The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.

As the most prevalent chronic liver disease globally, NAFLD encompasses a pathological process that ranges from simple steatosis to NASH, fibrosis, cirrhosis, and HCC, closely associated with numerous extrahepatic diseases. While the initial etiology was believed to be hepatocyte injury caused by lipid toxicity from accumulated triglycerides, recent studies suggest that an imbalance of cholesterol homeostasis is of greater significance. The role of nuclear receptors in regulating liver cholesterol homeostasis has been demonstrated to be crucial. This review summarizes the roles and regulatory mechanisms of nuclear receptors in the 3 main aspects of cholesterol production, excretion, and storage in the liver, as well as their cross talk in reverse cholesterol transport. It is hoped that this review will offer new insights and theoretical foundations for the study of the pathogenesis and progression of NAFLD and provide new research directions for extrahepatic diseases associated with NAFLD.

Does Complexity Equal Anything?

We present a new infinite class of gravitational observables in asymptotically anti-de Sitter space living on codimension-one slices of the geometry, the most famous of which is the volume of the maximal slice. We show that these observables display universal features for the thermofield-double state: they grow linearly in time at late times and reproduce the switchback effect in shock wave geometries. We argue that any member of this class of observables is an equally viable candidate as the extremal volume for a gravitational dual of complexity.

Bi-Basal Ganglia Involvement with Signal Evolution in a Case of Anti-LGI1 Encephalitis.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of non-paraneoplastic limbic encephalitis (LE) mainly characterized by seizures, cognitive disorder, faciobrachial dystonic seizures (FBDS), hyponatremia, insomnia, and autonomic dysfunction. Here, we report the case of an elderly female patient who tested positive for antibodies against LGI1 and was initially thought to have Hashimoto encephalopathy (HE) due to its similar clinical features and the patient's high titers of antithyroid antibody. Interestingly, during the course of the disease, the patient exhibited typical FBDS and brain magnetic resonance imaging (MRI) showed a hyperintense signal evolution from T2/Fluid attenuated inversion recovery (FLAIR) to T1-weighted image in the bilateral basal ganglia (BG), which have rarely been reported previously.

Erratum: Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3ß Signaling Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.32873.].

Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Jiedu Sangen decoction inhibits chemoresistance to 5-fluorouracil of colorectal cancer cells by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway.

Drug resistance is a major obstacle in the development of effective colorectal cancer (CRC) therapy. Our study aimed to explore the reversal abilities of Jiedu Sangen decoction (JSD) on the 5-fluorouracil (5-FU) resistance and its underlying molecular mechanisms. Expression changes in HIF-1 of CRC tissues were firstly revealed by bioinformatics analysis. Afterwards, cell viabilities of JSD and 5-FU treatments on 5-FU resistant human colon cancer cells (HCT-8/5-FU) were determined. Expressions of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT)/p-AKT, hypoxia-inducible factor 1 (HIF-1α), as well as glycolysis related proteins such as L-lactate dehydrogenase A (LDHA), Glucose transporter type 1 (Glut1), Hexokinase 2 (HKII), and cysteinyl aspartate specific proteinase (Caspase) family members in HCT-8/5-FU cells, HIF-1α silenced HCT-8/5-FU cells and tumor tissues were detected by western blotting. HIF-1α was found over expressed in CRC tissues according to public available datasets in Oncomine. Growth inhibition rates of HCT-8/5-FU cells were increased along with the increase of JSD concentrations. JSD caused down-regulated HIF-1α, PI3K, AKT/p-AKT, HKII and Glut1, as well as up-regulated Caspase3 and Caspase9 in HCT-8/5-FU cells and tumor tissues. In HIF-1α silenced HCT-8/5-FU cells, synergistic group showed significantly reduced expression levels of PI3K, AKT, p-AKT. Additionally, up-regulated expressions of Caspase6 and Caspase7 were observed. JSD combined with 5-FU also exhibited obvious inhibitory efficiency on tumor growth in vivo. JSD may reverse 5-FU resistance by suppressing glycolysis via PI3K/AKT/HIF-1α signaling pathway, thereby inhibiting glycolysis and induce apoptosis to enhance anti-tumor activity.

Long non-coding RNAs towards precision medicine in gastric cancer: early diagnosis, treatment, and drug resistance.

