Objective To explore the relationship between serum growth differentiation factor-15(GDF-15),chemerin,pentraxin 3(PTX3)levels and obesity,insulin resistance and inflammatory factors in patients with type 2 diabetes mellitus(T2DM),and to construct and evaluate the predictive efficacy.Methods A total of 231 T2DM patients admitted to the hospital from February 2020 to September 2022 were selected as T2DM group.Another 100 healthy subjects who came to the hospital for physical examination during the same period were selected as the control group.Serum GDF-15,chemerin and PTX3 levels of the two groups were detected and compared by enzyme-linked immunosorbent assay(ELISA).Clinical data of the two groups were collected and compared.Pearson correlation analysis and multiple linear regression were used to analyze the relationship between serum GDF-15,chemerin,PTX3 levels and obesity,insulin resistance and inflammation.Multivariate Logistic regression was used to evaluate the independent risk factors for T2DM development,and the com-bined prediction model of serum GDF-15,chemerin and PTX3 was constructed,and receiver operating charac-teristic(ROC)curve was plotted to evaluate its predictive efficacy for T2DM development.Results Compared with the control group,body mass index(BMI),waist-to-hip ratio(WHR),systolic blood pressure,total cho-lesterol,triglyceride,fasting blood glucose,fasting insulin(FINS),homeostasis model assessment of insulin re-sistance(HOMA-1R),interleukin(IL)-1β,IL-6,GDF-15,chemerin and PTX3 were all increased in T2DM group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that se-rum GDF-15,chemerin and PTX3 levels were positively correlated with BMI,WHR,FINS,HOMA-IR,IL-1βand IL-6 in T2DM group(P＜0.05).Multiple linear regression analysis showed that BMI,FINS,HOMA-IR,IL-1β and IL-6 were positively correlated with serum GDF-15,chemerin and PTX3 levels(P＜0.05).Multiva-riate Logistic regression analysis showed that the increase of serum GDF-15,chemerin and PTX3 levels was an independent risk factor for T2DM development(P＜0.05).ROC curve analysis results showed that the com-bined prediction model of serum GDF-15,chemerin and PTX3 had better prediction efficiency,and its area un-der the curve,sensitivity,specificity and accuracy were higher than those applied alone.Conclusion The levels of GDF-15,chemerin and PTX3 in serum of T2DM patients are elevated,and their levels increase with the ex-acerbation of obesity,insulin resistance and inflammatory response in T2DM patients.The combined predic-tion model constructed in this study has good predictive efficacy and has high predictive value for the occur-rence of T2DM.

The aim of this study was to investigate the impact of overexpressing 70-kD heat shock pro-teins(Hsp70)on glycolysis in C2C12 cells during myogenesis and adipogenesis.Using C2C12 cells as the research material,adenovirus was used to overexpress the Hsp70 gene,and changes in the expression of glycolytic genes were detected using fluorescence quantitative PCR and Western blotting techniques.The study indicated that during C2C12 cell myogenic differentiation,the expression trend of the Hsp70 gene was consistent with that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,suggesting a relationship between Hsp70 and the glycolytic pathway during myogenic differentiation.Overexpression of Hsp70 in the later stages of myogenic differentiation significantly upregulated the expression of Gsk3β,Pkm,Prk-ag3,and Pfkm genes(P＜0.05),with no significant impact on Hk-2 gene expression(P＞0.05).Dur-ing C2C12 cell adipogenic induction,the expression trend of the Hsp70 gene was similar to that of Gsk3β,Pkm,Prkag3,Pfkm,and Hk-2 genes,indicating a relationship between Hsp70 and the glycolytic path-way during adipogenic induction.Following Hsp70 overexpression,in the later stages of adipogenic in-duction,the number of lipid droplets was significantly higher compared to the control group,with a sig-nificant upregulation of Gsk3β,Pkm,Prkag3,and Pfkm gene expression(P＜0.05),while Hk-2 gene expression was not significantly affected(P＞0.05).In conclusion,Hsp70 in C2C12 cells in myogenic and adipogenic states promoted the breakdown of glycogen into 6-phospho-glucose,thereby enhancing the glycolytic pathway,providing insights into the functional role of the Hsp70 gene in glycolysis in C2C12 cells.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

OBJECTIVE: To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI). METHODS: Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO₁₅) and Shen (CO₁₀), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores. RESULTS: The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036). CONCLUSION The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
Humans ; Depression/therapy* ; Magnetic Resonance Imaging/methods* ; Vagus Nerve Stimulation/methods* ; Brain/diagnostic imaging* ; Transcutaneous Electric Nerve Stimulation/methods* ; Vagus Nerve

OBJECTIVE: To observe the effects of the Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on hemorrhagic transformation and limb motor function after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) in stroke patients. METHODS: A total of 130 stroke patients after rt-PA thrombolytic were divided into an acupuncture group (58 cases, 1 case dropped off) and a non-acupuncture group (72 cases, 7 cases dropped off) according to whether they received acupuncture treatment. Propensity score matching (PSM) was used to match each group, with 38 patients in each group. The patients in the non-acupuncture group received rt-PA thrombolytic therapy and western medical basic treatment. In addition to the basic treatment, the patients in the acupuncture group received Xingnao Kaiqiao acupuncture at Shuigou (GV 26), bilateral Neiguan (PC 6), and ipsilateral Sanyinjiao (SP 6), Chize (LU 5), once a day for 14 days. The incidence of hemorrhagic transformation within 30 days after onset was compared between the two groups. The Fugl-Meyer assessment (FMA) score and activities of daily living (ADL) score were observed at baseline and 30 days, 6 months, 1 year after onset in the two groups. The disability rate at 6 months and 1 year after onset was recorded, and safety was evaluated in both groups. RESULTS: The incidence of hemorrhagic transformation in the acupuncture group was 5.3% (2/38), which was lower than 21.1% (8/38) in the non-acupuncture group (P<0.05). At 30 days, 6 month, and 1 year after onset, the FMA and ADL scores of both groups were higher than those at baseline (P<0.01), and the scores in the acupuncture group were higher than those in the non-acupuncture group (P<0.01). The disability rate in the acupuncture group at 1 year after onset was 10.5% (4/38), which was lower than 28.9% (11/38) in the non-acupuncture group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). CONCLUSION The Xingnao Kaiqiao acupuncture method could reduce the incidence of hemorrhagic transformation in stroke patients after intravenous thrombolysis with rt-PA, improve their motor function and daily living ability, and reduce the long-term disability rate.
Humans ; Tissue Plasminogen Activator/adverse effects* ; Activities of Daily Living ; Prospective Studies ; Stroke ; Acupuncture Therapy ; Thrombolytic Therapy/adverse effects*

