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Background Sphingolipids produce pleiotropic signaling pathways, and participate in the pathological mechanism of hepatocyte apoptosis and necrosis during liver injury. However, the role of glucosylceramide synthase (GCS)–key enzyme that catalyzes the first glycosylation step, in liver injury is still vague. Methods All experiments were conducted using 7–9-week-old pathogen-free male C57BL/6 mice. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were detected in murine models of liver disease, in addition to histological characterization of liver injuries. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expression of the GCS, matrix metallopeptidase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes. The GCS was observed through a fluorescence microscope, and the flow cytometry was used to detect hepatocyte apoptosis. The concentrations of serum IL-4, IL-6, and IL-10 were measured using enzyme-linked immune-sorbent assay (ELISA) kit. MMP-1 and TIMP-1 protein expression was measured via western blot (WB) analysis. Results Con A is often used as a mitogen to activate T lymphocytes and promote mitosis. A single dose of Con A injected intravenously will cause a rapid increase of ALT and AST, which is accompanied by the release of cytokines that cause injury and necrosis of hepatocytes. In this study, we successfully induced acute immune hepatitis in mice by Con A. Con A administration resulted in GCS upregulation in liver tissues. Moreover, the mice in the Con A group had significantly higher levels of ALT, AST, IL-4, IL-6, IL-10 and increased hepatocyte apoptosis than the control group. In contrast, all of the aforementioned genes were significantly downregulated after the administration of a GCS siRNA or Genz-123346 (i.e., a glucosylceramide synthase inhibitor) to inhibit the GCS gene. Additionally, the histopathological changes observed herein were consistent with our ALT, AST, IL-4, IL-6, and IL-10 expression results. However, unlike this, hepatocyte apoptosis has been further increased on the basis of the Con A group. Moreover, our qRT-PCR and WB results indicated that the expression of MMP-1 in the Con A group was significantly lower than that in the control group, whereas TIMP-1 exhibited the opposite trend. Conversely, MMP-1 expression in the GCS siRNA and Genz-123346 groups was higher than that in the Con A group, whereas TIMP-1 expression was lower. Conclusions GCS inhibition reduces Con A-induced immune-mediated liver injury in mice, which may be due to the involvement of GCS in the hepatocyte repair process after injury.

To evaluate whether low-frequency ultrasound-facilitated transdermal delivery of a Chinese medicine (CM) formula could improve the efficacy of intrapleural administration of interleukin-2 (IL-2) in treatment of malignant pleural effusion (MPE). A total of 110 eligible participants were randomized into the low-frequency sonophoresis (LFS) of CM (LSF/CM) group (55 cases) and the control group (55 cases) by simple randomization using a random number table. The control group was treated with an intrapleural administration of IL-2; and the LFS/CM group was treated with LFS of a CM gel formulation, combined with the same IL-2 injection as in the control group. The CM formula consisted of Semen Lepidii, Semen Sinapis, Ramulus Cinnamomi, Poriacocos, Herba Lycopi, and Radix Paeoniae Rubra. After 2-week treatment, the therapeutic outcome was determined by the change of the amount of MPE, which was evaluated by B-scan ultrasound and/or chest X-ray, and the change of quality of life (QOL) scores, which were evaluated by the Eastern Cooperative Oncology Group (ECOG) performance status. A significantly higher objective remission rate (ORR) was obtained with intrapleural IL-2 plus LFS/CM than IL-2 treatment alone (P=0.049). In addition, more patients in the LFS/CM group than in the control group had an improved QOL score (P=0.048), and no patients in the LFS/CM group had a reduced QOL. Conclusion: LFS of CM formulation could effectively alleviate MPE and improve the QOL of cancer patients.

To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (加味大承气汤, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design. Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators. Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed. Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

BACKGROUND The relationship between non-cholestatic liver disease and total bile acid (TBA) remains obscure. The present study aimed to verify this relationship in patients with non-cholestatic chronic hepatitis B virus (HBV) infection. METHODS A total of 922 consecutive chronic HBV infected patients with alkaline phosphatase (ALP) ≤ 1.5 upper limit of normal (ULN) and gamma-glutamyl transferase (GGT) ≤ 3 ULN were rigorously included in this cross-sectional study. Liver biopsy was performed in 53 patients and Scheuer scoring system was used to evaluate inflammation grade. G3/G4 or Child-Pugh B/C were considered to be significant liver injury. RESULTS Compared to Child-Pugh A, TBA, total bilirubin (TBIL), ALP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and AST to ALT ratio (AST/ALT) were significantly higher in Child-Pugh B/C, while TBIL to TBA ratio (TBIL/TBA) was significantly lower (all p < 0.001). In multivariate analysis, TBA and AST/ALT were independently correlated with Child-Pugh B/C [odds ratio (OR) = 1.04, p < 0.001; OR = 1.79, p < 0.001, respectively]. The area under the curve (AUC) of TBA (0.82) was significantly higher than that of AST (0.73, p < 0.001) and ALT (0.63, p < 0.001). Furthermore, in patients with liver biopsy, TBA was also significantly higher in G3/G4 while TBIL/TBA was significantly lower (p < 0.05). After adjusting the factors related to bile excretion, TBIL/TBA was independently associated with G3/G4 (OR = 0.89, p = 0.037). CONCLUSIONS Serum TBA shows a close relationship with significant liver injury in chronic HBV infected patients without cholestasis. Assessment of TBA, especially in combination with TBIL/TBA, may serve as a non-invasive marker for the diagnosis of non-cholestatic hepatic damage.

