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 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.

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.

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 improve awareness about infratentorial dural arteriovenous fistula (DAVF).Methods:Three cases of DAVF in the First Affiliated Hospital of Soochow University from September 2017 to September 2019 were retrospectively analyzed in terms of clinical features, cerebrospinal fluid (CSF) analysis, brain imaging and treatment, and followed up through telephone call.Results:Case 1: A 43-year-old woman, in chronic but acute aggravated course, presented with weakness of both lower limbs and urination and defecation dysfunction. Brain magnetic resonance imaging (MRI) revealed abnormal signal in medulla. CSF analysis demonstrated aquaporin-4 antibodies positive. Misdiagnosed as neuromyelitis optica spectrum disorders, the treatment was poor. Then digital subtraction angiography (DSA) showed DAVF at the left infratentorial area, and endovascular treatment was operated. Relapse was not observed in two-year follow up. Case 2: A 57-year-old woman, in chronic progressive course, mainly manifested as memory loss, but progressed with dysphagia, fever, coma. Treatment as “central nervous infection” was poor. Then DSA showed DAVF at the bilateral transverse-sigmoid sinus area, and endovascular treatment was operated with embolized partial fistulas. The patient died from lung infection within two months. Case 3: A 52-year-old man, in subacute course, was treated in the Gastroenterology Department with clinical manifestion of stubborn nausea and vomiting. Brain MRI revealed abnormal signal in medulla, with prominent vessel flow voids nearby. Then DSA showed DAVF at the craniocervical junction, and endovascular treatment was operated. Relapse was not observed in six-month follow up.Conclusions:DAVF has a variety of clinical manifestations, and infratentorial DAVF can manifest as acute neurological dysfunction involving the brain stem, cerebellum, spinal cord, which may be easily misdiagnosed. When brain MRI showed intracranial abnormal signal, the possibility of DAVF should be considered. DSA remains the gold standard to diagnose DAVF. Endovascular embolization is the main treatment of infratentorial DAVF at present. Prognosis depends on clinical presentation and fistula classification.

OBJECTIVE: To investigate the correlation between psychological disorder and vestibular dysfunction in patients suffering from peripheral vertigo. METHOD: Retrospective review of 17 peripheral vertiginous patients with intractable Meniere's disease recruited from the EENT hospital whom underwent intratympanic gentamicin injection. Hospital anxiety and depression scale, self-rating anxiety scale, self-rating depression scale, symptom checklist-90 were used in this study. Pre- and postoperative scores where compared. RESULT: The vertigo control rate of 17 patients reached 88%, with hearing impairment noted only in 17.6% of the patients. 33.3% of the preoperative tinnitus patients and 76.9% of the preoperative aural fullness patients had their symptoms relieved respectively. The outcomes of hospital anxiety and depression scale, self-rating anxiety scale, self-rating depression scale, symptom checklist-90 are significantly greater in vertiginous group than that in normal controls (P < 0. 01). The preoperative scores of these 4 questionnaires are greater than the postoperative scores in vertiginous patients (P < 0.05). No significant difference was noted between male and female participants in all the questionnaires used (P > 0.05). CONCLUSION Significant differences were noted between peripheral vertiginous patients and normal controls in psychiatric questionnaires, suggesting that psychological dysfunction may contribute to the vertigo attack.
Adult ; Anxiety ; psychology ; Female ; Humans ; Male ; Meniere Disease ; psychology ; Middle Aged ; Mood Disorders ; psychology ; Psychiatric Status Rating Scales ; Retrospective Studies ; Vertigo ; psychology

Objective To explore the relation between glucose fluctuation state and diabetic chronic compli-cations in type 2 diabetes mellitus. Methods 169 cases with type 2 diabetes mellitus were divided into two groups: 78 cases with constant high glucose(group Ⅰ) and 91 cases with glucose fluctuation state( group Ⅱ ). The clinical data such as fasting plasma glucose(FBG) ,fasting blood insulin(FINS) ,fasting blood C peptide,2 hours postprandial plasma glucose (2hPG) ,2 hours postprandial blood insuline (2hINS) ,2 hours postprandial blood C peptide, glycosy-lated hemoglobin A1c (HbA1c), and blood pressure (BP), body mass index ( BMI ), urinary albumin excretion rote (UAER) ,triglyeeride(TG) ,total cholesterol(TC) ,high density lipoprotein cholesterol(HDL-C) ,low density lipopro-tein cholesterol(LDL-C) were measured. Results 2hPG in group Ⅱ was much higher than that in group Ⅰ (P<0.01) ,but 2 hours postprandial blood insuline and 2 hours postprandial blood C peptide in group Ⅱ were much lower than those in group Ⅰ (P<0.01). The incidence of diabetic chronic complications was higher in group Ⅱ compared with that in group Ⅰ (P<0.01). Conclusion These findings suggest that glucose fluctuation state with type 2 dia-betes mellitus had increased diabetic chronic complications.

Objective To comprehend the metabolic disorder of the obese patients with type 2 diabetes mellitus(T2DM).Methods According to body mass index( BMI),176 cases of T2DM were divided into 2 groups;obesity(95 cases) and non-obesity(81 cases),the waist circumference(W) ,hip circumference(H) ,fasting plasma glucose(FBG) ,2-hour postprandial plasma glucose(2hBG) ,fasting blood insulin(FINS),2 hours postprandial blood insuline(2hINS), renal function, triglycetide(TG), total cholesterol(TC), high density lipoprotein cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C ), glycosylated hemoglobin(HbA1c) and blood pressure(BP) were tested.Results The BMI,the ratio of W/H (WHR), serum uric acid (BUA), FINS, 2bINS, FCP and 2hCP in the obese group were higher than those in non-obese group(P <0.01);systolic blood pressure and diastolic blood pressure in obese patients were higher than those in the non-obese group(P >0.05) ,while the prevalence of abdorminal obesity.Hypertension significantly increased in obese group than those in non-obese group.Conclusion Among the T2DM ,metabolic disorder in obese patients is even more serious.It is very improtant for obese patients with T2DM to be given combined treatment to improve the metabolic disorder,that includes controlling blood glucose, decreasing weight and lightening insulin resistance.