Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients

Background/Aims@#Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). @*Methods@#Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. @*Results@#The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65–0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61–0.68; untreated models: 0.51–0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. @*Conclusions@#The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Comparison of high-risk human papillomavirus infection rate and genotype distribution between Han and Mongolian women / 中华流行病学杂志

Objective@#To understand the infection rate and genotype distribution of high risk-human papillomavirus (HR-HPV) and the detection rate of different grades of cervical lesions in Han and Mongolian women in China and provide evidence for the development of screening and vaccination strategies for the prevention and control of cervical cancer in different ethnic groups.@*Methods@#In June 2017, a multicenter, population-based study for cervical cancer screening in low-resource settings in China was conducted in three rural areas: Xiangyuan and Yangcheng counties in Shanxi province, and Etuoke county in Inner Mongolia Autonomous Region. A total of 9 517 women aged 30-65 years were included in the study, and two cervical and vaginal secretion samples were collected from them for HPV and PCR-based HPV DNA tests. The positive samples in any of two tests were used for PCR-based HPV genotyping test by using Sansure-pioneered One-Step Fast Release technology. Women with positive results in any the HPV tests were referred for colposcopy and punch biopsy was given if cervical intraepithelial neoplasia lesion (low-grade lesion or worse) was suspected in colposcopy evaluation. Endocervical curettage was performed if women had an unsatisfactory colposcopy exam (the squamocolumnar junction was not completely visible). Pathological detection result was used as the golden standard of diagnosis.@*Results@#HR-HPV infection rates in Han and Mongolian women were 21.83% (1 842/8 438) and 24.93% (269/1 079), respectively. There were statistical differences in HPV infection rates between the two ethnic groups (χ2=5.328, P=0.021). The detection rate of cervical intraepithelial neoplasia grade 1 in Mongolian women (2.83%) was higher than that in Han women (0.87%), and the difference was statistically significant (χ2=33.509, P<0.001). There were no significant differences in cervical intraepithelial neoplasia grade 2 or worse detection rate between the two ethnic groups [Mongolian woman: 1.04% (11/1 059), Han Woman: 0.95% (80/8 378), χ2=0.069, P=0.793]. Among Han and Mongolian women with cervical intraepithelial neoplasia grade 2 or worse, the three most common HR-HPV types were HPV16, HPV52 and HPV58. There was no significant difference for multiple infection rate between Han and Mongolian women (41.37% vs. 44.35%, χ2=0.764, P=0.382).@*Conclusions@#The results show that HPV infection rate in Mongolian women was higher than that in Han women. Close attention should be paid to HPV16, 52 and 58 in the prevention and control of cervical cancer in Han and Mongolian women.

Role of HPV viral loads in random biopsy under normal colposcopy / 中华预防医学杂志

Objective@#To explore the role of HPV viral loads in random biopsy under normal colposcopy.@*Methods@#908 atypical squamous cells of undetermined significance (ASC-US) and HPV positive women, recruited in cluster sampling in 9 provinces including 5 urban areas and 9 rural areas in China from 1999 to 2008 and meeting the inclusion and exclusion criteria were included in this analysis. According to relative light units/cutoff (RLU/CO) value, subjects were stratified as low (286 cases), intermediate (311 cases) and high (311 cases) viral load groups. Risks of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among different viral load groups were compared with linear trend Chi-square test.@*Results@#Detection rate of CIN3+ in low, intermediate and high viral load groups were 2.1% (6 cases), 2.6% (8 cases) and 6.8% (21 cases) (Chi-square test for trend χ2=8.91, P=0.003) and were 60.3, 74.0 and 201.3 times higher than ASC-US and HPV negative women, respectively. Among 908 subjects, 27.0% (245 cases) were abnormal under colposcopy and 68.6% (623 cases) diagnosed as normal. Under normal colposcopy, detection rate of CIN3+ in low, intermediate and high viral load groups were 0.9% (2 cases), 0.9% (2 cases) and 3.8% (7 cases) (χ2=6.42, P=0.040).@*Conclusion@#HPV viral loads display satisfactory risk stratification ability among ASC-US and HPV positive women under normal colposcopy. Women with high HPV viral loads show a significantly increased detection rate of existing CIN3+ and could be recommended to perform random biopsy for histologic diagnosis.

