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ObjectiveNocardia is an apathogen that causes opportunistic infections in humans and has a global distribution. In recent years， resistance of Nocardia to commonly used drugs have been observed， highlighting the urgent need for the identification of new drug targets and the development of novel antimicrobial agents against Nocardia. MethodsThirty-one complete genome sequences of Nocardia strains were retrieved from the GenBank database. Pan-genomic analysis was performed using BPGA， and drug target candidates were screened using subtractive proteomics. Homology modeling was employed to predict the 3D structures of target proteins， and potential drugs targeting these proteins were predicted using DrugBank. Molecular docking techniques were utilized to validate the binding activity between the drugs and target proteins. ResultsThe pan-genomic analysis of the 31 Nocardia strains revealed 1 421 core proteins. Fifteen candidate drug target proteins were identified through subtractive proteomics analysis. Among them， the physicochemical properties of the OG1493 protein （such as amino acid count， molecular weight， isoelectric point， grand average of hydropathicity， fat index，and instability index Ⅱ） were found to be most suitable for a drug target protein. Using the DrugBank database， seven compounds， namely Adenosine-5'-Rp-Alpha-Thio-Triphosphate， alpha，beta-Methyleneadenosine 5'-triphosphate， Phosphoaminophosphonic Acid-Adenylate Ester ，Radicicol，2-Hydroxyestradiol， p-Coumaric acid， and Ethylmercurithiosalicylic acid were identified as potential compounds capable of exerting anti-Nocardia effects by targeting this protein. Molecular docking results indicated a strong binding affinity between the target protein and these compounds. The experimental result showed that that Radicicol could be a potential antibacterial drug targeting this particular protein. ConclusionPan-genomic analysis and subtractive proteomics are valuable approaches for mining novel anti-Nocardia drug targets.
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The severe acute syndrome coronavirus 2(SARS-CoV-2)is responsible for the global pandemic of 2019 novel coronavirus disease(COVID-19). Understanding the pathogenic mechanisms of SARS-CoV-2 is of great significance to the prevention and control of the COVID-19 epidemic. The spike(S)protein of SARS-CoV-2 is a major target of protective immunity. The mutations of S protein impact the transmission and pathogenic capacity of SARS-CoV-2. In addition, angiotensin-converting enzyme 2(ACE2)is the receptor of SARS-CoV-2 S protein and mediates viral entry into target cells. The genetic polymorphisms of the ACE2 gene may lead to the difference of incidence of COVID-19 among different populations. Protease can promote the infection of SARS-Cov-2 by activating the S protein. This review summarized the current understanding of the function and genetic variants of S protein, ACE2, and the related proteases. The synergistic effect of these three molecules on the susceptibility of SARS-CoV-2 infection was further discussed.
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To retrospectively analyze the application trend of cohort study in the field of liver cancer in past 27 years and to look forward to the future development trend. Chinese and English papers reporting the cohort studies of liver cancer conducted in the mainland of China since 1991 were included. The literature management software was used to analyze the publication time, institution, type and objective of the studies and the follow-up performance. Statistical analysis was carried out by using SPSS 21.0. The number and quality of the papers reporting liver cancer-related cohort studies increased significantly in past 27 years and a core English journal group of this field has formed. The average annual growth rates of Chinese and English papers published were 20.4 and 35.2 respectively. About 52.3 of the Chinese papers and 73.5 of the English papers were published in past five years and the quality of these papers was high. The Chinese papers published on Chinese core journals accounted for 49.2, and the English papers published on SCI periodicals (IF>3) accounted for 47.3. For the study objective, those published on the domestic journals mainly focused on the pathogenesis of hepatoma (41.5), studies with large sample size was the common form. The SCI studies mainly focused on the prognosis of liver cancer (40.7). High-quality SCI papers are more interested in the studies of prognosis, and survival analysis was the common form. The application of cohort study in the field of liver cancer gradually increased in China. Large-scale study and prognosis analysis were conducted commonly. However, it is necessary to further improve the researchers' understanding of cohort study, improve the follow-up quality, and increase the application of scientific evaluation methods, such as survival analysis, for the better solving of clinical problems.
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Chronic primary immune thrombocytopenia (CITP) is the most common acquired autoimmune disease that seriously threaten the physical and mental health of patients. Compared with Western medicine treatment, the intervention and treatment of Chinese medicine (CM) has shown certain therapeutic advantages. This paper reviewed the new pathogenesis progress on T cell immune abnormality in CITP, and CM studies on interferes effects of cellular immune regulation of CITP in recent years. Qi deficiency failing to control blood and internal obstruction of blood stasis are the two common types of CM syndromes in CITP patients, the corresponding treatments include invigorating Pi (Spleen), supplementing qi, activating blood, as well as tonifying qi and activating yang, regulating Gan (Liver) to invigorate Pi. The authors also mentioned the problems in the research field of CM for CTIP treatment, and put forward new ideas for the research in the future.
