Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

To introduce a new design needle and a device of microcatheter protection for lumbar intrathecal catheterization in rats,and evaluate its feasibility and effectiveness. Sixty pathogen-free adult male Sprogue-Dawley rats were randomly divided into two groups(n=30 in each group), the control group (group C) and the modification group(group M). The traditional puncture device, 20G needle, was used in the group C without extemal shielding protection. The new design puncture needle and the microinjection cock were used in the group M. All rats were assessed for motor function on postoperative. The motor function was evaluated 1 day afteroperation. Lidocaine was injected in the catheter at 1st,3rd,7th,14th,21st day post-catheterization, methylene blue was injected in intrathecal at 30th day after operation, and the catheter location was observed. The paw withdrawal threshold(PWT) was measured at 1st,3rd,7th,14th,21st,30th day after operation, open-field test was tested at preoperative and one week postoperative for the purpose of evaluating the autonomous behavior of rats. About motor function:level Ⅰ 75.9%,level Ⅱ 20.7%,level Ⅲ 3.4% in group C, and level Ⅰ 96.7%,level Ⅱ 3.3% in group M, Compared with group C,group M had higher percentage of the level Ⅰ in motor function (P＜0.05);Lidocaine test and methylen blue location showed that each one case of catheter was removed on the 14th and 21st day after intubation in group C, and total four cases were removed till the 30th day, while all catheters were in normal location in group M. There was significant difference between two groups in protection of the extemal portion of catheter(P＜0.05); The time of intrathecal injection in group M was only 1 minute, and it spent more than 3 minutes in group C. Compared with group C,the time of intrathecal injection is significantly shorter in group M(P＜0.01);PWT was reduced to the lowest on the third day after catheterization, and there was significant difference compared with preoperative(P＜0.05), PWT recovered on the 7th day and there were no significant difference between two groups; Compared with preoperative, there was no significant difference in the parameters of the group M in the open field test, neither between two groups. The new design puncture needle by its less injury and higher efficiency can be used in intrathecal catheterization. The microinjection cock is reliable and convenient for repeat injection with a perfect protection function of the external portion of catheter, meanwhile it has no impact on rats' autonomous behavior so that it is worthy of further promoting.

Objective To explore the associations of body mass index (BMI), waist circumference (WC), waist height ratio (WHtR) and the prevalence of hypertension in elderly residents over 60 years in Baodi district, Tianjin. Methods Residents over 60 who underwent medical examinations in the Koudong Health Center, Baodi district, Tianjin, were all invited to participate in the study from April to May, 2018. Participants were asked to fill out structured questionnaires and undergo physical examinations. Stratified analysis and logistic regression analysis were applied to examine joint effects and interactions of BMI and WC (or WHtR) on the risk of hypertension. Results A total of 1 417 residents (83.75%) out of 1 692 residents participated in the study. The prevalence of hypertension in the participants was 46.36%. 66.50% of the participants were BMI overweight or obese. Participants with central obesity accounted for 74.66% (measured by the WC) and 75.38% (by the WHtR). Compared to the normal weight measured by the BMI or the WC, BMI overweight (OR=1.65, 95%CI: 1.19-2.30) or obesity (OR=3.41, 95%CI: 2.23-5.20) and WC central obesity (OR: 1.49, 95%CI: 1.00-2.23) were associated with increased risk of hypertension. The joint effects of BMI and WC (OR=2.49, 95%CI: 1.78-3.46), or BMI and WHtR (WHtR overweight: OR=2.05, 95%CI: 1.41-2.99; WHtR obesity: OR=2.37, 95%CI: 1.50-3.76) were greater than the single effect of the latter (WC overweight/obesity: OR=1.39, 95%CI: 0.90-2.15; WHtR overweight: OR=1.02, 95%CI: 0.62-1.66; WHtR obesity: OR=1.44, 95%CI：0.55-3.81). Conclusions Of the three indices, BMI is strongly correlated with the risk of hypertension. BMI overweight or obesity has enhanced the association of WC or WHtR and the risk of hypertension, suggesting that weight control in the normal range, especially measured by the BMI index, may prevent and control hypertension.

