Clinical efficacy and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis in children with different center temperatures / 中国热带医学

@#Abstract: Objective To investigate the clinical outcomes and influencing factors of mild therapeutic hypothermia for influenza-associated encephalopathy/encephalitis (IAE) in children with different center temperatures, and to provide ideas and references for new mild therapeutic hypothermia scheme. Methods　A total of 115 hospitalized children with IAE who were scheduled to receive mild therapeutic hypothermia in Zhongshan Hospital Affiliated to Xiamen University from January 2019 to February 2022 were collected as subjects. They were randomly divided into two groups, namely, the 33 ℃ group (n=60) and the 35 ℃ group (n=55). The clinical features and clinical outcomes of the two groups were analyzed. Univariate and multivariate logistic regression analysis was performed for 6-month to investigate the factors affecting neurological disability. Results　The baseline indicators after treatment, such as Glasgow Coma Scale (GCS) score, cerebrospinal fluid total protein (CSF-TP), CSF lactate dehydrogenase (CSF-LDH), lymphocyte (Lym), creatine kinase-MB (CK-MB), LDH, and neuron-specific enolase (NSE), revealed no significant differences between the two groups before treatment or after treatment (P>0.05). There was no significant difference between the two groups after treatment in the clinical outcomes including GCS score D-value, time of hospitalization, 6-month neurological disability rate and mRS score, CSF-TP D-value, CSF-LDH D-value, Lym D-value, CK-MB D-value, LDH D-value, NSE D-value, improvement rate of EEG and MRI (P>0.05). Univariate and multivariate logistic regression analyses [OR=1.185, 95%CI (1.026~1.369), P=0.021] indicated that the delay of the onset of mild therapeutic hypothermia treatment was an independent risk factor for neurological disability in children with IAE after mild therapeutic hypothermia treatment of 6 months. Conclusion　There was no significant difference in the clinical outcomes between 33 ℃ and 35 ℃ mild therapeutic hypothermia for children with IAE. Therefore, mild therapeutic hypothermia for children with IAE may not require a strict requirement. Timely receipt of mild therapeutic hypothermia is a key measrue to reduce the risk of neurological disability in children with IAE.

Correlation analysis between SLC52A2 gene expression and prognosis of patients with uveal melanoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the correlation between SLC52A2 and uveal melanoma(UM)based on the cancer genome atlas(TCGA)database, and preliminarily explore the influence of SLC52A2 on the prognosis of UM patients and potential mechanism.METHODS: The clinical information on 80 patients with UM and mRNA expression data of SLC52A2 were collected from TCGA database. According to the expression level of SLC52A2, 80 patients were divided into high and low expression groups by median method. The relationship between the expression of SLC52A2 and clinical pathological features, as well as the prognosis was analyzed. The age, sex, clinical stage, pathological stage, and mRNA expression of SLC52A2 were analyzed by univariate and multivariate Cox analysis to search the prognostic factors of UM. Enrichment analyses were used to predict the possible regulatory pathway of SLC52A2 in UM.RESULTS: The survival prognosis of patients with low expression of SLC52A2 was better than that of patients with high expression of SLC52A2(P<0.05). The level of SLC52A2 has no significant correlation with the age, sex, clinical stage, and pathological stage of patients in both groups(P>0.05). Multivariate Cox analysis showed that the high expression of SLC52A2 was a risk factor for poor prognosis. The nomogram prediction model developed by combining the expression of SLC52A2 with clinical pathological features could accurately predict the survival probability of UM patients. The infiltration abundance of Th2 and Treg cells in both groups has difference(all P<0.001). GSEA analysis showed that the gene of JAK-STAT(FDR=0.028, P=0.004)and PI3K/AKT(FDR=0.017, P=0.002)were rich in samples with high expression of SLC52A2.CONCLUSION: The high expression of SLC52A2 is a risk factor for the prognosis of UM patients. SLC52A2 can be used as a biomarker to predict the prognosis and to become a new target for the treatment of patients with UM.

