Objective To study the application effect of Glisson hepatic pedicle priority approach marked by APR triangle in laparoscopic anatomic right hemihepatectomy(LARH).Methods The clinical data of 66 patients underwent LARH in the Affiliated Hospital of Tangshan Vocational and Technical College were retrospectively analyzed.According to the surgical approaches,the patients were divided into the extrathecal group and the APR group.The 35 patients of the extrathecal group underwent LARH via Glisson hepatic pedicle extrathecal approach.The 31 patients of the APR group were treated with LARH through the Glisson hepatic pedicle priority approach marked by APR triangle.The clinical data including perioperative indexes,postoperative complications,oxidative stress and liver function indexes of patients in the two groups were statistically analyzed,and the differences between the two groups were compared.Results The operative time and intraoperative blood loss of patients in the APR group were significantly shorter/less than those in the extrathecal group,with statistically significant differences(P<0.05).There was no significant differences in the intraoperative blood transfusion ratio,drainage tube indwelling time,first exhaust time,postoperative hospitalization time or postoperative complications of patients between the two groups(P>0.05).The levels of malondialdehyde(MDA),cortisol(Cor)and superoxide dismutase(SOD)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05),and the levels of MDA,Cor and SOD at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).The levels of albumin(ALB),total bilirubin(TBil),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)at each time point after surgery of patients in the two groups were significantly different from those before surgery(P<0.05).Moreover,the levels of ALB,TBil,AST and ALT at each time point after surgery of patients in the APR group were significantly better than those in the extrathecal group(P<0.05).Conclusion Compared with the Glisson hepatic pedicle extrathecal approach,the Glisson hepatic pedicle priority approach marked by APR triangle in LARH has shorter operation time,less bleeding and less oxidative stress reaction,which is beneficial to the recovery of liver function after surgery.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

LIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28's role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.
Animals ; Cell Differentiation ; Embryo, Mammalian/metabolism* ; Embryonic Development ; Mice ; Pluripotent Stem Cells/metabolism* ; RNA, Messenger/genetics* ; RNA, Ribosomal ; RNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism* ; Zygote/metabolism*

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Dyslipidemias ; drug therapy ; Glycemic Load ; drug effects ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Stilbenes ; pharmacology

BACKGROUND: Psoriasis is a chronic inflammatory skin disease, affecting about 0.6% of the Chinese population. Many patients are not well controlled by conventional treatments, thus there is need for new treatment regimens. In this study, we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis. METHODS: This study was a 52-week, multicentre, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 trial. A sub-population of study participants (≥18 years) of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab, or placebo. The co-primary endpoints were psoriasis area severity index (PASI) 75 and Investigator's Global Assessment (IGA) 0/1 at Week 12. RESULTS: A total of 441 Chinese patients were enrolled in this study. Co-primary outcomes were achieved; 300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75 (97.7% and 87.2% vs. 3.7%, respectively; P < 0.001), and IGA 0/1 (82.3% and 69.7% vs. 2.7%; P < 0.001) at Week 12. Treatment efficacy was maintained until Week 52. There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period. CONCLUSION: Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. TRIAL REGISTRATION ClinicalTrials.gov, NCT03066609; https://clinicaltrials.gov/ct2/show/record/NCT03066609.
Antibodies, Monoclonal/therapeutic use* ; Antibodies, Monoclonal, Humanized ; China ; Double-Blind Method ; Humans ; Psoriasis/drug therapy* ; Severity of Illness Index ; Treatment Outcome

