Background: We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. Conclusion miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

Objective To investigate the efficacy and safety of domestic oseltamivir in patients with influenza. Methods A randomized, single-blinded, controlled clinical trial was performed.Patients in the study group received domestic oseltamivir, while the patients in control group received foreign oseltamivir. The doses were both 75 mg every time, twice a day. The treatment durations in both groups were 5 days. Chi square test was performed to compare baseline characteristics and the difference of side effects. Paired t test was used to compare the efficacy. Results Two hundred and nine patients were enrolled in this study (98 cases in study group. 111 cases in control group). The trend in body temperature change was similar in the two groups (t = 0. 061, P>0. 05). The score of symptom severity decreased more quickly in patients treated with foreign oseltamivir compared to those treated with domestic oseltamivir during the period from 24 h to 48 h. However, the difference between the two groups diminished gradually and was not statistically significant at 72 h (t=0. 875,P>0. 05). The safety of the domestic and foreign oseltamivir were comparable(X2 = 0. 197,P>0. 05). Conclusion The domestic oseltamivir is as effective and safe as the foreign oseltamivir.

OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments, but its side effects often limit the clinical usage. Metabolic disorders are one of the side effects induced by cisplatin, which closely relate to the onset of chemotherapy-induced anorexia (CIA) in cancer patients but lacks effective controls. Liujunzi decoction (LJZD) is a traditional Chinese formula that has a promising effect in treating CIA. However, whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow. The present study evalu?ated the mechanism of cisplatin-induced metabolic disorders, and the effect of LJZD in ameliorating these disturbances. METHODS 42 male Sprague-Dawley (SD) rats (180-220 g) were randomly divided into 3 groups:normal control group (distilled water+saline), model group (distilled water+cisplatin), LJZD group (4.8 g·kg-1 Liujunzi decoction ingredients+cisplatin). Intragastrical administered each drug twice a day (7:00-19:00) since day 0 for 4 d, animals were intraperito?neal injected with cisplatin 6 mg·kg-11 h after administration while normal control groups were injected with same volume of saline. On day 3, each group was anesthetized with pentobarbital sodium 45 mg · kg-1 (ip), and blood samples were collected from aorta abdominalis. Then the samples were analyzed using an LC-ESI-MS/MS system. Significantly regu?lated metabolites between groups were determined by VIP≥1 and absolute Log2FC (fold change)≥1. Identified metabo?lites were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Metaboanalyst 5.0 (https://www.metaboanalyst.ca/). RESULTS A total of 133, 77 and 32 differential metabolites were filtrated in control vs model, control vs LJZD and model vs LJZD groups respectively. Comparing to control, the levels of hexadecanoic acid (Log2FC=6.3153), linoleic acid (Log2FC=5.3478), and 8, 11-icosadienoic acid (Log2FC=5.2342) significantly increased, and the levels of N-acetyl-L-tyrosine (Log2FC = -2.6283), cinnamic acid (Log2FC = -2.3381), N-acetylphenylalanine (Log2FC = -2.2501) significantly decreased in model group. The KEGG pathway enrichments of these metabolites indi?cated that, cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid, unsaturated fatty acids, and phenylalanine. Compared to control, treatment of LJZD significantly increased the levels of 4-hydroxytryptamine (Log2FC =12.0186), hexadecanoic acid (Log2FC = 5.7412), linoleic acid (Log2FC = 5.1877) and significantly decreased the levels of N-acetylmethionine (Log2FC=-1.7317), 2-aminoethanesulfinic acid (Log2FC=-1.6578), N-acetyl-L-tyrosine (Log2FC=-1.5355). And com?paring to the model group, 4-hydroxytryptamine (Log2FC = 12.0186), 7, 12-diketocholic acid (Log2FC = 2.0998), N-acetylneuraminic acid (Log2FC = 2.0560) markedly increased, and 3-hydroxy-3-methylpentane-1 (Log2FC = -1.9202), 5-dioic acid (Log2FC = -1.7166), N-isovaleroylglycine, hexanoyl glycine (Log2FC = -1.4958) markedly decreased in LJZD group. It was worth noting that, there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups, which were the key metabolites of LJZD in treating CIA. Among these 23 common metabolites, there were 16 metabolites excluding the control vs LJZD group, that was, LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites. Cisplatin-induced downregula?tion of 11 metabolites such as hydrocinnamic acid, (±)12(13)epoxy-9Z-octadecenoic acid, cinnamic acid were upregulated after LJZD treatment, and cisplatin-induced upregulation of imidazoleacetic acid, 2'-deoxycytidine-5'-monophosphate and other 5 metabolites were downregulated by LJZD. The KEGG pathway analysis indicated that the linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism were the most enriched metabolic pathway. Thus, cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism, and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA. CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabo?lism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments, relating to the regulation of linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism.

Non-alcoholic fatty liver disease(NAFLD)is one of the common chronic liver diseases in the world.The molecular mechanism of NAFLD is complex,involving many signal molecules,and the vitamin D(VD)/VDBP/vitamin D receptor(VDR)axis is also involved.VD is a lipid-soluble steroid,which can participate in the regula-tion of lipid metabolism,insulin secretion,immune function,inflammatory response and other biological processes.Stud-ies have shown that VD deficiency is closely related to liver lipid accumulation,inflammation,insulin resistance,oxida-tive stress,intestinal flora imbalance,autophagy,apoptosis,pyroptosis and fibrosis,and plays an important role in the oc-currence and development of NAFLD.This paper reviews the research progress on Vitamin D in recent years in the field of NAFLD,including the physiological characteristics of VD and its role in the NAFLD mechanism,so as to provide referenc-es for the prevention and treatment of NAFLD.

