To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.

To investigate the therapeutic effects of ZLY16, a novel peroxisome proliferator-activated receptor (PPAR) β agonist, on Duchenne muscular dystrophy (DMD), C57BL/10ScSnJGpt-Dmdem3Cd4/Gpt (mdx) mice were gavaged with 30 mg/kg ZLY16 for 6 weeks. Expression of proteins associated with muscle regeneration, exercise ability, blood lipids content and skeletal muscle damage in mdx mice were investigated by behavioral experiments, histopathology, blood biochemical analysis, immunofluorescence and Western blot. A high-fat-induced myoblast differentiation inhibition model was established to examine lipid content and myoblast differentiation-related protein expression in myoblasts using Nile Red staining, immunofluorescence and Western blot. The results demonstrated that ZLY16 increased muscle grip strength, reduced triglyceride (TG) and total cholesterol (TC) levels, attenuated muscle fiber necrosis, fibrosis and inflammatory cell infiltration, and promoted muscle regeneration in mdx mice. ZLY16 promoted myoblast differentiation and myotube fusion in vitro by reducing lipid accumulation in murine skeletal muscle myoblast line (C2C12) cells. These findings suggest that ZLY16 improves motor function in mdx mice by decreasing lipid accumulation and promoting muscle regeneration.

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G₂ phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.
Animals ; Mice ; T-Lymphocytes, Regulatory ; Psoriasis/drug therapy* ; Arthritis, Rheumatoid ; Biological Assay ; Glucosides/pharmacology*

ObjectiveTo establish a more accurate and sensitive liquid chromatography-ultraviolet (LC-UV) method for the determination of uric acid in rat serum, and compare the results with those of commercial kits, providing a new method for the accurate determination of uric acid in the rat hyperuricemia model induced by potassium oxonate.Methods A hyperuricemia model was established by intraperitoneal injection of potassium oxonate (300 mg/kg) into SPF-grade male SD rats, and the control group was administered an equal amount of 0.5% sodium carboxymethylcellulose solution. Blood samples were collected from the posterior orbital venous plexus and centrifuged to obtain serum samples. After precipitation with 0.1% trifluoroacetic acid-acetonitrile (containing the internal standard 3,4-dihydroxybenzylamine hydrobromide), the supernatant was injected for analysis. Uric acid was separated on a Waters XBridge HILIC column (150 mm×4.6 mm, 3.5 μm) using acetonitrile (containing 0.5% formic acid and 2 mmol/mL ammonium formate) as the organic phase and methanol solution (methanol∶water=1∶1, containing 0.5% formic acid with 2 mmol/L ammonium formate) as the aqueous phase for isocratic elution and detection at 290 nm. Serum samples treated with activated carbon were used as substitute matrices for the methodological verification. Serum uric acid levels in rats with potassium oxonate-induced hyperuricemia were measured using the established LC-UV method and commercially available kits (uricase and phosphotungstic acid methods), and the accuracies of the three methods were compared.Results Serum uric acid showed a good linear relationship (R>0.999) at mass concentration of 10–200 μg/mL in rats, the lower limit of quantification was 10 μg/mL, the accuracy ranged from -2.17% to 2.21%, the intra-batch precision ranged from 0.52% to 1.95%, the inter-batch precision ranged from 3.04% to 4.90%, and the extraction recovery ranged from 83.12% to 89.91%. In the rat model, the results obtained using the commercially available phosphotungstic acid method kit were significantly higher than those of the LC-UV method, and those obtained using the commercially available uricase method kit were significantly lower than those of the LC-UV method, but the LC-UV method showed the best recovery of the spiked sample (95.90%–99.96%).ConclusionThe LC-UV method developed in this study can determine the concentration of uric acid in rat serum with higher accuracy than commercially available kits and is recommended for the determination of serum uric acid in the rat model of hyperuricemia induced by potassium oxonate.

Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects.

