Specific DNA barcodes screening, germplasm resource identification, and genetic diversity analysis of Platycodon grandiflorum / 药学学报

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Identification and expression analysis of cellulose synthase family genes in Aquilaria sinensis / 药学学报

Cellulose synthase (CesA), one of the key enzymes in the biosynthesis of cellulose in plants, plays an important role in plant growth and plant resistance. In this study, a total of 21 AsCesA genes from Aquilaria sinensis were systematically identified and the physico-chemical characteristics were analyzed based on genome database and bioinformatical methods. The phylogenetic tree was constructed and the gene location on chromosome, cis-acting elements in the 2 000 basepairs upstream regulatory regions and conservative motifs were analyzed. The AsCesA proteins were mainly located on the plasma membrane. The number of amino acids of the proteins ranged from 390 to 1 261. The isoelectric point distributed from 5.67 to 8.86. All of the 21 AsCesA proteins possessed the transmembrane domains, the number of which was from 6 to 8. The genes were classified into 3 groups according to the phylogenetic relationship. Obvious differences were observed in motif composition in genes from different groups. However, motif2, motif6, motif7 and motif10 were observed in all of AsCesA proteins. Analysis of cis-acting elements indicated that AsCesA genes family has cis-acting elements related to plant hormones, abiotic stresses, and biological processes. Seven AsCesA genes with differential expression were selected according to the calli transcriptome data induced by NaCl at different times and their expression levels under different abiotic stresses were analyzed by quantitative real-time PCR. The results indicated that salt, low temperature, drought, and heavy metal stresses could affect the expression level of AsCesA genes, and the abundance of AsCesA1, AsCesA3 and AsCesA20 showed a significant change, implying their potential important roles to the abiotic stresses. The accumulation pattern of cellulose content under different abiotic stresses was similar to the expression trend of AsCesA genes. Our results provide valuable insights into the role of cellulose synthase in A.sinensis in plant defense.

Current status and influencing factors of different initiation time of antiretroviral therapy in HIV/AIDS patients / 上海预防医学

ObjectiveTo investigate the status of different antiretroviral therapy（ART） initiation times in patients with HIV/AIDS and analyze the relevant characteristics and influencing factors of delayed ART. MethodsFrom December 2018 to December 2020， a survey was conducted among adult HIV/AIDS patients treated in 28 designated AIDS prevention and treatment institutions in Beijing， Shanghai， Guangdong， Jiangsu， Henan， Jiangxi， Guangxi， Yunnan and other places. Data of the basic demographic information， lifestyle and chronic disease prevalence， and characteristics of diagnosis and treatment were collected. The characteristics and related factors of delayed ART were compared and analyzed. ResultsThe median age of 1 741 patients was 41 years old （IQR： 32‒52）. The initial CD4 count of most patients was less than 200 cells·μL-1（51.4%）. Among them， 1 027 patients had delayed ART （59.0%）， and the association between ART initiation time and initial CD4 count varied with the time of diagnosis of HIV infection. Multivariate logistic analysis showed that the older age （aOR=0.99， 95%CI： 0.98‒0.99） was associated with a higher rate of starting ART within 1 month after diagnosis， while those diagnosed before 2017 and with the initial CD4 count >200 cells·μL-1 were more likely to delay ART. Delayed initiation of ART may be a risk factor for poor sleep quality and co-infection in HIV/AIDS patients. ConclusionWith the expansion of free ART in China， the proportion of delayed ART with HIV/AIDS shows a downward trend. Timely ART management should be strengthened for the young HIV/AIDS patients and patients with high CD4 counts.

Effects of prenatal nicotine exposure on enamel formation of offspring mice / 中华口腔医学杂志

