A new strategy for evaluating antitumor activity in vitro with time-dimensional characteristics of RTCA technology / 中国药理学通报

Aim To analyze the anti-A549 and HI299 lung ade-nocarcinoma activities via using examples of baicalin, astragalo-side, hesperidin and cisplatin based on real time cellular analysis (RTCA) technology, and to build a new strategy for EC50 e-valuation reflecting the time-dimensional characteristic. Methods Using RTCA Software Pro for data analysis and GraphPad Prism and Origin Pro plotting, the in vitro anti-A549 and H1299 lung adenocarcinoma activities of baicalin, astragaloside, hesperidin, and cisplatin were characterized using the endpoint method and time dimension, respectively. Results (X) There were significant differences in EC50 values of A549 and H1299 cells at 24 h and 48 h endpoint methods. (2) The correlation coefficient of the curve fitted with the four-parameter equation was > 0. 9, and the dynamic change of EC50 remained relatively stable (the linear fitting of EC50 at adjacent 4 points I slope 1

A case-control study on gut microbiota diversity and species composition in obese/overweight children aged 2-6 years in Shanghai / 环境与职业医学

Background Multiple studies have shown a close relationship between changes in gut microbiota composition and obesity, and research results are influenced by factors such as race and geographical location, but there are few studies on children. Objective To analyze the diversity of gut microbiota related to obesity in a population of 2-6 years old, observe the distribution characteristics and species differences of gut microbiota between obese/overweight and normal weight groups, and explore the association betweenobese/overweight and gut microbiota diversity. Methods Fecal samples were collected from 74 children aged 2-6 years in Shanghai, including 18 obese/overweight individuals, 6 males and 12 females (male to female ratio of 1∶2), and 56 normal weight individuals, 18 males and 38 females (male to female ratio is nearly 1∶2). The 16S rDNA was extracted from bacteria in fecal samples, followed by PCR amplification, cDNA construction, and high-throughput sequencing. Naive Bayes algorithm was used to perform taxonomic analysis (phylum, class, order, family, genus, species) and community diversity analysis (Sobs index, Shannon index, Shannoneven index, Coverage index, PD index, and principal co-ordinates analysis) on representative sequences and abundance of amplicon sequence variants (ASV). Wilcoxon rank sum test, P-value multiple test correction, and analysis of similarities were used to test differences between the two groups to obtain information on the distribution characteristics and species differences of intestinal microbiota in children. Results Seventy-four fecal samples were sequenced, and the sequencing results were subjected to quality control and filtering. A total of 4905306 optimized sequences were obtained, resulting in 1860 ASVs. The diversity data analysis of ASVs generated 889 species annotation results at 8 taxonomic levels. The alpha diversity analysis showed that the richness (Sobs index), diversity (Shannon index), evenness (Shannoneven index), and phylogenetic diversity (PD index) of fecal community of the obese/overweight children were increased compared to those of the normal weight children, but there were no statistical differences between the two groups (P>0.05). The beta diversity analysis showed that there was little difference in the composition of microbial species between the two groups, and no significant clustering separation was observed. The results of species composition analysis at phylum, order, family, and genus levels of 74 samples showed a consistent core microbiota structure in the two groups of gut microbiota, but there were differences in microbiota composition. The differences in microbial community composition between the two groups were manifested at the taxonomic levels of order, family, and genus, among which phylum Firmicutes, order Erysipelotrichales, family Erysipelatocyclostridiaceae, genus Erysipelotrichaceae_ UCG-003 and genus Catenibacterium were significantly enriched in the obese/overweight group and contributed significantly to the phenotypic difference of obese/overweight [linear discriminant analysis (LDA)=3.72, P<0.01; LDA=3.29, P<0.05). Phylum Proteobacteria, order Enterobacterales, family Enterobacteriaceae, genus unclassified was significantly enriched in the normal weight group and contributed significantly to the phenotypic difference of normal body weight (LDA=3.93, P<0.05). Conclusion The richness and diversity of gut microbiota in obese/overweight children aged 2-6 years in Shanghai are increased, but there is no difference compared to normal weight children. There is a difference in the composition of gut microbiota between the obese/overweight group and the normal weight group.