Common bile duct (CBD) stones are a frequent problem in Chinese populations, and their incidence is particularly high in certain areas (Wang et al., 2013). In recent years, laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) have been the main surgical procedures for CBD stones, although each has different advantages and disadvantages in the treatment of choledocholithiasis (Loor et al., 2017; Zhou et al., 2017). For patients with large stones, a dilated CBD, especially concurrent gallstones, LCBDE is the preferred and most economical minimally invasive procedure (Koc et al., 2013). However, a T-tube is often placed during LCBDE to prevent postoperative bile leakage; this is associated with problems such as bile loss, electrolyte disturbance, and decreased gastric intake (Martin et al., 1998). In addition, the T-tube usually must remain in place for more than a month, during which time the patient's quality of life is seriously compromised. Many skilled surgeons currently perform primary closure of the CBD following LCBDE, which effectively speeds up rehabilitation (Hua et al., 2015). However, even in sophisticated medical centers, the incidence of postoperative bile leakage still reaches ≥10% (Liu et al., 2017). Especially for a beginner, bile leakage remains a key problem (Kemp Bohan et al., 2017). Therefore, a safe and effective minimally invasive surgical approach to preventing bile leakage during primary closure of the CBD after LCBDE is still urgently needed.
Aged ; Aged, 80 and over ; Choledocholithiasis ; Common Bile Duct Diseases ; Drainage/methods* ; Female ; Gallstones ; Gastroscopy ; Humans ; Laparoscopy ; Male ; Middle Aged

OBJECTIVETo investigated the curative effect of autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphoma.

METHODSThe clinical data of 81 patients with malignant lymphoma received ASCT from April 1999 to October 2013 were retrospectively analyzed. Of 81 patients, 70 were non-Hodgkin's lymphoma (NHL) and 11 Hodgkin's lymphoma (HL). High dose of etoposide combined with G-CSF was used to mobilize peripheral hematopoietic stem cell. Preconditioning regimen was BEAM (carmustine + cytarabine + etoposide + melphalan).

RESULTSEnough peripheral blood stem cells were collected from all patients. All of the patients after transplantation achieved hematopoietic reconstitution, the median time of the absolute neutrophil count (ANC) recovery to >0.5×10⁹/L time was 10(7-16) d, and the median time of platelet count recovery to >20×10⁹/L was 10(6-17) d. With the follow-up of 23(2-139) months, progression free survival (PFS) was 72.7%, and overall survival (OS) was 88.6%. The median PFS and OS were not reached. Complete remission (CR) before ASCT was an independent prognostic factor of PFS. No transplant related death happened.

CONCLUSIONASCT was a safe and effective method for treatment of malignant lymphoma.

Adolescent ; Adult ; Aged ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Transplantation, Autologous

OBJECTIVETo establish a detection method based on gas chromatography-mass spectrometry (GC-MS) for concentrations of volatile nitrosamine compounds in urine, and apply it to the test of real samples.

METHODSTarget compounds dichloromethane in urine samples was extracted with dichloromethane through liquid-liquid extraction, then the dichloromethane extract was filtrated, evaporated with nitrogen at 40°C to dryness, and the volume was set with 0.2 ml dichloromethane. Analysis of nine volatile nitroso-compounds were performed with GC-MS under selected ion monitoring mode, external reference method was used for quantification, and the detection limit, repeatability and sensitivity were evaluated. In addition, nine volatile nitroso-compounds of 92 urine samples in a town of Anhui province were measured.

RESULTSA good linear range of 2 - 200 ng/ml (with correlation coefficient 0.9985 - 0.9999) were obtained for the above mentioned nine kinds of analyte, and the lowest examination concentration was 0.05 - 0.50 ng/ml. The addition standard recoveries were 68%-102% with the RSD of 0.4% - 5.5% (n = 3). The detection limits were 0.001 - 0.013 ng/ml urine. The detection rate of N-nitrosodimethylamine (NDMA), N-nitrosomethylethylamine (NMEA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR), N-nitrosopiperidine (NPIP), N-nitrosodi-n-butylamine (NDBA) and N-nitrosodiphenylamine (NDPhA) were 71% (65), 74% (68), 65% (60), 80% (73), 92% (85), 78% (72), 76% (70), 87% (80), 98% (90), respectively, with the results (0.27 ± 0.12), (0.75 ± 0.29), (0.06 ± 0.02), (0.16 ± 0.07), (23.66 ± 5.18), (1.01 ± 0.35), (0.38 ± 0.11), (2.47 ± 0.52) and (15.13 ± 3.48) nmol/g creatinine.

