Application progress of artificial intelligence in the screening and identification of drug targets / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has developed rapidly, with improved computing power and algorithms, which has greatly facilitated the collection and processing of biological, chemical information and clinical data, injecting new vitality into the research and development of new drugs.In this review, we began with a brief overview of the development and the main algorithms of AI in drug discovery.Then we elaborated through several specific cases on the various scenarios of AI application, including target identification, protein structure prediction, hit generation and optimization etc.Finally, we focused on a recent example to discuss the high efficiency of "end-to-end" application of AI.

Study on the fecal metabolomics of CUMS-susceptible and CUMS-resilient rats / 药学学报

Proton nuclear magnetic resonance (1H NMR) based metabolomics was applied to characterize the fecal metabolic profiles of chronic unpredictable mild stress (CUMS)-depression (CUMS-D) and CUMS-resilience (CUMS-R) rats. The fecal biomarkers and metabolic pathways involved in CUMS-D and CUMS-R were screened and identified, revealing the underlying mechanisms of two different responses of the body to the same stresses. Firstly, the classic depression model, i.e. CUMS, was constructed. According to the fecal metabolomics profiles, the model rats were divided into two groups, i.e. the CUMS-D group and the CUMS-R group. And then, the depression statuses of CUMS-D rats and CUMS-R rats were verified by their sucrose preference rates. Lastly, multivariate data analysis was applied to clarify the fecal biomarkers and corresponding metabolic pathways involving in CUMS-D and CUMS-R. The results show that compared with the control rats, the sucrose preference rates of CUMS-D rats were significantly reduced. By contrast, the sucrose preference rates of CUMS-R rats had no significant difference. At the same time, CUMS-D and CUMS-R showed both unique and shared biomarkers and pathways. Three pathways are significantly related to CUMS-D, including taurine and hypotaurine metabolism, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Glycerolipid metabolism and tryptophan metabolism are specific pathways related to CUMS-R. This study explores the mechanisms of the emergence of susceptible and resilience of rats under the same stimulus from a metabolomics perspective. The current findings provide not only a new perspective for studying depression, and personalized and precision treatments in clinic, but also the research and development of antidepressants.

Effects and molecular mechanism of exogenous L-carnitine on excessive endoplasmic reticulum stress-mediated hepatic pyroptosis in severely scald rats / 中华烧伤杂志