Effect of pre-pregnancy obesity on trimester-specific thyroid dysfunction / 上海预防医学

ObjectiveTo explore the risk of different levels of pre-pregnancy obesity on trimester-specific thyroid dysfunction. MethodsQuestionnaire information， blood samples， and urine samples from a 2017 pregnancy cohort study in Shanghai， China were collected. A total of 2 455 pregnant women were included in the analysis. Pre-pregnancy BMI was calculated based on the height and self-reported pre-pregnancy weight. Serum TSH， total thyroxine （TT4）， free thyroxine （FT4）， total triiodothyronine （TT3）， free triiodothyronine （FT3）， thyroid globulin antibody（TgAb）， and Thyroid peroxidase antibody （TPOAb） were measured using the electrochemiluminescence method. Urine iodine levels were measured using the acid digestion method. Levels of thyroid function indexes of pregnant women with different degrees of obesity during pre-pregnancy were compared， and trimester-specific thyroid dysfunction was evaluated according to the reference range of trimester-specific thyroid hormone established by this cohort. Multivariate logistic regressions analysis was used to assess the correlation between pre-pregnancy obesity and trimester-specific thyroid dysfunction. ResultsAs the degree of obesity increased， maternal levels of FT3 and TT3 gradually increased during pregnancy （P<0.001， P=0.001）， while FT4 levels gradually decreased （P=0.001）. Multivariate logistic regression analysis showed that compared with the normal weight group， pregnant women who were overweight or obesity before pregnancy had a significantly higher risk of hypothyroxinemia （OR=3.85， 95%CI： 2.08‒7.14， P<0.001） and high TT3 （OR=2.78， 95%CI： 1.45‒5.26， P=0.002） during pregnancy. ConclusionPre-pregnancy overweight or obesity can increase the risk of thyroid dysfunction during pregnancy.

Preparation of silk fibroin/hyaluronic acid composite hydrogel based on thiol-ene click chemistry / 浙江大学学报·医学版

OBJECTIVES@#To design and prepare silk fibroin/hyaluronic acid composite hydrogel.@*METHODS@#The thiol modified silk fibroin and the double-bond modified hyaluronic acid were rapidly cured into gels through thiol-ene click polymerization under ultraviolet light condition. The grafting rate of modified silk fibroin and hyaluronic acid was characterized by 1H NMR spectroscopy; the gel point and the internal microstructure of hydrogels were characterized by rheological test and scanning electron microscopy; the mechanical properties were characterized by compression test; the swelling rate and degradation rate were determined by mass method. The hydrogel was co-cultured with the cells, the cytotoxicity was measured by the lactate dehydrogenase method, the cell adhesion was measured by the float count method, and the cell growth and differentiation on the surface of the gel were observed by scanning electron microscope and fluorescence microscope.@*RESULTS@#The functional group substitution degrees of modified silk fibroin and hyaluronic acid were 17.99% and 48.03%, respectively. The prepared silk fibroin/hyaluronic acid composite hydrogel had a gel point of 40-60 s and had a porous structure inside the gel. The compressive strength was as high as 450 kPa and it would not break after ten cycles. The water absorption capacity of the composite hydrogel was 4-10 times of its own weight. Degradation experiments showed that the hydrogel was biodegradable, and the degradation rate reached 28%-42% after 35 d. The cell biology experiments showed that the cytotoxicity of the composite gel was low, the cell adhesion was good, and the growth and differentiation of the cells on the surface of the gel were good.@*CONCLUSIONS@#The photocurable silk fibroin/hyaluronic acid composite hydrogel can form a gel quickly, and has excellent mechanical properties, adjustable swelling rate and degradation degree, good biocompatibility, so it has promising application prospects in biomedicine.

The developments of silicosis drugs / 药学学报

Pneumoconiosis is the most common occupational disease in China, which severely endangers people's health. Depending on the inhaled air pollutants, pneumoconiosis is classified as anthracosis, silicosis, asbestosis, etc., among which silicosis is the most common and serious. Silicosis is a systemic, poor prognostic disease characterized by diffuse fibrosis of lung tissue, which is caused by long-term exposure to dust with high levels of free silicon dioxide (SiO2) in the occupational environment. Appropriate treatment in time is important for the disease. Unfortunately, no effective drugs have been approved to delay or even reverse pulmonary fibrosis caused by SiO2. This review briefly classifies potent therapeutic drugs and compounds in term of mechanisms, providing the probability for clinical treatment of silicosis.

