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

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 establish a quantitative analysis of multi-components by single marker(QAMS)method for determination of cephaeline,emetine,ipecoside in Xiao'er Huatan Zhike granules.Methods:The column was Agilent Eclipse C18(4.6 mm ×250 mm,5 μm).The mobile phase was acetonitrile-0.1％phosphoric acid solu-tion with gradient elution at the flowrate of 1.0 mL·min-1.The column temperature was 35 ℃,and the detection wavelength was 203 nm.Taking cephaeline as the internal reference,the relative correction factors of emetine and ipecoside were calculated,and then the content determination were carried out.Results:The three components showed good linear relationships within their own ranges(r＞0.999 0),and the average recoveries were 96.78％-105.01％with the RSDs of 2.20％-3.24％.There were no significant differences between the values obtained by QAMS and those obtained by an external standard method.Conclusion:The established QAMS method can be used for simultaneously determining the contents of 3 alkaloids in Xiao'er Huatan Zhike granules.

Objective:To establish a quantitative analysis of multi-components by single marker(QAMS)method for determination of cephaeline,emetine,ipecoside in Xiao'er Huatan Zhike granules.Methods:The column was Agilent Eclipse C18(4.6 mm ×250 mm,5 μm).The mobile phase was acetonitrile-0.1％phosphoric acid solu-tion with gradient elution at the flowrate of 1.0 mL·min-1.The column temperature was 35 ℃,and the detection wavelength was 203 nm.Taking cephaeline as the internal reference,the relative correction factors of emetine and ipecoside were calculated,and then the content determination were carried out.Results:The three components showed good linear relationships within their own ranges(r＞0.999 0),and the average recoveries were 96.78％-105.01％with the RSDs of 2.20％-3.24％.There were no significant differences between the values obtained by QAMS and those obtained by an external standard method.Conclusion:The established QAMS method can be used for simultaneously determining the contents of 3 alkaloids in Xiao'er Huatan Zhike granules.

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 evaluate the efficacy and safety of neoadjuvant arterial interventional chemotherapy(NAIC)and neoadjuvant intravenous chemotherapy(NIVC)for the treatment of locally advanced cervical cancer(LACC).Methods Randomized controlled trials(RCTs)which fit the theme were included by searching PubMed,Web of Science,Embase,CNKI,and Wanfang databases.After study quality assessment and data extraction,statistical analysis was performed using Stata 17.0,and outcome quality was assessed using the GRADE system.Results A total of 14 RCTs were included,with 1 063 LACC patients.The results of the Meta-analysis showed that NAIC and NIVC had a positive effect on the effectiveness indicators:complete response(CR)[RR=1.23,95％CI(0.91,1.67),P=0.174],partial response(PR)[RR=1.10,95％CI(0.86,1.20),P=0.874],total response(TR)[RR=1.10,95％CI(0.95,1.25),P=0.212],no change(NC)[RR=0.62,95％CI(0.33,1.16),P=0.137]and progressive disease(PD)[RR=1.43,95％CI(0.41,4.99),P=0.574]were not statistically significant.Differences in safety indicators:gastrointestinal reactions[RR=0.96,95％CI(0.76,1.23),P=0.755],hepatic and renal impairment[RR=0.71,95％CI(0.41,1.23),P=0.226]were not statistically significant.While in the incidence of myelosuppression[RR=0.62,95％CI(0.45,0.86),P=0.04],NAIC was superior to NIVC.In addition,the GRADE score results showed CR,PR,TR,and NC were high-quality evidence.Conclusion For LACC patients,the incidence of myelosuppression after treatment with NAIV is lower and safer than that with NIVC,and no significant difference was found between the two in terms of other efficacy and safety indicators.Clinicians should choose the appropriate neoadjuvant chemotherapy regimen based on a comprehensive assessment of the patient's actual condition.

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.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

Objective:To investigate the effects of subcutaneous immunotherapy (SCIT) on patients′ immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers.Methods:A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results:After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT: Z=-2.298, P<0.05; DM-SCIT: Z=-3.411, P<0.001); total ACT score (SM-SCIT: Z=-2.054, P<0.05; DM-SCIT: Z=-2.014, P<0.05) and total medication scores (SM-SCIT: Z=-3.799, P<0.000 1; DM-SCIT: Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group ( t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group ( P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated ( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions( Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions ( Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment ( Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment ( Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 ( r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 ( r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion:Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.