Objective: To investigate the effects of nicotine on the morphology, structure of offspring's dental germ, enamel organ and other dental tissues and the further potential epigenetic mechanisms by establishing prenatal nicotine exposure mouse model. Methods: Ten C57BL/6 pregnant mice were randomly divided into control group (physiological saline subcutaneous injection) and prenatal nicotine exposure (PNE) group (nicotine subcutaneous injection) by using a random number table. Postnatal day 0 (P0), postnatal day 14 (P14) and postnatal day 25 (P25) offspring mice were collected for subsequent experiments. The offspring mice were divided into offspring control group and offspring PNE group according to the maternal group respectively. Weights of P0 and P25 offspring mice were recorded. Micro-CT, scanning electron microscope (SEM) and Vickers hardness test were performed to analyze the related parameters of hard tissues including alveolar bones and mandibular incisors. Total RNAs were extracted from mandible tissues and the third generation of dental epithelial stem cells (DESC) in P25 mice. The relative expression levels of osteogenic and ameloblastic differentiation related genes were measured by real-time quantitative PCR (RT-qPCR). Immunohistochemical stainings of paraffin sections were then performed to observe the distribution and expression level of proliferating cell nuclear antigen (Pcna), amelogenin (Amelx), histone H3 trimethylated at lysine 27 (H3K27me3) and enhancer of zeste homolog 2 (Ezh2). Cell counting kit-8 (CCK-8) assays were used to detect the cell viabilities of DESCs after administrations of different concentrations of nicotine (0.01, 0.1, 1 mmol/L) and GSK126 (an inhibitor of histone methyltransferase Ezh2). Results: Compared with the control group, pregnant mice in PNE group were more likely to have adverse pregnancy outcomes, such as significantly lower offspring body weight [P0: offspring control (1.20±0.04) g, offspring PNE (0.99±0.02) g, P<0.001; P25: offspring control (15.26±1.70) g, offspring PNE (9.65±1.32) g, P<0.001] and increased stillbirths rate [offspring control (0), offspring PNE (46.40±9.30) %, P<0.001]. At P14 and P25, the distance parameters between the enamel mineralized deposits of mandibular incisors and the mesial surface of the first molar in offspring PNE group [P14: (-1 349±45) μm; P25: (-1 192±147) μm] was significantly decreased compared with the control group [P14: (-506±380) μm, P25: (504±198) μm] (P<0.05, P<0.001). The enamel column and enamel column stroma of incisors in offspring PNE group were blurred, arranged loosely and disorderly than those in the control group, while the microhardness of incisor enamel in offspring PNE group [(245.7±18.4) MPa] was significantly lower compared to the control group [(371.9±28.7) MPa] (P<0.001). HE staining showed disordered pre-ameloblast (Pre-Am) arrangement and delayed mineralization deposition point in offspring PNE group compared with the control group, while the length of transit-amplifying cell (TA) and Pre-Am region were prolonged as well. Immunohistochemical staining results displayed that the overall Pcna (P<0.05), H3K27me3 (P<0.01), Ezh2 (P<0.01) expression of labial cervical loop (LaCL) in PNE group were increased, while the positive signal of Amelx in ameloblast cytoplasm was impaired. In vitro, the addition of 1 mmol/L nicotine could significantly upregulate the expression level of Pcna (P<0.01) and downregulate the expression levels of B lymphoma Mo-MLV insertion region 1 (P<0.05), leucine rich repeats and immunoglobulin like domains 1 (P<0.05), Amelx (P<0.01). In addition, 1 mmol/L nicotine could also significantly enhance the proliferation activity of DESCs (P<0.001). Addition of 10 μmol/L GSK126, could rescue the proliferation activation effect of 1 mmol/L nicotine on DESCs. Conclusions: PNE may delay the process of enamel formation and lineage differentiation, leading to the abnormal proliferation of DESCs and changes of epigenetic modification state in H3K27me3, which affect the development of enamel in offspring mice,suggesting PNE might be one of risk environmental factor for tooth development.

Acupuncture therapy reduces cervical and shoulder pain in patients with stroke / 中国基层医药