Duchene muscular dystrophy (DMD) is a serious progressive muscular dystrophy.Reports in recent years about abnormal lipid in DMD patients have increased, yet little attention has been paid to liver lipid.This study aimed to explore the effect of dystrophin gene defect on liver lipid synthesis.7-week-old mdx male mice were used as DMD model.The conditions of liver function, liver lipid accumulation and liver lipid synthesis were determined through liver tissue morphological examination, blood biochemical examination, and detection of hepatic gene and protein expression.The results showed that lipid droplets in liver of mdx mice increased significantly.The contents of total cholesterol and triglyceride in liver, aspartate aminotransferase and alanine aminotransferase in serum increased.The gene and protein expression of hepatic lipid synthesis-related enzymes such as fatty acid synthase, acetyl CoA carboxylase, and sterol regulatory element binding protein 1-c were up-regulated.These results showed accumulation of liver lipid in 7-week-old mdx male mice.

Objective To analyze the use of antidepressants and its influencing factors in patients with depressive disorders in Haikou City,and to provide some reference for clinical rational drug use.Methods 310 patients with depressive disorder in Haikou were selected.All patients were assessed with the selfdesigned General Situation and Drug Use Questionnaire,General Self-efficacy Scale (GSES),Quality of Life Questionnaire for Psychiatric Patients (QOL-P) and Hamilton Depression Scale (HAMD-17).Results (1)The usage rate of serotonin reuptake inhibitors (SSRIs) was 53.22％,30.32％ for tricyclic antidepressants (TCAs) and 16.45％ for other new antidepressants.(2)Patients'self-efficacy (β=-0.473,OR=0.713,P=0.030),social function (β=0.371,OR=1.437,P=0.036),family income (β=-1.242,OR=0.423,P=0.001) were the factors influencing patients' choice of TCAs;family income (β=-1.762,OR=0.234,P=0.001),payment method (β =0.248,OR =1.157,P =0.030) were the factors influencing the choice of SSRIs drugs;self-efficacy (β=0.563,OR=1.913,P=0.041) and depression (β=0.543,OR=2.225,P=0.026) were the factors influencing the choice of other new antidepressants.Conclusion Traditional antidepressants such as serotonin reuptake inhibitors and tricyclic antidepressants are still widely used in patients with depressive disorders.Self-efficacy,social function,income,and payment methods can influence the drug selection of depressive patients.

Objective: To understand the epidemiological and etiological characteristics of enterovirus (EV)-associated diseases among children in Beijing from 2010 to 2016. Methods: This was a repeated cross-sectional study. The throat swabs were collected from children with probable EV-associated diseases at the Children' s Hospital Affiliated to Capital Institute of Pediatrics from 2010 to 2016. The samples were sent for pan-EV, enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) detection by real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR) . The viral types of non-EV-A71 and non-CV-A16 EV-positive samples were identified using modified RT-PCR and sequencing with CV-A6, EV-A/B group and 5 'UTR universal primers. The constituent ratios of the prevalence of different EV types in different age and gender groups were compared. Results: Of the 2 703 throat swabs, 1 992 (73.7%) samples were positive for EV, including EV-A71 (19.1%, 516/2 703), CV-A16 (24.3%, 658/2 703), CV-A6 (22.2%, 600/2 703), CV-A10 (4.5%, 122/2 703) and other types of EV (3.5%, 95/2 703). There was 1 case of EV-A71 and CV-A16 co-infection. The positive detection rate of EV-A group (excluding EV-A71, CV-A16, CV-A6 and CV-A10) increased from 11.3% (7/62) to 95.2% (59/62) after using the modified VP1-specific primers and PCR amplification conditions. During the period between 2010 and 2012, CV-A16 and EV-A71 predominated in EV-positive samples. However, CV-A6 accounted for 60.7% (68/112) in 2013, much higher than CV-A16 (23.2%, 26/112) and EV-A71 (12.5%, 14/112). In 2014, EVs were mainly of CV-A16 and EV-A71, but CV-A6 was the predominant type in 2015 (68.2%, 232/340) and in 2016 (38.6%, 151/391). The epidemic season of EVs was mostly from April to August, but CV-A6 showed a small epidemic peak from October to November. The male-to-female ratio of EV-positive patients was 1.50∶1, and EV-associated diseases mostly occurred in children under 5 years of age. Younger children were more susceptible to CV-A6 than to EV-A71 and CV-A16. Conclusions From 2010 to 2016, there was a significant change in the spectrum of EVs in children with EV-associated diseases in Beijing. Since 2013, non-EV-A71 and non-CV-A16 increased, and CV-A6 gradually became one of the major pathogens of EV-associated diseases. The modified PCR primers and amplification conditions can effectively improve the reliability of test results.