Objective: To investigate the effects and molecular mechanism of exogenous L-carnitine on hepatic pyroptosis mediated by excessive endoplasmic reticulum stress in severely scald rats. Methods: The experimental research method was adopted. According to the random number table (the same group method below), fifteen female Sprague Dawley rats aged 6-8 weeks were divided into sham-injury group, scald alone group, and scald+carnitine group (with 5 rats in each group), and full-thickness scald of 30% total body surface area were made on the back of rats in scald alone group and scald+carnitine group, and rats in scald+carnitine group were additionally given intraperitoneal injection of L-carnitine. At post injury hour (PIH) 72, The levels of aspartate aminotransferase (AST) and alanine dehydrogenase (ALT) of biochemical indicators of liver injury were detected by automatic biochemical analyzer with the sample number of 5. At PIH 72, liver tissue damage was detected by hematoxylin-eosin staining. At PIH 72, The mRNA levels of nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), cysteine aspartic acid specific protease 1 (caspase-1), gasderminD (GSDMD), and interleukin 1β(IL-1β) in liver tissue as pyroptosis-related markers and glucose regulatory protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) in liver tissue as endoplasmic reticulum stress-related markers were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR). Protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue were detected by Western blotting, and the sample numbers were all 5. HepG2 cells as human liver cancer cells were divided into dimethyl sulfoxide (DMSO) group, 0.1 μmol/L tunicamycin (TM) group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group and were treated accordingly. After 24 h of culture, cell viability was detected by cell counting kit 8, and the intervention concentration of TM was screened, and the sample number was 5. HepG2 cells were divided into DMSO group, TM alone group, and TM+carnitine group, and treated accordingly. After 24 h of culture, the protein expression levels of GRP78, CHOP, NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in cells were detected by Western blotting, and the sample numbers were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference-t test. Results: At PIH 72, the AST and ALT levels of serum in scald alone group were (640±22) and (157±8) U/L, which were significantly higher than (106±13) and (42±6) U/L in sham-injury group, respectively, with t values of -46.78 and -25.98, respectively, P<0.01. The AST and ALT levels of serum in scald+carnitine group were (519±50) and (121±10) U/L, which were significantly lower than those in scald alone group, respectively, with t values of 4.93 and 6.06, respectively, P<0.01. At PIH 72, the morphology of liver tissue of rats in sham-injury group were basically normal with no obvious inflammatory cell infiltration; compared with those in sham-injury group, the liver tissue of rats in scald alone group showed a large number of inflammatory cell infiltration and disturbed cell arrangement; compared with that in scald alone group, the liver tissue of rats in scald+carnitine group showed a small amount of inflammatory cell infiltration. At PIH 72, the mRNA expression on levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 34.42, 41.93, 30.17, and 15.68, respectively, P<0.01); the mRNA levels of NLRP3, caspase-1, GSDMD, and IL-1β in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 34.40, 37.20, 19.95, and 7.88, respectively, P<0.01). At PIH 72, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 12.28, 26.92, 5.20, 10.02, and 24.78, respectively, P<0.01); compared with those in scald alone group, the protein expression levels of NLRP3, caspase-1, caspase-1/p20, GSDMD-N, and cleaved IL-1β in liver tissue of rats in scald+carnitine group were significantly decreased (with t values of 10.99, 27.96, 12.69, 8.96, and 12.27, respectively, P<0.01). At PIH 72, the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 21.00 and 16.52, respectively, P<0.01), and the mRNA levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 8.92 and 8.21, respectively, P<0.01); the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald alone group were significantly higher than those in sham-injury group (with t values of 22.50 and 14.29, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in liver tissue of rats in scald+carnitine group were significantly lower than those in scald alone group (with t values of 14.29 and 5.33 respectively, P<0.01). After 24 h of culture, the cell survival rates of 0.1 μmol/L TM group, 0.2 μmol/L TM group, 0.4 μmol/L TM group, and 0.8 μmol/L TM group were significantly decreased than that in DMSO group (with t values of 4.90, 9.35, 18.64, and 25.09, respectively, P<0.01). Then 0.8 μmol/L was selected as the intervention concentration of TM. After 24 h of culture, compared with that in DMSO group, the protein expression levels of GRP78 and CHOP in cells in TM alone group were significantly increased (with t values of 10.48 and 17.67, respectively, P<0.01), and the protein expression levels of GRP78 and CHOP in TM+carnitine group were significantly lower than those in TM alone group (with t values of 8.08 and 13.23, respectively, P<0.05 or P<0.01). After 24 h of culture, compared with those in DMSO group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM alone group were significantly increased (with t values of 13.44 and 27.51, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05); compared with that in TM alone group, the protein expression levels of NLRP3 and GSDMD-N in cells in TM+carnitine group were significantly decreased (with t values of 20.49 and 21.95, respectively, P<0.01), but the protein expression levels of caspase-1, caspase-1/p20, and cleaved IL-1β in cells were not significantly changed (P>0.05). Conclusions: In severely scald rats, exogenous L-carnitine may play a protective role against liver injury by inhibiting the pathways related to excessive endoplasmic reticulum stress-mediated pyroptosis.

Mechanism of Xiaoyao San in treatment of depression,breast hyperplasia,and functional dyspepsia based on network pharmacology / 中国中药杂志

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.

Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats / Ambiente enriquecido alivia o comprometimento cognitivo pós-AVC em ratos por meio do aumento da expressão de α7-nAChR

ABSTRACT Background: Enriched environment (EE) is a simple and effective intervention to improve cognitive function in post-stroke cognitive impairment (PSCI), partly due to the rebalancing of the cholinergic signaling pathway in the hippocampus. α7-nicotinic acetylcholine receptor (α7-nAChR) is a cholinergic receptor whose activation inhibits inflammation and promotes the recovery of neurological function in PSCI patients. However, it is still unclear whether EE can regulate α7-nAChR and activate the cholinergic anti-inflammatory pathway (CAP) in PSCI. Objective: To investigate the effects of EE on cognitive impairment, and the role of α7-nAChR in PSCI. Methods: A PSCI rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R) and were reared in standard environment (SE) or EE for 28d, control group with sham surgery. Cognitive function was determined by Morris water maze test. The long-term potentiation (LTP) was assessed by Electrophysiology. Histopathological methods were used to determine infarct volume, α7-nAChR expression and the cytokines and cholinergic proteins expression. Results: Compared with SE group, rats in EE group had better cognitive function, higher expression of α7-nAChR positive neurons in hippocampal CA1 region. In addition, EE attenuated unfavorable changes induced by MCAO/R in cytokines and cholinergic proteins, and also enhanced LTP promoted by nicotine and attenuated by α-BGT; but showed no significantly difference in infarct volume. Conclusions: EE markedly improves cognitive impairment and enhances neuroplasticity in PSCI rats, which may be closely related to enhancement of α7-nAChR expression.