Objective:To investigate the clinical effects of acupuncture therapy on post-hemiplegia neck and shoulder pain.Methods:Eighty patients with post-stroke hemiplegia with neck and shoulder pain who received treatment in Department of Acupuncture, Massage and Physiotherapy, Zhejiang Provincial Armed Police Corps Hospital between December 2020 and June 2021 were included in this study. They were randomly assigned to undergo either conventional rehabilitation treatment and analgesic tablets (control group, n = 40) or conventional rehabilitation treatment, analgesic tablets and acupuncture therapy in combination (observation group, n = 40). Traditional Chinese medicine efficacy, western medicine efficacy, degree of neurological deficits, ability of daily living, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, traditional Chinese medicine efficacy and western Chinese medicine efficacy in the observation group were significantly higher than those in the control group (87.50% vs. 52.50%, 82.50% vs. 55.00%), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (17.50% vs. 42.50%, χ2 = 21.48, 16.33, 9.12, all P < 0.05). In the control group, National Institutes of Health Stroke Scale (NIHSS) score measured after treatment was significantly lower than that measured before treatment [(7.58 ± 1.87) points vs. (14.87 ± 1.36) points, t = -9.58, P < 0.001], and Barthel Index (BI) measured after treatment was significantly higher than that measured before treatment [(53.78 ± 1.34) points vs. (37.92 ± 1.74) points, t = 6.35, P < 0.001]. In the observation group, NIHSS score measured after treatment was significantly lower than that measured before treatment [(5.44 ± 2.11) points vs. (14.51 ± 0.34) points, t = -12.69, P < 0.001], and BI measured after treatment was significantly higher than that measured before treatment [(62.02 ± 0.68) points vs. (37.73 ± 1.58) points, t = 7.45, P < 0.05]. BI post-measurement in the observation group was significantly higher than that in the control group [(62.02 ± 0.68) points vs. (53.78 ± 1.34) points, t = 4.35, P < 0.05]; NIHSS score post-measurement in the observation group was significantly lower than that in the control group [(5.44 ± 2.11) points vs. (7.58 ± 1.87) points, t = -8.48, P < 0.05]. Conclusion:Acupuncture treatment for post-hemiplegia neck and shoulder pain can markedly reduce pain in patients, improve prognosis and increase clinical efficacy.

Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia / 中国中药杂志

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.

Prediction of plasma protein binding rate based on machine learning / 中国药科大学学报

@#Predicting the protein binding rate of drugs in plasma is helpful to us in understanding the pharmacokinetic characteristics of drugs, with much value of reference for early research on drug discovery. In this study, plasma protein binding rate information of 2 452 clinical drugs were collected.Two pieces of software, Molecular Operating Environment (MOE) and Mordred, were used to calculate molecular descriptors, which were used as input features of the model.Extreme gradient boosting (XGBoost) algorithm and random forest (RF) algorithm were then used to build a machine learning model.The results showed that, compared with MOE, the prediction performance of the constructed model was better using the molecular descriptor calculated by Mordred as the input of the model.The prediction performance results of the model constructed using the XGBoost algorithm and the RF algorithm were similar, and the R2 of the optimal model were both 0.715.According to the research results, it can be concluded that the drug plasma protein binding rate is closely related to some physical and chemical properties of the drug molecule, such as water solubility, octanol/water partition coefficient and conjugated double bonds.Using these parameters to predict the plasma protein binding rate of drugs has the advantages of convenience and efficiency, which can provide reference for related pharmacokinetic studies.

Effects of cervical rotatory manipulation on severe rabbit carotid atherosclerosis in flow sheer stress / 解剖学报

Objective: To investigate the effects of cervical rotatory manipulation (CRM) on severe carotid atherosclerosis of rabbits in hemodynamics. Methods: Totally 40 New Zealand rabbits were divided randomly into 3 groups, including the manipulation group, the model group and the control group. Left carotid atherosclerotic plaques models were developed in the rabbits of manipulation group and model group. Then, the manipulation group was treated with CRM lasting for 2 weeks; meanwhile no intervention was given on rabbits in the model group and control group. At the end of manipulation, flow sheer stress (FSS) was calculated with velocity and viscosity of blood. One way AN OVA and LSR-t test were performed to explore the significance. Results: FSS of left carotid artery in rabbit decreased significantly in the manipulation group and the model group, in comparison with the control group. Moreover, FSS in the manipulation group was lower than that in the model group. Conclusion: FSS of severe atherosclerotic carotid artery in rabbit may become decreased following with CRM.