CONCLUSIONSA gas chromatography-mass spectrometry detect method was developed for low level volatile nitrosamines in urine samples.

Gas Chromatography-Mass Spectrometry ; Humans ; Nitrosamines ; urine ; Urinalysis ; methods ; Volatile Organic Compounds ; urine

BACKGROUNDTransradial access has been increasingly used during primary percutaneous coronary intervention (PCI) for patients with acute ST-segment elevation myocardial infarction (STEMI) in last decade. Clinical benefits of upstream use of tirfiban therapy in STEMI patients treated by primary PCI have been reported. We investigated the merits of transradial vs. transfemoral access in primary PCI for STEMI patients with upstream use of tirofiban.

METHODSPatients with STEMI treated with tirofiban between December 2006 and October 2012 then by primary PCI were compared between transradial (n = 298) and transfemoral (n = 314) access. Baseline demographics, angiographic and PCI features and primary endpoint of major adverse cardiac events (MACE) at 30-day clinical follow-up were recorded.

RESULTSBaseline and procedural characteristics were comparable between the two groups, apart from more patients in transradial group had hypertension and were treated by thrombus aspiration during primary PCI. Significantly fewer MACE occurred in the transradial group (5.4%) compared with the transfemoral group (9.9%) at 30-day clinical follow-up. Major bleeding events at 30-day clinical follow-up were 0 in transradial group and in 2.9% of transfemoral group. Multivariate analysis confirmed transradial approach as an independent negative predictor of 30-day MACE (HR 0.68; 95%CI 0.35 - 0.91; P = 0.03).

CONCLUSIONSUsing transradial approach in primary PCI for acute STEMI infarction patients treated with tirofiban was clearly beneficial in reducing bleeding complications and improving 30-day clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; drug therapy ; therapy ; Percutaneous Coronary Intervention ; methods ; Tyrosine ; analogs & derivatives ; therapeutic use

BACKGROUNDThe clinical significance of ischemic chest pain before acute ST-elevation myocardial infarction (STEMI) remains an interesting issue of investigation particularly in the era of percutaneous coronary intervention (PCI). This study aimed to assess the impact of angina prior to STEMI on short-term clinical outcomes in patients with acute STEMI undergoing primary PCI.

METHODSAmong a total of 875 consecutive patients with STEMI undergoing primary PCI, 292 had episodes of angina within 24 hours of STEMI (PA group) and the remaining 583 were free of anginal symptoms (non-PA group). Clinical characteristics, angiographic and procedural features, and in-hospital and 30-day outcomes were compared between the two groups.

RESULTSDiabetes was less common (17.5% vs. 23.3%, P = 0.04) and symptom-to-door time was shortened ((191.6 ± 96.8) minutes vs. (357.2 ± 341.9) minutes, P < 0.001) in the PA group than in the non-PA group. Patients with angina prior to STEMI had fewer totally or nearly totally occluded infarct-related artery (TIMI flow grade 0 - 1) at initial angiography (75.0% vs. 90.7%, P < 0.001), and achieved more TIMI flow grade 3 after primary PCI (84.2% vs. 78.2%, P = 0.04). These were associated with higher rates of overall procedural success (95.9% vs. 91.8%, P = 0.02) and of complete ST-segment resolution at 90 minutes after the procedure (51.7% vs. 40.3%, P = 0.001). During a 30-day clinical follow-up, the left ventricular ejection fraction was significantly improved ((53.0 ± 8.6)% vs. (51.1 ± 9.7)%, P = 0.002) and the primary endpoint of major adverse cardiac events was reduced in the PA group (7.2% vs. 12.7%, P = 0.01).

CONCLUSIONPresence of angina prior to acute STEMI is associated with better outcome at a 30-day clinical follow-up in patients undergoing primary PCI.

Acute Coronary Syndrome ; therapy ; Aged ; Angina, Unstable ; physiopathology ; Angioplasty, Balloon, Coronary ; Coronary Angiography ; Electrocardiography ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Prospective Studies