Paeoniae Radix Alba (PRA, dried root of Paeonia lactiflora Pall.) is a widely used as traditional Chinese medicine and tannins are one of their main bioactive ingredients. However, there are rarely systematically investigated in this study. This study aimed to establish a rapid, high selective, high sensitive and effective method based on UHPLC-Q-Exactive Orbitrap MS for simultaneous identification the tannins in PRA. Separation was performed on Thermo Scientific Hypersil GOLD™ aQ (100 mm × 2.1 mm, 1.9 μm) using gradient elution consist of 0.1% formic acid acetonitrile and 0.1% formic acid water as the mobile phase at a flow rate of 0.3 mL/min. The mass spectrometer was operated with Q-Exactive Orbitrap spectrometer in negative ion mode. Finally, a total of 106 constituents were identified in PRA by UHPLC-Q-Exactive Orbitrap MS, 75 of those were reported from PRA for the first time. This result laid the foundation for in-depth research on the material basis efficacy and provided scientific basis for the selection of quality marker of PRA.

To evaluate the efficacy and safety of topical delivery of modified Da-Cheng- Qi Decoction (, MDCQD) by low-frequency ultrasound sonophoresis (LFUS) in patients with refractory metastatic malignant bowel obstruction (MBO) using an objective performance criteria (OPC) design.Fifty patients with refractory metastatic MBO were enrolled in this open-label single-arm clinical trial. Alongside fasting, gastrointestinal decompression, glycerol enema, intravenous nutrition and antisecretory therapy, a 50 g dose of MDCQD (prepared as a hydrogel) was applied through topical delivery at the site of abodminal pain or Tianshu (S 25) using LFUS for 30 min, twice daily for 5 consecutive days. The overall outcome was the remission of intestinal obstruction, and improvement on abdominal pain, abdominal distention, nausea and vomiting scores. Indicators of safety evaluation included liver and renal function as well as blood coagulation indicators.Among 50 patients, 5 patients (10%) showed complete remission of intestinal obstruction and 21 patients (42%) showed improvement of intestinal obstruction. The overall remission rate of bowel obstruction was 52%. The results of the symptom score, based on the severity and frequency of the episode, are as follows: 26 patients (52%) showed improvment on symptom scores, 20 patients (40%) did not respond to treatment, and 4 patients (8%) discontinued treatment due to intolerance. No serious adverse effects or abnormal changes on liver and renal function or blood coagulation were observed.Topical delivery of MDCQD at 100 g/day using LFUS can improve the treatment response in patients with refractory metastatic MBO.

Dermatologic toxicities resulting in dose reduction or discontinuation of treatment pose challenges for targeted anticancer therapies. We conducted this randomized, double-blind, placebo-controlled trial to investigate the efficacy of topical application of Compound Danxiong Granules (CDG) for treatment of dermatologic toxicities associated with targeted anticancer therapies. One hundred and ten patients with dermatologic toxicities induced by targeted anticancer therapies were randomly assigned to CDG or placebo group. Each crude herb (Rhizoma Chuanxiong, Paeonia suffruticosaAndr.,Cortex Phellodendri, Geranium sibiricumL., andFlos Carthami) was prepared as an instant herbal powder. Application of the CDG via topical washes lasted 20 minutes, twice daily, for 10 days. The primary outcome was the total effective rate, defined as reduction in at least one grade of skin toxicity. The total effective rate was 77.61% (52/67) in the CDG group and 27.27% (9/33) in the placebo group (P<0.0001). Compared to the placebo treatment, CDG treatment achieved a higher total effective rate for hand-foot skin reaction (95.45% versus 27.27%), acneiform eruption (69.23% versus 30.78%), and paronychia (68.42% versus 22.22%). Topical application of CDG can effectively attenuate dermatologic toxicities induced by targeted anticancer therapies. The effect of CDG was more pronounced in hand-foot skin reaction.