RESUMO Introdução: O ambiente enriquecido (AE) é uma intervenção simples e eficaz para melhorar a função cognitiva no comprometimento cognitivo pós-AVC, em parte devido ao reequilíbrio da via de sinalização colinérgica no hipocampo. O receptor nicotínico α7 de acetilcolina (α7-nAChR) é um receptor colinérgico cuja ativação inibe inflamação e promove a recuperação da função neurológica em pacientes com comprometimento cognitivo pós-AVC. No entanto, ainda não está claro se o AE pode regular α7-nAChR e ativar a via anti-inflamatória colinérgica (VAC) em comprometimento cognitivo pós-AVC. Objetivo: Investigar os efeitos do AE no comprometimento cognitivo e o papel do α7-nAChR no comprometimento cognitivo pós-AVC. Métodos: Modelo de comprometimento cognitivo pós-AVC foi induzido em ratos por oclusão e reperfusão da artéria cerebral média (MCAO/R), que foram criados em ambiente padrão (AP) ou em AE por 28d; grupo controle com cirurgia simulada. A função cognitiva foi determinada pelo teste do labirinto aquático de Morris. A potenciação de longo prazo (PLP) foi avaliada por eletrofisiologia. Métodos histopatológicos foram usados para determinar o volume do infarto, a expressão de α7-nAChR e a expressão de citocinas e proteínas colinérgicas. Resultados: Em comparação com o grupo AP, os ratos do grupo AE tiveram melhor função cognitiva, com maior expressão de neurônios positivos para α7-nAChR na região CA1 do hipocampo. Além disso, o AE atenuou alterações desfavoráveis induzidas por MCAO/R em citocinas e proteínas colinérgicas, e também aumentou a PLP promovida pela nicotina e atenuada por α-BGT, mas não mostrou nenhuma diferença significativa no volume do infarto. Conclusão: O AE melhora acentuadamente o comprometimento cognitivo e aumenta a neuroplasticidade em ratos com comprometimento cognitivo pós-AVC, o que pode estar intimamente relacionado ao aumento da expressão de α7-nAChR.

Concentration of target genes of SARS-CoV-2 and influencing factors in the confirmed cases with COVID-19 in Ningbo / 预防医学

Objective@#To learn the concentration of target genes of severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) and the influencing factors in the confirmed cases with coronavirus disease 2019 ( COVID-19 ) in Ningbo.@*Methods@#Demographic information and clinical diagnosis of COVID-19 cases reported in Ningbo from January 21 to February 20, 2020 were collected through China Disease Control and Prevention Information System. The Ct values of ORF1ab and N of the cases were collected through Ningbo Center for Disease Control and Prevention and designated hospitals, and analyzed in terms of gender, age, severity, clinical classification, source of case, sampling time and specimen type. @*Results@#There were 157 confirmed COVID-19 cases, including 56 males ( 35.67% ) and 101 females ( 64.33% ). Sixty-seven cases ( 42.68% ) aged between 40 and 60 years old. The Ct values of ORF1ab and N in females were 29.96±5.28 and 30.38±4.90, which were higher than 27.56±4.94 and 28.03±4.88 in males ( P<0.05 ). The Ct values of ORF1ab and N were the lowest when sampled at 1-7 days after onset ( P<0.05 ), which were 27.84±4.80 and 28.35±4.65. The Ct values of ORF1ab ( rs=0.288, P=0.001 ) and N ( rs=0.296, P=0.001 ) were positively correlated with sampling time. The Ct values of ORF1ab in pharyngeal swab and sputum were 29.19±4.85 and 28.74±6.40, the Ct values of N in pharyngeal swab and sputum were 29.61±4.60 and 29.22±6.10, both without significant differences between different samples ( P>0.05 ). @*Conclusions@#Sampling time has a great influence on the Ct values of ORF1ab and N of SARS-CoV-2.