Persistent depression is a predictor of quality of life in stroke survivors: results from a 5-year follow-up study of a Chinese cohort / 中华医学杂志(英文版)

BACKGROUND@#Whether the time course of post-stroke depression (PSD) can be used to predict the quality of life (QoL) of patients with late-stage stroke remains unclear, this study investigated whether persistent depression at 1 year after stroke predicts QoL at 5 years following stroke.@*METHODS@#We analyzed the demographic and clinical data of patients with stroke in 56 hospitals across China that participated in the Prospective Cohort Study on the Incidence and Outcome of Patients with PSD in China Study. Follow-up assessments were performed at the following time points after stroke: in person, 2 weeks, 3 months, 6 months, and 1 year; by telephone, 5 years. National Institutes of Health Stroke Scale (NIHSS) score on admission, recurrence, disability, depression, QoL, and chronic complications were recorded. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. QoL was measured using short form-12 (SF-12). Multivariable ordinal logistic regression analysis was used to identify factors that independently affected the physical component summary (PCS) and mental component summary (MCS) scores of the SF-12.@*RESULTS@#Of the 801 patients evaluated in this study, 80 had persistent depression. The multivariable regression analysis of data obtained at 5 years showed that persistent depression at 1 year (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29-0.81) and disability at 5 years (OR: 0.34; 95% CI: 0.23-0.49) were associated with poor MCS scores at 5 years. Old age, a high NIHSS score on admission, disability at 5 years, and stroke recurrence within 5 years were associated with poor PCS scores at the 5-year follow-up.@*CONCLUSIONS@#Persistent depression at the 1-year follow-up could predict poor MCS scores at the 5-year follow-up. The development of interventional strategies targeting post-stroke patients with persistent depression is warranted.

Persistent depression is a predictor of quality of life in stroke survivors: results from a 5-year follow-up study of a Chinese cohort / 中华医学杂志(英文版)

Background@#Whether the time course of post-stroke depression (PSD) can be used to predict the quality of life (QoL) of patients with late-stage stroke remains unclear, this study investigated whether persistent depression at 1 year after stroke predicts QoL at 5 years following stroke.@*Methods@#We analyzed the demographic and clinical data of patients with stroke in 56 hospitals across China that participated in the Prospective Cohort Study on the Incidence and Outcome of Patients with PSD in China Study. Follow-up assessments were performed at the following time points after stroke: in person, 2 weeks, 3 months, 6 months, and 1 year; by telephone, 5 years. National Institutes of Health Stroke Scale (NIHSS) score on admission, recurrence, disability, depression, QoL, and chronic complications were recorded. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders. QoL was measured using short form-12 (SF-12). Multivariable ordinal logistic regression analysis was used to identify factors that independently affected the physical component summary (PCS) and mental component summary (MCS) scores of the SF-12.@*Results@#Of the 801 patients evaluated in this study, 80 had persistent depression. The multivariable regression analysis of data obtained at 5 years showed that persistent depression at 1 year (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.81) and disability at 5 years (OR: 0.34; 95% CI: 0.23–0.49) were associated with poor MCS scores at 5 years. Old age, a high NIHSS score on admission, disability at 5 years, and stroke recurrence within 5 years were associated with poor PCS scores at the 5-year follow-up.@*Conclusions@#Persistent depression at the 1-year follow-up could predict poor MCS scores at the 5-year follow-up. The development of interventional strategies targeting post-stroke patients with persistent depression is warranted.

Brain functional connectivity network studies of acupuncture: a systematic review on resting-state fMRI / 中西医结合学报

<p><b>BACKGROUND</b>Functional magnetic resonance imaging (fMRI) is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused on the brain functional connectivity network of acupuncture stimulation.</p><p><b>OBJECTIVE</b>To offer an overview of the different influences of acupuncture on the brain functional connectivity network from studies using resting-state fMRI.</p><p><b>SEARCH STRATEGY</b>The authors performed a systematic search according to PRISMA guidelines. The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language.</p><p><b>INCLUSION CRITERIA</b>Electronic searches were conducted in PubMed using the keywords "acupuncture" and "neuroimaging" or "resting-state fMRI" or "functional connectivity".</p><p><b>DATA EXTRACTION AND ANALYSIS</b>Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors.</p><p><b>RESULTS</b>Forty-four resting-state fMRI studies were included in this systematic review according to inclusion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro-acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connectivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupuncture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas.</p><p><b>CONCLUSION</b>It can be presumed that the functional connectivity network is closely related to the mechanism of acupuncture, and central integration plays a critical role in the acupuncture mechanism.</p>

Effect of astilbin on cerebral monoamine mediators dopamine and 5-hydroxytryptamine in depression mice / 新乡医学院学报