Clinical significance of infiltration of M2 tumor-associated macrophage in hepatocellular carcinoma / 中华消化杂志

Objective:To investigate the distribution of M2 tumor-associated macrophage (TAM) in hepatocellular carcinoma (HCC) and their correlation with clinicopathological features, and the significance of programmed death-ligand 1 (PD-L1) expression.Methods:From January 1, 2012 to December 31, 2020, a total of 320 HCC patients who underwent surgical resection at the Third People′s Hospital of Nantong were included. The distribution of CD163 labeled and PD-L1 CD163 double-labeled M2 TAM in HCC tissues was detected by immunohistochemistry, and the cell density was calculated. The cell density> the average cell density (112/mm 2) was judged as high-density, the cell density≤ the average cell density was judged as low-density. The correlation between CD163 positive and PD-L1 CD163 double positive M2 TAM density and the clinical pathological characteristics of HCC and its impact on prognosis were analyzed. Chi-square test was used to analyze the correlation between M2 TAM expression and the clinical pathological characteristics of HCC. Kaplan-Meier method was used to draw survival curves, and log-rank test was used for inter group comparison. Univariate and multivariate Cox proportional hazards regression analysis was used to indentify the relevant factors affecting the prognosis of HCC. Results:TAM were mainly distributed in the tumor edge stroma and tumor sinusoids, CD163 positive M2 TAM were the main macrophage subtype. PD-L1 expression was observed in CD163 positive M2 TAM in HCC tissues, and PD-L1 positive M2 TAM were mainly distributed in the tumor edge stroma. The rate of high-density CD163 positive M2 TAM in HCC tissues was 44.4% (142/320). High-density CD163 positive M2 TAM was correlated with histological grade, TNM stage, and PD-L1 expression on tumor infiltrating immune cells in HCC tissues ( χ2=4.65, 6.72 and 42.19, P=0.031, =0.011 and <0.001). High-density PD-L1 and CD163 double positive M2 TAM in HCC tissues was correlated with microvascular invasion and TNM stage ( χ2=11.96 and 8.74, P=0.001 and 0.004). The median disease-free survival (DFS) time and overall survival (OS) time of patients with high-density CD163 positive M2 TAM were 21 and 36 months, respectively, which were lower than those of patients with low-density CD163 positive M2 TAM (50 and 103 months, respectively); the median DFS time and OS time of patients with high-density PD-L1 CD163 double-positive M2 TAM were 12 and 15 months, respectively, which were lower than those of patients with low-density PD-L1 CD163 double-positive M2 TAM (28 and 45 months, respectively), and the differences were statistically significant (all log-rank tests, all P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that high-density CD163 positive M2 TAM, microvascular invasion and high TNM stage were independent risk factors for evaluating DFS and OS of patients with HCC (DFS time: HR=2.408 (95% confidence interval (95% CI) 1.778 to 3.261), 2.603 (95% CI 1.860 to 3.641), 4.032 (95% CI 2.833 to 5.747), all P<0.001. OS time: HR=2.007 (95% CI 1.457 to 2.764), 4.144 (95% CI 2.881 to 5.960), 4.292 (95% CI 2.915 to 6.329), all P<0.001). Conclusions:High-density of CD163 positive M2 TAM in HCC tissues indicates high malignancy and poor prognosis, and it is an independent prognostic risk factor. The expression of PD-L1 in M2 TAM suggests stronger tumor aggressiveness and worse prognosis in HCC.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Analysis of gene variation and clinical characteristics of Wiedemann-Steiner syndrome / 中华儿科杂志

Objective: To summarize and analyze the clinical characteristics and gene mutations of 6 patients with Wiedemann-Steiner syndrome (WDSTS). Methods: To review and analyze the clinical data, including general conditions, clinical manifestations, growth hormone, cranial or pituitary gland magnetic resonance imaging (MRI),gene results and other data, 6 cases with WDSTS admitted to the Department of Endocrinology, Genetics and Metabolism of Jiangxi Provincial Children's Hospital and the Department of Child Care of Pingxiang Maternity and Child Care from April 2017 to February 2021 were recruited. Results: Of the 6 patients, 2 were male and 4 were female. The age of the first visit ranged from 1.0 to 11.2 years. All the 6 children presented with growth retardation and mental retardation and they all had typical facial dysmorphism and hypertrichosis (mainly on the back and limbs). Among them, case 5 had a growth hormone deficiency, and case 2 and 4 had abnormalities revealed by cranial MRI. Variations in KMT2A gene were identified in these 6 patients: c.10900+2T>C,c.10837C>T(p.Gln3613*), c.4332G>A(p.E1444E), c.2508dupC(p.W838Lfs*9), c.11695_11696delinsT(p.T3899Sfs*73), c.9915dupA (p.P3306Tfs*22).Among these variations, c.4332G>A, c.11695_11696delinsT and c.9915dupA were novel mutations. Therefore, the final diagnosis of these patients was WDSTS. Conclusions: Patients presented with short stature and mental retardation, typical facial dysmorphism and hypertrichosis should be considered WDSTS. Whole-exome sequencing plays an important role in disease diagnosis and genetic counseling.