Gastric cancer is a deadly disease and remains the third leading cause of cancer-related death worldwide. The 5-year overall survival rate of patients with early-stage localized gastric cancer is more than 60%, whereas that of patients with distant metastasis is less than 5%. Surgical resection is the best option for early-stage gastric cancer, while chemotherapy is mainly used in the middle and advanced stages of this disease, despite the frequently reported treatment failure due to chemotherapy resistance. Therefore, there is an unmet medical need for identifying new biomarkers for the early diagnosis and proper management of patients, to achieve the best response to treatment. Long non-coding RNAs (lncRNAs) in body fluids have attracted widespread attention as biomarkers for early screening, diagnosis, treatment, prognosis, and responses to drugs due to the high specificity and sensitivity. In the present review, we focus on the clinical potential of lncRNAs as biomarkers in liquid biopsies in the diagnosis and prognosis of gastric cancer. We also comprehensively discuss the roles of lncRNAs and their molecular mechanisms in gastric cancer chemoresistance as well as their potential as therapeutic targets for gastric cancer precision medicine.

Jiedu Sangen Decoction Reverses Epithelial-to-mesenchymal Transition and Inhibits Invasion and Metastasis of Colon Cancer via AKT/GSK-3ß Signaling Pathway.

Ethnopharmacology relevance: Jiedu Sangen Decoction (JSD), an empirical prescription of Traditional Chinese Medicine (TCM), has been reported to inhibit invasion and metastasis of colon cancer in our previous study. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. Methods: In vitro, AKT1 knockdown (si-AKT1) or overexpression (oe-AKT1) cells were successfully constructed both in SW480 and SW620 cell lines. Si-AKT1 and oe-AKT1 cells were then treated with or without JSD. Cell invasion, metastasis potential and expression of epithelial-mesenchymal transformation (EMT)-related and AKT1/GSK-3ß proteins were then observed by wound healing, transwell, and western blot assays. In vivo, liver metastasis model mice were developed by inoculating SW480 cells. After JSD diet intervention, living fluorescence imaging and weight measurements were carried out to investigate JSD induced inhibition effects on liver metastasis of colon cancer. Immunohistochemistry and western blot assays were performed to observe tissue features and detect protein expression. Results: Invasion and metastasis potential, as well as EMT of colon cancer, can be markedly inhibited by JSD treatment or AKT1 knockdown, while enhanced by AKT1 overexpression. JSD-induced inhibition effects were significantly weakened when AKT1 was knocked down, while clearly enhanced when AKT1 was overexpressed. Additionally, JSD could lead to an increase in expression of E-cadherin, and a decrease in expression of N-cadherin, Vimentin, p-AKT1, AKT1, p- GSK-3ß, Snail, Slug, and Twist in colon cancer cells. Conclusion: JSD reverses EMT and inhibits invasion and metastasis of colon cancer through the AKT/GSK-3ß signaling pathway.

First Law of Holographic Complexity.

We investigate the variation of holographic complexity for two nearby target states. Based on Nielsen's geometric approach, we find the variation only depends on the end point of the optimal trajectory, a result which we designate the first law of complexity. As an example, we examine the complexity=action conjecture when the anti-de Sitter vacuum is perturbed by a scalar field excitation, which corresponds to a coherent state. Remarkably, the gravitational contributions completely cancel and the final variation reduces to a boundary term coming entirely from the scalar field action. Hence, the null boundary of Wheeler-DeWitt patch appears to act like the "end of the quantum circuit".

Antimony contamination, consequences and removal techniques: A review.

A significant amount of antimony (Sb) enters into the environment every year because of the wide use of Sb compounds in industry and agriculture. The exposure to Sb, either direct consumption of Sb or indirectly, may be fatal to the human health because both antimony and antimonide are toxic. Firstly, the introduction of Sb chemistry, distribution and health threats are presented in this review, which is essential to the removal techniques. Then, we provide the recent and common techniques to remove Sb, including adsorption, coagulation/flocculation, membrane separation, electrochemical methods, ion exchange and extraction. Removal techniques concentrate on the advantages, drawbacks, economical efficiency and the recent achievements of each technique. We also take an overall consideration of experimental conditions, comparison criteria, and economic aspects.

Newly identified transcripts of UL4 and UL5 genes of human cytomegalovirus.