Objective To evaluate the anti-depression effect of astilbin on mice with depressive disorder and to explore its mechanism of action.Methods Seventy-two male mice (C57BL/6J type) were randomly divided into control group,model group,low,middle,high dose of astilbin group and imipramine(IMI) group,with 12 mice in each group.The mice in the control group were adopted in a normal way.The rats in the model group,low,middle,high dose of astilbin group and IMI group were adopted in chronic unexpected mild stress (CUMS) to establish depression model,and the stress was continuously kept for three weeks and daily medicine with physiological saline,10,20,40 mg · kg-1 astilbin and 10 astilbin imipramine were provided in the way of intraperitoneal injection.Examination for behavioural changes of animals was implemented via tail suspension test,forced swimming test,sucrose preference test,open field test.High performance liquid chromatography (HPLC) was adopted to examine the level of dopamine (DA) and 5-hydroxytryptamine(5-HT)in prefrontal cortex.Results There was no significant difference in the number of horizontal movement and vertical movement among the control group,model group,IMI group and low,middle,high dose of astilbin group(P ＞ 0.05).Compared with the control group,the dead time of tail suspension test and forced swimming test in the model group was longer (P ＜ 0.05),and sugar preference,DA and 5-HT in prefrontal cortex decreased dramatically (P ＜ 0.05).Compared with the model group,the dead time of tail suspension test and forced swimming test in the low,middle,high dose of astilbin group was shorter (P ＜ 0.05),and sugar preference and DA level in prefrontal cortex increased dramatically (P ＜ 0.05).The 5-HT level in prefrontal cortex in the middle,high dose of astilbin group and IMI group was higher than that in the model group (P ＜ 0.05),but there was no significant difference in the 5-HT level in prefrontal cortex between low dose of astilbin group and model group (P ＞ 0.05).There was no significant difference in the dead time of tail suspension test and forced swimming test and sugar preference among the control group,IMI group and low,middle,high dose of astilbin group (P ＞ 0.05).Conclusion Astilbin works excellently in anti-depression,and the major mechanism may involve in up-regulating the level of DA and 5-HT in prefrontal cortex.

Experience of Professor ZHU Xiaoying for Treating Lumbar Disc Herniation and Sciatica with Acupuncture / 浙江中医药大学学报

[Objective]To summarize the clinical experience of Professor ZHU Xiaoying on treating lumbar disc herniation and sciatica with acupuncture.[Method]Via studying with Professor ZHU, and collecting some cases, consulting the related literature and data. Finally, discuss and summarize it. [Result] Professor ZHU believes in TCM holism and distinguishes different types of syndrome from sign, tongue, pulse and so on. She emphasizes warming kidney, smoothing Du meridian, strengthening spine in therapeutical principle. In the treatment of it, she combines the theory of Du meridian with foot-sanyang meridians to choose the points and method. There are also acupuncture and Chinese herbs, and treating both root causes and symptoms. In clinic, the curative effects are remarkable. She chooses Du meridian as a main therapy and uses also acupuncture and Chinese herbs. Clinically, the curative effects are remarkable. [Conclusion]Application of the theory of Du meridian on treating lumbar disc herniation has obvious curative effect. It is worth a deep study and spreading.

Advances in the treatment of cancer by PROTACs / 药学学报

Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4CRBN, CRL2VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.

A new model in the teaching of medical microbiology in clinical medicine / 基础医学与临床

Objective To develop an appropriate new model in current framework of 8-year curriculum .Methods Totally 457 third grade students in Peking Union Medical College were enrolled in the project of learning Medical Microbiology .Anonymous questionnaires were used to investigate the subjective feeling of students for frame -work based learning ( FBL) , performance of students during FBL presentation was evaluated using concerned tables , the distribution of different topics involved in FBL self-oriented ( ORL ) learning was also analyzed .Simultaneously , students'subjective feeling and suggestion were collected .Additionally, the effects of three different teaching/learn-ing methods underlying FBL were investigated by objective tests .With that we developed a preliminary design of teaching model in Medical Microbiology .Results Scores of anonymous evaluation of FBL ranged from ( 2.54 ± 0.74)to(3.43±0.56), and scores in the evaluation of FBL presentation ranged from (4.22±0.32) to (4.77±0.22).Percentages of topics involved in non-Medical Microbiology curriculums were respectively 21.43%, 7.14%, 38.89%, 57.14%, 33.33%and 38.89%in 6 grades from 2008 to 2013 .Conclusions In the teaching of Medical Microbiology , FBL exhibited good effects for students performance in presentation and a potential populization in the learning of other medical courses in addition to Medical Microbiology .Recent studies indicated that blended teaching model including traditional methods , peer education , ORL based on FBL may have very positive impact on students ' learning .

