OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis. METHODS: HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro. RESULTS: Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all P<0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (P<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated PDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis. CONCLUSIONS Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
Acitretin/therapeutic use* ; Psoriasis/drug therapy* ; Animals ; Imiquimod ; Humans ; Glucose/metabolism* ; Homeostasis/drug effects* ; Mice ; Lipid Metabolism/drug effects* ; Mice, Inbred BALB C ; Female ; Hep G2 Cells ; Disease Models, Animal

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Objective:To evaluate the efficacy of hybrid closed-loop insulin delivery system (CLS) in glycemic control in young children with type 1 diabetes mellitus (T1DM).Methods:This retrospective observational self-controlled study analyzed data from 14 children (aged 3-9 years) with T1DM treated at the Endocrinology and Metabolism Department of Anhui Provincial Children′s Hospital between August 2021 and February 2024. All the patients had undergone continuous subcutaneous insulin infusion (commonly known as insulin pump therapy) with continuous glucose monitoring system (CGMS) for at least 4 weeks and CLS for over 6 months. Data collected included age, sex, body mass index (BMI), diabetes duration, duration of insulin pump use, baseline glycated hemoglobin (HbA1C), and pre-and post-treatment glycemic metrics. Based on the duration of combined CLS therapy, groups were divided as follows: baseline (before combined CLS therapy), 0-<4 weeks, 4-<8 weeks, 8-<12 weeks, 12-<24 weeks. Independent sample t-test and ANOVA were used to compare intergroup and multigroup differences, respectively, in glycemic levels before and after hybrid CLS therapy. Results:Among the 14 pediatric patients, 8 were male and 6 were female. Their age was (6.5±0.5) year old, BMI was (16.1±1.3) kg/m2, duration of diabetes was (20.1±2.6) months, duration of CGMS insulin pump use was (13.8±2.6) months, and baseline HbA1C was (10.2±0.8)%. One-way ANOVA revealed that hybrid CLS therapy significantly improved glycemic control, compared to pre-treatment, at 6 months follow-up, the following outcomes were observed: increased time-in-range (TIR), reduced time in hyperglycemia and hypoglycemia, lower HbA1C and mean glucose level, improved daytime TIR, and decreased mean glucose levels at fasting, postprandial (three meals), and bedtime (22:00), and scores on the pediatric quality of life inventory significantly increased ( F=3.16, 2.94, 2.56, 13.84, 2.36, 7.00, 40.48, 115.90, 192.50, 122.70, 75.55, t=11.00, all P<0.05). Conclusions:Compared to baseline insulin pump therapy, hybrid CLS improves glycemic control and quality of life in young children with T1DM, while reducing the risk of hypoglycemia over a 6-month treatment period.

Objective To identify potential quality risks of Xiaoer Huatan Zhike Granules(Pediatric Phlegm-Resolving and Cough-Relieving Granules)through National Drug Sampling and Inspection,evaluate their overall quality,and propose improvements to the quality standards.Methods Samples from 34 manufacturers were tested using official standards.Exploratory methods were developed to enhance risk analysis,including thin-layer chromatography(TLC)identification,content uniformity testing,quantitative assays,and screening for unauthorized additives(e.g.,colorants).Results All batches met the official standards(100.0%compliance rate).However,deficiencies were observed:most manufacturers lacked controls for ephedrine hydrochloride content uniformity and quantification,omitted key ingredient identifications(e.g.,herbal components),and exhibited insufficient TLC specificity(e.g.,TLC of Ipecac tincture showed only one spot instead of multiple alkaloid-specific spots).Exploratory studies revealed risks in total emetine/cephaeline content,morroniside A/platycodin D content,ephedrine hydrochloride uniformity,and unauthorized colorant addition.Conclusions The overall quality of this variety is good,but the enterprise should improve the quality control measures throughout the entire process and establish stricter internal control standards;The official standards,unchanged for approximately 30 years,fail to address current regulatory requirements.The statutory quality standards need to be revised and improved.Qualitative or quantitative indicators for all drug flavors in the prescription should be added,and the content uniformity inspection of ephedrine hydrochloride should be increased.