Human cytomegalovirus (HCMV) UL4 and UL5 genes are two members of the RL11 gene family. In an earlier study, three UL4 transcripts of about 1.7, 1.5 and 1.4 kb were found in early and late classes after infection by the Towne strain by nuclease protection and primer extension analyses. In the present study, two UL4 transcripts (1.5 and 1.7 kb) were found by cDNA library screening, Northern blot, 3' and 5' RACE analyses to appear initially in the immediate early phase and one UL4 transcript (1.4 kb) in the late phase in a low-passage clinical isolate. Furthermore, two novel low-abundance UL5 transcripts with the same 3' terminus as the identified UL4 transcripts in the UL4-UL5 gene region were found in late class RNAs.

[Beta-HIVS combined cisplatin inhibited activities of human ovarian cancer cell line SKOV3 in vitro].

OBJECTIVE: To study the effect of beta-hydroxyisovaleryl shikonin (beta-HIVS) combined cisplatin on activities of ovarian cancer cell line SKOV3 in vivo and its possible mechanisms. METHODS: Cells were divided into the blank control group and six beta-HIVS groups (2 - 30 micromol/L). Effect of beta-HIVS at different concentrations on the activities of ovarian cancer cell line SKOV3 was detected using MTT assay. SKOV3 cells were treated with cisplatin (10, 20, and 40 micromol/L) and beta-HIVS (0.25, 1, and 2.5 micromol/L) combined cisplatin. Effect of beta-HIVS combined cisplatin on the activities of ovarian cancer cell line SKOV3 was determined by MTT assay. The expression of Bcl-2 and Bax after treated by different concentrations of beta-HIVS was detected by Western blot. RESULTS: The activities of SKOV3 were inhibited by different concentrations of beta-HIVS dose-dependently. The 50% inhibition rate (IC50) was 7.37 micromol/L. There was statistical difference in IC50 between each concentration beta-HIVS group and the blank control group (P < 0.05). There was statistical difference in IC50 between the beta-HIVS (1 and 2.5 micromol/L) combined cisplatin groups and the cisplatin group (P < 0.05, P < 0.01). The synergistic effect on beta-HIVS showed dose-dependent manner. Results of Western blot showed beta-HIVS at different concentrations (5, 7.5, and 10 micromol/L) could obviously up-regulate the expression level of Bax protein and inhibit the expression level of Bcl-2 protein, showing statistical difference when compared with the control group (P < 0.01). CONCLUSIONS; HIVS could obviously inhibit in vitro growth of SKOV3 in a dose-dependent manner. With the range of concentration, beta-HIVS showed synergetic effect with cisplatin. Besides, along with increasing beta-HIVS concentrations, the synergetic effect was more significant. The synergetic effect might accelerate the apoptosis of SKOV3 through up-regulating Bax expression and inhibiting Bcl-2 expression.

[Surgical resection versus radiofrequency ablation for primary hepatocellular carcinoma of 3-5 cm in diameter: a meta-analysis].

OBJECTIVE: To compare the therapeutic effects of surgical hepatic resection (HR) and radiofrequency ablation (RFA) in treatment of primary hepatocellular carcinoma of 3-5 cm in diameter. METHODS: The databases PubMed, CBMdisc, CNKI, WanFang Data and VIP databases were searched for controlled clinical trials on evaluating the efficacy between RFA and HR in treatment of primary hepatocellular carcinoma of 3-5 cm in diameter published from January 1990 to February 2014. Two reviewers independently screened the literature, extracted the data and assessed the methodological quality of the studies included. Then the meta-analysis was performed by using RevMan5.0 software. RESULTS: Eleven controlled clinical trials were included, including one randomized controlled trial and 10 non-randomized controlled trials. A total of 811 patients were involved: 404 patients were treated with RFA as the initial treatment and 407 patients with surgical resection. Meta-analysis showed that for a single lesion with diameter of 3-5 cm of primary hepatocellular carcinoma, the 3-， 5-year disease-free survival rates in HR group was significantly higher than those in RFA group (all P<0.05). There were no significant difference in the 1-， 3-， 5-year overall survival rates and 1-year disease-free survival rate between RFA group and HR group (P>0.05). For 1-2 nodules with diameters of 3-5 cm of primary hepatocellular carcinoma, the 3-， 5-year disease-free survival rates and 5-year overall survival rates in HR group was significantly higher than those in RFA group (all P<0.05). No significant difference in 1-， 3-year overall survival rates and 1-year disease-free survival rate was found between RFA group and HR group (P>0.05). For maximum nodule of 3-5 cm of multiple primary hepatocellular carcinoma, the 5-year overall survival rates in HR group was significantly higher than that in RFA group (all P<0.05). No significant difference in 1-， 5-year overall survival rates was noted between RFA group and HR group (P>0.05). CONCLUSION: For primary hepatocellular carcinoma of 3-5 cm in diameter, HR is better than RFA. For the limitation of quality and quantity of included studies, this conclusion needs to be confirmed by more high quality studies.