Research progress in combination applications of antidepressant drugs / 中国中药杂志

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population: A Prospective Study in a Community-Based Chinese Cohort / 中华医学杂志(英文版)

<p><b>Background</b>Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort.</p><p><b>Methods</b>This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage.</p><p><b>Results</b>We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min·1.73 m and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min·1.73 m and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01).</p><p><b>Conclusion</b>An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.</p>

Application of Real-time Quantitative PCR in Detecting Atypical BCR/ABL mRNA Transcripts in Chronic Myelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect atypical BCR/ABL mRNA transcript by real-time quantitative PCR in CML patients without e13a2/e14a2,e19a2 or e1a2 transcripts, and investigate its value of clinical application.</p><p><b>METHODS</b>Twelve cases of CML with positive for t(9;22) translocation, but negative for common major and minor breakpoint cluster regions comfirmed by chromosome karyotyping or FISH analysis, were collected from July 2012 to December 2015. These 12 cases were then detected for b2a3(e13a3), b3a3(e14a3), e6a2, e8a2 and e1a3 fusion variants by real-time quantitative PCR.</p><p><b>RESULTS</b>Among 12 cases 4 variant transcripts were detected, including e1a3 in 1 case (8.33%), e8a2 in 2 cases (16.67%), b2a3 in 5 cases (41.67%) and b3a3 in 4 cases (33.33%), with total positivity of 100%, moreover b2a3 and b3a3 were predominant.</p><p><b>CONCLUSION</b>The detecting atypical BCR/ABL mRNA transcripts by real-time quantitative PCR is suitable for the diagnosis of CML negative for P210, P190 and P230 by standard real-time PCR test, and this detection is still the standard and economic method for monitoring minimal residual disease in CML patients with variants of BCR/ABL fusion gene.</p>

Laparoscopic versus open splenectomy and devascularization for massive splenomegaly due to portal hypertension / 华中科技大学学报（医学）（英德文版）

Although the clinical benefit of laparoscopic splenectomy and devascularization (LSD) has been elaborated in many studies, its application in massive splenomegaly remains controversial. We conducted a retrospective research to assess the curative efficacy of LSD for massive splenomegaly due to portal hypertension. Forty-seven patients with massive splenomegaly due to portal hypertension were enrolled in this study, and divided into two groups. Twenty-one patients underwent open splenectomy and devascularization (OSD) from June 2010 to October 2012 (OSD group). From March 2013 to February 2015, LSD was performed on 26 patients (LSD group). Perioperative variables were analyzed. Compared to OSD, LSD was associated with less blood loss (241.9±110.0 mL vs. 319.0±139.5 mL, P<0.05), more rapid resumption of oral diet (2.46±0.95 days vs. 3.76±1.09 days, P<0.05), and shorter postoperative hospital stay (5.35±1.65 days vs. 7.24±1.55 days, P<0.05). It was concluded that for patients with massive splenomegaly due to portal hypertension, LSD is feasible and as safe as OSD.

Optimization of primary human eccrine sweet glands' isolation in vitro / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To optimize the methods of isolating human eccrine sweat gland cells in vitro so as to get efficiently primary human sweat glands.</p><p><b>METHODS</b>The fresh and normal skin tissue was cut into pieces of microskin about 1mm3 and the following 3 group digestion buffer was applied to isolated gland cells. The digestion buffer of group A was the equivoluminal mixture of Trypsin-Ethylene Diamine Tetraacetic Acid (EDTA) and collagenase-II (2 mg/ml). The digestion buffer of group B was collagenase-II (2 mg/ml) traditionally and group C was Trypsin-EDTA. These three groups were placed into an incubator simultaneously and the emerging time of dissociated sweat glands was calculated. Sweat glands were sorted out and then placed in culture dish. The adherence and the growth of cells were observed. The proliferation index was detected by flow cytometry. The identification of cultured cells was performed by immunocytochemical staining.</p><p><b>RESULTS</b>After digesting 30 min in group A and C, a very few of dissociated sweat glands were emerging. But after digesting for 2 h, there were lots of dissociated sweat glands emerging in group A rather than in group C. The emergence of dissociated sweat glands in group B would require at least 6 hours. After seeded in culture dishes, the sweat glands in group C couldn't adhere to the wall of dish, but the sweat glands in group A and B adhered very well and even grew like paving stones after 9 days. In addition, the proliferation index were (18 ± 4) % and (17 ± 6) % respectively, there was no statistical difference. The results of immunocytochemical staining showed that the cells expressed carcino-embryonic antigen (CEA) and cytokeratin 7(CK7) in group A and B.</p><p><b>CONCLUSION</b>Trypsin-EDTA combined with collagenase-II can shorten the time of isolating sweat gland cells and have no effect on cell activity and proliferation.</p>

