56% (373/463))(χ 2 values were 0.23 and 0.46; P values were 0.632 and 0.496). The proportion of cervical columnar epithelium displacement (43.51% (57/131)) and abnormal liquid-based thin-layer cytology (87.79%(115/131)) in the postmenopausal group were lower than those in the non postmenopausal group (64.36%(298/463) and 93.74%(434/463)). There was significant difference between the two groups (χ 2 values were 18.46 and 5.16; P values were < 0.001 and 0.023). The positive rate of ECC (62.60%(82/131)), cervical type Ⅲ transformation area (73.28%(96/131)), the proportion of pathological upgrading after conization (9.92%(13/131)) and the positive rate of cutting edge after conization (24.43%(32/131)) in menopausal group were higher than those in non menopausal patients (46.22%(214/463), 26.78%(124/463), 1.73%(8/463) and 5.40%(25/463)). There were significant differences between the two groups (χ 2 values were 10.95, 94.68, 20.11 and 42.62; P values were 0.001, <0.001, <0.001 and <0.001). Multivariate Logistic regression analysis showed a high proportion of cervical type Ⅲ transformational zones ( OR=6.569, 95% CI 4.130-10.446), high ECC positivity ( OR=1.978, 95% CI 1.250-3.128), the positive rate of cone incision margins was high ( OR=4.581, 95% CI 2.386-8.794), the proportion of pathological escalation after cone surgery ( OR=4.612, 95% CI 1.557-13.668) and the proportion of smooth cervical appearance were high ( OR=0.464, 95% CI 0.294-0.731), which was the clinicopathological feature of postmenopausal HSIL ( P values were <0.001, 0.004, <0.001, 0.006 and 0.001). Conclusion:There were differences in HSIL in patients before and after menopause, clinical symptoms and screening manifestations were atypical, and lesions are easy to involve the cervical canal, the positive rate of the cut margin after coneectomy was high, and the proportion of pathological escalation was high, so more aggressive intervention should be taken for women diagnosed with precancerous cervical lesions after menopause

Severe COVID-19-associated sepsis is different from classical sepsis induced by pulmonary infection with carbapenem-resistant klebsiella pneumonia (CrKP) / 中华创伤杂志(英文版)

PURPOSE@#COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis.@*METHODS@#In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively.@*RESULTS@#A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO@*CONCLUSION@#Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.

Literature analysis of hot topics on occupational noise-induced hearing loss / 中华劳动卫生职业病杂志

Objective: To analyze the literature of related research reports on occupational hearing loss (ONIHL) , study the characteristics of the subject and determine the research hotspots. Methods: In December 2020, PubMed database was searched by bibliometrics for ONIHL published in PubMed database from January 1971 to December 2020. Bicomb 2.03 software was used to extract the subject. The publication year, publication country, source magazine and subject words were summarized and analyzed. Results: A total of 1 473 papers were included in this study, and the number of papers was 66 from 1971 to 1980, and 628 from 2011 to 2020, an increase of nearly 10 times. The top three countries were the United States, China and Germany, with 31.5% (464/1473) , 11.5% (171/1473) and 6.2% (91/1473) ; The cross-sectional study was the most applied type; The top five words for 2011-2020: Mental Illness, polymorphism, cardiovascular disease, high frequency hearing impairment and standards and regulations. Conclusion: Susceptibility Genes, Psychological Disorders, Cardiovascular Diseases and Risk Assessment are hot areas in ONIHL at present. Researchers should focus on major fields and grasp future trends as a whole.

Application value of intravoxel incoherent motion imaging in preoperative evaluating the perineural invasion of esophageal squamous cell carcinoma: a prospective study / 中华消化外科杂志