Comparison of screening performance between primary high-risk HPV screening and high-risk HPV screening plus liquid-based cytology cotesting in diagnosis of cervical precancerous or cancerous lesions / 中华预防医学杂志

Objective@#To evaluate and compare the screening performance of primary high-risk HPV(HR-HPV) screening and HR-HPV screening plus liquid-based cytology (LBC) cotesting in diagnosis of cervical cancer and precancerous lesions (CIN2+).@*Methods@#We pooled 17 population-based cross-sectional studies which were conducted across China from 1999 to 2008. After obtaining informed consent, all women received liquid-based cytology(LBC)testing, HR-HPV DNA testing. Totally 28 777 women with complete LBC, HPV and biopsy results were included in the final analysis. Screening performance of primary HR-HPV DNA screening and HPV screening plus LBC co-testing in diagnosis of CIN2+ were calculated and compared among different age groups.@*Results@#Among the whole population, the detection rates of primary HR-HPV screening and HR-HPV screening plus LBC co-testing are 3.05% (879 CIN2+) and 3.13%(900 CIN2+), respectively. The sensitivity were 96.4% and 98.7% (χ2=19.00, P<0.001), and the specificity were 86.2% and 78.8% (χ2=2 067.00, P<0.001), respectively. Areas under the receiver operating characteristic (ROC) curve (AUC) showed that the primary HR-HPV screening performed better than co-testing (AUC were 0.913 and 0.888; Z=6.16, P<0.001). Compared with primary HR-HPV screening, co-testing showed significantly higher colposcopy referral rates (16.5% and 23.6%, respectively, χ2=132.00, P<0.001) and the number of colposcopy examination for detecting per CIN2+ (5.4 and 7.6, respectively).In the group aged 25-29, the colposcopy referral rates was 8.7 (10.9%(199 cases) vs 1.3%(23 cases)) times as much as the detection rate of primary HR-HPV screening in diagnosis of CIN2+, and was 12.5 (15.7%(288 cases) vs 1.3%(23 cases)) times as much as the detection rate of HR-HPV screening plus cytology contesting.@*Conclusion@#Compared with primary HR-HPV screening, HR-HPV screening plus cytology co-testing does not show better results in the screening performance for CIN2+ detection, and the cost-effectiveness is not good enough, especially in younger age group.

The research of clopidogrel resistance of CYP2C19 gene polymorphisms and the crowd of ischemic cerebral apoplexy in northern China / 国际检验医学杂志

Objective To investigate the correlation between CYP2C19 gene polymorphism and clopidogrel resistance(CR)in patients with ischemic stroke in the north of China.Methods The patients with ischemic stroke were selected as the research object from the First Hospital of Hohhot during September 2015 to No-vember 2016.The polymorphism of CYP2C19 gene was detected by Taqman probe method.Results The clo-pidogrel resistance ratio of the study population is 59%.There is a strong correlation between the CYP2C19* 2 mutant strains with clopidogrel resistance(P=0.006),and we foundd that the increased glutamic oxala-cetic transaminase was associated with clopidogrel resistance.Conclusion Patients with the CYP2C19*2 al-lele were at greater risk of clopidogrel resistance during antithrombotic therapy.

Safety and efficacy of hand-assisted laparoscopic versus open distal gastrectomy for gastric cancer: A systematic review and meta-analysis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To systematically assess the safety and efficacy of hand-assisted laparoscopic distal gastrectomy (HALG) versus open distal gastrectomy (ODG) for gastric cancer.</p><p><b>METHODS</b>Chinese or English literature regarding comparison of HALG and ODG were collected by searching in databases (such as PubMed, Cochrane Library, CNKI, Wanfang database) between January 1996 and September 2016. The data of operative time, incision length, blood loss, number of harvested lymph nodes, time to flatus, hospital stay, postoperative complication morbidity and long-term outcomes were compared between the two procedures. Then funnel plot was used to evaluate publication bias and sensitivity analysis was used to evaluate the stability of the results. All these data analyses were performed using the Meta for or Meta package of R version 3.3.1.</p><p><b>RESULTS</b>A total of 7 studies with 835 patients (323 cases in HALG group and 512 cases in ODG group) were included. Compared with ODG, HALG had a longer operative time (WMD=28.93 minutes, 95%CI=9.59 to 48.28, Z=2.93, P=0.000), a shorter incision length (WMD=-10.31 cm, 95%CI=-14.01 to -6.62, Z=-5.47, P=0.000), less blood loss (WMD=-140.08 ml, 95%CI=-215.07 to -65.09, Z=-3.66, P=0.000), faster gastrointestinal recovery (WMD=-1.23 days, 95%CI=-1.89 to -0.56, Z=-3.62, P=0.000), shorter postoperative hospital stay (WMD=-3.24 days, 95%CI=-5.47 to -1.02, Z=-2.85, P=0.000). In subgroup analysis, 3 studies published before 2013 vs. 4 studies published afterwards, the number of harvested lymph nodes (WMD=-0.78, 95%CI=-2.05 to 0.50, Z=-1.19, P=0.235) and postoperative complication morbidity (RR=1.02, 95%CI=0.43 to 2.44, Z=0.05, P=0.961) did not differ significantly between two groups. Compared with ODG, the RR(95%CI) of ileus of HALG was 0.43 (0.07 to 2.82), but the difference was not statistically significant (P=0.383). One study reported the 5-year overall survival rates of HALG and ODG were 81.0% vs 67.5%, and the tumor recurrence rates were 7.1% vs 22%, respectively, but the differences were not statistically significant(all P>0.05). Sensitivity analysis showed that the above results were stable. The funnel plots of the lymph nodes and postoperative complication morbidity did not present significant publication bias.</p><p><b>CONCLUSIONS</b>HALG has the advantages of minimal invasiveness such as shorter incision length and quicker recovery. Furthermore, the short-term efficacy of HALG is similar to conventional open surgery. However, the long-term efficacy is lack of support from multicenter long-term follow-up results.</p>

