Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Role of macrophages in heart failure and traditional Chinese medicine intervention / 中国中药杂志

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

Gene expression profile in human cervical epithelial cells infected with Chlamydia trachomatis / 中华微生物学和免疫学杂志

Objective:To compare gene expression profiles in normal human cervical epithelial cells (HcerEpic) before and after Chlamydia trachomatis ( Ct) infection. Methods:HcerEpic cells that were pretreated with DEAE-D were infected with Ct serotype E standard strain and then cultured for 44 h. Uninfected HcerEpic cells were used as the control group. Total RNA was extracted from the cells in each group and reverse transcribed to construct a cDNA library. Differences in gene expression profiles between the two groups were analyzed by high-throughput sequencing and the representative genes were selected for verification by qPCR. Results:A total of 23 997 genes were detected, including 125 differentially expressed genes. Among the 125 genes, 119 were up-regulated and six were down-regulated. GO analysis showed that the differentially expressed genes were enriched in several biological processes including defense response to virus, typeⅠinterferon signaling pathway and cellular responses to typeⅠinterferons. KEGG enrichment analysis showed the differentially expressed genes were mainly enriched in the pathways related to virus infections, such as influenza A virus, herpes simplex virus, EB virus and HPV, and NOD-like receptor pathway.Conclusions:There were significant differences in transcriptome profiles of HcerEpic cells before and after Ct infection. The differentially expressed genes were mainly enriched in the interferon pathway, which was closely related to the antiviral processes in cells. qPCR verified the differentially expressed genes and the genes closely related to the interferon pathway, such as ISG15, IFIT2, OASL and UBE2L6.

Bushen Anshen acupuncture for perimenopausal insomnia of kidney-yin deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of Bushen Anshen acupuncture (acupuncture for tonifying kidney and calming spirit ) in treating perimenopausal insomnia (PMI) of kidney-yin deficiency.@*METHODS@#A total of 72 patients with PMI of kidney-yin deficiency were randomized into an observation group (36 cases, 1 case dropped off) and a control group (36 cases, 1 case dropped off). Acupuncture was applied at Baihui (GV 20) and bilateral Shenshu (BL 23), Taixi (KI 3), Anmian (Extra) in the observation group, while sham acupuncture of shallow needling at non-acupoints was applied in the control group. The treatment was required once every other day, 3 times a week for 10 times in the two groups. Before and after treatment, Pittsburgh sleep quality index (PSQI) was used to evaluate the subjective sleep quality, and polysomnography (PSG) was used to monitor the objective sleep quality in the two groups.@*RESULTS@#After treatment, the scores of sleep quality, sleep latency, sleep duration, sleep efficiency, hypnotic, daytime dysfunction and total score of PSQI were decreased compared with those before treatment in the observation group (P<0.01), the scores of sleep duration, sleep efficiency and total score of PSQI were decreased compared with those before treatment in the control group (P<0.05); the scores of sleep quality, sleep latency, sleep efficiency, hypnotic and total score of PSQI in the observation group were lower than those in the control group (P<0.05). After treatment, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index was reduced (P<0.01) when PSG indexes were monitored, and the percentage of non-rapid eye movement sleep period 1 (N1%) was decreased while the percentage of non-rapid eye movement sleep period 3 (N3%) was increased (P<0.05) compared with those before treatment in the observation group; there was no statistical difference in the PSG indexes compared with those before treatment in the control group (P>0.05). After treatment, compared with the control group, the sleep time was prolonged, the sleep efficiency was improved, the sleep latency and the awake time after falling asleep were shortened, the arousal awake index and N1% were decreased in the observation group (P<0.01).@*CONCLUSION@#Bushen Anshen acupuncture can effectively improve the subjective and objective sleep quality in PMI patients of kidney-yin deficiency.