Objective To investigate the clinical outcomes of patients with locally advanced uterine cervical cancer (UCC) treated by 3-dimensional high dose rate-intracavitary brachytherapy (3D HDR-ICBT) combined with complementary applicator-guided external beam radiotherapy (EBRT).Methods A total of 120 patients pathologically diagnosed with locally advanced UCC (tumors with a maximum diameter≥6 cm or ≥5 cm complicated with eccentric tumor growth) treated with concurrent chemoradiotherapy (CCRT) from June 2010 to June 2015 were recruited.Five fractions of 3D HDR-ICBT combined with complementary applicator-guided external beam radiotherapy were performed.The prescribed dose for HR-CTV and IR-CTV was 7 Gy (D9o) and 5-6 Gy (D90).The rectum,sigmoid colon,bladder and adjacent small intestine were delineated as the organs at risk.Intensity-modulated radiation therapy (IMRT) was used for EBRT (45 Gy/ 25f) combined with cisplatin-based chemotherapy every three weeks (75 mg/m2).Results The median follow-up time was 46 months (14-96 months).The 5-year local control rate (LCR),disease-free survival (DFS),and overall survival (OS) were 92.8％,76.6％ and 81.0％,respectively.The incidence rate of grade Ⅰ-Ⅱ genitourinary and gastrointestinal acute toxicities were 57.8％ and 14.6％,whereas 8.1％ and 2.9％ for grade Ⅲ toxicities.The incidence rate of later grade Ⅰ-Ⅱ genitourinary and gastrointestinal toxicities were 8.4％ and 5.3％,and 0.97％ and 1.3％ for grade Ⅲ late toxicities.Conclusions The combination of HDR-ICBT with an applicator-guided IMRT (ICBT+IMRT) yields low incidence of severe adverse events,relatively high LC and OS rate for locally advanced UCC.It is an efficacious comprehensive treatment of locally advanced bulky UCC.

ObjectiveTo investigate the clinical efficacy and safety of Huanshao Capsules (HSC) in the treatment of oligoasthenospermia with spleen and kidney asthenia.

METHODSThis randomized, open, multicentered, positive drug controlled clinical trial included 200 cases of oligoasthenospermia with spleen and kidney asthenia, which were assigned to a trial and a control group of equal number to be treated with HSC at the dose of 3 capsules tid and Wuziyanzong Pills at 6 g bid, respectively, both for 12 weeks. We compared the semen volume, sperm concentration, sperm count, sperm motility and percentage of progressively motile sperm (PMS) as the main therapeutic indicators as well as the pregnancy rate as the secondary therapeutic indicator between the two groups of patients before and at 4, 8 and 12 weeks after medication.

RESULTSTotally, 190 of the patients completed the clinical observation, 96 in the trial and 94 in the control group. Compared with the baseline, the patients of the trial group showed significant time-dependent increases at 4, 8 and 12 weeks after medication in the mean sperm concentration (14.78 vs 15.33, 20.98 and 28.78 ×10⁶/ml, P < 0.05), percentage of grade a sperm (12.17% vs 15.05%, 21.17% and 26.97%, P < 0.05), PMS (24.78% vs 28.97%, 37.23% and 47.67%, P < 0.05), and sperm viability (38.64% vs 44.18%, 51.67% and 60.45%, P < 0.05). The pregnancy rate was significantly higher in the trial than in the control group 29.17% vs 18.09%, P < 0.05).

CONCLUSIONSHuanshao Capsules can improve the semen quality and pregnancy rate in the treatment of oligoasthenospermia patients with spleen and kidney asthenia, and therefore deserves a wide clinical application.

Capsules ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Oligospermia ; drug therapy ; Pregnancy ; Pregnancy Rate ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Treatment Outcome

OBJECTIVETo identify the mutation of ENG and ALK1 genes in a hereditary hemorrhagic telangiectasia pedigree.

METHODS14 exons of ENG gene and 9 exons of ALK1 gene in 11 menbers of this pedigree 4 generation were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the PCR products were screened by direct sequencing.

RESULTSA nonsense mutation c.447G > A was found in exon 4 of ENG gen of the pedigreee, resulting in change of Trp 149 into Stop, while no gene mutation was found in ALK1 gene.

CONCLUSIONThe hereditary hemorrhagic telangiectasia in this pedigree is caused by the nonsense mutation c.447G > A in ENG gene.