Plasma α1-antitrypsin: a neglected predictor of angiographic severity in patients with stable angina pectoris / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As an acute phase protein, α1-antitrypsin (AAT) has been extensively studied in acute coronary syndrome, but it is unclear whether a relationship exists between AAT and stable angina pectoris (SAP). The purpose of the present study was to investigate the association between AAT plasma levels and SAP.</p><p><b>METHODS</b>Overall, 103 SAP patients diagnosed by coronary angiography and clinical manifestations and 118 control subjects matched for age and gender were enrolled in this case-control study. Plasma levels of AAT, high-sensitivity C-reactive protein (hsCRP), lipid profiles and other clinical parameters were assayed for all participants. The severity of coronary lesions was evaluated based on the Gensini score (GS) assessed by coronary angiography.</p><p><b>RESULTS</b>Positively correlated with the GS (r = 0.564, P < 0.001), the plasma AAT level in the SAP group was significantly higher than that in the control group (142.08 ± 19.61 mg/dl vs. 125.50 ± 19.67 mg/dl, P < 0.001). The plasma AAT level was an independent predictor for both SAP (odds ratio [OR] = 1.037, 95% confidence interval [CI]: 1.020-1.054, P < 0.001) and a high GS (OR = 1.087, 95% CI: 1.051-1.124, P < 0.001) in a multivariate logistic regression model. In the receiver operating characteristic curve analysis, plasma AAT level was found to have a larger area under the curve (AUC) for predicting a high GS (AUC = 0.858, 95% CI: 0.788-0.929, P < 0.001) than that of hsCRP (AUC = 0.665, 95% CI: 0.557-0.773, P = 0.006; Z = 2.9363, P < 0.001), with an optimal cut-off value of 137.85 mg/dl (sensitivity: 94.3%, specificity: 68.2%).</p><p><b>CONCLUSIONS</b>Plasma AAT levels correlate with both the presence and severity of coronary stenosis in patients with SAP, suggesting that it could be a potential predictive marker of severe stenosis in SAP patients.</p>

The genetic and epigenetic alterations in human hepatocellular carcinoma: a recent update

Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies worldwide with very poor prognosis. It is generally accepted that the progression of HCC is a long-term process with accumulation of multiple genetic and epigenetic alterations, which further lead to the activation of critical oncogenes or inactivation of tumor suppressor genes. HCC is characterized with multiple cancer hallmarks including their ability to proliferate, anti-apoptosis, invade, metastasis, as well as the emerging features such as stem cell properties and energy metabolic switch. The irreversible alterations at genetic level could be detected as early as in the pre-neoplastic stages and accumulate during cancer progression. Thus, they might account for the cancer initiating steps and further malignant transformation. In addition to genetic alterations, epigenetic alterations can affect the cancer transcriptome more extensively. Alterations in DNA methylation, histone modification, miRNAs, RNA editing, and lncRNAs might result in disrupted gene regulation networks and substantially contribute to HCC progression. In this review, the genetic and epigenetic alterations which significantly contribute to the malignant capabilities of HCC will be updated and summarized in detail. Further characterization of those critical molecular events might better elucidate the pathogenesis of HCC and provide novel therapeutic targets for treatment of this deadly disease.

Influence of soy isoflavone on lindane cumulant in sprague-dawley rats / 生物医学与环境科学（英文）

Female Sprague-Dawley rats weighing 60-80 g were given different dosages of soy isoflavones and/or lindane for four weeks. Soy isoflavones was added in feed and lindane was given by oral gavage. We found that soy isoflavones could reduce the level of lindane in rat's serum and brain, but might cause the uterus hyperplasia. Lindane could inhibit the effect of soy isoflavones on uterus and significantly decrease the level of estradiol and testosterone in serum. This study indicated that soy isoflavones could reduce the level of lindane in rat's body. Lindane could reduce the level of hormones and decreased the effect of soy isoflavones on rat's uterus.

