Gadoxetic acid-enhanced magnetic resonance imaging can predict the pathologic stage of solitary hepatocellular carcinoma

BACKGROUND Although important for determining long-term outcome, pathologic stage of hepatocellular carcinoma (HCC) is difficult to predict before surgery. Current state-of-the-art magnetic resonance imaging (MRI) using gadoxetic acid provides many imaging features that could potentially be used to classify single HCC as pT1 or pT2. AIM To determine which gadoxetic acid-enhanced MRI (EOB-MRI) findings predict pathologic stage T2 in patients with solitary HCC (cT1). METHODS Pre-operative EOB-MRI findings were reviewed in a retrospective cohort of patients with solitary HCC. The following imaging features were examined: Hyperintensity in unenhanced T2-weighted images, hypointensity in unenhanced T1-weighted images, arterial enhancement, corona enhancement, washout appearance, capsular appearance, hypointensity in the tumor tissue during the hepatobiliary (HB) phase, peritumoral hypointensity in the HB phase, hypointense rim in the HB phase, intratumoral fat, hyperintensity on diffusionweighted imaging, hypointensity on apparent diffusion coefficient map, mosaic appearance, nodule-in-nodule appearance, and the margin (smooth or irregular). Surgical pathology was used as the reference method for tumor staging. Univariate and multivariate analyses were performed to identify predictors of microvascular invasion or satellite nodules. RESULTS There were 39 (34.2%;39 of 114) and 75 (65.8%;75 of 114) pathological stage T2 and T1 HCCs, respectively. Large tumor size (≥ 2.3 cm) and two MRI findings, i.e., corona enhancement [odds ratio = 2.67;95% confidence interval: 1.101-6.480] and peritumoral hypointensity in HB phase images (odds ratio = 2.203;95% confidence interval: 0.961-5.049) were associated with high risk of pT2 HCC. The positive likelihood ratio was 6.25 (95% confidence interval: 1.788-21.845), and sensitivity of EOB-MRI for detecting pT2 HCC was 86.2% when two or three of these MRI features were present. Small tumor size and hypointense rim in the HB phase were regarded as benign features. Small HCCs with hypointense rim but not associated with aggressive features were mostly pT1 lesions (specificity, 100%). CONCLUSION Imaging features on EOB-MRI could potentially be used to predict the pathologic stage of solitary HCC (cT1) as pT1 or pT2.

Distribution and changes in hepatitis C virus genotype in China from 2010 to 2020

BACKGROUND Hepatitis C virus(HCV)causes a large number of infections worldwide.New infections seem to be increasing according to a report of the World Health Organization in 2015.Although direct-acting antivirals are quite effective for most genotypes of the HCV,some genotypes fail to respond.Therefore,the trend of genotype distribution is vital to better control the development of this infection.AIM To analyze the distribution and trends of the HCV genotype before and after the emergence of direct-acting antivirals in China.METHODS We searched all literature published in five electronic databases-China National Knowledge Infrastructure,Wan Fang Data,VIP Chinese Journal Database,Chinese Biomedical Literature Service System,and PubMed-from January 1,2010 to December 31,2020.The search strategy combined medical subject headings and free-text terms,including“hepatitis C virus”or“HCV”and“genotype”or“subtype”and“China”or“Chinese”.Additional relevant articles were searched by manual selection.Data were extracted to build a database.All of the data were totaled according to regions,periods,routes of transmission,and sexes.The percentages in various stratifications were calculated.RESULTS There were 76110 samples from 30 provinces included in the study.Genotype 1(G1)accounted for 58.2%of cases nationwide,followed by G2,G6,G3b,G3a,unclassified and mixed infections(17.5%,7.8%,6.4%,4.9%,1.8%,and 1.2%,respectively).The constitution of genotype varied among different regions,with G6 and G3b being more common in the south and southwest,respectively(28.1%,15.4%).The past ten years have witnessed a decrease in G1 and G2 and an increase in G3 and G6 in almost all regions.The drug-use population had the most abundant genotypes,with G6 ranking first(33.3%),followed by G1 and G3b(23.4%,18.5%).CONCLUSION G3 and G6 pose a new challenge for HCV infection.This study revealed the distribution of HCV genotypes in China over the past 10 years,providing information for HCV management strategies.