Medication guidelines for glucagon-like peptide-1 receptor agonist （2023 edition） / 中国药房

The prevalence of diabetes in China is increasing year by year， and has become a health issue of close concern to the whole society. Glucagon-like peptide-1 （GLP-1） receptor agonist （GLP-1RA）， as a new class of glucose-lowering drugs， is now widely used in the treatment of type 2 diabetes mellitus （T2DM） because of its significant glucose-lowering efficacy and low risk of hypoglycemia. As the level of evidence for its effects on improving cardiovascular system and renal protection and reducing body mass continues to improve， its status in the treatment guidelines for T2DM is gradually increasing. Currently， nine GLP-1RA drugs have been approved for the clinical treatment of T2DM in China. Although all of these drugs exert hypoglycemic effects based on the activation of GLP-1 receptors in the body， the differences in their own structures and natural GLP-1 amino acid homology lead to large differences in pharmacokinetic parameters and clinical efficacy among different analogs. In order to enable clinicians and pharmacists to have a full understanding of the characteristics and clinical evidence of these analogs and to better perform their therapeutic effects， Liaoning Provincial Pharmaceutical Society organized clinical medicine and pharmacy experts to develop a medication guide for nine GLP-1RA drugs to provide a reference for clinical medication needs and promote rational and standardized use by compiling and summarizing the pharmacological characteristics， clinical applications， adverse reactions， interactions， the medications in special populations and medication management.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Pure single-port lumpectomy non-lipolysis breast-conserving surgery in the treatment of early-stage breast cancer / 中华内分泌外科杂志

Objective:To summarize the clinical data and experience of pure single-port lumpectomy non-lipolysis breast-conserving surgery (PSLN-BCS) in patients with early-stage breast cancer.Methods:A retrospective analysis was conducted on 400 patients who underwent breast-conserving surgery for early-stage breast cancer in the Second Department of Breast Surgery at Harbin Medical University Cancer Hospital from Jan. 2022 to Jan. 2023. Patients were divided into two groups: PSLN-BCS group ( n=200) and conventional breast-conserving surgery (C-BCS) group ( n=200). The surgical time, intraoperative blood loss, postoperative drainage within three days, and short-term (3 months to 6 months after surgery) complications, including the incidence of residual fluid after drain removal and incision infection were observed. Long-term (6 months after surgery) complications, including the incidence of skin and pectoralis major muscle adhesions in the surgical area and cosmetic results after breast-conserving surgery, were also evaluated. Statistical analysis was performed using R language, and quantitative data were expressed as mean ± standard deviation ( ± s) and analyzed using t-test, while count data were analyzed using χ2 test. A p-value less than 0.05 was considered statistically significant. Results:PSLN-BCS had a longer average surgical time than C-BCS (198.341min vs 62.961min, P<0.001, 95% CI:132.028 vs 138.732). PSLN-BCS had less intraoperative bleeding (18.824 ml vs 22.627 ml, P=0.003, 95% CI: -6.294 vs -1.311) and lower postoperative drainage volume (346.157 ml vs 406.191 ml, P<0.001, 95% CI: -70.571-a-49.496). There were no significant differences in short-term postoperative complications such as subcutaneous fluid accumulation ( χ2=2.33, P=0.127) or incisional infection ( χ2=0.14, P=0.708) between the two groups. The incidence of skin and muscle adhesions in the surgical area was lower in patients who underwent PSLN-BCS at 6 months postoperatively ( χ2=11.58, P<0.001). Patients who received PSLN-BCS achieved better cosmetic outcomes, with a statistically significant difference ( χ2=273.00, P<0.001) compared to those who received C-BCS. Conclusion:Pure single-port lumpectomy non-lipolysis breast-conserving surgery is a safe and effective treatment option for early-stage breast cancer and can be considered as a surgical option for patients with cosmetic requirements.

Lipopolysaccharides protect mesenchymal stem cell against cardiac ischemia-reperfusion injury by HMGB1/STAT3 signaling / 老年心脏病学杂志（英文版）

BACKGROUND@#Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.@*METHODS@#In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.@*RESULTS@#The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.@*CONCLUSIONS@#These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis / 中国中药杂志

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1β, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1β, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1β, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1β, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

PDCD6 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the AKT/GSK3β/β-catenin Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#Programmed cell death 6 (PDCD6), a Ca 2+-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs).@*METHODS@#The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.@*RESULTS@#The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.@*CONCLUSION@#PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.