Codon, Nonsense ; Exons ; Humans ; Mutation ; Pedigree ; Polymerase Chain Reaction ; Telangiectasia, Hereditary Hemorrhagic

Growth suitability as assessment indicators for medicinal plants cultivation was proposed based on chemical quality determination and ecological factors analysis by Maxent and ArcGIS model. Notopterygium incisum, an endangered Chinese medicinal plant, was analyzed as a case, its potential distribution areas at different suitability grade and regionalization map were formulated based on growth suitability theory. The results showed that the most suitable habitats is Sichuan province, and more than 60% of the most suitable areawas located in the western Sichuan such as Aba and Ganzi prefectures for N. incisum. The results indicated that habitat altitude, average air temperature in September, and vegetation types were the dominant factors contributing to the grade of plant growth, precipitation and slope were the major factors contributing to notopterol accumulation in its underground parts, while isoimperatorin in its underground parts was negatively corelated with precipitation and slope of its habitat. However, slope as a factor influencing chemical components seemed to be a pseudo corelationship. Therefore, there were distinguishing differences between growth suitability and quality suitability for medicinal plants, which was helpful to further research and practice of cultivation regionalization, wild resource monitoring and large-scale cultivation of traditional Chinese medicine plants.
Apiaceae ; growth & development ; China ; Ecosystem ; Environment ; Geographic Information Systems ; Soil ; chemistry ; Temperature

OBJECTIVETo analyze the 5' and 3'-untranslated region sequences of the UGT1A1 gene in Chinese Han population and to find polymorphic variants within the untranslated region.

METHODSGenomic DNA was extracted from peripheral leukocytes in 220 healthy Han individuals. The 5' and 3'-untranslated region sequences of the UGT1A1 gene were amplified by polymerase chain reaction, and followed by DNA sequencing.

RESULTSTwo polymorphic loci were identified in the 5'-untranslated region of the UGT1A1 gene with -64(G/C) and A(TA)6TAA/A(TA)7TAA in TATAA box region among Chinese Han population. Genotype frequencies were 98.4% (G) and 1.6% (C) in -64 locus of the UGT1A1 gene among the 220 individuals. The allele frequency of A(TA)6TAA and A(TA)7TAA within the promoter region was found to be 93.4% and 6.6%, respectively. Two polymorphic loci of 1813(C/T) and 1941(C/G) were detected in the 3'-untranslated region of the UGT1A1 gene, they showed a homozygous state at two loci with cosegregation pattern at 1813 and 1941 locus. The haplotype frequencies were 73.6% (CC/1813+CC/1941) and 26.4% (TT/1813+GG/1941) for 1813 and 1941 loci in the UGT1A1 gene.

CONCLUTIONCosegregation pattern, at 1813 and 1941 locus with homozygous state in the 3'-untranslated region of the UGT1A1 gene may be selected from the human genome among Chinese Han population. More studies should be focused on the mechanism of homozygous cosegregation.

Alleles ; Asian Continental Ancestry Group ; Base Sequence ; DNA ; Gene Frequency ; Genotype ; Glucuronosyltransferase ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis ; Untranslated Regions

OBJECTIVETo investigate the effect of FCGR3A polymorphisms on the antibody-dependent cell-mediated cytotoxicity (ADCC) activity induced by cetuximab against A549 cells.

METHODSA549 cell line was used as target cells and NKTm cells as effector cells. FCGR3A polymorphisms were detected by direct sequencing. The ADCC activity mediated by cetuximab was assessed by CCK-8 assay.

RESULTSThree genotypes of FCGR3A were detected:V/V,V/F,and F/F. The ADCC activity of NKTm cells with these three different genotypes mediated by cetuximab were significantly different (P=0.0015). NKTm cells with FCGR3A-158V/V genotypes had significantly higher ADCC activity than FCGR3A-V/F or F/F genotypes (P<0.01),whereas the ADCC activity between V/F and F/F genotype showed no statistical significance(P>0.05).

CONCLUSIONFCGR3A polymorphisms have an impact on ADCC activity mediated by cetuximab in NKTm cells.

Antibody-Dependent Cell Cytotoxicity ; Cell Line, Tumor ; Cetuximab ; Genotype ; Humans ; Polymorphism, Genetic ; Receptors, IgG

Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.
Allografts ; Animals ; Apoptosis ; Brain Death ; China ; Death ; Heart Arrest ; Hepatocytes ; pathology ; ultrastructure ; Humans ; In Situ Nick-End Labeling ; Liver ; pathology ; ultrastructure ; Liver Transplantation ; methods ; Microscopy, Electron ; Organ Preservation ; methods ; Swine ; Tissue Donors ; Tissue and Organ Procurement ; methods