Expression of programmed death receptor ligand 2 protein in hepatocellular carcinoma and its relationship with clinicopathological features and prognosis of patients / 肿瘤研究与临床

Objective:To explore the expression of programmed death receptor ligand 2 (PD-L2) in hepatocellular carcinoma (HCC) and its relationship with clinicopathological features and prognosis of patients.Methods:The data of 344 patients with HCC who underwent surgery in the Third People's Hospital of Nantong from January 2008 to December 2016 were retrospectively analyzed. Taking HCC tissue samples to make the tissue microarray, and the expression of PD-L2 protein was detected by immunohistochemical method. The relationship between PD-L2 protein expression and clinicopathological features was analyzed. Kaplan-Meier method was used to analyze the overall survival (OS) and disease-free survival (DFS) of patients, and the prognostic factors were analyzed by univariate and multivariate Cox proportional hazards model.Results:The positive expression rate of PD-L2 protein in 344 patients with HCC was 54.4% (187/344). The positive expression of PD-L2 protein was correlated with maximum tumor diameter >3 cm ( χ2 = 8.20, P < 0.01) and high histological grade ( χ2 = 9.46, P < 0.05); OS and DFS in PD-L2 positive expression group were worse than those in PD-L2 negative expression group (OS: P = 0.001; DFS: P = 0.015). PD-L2 positive expression was not an independent adverse influencing factor for OS and DFS (OS: HR = 1.321, 95% CI 0.955-1.829, P = 0.093; DFS: HR = 1.209, 95% CI 0.990-1.624, P = 0.209). Conclusions:PD-L2 is highly expressed in HCC tissues, which may be related to the degree of malignancy. PD-L2 is not an independent risk factor for the prognosis of HCC.

Exploration of Ideas and Strategies for TCM Modernization Experimental Research Based on Precise Messenger Targeting of Exosomes and TCM Supramolecular "Qi Chromatography" Theory / 中国实验方剂学杂志

Exosomes are lipid bilayer membranous vesicles actively secreted by various cells in the organism， which are like nanoparticles and have messenger targeting. Combining with the theory of supramolecular "Qi chromatography" of traditional Chinese medicine （TCM）， research ideas and strategies of modernization of TCM can be constructed. Exosomes are secreted by cells， and the membrane contains nucleic acids， proteins， lipids and small molecular metabolites and others， which can accurately coordinate the functions of each cell， concentrate and transmit the functional information of the parent cell， and is the concise form of reflecting cell functions. At the same time， it is loaded with the "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM. If the "imprinted templates" carrying rules among the gene-protein-lipid-small molecules wrapped in it is studied， the modern experimental research ideas and strategies of TCM theory can be established for revealing the functions of the body's meridians and viscera. Firstly， the present situation of exosomes， including discovery， secretion， characteristics， functions， attribution， uptake， research methods and application status， were reviewed in this paper. And the natural properties of its precise messenger targeted delivery vehicle were elaborated， reflecting the operation law of microscopic substances in meridians and viscera. Secondly， to explore it as an important carrier of the concentrated "imprinted templates" of the supramolecular "Qi chromatography" theory of TCM， and integrating the research methods of exosomes and supramolecular chemistry of TCM， this paper proposes experimental research ideas and strategies on the microscopic material basis of meridians and viscera， compatibility of TCM compound， and targeting of TCM targeted preparations.