Analysis of urine Alzheimer-associated neuronal thread protein level and related factors of middle-aged and elderly people in Mianyang / 四川精神卫生

ObjectiveTo investigate the Alzheimer-associated neurofilament protein （AD7c-NTP） in urine of middle-aged and elderly people and its correlation between common metabolites. MethodsA total of 1 150 middle-aged and elderly people who did their physical exmanination in the health examination center of the Sichuan Science City Hospital and the Third Hopital of Mianyang were recruited from March 2017 to March 2020. The level of urine AD7c-NTP were measured by enzyme-linked immunosorbent assay （ELISA）， and common metabolites in blood were measured by biochemical analyzer. Based on urine AD7c-NTP level ≤1.5 ng/mL， the objects was divided into normal group （n=956） and elevated group （n=194）. Thier demographic data and blood biochemical indicators were collected. ResultsThe urine AD7c-NTP level in middle-aged and elderly people was 0.60（0.30~1.20） ng/mL. The urine AD7c-NTP level was higher in women than that in men ［1.04（0.40~1.30） ng/mL vs. 0.84（0.30~1.00） ng/mL， Z=4.202， P˂0.01］. And the urine AD7c-NTP level was lower in the normal group than that in the elevated group ［0.50（0.30~0.90） ng/mL vs. 2.10（1.70~2.10） ng/mL， Z=22.035， P˂0.01］. The results of the univariate comparison showed that， the differences between the two groups in age （Z=6.545）， fasting glucose （Z=3.506）， blood uric acid （Z=2.574）， urea nitrogen （Z=2.891）， creatinine （Z=2.243）， total bilirubin （Z=3.936）， glutathione （Z=0.969）， total cholesterol （t=3.956） and low density lipoprotein （Z=-5.678） were were statistically significant （P˂0.05 or 0.01）. Spearman correlation analysis showed that， the urine AD7c-NTP level was positively correlated with age and the levels of urea nitrogen， glucose， total cholesterol and low density lipoprotein （r=0.177， 0.178， 0.171， 0.109， 0.149， P˂0.01）， and negatively correlated with the level of total bilirubin （r=-0.172， P˂0.01）. Conclusionthe urine AD7c-NTP level in middle-aged and elderly females was signifitcantly higher than in middle-aged and elderly males.The urine AD7c-NTP level of middle-aged and elderly people was positively correlated with age， urea nitrogen， glucose， total cholesterol and low density lipoprotein， and negatively correlated with total bilirubin.

A case of corrosive digestive tract and lung injury caused by ingestion of pipeline dredging agent / 中华劳动卫生职业病杂志

Ingestion of corrosive substances can severely burn the upper digestive tract leading to bleeding or perforation, and may even be life-threatening. Less commonly, damage to the trachea and bronchi is involved. In this paper, a case of corrosive digestive tract injury and lung injury after oral administration of pipeline dredging agent (the main components are hydroxide, sodium carbonate, sodium hypochlorite, etc.) was analyzed. After active rescue treatment, the patient died of massive hemoptysis. It is suggested that serious complications may occur after ingestion of corrosive substances. Timely diagnosis and reasonable medical management are needed to improve the level of recognition and treatment of such diseases.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients / 中华预防医学杂志

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Acupuncture for delayed sleep-wake phase disorder: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for delayed sleep-wake phase disorder (DSWPD).@*METHODS@#A total of 84 patients with DSWPD were randomized into an observation group (42 cases, 2 cases dropped off) and a control group (42 cases, 3 cases dropped off). On the basis of sleep hygiene education, acupuncture was applied at Shenmai (BL 62), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, while placebo acupuncture was applied at the same acupoints in the control group. The treatment lasted for 8 weeks, once every other day, 3 times a week in the 1st to 4th weeks; once every 3 days, 2 times a week in the 5th to 8th weeks. Before and after treatment, the actigraphy (ACT) indexes of objective sleep (total time of stay in bed, total sleep time, sleep efficiency, the number of awakenings and the wake time after falling asleep) and plasma cortisol (CORT) level were observed; before and after treatment and in follow-up of 1, 3 months after treatment, the scores of morningness-eveningness questionnaire (MEQ), insomnia severity index (ISI), fatigue severity scale (FSS) and Epworth sleepiness scale (ESS) were observed in the two groups.@*RESULTS@#Compared before treatment, the total sleep time was prolonged, the sleep efficiency was improved, the number of awakenings was reduced, and the wake time after falling asleep was shortened after treatment in the observation group (P<0.01, P<0.05), and those in the observation group after treatment were superior to the control group (P<0.01, P<0.05). Compared before treatment, the MEQ scores after treatment in both groups and in the follow-up of 1, 3 months after treatment in the observation group were increased (P<0.01), and the MEQ score of each time point after treatment in the observation group was higher than the control group (P<0.01). The scores of ISI, FSS and ESS after treatment, and the scores of ISI、ESS in follow-up of 1, 3 months after treatment in the observation group were decreased compared with those before treatment (P<0.01, P<0.05), and in the observation group, the scores of ISI, FSS and ESS of each time point after treatment were lower than those in the control group (P<0.01, P<0.05). After treatment, the plasma CORT level in the observation group was decreased compared with that before treatment and that in the control group (P<0.01, P<0.05).@*CONCLUSION@#Acupuncture can improve the sleep and wake phase of patients with DSWPD, improve sleep quality and daytime function, and its mechanism may be related to the down-regulation of plasma CORT level.

Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models.@*RESULTS@#The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C.@*CONCLUSION@#Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.

Effect of intermedin on activation of nucleotide-binding oligomerization domain-like receptor protein 3 and pyroptosis in lipopolysaccharide induced macrophages / 中华风湿病学杂志

Objective:The effect of intermedin (IMD) on ATP-induced activation of inflammatory bodies and pyroptosis of cells and its mechanism were studied using lipopolysaccharide (LPS)-sensitized mouse macrophage line RAW 264.7.Methods:The cells were divided into the control groups, the LPS groups, LPS+IMD groups, and LPS+IMD+LY294002 groups. The expression of interleukin (IL)-1β and IL-18 and the activation of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory cells were detected by real-time PCR and western blotting, and the pyroptosis of cells was detected by propidium iodide (PI) staining. The measurement data was represented by MS± SD, and the inter-group difference was compared with ANOVA calculations, and P<0.05 represented the difference with statistical significance. Results:Compared with the control group [(0.83±0.09) vs (0.49±0.04)], the ratio of phosphorylated phosphatidylinositol-3-kinase, p-PI3K)/phosphatidylinositol-3-kinase (PI3K) (0.44±0.05) and p-Akt/Akt (0.27±0.06) in the LPS group was significantly decreased. The ratios of p-PI3K/PI3K (1.22±0.18) and pAkt/Akt (0.83±0.09) in LPS+IMD group was significantly increased ( F=31.40, P<0.001; F=50.88, P<0.001). Compared with the control group, the mRNA and protein expressions of IL-1β, IL-18 and NLRP3 inflammasome (NLRP3, caspase-1, ASC) in RAW264.7 cells were up-regulated in the LPS group (LPS and ATP). Compared with LPS group, IMD treatment inhibited the expression of inflammatory cytokines IL-1β, IL-18 and NLRP3 inflammasome, which was blocked by LY294002, a blocker of PI3K/Akt pathway. The results of real-time PCR showed that the relative expression of IL-1β mRNA was (1.00±0.11) in the control group, (8.32±0.61) in the LPS group, (8.32±0.55) in the LPS+IMD group, and (7.23±0.41) in the LPS+IMD+LY group ( F=15.42, P<0.001). The relative expression of IL-18 mRNA in the control group was (1.00±0.17), (1.82±0.21) in the LPS group, (1.14±0.15) in the LPS+IMD group, and (1.53±0.11) in the LPS+IMD+LY group respectively ( F=18.16, P<0.001). The relative expression of NLRP3 mRNA in the control group was (1.00±0.13), (2.58±0.18) in the LPS group, (1.07±0.17) in the LPS+IMD group, and (1.33±0.32) in the LPS+IMD+LY group respectively ( F=15.98, P< 0.001); The relative expression of caspase-1 mRNA in the control group was (1.00±0.09), (6.20±0.19) in the LPS group, (3.43±0.06) in the LPS+IMD group, and (5.50±0.45) in the LPS+IMD+LY group respectively ( F=18.39, P<0.001). The relative expression of ASC mRNA in the control group was (1.00±0.21), (4.58±0.48) in the LPS group, (2.07±0.51) in the LPS+IMD group, and (3.33±0.32) in the LPS+IMD+LY group respectively ( F=15.19, P<0.001). Western blotting results showed that the relative expression of IL-1β protein was as follows: (100%) in the control group, [(188±14)%] in the LPS group, [(112±11)%] in the LPS+IMD group, and [(171±27)%] in the LPS+IMD+LY group respectively ( F=21.25, P<0.001). The relative expression of IL-18 protein in the control group was 100%, [(183±16)%] in the LPS group, [(115±19)%] in the LPS+IMD group, and [(179±23)%] in the LPS+IMD+LY group respectively ( F=19.62, P<0.001). The relative expression of NLRP3 protein was 100% in the control group, [(149±15)%] in the LPS group, [(106±10)%] in the LPS+IMD group, and [(144±15)%] in LPS+IMD+LY group respectively ( F=14.35, P<0.001). The relative expression of ASC protein was 100% in the control group, [(188±12)%] in the LPS group, [(110±18)%] in the LPS+IMD group, and [(192±8)%] in the LPS+IMD+LY group ( F=15.79, P<0.001). Conclusion:IMD inhibits the activation of NLRP3 inflammasome and cell pyroptosis by regulating PI3K/Akt activity.