Expression profiles and regulatory network of microRNA, long non-coding RNA and circular RNA in rat chronic stress depression model based on whole transcriptome technology / 解剖学报

[Abstract] Objective To explore the potential pathophysiological mechanism of depression by screening the expression profiles and competing endogenous RNA (ceRNA) regulatory network microRNA(miRNA), long non-coding RNA(lncRNA) and circular RNA (circRNA) in the hippocampus of chronic stress depression rat model. Methods Twelve SD rats were divided into blank group and model group. Chronic mild unpredictability stress (CUMS) was used to construct the rat model of depression. The whole transcriptome analysis was performed on the hippocampus of the rats, and the possible regulatory networks among lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were explored by bioinformatics method. Results According to the | fold change | ≥1. 5 and P≤0. 05, 29 differentially expressed miRNAs (21 up-regulated and 8 down-regulated), 686 differentially expressed lncRNAs (163 up-regulated and 523 down-regulated) and 8 differentially expressed circRNAs (3 up-regulated and 5 down-regulated) were identified. Gene Ontology (GO) and Kytot Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the target genes of miRNAs were mainly enriched in the Golgi apparatus and calcium ion binding process in the cell membrane, the functions of lncRNAs target genes involved nucleic acid binding regulation, cytokine and protein ubiquitination, etc, and the functions of host genes of circRNAs were associated with cellular stimulation response, metabolic process, catalytic activity and other processes. The ceRNA network of lncRNAs and circRNAs showed complex interactions between non-coding RNA (ncRNA) and mRNA related to synaptic plasticity, such as protein Wnt-sa(WNT5a) and collagentype III alpha1(COL8a1) related to axon orientation and laminin A2(LAMA2) related to neurodevelopment. Conclusion The ceRNA network of lncRNA and circRNA shows that the complex interaction betweens ncRNA and mRNA is highly associated with the neuroplasticity, which support the neuroplasticity hypothesis of depression.

Changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute isovolumic hemodilution and its influence on anesthetic effect after reinfusion / 中国临床药理学与治疗学

To investigate the changes of anesthetic drug concentration in plasma during isolation of autologous blood with acute normovolemic hemodiluti-on and its influence on the depth of anesthesia, muscle relaxant effect and blood drug concentration after reinfusion. METHODS: Forty patients of both sexes, aged 20-60 yr, American Society of Anesthesiologists physical status or Ⅱ, hemoglobin (Hb) >120 g / L, hematocrit (Hct) >35%, undergoing eletive multilevel spinal surgery were included, were divided into 2 groups (n=20 each) using a random number table. ANH group (group A): ANH was performed after stable induction of anesthesia, the target Hct value was 28%-30%, and autologous blood was reinfused after the main operation steps. Control group (group C): routine transfusion and infusion treatment. The bispectral index (BIS) and Train-of-Four stimulation (TOF) were observed and recorded at the stable induction of anesthesia (T1), 30 minutes of stable induction (T2), the end of operation (T3), 30 minutes after the end of the operation (T4), 1 hour after the end of the operation (T5) and 2 hours after the end of the operation (T6). The concentrations of propofol and cisatracurium besylate in plasma at T1-T6, stored blood at 1 h (TS1), 2 h (TS2), and before reinfusion (TS3) were detected by Liquid Chromatography-tandem Mass Spectrometry. The extubation time and recovery score at T4-6 hours were recorded. RESULTS: There was no significant difference in propofol between the two groups at each time point (P > 0.05). The plasma concentration of cisatracurium besylate in group A was higher than that in group C at T3 (P0.05). The BIS value at T4 and TOF value at T3 in group A were significantly lower than those in group C. The recovery score of group A was lower than that of group C at T4 (P0.05). CONCLUSION: The plasma concentrations of propofol and cisatracurium besylate were basically unchanged during the in vitro isolation of ANH autologous blood. The plasma concentrations of cisatracurium besylate were only temporarily affected after the main operation steps, but the postoperative muscle relaxation recovery and recovery quality were not significantly affected.

Application characteristics and modern research progress of "bone-approaching" acupuncture / 中国针灸

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.

Historical perspective and recent progress in cardiac ion channelopathies research and clinical practice in Hong Kong

Cardiac ion channelopathies encompass a set of inherited or acquired conditions that are due to dysfunction in ion channels or their associated proteins, typically in the presence of structurally normal hearts. They are associated with the development of ventricular arrhythmias and sudden cardiac death. The aim of this review is to provide a historical perspective and recent advances in the research of the cardiac ion channelopathies, Brugada syndrome, long QT syn‑ drome and catecholaminergic polymorphic ventricular tachycardia, in Hong Kong, China. In particular, recent works on the development of novel predictive models incorporating machine learning techniques to improve risk strati‑ fication are outlined. The availability of linked records of affected patients with good longitudinal data in the public sector, together with multidisciplinary collaborations, implies that ion channelopathy research efforts have advanced significantly.