Progress of research on microRNA and Alzheimer's disease / 中华医学遗传学杂志

MicroRNA are a group of non-coding RNA which, through regulating expression of proteins at post-transcription level, plays an important role in modulating growth and development of nervous system, cell differentiation and functions. Altered expression of microRNA in the brain may influence development and advance of Alzheimer's disease from multiple perspectives. Research on microRNA will facilitate in depth understanding of the pathogenesis of Alzheimer's disease.

Effect of thymosin alpha-1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro

Thymosin alpha 1 (Tα1) has been shown to have beneficial effects on numerous immune system parameters, but little is known about the effects of Tα1 on patients with gastric carcinoma. The objective of this study was to determine the effect of Tα1 on subpopulations of Th1, Th2, Th17, and regulatory T cells (Tregs) in vitro, and to evaluate its efficacy as an immunoregulatory factor in patients with gastric carcinoma. We compared the effect of Tα1 on the frequency of CD4+ and CD8+ T cells, especially the CD4+CD25+Foxp3+ Tregs in peripheral blood mononuclear cells (PBMCs) from gastric carcinoma patients (N = 35) and healthy donors (N = 22). We also analyzed the changes in the proliferation of PBMCs in response to treatment with Tα1, and examined the production of Th1, Th2, and Th17 cytokines by PBMCs and tumor-infiltrating lymphocytes. The treatment of PBMCs from gastric cancer patients, with Tα1 (50 µg/mL) alone increased the percentage of CD4+CD25+Foxp3+ (suppressive antitumor-specific Tregs) from 1.68 ± 0.697 to 2.19 ± 0.795 percent (P < 0.05). Our results indicate that Tα1 increases the percentage of Tregs and IL-1β, TNF-α, and IL-6 in vitro.

Feasibility study on global peste des petits ruminants eradication based on rinderpest eradication / 病毒学报

Eradication can be defined as permanent elimination of the occurrence of a given infectious disease. A joint FAO/OIE announcement of global rinderpest eradication was declared in 2011. The announcement from two international organizations indicates that the rinderpest virus, like the smallpox virus, will remain only in authorized laboratories. After rinderpest eradication, the relevant researchers shifted their focus on next target-peste des petits ruminants, since they mostly share similarities in such characteristics as etiology and pathology. This paper, on the one hand, analyzed objective and subjective factors in global rinderpest eradication, and on the other hand, reviewed the pros and cons of global peste des petits ruminants eradication.

Financial Barrier against Access to Diagnostic Procedures among Enteric Fever Suspects in Highly-endemic Areas of China.

There is currently no public financial system that fully covers enteric fever suspects in China. This study aimed at documenting the level of access to definitive diagnostic procedures, especially haemoculture, for these patients and examining the effect of health insurance on access to such care. A hospital-based cross-sectional study was conducted in six counties of Yunnan province, using a structured questionnaire and data extraction from medical records. In total, 714 subjects were recruited. Chi-square test and logistic regression were employed for analysis of data. The majority of the subjects were young adults (52%) and farmers (55%) from low-income families (49%). Only 407 (57%) could afford haemoculture routinely advised by their doctors. Of these, 123 (30%) had haemoculture positive for Salmonella Typhi. After adjustment for income, not getting haemoculture was marginally associated with percentage of reimbursement from the insurance (p value for trend=0.047). Illiteracy was also an independent risk factor for this outcome. The poor coverage of haemoculture for patients suspected of having enteric fever in this endemic area was due to financial barrier. The current health-insurance system inadequately relieved the problem. Further financial reform to help patients suspected with enteric fever is required.