Polymerase chain reaction-based assays facilitate the breeding and study of mouse models of Klinefelter syndrome / 亚洲男科学杂志(英文版)

Klinefelter syndrome (KS) is one of the most frequent genetic abnormalities and the leading genetic cause of nonobstructive azoospermia. The breeding and study of KS mouse models are essential to advancing our knowledge of the underlying pathological mechanism. Karyotyping and fluorescence in situ hybridization are reliable methods for identifying chromosomal contents. However, technical issues associated with these methods can decrease the efficiency of breeding KS mouse models and limit studies that require rapid identification of target mice. To overcome these limitations, we developed three polymerase chain reaction-based assays to measure specific genetic information, including presence or absence of the sex determining region of chromosome Y (Sry), copy number of amelogenin, X-linked (Amelx), and inactive X specific transcripts (Xist) levels. Through a combined analysis of the assay results, we can infer the karyotype of target mice. We confirmed the utility of our assays with the successful generation of KS mouse models. Our assays are rapid, inexpensive, high capacity, easy to perform, and only require small sample amounts. Therefore, they facilitate the breeding and study of KS mouse models and help advance our knowledge of the pathological mechanism underlying KS.

Diagnostic and prognostic valuation of CD64, heparin binding protein and procalcitonin in children with sepsis shock / 中国医师进修杂志

Objective:To investigate the value of serum CD64, heparin binding protein (HBP) and procalcitonin (PCT) in early diagnosis of septic shock and its prognostic value.Methods:The clinical data of 40 children with sepsis (sepsis group) and 40 children with septic shock (septic shock group) in Children′s Hospital of Xuzhou Medical University from January 2018 to November 2021 were retrospectively analyzed. PCT was detected by chemiluminescence, HBP was detected by enzyme-linked immunosorbent assay, and CD 64 was detected by flow cytometry. All children were followed up within 1 month after discharge, and the occurrence of poor prognosis (including multiple organ failure and death) was recorded. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum CD 64, HBP and PCT for septic shock. Multivariate Logistic regression was used to analyze the independent risk factors for poor prognosis in children with septic shock. Results:The serum CD 64, HBP and PCT in septic shock group were significantly higher than those in sepsis group: 0.667 ± 0.120 vs. 0.501 ± 0.115, (116.46 ± 11.41) μg/L vs. (87.34 ± 23.49) μg/L and (11.41 ± 1.25) μg/L vs. (9.29 ± 1.31) μg/L respectively, and there were statistical differences ( P<0.05). ROC curve analysis result showed that the area under curve (AUC) of serum CD 64, HBP and PCT for predicting septic shock were 0.837, 0.894 and 0.880 respectively, and the optimal cut-off values were 0.586, 106.2 μg/L and 11.28 μg/L respectively; the AUC of serum CD 64, HBP and PCT combined detection for predicting septic shock was 0.914, with a sensitivity of 75.7%, specificity of 96.0%, and accuracy of 71.7%. According to the optimal cut-off values of serum CD 64, HBP and PCT, 40 children with septic shock were divided into high expression group and low expression group. The prognosis was good in 25 cases and bad in 15 cases. The incidence of poor prognosis in CD 64 high expression group, HBP high expression group and PCT high expression group was significantly higher than that in corresponding CD 64 low expression group, HBP low expression group and PCT low expression group: 56.52% (13/23) vs. 2/17, 10/17 vs. 21.74% (5/23) and 11/18 vs. 18.18% (4/22), and there was statistical difference ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that serum CD64, HBP and PCT were independent risk factors for poor prognosis in children with septic shock ( OR = 0.818, 1.204 and 3.633; 95% CI 0.674 to 0.994, 1.022 to 1.419 and 1.090 to 12.108; P = 0.043, 0.026 and 0.036). Conclusions:The serum levels of CD 64, HBP and PCT in children with septic shock are significantly increased, which play an important role in the occurrence and development of septic shock, and which have predictive value for septic shock. The combined detection of the 3 indexes could be used to evaluate the prognosis, with a higher predictive value.