Comparison of direct immune-fluorescent assay and real-time quantitative PCR in detecting the Hantavirus / 中华预防医学杂志

<p><b>OBJECTIVE</b>To compare the differences between the direct immuno-fluorescent assay (DFA) and real-time quantitative PCR in detecting the Hantavirus (HV) in rat lungs.</p><p><b>METHODS</b>From April to October in 2012, a total of 479 rats were caught by mouse-trap in residential or wild areas in Huxian, Jingyang, and Meixian of Shaanxi province, where haemorrhagic fever with renal syndrome (HFRS) was highly prevalent. The rats were dissected to take the two lungs, one was frozen and applied immuno-fluorescent assay to detect HV antigen while the other one was extracted its RNA and detected HV nucleic acid by real-time quantitative PCR. Then we compared the positive rate of the two methods.</p><p><b>RESULTS</b>Out of the 479 rats, 105 were caught from residential areas and the other 374 were caught from wild areas. Among the 105 rats caught from residential areas, no HV were detected out neither by DFA nor by real-time quantitative PCR. Among the 374 wild rats, 13.1% (49/374) were detected HV positive by DFA and 14.7% (55/374) were detected HV positive by real-time quantitative PCR. The difference showed no statistical significance (χ(2) = 0.402, P = 0.526). When detecting each lung sample, the HV positive rate was 10.2% (49/479) under the detection by DFA while the HV positive rate was 11.5% (55/479) under the detection by real-time quantitative PCR. The difference had no statistical significance (χ(2) = 1.286, P = 0.257) and the consistency coefficient was 68.2% under the paired chi-square test analysis, which showed high consistency (u = 11.759, P < 0.05). The sensitivity of real-time quantitative PCR to detect HV was 77.6% (38/49) comparing with DFA as standard, and the specificity was 96.1% (413/430). Out of the 9 suspected HV positive sample detected by DFA, 6 were confirmed positive by real-time quantitative PCR and 3 were denied.</p><p><b>CONCLUSION</b>Compared with the DFA, real-time quantitative PCR could also be used to detect the infection of HV in rats, and the result might be more stable.</p>

The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alteration in the protein composition of high-density lipoprotein (HDL) has been proposed as a mechanism for the development of coronary heart disease (CHD). In HDL, an increase in serum amyloid A protein (SAA) accompanying the decrease in apolipoprotein A-I (apoA-I) has been found during the acute inflammation period. However, whether this phenomenon persists in CHD patients, a disease related to inflammation, is unknown. The purpose of the present study was to explore the relationship between SAA and apoA-I in HDL isolated from CHD patients.</p><p><b>METHODS</b>Overall, 98 patients with confirmed stable CHD and 90 control subjects matched for age and gender were enrolled in this case-control study. Potassium bromide (KBr) density gradient ultracentrifugation was used to isolate HDL from plasma. The levels of SAA and apoA-I in the HDL samples were detected by enzyme-linked immunosorbent assay kits. Pearson's correlation and general linear models were used in the analysis.</p><p><b>RESULTS</b>Compared with controls, patients with CHD had a significant decrease in the amount of apoA-I ((14.21 ± 8.44) µg/ml vs. (10.95 ± 5.95) µg/ml, P = 0.003) in HDL and a significant increase in the amount of log SAA (1.21 ± 0.46 vs. 1.51 ± 0.55, P < 0.00001). Differences were independent of age, body mass index (BMI), HDL cholesterol (HDL-C), and other factors. An independently and statistically significant positive correlation between log SAA and apoA-I in HDL was observed only in the CHD group (β = 2.0, P = 0.026). In the general linear model, changes in log(SAA), age, age2, gender, BMI and HDL-C could explain a statistically significant 43% of the variance in apoA-I.</p><p><b>CONCLUSIONS</b>This study provides direct evidence for the first time that there was an independent positive correlation between log SAA and apoA-I in the HDL of CHD patients, indicating the alteration of protein composition in HDL. However, the question of whether this alteration in HDL is associated with impairment of HDL functions requires further research.</p>