[Jiedu sangen decoction intervened carcinoma-associated fibroblasts and inhibited migration and invasion of colon cancer: an experimental research].

OBJECTIVE: To observe the effect of Jiedu Sangen Decoction (JSD, consisting of Polygonum cuspidatum, Geum Japonicum Thumnb, Radix Actinidiae Chinensis) on the migration capability of colon cancer CT-26 cells were observed, and on expressions of carcinoma-associated fibroblasts (CAFs) such as transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinase 9 (MMP-9), and alpha-smooth muscle actin (alpha-SMA). METHODS: The BALB/C mice were subcutaneously inoculated with colon cancer CT-26 cells (1.2 x 10(6)mL) and then randomly divided into 3 groups, i.e., the normal control group, the model group, the JSD treated group. The effects of three different serums on the migration ability of colon cancer CT-26 cells were observed using Transwell. The expression quantities of TGF-beta1 and MMP-9 in the supernatant of CAFs were detected using ELISA. The mRNA expression quantities of TGF-beta1 and alpha-SMA in CAFs were detected by real-time fluorescence quantitative PCR. RESULTS: The number of semi-permeable film cells in the JSD treated group significantly decreased, when compared with the model group, showing statistical significance (P < 0.01). Compared with the model group, the expressions of TGF-beta1 and MMP-9 in the supernatant of CAFs decreased in the JSD treated group at 24 and 48 h, showing statistical difference (P < 0.05, P < 0.01). Compared with the model group, the mRNA expressions of TGF-beta1 and alpha-SMA in the JSD treated group obviously decreased, showing statistical difference (P < 0.01). CONCLUSION: JSD could decrease expressions of TGF-beta1 and MMP-9 in the supernatant of CAFs, lower mRNA expressions of alpha-SMA and TGF-beta1, which might be possible mechanisms for inhibiting the migration and invasion of tumor cells.

Plasma visfatin, a possible prognostic marker in aneurysmal subarachnoid hemorrhage.

Visfatin is linked to inflammation and associated with clinical outcomes of intracerebral hemorrhage. This study was designed to investigate whether visfatin might serve as a marker of severity and prognosis in aneurysmal subarachnoid hemorrhage. In this study, plasma visfatin levels of 172 consecutive patients and 172 sex and age-matched healthy subjects were determined using enzyme-linked immunosorbent assay. The recorded clinical outcomes included in-hospital mortality and 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score of 1-3). Plasma visfatin level was substantially higher in patients than in healthy controls (92.1 ± 20.5 ng/mL vs. 12.4 ± 3.2 ng/mL; P<0.001), was significantly associated with the World Federation of Neurological Surgeons (WFNS) score (r=0.569, P<0.001) and Fisher score (r=0.657, P<0.001), was an independent predictor of in-hospital mortality [odds ratio (OR), 1.378; 95% confidence interval (CI), 1.036-1.866; P=0.002] and 6-month mortality (OR, 1.261; 95% CI, 1.018-1.745; P=0.004) and unfavorable outcome (OR, 1.207; 95% CI, 1.012-1.682; P=0.008) in multivariate logistic regression analysis and had high predictive value for in-hospital mortality [area under curve (AUC), 0.849; 95% CI, 0.787-0.899; P<0.001] and 6-month mortality (AUC, 0.868; 95% CI, 0.808-0.915; P<0.001) and unfavorable outcome (AUC, 0.859; 95% CI, 0.797-0.907; P<0.001) using receiver operating characteristic curves. AUCs of visfatin were similar to those of WFNS score and Fisher score (all P>0.05), but visfatin did not improve the predictive values of WFNS score and Fisher score (all P>0.05). Thus, visfatin may be associated with clinical severity of aneurysmal subarachnoid hemorrhage and also have prognostic value for clinical outcomes.

Inhibition of breast cancer metastasis via PITPNM3 by pachymic acid.