Screening and identification of key genes ATP1B3 and ENAH in the progression of hepatocellular carcinoma: based on data mining and clinical validation / 南方医科大学学报

OBJECTIVE@#To explore the marker genes correlated with the prognosis, progression and clinical diagnosis of hepatocellular carcinoma (HCC) based on bioinformatics methods.@*METHODS@#The TCGA-LIHC, GSE84432, GSE143233 and GSE63898 datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. The differentially expressed genes (DEGs) shared by different disease types were obtained using GEO2R and edge R packages, and Gene Ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) enrichment analyses of the DEGs were performed. The expression levels of these DEGs in normal and cancerous tissues were verified in TCGA-LIHC to identify the upregulated genes in HCC. Survival analysis, receiver-operating characteristic (ROC) curve analysis, and correlation analysis between the key genes and the clinical features of the patients were carried out using the R language. The differential expressions of 15 key genes were verified in clinical samples of HCC and adjacent tissues using RT-qPCR.@*RESULTS@#A total of 118 common DEGs were obtained in the database, and among them two genes, namely ATPase Na +/K + transport subunit beta 3 (ATP1B3) and actin regulator (ENAH), showed increased expressions with disease progression. Survival analysis combined with the TCGA-LIHC dataset suggested that high expressions of ATP1B3 and ENAH were both significantly correlated with a poor prognosis of HCC patients (P < 0.05), and their AUC values were 0.821 and 0.933, respectively. A high expression of ATP1B3 was correlated with T stage, pathological stage and pathological grade of the tumors (P < 0.05), while that of ENAH was associated only with an advanced tumor grade (P < 0.05). The results of RT-qPCR showed that ATP1B3 and ENAH were both significantly upregulated in clinical HCC tissues (P < 0.05).@*CONCLUSION@#ATPIB3 and ENAH are both upregulated in HCC, and their high expressions may serve as biomarkers of progression of liver diseases and a poor prognosis of HCC.

Effect of Buyi Pishen acupuncture on inflammatory factor and cartilage matrix in adjuvant arthritis rats / 中国针灸