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Objective To explore SECTRA 3D real-time reconstruction of virtual simulation technology in the anat-omy teaching of otolaryngology. Methods Eighty medical students who have received traditional class teaching of otolaryngology anatomy joined the SECTRA 3D real-time reconstruction class to study the major anatomic knowledge of otolaryngology. Questionnaires and exams were provided for them before and after the SECTRA 3D real-time re-construction class. Results The test scores were 79.19±10.39 before 3D class and 87.69±10.25 after 3D class. After teaching, the scores improved significantly.Conclusions Application of SECTRA real-time reconstruction of 3D virtual simulation technology in otolaryngology anatomy teaching, can help medical students to master the ana-tomical knowledge better than the traditional class teaching and can stimulate their interests to learn otolaryngology anatomy.
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Objective To establish a species identification system based on DNA genetic markers for plant evidence. Methods Two hundred common plants in Shanghai were collected and identified by mor-phological characteristics. The primers of gene segments rbcL, matK, and ITS were designed and amplified. The PCR amplicon was detected by agarose gel electrophoresis. After the sequencing, the universality and the identification capacity of the three markers were evaluated. Results The success rate of amplifi-cation was in order of rbcL (99.5％) >matK (92.5％) > ITS (86.0％). The identification capacity of the combination of rbcL and matK was better than that of rbcL or matK, by which most plant species could be identified to the genus or higher. ITS was not suitable to be a unique marker because of its unstable result, but it still could be a powerful supplement. The identification capacity of the combination of rbcL, matK and ITS was higher than that of rbcL and matK, by which most plant species could be identified to the genus or lower. Conclusion The identification system with the combination of rbcL, matK and ITS as markers has excellent universality for plant evidence, which can distinguish most plant species to the genus or lower.
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Through literature review and theoretical analysis,an initial scale was designed with five dimensions namely"evidence influence","organizational support","channel connectivity","communication and collabora-tion"and"decision-makers impetus". The reliability and validity of the scale were evaluated through questionnaire survey on HTA researchers. It is reported that the overall Cronbach's α coefficient of the questionnaire was 0.904, meanwhile the Cronbach's α coefficient of each dimension was more than 0.80 except the dimension of"decision-makers impetus". The average variance extraction of each dimension was more than 0.50. The maximum of correla-tion coefficients between each dimension was 0.571,which was less than the threshold value of 0.85. Additionally, for certain dimensions,the standardized correlation coefficients to each other dimensions was less than regarding arith-metic square root of average variance extraction.
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Primary gastric cancer (GC) is one of the most frequently diagnosed cancers worldwide.The incidence of GC in male is approximately twice the incidence thereof in female.Before 60 years of age, the male-female ratio of GC incidence has no geographic and ethic differences, and rises with the increase of age.Studies of classic and molecular epidemiology have proved that the sexual dimorphism in GC is due to synergetic effects of various factors including chronic infection, dietary habit, gene mutation, genetic susceptibility, estrogenic effects and differences in lifestyle behaviors, etc.Studies on the above-mentioned factors can not only help clarify the carcinogenesis of GC, but also help improve the strategies of GC control and prevention, and reducing GC incidence subsequently.
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide.About 50% of the total number of HCC cases and deaths worldwide occurred in China.Male has high incidence rates of HCC.Epidemiological data showed that ratio between the male incidence of HCC and the female incidence was from 2∶1 to 5∶1 in China.Up to now, risk factors found to be able to give rise to the sexual dimorphism in HCC incidences include infection and mutation of hepatitis B virus, immune genetic susceptibility and functions of hormone receptors.Relevant studies can not only help clarify the specific biological processes of hepatocarcinogenesis, but also uncover the biological indications that associate the incidences and prognoses of HCC with the sexual dimorphism, thus playing an important role in improving the strategies of control and prevention.
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Multidrug resistance (MDR) is a major problem in the current treatment of liver cancer.ATP binding cassette (ABC) transports induce drug effluxes in cancer cells, thus contributing to MDR.ABCB1 is a main subtype of ABC transports that mediates the MDR of liver cancer.The expression of ABCB1 is related to the stemness characteristics of liver cancer cells.The key molecules of a variety types of signaling pathways related to inflammation and cancer collaborate with one another and adjust the expression of ABC transports.Verapamil can reverse the MDR of liver cancer through inhibiting ABCB1.Further investigations of the relation between ABC transporters and the MDR in liver cancer can improve treatment strategy for cancer and reduce mortality.