OBJECTIVETo analyze the genotype, epidemic pattern and the characteristics of the disease of enteroviruses during the epidemic season of hand, foot and mouth disease (HMFD) in children from 2013 to 2014 in Beijing to provide the scientific evidence for prevention and treatment of HFMD.

METHODDuring April to September in 2013 and March to October in 2014, a total of 977 throat swabs were collected from children who visited the Children's Hospital Affiliated to Capital Institute of Pediatrics, including 147 from patients with HFMD in 2013, 343 with HFMD, 201 with atypical HFMD, 83 with herpangina, 25 with fever with convulsions, 64 fever with rash and 114 with rash in 2014. Enteroviruses universal type (EV), Enteroviruses type 71 (EV71) and Coxsackievirus group A 16 (CA16) were detected by real-time RT-PCR respectively. The nucleic acid of specimens which were identified with non-EV71, non-CA16 was tested by nested PCR and analyzed by VP1 sequencing. The detection rate and epidemic pattern of different genotypes of enterovirus were analyzed among different age groups and between 2013 and 2014.

RESULTOf 977 throat swabs, 80. 1% samples were detected positive for enteroviruses. The positive rates of CA16, EV71, CA6, CA10, CA4 and other EVs were 25. 6% (250/977), 18. 9% (185/977), 20. 0% (195/977), 5. 0% (49/977), 1.5% (15/977) and 9.1% (89/977), respectively. Twenty six of the 89 other EVs included CA2, CA5, CA8, CA9, CA12, CA14, CB2, CB5, E6, E9 and E25, each genotype of which was no more than 3. The nucleotide homologies shared among CA6, CA10 and CA4 strains between 2013 and 2014 were 94. 3% - 100%, 93. 8% - 99. 1% and 92.7% - 99. 8%, respectively. The positive rates of ≤1 year group were 71. 1% (106/149), which was lower than that of other age groups (all P <0. 05), but similar to that of >5 year group (χ2 =1. 181,P = 0. 277). In 2013, the positive rate of EV was 85. 7% (126/147) and the predominant genotype was CA6 54. 8% (69/126), followed by CA16 20. 6% (26/126) and EV71 11. 9% (15/126). In 2014, the positive rate of EV was 85. 4% (293/343) in the 343 children with HFMD, the predominant genotypes were CA16 with the positive rate of 42. 7% (125/293), EV71 with 38. 2% (112/293) and CA6 with only 11. 3% (33/293). In 2014, the positive rates of EV in 201 atypical HFMD, 83 herpangina, 25 fever with convulsions, 64 fever with rash and 114 rash were 83. 6% (168/201), 80. 7% (67/83), 76. 0% (19/25), 64. 1% (41/64) and 60. 5% (69/114), respectively. All genotypes of enteroviruses peaked mainly during May to August every year, but there were no obvious epidemiological pattern about each genotype.

CONCLUSIONCA6 became the main causative agent of HFMD in 2013, however, CA16 and EV71 predominated again in 2014 in Beijing. The clinical manifestations caused by CA6, CA10, CA4 and other genotype of enteroviruses differed from EV71 and CA16. Besides EV71 and CA16, more attention should be paid to CA6, CA10, CA4 and other type of enteroviruses.

Beijing ; epidemiology ; Child, Preschool ; Enterovirus A, Human ; classification ; Enterovirus Infections ; epidemiology ; virology ; Exanthema ; Fever ; Genotype ; Hand, Foot and Mouth Disease ; epidemiology ; virology ; Humans ; Infant ; Real-Time Polymerase Chain Reaction

Humans ; Liver Failure ; Lymphohistiocytosis, Hemophagocytic