One-stage surgery in patients with both cardiac and non-cardiac diseases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the possibility and feasibility of one-stage cardiac and non-cardiac surgery.@*METHODS@#From July 1999 to August 2018, one hundred and eleven patients suffering from cardiac and non-cardiac diseases were treated by one-stage cardiac and non-cardiac operation in Department of Cardiac Surgery and Thoracic Surgery, General Surgery, Urinary Surgery, and Gynecology, Peking University First Hospital. There were 83 males (74.8%) and 28 females (25.2%), aged 41 to 84 years [mean age: (64.64±8.97) years]. The components of the cardiac disease included coronary heart disease, valvular heart disease, cardiac tumors, chronic constrictive pericarditis and congenital heart disease. The components of the non-cardiac diseases included lung benign and malignant diseases, thymoma and thymic cyst, breast cancer, chest wall giant hemangioma, digestive tract benign and malignant diseases, urinary system carcinoma and gynecological diseases.@*RESULTS@#Two patients died after operations in hospital; thus, the hospital mortality rate was 1.8%. One patient died of multiple organ failure on the 153th days after emergency coronary artery bypass grafting (CABG) combined with radical resection of bladder cancer. The other of pericardium stripping with lung cancer operation died of the multiple organ failure on the tenth day after surgery. The remaining 109 patients recovered and were discharged. There were 13 cases of complications during the days in hospital. The total operative morbidity was 11.7%: postoperative hemorrhage in 2 cases (1.8%), pulmonary infection and hypoxemia in 3 cases (2.7%), hemorrhage of upper digestive tract in 1 case (0.9%), incisional infection in 3 cases (2.7%), subphrenic abscess in 1 case (0.9%), and postoperative acute renal failure and hemofiltration in 3 case (2.7%). Of the 109 patients discharged, 108 patients were followed up. All the patients survived for 6 months, and 21 patients died due to tumor recurrence or metastasis within 1 to 5 years of follow-up, but no cardiogenic death. During the follow-up period, 1 patient developed cardiac dysfunction, 1 patient underwent percutaneous coronary intervention (PCI), 1 patient had cerebral hemorrhage due to excessive postoperative anticoagulation, and 1 patient suffered from incisional hernia.@*CONCLUSION@#One-stage surgeries in patients suffering from both cardiac and non-cardiac benign or malignant diseases are safe and possible with satisfactory short-term and long-term survival.

Analysis of the influence of tracking error of Xsight lung tracking system caused by cardiac beating / 中华放射肿瘤学杂志

Objective:To analyze the influence of tracking error of Xsight lung tracking system caused by cardiac beating.Methods:48 patients with lung tumors adjacent to the heart were enrolled into this study. The tumor movement curves were collected by the Xsight lung tracking system and recorded in the treatment log files during the Cyberknife treatment process. The curves were subject to filtering analysis and the respiratory motion of < 1 Hz and the cardiac beating motion of > 1 Hz were separated. According to the filtering results, the patient treatment tracking data were divided into two groups based on whether the cardiac beating wave of >1 Hz existed. The tracking errors were statistically compared between two groups based on the X-ray imaging data collected by Xsight lung tracking system during treatment.Results:For the fractionation with cardiac beat information, the tracking errors of the patient′s related models were (1.45 ± 0.99), (0.46 ± 0.21) and (0.70 ± 0.54) mm in the left-right, superior-inferior and anterior-posterior direction, respectively. For the fractionation without cardiac beat information, the tracking errors of the patient′s related models were (1.52 ± 1.17), (0.63 ± 0.37) and (1.07 ± 0.62) mm in the left-right, superior-inferior and anterior-posterior direction, respectively. The tracking errors in the superior-inferior and anterior-posterior direction of patients with accurate cardiac beat models were 28.34% and 34.86% less than those of their counterparts without accurate cardiac beat models and there was significant difference (both P<0.05). Conclusion:The tracking accuracy of Xsight lung tracking system will be significantly improved if the cardiac beat model is accurately established.

Ginsenoside Rb1 activates janus kinase 2/signal transducer and activator of transcription 3 pathway to reduce myocardial injury in mice with Kawasaki disease / 中国小儿急救医学