HPLC Determination of Five Flavonoids Ingredients in Epimedium Flavonoids Capsule / 世界科学技术-中医药现代化

This study was aimed to establish an HPLC method for the content determination ofepimedin A, epimedinB,epimedinC,epimedium glycoside,baohuosideI in epimedium flavonoids capsule. The elusion was performed on an Eclipse Plus C18column (250 mm× 4.6 mm, 5μm). The mobile phase was composed of acetonitrile and water with a gradient elution. The flow rate was set at 1 mL·min-1. The detection wave length was set at 270 nm. The column temperature was 25℃. The results showed that the linear ranges of epimedin A,epimedinB,epimedinC,epimedium glycoside,baohuosideI were 3.10-62.00μg·mL-1, 5.70-114.00μg·mL-1, 9.14-182.80μg·mL-1, 15.20-304.00μg·mL-1, and 1.56-31.20μg·mL-1, respectively. The correlation coefficientr was more than 0.999 3. The average recoveries were 101.06% (RSD = 1.05%,n = 6), 100.78% (RSD = 1.08%,n = 6), 99.17% (RSD = 1.14%,n = 6), 100.23% (RSD = 0.68%,n = 6), and 99.09% (RSD = 1.30%,n = 6), respectively. This experiment was precise, reproducible and stable. It was concluded that the method was simple and accurate, which provided a certain reference value for the multi-component assaying of epimedium flavonoids capsule.

Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: two cases report and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics, treatment and prognosis of Guillain-Barre syndrome (GBS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).</p><p><b>METHODS</b>Two cases with GBS after allo-HSCT were admitted to our hospital and a review of literatures concerning GBS developed after allo-HSCT. The clinical characteristics, treatment and prognosis were investigated.</p><p><b>RESULTS</b>Two patients experienced sensory disturbance and progressive muscle weakness 2 months after HSCT. The diagnosis of GBS was established after cranial MRI, lumbar puncture and EMG. Both patients died of GBS progression even after the treatment of steroid, intravenous immunoglobulin (IVIG) and plasma exchange.</p><p><b>CONCLUSION</b>GBS was a rare complication after allo-HSCT. The common clinical practices in treating GBS included IVIG and plasma exchange. Due to the primary malignant disease and low immunity posttransplant, infection, GVHD and other complications, prognosis of GBS was poor with high mortality.</p>

Roles of SphK-S1P-S1PR signaling pathway in pathogenesis of tumors / 国际肿瘤学杂志

Sphingosine-1-phosphate (S1 P) is a kind of bioactive messenger which is catalyzed by sphingosine kinases (SphK) and mediates various biological behaviors through binding to sphingosine-1-phosphate receptors(S1PR).Researches demonstrate that the aberration of SphK,S1P and S1PR is closely related to the occurrence and development of cancers,such as leukemia,breast cancer,colorectal cancer and lymphoma.The interaction between S1PR1 and signal transducer and activator of transcription 3 (STAT3) is shown to take part in the pathogenesis of malignant tumors as well.Therefore,they are considered to have the potential tumor-treatment value.