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Stampede accidents are one kind of mass disaster that may cause heavy casualties and usually occurs at mass gathering events .Once a stampede accident occurs , it is difficult to stop panic spreading and to rescue the injured .Therefore, prevention and disaster preparation play a central role in reducing group casualties .In order to help promote a basic understanding of this mass disaster , this paper analyzes the psychosocial characteristics of crowds which may easily give rise to stampede accidents , summarizes relevant risk factors and put forward suggestions regarding these risk factors .The real-time monitoring and control of the density and movement of crowds are crucial points in preventing stampede accidents.A detailed emergency response plan as well as supporting facilities shall be made available for mass gathering events so as to stop contingencies from becoming stampede accidents .
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Human violent behavior is a complex behavior which is influenced by genetic and environmental factors. There is a trend in investigating the mechanism of violent behavior by using the genetic methods. This article reviews several candidate genes and advances in epigenetics which are associated with violent behavior. The prospects and significance of violent behavior research from the view of gene polymorphism and epigenetics are also discussed.
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Humans , Aggression , Epigenesis, Genetic , Forensic Genetics , Polymorphism, Genetic , ViolenceABSTRACT
Objective] To investigate the relationship between hepatitis B virus( HBV) genotype and their mutations on the development of hepatocellular carcinoma ( HCC ) . [ Methods ] A cohort study on patients with chronic HBV infection was followed up.HBV genotypes were identified by nested multiplex PCR and multiplex PCR.And HBV mutations in the basic core promoter region were sequencing by PCR amplification. [ Results] The patients infected with genotype B were followed up for an average of 8.52 years (IQR:6.67-10.75), of whom the incidence of HCC was 6.55/1 000 person-years.After follow up with an average of 8.87 years (IQR:6.85-11.33), the incidence of HCC was 11.63/1 000 person-years for the patients infected with genotype C, which were significantly higher than those infected with genotype B (P=0.006).In genotype B HBV infected patients, age (≥60 years), cirrhosis can in-crease the risk of HCC, and in genotype C patients, male, age (≥40 years), cirrhosis, C1653T, T1753V, A1762T/G1764A mutation as well.Interferon therapy can reduce the risk of HCC.In genotype C group, interferon treatment reduced HCC risk in patients carrying A1762T/G1764A mutation (HR=0.21, P=0.008) and in those without T1753V ( HR=0.08, P=0.012) and C1653T mutation ( HR=0.17, P=0.013). [Conclusion] HBV genotypes and mutation are closely associated with HCC.Patients infected with genotype C, carrying 1762T/G1764A mutation should be given priority of receiving antiviral treatments in order to prevent HCC;those carrying C1653T or T1753V mutation should be monitored closely to detect early HCC and receive timely surgical resection.
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Objective] To explore disaster response capability and the vulnerability as well as the current level and training needs of disaster medicine knowledge in urban populations . [ Methods] Five communities in Yangpu District of Shanghai were randomly enrolled in this study .The study populations were then stratified by age groups .A total of 1700 residents were recruited , 1643 of which completed a structured questionnaire designed by the investigators . [ Results] Eight-nine percent of the residents be-lieved the importance of understanding disaster medicine -related knowledge .The correct answer rates of “pro-tective measures of nuclear leakage issues” and “self-rescue measures in a high building fire” reached over 80%;however , the overall correct answer rate of “cardiorespiratory resuscitation operation” was less than 40%.The main channels of community residents accessing disaster medicine knowledge were mainly news -papers, magazines, and internet (52.1%);whereas only 5.3%of them obtained the knowledge from school education .Community residents most liked to obtain “first aid skills”and“basic theory of disaster medicine”through formal lectures (72.4%). [Conclusion] School education lacks disaster-related knowledge , pos-sibly resulting in the fact that community residents have a limited ability to save both oneself and others in disaster .There are significant differences between residents with different education levels .Community resi-dents have limited knowledge of disaster occurrence and development , and lack capabilities of self-rescue and mutual aid .Colleges should increase the contents of disaster medicine education in their curriculum .Disaster education should be enforced in school education .Continued education and simulation of disaster-related knowledge should be regularly offered to community residents to greatly reduce their vulnerability to disasters .