OBJECTIVE@#To observe the effect of Buyi Pishen acupuncture (acupuncture for invigorating spleen and kidney) on inflammatory factor and synovial cartilage matrix in adjuvant arthritis (AA) rats, and to explore the mechanism of acupuncture for rheumatoid arthritis (RA).@*METHODS@#A total of 60 clean male Wistar rats were randomized into a normal group, a model group, a tripterygium wilfordii polyglycoside tablet (TWP) group and an acupuncture group, 15 rats in each group. Rats in the model group, the TWP group and the acupuncture group received intradermal injection of Freund's complete adjuvant (FCA) at right hind foot pad to induce the AA model. TWP suspension of 8 mg/kg was given by gavage in the TWP group. Acupuncture was applied at "Shenshu" (BL 23), "Pishu" (BL 20) and right "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Yanglingquan" (GB 34) in the acupuncture group, 15 min a time, once a day. The intervention was given 15 days in both TWP group and acupuncture group. The foot-pad swelling degree before modeling, before and after intervention and the arthritis index (AI) score before and after intervention were calculated; the serum levels of interleukin (IL)-1β, IL-4, IL-10 and tumor necrosis factor-α (TNF-α) were detected by ELISA method; the ultrastructure and histomorphological changes of synovium issue were observed by transmission electron microscope and HE staining; the positive expression of matrix metalloproteinase (MMP)-3 and MMP-9 in synovium issue was detected by immunohistochemistry method.@*RESULTS@#Before intervention, foot-pad swelling degree of the model group, the TWP group and the acupuncture group was increased compared with the normal group (P<0.01). After intervention, foot-pad swelling degree and AI score were increased compared with the normal group (P<0.01), foot-pad swelling degree and AI scores in the TWP group and the acupuncture group were lower than the model group (P<0.05), and those in the acupuncture group were decreased compared with the TWP group (P<0.05). The model group exhibited unclear nuclear membrane of synovial cells, chromatin pyknosis, massive inflammatory cell infiltration and hyperplasia in synovial tissue; the TWP group and the acupuncture group exhibited clear and smooth nuclear membrane of synovial cells, inapparent chromatin pyknosis, less inflammatory cell infiltration and hyperplasia in synovial tissue, the acupuncture group exhibited less matrix destruction as well. Compared with the normal group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were increased (P<0.01), while serum levels of IL-4 and IL-10 were decreased (P<0.01) in the model group. Compared with the model group, serum levels of IL-1β and TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05, P<0.01), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the TWP group and the acupuncture group; compared with the TWP group, serum level of TNF-α and positive expression of MMP-3 and MMP-9 in synovium issue were decreased (P<0.05), while serum levels of IL-4 and IL-10 were increased (P<0.05) in the acupuncture group.@*CONCLUSION@#Buyi Pishen acupuncture can effectively improve the injury of articular cartilage in AA rats, its mechanism maybe related to reducing the inflammatory reaction in synovium and inhibiting the degradation of articular cartilage matrix.

Risk signal mining of adverse event related to adalimumab based on FAERS / 中国药房

OBJECTIVE To provide reference for clinical safe and rational use of adalimumab by mining the risk signals of adverse event （AE）. METHODS AE reports related to adalimumab were collected from FDA adverse event reporting system （FAERS）from Jan. 1st，2015 to Dec. 31th，2021. The reporting odds ratio （ROR）method and the Medicines and Healthcare Products Regulatory Agency （MHRA） method were adopted to mine the AE risk signals related to adalimumab ，AEs were classified and described by using the preferred system organ class （SOC）and preferred term （PT）of Medical Dictionary for Regulatory Activities （23.0）. RESULTS A total of 149 203 AE reports related to adalimumab were screened ，among which 65 218 cases（43.71％）were severe AE reports. A total of 2 660 PTs were mined ，involving 27 SOCs. PTs related to primary disease （arthralgia，Crohn’s disease ，rheumatoid arthritis ，abdominal pain ，osteoarthritis，intestinal obstruction ，psoriasis，joint swelling ， arthritis，etc.）were more frequently reported ，followed by PTs related to inflammation and pain （procedural pain ，inflammation， etc.）. The main SOC included musculoskeletal and connective tissue diseases （68 227 cases），gastrointestinal diseases （50 682 cases），injury，poisoning and procedural complications （32 404 cases），infections and infestations （15 651 cases），general disorders and administration site conditions （15 424 cases），etc. CONCLUSIONS It is suggested to pay attention to the possible occurrence of paradoxical psoriasis and lupus-like syndrome related to the autoimmune system when using adalimumab clinically ； at the same time ，the attention should be paid to serious infection ，tuberculosis，malignant tumors ，demyelination，congestive heart failure and other AEs. If related AEs occurs ，intervention measures should be taken in time. Great importance should be paid to intracranial aneurysms ，ovarian cysts ，coronary artery occlusion ，thyroid masses and other AEs not mentioned in the instrcution ，to ensure the medication safety of patients.