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ²=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ²=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans ; Child ; Male ; Female ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; Dermatitis, Atopic/psychology* ; Cross-Sectional Studies ; Retrospective Studies ; Severity of Illness Index ; Hospitals ; Quality of Life

To analyze the clinical characteristics and treatment status of atopic dermatitis (AD) in children in the outpatient department of a children's hospital in Beijing from 2015 to 2019. This study used a cross-sectional study method to retrospectively analyze the data of AD patients who visited the Dermatology outpatient department of Beijing Children's Hospital, Capital Medical University, from April 2015 to April 2019. A total of 1 926 AD patients aged 0-17.5 years old living in Beijing and its surrounding areas were included, and the general situation, severity and distribution of AD disease, clinical characteristics and severity of AD, relevant influencing factors of AD onset, AD disease prognosis and treatment status were recorded. SAS 9.4, SPSS19.0, and R software were used for data processing, and descriptive statistical analysis, Chi-square test, Analysis of Variance, and correspondence analysis were used for statistical analysis. The results showed that the male to female ratio of AD patients in children included in this study was 1.4∶1; 79.0% (1 522/1 926), 86.1%(1 658/1 926), 91.3%(1 758/1 926), and 97.3%(1 907/1 926) of AD onset at the age of 6 months, 1 year, 2 years, and 5 years, respectively; mild of AD patients accounted for 13.2% (255/1 926)(SCORAD score 0-24), moderate of AD patients accounted for 50.1%(965/1 926) (SCORAD score 25-50), and severe of AD patients accounted for 36.7% (706/1 926)(SCORAD score>50).The age of severe AD patients were younger than mild and moderate AD patients. The face, head, trunk, and lower limbs were common areas of onset for moderate to severe AD, while the hands, feet, and ears were common areas of onset for severe AD patients. Temperature changes, hot water factors, mental and emotional states, and spring and winter were the main aggravation factors of AD;35.2% (678/1 926) aggravated and 61.8% (1 191/1 926) persistent. The more frequent bathing, the less severity of AD disease (χ²=29.791,P<0.001); 28.0% (520/1 856) of AD patients have no moisturizing habits, which were correlated with the severity of AD disease (χ²=15.908, P<0.05); the proportion of combined treatment medications in children with moderate to severe AD was significantly higher than mild AD patients. In conclusion, the patients with AD who went to specialist clinics were mainly moderate to severe patients and developed disease before the age of 5 years from 2015 to 2019.The severity of AD were mainly moderate to severe, and most of these patients had poor disease control. Traditional treatment plans had limitations. Identifying the clinical characteristics and treatment status of childhood AD would help us to carry out more targeted prevention and management work.
Humans ; Child ; Male ; Female ; Infant, Newborn ; Infant ; Child, Preschool ; Adolescent ; Dermatitis, Atopic/psychology* ; Cross-Sectional Studies ; Retrospective Studies ; Severity of Illness Index ; Hospitals ; Quality of Life

OBJECTIVE: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons. METHODS: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway. RESULTS: MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01). CONCLUSION TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
Animals ; Beclin-1 ; Brain Ischemia/metabolism* ; Glucose ; Infarction, Middle Cerebral Artery/drug therapy* ; Mammals/metabolism* ; Neuroprotection ; Neuroprotective Agents/therapeutic use* ; Oxygen ; Panax notoginseng ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Reperfusion Injury/metabolism* ; Saponins/therapeutic use* ; TOR Serine-Threonine Kinases/metabolism*

Inflammatory bowel disease (IBD) is an, intractable inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs), owing to their immunosuppressive capabilities, have the potential to rescue IBD. But the therapeutic effectiveness of MSCs is sometime thwarted by their variable immunomodulatory ability in vivo. In the present study, we produced engineered MSCs that secrete interleukin10 (IL-10) and evaluated their therapeutic potential in IBD mouse model. The MSCs maintained the phenotype and cell proliferation rate after overexpression of IL-10 by lentivirus (LV) infection. Immune cells and MSCs in vitro co-culture systems exhibited that relative to unmodified MSCs, immune cells co-cultured with IL-10-overexpressing MSCs had significantly lower numbers of T helper 1 cells (Th1) and T helper 17 cells (Th17) (P<0.05), the content of TNF-α in the supernatant of macrophage cells co-cultured with MSCs overexpressing IL-10 was significantly decreased (P<0.0001). Tail vein injection of the IL-10 overexpressing MSCs achieved a better therapeutic effect in the dextran sodium sulfate (DSS) induced colitis mouse model than that of the unmodified MSCs, as indicated by colon length, disease activity index (DAI) and colonic cytokines expression. The experimental results were statistically different (P>0.05). Overall, LV induced MSCs overexpressing IL-10 might be a promising alternative therapeutic option for the treatment of IBD.