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The process of carcinogenesis starts in the proinflammatory microenvironment and is abided by Darwinian evolution theory: mutation-selection-adaption; and the genetic basis of this process is the generation and accumulation of somatic mutations. Currently the molecular mechanisms of massive nucleotide alterations and natural selection of mutant cells under environment pressure still remain unclear. The apolioprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of cytidine deaminases, which is transcriptionally induced by proinflammatory cytokine and chemokine, plays important roles in the innate and adaptive immunities of human organism. APOBECs can not only inhibit viral replication but also facilitate the generation of cancer-promoting viral mutants; they can also facilitate the generation of driver mutations in the host genes, thus contribute to the development of cancers. APOBECs, as hallmark enzymes bridging inflammation and cancer, play an important role in cancer evolution.
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AIM:To explore the involvement of oxidative stress and apoptosis in the pathogenesis of diabetic cataract induced by Streptozotocin ( STZ) and the interventions of puerarin in order to supply references for clinical treatment. METHODS:Male SD rats were divided into four groups randomly, control group, diabetic group, apocynin group and puerarin group. The diabetic group were replicated by single injection of STZ (65mg/kg, ip). The expression of p22, p47, p67, Bax/Bcl2, Caspase 3 and P53 proteins were detected by Western Blotting. RESULTS:The diabetic rats were replicated successfully and the expression of Bcl2 was downregulated while the expression of p22, p47, p67, Bax, Caspase 3 and P53 were upregulated in diabetic group with a significant statistical differences when compared with control group (PCONCLUSION: NADPH oxidase mediated oxidative stress and P53, Bax/Bcl2 mediated apoptosis are involved in the pathogenesis of diabetic cataract and puerarin can alleviate cataract greatly by inhibiting the aforementioned signal pathway.
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<p><b>OBJECTIVE</b>To investigate the results of surgical treatment for primary liver cancer of segment VII or VIII.</p><p><b>METHODS</b>The clinical data of 149 patients with primary liver cancer who underwent hepatectomy between January 2005 and December 2010 was retrospectively analyzed. There were 120 male and 29 female patients, aging from 19 to 75 years with a mean of 53.1 years. Among 149 patients, tumors were located at segment VII, VIII or several segments containing VII or VIII (VII/VIII group) in 53 patients, located at other segments (non-VII/VIII group) in 96 patients. The results of surgical treatment for VII/VIII group and non-VII/VIII group were compared by using t test, χ(2) test, Kaplan-Meier survival analysis and Cox proportion hazard regression analysis.</p><p><b>RESULTS</b>Right liver lobe was turned over completely in VII/VIII group, hepatic lobe which tumor was located at was not or partly turned over in non-VII/VIII group. Compared with non-VII/VIII group, VII/VIII group had longer operative time ((215 ± 68) min vs. (123 ± 36) min, t = 2.860, P = 0.01). No significant difference was found for tumor size, tumor number, tumor encapsulation, microvascular invasion, Edmondson grade, pTNM stage, intraoperative blood loss, blood transfusion rate, R0 resection rate and postoperative complication rate between two groups. The cumulative 1-, 3-, and 5-year overall survival rates were 74.6%, 42.3%, 15.4% respectively, in VII/VIII group, and 89.3%, 63.0%, 40.4% respectively, in non-VII/VIII group (χ(2) = 13.501, P = 0.000). Univariate and multivariate analysis of prognostic factors indicated that tumor location (tumor was located at segment VII or VIII) had unfavorable prognostic influence on overall survival (χ(2) = 10.329, P = 0.001; HR = 1.693, 95%CI: 1.232 - 2.694, P = 0.013).</p><p><b>CONCLUSION</b>The results of surgical treatment for primary liver cancer located at segment VII or VIII are worse than that located at other segments.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Follow-Up Studies , Kaplan-Meier Estimate , Liver Neoplasms , Diagnosis , General Surgery , Prognosis , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the manifestation, characteristics and treatment of lipoid proteinosis (LP) in larynx.</p><p><b>METHODS</b>Sixteen cases of LP with hoarseness as the first sign were reported. The onset was in the newborn period in 10 cases. The upper eyelids were infiltrated in all cases, 13 of them reported an age of onset older than 6 - 8 years. The laryngeal behaviors and its treatment, multisystem manifestations, and characteristics of histopathology were evaluated.