Single-nucleotide polymorphism screening and RNA sequencing of key messenger RNAs associated with neonatal hypoxic-ischemia brain damage

A single-nucleotide polymorphism(SNP)is an alteration in one nucleotide in a certain position within a genome.SNPs are associated with disease susceptibility.However,the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive.Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model.SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing.Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism.We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2.Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis,wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels.Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses,long-term depression and oxytocin signaling.Moreover,intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1,DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy.Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons.Our results indicate that CSRNP1,DUSP5 and LRRC25,containing SNPs,may be involved in the pathogenesis of hypoxic ischemic encephalopathy.These findings indicate a novel direction for further hypoxic ischemic encephalopathy research.This animal study was approved on February 5,2017 by the Animal Care and Use Committee of Kunming Medical University,Yunnan Province,China(approval No.kmmu2019038).Cerebral tissue collection from a human fetus was approved on September 30,2015 by the Ethics Committee of Kunming Medical University,China(approval No.2015-9).

Computational prediction and experimental validation of novel markers for detection of STEC O157:H7

AIM:To identify and assess the novel makers for detection of Shiga toxin producing Escherichia coli (STEC) O157:H7 with an integrated computational and experimental approach. METHODS:High-throughput NCBI blast (E-value cutoff e-5) was used to search homologous genes among all sequenced prokaryotic genomes of each gene encoded in each of the three strains of STEC O157:H7 with complete genomes,aiming to find unique genes in O157:H7 as its potential markers. To ensure that the identified markers from the three strains of STEC O157:H7 can serve as general markers for all the STEC O157:H7 strains,a genomic barcode approach was used to select the markers to minimize the possibility of choosing a marker gene as part of a transposable element. Effectiveness of the markers predicted was then validated by running polymerase chain reaction (PCR) on 18 strains of O157:H7 with 5 additional genomes used as negative controls. RESULTS:The blast search identified 20,16 and 20 genes,respectively,in the three sequenced strains of STEC O157:H7,which had no homologs in any of the other prokaryotic genomes. Three genes,wzy,Z0372 and Z0344,common to the three gene lists,were selected based on the genomic barcode approach. PCR showed an identification accuracy of 100% on the 18 tested strains and the 5 controls. CONCLUSION:The three identified novel markers,wzy,Z0372 and Z0344,are highly promising for the detection of STEC O157:H7,in complementary to the known markers.

An Investigation and Suggestions for the Improvement of Brain Death Determination in China

Background: Brain death is the irreversible cessation of the function of the brain including the brainstem. In 2013, the Brain Injury Evaluation Quality Control Centre (BQCC) of the National Health and Family Planning Commission issued criteria and practical guidelines for the determination of brain death. This study aimed to evaluate whether the institutions have adopted these guidelines and to make suggestions for the improvement of the current criteria and practical guidelines for brain death determination in China. Methods: Consecutive brain death cases from 44 hospitals were evaluated for summary statistics for the following data: the performance of BQCC criteria and practical guidelines, clinical examination, apnea testing, ancillary testing, and the number of examinations as well as the waiting periods between examinations and details of who determined brain death. Data analysis was conducted from January 2013 to December 2017. Results: A total of 550 cases were obtained. All patients were determined to have deep coma and met the prerequisites for clinical testing. The performance rates of four brainstem reflex examinations (except cough reflex) ranged from 97.5% to 98.0%, and the completion rate as well as the coincidence rate were both 100.0%. The 238 cases (50.7%) completed apnea testing, and 231 cases (42.0%) had to stop apnea testing during the examination because of instability. The performance rates of the three ancillary tests, including electroencephalogram, short-latency somatosensory evoked potential, and transcranial Doppler, were 89.5%, 67.5%, and 79.5%, respectively;furthermore, the coincidence rates were 98.6%, 96.5%, and 99.5%, respectively. The combination of two ancillary tests was more accurate than one single ancillary test. A total of 401 (72.9%) cases successfully underwent two separate examinations to determine brain death with at least a 12-h waiting period. All brain death cases were determined by at least two qualified physicians. Conclusion: This study might provide suggestions for brain death determination in China.

Trans-cranial Doppler predicts early neurologic deterioration in anterior circulation ischemic stroke after successful endovascular treatment