A comparable analysis of IPSS and IPSS-R for evaluating prognosis of myelodysplastic syndrome / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification.</p><p><b>RESULTS</b>With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.56% with abnormal karyotype, including the most common abnormality +8 (20/153, 12.6%). 34 of 142 patients transformed into leukemia. Age and the level of β2 micro-globulin were the prognostic factors by multivariate analysis and IPSS-R had a better prognostic significance. The differences in cumulative survival between IPSS subgroups were significant (P<0.05) except that between low- and intermediate I-risk group (P>0.05). There were statistical differences for IPSS-R low risk group vs high or very high risk group, and intermediate risk group vs high or very high risk group (P<0.05). IPSS-R enables IPSS subgroups re-stratification and split IPSS intermediate I-risk group into two subgroups with different prognosis.</p><p><b>CONCLUSION</b>There were significant differences in age of onset, distribution of prognosis scoring system subgroups and abnormal karyotype compared with those in Europe and America. The proportion of higher risk (worse than good karyotype) in IPSS-R was higher than that in Europe and America. Age and the level of β2 micro-globulin were prognostic factors. Both IPSS and IPSS-R were applicable in Chinese MDS patients and the latter performed better. Applying IPSS-R to re-stratify IPSS subgroups helps evaluate prognosis more accurately and improve treatment outcomes.</p>

Preparation of salbutamol polyclonal antibodies and development of indirect competitive enzyme-linked immunoassay / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To prepare the antibodies against salbutamol (SAL) with high sensitivity and to develop an indirect competitive enzyme-linked immunoassay (ic-ELISA) for fast detection of SAL.</p><p><b>METHODS</b>The New Zealand white rabbits were immunized with SAL in a small dose and long period mode. The method of ic-ELISA was optimized and adopted for the detection of a series of SAL samples, then the standard curve of SAL was established. The precision and the recoveries of the method were determined.</p><p><b>RESULTS</b>The antibodies with high sensitivity towards SAL were prepared with a IC50 of 12.21 ng/ml. The ic-ELISA method for SAL measurement was established, the recoveries of measurement was between 95%-105% and the CV was <3%.</p><p><b>CONCLUSION</b>The antibodies against salbutamol have been prepared and an indirect competitive enzyme-linked immunoassay for fast and specific detection of SAL has been developed.</p>

Synthesis of artificial diethylstilbestrol antigen for preparation of polyclonal antibodies / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To synthesize artificial diethylstilbestrol (DES) antigen and to prepare DES polyclonal antibody with high titer and sensitivity.</p><p><b>METHODS</b>The derivative of DES (DES-HS) was synthesized from diethylstilbestrol, ethyl bromoacetate,bovine serum albumin (BSA) and chicken ovalbumin (OVA) with the nucleophilic substitution reaction; the compound was identified by electrospray ionization mass spectrometry(ESI-MS). The DES-HS and the carrier proteins (BSA, OVA) were cross-linked to prepare the artificial antigen; the UV absorption spectrophotometry and high performance liquid chromatography (HPLC) were used to identify the prepared artificial antigen. The rabbits were immunized with the DES artificial antigen to prepare the DES polyclonal antibodies.</p><p><b>RESULTS</b>The DES-HS was synthesized. The DES artificial antigen was prepared successfully with a coupling rate of 22:1. The DES polyclonal antibodies with a titer of 1:25 600 and IC50 of 10.81 ng/ml were prepared with DES artificial antigen.</p><p><b>CONCLUSION</b>A set of methods to synthesize DES artificial antigen and to prepare the DES polyclonal antibodies has been developed successfully.</p>

A clinical analysis of myelodysplastic syndrome and aplastic anemia combined with autoimmune disease / 白血病·淋巴瘤

Objective To investigate the characteristics of pathogenesis and therapeutics of myelodysplastic syndrome(MDS)and aplastic anemia(AA)combined with autoimmune disease(AID).Methods Retrospective analysis and follow-up visit of 111 patients with MDS and 56 patients with AA in our hospital were studied.Results There were 9(8.1%)of 111 patients with MDS and 2 (3.6%)of 55 patients with AA coexistent with AID.Autoimmune hemolytic anemia(36.4%)and Behcet Disease(18.2%)were common among those combined with AID.5 patients had AID proceeding to the occurrence of MDS/AA.4 patients had simultaneous occurrence of AID and MDS/AA.2 patients developed AID three years later after the diagnosis of MDS.Conclusion There was a certain intrinsic relationship between MDS/AA and AID.