Six1 gene methylation status in gastric cancer and relationship with clinicopathological characteristics and prognosis / 中国医师进修杂志

Objective:To detect the methylation status of sine oculis homeobox homolog1 (Six1) in patients with gastric cancer and analyze its relationship with the clinicopathological characteristics and prognosis of patients.Methods:The tumor and para-cancerous tissues of 148 patients with gastric cancer diagnosed and treated in Aerospace Center Hospital from September 2015 to December 2017 were collected. The methylation-specific PCR method (MSP) was used to detect the methylation status of the Six1 gene, and 100 normal people who underwent gastroscopy biopsy during the same period served as the control group. Univariate analysis and multivariate Logistic regression model were used to analyze the relationship between Six1 methylation status and clinical pathological characteristics of patients. Kaplan-Meier survival curve was used to analyze the relationship between Six1 methylation status and prognostic survival in patients with gastric cancer.Results:Six1 gene methylation rate in tumor tissue was lower than that in adjacent tissues or in control group, and the differences were statistically significant: 24.32%(36/148) vs. 89.19%(132/148), 96.00%(96/100)( P<0.05). Univariate analysis showed that Six1 gene methylation rate was higher in patients with tumor diameter <5 cm ( χ2 = 8.79, P = 0.003), TNM stage Ⅰ-Ⅱ ( χ2 = 4.93, P = 0.026), highly differentiated tumor ( χ2 = 8.74, P = 0.013), no lymph node metastasis ( χ2 = 4.64, P = 0.031), no distant metastasis ( χ2 = 4.38, P = 0.036), and no invasion of the serosa ( χ2 = 9.85, P = 0.002), and the differences were statistically significant. Multivariate analysis showed that TNM staging ( OR = 4.397, 95% CI 3.141 - 5.157, P = 0.014), tumor differentiation ( OR = 4.491, 95% CI 3.527 - 6.118, P = 0.007), lymph node metastasis ( OR = 4.208, 95% CI 3.823 - 5.195, P = 0.031), distant metastasis ( OR = 4.225, 95% CI 3.956 - 5.437, P = 0.026), and depth of invasion ( OR = 4.509, 95% CI 3.206 - 5.275, P = 0.011) of patients with gastric cancer were independent risk factors for Six1 gene methylation status. Till to March 2020, the mortality rate of the Six1 gene methylation group was lower than that of the Six1 gene unmethylated group: 44.44%(16/36) vs.71.43% (80/112), the difference was statistically significant ( χ2 = 8.70, P<0.05). The median survival time of gastric cancer patients with Six1 gene methylation was higher than that of Six1 gene unmethylated (49 months vs. 37 months), and the difference was statistically significant ( P = 0.019). Conclusions:There is unmethylation of Six1 gene in patients with gastric cancer, which may be involved with the occurrence of gastric cancer. Patients′ TNM stage, tumor differentiation degree, and lymph node metastasis are independent risk factors for Six1 gene methylation status in gastric cancer patients. The prognosis of gastric cancer patients with Six1 gene methylation is better.

Machine learning techniques for arrhythmic risk stratification: a review of the literature

Ventricular arrhythmias (VAs) and sudden cardiac death (SCD) are significant adverse events that affect the morbidity and mortality of both the general population and patients with predisposing cardiovascular risk factors. Currently, conventional disease-specific scores are used for risk stratification purposes. However, these risk scores have several limitations, including variations among validation cohorts, the inclusion of a limited number of predictors while omitting important variables, as well as hidden relationships between predictors. Machine learning (ML) techniques are based on algorithms that describe intervariable relationships. Recent studies have implemented ML techniques to construct models for the prediction of fatal VAs. However, the application of ML study findings is limited by the absence of established frameworks for its implementation, in addition to clinicians’ unfamiliarity with ML techniques.This review, therefore, aims to provide an accessible and easy-to-understand summary of the existing evidence about the use of ML techniques in the prediction of VAs. Our findings suggest that ML algorithms improve arrhythmic prediction performance in different clinical settings. However, it should be emphasized that prospective studies comparing ML algorithms to conventional risk models are needed while a regulatory framework is required prior to their implementation in clinical practice