Objective:To investigate the application value of intravoxel incoherent motion (IVIM) imaging in preoperative evaluating perineural invasion (PNI) of esophageal squamous cell carcinoma (ESCC).Methods:The prospective study was conducted. The clinicopathological data of 63 ESCC patients who underwent IVIM imaging before surgery in the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital from January 2016 to April 2019 were selected. Patients underwent routine magnetic resonance imaging scan and IVIM sequence examination. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*) and pseudodiffusion fraction (f) values were measured. Observation indicators: (1) situations of enrolled patients; (2) IVIM examination of PNI of ESCC and its diagnostic efficiency. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The interclass correlation coefficient (ICC) was used to evaluate cosistency of results. The receiver operating characrteristic curve was used to evaluate diagnostic efficiency. Results:(1) Situations of enrolled patients. A total of 63 patients were selected for eligibility. There were 41 males and 22 females, aged 60(range, 43?74)years. Of the 63 ESCC patients, 17 cases had PNI and 46 cases had no PNI. Cases with well differentiated tumor, moderate differentiated tumor or low differentiated tumor, cases in stage T1, T2, T3, T4 of infiltra-tion depth, cases with or without lymph node metastasis were 0, 6, 11, 0, 3, 13, 1, 15, 2 in patients with PNI, versus 6, 24, 16, 1, 22, 23, 0, 12, 34 in patients without PNI, showing significant differences between them ( Z=?2.32, ?2.49, χ2=19.58, P<0.05). (2) IVIM examination of PNI of ESCC and its diagnostic efficiency. The ADC, D, D*, f values were (2.21±0.33)×10 ?3 mm 2/s, (1.46±0.31)×10 ?3 mm 2/s, 32.50 (15.55,46.75)×10 ?3 mm 2/s, (0.34±0.09)×10 ?3 mm 2/s in patients with PNI, versus (2.45±0.45)×10 ?3 mm 2/s, (1.72±0.38)×10 ?3 mm 2/s, 34.85(23.43,51.20)×10 ?3 mm 2/s, (0.42±0.13)×10 ?3 mm 2/s in patients without PNI, showing significant differences in the ADC, D and f values between them ( t=?2.03, ?2.52, ?2.34, P<0.05) and no significant difference in the D* value between them ( Z=?0.84, P>0.05). The cosistency of ADC, D, D* and f values in the 63 ESCC patients measured by 2 radiologists was good, with the ICC as 0.96, 0.92, 0.89 and 0.95. The receiver operating characrteristic curve demons-trated the best cut-off value of ADC, D and f values were 2.50×10 ?3 mm 2/s, 1.68×10 ?3 mm 2/s and 0.41, with the areas under the curve as 0.67 (95% confidence interval as 0.54?0.79), 0.70 (95% confidence interval as 0.58?0.81) and 0.69 (95% confidence interval as 0.57?0.80), respectively. The combina-tion of D and f value for diagnosing PNI of ESCC had the area under the curve as 0.74 (95% confidence interval as 0.62?0.84), with the cut-off value as 0.20, sensitivity and specificity as 94.1% and 56.5%. Conclusions:IVIM parameters D and f values can evaluate and predict the PNI of ESCC preopera-tively. The combination of D and f values can further improve the diagnostic efficiency.

Treatment and prognosis of 826 infants with critical congenital heart disease: a single center retrospective study / 中华心血管病杂志

Objective: To analyze the current status of clinical treatment and factors influencing postoperative mortality in infants with critical congenital heart disease (CCHD) in China, optimize the perioperative management of CCHD, and provide a new scientific basis for clinical decision-making for the optimal management of these patients. Methods: This is a retrospective single-center study. Infants diagnosed with CCHD in Guangdong Provincial People's Hospital from January 2017 to December 2019 (aged 0-1 years at admission) were enrolled. General clinical information, inpatient treatment information, prognosis and complications were collected and analyzed. Multivariate logistic regression analysis was used to explore the independent risk factors of postoperative death in infants with CCHD. Results: A total of 826 infants with CCHD were included, including 556 males (67.3%) and the age at first admission was 51.0 (5.0,178.3) days. 264 (32.0%) cases were tetralogy of Fallot and 137 (16.6%) cases were total anomalous pulmonary venous return. 195 cases (23.6%) were diagnosed prenatally. 196 cases (23.7%) were treated with prostaglandin. The preoperative invasive ventilation time was 0 (0, 0) hour, and the postoperative invasive ventilation time was 95.0 (26.0, 151.8) hours. A total of 668 cases (80.9%) underwent surgical treatment. The age was 100.5 (20.0, 218.0) days during operation and the operation time was 190.0 (155.0, 240.0) hours. Sixty-two cases (7.5%) received medical treatment, and 96 cases (11.6%) gave up treatment. A total of 675 cases (81.7%) were discharged with improvement, 96 cases (11.6%) were discharged after giving up treatment, 55 cases (6.7%) died and 109 cases (13.2%) were readmitted within one year. Complications occurred in 565 (68.6%) cases, including pneumonia in 334 cases (40.4%) and cardiac arrhythmias in 182 cases (22.0%). Multifactorial analysis showed that delayed chest closure (OR=49.775, 95%CI 3.291-752.922, P=0.005), prolonged post-operative invasive ventilator ventilation (OR=1.003, 95%CI 1.000-1.005, P=0.038) and cardiac hypoplasia syndrome (OR=272.658, 95%CI 37.861-1 963.589, P<0.001) were the independent risk factors for mortality in CCHD infants post-operation. Conclusions: Tetralogy of Fallot and total anomalous pulmonary venous return account for the majority of infants with CCHD. The proportion of infants diagnosed prenatally was less than 1/4. The majority CCHD infants received surgical treatment. The main complications are pneumonia and arrhythmia. Delayed chest closure, prolonged postoperative invasive ventilator ventilation and low cardiac output syndrome are the independent risk factors for postoperative death in infants with CCHD.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.