Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0％(126/140)were newly diag-nosed,9.3％(13/140)had compensated cirrhosis,92.9％(130/140)received 12 weeks of treatment,and 7.1％(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4％(108/112),and at the end of treatment was 100％(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4％)patients,and none were considered to be drug-related.Sixty-six(47.1％)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.

OBJECTIVEMalignant transformation of epithelial cell frequently coincides with loss of E-cadherin. Here we study the expression of Snail and E-cadherin and correlate their expression with cell differentiation and in vitro invasion.

METHODSThe expression and localization of Snail and E-cadherin were studied by Northern blot and laser confocal microscopy in two normal cell lines (MDCK, NIH 3T3) and six carcinoma cell lines (A431, MCF-7, MDA-MB-453, HepG2, MDA-MB-435s, MDA-MB-231). Boyden chamber assay was done to detect the invasive ability of cells in vitro.

RESULTSSnail mRNA and protein were detected in fibroblasts NIH 3T3 and poorly differentiated carcinoma cell lines HepG2, MDA-MB-435s and MDA-MB-231. On the contrary, E-cadherin mRNA and protein were detected in normal epithelial cell line MDCK and well differentiated carcinoma cell lines A431 and MDA-MB-453. In MCF-7 cells, Snail and E-cadherin expressions were revealed both at mRNA and protein levels. The cells with higher expression of Snail had stronger ability of invasion than those with lower expression of Snail.

CONCLUSIONThere is an inverse correlation between Snail and E-cadherin expressions and their expressions are correlated with cell differentiation and tumor invasiveness.

3T3 Cells ; metabolism ; Animals ; Cadherins ; biosynthesis ; genetics ; Cell Differentiation ; Cell Line ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; metabolism ; Dogs ; Epithelial Cells ; cytology ; metabolism ; Humans ; Mice ; Neoplasm Invasiveness ; Snail Family Transcription Factors ; Transcription Factors ; biosynthesis ; genetics

There are irreversible eyeball structural changes in high myopic patients. These changes include axial length, corneal radius, anterior chamber depth, fundus degeneration, macula thickness, etc. There is a close relationship between the damage degree of visual function and these changes. The incidence of complications, such as vitreous opacity, posterior vitreous detachment, cataract, glaucoma, posterior staphyloma and retina detachment, is also highly related to the myopia diopter. More and more researches have indicated that the myopia diopter and the level of visual function are affected by multiple factors. It is promising to detect all of these changes by different kinds of methods, and to assess visual function through these changes. By clarifying these changes, it is also useful to distinguish traumatic damage from disease to provide evidence for forensic assessment of eye injuries.
Eye/physiopathology* ; Forensic Medicine ; Humans ; Myopia/pathology* ; Vision, Ocular/physiology*

Objective To investigate the epidemiological characteristics and the influencing factors of the unintentional injuries among Wenzhou elementary school children. Methods A total of 3 050 students were selected from the 1st to 6th grades in 6 primary schools in Wenzhou urban area by multi - stage sampling and were investigated during 2013 to 2015. Results 2 859 students completed the investigation. The morbidity of annual average unintentional injuries was 30. 81%(95% CI:29. 12% - 32. 50% )and the occurrence density was 2. 79. Unintentional injuries occurred mainly at home (37. 69% )and school(32. 39% ),and the most common site of injuries were leg(35. 02% )and hand(33. 79% ). For overall incidence,the slip falling injury(35. 64% )was highest,followed by cut or pierced(33. 40% )and crush injury (25. 08% ). Schoolgirl was a protective factor of the injury of crushed,electrical,traffic accident,bashed,burn , exploded,drown,poisoning and bit(OR ﹤ 1),but was a risk factor of multiple injuries(OR = 1. 323). Age was a risk factor of injury of fallen,crushed,bashed,burn,cut or pierced,exploded and bit(OR ﹥ 1. 1),but was a protective factor of poisoning(OR = 0. 671). compared with the students who walked to school alone,the children who were accompanied by their family member and rode alone to school were protective factors of the traffic accident. Conclusion The incidences of the unintentional injuries of elementary school children were increased with the age,and the boy was easier to be hurt. It was suggested for parents,schools and the government to strengthen healthy education for children at the early age.

Objective:To investigate the expression of intestinal alkaline phosphatase (IAP) in intestinal mucosa with bile deficiency and the effect of bile on the expression of IAP in intestinal epithelial Caco-2 cell model.Methods:Thirty healthy male SD rats were randomly divided into control group (Ctrl, n=10), external drainage group (ED, n=10) and obstructive jaundice group (OJ, n=10). Ileum specimens were collected on the 7th day after modeling. Western blot and immunohistochemical staining were used to determine the expression of IAP in rat intestinal mucosa. Different concentrations of human bile were used to treat on Caco-2 cells, and Western blot was used to detect the changes in IAP expression in Caco-2 cells. Results:Rat models were successfully established. The expression level of IAP in the intestinal mucosa of ED group [(9.19±1.67)%] was significantly lower than that of the Ctrl group [(15.09±0.61)%, P<0.05]; the expression of IAP in the intestinal mucosa of OJ group [(6.86±1.07)%] was significantly lower than that of the Ctrl group ( P<0.05). Through in vitro cell experiments, expression of IAP in Caco-2 cells was increased in a time and dose-dependent manner when treated with human bile. Conclusions:Bile deficiency in the intestine can cause inhibition of IAP in the intestinal mucosa. Bile can promote the expression of IAP in intestinal mucosal epithelial cells.