Advances in mechanisms for inflammation-associated colon carcinogenesis and chemoprevention / 药学学报

Colorectal cancer is a common malignant tumor of digestive tract, and the risk of inflammatory bowel disease developing into colorectal cancer is significantly increased. Immune signaling pathways NF-κB, IL-6/STAT3, COX-2/PGE2, IL-23/Th17 and TLRs have been confirmed to promote the transformation from colitis to colorectal cancer. NOD2 and intestinal microbes also participate in the regulation of inflammation mediated carcinogenesis. Chronic inflammation is a potential risk for colorectal cancer, and anti-inflammatory drugs may play a chemical preventive role. In this review, we summarize the signaling pathways involved in inflammation-associated colon carcinogenesis and evaluate the chemoprophylaxis of colon cancer.

Role and mechanism of IGF2BP3 in malignant transformation of human gastric epithelial cells induced by MNNG / 环境与职业医学

Background N6-methyladenosine (m6A) RNA methylation may play an important role in the process of malignant transformation of cells induced by environmental carcinogens. However, the specific roles and mechanisms need to be further explored. Objective To explore the role and mechanism of m6A binding protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the malignant transformation of human gastric mucosal epithelial cells GES-1 induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods Based on the GES-1 malignant transformation cells MC-30, a stable knockdown IGF2BP3 MC-30 cell line (MC30-shIGF2BP3, abbreviated as MC30-shI3) was constructed by lentiviral transfection technology, and a negative control group (MC30-NC) was also prepared. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were applied to detect the mRNA expression and protein levels of IGF2BP3. RNA binding protein immunoprecipitation (RIP-qPCR) was used to examine the combination between IGF2BP3 protein and MYC mRNA in malignant cells MC-30. Furthermore, the stability of MYC mRNA was detected by actinomycin D assay. CCK-8 and Transwell respectively were employed to detect cell proliferation, migration, and invasion. Western blotting was applied to detect the expression of EMT markers (N-cadherin, Vimentin, α-SMA, and Snail). The role of the downstream target gene MYC was further elucidated by a rescue assay in MC30-shI3 cells transfected with a plasmid overexpressing MYC to observe changes in cellular phenotypes (proliferation, migration, invasion) and expression of key EMT proteins. Results Compared with the control group, the expression of IGF2BP3 mRNA was up-regulated after 5, 10, 20, and 40 μmol·L−1 MNNG infection of GES-1 cells (P<0.05). After 20 μmol·L−1 MNNG infection, the expression level of IGF2BP3 mRNA increased with prolongation of exposure time (P<0.05). Compared with the control group, the mRNA and protein expression levels of IGF2BP3 were up-regulated in the 10th, 20th, and 30th generations of 5 μmol·L−1 MNNG malignant transformation (P<0.05). The results of qRT-PCR and Western blotting showed that, compared with the MC30-NC group, the IGF2BP3 and MYC mRNA expression and protein expression decreased in the MC30-shI3 group (P<0.01). The CCK8 and transwell assay results showed that, compared with the MC30-NC group, the cell proliferation, migration, and invasion abilities significantly reduced in the MC30-shI3 group (P<0.01). The results of the Western blotting showed that, compared with the MC30-NC group, the protein levels of EMT markers N-cadherin, Vimentin, α-SMA, and Snail decreased in the MC30-shI3 group (P<0.01). The results of RIP-qPCR showed that, compared with the IgG group, the mRNA level was higher for the enriched MYC in the IGF2BP3 group (P<0.01); the results of the actinomycin D assay showed that, compared with the MC30-NC group, the stability of MYC mRNA significantly reduced in the MC30-shI3 group (P<0.01). While the rescue experiment showed that, compared with the IGF2BP3 knock-down+vector group, the MYC protein level significantly increased in the IGF2BP3 knock-down + MYC over-expression group (P<0.01), the proliferation, migration, and invasion abilities significantly enhanced (P<0.01), and the EMT key proteins (N-cadherin, Vimentin, α-SMA, Snail) increased in the MC30-shI3+MYC group (P<0.01). Conclusion Exposure to MNNG could result in up-regulation of IGF2BP3 expression in GES-1 cells. IGF2BP3 may enhance the proliferation, migration, and invasion of malignantly transformed human gastric epithelial cells by binding to MYC mRNA and increasing its stability and expression level and thus promoting the EMT process, which in turn affects the progression of malignant transformation.