Objective To identify potential quality risks of Xiaoer Huatan Zhike Granules(Pediatric Phlegm-Resolving and Cough-Relieving Granules)through National Drug Sampling and Inspection,evaluate their overall quality,and propose improvements to the quality standards.Methods Samples from 34 manufacturers were tested using official standards.Exploratory methods were developed to enhance risk analysis,including thin-layer chromatography(TLC)identification,content uniformity testing,quantitative assays,and screening for unauthorized additives(e.g.,colorants).Results All batches met the official standards(100.0%compliance rate).However,deficiencies were observed:most manufacturers lacked controls for ephedrine hydrochloride content uniformity and quantification,omitted key ingredient identifications(e.g.,herbal components),and exhibited insufficient TLC specificity(e.g.,TLC of Ipecac tincture showed only one spot instead of multiple alkaloid-specific spots).Exploratory studies revealed risks in total emetine/cephaeline content,morroniside A/platycodin D content,ephedrine hydrochloride uniformity,and unauthorized colorant addition.Conclusions The overall quality of this variety is good,but the enterprise should improve the quality control measures throughout the entire process and establish stricter internal control standards;The official standards,unchanged for approximately 30 years,fail to address current regulatory requirements.The statutory quality standards need to be revised and improved.Qualitative or quantitative indicators for all drug flavors in the prescription should be added,and the content uniformity inspection of ephedrine hydrochloride should be increased.

Objective:To evaluate the efficacy of hybrid closed-loop insulin delivery system (CLS) in glycemic control in young children with type 1 diabetes mellitus (T1DM).Methods:This retrospective observational self-controlled study analyzed data from 14 children (aged 3-9 years) with T1DM treated at the Endocrinology and Metabolism Department of Anhui Provincial Children′s Hospital between August 2021 and February 2024. All the patients had undergone continuous subcutaneous insulin infusion (commonly known as insulin pump therapy) with continuous glucose monitoring system (CGMS) for at least 4 weeks and CLS for over 6 months. Data collected included age, sex, body mass index (BMI), diabetes duration, duration of insulin pump use, baseline glycated hemoglobin (HbA1C), and pre-and post-treatment glycemic metrics. Based on the duration of combined CLS therapy, groups were divided as follows: baseline (before combined CLS therapy), 0-<4 weeks, 4-<8 weeks, 8-<12 weeks, 12-<24 weeks. Independent sample t-test and ANOVA were used to compare intergroup and multigroup differences, respectively, in glycemic levels before and after hybrid CLS therapy. Results:Among the 14 pediatric patients, 8 were male and 6 were female. Their age was (6.5±0.5) year old, BMI was (16.1±1.3) kg/m2, duration of diabetes was (20.1±2.6) months, duration of CGMS insulin pump use was (13.8±2.6) months, and baseline HbA1C was (10.2±0.8)%. One-way ANOVA revealed that hybrid CLS therapy significantly improved glycemic control, compared to pre-treatment, at 6 months follow-up, the following outcomes were observed: increased time-in-range (TIR), reduced time in hyperglycemia and hypoglycemia, lower HbA1C and mean glucose level, improved daytime TIR, and decreased mean glucose levels at fasting, postprandial (three meals), and bedtime (22:00), and scores on the pediatric quality of life inventory significantly increased ( F=3.16, 2.94, 2.56, 13.84, 2.36, 7.00, 40.48, 115.90, 192.50, 122.70, 75.55, t=11.00, all P<0.05). Conclusions:Compared to baseline insulin pump therapy, hybrid CLS improves glycemic control and quality of life in young children with T1DM, while reducing the risk of hypoglycemia over a 6-month treatment period.

