Objective To clarify the protective effect of allopregnanolone (APα) on cell line SH-SY5Y damaged by 6-hydroxydopamine (6-OHDA) and its possible molecular mechanism. Methods 6-OHDA, APα, γ-aminobutyric acid A receptor (GABAAR) antagonist, voltage-gated L-type Ca2

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult

[ Abstract] Objective To investigate the effects of allopregnanolone (APα) on the dopaminergic neurons in substantia nigra, striatal dopaminergic neural fibers and behavioral performance in Parkinson’ s disease (PD) model mice, as well as its possible molecular mechanisms. Methods C57BL / 6 adult male mice with 20-25 g at 3-month old (n = 90) were successively injected with 6-hydroxydopamine (6-OHDA) to generate a PD animal model. APα and its receptor γ-aminobutyric acid A receptor (GABAAR) antagonist—bicuculline (Bic) were successively injected. ELISA was used to detect the APα or dopamine concentration in the serum, cerebral cortex and striatum. The number of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatal dopaminergic neural projections were examined by immunohistochemical staining. The expression levels of GABAAR in membrane fractions and Ca

BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.

DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

OBJECTIVETo study the mechanism underlying the inhibitory effects of peroxisome proliferator-activated receptor γ (PPARγ) agonists on transforming growth factor β1 (TGF-β(1))-induced scarring of skin.

METHODSFibroblasts isolated from healthy adult skin were cultured in vitro and divided into blank control group (serum-free DMEM culture), TGF-β(1) group (with stimulation of 10 ng/mL TGF-β(1) for 48 hours), troglitazone group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L troglitazone for 2 hours), and 15-dioxygen prostaglandin J2 (15d-PGJ2) group (with the same treatment as in TGF-β(1) group after stimulation of 10 µmol/L 15d-PGJ2 for 2 hours) according to the stimulation added into DMEM. The expression of connective tissue growth factor (CTGF) was determined with Western blot. The mRNA levels of CTGF, matrix metalloproteinase-1 (MMP-1) and platelet-derived growth factor (PDGF) were determined with real-time fluorescence RT-PCR. Data were processed with one-way analysis of variance.

RESULTSThe expression of CTGF at mRNA and protein levels in skin fibroblasts were significantly increased in TGF-β(1) group as compared with control group; while expression of CTGF at mRNA and protein levels in 15d-PGJ2 and troglitazone groups were significantly decreased as compared with that in TGF-β(1) group. The mRNA level of MMP-1 in TGF-β(1) group (0.193 ± 0.051) was obviously lower than that in blank control group (1.281 ± 0.195, F = 12.811, P < 0.01), while the mRNA levels of MMP-1 in troglitazone group (0.417 ± 0.043) and 15d-PGJ2 group (0.485 ± 0.027) were significantly increased as compared with that in TGF-β(1) group (F = 12.811, P values all below 0.01). The mRNA level of PDGF in TGF-β(1) group (1.044 ± 0.237) was obviously higher than that in control group (0.349 ± 0.057, F = 16.848, P < 0.01), while the levels in troglitazone group (0.677 ± 0.055) and 15d-PGJ2 group (0.511 ± 0.017) were significantly decreased as compared with that in TGF-β(1) group (F = 16.848, P values all below 0.01).

CONCLUSIONSThe inhibitory effect of activated PPARγ on the expression of CTGF induced by TGF-β(1) may be the main mechanism of its inhibitory effect on TGF-β(1)-induced scarring on skin, and its influence on MMP-1 and PDGF may also be one of the underlying mechanisms.

Cell Line ; Connective Tissue Growth Factor ; metabolism ; Fibroblasts ; drug effects ; metabolism ; Humans ; Matrix Metalloproteinase 1 ; metabolism ; PPAR gamma ; agonists ; Receptors, Platelet-Derived Growth Factor ; metabolism ; Signal Transduction ; Transforming Growth Factor beta1 ; metabolism

Adult ; Female ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; surgery ; Sarcoma ; diagnosis ; surgery ; Tomography, X-Ray Computed

OBJECTIVETo observe the effects of early goal-directed fluid therapy with hydroxyethyl starch 130/0.4 on intra-abdominal hypertension (IAH), multiple organ dysfunction and fluid balance in severe acute pancreatitis (SAP) patients.

METHODSAccording to the criteria of selection and exclusion, 120 SAP patients within 72 hours after the symptom occurred from 4 study sites were recruited. They were given standard medication according to "the guideline of diagnosis and treatment of SAP in China" in SICU or PICU. The patients were randomly divided into two groups with crystalloid (control group) and colloid plus crystalloid resuscitation (research group). The objective of fluid therapy was to keep steady hemodynamics for 8 days. IAP was measured three times daily by means of urinary bladder transduction. Function of liver, renal and lung were detected daily. APACHE II score and fluid balance were calculated daily.

RESULTSTotal 120 cases were recruited into research group (n = 59) and control group (n = 61). The demography and baseline data were comparable. IAP was lower in research group than that in control group at day 4 and day 5 (P < 0.05). There was no significant difference in APACHE II scores between two groups pre- and after admission. The decline of daily IAP to baseline (DeltaIAP) in research group was significantly higher than in research group from day 2 to day 8(P < 0.05), whilst the decline of daily APACHE II score to baseline (DeltaAPACHE II score) in research group were significantly higher from day 4 to day 8 (P < 0.05). Negative fluid balance emerged much earlier in the research group (P = 0.036). Percentage of patients with negative fluid balance within 8 days was significantly higher in research group than that in control group (94.9% vs. 62.3%). The amount of positive fluid balance was significantly lower in research group (P = 0.039). IAP correlated significantly with APACHE II score (r(2) = 0.322, P = 0.000). PaO2/FiO2 was significantly higer in research group at day 4 and day 8.