Preoperative assessment of tricuspid valve replacement with LuX-Valve by CT: our initial exploration / 中华胸心血管外科杂志

Objective:To evaluate the value of CT in preoperative assessment of tricuspid valve replacement with LuX-Valve.Methods:145 consecutive patients with severe tricuspid regurgitation from October 2020 to April 2021 were selected. The multi-slice spiral CT (256 slice and above) scans were used to measure related indicators. Then analyses were made to determine whether the patients were suitable for valves replacement and to select the appropriate valve model.Results:49 cases were excluded after CT measurements, including 8 cases because of the values of the valve annulus and the remaining 41 due to comprehensive indicators includes: valve annulus size and shape, fixation method and operational safety. A total of 96 TTVR operations were performed, of which 6 were treated with thoracic surgery, 1 had moderate valve regurgitation, and the rest had no or mild regurgitation or paravalvular leaks. The operations showed a high success rate of 92.7%. After comprehensive analysis, it was found that among the 89 successful tricuspid valve replacements with LuX-Valve, 26 cases had annulus models consistent with the measurements of the diameter from tricuspid annular circumferences, while the remaining 63 had valve models larger than the diameter measurements. The results indicate that the size of right atrium was statistically significant to the enlargement of the valve size.Conclusion:CT has important application value in the preoperative screening of TTVR. For non-radial force LuX-Valve, the annulus size is not the only decisive factor, and the valve model should be comprehensively judged considering all the measurement indicators.

Protective effect of Asarum polysaccharide on H1N1 influenza virus infection and expression of inflammatory factors / 中国中药杂志

In this paper, Asarum polysaccharides(AP) were extracted, and its composition was analyzed to study the activity against H1 N1 influenza virus in vitro and its intervention effect on mice with kidney Yang deficiency syndrome. AP was prepared by the strategy of water extraction and alcohol precipitation, the content was determined, and its monosaccharide composition was analyzed. The cell Real-time monitoring system and Reed-Muench model were adopted to evaluate the antiviral activity of AP in vitro. And the mouse model of kidney Yang deficiency syndrome was established in vivo to compare the efficacy of Mahuang Xixin Fuzi Decoction(MXF) and AP. MXF group and AP group were treated with clinical equivalent doses of 1.8 g·kg~(-1)·d~(-1) and 0.077 g·kg~(-1)·d~(-1) respectively, once a day for 6 consecutive days. Real-time PCR was used to detect the relative expression of M gene of H1 N1 influenza virus and cytokines in lung tissue. The content of AP in Asarum was 25.22%, and the protein content was 0.8%. And the monosaccharide composition was identified as L-rhamnose, D-arabinose, D-xylose, D-glucose, D-galactose and D-mannose. TI values of Tamiflu, MXF and AP were 30.00, 8.06 and 10.33, respectively. Three different doses of AP could significantly reduce the concentration of virus in supernatant. Compared with the model mice, lung indexes of MXF group and AP group decreased significantly(P<0.05), and the relative expression of M gene decreased significantly(P<0.05). The relative expressions of IL-10 and IFN-γ were up-regulated to varying degrees, while the relative gene expressions of IL-1β, IL-6 and MCP-1 were down-regulated to different degrees. In addition, AP could significantly enhance the expression of TNF-α(P<0.01). AP had a good anti-influenza virus activity in vitro, and could protect mice with kidney Yang deficiency syndrome by reducing the viral load in lung tissue, decreasing inflammation damage in lung tissue, and regulating the expression of inflammatory cytokines. Compared with the prescription of MXF, AP had a better antiviral activity.

Expression and clinical significance of receptor-interacting protein kinase-3 levels in children with mycoplasma pneumoniae pneumonia and their relationship with inflammatory factors / 中国综合临床

Objective:To explore the level of expression, clinical significance of receptor-interacting protein kinase-3(RIPK3) in the bronchoalveolar alveolar lavage fluid (BALF) of mycoplasma pneumoniae pneumonia(MPP) in children and the relationship between RIPK3 and various cytokines.Methods:Using a case-control study, 30 refractory mycoplasma pneumoniae pneumonia children treated in Children′s Hospital of Xuzhou Medical University from February 2019 to February 2021 were selected as the MRPP group, 35 mycoplasma pneumoniae pneumonia children as the RPP group.Meanwhile, 20 sex- and age-matched hospitalized children with bronchial foreign body were selected as the case-control group.In all subjects, protein levels of RIPK3 and mixed lineage kinase domain-like protein(MLKL) were determined by Western Blot.Meanwhile, levels of IL-6, IL-1β and TNF-α were determined by enzyme linked immuno sorbent assay(ELISA). Compare levels of different parameters between the three groups and analyze the correlation between levels of RIPK3 and MLKL, L-6, IL-1β, TNF-α in the BALF of MPP children using Spearman rank correlation analysis.Results:There were statistically significant differences in the levels of RIPK3, MLKL, IL-6, IL-1β and TNF-α in BALF between RMPP group, MPP group and control group (all P<0.001). Pairwise comparisons also showed statistical differences, and the RMPP group was the highest, followed by MPP group, and the control group was the lowest.The level of RIPK3 in BALF of MPP children was positively correlated with MLKL, IL-6, IL-1β and TNF-α ( r=0.711, 0.676, 0.725, 0.651, P<0.001). Linear regression analysis shows: MLKL=0.432×RIPK3. Conclusion:RIPK3 may be involved in the occurrence and development of MPP in children, and is closely related to cytokines such as IL-6, IL-1β and TNF-α.