Objective:To analyze the application value of autophagy related molecular markers in placenta tissue in predicting fetal growth restriction in pregnant women with preeclampsia.Methods:A total of 46 pregnant women admitted to Changsha Hospital for Maternal and Child Health Care from January 2021 to August 2023 were collected. A cross-sectional study was conducted, and they were divided into a normal delivery group (control group, 23 cases) and an observation group with preeclampsia combined with fetal growth restriction (observation group, 23 cases) based on pregnancy outcomes. Transmission electron microscopy was used to observe the occurrence of autophagic vesicles in trophoblast cells in the placental tissue of both groups; The expression of Beclin-1, LC3, and P62 in placental tissues of two groups was detected by immunohistochemistry, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), and Western blot.Results:The transmission electron microscopy results showed that the presence of autophagic vesicles could be observed in the placental trophoblast cells of both the control group and the observation group, but the number of autophagic vesicles in the trophoblast cells of the observation group was higher than that in the control group ( P<0.05). The immunohistochemical results showed that the colorimetric values of Beclin-1 and LC3 in the placental tissue sections of the observation group were higher than those of the control group (all P<0.001), while the colorimetric values of p62 were lower than those of the control group ( P<0.001). The qRT-PCR and Western blot results showed that the mRNA and protein expression levels of Beclin-1 and LC3 in the observation group were significantly higher than those in the control group (all P<0.001), while the expression levels of p62 mRNA and protein were lower than those in the control group (all P<0.001). Conclusions:The autophagy activity of placental tissue trophoblasts in patients with preeclampsia combined with fetal growth restriction is enhanced, indicating a close correlation between elevated autophagy levels and the occurrence of preeclampsia combined with fetal growth restriction. Excessive autophagy may be involved in the occurrence of preeclampsia combined with fetal growth restriction.

Many natural products can be bio-converted by the gut microbiota to influence pertinent efficiency. Ginsenoside compound K (GCK) is a potential anti-type 2 diabetes (T2D) saponin, which is mainly bio-transformed into protopanaxadiol (PPD) by the gut microbiota. Studies have shown that the gut microbiota between diabetic patients and healthy subjects are significantly different. Herein, we aimed to characterize the biotransformation of GCK mediated by the gut microbiota from diabetic patients and healthy subjects. Based on 16S rRNA gene sequencing, the results indicated the bacterial profiles were considerably different between the two groups, especially Alistipes and Parabacteroides that increased in healthy subjects. The quantitative analysis of GCK and PPD showed that gut microbiota from the diabetic patients metabolized GCK slower than healthy subjects through liquid chromatography tandem mass spectrometry (LC-MS/MS). The selected strain A. finegoldii and P. merdae exhibited a different metabolic capability of GCK. In conclusion, the different biotransformation capacity for GCK may impact its anti-diabetic potency.
Humans ; Gastrointestinal Microbiome/genetics* ; Chromatography, Liquid/methods* ; Healthy Volunteers ; RNA, Ribosomal, 16S ; Feces/microbiology* ; Tandem Mass Spectrometry ; Biotransformation ; Diabetes Mellitus, Type 2/drug therapy*

Objective:To explore the clinical characteristics of various types of severe drug eruption and common sensitized drugs,and to provide clinical references for reducing the incidence of severe drug eruption.Methods:The clinical data regarding 126 cases of severe drug eruption were analyzed retrospectively from June 2009 to May 2017 in Xiangya Hospital,Central South University.Results:In the 126 cases of severe drug eruption,the distribution of men and women ratio was 1∶1.38.The length of stay was (12.7±9.8) d.The most common type was Steven-Johnson syndrome;the most dangerous type was drug-induced bullosa epidermolysis,The most common sensitized drug category in these patients was antibiotics;the most common single sensitizing drug was carbamazepine,following by allopurinol.Conclusion:Severe drug eruption occurs mostly in young and middle-aged people.Steven-Johnson syndrome is the most common type;drug hypersensitive syndrome has the longest length of hospital course.Mortality rate of drug-induced bullosa epidermolysis is the highest.Timely stop using of allergens,early using glucocorticoids,and timely combination of non-glucocorticoids treatment (such as intravenous immunogloblin,plasma exchange and hemodialysis),can improve the efficacy and reduce the complications and mortality.