CONCLUSIONSIt is very important to pay close attention to IAP in early fluid therapy of SAP patients. Early goal-directed fluid therapy with HES130/0.4 shortens the duration of positive fluid balance, decreases the amount of positive fluid balance, reduces APACHE II score, relieves IAH, and improves PaO2/FiO2.

Fluid Therapy ; Goals ; Humans ; Intra-Abdominal Hypertension ; Multiple Organ Failure ; Pancreatitis

OBJECTIVETo observe the precise time of the recurrence after resection of hepatocellular carcinoma (HCC) and to further explore the risk factors associated with postoperative recurrence.

METHODSTotally 94 patients who had undergone resection of HCC were divided into three groups based on the time of recurrence, which was indicated by the digital subtraction angiography (DSA) examination: recurrence between 1 to 6 months, recurrence between 7 to 12 months, and tumor-free after 12 months. Patients with intra-hepatic recurrence were treated with transcatheter arterial chemoembolization and confirmed by CT scans after embolization, contrast-enhanced ultrasound, or magnetic resonance imaging.

RESULTSThe recurrence rates of 6 months and 1 year were 30.9% and 36.2%, respectively. No statistically significant difference between 6-month and 1-year recurrence rates was observed. Nine (26.5%) patients with recurrence and five (8.3%) patients free of tumor had previously presented as multifocal HCC, which showed a statistical significance (P = 0.032). The diagnostic accuracy of DSA was 87.2%, which was eventually confirmed by the other investigations.

CONCLUSIONSMost recurrences occure within the first six months postoperatively and multifocal carcinogenesis is one of the risk factors associated with early recurrence after liver resection for advanced HCC. DSA is an important surveillance for early detection of intra-hepatic recurrence after surgery; meanwhile, it also provides information for early management to control the disease progression and for future active therapies.

Adult ; Aged ; Carcinoma, Hepatocellular ; diagnostic imaging ; pathology ; surgery ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnostic imaging ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Postoperative Period ; Tomography, X-Ray Computed

OBJECTIVETo establish a three-dimentional liver function evaluation system using 99mTc-diethyl iminodiacetic acid (99mTc-EHIDA) scintigraphy based on single photon emission computed tomography (SPECT).

METHODSTotally 16 patients with liver lesions were divided into cirrhosis group and non-cirrhosis group. SPECT was performed 2 days before operation and 5 days after operation. Serum liver functions were examined on the same day of scintigraphy. SPECT images of areas of interest of heart and liver were aquired. Time of the peak of EHIDA density in liver (Tpeak), five-minutes heart liver index (HLI5), blood clearance index (HH15), receptor index (LHL15), and the predictive values were calculated.

RESULTSTpeak was not significantly different between two groups, while HLI5, HH15, and LHL15 were significantly different (P = 0.033, P = 0.001, and P = 0.005). HLI, and LHL15 were significantly correlated with preoperative total protein and prealbumin levels (P = 0.003, P = 0.015, P = 0.022, P = 0.038) and post-operative prealbumin (P = 0.037, P = 0.042). The predictive values of HLI5 and LHL15 correlated well with postoperative HLI5 and LHL15 (r = 0.675, P = 0.016; r = 0.629, P = 0.028).

CONCLUSIONThe three-dimentional liver function evaluation system using 99mTc-EHIDA based on liver SPECT may facilitate the further studies of risks of liver surgery.

Adult ; Aged ; Animals ; Female ; Humans ; Liver Diseases ; diagnosis ; diagnostic imaging ; physiopathology ; Liver Function Tests ; Male ; Middle Aged ; Postoperative Period ; Preoperative Period ; Radiopharmaceuticals ; administration & dosage ; Technetium Tc 99m Diethyl-iminodiacetic Acid ; administration & dosage ; Tomography, Emission-Computed, Single-Photon

OBJECTIVETo summarize the surgical experiences, risks, complications, and managements for hepatic masses in difficult sites.

METHODSTotally 47 patients were divided into three groups based on the liver tumor sites: primary porta hepatis group, secondary porta hepatis group, and caudate lobe group. All patients underwent different portion of hepatectomy.

RESULTSThe surgery duration was (289.6 +/- 62.2) ml-nutes, intra-operative blood loss was (602.3 +/- 256.4) ml, and intra-operative blood transfusion was (524.0 +/- 325.9) ml. Incidence of surgical complications in each group was 61.5%, 26.9%, and 25%, respectively. Serious complications observed were biliary leakage (27.7%), bleeding (6.4%), and post-operative liver failure (2.1%). Three perioperative deaths were reported: two patients died of bleeding, and one patient died from liver failure.

CONCLUSIONSDissection of the liver and exposure of major blood vessels and biliary ducts are of critical importance in the surgeries for hepatic masses in difficult sites, and post-operative complications may be remarkably reduced through delicate manipulations of the small intra-hepatic vessels and biliary ducts during resection. A thorough pre-operative evaluation plays a key role in predicting the feasibility and risks of the surgery. Damage to the major blood vessels adjacent to the tumor, in addition to bleeding, may result in in-flow or outflow obstruction and cause necrosis of the corresponding hepatic lobe. Compared with damage to the primary portal area, vascular damage to the secondary porta is generally associated with higher fatality.

Adult ; Aged ; Blood Loss, Surgical ; Female ; Hepatectomy ; adverse effects ; Humans ; Liver Neoplasms ; pathology ; surgery ; Male ; Middle Aged ; Postoperative Complications ; Preoperative Care