Objective:To investigate the therapeutic effect and signaling pathway of ginsenoside Rb1 on myocardial injury in mice with Kawasaki disease.Methods:BALB/C mice aged 5-6 weeks were randomly divided into control group, model group, aspirin group, ginsenoside Rb1 low dose group(50 mg/kg) and high dose group(100 mg/kg), with 12 mice in each group.Except the control group, other groups were treated with intermittent intraperitoneal injection of 10% bovine serum albumin saline solution to induce Kawasaki disease myocardial injury pathological model with a total of 6 days(twice a day); aspirin group, Rb1 low and high-dose group were given corresponding drugs by gavage for 20 days after modeling.The pathological changes of myocardial tissue were observed by hematoxylin eosin staining.The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and cardiac troponin I(cTnI) in serum and myocardial tissue were detected by ELISA.The activities of creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase(α-HBDH) and aspartate aminotransferase(AST) in serum were detected by enzyme coupling method.The expression levels of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway related proteins in myocardial tissue were detected by Western blot.Results:High dose of Rb1 significantly improved myocardial fiber rupture and tear, inflammatory infiltration and necrosis induced by myocardial injury in model group.ELISA results showed that, compared with the model group, high-dose Rb1 could significantly inhibit the high expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, which were restored to the level of the control group, and there was a dose-dependent relationship between the low and high-dose groups( P<0.05). The results of enzyme coupling method showed that creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate aminotrasferase in Rb1 high-dose group were restored to the level in control group, and there was a dose-dependent relationship between low and high-dose group( P<0.05). At the same time, compared with model group, Rb1 high-dose group significantly down regulated the expression level of cardiac troponin I( P<0.05). Western blot results showed that, compared with the model group, Rb1 significantly increased the relative expression levels of p-JAK2/JAK2, p-STAT3/STAT3 and B-cell lymphoma-2(Bcl-2)/β-actin, and significantly decreased the expression levels of Cleaved caspase-3/β-actin in a dose-dependent manner( P<0.05). Conclusion:Ginsenoside Rb1 can effectively reduce the myocardial injury induced by Kawasaki disease mice.The high-dose group of Rb1 can recover to the level of the control group, and the curative effect is related to the dosage of Rb1.Ginsenoside Rb1 may activate JAK2/STAT3/Bcl-2 signaling pathway, thus down regulate the expression of Cleaved caspase-3, and inhibit cardiomyocyte apoptosis and inflammation.

Advances in Clinical Application and Hemostatic Mechanism of Charcoal Drugs of Chinese Materia Medica / 中国实验方剂学杂志

Under the guidance of the theory of traditional Chinese medicine （TCM）， charcoal drugs are widely used in clinical treatment of various bleeding syndromes， in addition， they also have the effect in anti-diarrhea and anti-ulcer， but charcoal drugs are especially effective in stopping bleeding. According to the changes in the properties after processing， the hemostatic effect of charcoal drugs can be roughly divided into two categories. One is not used for hemostasis itself， but used for hemostasis after processing. The other is used for hemostasis itself， and the drug properties are changed or the hemostatic ability is enhanced after processing. By summarizing researches on historical evolution， processing mechanism and pharmacological effects of the commonly used hemostatic charcoal drugs， the author found that preservation or increase of active substances after processing was closely related to the hemostatic effect of charcoal drugs. The hemostatic mechanism mainly involves the influence of coagulation system and platelet function， etc. At the same time， combined with the theory of Qi chromatograph of TCM supramolecular， this paper puts forward the supramolecular research strategy on hemostatic mechanism of charcoal drugs， in order to provide reference for revealing the scientific connotation of charcoal drugs for hemostasis.

The Local Alternative Ti-6Al-4V Alloy Coating of Surgery Steel Instruments for Laser Deposition Forming / 中国医疗器械杂志

Aiming at the medical practice problems of the surgical steel medical instruments, such as the crevice corrosion, the poor mechanical compatibility and the Ni, Cr plasma exudation, the laser deposition of Ti-6Al-4V alloy cladding layer at the local functional area as alternative coating was proposed and realized as a new process method. The accurate element content and good formability Ti-6Al-4V cladding powder was chosen, the low power and high duty cycle optimized laser process was adopt, the alternative coating of good fusion and low dilution was prepared. Through the elemental line scanning, the interface microstructure analysis and the experiments of basic mechanical properties, the basic properties of the cladding were characterized and verified. The experiments results showed that, the Ti, Al and V contents of the top coating were respectively about 88%, 4.9% and 3.9%, no sensitizing ions such as Cr and Ni were detected. Initial equiaxed α phase, flake β phase dist were distributed in the coating and interface, the α' martensite was precipitated at the boundary of the flake β phase, some refined granular β phase dispersion pinned to the grain boundary of basket structure. The microhardness of cladding layer was 352.08~312.76 HV0.1. The friction coefficient of the cladding layer was about 0.22~0.65. A new technology and method reference for improving and upgrading the performance of surgical medical devices is provided by this research.