Hysteresis in human HCN4 channels: a crucial feature potentially affecting sinoatrial node pacemaking / 生理学报

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate and regulate cardiac rhythm and rate. It has been suggested that, unlike the HCN1 and HCN2 channels, the slower HCN4 channel may not exhibit voltage-dependent hysteresis. We studied the electrophysiological properties of human HCN4 (hHCN4) channels and its modulation by cAMP to determine whether hHCN4 exhibits hysteresis, by using single-cell patch-clamp in HEK293 cells stably transfected with hHCN4. Quantitative real-time RT-PCR was also used to determine levels of expression of HCNs in human cardiac tissue. Voltage-clamp analysis revealed that hHCN4 current (I(h)) activation shifted in the depolarizing direction with more hyperpolarized holding potentials. Triangular ramp and action potential clamp protocols also revealed hHCN4 hysteresis. cAMP enhanced I(h) and shifted activation in the depolarizing direction, thus modifying the intrinsic hHCN4 hysteresis behavior. Quantitative PCR analysis of human sinoatrial node (SAN) tissue showed that HCN4 accounts for 75% of the HCNs in human SAN while HCN1 (21%), HCN2 (3%), and HCN3 (0.7%) constitute the remainder. Our data suggest that HCN4 is the predominant HCN subtype in the human SAN and that I(h) exhibits voltage-dependent hysteresis behavior that can be modified by cAMP. Therefore, hHCN4 hysteresis potentially plays a crucial role in human SAN pacemaking activity.

Chili arsenic contamination in southwest China and its influencing factors / 中国地方病学杂志

Objective To determine the distribution and influencing factors(dehydration method, storage time and chili varieties) of arsenic contents in chilies from southwest China, and the relationship between arsenic content and selenium content in chilies. Methods There were 272 dried chili samples, 76 groups of fresh chili samples and its corresponding soil samples, which were collected from the markets and peasant households in 76 counties of 9 regions in southwest China, and 36 dried chilies from other regions in China and abroad as a comparison. Their dehydration methods and storage time were investigated. The chilies were classified by Bailey Criteria. Arsenic content and selenium content in chilies were determined with hydride generation atomic fluorescence spectrometry. Arsenic content in soils were determined with water bath hydride generation atomic fluorescence spectrum. Results Their ranges of arsenic content in dried chili and fresh chili were 0.2 - 16 637.3,0.2 - 295.8 μg/kg, respectively. The median of arsenic content in the dried chili was 106.9 μg/kg while it was 0.2 μg/kg (dry weight) in the fresh chili. The chilies median arsenic of different drying methods and storage time, in order were: the furnace-dried stored for more 1 than year( 197.3 μg/kg), the sun-dried stored for more than 1 year (130.7 μg/kg), the furnace-dried stored for less than 1 year(94.1 μg/kg), the sun-dried stored for less than 1 year (55.5 μg/kg). The arsenic content of different kinds of solar-dried chilies and roast chilies were different. In solar-dried chilies, the median of arsenic contents from a order of high to low sequences were cluster chili (101.5 μg/kg), cherry chili (95.6 μg/kg), corn chili (86.8 μg/kg), and long chili (47. 1 μg/kg); in roast chilies, the median of arsenic contents from a order of high to low sequences were cherry chili(275.5 μg/kg), cluster chili (173.0 μg/kg), corn chili( 164.3 μg/kg), and long chili( 136.8 μg/kg). The medians of chilies from other regions of China and Turkey were higher than that of southwest China, their median were 125.8,112.3 μg/kg, respectively;the medians of chilies from America, France, and other countries were lower than that of southwest China, their median were 29.4,54.1,85.3 μg/kg, respectively. There was no significant correlation between fresh chilies and its corresponding soil arsenic(r = 0.010, P ＞ 0.05). There was a significant positive correlation between the amount of arsenic and selenium in chilies(r = 0.616, P ＜ 0.05). Conclusions The arsenic of dried chilies from southwest China was higher than that of fresh chilies. The arsenic of chili was different with different dehydration methods and storage time. There was a significant positive correlation between the amount of arsenic and selenium in chilies.