Investigation of Host-guest Complexation Between 4-Sulfonylcalix 6 Arene and 15 Alkaloids from Traditional Chinese Medicines and Inhibitory Effect of Binding System on Proliferation of HepG2 and H9c2 Cells / 中国实验方剂学杂志

Objective:To investigate bonding ability between 4-sulfonylcalix ［6］ arene （SCA6） and 15 alkaloids （matrine， allomatrine， dauricine， daurisoline， quinidine， quinine， crotaline， vincristine， gelsemine， koumine， tetrandrine， aloperine， oxymatrine， sophocarpine and sinomenine）， and to evaluate viability<italic> in vitro</italic> of HepG2 and H9c2 cells with 12 alkaloids/SCA6 bonding systems （except allomatrine， oxymatrine， sinomenine）. Method:Fluorescence competitive titration was used to determine the binding constants of alkaloids and SCA6， the inhibitory effect of alkaloid/SCA6 complex on proliferation of HepG2 and H9c2 cells was investigated by cell counting kit-8 （CCK-8）. Result:All the 15 alkaloids had good bonding with SCA6 at the ratio of 1∶1 （the binding constants >1×10⁵ mol·L^-1， <italic>R</italic>²>0.98）， the aloperine （quinolizidine alkaloids） and SCA6 had the biggest binding constant （20.55×10⁶ mol·L^-1）. In addition to gelsemine， crotaline， matrine and sophocarpine， 8 alkaloids （including aloperine， tetrandrine， dauricine， daurisoline， quinidine， quinine， vincristine and koumine） exhibited significant anti-tumor effects on HepG2 cells. Except for daurisoline， the anti-proliferation effect of the other 11 alkaloids before and after binding with SCA6 had no difference in HepG2 cells. In addition to gelsemine， crotaline， matrine and sophocarpine， the anti-proliferation effect of the other 8 alkaloids before and after binding with SCA6 had no difference in H9c2 cells. Conclusion:SCA6 shows intense binding ability with bisbenzylisoquinoline， quinolizidine and indole alkaloids. It can improve the solubility of alkaloids without affecting their anti-tumor activity， which provides a reference for subsequent related applications of SCA6 as a drug delivery carrier.

Relationship between the living environment and respiratory diseases in primary school students in Taizhou City / 上海预防医学

Objective:To understand the relationship between the living environment and respiratory diseases in primary school students in Taizhou City of Zhejiang Province， and to explore the related factors. Methods:From 2018 to 2019， a total of 1 044 students from grade 2 to grade 5 of a primary school in Taizhou were selected by cluster random sampling method for two consecutive years to conduct a questionnaire survey during November 15 to December 31. Correlation between living environment and respiratory diseases in primary school students was analyzed. Results:Among the 1 044 students completed valid questionnaires， 224 students had suffered from respiratory diseases in the past year， accounting for 21.5% from 2018 to 2019. Logistic regression analysis showed that existence of waste collection site within 100 m of household （OR=2.522， 95%CI：1.105-5.752）， family passive smoking exposure （OR=1.781， 95%CI： 1.234-2.571）， and household use of air pollution chemicals （OR=1.915， 95%CI：1.396-2.627） were independent risk factors for respiratory diseases in primary school students. Conclusion:There are some risk factors of respiratory diseases in the living environment of primary school students in Taizhou， and prevention should be carried out in daily life to reduce the prevalence of respiratory diseases among primary school students.