Lapiferin protects against H1N1 virus-induced pulmonary inflammation by negatively regulating NF-kB signaling

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.

Long-term efficacy and adverse reactions of intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma in non-endemic northwest China / 中华放射肿瘤学杂志

Objective To retrospectively analyze the characteristics of nasopharyngeal carcinoma,long-term efficacy,adverse reactions of intensity-modulated radiotherapy (IMRT) in non-endemic northwest China and summarize the experience of IMRT in the treatment of nasopharyngeal carcinoma in the past decade.Methods Clinical data of 658 patients newly diagnosed with nasopharyngeal carcinoma without distant metastasis admitted to First affiliated hospital from January 2006 to December 2016 were retrospectively analyzed.All patients were treated with IMRT.The survival analysis was performed by Kaplan-Meier method.The multivariate analysis was conducted with Cox's regression model.Results In non-endemic northwest China,a large proportion of patients were newly diagnosed with locally advanced nasopharyngeal carcinoma,and a majority of them were pathologically characterized as differentiated subtypes.The 5-year overall survival (OS),disease-free survival (DFS),local recurrence-free survival (LRFS),regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) rates were 75.7％,70.1％,91.2％,97.0％ and 81.0％,respectively.Multivariate analysis showed that age,pathological type,nasopharyngeal tumor volume＞23 cm3 and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DFS (all P＜0.05).Age,pathological type,neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of OS (all P＜0.05).N stage and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DMFS (both P＜0.05).Conclusions Similar clinical efficacy has been achieved in terms of IMRT for nasopharyngeal carcinoma in non-endemic northwest China compared with that in endemic area.Induction chemotherapy combined with concurrent radiochemotherapy can provide clinical benefits for patients with locally advanced nasopharyngeal carcinoma in non-endemic area.

Long-term efficacy and adverse reactions of intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma in non-endemic northwest China / 中华放射肿瘤学杂志

Objective@#To retrospectively analyze the characteristics of nasopharyngeal carcinoma, long-term efficacy, adverse reactions of intensity-modulated radiotherapy (IMRT) in non-endemic northwest China and summarize the experience of IMRT in the treatment of nasopharyngeal carcinoma in the past decade.@*Methods@#Clinical data of 658 patients newly diagnosed with nasopharyngeal carcinoma without distant metastasis admitted to First affiliated hospital from January 2006 to December 2016 were retrospectively analyzed. All patients were treated with IMRT. The survival analysis was performed by Kaplan-Meier method. The multivariate analysis was conducted with Cox’s regression model.@*Results@#In non-endemic northwest China, a large proportion of patients were newly diagnosed with locally advanced nasopharyngeal carcinoma, and a majority of them were pathologically characterized as differentiated subtypes. The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) rates were 75.7%, 70.1%, 91.2%, 97.0% and 81.0%, respectively. Multivariate analysis showed that age, pathological type, nasopharyngeal tumor volume>23 cm3 and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DFS (all P<0.05). Age, pathological type, neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of OS (all P<0.05). N stage and neck lymph node metastasis complicated with necrosis were the factors of poor prognosis of DMFS (both P<0.05).@*Conclusions@#Similar clinical efficacy has been achieved in terms of IMRT for nasopharyngeal carcinoma in non-endemic northwest China compared with that in endemic area. Induction chemotherapy combined with concurrent radiochemotherapy can provide clinical benefits for patients with locally advanced nasopharyngeal carcinoma in non-endemic area.

Quality Control of Dynamic Volatile Components in Lonicerae Japonicae Flos and Lonicerae Flos / 中国实验方剂学杂志