Grass height and transmission ecology of Echinococcus multilocularis in Tibetan communities, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alveolar echinococcosis is a major zoonosis of public health significance in western China. Overgrazing was recently assumed as a potential risk factor for transmission of alveolar echinococcosis. The research was designed to further test the overgrazing hypothesis by investigating how overgrazing influenced the burrow density of intermediate host small mammals and how the burrow density of small mammals was associated with dog Echinococcus multilocularis infection.</p><p><b>METHODS</b>The study sites were chosen by previous studies which found areas where the alveolar echinococcosis was prevalent. The data, including grass height, burrow density of intermediate host small mammals, dog and fox fecal samples as well as Global Positioning System (GPS) position, were collected from field investigations in Shiqu County, Sichuan Province, China. The fecal samples were analyzed using copro-PCR. The worms, teeth, bones and hairs in the fecal samples were visually examined. Single factor and multifactor analyses tools including chi square and generalized linear models were applied to these data.</p><p><b>RESULTS</b>By using grass height as a proxy of grazing pressure in the homogenous pasture, this study found that taller grass in the pasture led to lower small mammals' burrow density (chi(2) = 4.670, P = 0.031, coefficient = -1.570). The Echinococcus multilocularis worm burden in dogs was statistically significantly related to the maximum density of the intermediate host Ochotona spp. (chi(2) = 5.250, P = 0.022, coefficient = 0.028). The prevalence in owned dogs was positively correlated to the number of stray dogs seen within a 200 meter radius (Wald chi(2) = 8.375, P = 0.004, odds ratio = 1.198).</p><p><b>CONCLUSIONS</b>Our findings support the hypothesis that overgrazing promotes transmission of alveolar echinococcosis and confirm the role of stray dogs in the transmission of alveolar echinococcosis.</p>

Biological approaches to generating cardiac biopacemaker for bradycardia / 生理学报

Normal rhythm in a healthy human heart originates from the natural biological pacemaker, the sinoatrial (SA) node which locates in the right atrium. SA node dysfunction or atrial-ventricular (AV) conduction block causes improper heart rate (bradycardia). Such dysfunction, if severe enough, is currently treated by implanting an electronic pacemaker which has been well established technically, but there are some limitations and inadequacies. Recently, progress in developing engineered cardiac biopacemakers with use of genes or cells has been made in experimental animal models. The hyperpolarization-activated cyclic-nucleotide-modulated (HCN) channel (pacemaker channel) modulates cardiac automaticity via the hyperpolarization-activated cation current (I(f)). HCN genes have been delivered to animal myocardium via viral vectors or HCN-transferred cells for recreating biological pacemakers. Approaches with non-HCN genes or transplantation of beating cells are also novel and have been investigated for generating cardiac biopacers. This article summarizes the progresses in research on recreation of cardiac biopacemakers. Genetically engineered biological pacemaker holds great promise to potentially cure severe bradycardia if critical issues, such as their stability and longevity, are properly solved.

Impact of overgrazing on the transmission of Echinococcus multilocularis in Tibetan pastoral communities of Sichuan Province, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Overgrazing was assumed to increase the population density of small mammals that are the intermediate hosts of Echinococcus multilocularis, the pathogen of alveolar echinococcosis in the Qinghai Tibet Plateau. This research tested the hypothesis that overgrazing might promote Echinococcus multilocularis transmission through increasing populations of small mammal, intermediate hosts in Tibetan pastoral communities.</p><p><b>METHODS</b>Grazing practices, small mammal indices and dog Echinococcus multilocularis infection data were collected to analyze the relation between overgrazing and Echinococcus multilocularis transmission using nonparametric tests and multiple stepwise logistic regression.</p><p><b>RESULTS</b>In the investigated area, raising livestock was a key industry. The communal pastures existed and the available forage was deficient for grazing. Open (common) pastures were overgrazed and had higher burrow density of small mammals compared with neighboring fenced (private) pastures; this high overgrazing pressure on the open pastures measured by neighboring fenced area led to higher burrow density of small mammals in open pastures. The median burrow density of small mammals in open pastures was independently associated with nearby canine Echinococcus multilocularis infection (P = 0.003, OR = 1.048).</p><p><b>CONCLUSION</b>Overgrazing may promote the transmission of Echinococcus multilocularis through increasing the population density of small mammals.</p>