With the promotion and application in medicine and sanitary fields,the reporting quality of Bland-Altman agreement evaluation is worrying.This study aimed at developing a set of reporting standards for Bland-Altman agreement evaluation as the guidance for proper application to improve the reporting quality.A research group was launched to work on reporting standards for Bland-Altman agreement evaluation,and all the requirements for personnel on various levels were made clear.Early in the study,we carried out articles reviews,regular meetings,expert consultations,literary evaluation,item integration and extraction.Then,we invited a multi-disciplinary panel of experts to improve overall design,evaluate reporting items and form the first draft by brainstorming method.Multiple rounds of expert consultations were also conducted with reference to Delphi method to integrate expert advice and form the basic framework of reporting items.Finally,through the thorough analysis and demonstration,we proposed the reporting items for the agreement evaluation of Bland-Altman method (RiBAM) as the recommended report.A list of recommended items called RiBAM was formed,which consisted of 17 first-level items and 23 secondary-level items.RiBAM is more comprehensive and systematic as an important reference for improving the quality of reports by avoiding the omission of reporting contents and achieving the clarity,integrity and transparency of the report.RiBAM recommended items can be a guide for authors in reporting Bland-Altman agreement evaluation as well as a basic reference for journal editors,peer reviewers and readers.

Objective To explore the exact sample size calculation method of bioequivalence evaluation (BE) for highly variable drugs.Methods Based on the two one-sided tests of bioequivalence evaluation for conventional 2 × 2 cross-over design and the statistical distribution theories to elucidate the exact sample size estimation method.Under the Food and Drug Administration (FDA) guidance and the European Medicines Agency (EMA) guideline on the investigation of bioequivalence for highly variable drugs,by using the reference-scaled average bioequivalence(RSABE) criteria to define the relationship between biological equivalent limits and various within-subject variability of reference product,the sample size required for replicated 3-and 4-period cross-over design is deduced exactly respectively.Using SAS progranaming to calculate the exact listings of sample size for different parameter settings of two types of replicated cross-over design,and compared with the formula approximation results published.Results Because of stricter RSABE criteria for EMA guideline than for FDA guidance,the required sample size is larger under the same parameter settings for EMA guideline.Compared with the results of formula approximation method,when the geometric mean ratio(GMR) is 1.0,the exact sample sizes are greater.When the GMR is increased or decreased from 1.0 the required sample sizes rise,and the exact sample size is generally less than or equal to the approximation result.The SAS program codes are provided to easily calculate the exact sample size under various parameter settings.Conclusion The methods of the sample size calculation proposed under FDA guidance and EMA guideline are exact with rigorous statistical theory.The SAS program codes are concise and practical,hope to provide methodological support for the sample size calculation of bioequivalence evaluation for highly variable drugs.

Objective: To evaluate the safety and clinical efficiency of holmium laser enucleation of the prostate (HoLEP) in the treatment of small-volume BPH (SBPH) complicated by severe lower urinary tract symptoms (LUTS). METHODS: We retrospectively analyzed the clinical data on 82 cases of SBPH with severe LUTS treated by HoLEP from January 2017 to December 2018. The patients were aged (65.5 ± 7.6) years, with a mean prostate volume of <40 ml, a total IPSS of 24.8 ± 4.6, a QOL score of 5.2 ± 0.8, the maximum urinary flow rate (Qmax) of (7.6 ± 3.7) ml/s, and a mean PSA level of (1.8 ± 1.4) μg/L. RESULTS: All the operations were successfully completed, the mean operation time averaging (30.2 ± 5.0) min, enucleation time (26.7 ± 5.6) min and comminution time (3.5 ± 1.1) min, and the enucleated tissue weighing (20.3 ± 4.9) g. After surgery, the bladders were irrigated for (3.5 ± 1.9) h, with (3.0 ± 1.7) L of rinse solution, and catheterization lasted (24.8 ± 9.7) h. Histopathology revealed moderate or severe lymphocytic infiltration in 69 cases (84.1%). At 6 months after operation, significant improvement was observed in the IPSS, QOL, Qmax and PSA level compared with the baseline (P < 0.05). To date, no urethral stricture-related reoperation was ever necessitated. CONCLUSIONS HoLEP is safe and effective for the treatment of SBPH complicated by severe LUTS and can be employed after adequate preoperative evaluation of the patient.《.
Humans ; Lasers, Solid-State ; Lower Urinary Tract Symptoms/surgery* ; Male ; Prostate/surgery* ; Prostatic Hyperplasia/surgery* ; Quality of Life ; Retrospective Studies

Objective: To investigate the relationship of the serum adiponectin level with the development of prostate cancer (PCa) and its influence on the biological characteristics of PCa cells. METHODS: This retrospective case-control study included 45 cases of PCa and 50 non-PCa controls. We analyzed the relationship of the serum adiponectin level with the development of PCa. Using the lentiviral vector, we constructed a stably transfected cell line with adiponectin receptor deficiency, treated the PCa cells with adiponectin, and determined the influence of the adiponectin level on the biological behavior of the PC-3 cells by CCK-8 assay, flow cytometry, tube formation assay and scratch wound healing assay. RESULTS: The level of serum adiponectin was decreased in the PCa patients as compared with the controls and it was negatively correlated with the Gleason scores. Adiponectin suppressed the proliferation, migration and tube formation of the PC-3 cells and inhibited them from transforming into S-stage cells. In the condition of adiponectin receptor deficiency, the PC-3 cells exhibited even greater abilities of proliferation, migration and pro-angiogenesis. CONCLUSIONS The decreased level of the serum adiponectin or deficiency of adiponectin receptor may contribute to the development of prostate cancer.
Adiponectin ; blood ; Case-Control Studies ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Male ; Neoplasm Grading ; Prostatic Neoplasms ; blood ; etiology ; Receptors, Adiponectin ; deficiency ; Retrospective Studies ; Transfection

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.
Humans ; Students, Medical ; Cross-Sectional Studies ; Sedentary Behavior ; Sleep