Objective:The molecular connectivity index method and total statistical moment method were used to control the quality of traditional Chinese medicine （TCM）， and the stability and consistency of volatile components of Lonicerae Japonicae Flos and Lonicerae Flos were clarified. Method:Volatile oils in Lonicerae Japonicae Flos and Lonicerae Flos from different producing areas was extracted for GC-MS determination with electron bombardment ion source， ion source temperature of 230 ℃， and detection range of m/z 35-650. Then National Institute of Standards and Technology （NIST） 05 and ChemicalBook database were used for qualitative analysis of these volatile components， the peak area normalization method was used for quantitative analysis， and the total statistical moment parameters and the zero-order， first-order， second-order， third-order molecular connectivity indexes of the components were calculated. Result:Number of peaks （RSD were 28.5%， 33.4%， respectively）， total zero-order moments （RSD were 55.5%， 128.9%， respectively） and total second-order moments （RSD were 15.3%， 21.5%， respectively） of 10 batches of Lonicerae Japonicae Flos and Lonicerae Flos were unstable， indicating that the types and contents of volatile components fluctuated sharply， but the total first-order moments （RSD were 7.5%， 8.8%， respectively） and the zero-order， first-order， second-order and third-order molecular connectivity indexes （RSD ranged from 8.1% to 10.3% and 4.2% to 5.5%， respectively） were relatively stable， indicating that the overall "imprinting template" of the components was similar. Statistical analysis of each parameter found that there were no significant differences in the number of peaks， total first-order moments and zero-order， first-order， second-order， third-order molecular connectivity indexes between volatile oils from Lonicerae Japonicae Flos and Lonicerae Flos. Conclusion:Under the guidance of supramolecular gas evolution "imprinting template" theory， the molecular connectivity index method and total statistical moment parameters are used to jointly characterize the "imprinting template" of TCM components in vitro， which can control the stability and consistency of TCM quality.

Correlation between the expression of programmed death ligand-1 and clinicopathological factors and prognosis in hepatocellular carcinoma tissues / 中华消化杂志

Objective:To investigate the correlation between the expression of programmed death ligand-1 (PD-L1) and clinicopathological parameters and prognosis in hepatocellular carcinoma (HCC) tissues.Methods:From January 2008 to December 2016, 344 HCC patients underwent surgery in Nantong Third Hospital Affiliated to Nantong University were enrolled. The expression of PD-L1 in paraffin HCC tissues was detected by tissue microarray and immunohistochemistry. The correlation between the expression of PD-L1 in tumor cells, tumor-infiltrating immune cells and the clinicopathological parameters and prognosis of HCC patients were analyzed. And the related factors affecting the prognosis of patients were explored. Chi-square test, log-rank test and univariate and multivariate Cox regression analysis were used for statistical analysis.Results:Positive PD-L1 located in the membrane and/or cytoplasm of HCC tumor cells and tumor-infiltrating immune cells. The positive rate of PD-L1 expression in tumor cells was 21.8%(75/344). The expression of PD-L1 in tumor cells was related to histological grade and microvascular invasion, the positive rates of PD-L1 expression of patients with histological gradeⅠ, Ⅱ and Ⅲ were 7.7% (2/26), 16.5% (19/115) and 26.6% (54/203), respectively, the positive rates of PD-L1 expression of patients with or without microvascular invasion were 29.3% (34/116) and 18.0% (41/228), respectively, and the differences were statistically significant ( χ2=7.659 and 5.787, P=0.022 and 0.016). The positive expression rate of PD-L1 in tumor-infiltrating immune cells was 47.1% (162/344). The expression of PD-L1 in tumor-infiltrating immune cells was related with microvascular invasion, the positive rates of PD-L1 expression in patients with or without microvascular invasion were 56.9% (66/116) and 42.1% (96/228), respectively, and the differences were statistically significant ( χ2=6.751, P=0.009). The median survival time of patients with negative expression of PD-L1 in HCC tumor cells was 61 months (30 months, 92 months), while that of patients with positive PD-L1 expression was 16 months(6 months, 44 months), and the difference was statistically significant ( χ2=55.722, P<0.01). The expression of PD-L1 in HCC tumor cells was an independent risk factor affecting overall survival time (hazard ratio=3.090, P<0.01). Conclusions:The expression of PD-L1 in HCC tumor cells may be related to the malignancy and invasion of HCC, and may be a potential risk factor for prognosis.