In order to analyze failure phenomena and mechanical properties of propellant-liner interface material, both experimental study and modeling were carried out. The adhesive system was observed under tensile. Based on experiment, the finite element analysis was implemented. Results show that the failure is initiated on a certain point near the propellant and the deformation concentration of localization zone and the macro-cracks occur. The failure process can be modeled and stress distributions can be obtained by introducing cohesive element. The method offers references to interface designing

The mixing process of composite solid propellant slurry in kneading mixers is considered as the research object. POLYFLOW software is employed to solve the problems numerically. Turning the mixing tank instead of the revolution of the impellers, thus the planetary motion is carried out only by the autorotation of the impellers around their own axes. With mesh superposition technique and mesh refinement technique, the impellers and mixing tank are meshed. Visualization of flow process and flow pattern in a kneading mixer is realized and flow fields of velocity, shear stress, viscosity and mixing index are obtained.

To evaluate the impact of the intrauterine device (IUD) insertion on the mental state of women.From Jan. 2009 to Jun. 2010, a multi-center clinical observational study was performed. Totally 641 women were selected in the six provinces' 18 family planning service stations and hospitals for IUD insertion surgery study. Analysis of the change of women's mental state which was evaluated by symptom checklist-90 (SCL-90) scale before and after IUD insertion surgery.Before and after IUD insertion surgery, 10 factors' scores in SCL-90 of the observed objects were between 1.1 to 1.2, total scores were 107±27 and 105±25, respectively. Before and after surgery, total average score both were 1.2, the average score of positive items both were 2.1. The difference of the above results were not statistically significance (all P0.05). Preoperative and postoperative, the rate of positive items was 9.2%-19.6% and 7.7%-17.6%, respectively.In addition to anxiety and fear, the rate of other factors' positive items postoperative was significantly lower than those in the preoperative (all P0.05). The incidence of the observed objects postoperative of each factor score, "deteriorated" was in the range of 4.9% to 23.0%, "improved" was in the range of 26.3%-50.1%. The incidence of total scores, "deterioration" was 28.8% (166/575), "improved" was 45.6% (262/575). The incidence of the average score of positive items, "deterioration" was 3.7% (21/575), "improved" was 52.3% (301/575). Logistic analysis showed that, in addition to unit level, there were no other significant influencing factors for women' mental state of postoperative (all P0.05).IUD insertion surgery has no adverse effect on women's mental state.

The objective of the study was to explore parental perspectives and attitudes towards the provision of sexual and reproductive health (SRH) information and services to unmarried youth in Chengdu, China. A representative sample of parents was drawn using multi-stage stratified cluster sampling technique, and information was collected using a structured questionnaire. The eligible respondents were parents (both fathers and mothers) who had at least one unmarried adolescent and/or youth aged 15 to 24 years old. A total of 2,871 fathers and mothers were interviewed. Parents' SRH-related knowledge was poor and dissonant attitudes of tolerance and ambivalence towards provision of SRH information and services to unmarried youth were found. About 80% of parents accepted and understood unmarried youth seeking SRH counseling service, but the percentages of such positive attitude was much lower for premarital contraceptive use. Over half of the parents were supportive of providing SRH education and information to unmarried youth; whereas on the provision of contraceptive services to sexually active unmarried youth, 27% were negative, 25% accepted, 36% indicated an understanding, and the rest 12% had no opinion. Parents' SRH-related knowledge and attitudes were associated with parental social-demographic characteristics. Findings from this study suggest that parent-oriented programs are needed to apprise them of the existing SRH conditions of the unmarried youth in China, to allay fears and misconceptions of parents, and to enhance family-based sex education in terms of increasing parents' SRH knowledge and their capacity and skills of providing such information to unmarried youth.

To assess the safety and effectiveness of intrauterine device in Chinese women.In this multicenter randomized controlled trial, a total of 24 000 women were randomly (1:1:1) into 3 groups of Yuangong Cu 365 (YCu365), Copper T 380A (TCu380A) and Multiload Cu 375 (MLCu375). Clinical outcomes were assessed at 12 months post-insertion, including discontinuation due to pregnancy, expulsion, hemorrhage and downward displacement, etc. The overall and causal-specific discontinuation rates for adverse events were calculated.At the end of the first year, the discontinuation rate of YCu365 (4.21%) was the lowest, followed by TCu380A (8.42%) and MLCu375 (13.91%) (P0.01). The differences of discontinuation rates for pregnancy, expulsion, hemorrhage and downward displacement between these IUDs were also significant. MLCu375, side effect without medical treatment, fewer follow-ups, deeper uterine cavity and previous IUD failure were significantly associated with an increased risk of IUD discontinuation.The newly developed indomethacin-releasing YCu365 IUD appears to perform the best. However, its long-term safety and cost-effectiveness should be further evaluated.