Background:Early neurologic deterioration(END)may occur in patients with anterior circulation ischemic stroke(ACIS)after receiving endovascular treatment(EVT).Hemodynamic insufficiency,re-occlusion,and post-re-canalization hyper-perfusion are likely to play a critical role in END.We hypothesized that hemodynamic changes can predict END in patients with ACIS postsuccessful EVT using trans-cranial Doppler(TCD).Methods:We utilized a prospectively maintained database of ACIS patients treated with EVT between September 2016 and June 2018 in the Xuanwu Hospital,Capital Medical University.TCD parameters including peak systolic velocity(PSV),bilateral mean flow velocity(MFV),and pulse index(PI)were determined via the middle cerebral arteries within 72 h post-EVT.A logistic regression model was applied to detect independent predictors for END.Results:Totally,112 EVT patients were included in this study and 80/112 patients experienced successful re-canalization with<50%residual stenosis,while 17/80(21.3%)patients suffered END,for which vasogenic cerebral edema(11/17)was considered as a leading role and followed by symptomatic intra-cranial hemorrhage(4/17)and ischemia progression(2/17).For the 80 patients,the PSV(median:127 cm/s vs.116 cm/s,P=0.039),the ratio of ipsilateral-MFV/contra-lateral-MFV(iMFV/cMFV)(median:1.29 vs.1.02,P=0.036)and iMFV/mean blood pressure(MBP)(median:0.97 vs.0.79,P=0.008)in END patients were higher than those of non-END.Using the receiver-operating characteristic curve to obtain cut-off values for PSV,PI,iMFV/cMFV,and iMFV/MBP for END,we found that PI≥0.85(odds ratio:11.03,95%confidence interval:1.92–63.46,P=0.007)and iMFV/MBP≥0.84(odds ratio:9.20,95%confidence interval:2.07–40.84,P=0.004)were independent predictors of END in a multivariate logistic regression model,with a sensitivity of 82.4%and 76.5%and a specificity of 42.9%and 66.7%,respectively,and had the positive predictive values of 29.0%and 38.2%,and negative predictive values of 90.0%and 91.3%,with an area under the receiveroperating characteristic curve of 0.57 and 0.71,respectively.Conclusion:TCD examination of EVT patients may be used as a real-time tool to detect END predictors,such as the higher PI and iMFV/MBP,allowing for better post-thrombectomy management in ACIS patients.

基于大肠杆菌表达的重组九价人乳头瘤病毒(HPV 6/11/16/18/31/33/45/52/58型)疫苗免疫原性和安全性的Ⅱ期临床试验

人乳头瘤病毒(HPV)16/18型双价疫苗(大肠埃希菌)已上市并通过世界卫生组织预认证.本研究通过一项随机双盲Ⅱ期临床试验评估其第二代HPV6/11/16/18/31/33/45/52/58型九价疫苗在18~45岁健康女性中的免疫原性和安全性.来自江苏省东台市的627名女性志愿者1:1随机分配至九价疫苗组(313人)或对照组(314人),并按照0、1、6月接种程序分别接种三剂1.0 mL(270μg)九价疫苗或空白佐剂,主要终点为第7月时血清抗体阳转率和抗体水平.结果显示,几乎所有疫苗组符合方案人群在第7月时出现针对9种HPV型别的血清中和抗体阳转,仅2人未发生HPV11型阳转,1人未发生HPV52型阳转.九价疫苗组和对照组的总体不良事件发生率分别为80.8%和72.9%,绝大多数不良事件症状轻微并很快恢复,未发生疫苗相关严重不良事件.该研究证明候选九价疫苗具有良好的安全性和免疫原性,支持在更大人群中进一步进行效力研究.

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs.3 doses in young women

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women.A randomized,immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China.Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301)or 3 doses at months 0,1 and 6(n=304).Girls aged 15–17 years(n=149)and women aged 18–26 years(n=225)received 3 doses.The objectives included noninferiority analysis of the IgG geometric mean concentration(GMC)ratio(95%CI,lower bound>0.5)to HPV-16 and HPV-18 at month 7 in girls compared with women.In the per-protocol set,the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95%CI,1.56,1.99)for HPV-16 and 1.93(95%CI,1.69,2.21)for HPV-18)and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95%CI,1.25,1.62)for HPV-16 and 1.17(95%CI,1.02,1.33)for HPV-18).Noninferiority was also demonstrated for neutralizing antibodies.The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction: a mismatch negativity study