Acute cerebral infarction(ACI)has the characteristics of onset nasty and high mortality,and thus the rapid determination of the occurrence and development of ACI plays a key role in the diagnosis,treatment and prognosis of ACI patients.It has shown that the serum level of human haptoglobin(Hp)is related to ACI.In this study,surface enhanced Raman scattering(SERS)combined with immune recognition was applied to establish a quantitative analysis method for serum Hp.Firstly,the SERS substrate of silver nanoparticles was prepared on silicon wafer,and 4-mercaptobenzoic Acid(MBA)was used as a Raman probe by forming Ag—S bond and connecting it on the surface of nanoparticles.The carboxyl group of MBA was linked to amino group of self-made high-affinity antibody through forming CO—NH structure thus forming a SERS self-assembled chip of Hp(Ag/MBA/anti-Hp).Hp in serum could be specifically captured by antibodies on SERS substrate,which caused the shift of SERS characteristic peak of MBA.The results showed that there was a good linear relationship between the logarithm of Hp concentration and the SERS characteristic peak shift of MBA.The detection range was 1-1000 ng/mL(R2=0.988).The Hp concentrations in serum of 90 ACI patients were determined by this method,and the results were consistent with those of ELISA method,which proved the practicability and accuracy of this method.This method was highly specific,simple and convenient,which could realize the specific recognition and quantitative analysis of serum Hp,so as to be an effective means for clinical detection of serum Hp,thus providing a reference for the treatment and prognosis of ACI.

OBJECTIVETo investigate the inhibition of the expression of steroid receptor coactivator-1 (SRC-1) in the LNCap cell line through RNA interference (RNAi) and the effect of the silenced SRC-1 gene on LNCap cells.

METHODSThe experiment included four groups: siRNA transfection, siRNA negative control, bland vehicle (with Lipofectamine 2000 but no siRNA), and blank control (with neither Lipofectamine 2000 nor siRNA). LNCap cells were transfected with designed siRNA using the liposomes method, the expressions of SRC-1 determined by Q-PCR and Western blot, and the proliferation of the LNCap cells detected by the CCK-8 method.

RESULTSThe expression of SRC-1 mRNA in the transfected LNCap cells was decreased by 35% at 24 hours and 77% at 48 hours, with statistically significant differences from the blank control group (P < 0.05). The SRC-1 protein expression of the transfected group was 0.359 +/- 0.034 at 24 hours and 0.257 +/- 0.065 at 48 hours, markedly decreased as compared with that of the negative control (0.782 +/- 0.078 and 0.766 +/- 0.043) , bland vehicle (0.840 +/- 0.013 and 0.786 +/- 0.051), and blank control group (0.816 +/- 0.065 and 0.805 +/- 0.107) (P < 0.05). The LNCap cell growth inhibition rates were 25%, 52%, 55% and 60% at 24, 48, 72 and 96 hours, respectively.

CONCLUSIONThe expression of SRC-1 is correlated with the growth of LNCap cells; its high expression in androgen-independent prostate cancer cells may be involved in the progression to androgen-independence. Inhibiting the expression of SRC-1 may be an option for the treatment of androgen-dependent prostate cancer.

Cell Line, Tumor ; Gene Silencing ; Humans ; Male ; Nuclear Receptor Coactivator 1 ; genetics ; Prostatic Neoplasms ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics

OBJECTIVETo investigate the expression of keratin 8 (K8) in carbon tetrachloride (CCl(4))-induced liver injury of mice.

METHODSForty ICR mice were divided into four groups. CCl(4) 300 microl/kg body weight in olive oil was injected intraperitoneally for 0, 2, 4, 6 weeks in group A, B, C and D, respectively. Mice were sacrificed 3 d after the last injection and then the vital organs were collected and weighed. RT-PCR and immunohistochemistry methods were used to analyze the expression of keratin 8 in the liver.

RESULTSThe ratios of liver and body weight were increased significantly after administration of CCl(4), which were 5.60 %, 6.87%, 7.83 % and 7.76% at 0, 2, 4 and 6 weeks after injection, respectively. The expression of K8 was increased at the 2 w, 4 w and 6 w after CL(4) administration.

CONCLUSIONThe expression of K8 is positively correlated with the liver injury induced by CCl(4). The accumulation of K8 may be involved in the mechanism of liver injury.

Animals ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury ; metabolism ; Female ; Keratin-8 ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; RNA, Messenger ; genetics ; metabolism

OBJECTIVETo perform a Meta-analysis on peginterferon with interferon in treatment of HIV patients coinfected with refractory genotype HCV.

METHODSA literature search of Medline was conducted to identify eligible randomized controlled trials. Meta analysis was conducted to evaluate peginterferon and interferon in treatment of coinfected HCV genotype 1 or 4 in HIV patients.

RESULTSix trials of 88 matched the selection criteria. Total 1,131 patients with coinfection of HCV genotype 1 or 4 and HIV were included. Sustain viral response was higher in patients treated with peginterferon plus ribavirin compared with that of interferon plus ribavirin (26 % compared with 8 %) or peginterferon alone (26 % compared with 13 %). Severe adverse effects and withdrawal rates were similar for patients treated with peginterferon and patients treated with interferon.

CONCLUSIONPeginterferon plus ribavirin in treatment of patients with coinfection of genotype 1 or 4 HCV and HIV can achieve higher sustain viral response and the likelihoods of serious adverse effects and withdrawal rates are similar to other therapies.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; HIV Infections ; complications ; drug therapy ; immunology ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; complications ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Polyethylene Glycols ; administration & dosage ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; Ribavirin ; administration & dosage