</p><p><b>RESULTS</b>One patient had moderate hoarseness, and the others had severe hoarseness. Videolaryngoscopy revealed thickening of the interarytenoid region and irregularities along the rims and the surface of the vocal folds due to yellowish papules. Oral tissues showed yellow-white infiltrates in 13 cases (81.3%). Whitish moniliform papules on the upper eyelids were found in all cases. Pock-like or acneiform scars were particularly evident on the face and the limbs in 14 cases (87.5%). Histologically, it was characterized by deposition of hyaline material in the submucosa and dermis of the eyelid or larynx with periodic acid-Schiff-positive and Congo red stain-negative. Eight patients underwent microlaryngosurgery for the excision of deposits in the vocal folds. The vocal function was significantly improved after surgery.</p><p><b>CONCLUSIONS</b>One of the most common features of lipoid proteinosis is hoarseness since infancy with laryngeal involvement. LP patients also display skin or mucosa infiltration of multiple systems. Microlaryngosurgical excision of the deposits in the vocal fold could improve the voice.</p>
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Laryngeal Diseases , Diagnosis , Pathology , General Surgery , Larynx , Pathology , General Surgery , Lipoid Proteinosis of Urbach and Wiethe , Diagnosis , Pathology , General Surgery , Skin , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression and its clinical significance of estrogen receptor (ERα) and phosphorylated estrogen receptor (p-ERα) in patients with hepatocellular carcinoma. The associations between ERα, p-ERα and IL-6 were also analyzed.</p><p><b>METHODS</b>Immunohistochemistry was used to detect the expression of ERα, p-ERα and IL-6 in tumor tissues from 77 cases with hepatocellular carcinoma. The relations between ERα and the clinical pathological parameters and prognosis were also analyzed.</p><p><b>RESULTS</b>The positive rates of ERα, p-ERα and IL-6 in hepatocellular carcinoma were 39.0% (30/77), 45.4% (35/77) and 72.7% (56/77), respectively. The expression of ERα and p-ERα were negatively correlated with the expression of IL-6 (r=-0.468, P<0.01; r=-0.370, P<0.01, respectively). The positive rate of ERα in patients with tumor size≤5 cm, serum level of alpha-fetoprotein<400 µg/L, with complete encapsulation and non-microvascular invasion was significantly higher than those with tumor size>5 cm, serum level of alpha-fetoprotein≥400 µg/L, non-complete encapsulation and with microvascular invasion (all P<0.05). The overall survival rates of ERα-positive and ERα-negative patients were 66.7% and 23.4% (P<0.05). And the disease-free survival rates of ERα-positive and ERα-negative patients were 83.3% and 57.4% (P<0.05).</p><p><b>CONCLUSIONS</b>The tumor biological features of ERα-positive patients are better than that of ERα-negative patients. The role of ERα in hepatocellular carcinoma may be related to IL-6 level.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Carcinoma, Hepatocellular , Metabolism , Pathology , Estrogen Receptor alpha , Metabolism , Hepatitis B , Metabolism , Pathology , Interleukin-6 , Metabolism , Kaplan-Meier Estimate , Liver Neoplasms , Metabolism , Pathology , Phosphorylation , Prognosis , Proportional Hazards ModelsABSTRACT
<p><b>OBJECTIVE</b>To observe serum adiponectin, free fatty acid (FFA) profile and other glucose and lipid metabolic parameters in essential hypertensive patients with metabolic syndrome (HPMS) or without metabolic syndrome (HP).</p><p><b>METHODS</b>The serum adiponectin was measured with the radioimmunoassay, FFA profile measured with the gas chromatography and mass spectrometer in 72 HPMS, 56 HP and 43 normal control subjects.</p><p><b>RESULTS</b>Serum adiponectin were significantly lower in HPMS group than those in the HP and control group (P < 0.05 or P < 0.01). Serum total free fatty acid (TFA), unsaturated fatty acid (UFA, linoleic acid, oleic acid, arachidonic acid, docosahexaenoic acid, eicosatrienoic acid), polyunsaturated fatty acid (PUFA) and n6PUFA were significantly higher in HPMS group than those in the HP and control groups (P < 0.05 or P < 0.01). Adiponectin was negatively correlated with body mass index, waist circumferences, waist hip ratio, triglycerides (r = -0.222, -0.235, -0.179, -0.194, P < 0.01 or P < 0.05, respectively) and positively correlated with high-density lipoprotein cholesterol (r = 0.336, P < 0.01); TFA and PUFA were positively correlated with body mass index, waist circumferences, fasting blood glucose, mean arterial pressure (r = 0.241 and 0.280, 0.198 and 0.188, 0.226 and 0.298, 0.274 and 0.334, P < 0.01 or P < 0.05, respectively) in all subjects.</p><p><b>CONCLUSION</b>Our data suggest that changes in serum adiponectin, FFA and n6PUFA might promote the development of metabolic syndrome in essential hypertensive patients.</p>