Background:Although the rehabilitation of aphasia has been extensively studied,the prediction of language outcome still has not received sufficient attention.The aim of this study was to predict the language outcome using mismatch negativity(MMN)in patients with large left-hemispheric infarction.Methods:MMN was elicited by an oddball paradigm in which a standard tone(1000 Hz)and deviant tone(1500 Hz)were presented at 90%and 10%of the number of tones,respectively.The mean amplitudes and laterality indexes(LIs)of MMN were measured over the prefrontal,frontal,central,parietal,temporal,and perisylvian electrodes and both hemispheres during the first 7 days(session 1)and 10 to 20 days(session 2)post-onset.Mixed three-way analysis of variance(ANOVA)was used to investigate differences in these factors between two aphasia groups(the good recovery group and poor recovery group).The predictive value of the most significant LI was also compared with the score of National Institutes of Health Stroke Scale score and low-density volume on computed tomography.Results:A total of 18 patients were enrolled in this study.Mixed three-way ANOVA showed no interaction effect of session×region of interest(ROI)×group(F[3.59,57.38]=1.301,P=0.282)and no interaction effect of ROI×group(F[1.81,29.01]=0.71,P=0.487)and session×group(F[1.00,16.00]=0.084,P=0.776)for MMN amplitude.No interaction effect of session×ROI×group(F[1.79,28.58]=0.62,P=0.530),but an interaction effect of session×group(F[1.00,16.00]=5.21,P=0.036)was found for LIs.In the poor recovery group,the LIs of MMN over all the ROIs,except the parietal area,became more negative at session 2 than those at session 1(P<0.05),but this effect was not observed in the good recovery group.Additionally,significant differences were observed in the LIs at session 2 between the two groups(P<0.05).The LI over the perisylvian area at session 2 had the highest predictive value with an area under the curve of 0.963(95%confidence interval:0.884–1.000).An LI score>-0.36 over the perisylvian area suggested good recovery,but a score<-0.36 suggested poor recovery.The LI cut-off value of-0.36 had the highest sensitivity(90.0%)and specificity(87.5%)for predicting a good language outcome at 3 months post-stroke.Conclusion:LIs of MMN amplitudes at approximately 2 weeks post left-hemisphere stroke serve as more sensitive predictors of language outcome,among which the LI over the perisylvian area exhibits the best predictive value.

A five-compartment model of age-specific transmissibility of SARS-CoV-2

Background:The novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2,also called 2019-nCoV)causes different morbidity risks to individuals in different age groups.This study attempts to quantify the age-specific transmissibility using a mathematical model.Methods:An epidemiological model with five compartments(susceptible-exposed-symptomatic-asymptomatic-recovered/removed[SEIAR])was developed based on observed transmission features.Coronavirus disease 2019(COVID-19)cases were divided into four age groups:group 1,those≤14years old;group 2,those 15 to 44years old;group 3,those 45 to 64years old;and group 4,those≥65 years old.The model was initially based on cases(including imported cases and secondary cases)collected in Hunan Province from January 5 to February 19,2020.Another dataset,from Jilin Province,was used to test the model.Results:The age-specific SEIAR model fitted the data well in each age group(P<0.001).In Hunan Province,the highest transmissibility was from age group 4 to 3(median:β43=7.71×10-9;SAR43=3.86×10-8),followed by group 3 to 4(median:β34=3.07×10-9;SAR34=1.53×10-8),group 2 to 2(median:β22=1.24×10-9;SAR22=6.21×10-9),and group 3 to 1(median:β31=4.10×10-10;SAR31=2.08×10-9).The lowest transmissibility was from age group 3 to 3(median:β33=1.64×10-19;SAR33=8.19×10-19),followed by group 4 to 4(median:β44=3.66×10-17;SAR44=1.83×10-16),group 3 to 2(median:β32=1.21×10-16;SAR32=6.06×10-16),and group 1 to 4(median:β14=7.20×10-14;SAR14=3.60×10-13).In Jilin Province,the highest transmissibility occurred from age group 4 to 4(median:β43=4.27×10-8;SAR43=2.13×10-7),followed by group 3 to 4(median:β34=1.81×10-8;SAR34=9.03×10-8).Conclusions:SARS-CoV-2 exhibits high transmissibility between middle-aged(45 to 64 years old)and elderly(≥65 years old)people.Children(≤14 years old)have very low susceptibility to COVID-19.This study will improve our understanding of the transmission feature of SARS-CoV-2 in different age groups and suggest the most prevention measures should be applied to middle-aged and elderly people.

Criteria and practical guidance for determination of brain death in adults (2nd edition)

Statement: In 2013, we published "Criteria and practical guidance for determination of brain death in adults (BQCC version)" in Chinese Medical Journal (Chin Med J 2013, 126:4786–4790). Since then, China has the standard for the determination of brain death. In order to further promote the brain death related work, Brain Injury Evaluation Quality Control Center of National Health Commission (BQCC) aimed to revise and update "Criteria and practical guidance for determination of brain death in adults". This 2018 new edition was based on the 5-year clinical practice of brain death determination, BQCC quality control analysis of brain death cases, and the opinions and suggestions of BQCC expert committees, technical committees and advisory committees. We hope that the development of brain death determination will be more standardized and orderly in China.