Value of ginsenoside Rb1 in alleviating coronary artery lesion in a mouse model of Kawasaki disease / 中国当代儿科杂志

OBJECTIVE@#To study the effect and related signaling pathways of ginsenoside Rb1 in the treatment of coronary artery lesion (CAL) in a mouse model of Kawasaki disease (KD).@*METHODS@#BALB/c mice were randomly divided into a control group, a model group, an aspirin group, a low-dose ginsenoside Rb1 group (50 mg/kg), and a high-dose ginsenoside Rb1 group (100 mg/kg), with 12 mice in each group. All mice except those in the control group were given intermittent intraperitoneal injection of 10% bovine serum albumin to establish a mouse model of KD. The mice in the aspirin group, the low-dose ginsenoside Rb1 group, and the high-dose ginsenoside Rb1 group were given the corresponding drug by gavage for 20 days after modeling. Hematoxylin and eosin staining was used to observe the pathological changes of coronary artery tissue. ELISA was used to measure the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and coronary artery tissue. Western blot was used to measure the relative expression levels of proteins involved in the regulation of the AMPK/mTOR autophagy signaling pathway and the PI3K/Akt oxidative stress signaling pathway in coronary artery tissue.@*RESULTS@#The observation of pathological sections showed that compared with the model group, the high-dose ginsenoside Rb1 group had significant improvement in the symptoms of vascular wall thickening, intimal edema, fiber rupture, and inflammatory infiltration of endothelial cells. Compared with the control group, the model and low-dose ginsenoside Rb1 groups had significant increases in the levels of TNF-α, IL-6, and IL-1β in serum and coronary artery tissue (P0.05) and had significant increases in the expression levels of P-AKT/AKT and P-GSK-3β/GSK-3β (P<0.05), while the high-dose ginsenoside Rb1 group had significant increases in the relative protein expression levels of the above three proteins (P<0.05). Compared with the low-dose ginsenoside Rb1 group, the aspirin group and the high-dose ginsenoside Rb1 group had significant reductions in the levels of TNF-α, IL-6, and IL-1β (P<0.05); the high-dose ginsenoside Rb1 group had significant increases in the expression levels of P-PI3K/PI3K and P-AKT/AKT (P<0.05).@*CONCLUSIONS@#Ginsenoside Rb1 can effectively alleviate CAL in a mouse model of KD in a dose-dependent manner, possibly by regulating the AMPK/mTOR/P70S6 autophagy signaling pathway to inhibit CAL inflammation and regulating the PI3K/AKT/GSK-3β oxidative stress signaling pathway to exert a biological activity of protection against coronary artery endothelial cell injury.

Neuroprotective Effects of Spinosin on Recovery of Learning and Memory in a Mouse Model of Alzheimer's Disease

Previous studies have shown that spinosin was implicated in the modulation of sedation and hypnosis, while its effects on learning and memory deficits were rarely reported. The aim of this study is to investigate the effects of spinosin on the improvement of cognitive impairment in model mice with Alzheimer’s disease (AD) induced by Aβ1–42 and determine the underlying mechanism. Spontaneous locomotion assessment and Morris water maze test were performed to investigate the impact of spinosin on behavioral activities, and the pathological changes were assayed by biochemical analyses and histological assay. After 7 days of intracerebroventricular (ICV) administration of spinosin (100 µg/kg/day), the cognitive impairment of mice induced by Aβ1–42 was significantly attenuated. Moreover, spinosin treatment effectively decreased the level of malondialdehyde (MDA) and Aβ1–42 accumulation in hippocampus. Aβ1–42 induced alterations in the expression of brain derived neurotrophic factor (BDNF) and B-cell lymphoma-2 (Bcl-2), as well as inflammatory response in brain were also reversed by spinosin treatment. These results indicated that the ameliorating effect of spinosin on cognitive impairment might be mediated through the regulation of oxidative stress, inflammatory process, apoptotic program and neurotrophic factor expression, suggesting that spinosin might be beneficial to treat learning and memory deficits in patients with AD via multi-targets.

Schisantherin B Improves the Pathological Manifestations of Mice Caused by Behavior Desperation in Different Ages-Depression with Cognitive Impairment

Depression is a major mood disorder. Abnormal expression of glial glutamate transporter-1 (GLT-1) is associated with depression. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on depressive mice induced by forced swimming test (FST). Additionally, we also assessed the impairment of FST on cognitive function in mice with different ages. FST and open field test (OFT) were used for assessing depressive symptoms, and Y-maze was used for evaluating cognition processes. Our study showed that STB acting as an antidepressant, which increased GLT-1 levels by promoting PI3K/AKT/mTOR pathway. Although the damage is reversible, short-term learning and memory impairment caused by FST test is more serious in the aged mice, and STB also exerts cognition improvement ability in the meanwhile. Our findings suggested that STB might be a promising therapeutic agent of depression by regulating the GLT-1 restoration as well as activating PI3K/AKT/mTOR pathway.