Breast cancer metastasis is the most common cause of cancer-related death in women. Thus, seeking targets of breast tumor cells is an attractive goal towards improving clinical treatment. The present study showed that CCL18 from tumor-associated macrophages could promote breast cancer metastasis via PITPNM3. In addition, we found that pachymic acid (PA) could dose-dependently inhibit migration and invasion of MDA-MB-231 cells, with or without rCCL18 stimulation. Furthermore, evidence was obtained that PA could suppress the phosphorylation of PITPNM3 and the combination of CCL18 and PITPNM3. Therefore, we speculate that PA could inhibit breast cancer metastasis via PITPNM3.

[Effect of shuizhongcao granule on cellular immune function of experimental animal with recurrent aphthous stomatitis].

OBJECTIVE: To investigate the effect of Shuizhongcao Granule (SZCG) on cellular immune function in animal model of recurrent aphthous stomatitis (RAS). METHODS: Experimental animal model of RAS were established by immunological method. The modeled animals were randomized into 4 groups, Group A was the model control group, Group B was treated by Levamisole (2.5 mg/mL), Group C and D was treated with high-dose (0.5 g/mL) and low-dose (0.24 g/mL) SZCG respectively. The medication was administered via gastric perfusion, starting from the 7th week of the experiment, and continued for 28 days. Meanwhile, a normal control group was set up. Percentage of T-lymphocyte subsets, CD3, CD4 and CD8, and serum levels of interleukin 10 and 12 (IL-10 and IL-12) in peripheral blood were detected before and after treatment. RESULTS: Percentages of CD3, CD4 and CD4/CD8 ratio in the model control group were 40.50 +/- 7.46%, 30.80 +/- 5.33% and 79.56 +/- 8.32 respectively, all lower than those in the normal control group (P<0.05); level of serum IL-10 was higher (8.02 +/- 0.53 ng/L) and that of IL-12 was lower (15.51 +/- 1.35 ng/L) in the model animal than those in normal control (P<0.05). After treatment, levels of CD3, CD4, CD4/CD8 and IL-12 in Group B were 55.30 +/- 6.33%, 43.50 +/- 5.33%, 99.29 +/- 13.84 and 17.72 +/- 1.70 ng/L, those in Group C were 61.50 +/- 4.32%, 47.20 +/- 4.37%, 103.30 +/- 7.42 and 18.18 +/- 1.54 ng/L, and in Group D were 58.50 +/- 6.03%, 42.80 +/- 3.17%, 110.27 +/- 12.85 and 17.74 +/- 1.96 ng/L, respectively, all were higher than those in Group A, but levels of IL-10 in the three treatment groups were lower than that in Goup A (P<0.05 or P<0.01). CONCLUSION: The immune function of RAS model animals is in the suppressed condition; SZCG can improve the immune suppression to achieve its therapeutic effect on the disease.

[Childhood upper respiratory infection caused by Mycoplasma pneumoniae].

OBJECTIVE: This study was designed to investigate the prevalence, clinical characteristics and outcome of upper respiratory infection (URI) caused by Mycoplasma pneumoniae (MP) in children. METHODS: Pharyngeal cultures for MP antibody were performed in 960 children with acute URI. The samples were randomly collected from the outpatient room or emergency room (Observed group). Of the Observed group, there were 232 cases under 1 year of age, and the remainder, were between 1-12 years old. The samples from 100 healthy children aged from 6 months to 12 years were used as the Control group. The prevalence of MP infection between the two groups was compared. The clinical manifestations and the outcome between the patients with MP positive and negative were compared. RESULTS: MP antibody was positive in 31.7% (304/960) of the Observed group but only 9.0% (9/100) in the Control group (P < 0.05). The URI patients under 1 year of age had a lower positive rate of MP than those over 1 year old (P < 0.05). Coughs and tonsillitis were more common (P < 0.05), but catarrh, gastroenteritic symptoms, herpes, and tetter were rare (P < 0.01) in URI patients with MP positive compared with those with MP negative. Pneumonia developed in 14.8% of the patients with MP positive but only 7.0% in those with MP negative (P < 0.01). CONCLUSIONS: MP is one of the main pathogens of acute URI in children. Acute pharyngotonsillitis symptoms are predominately presented in children with MP infection. MP infection was commonly seen in children over 1 year old and they are prone to develop pneumonia.