ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Objective To comprehensively analyze the clinical characteristics and risk factors of children with refractory mycoplasma pneumonia(RMPP),precisely identify the joint predictors in these children,and construct a prediction model.This aims to offer a scientific foundation for the early identification of RMPP and the formulation of accurate treatment and medication strategies.Methods A retrospective analysis was performed on the clinical data of 282 children diagnosed with mycoplasma pneumoniae pneumonia(MPP)who were admitted to the Pediatric Department of the Seventh Medical Center of the Chinese People's Liberation Army General Hospital between August 1,2023,and February 29,2024.Among these children,119 with RMPP were classified into the RMPP group,while the remaining 163 with general MPP(GMPP)were assigned to the GMPP group.The clinical data of both groups,encompassing age,gender,duration of fever,symptoms,laboratory test indices,chest imaging data,complications,etc.,were compared.A logistic probability model(LogP model)for joint application was constructed.The discriminatory ability of the model was evaluated using the area under the receiver operating characteristic(ROC)curve,and the calibration of the model was assessed by means of a calibration curve.Results In comparison with the GMPP group,children in the RMPP group exhibited a significantly longer duration of fever(P=0.002).Moreover,they had a higher incidence of complications,including myocardial damage and coagulation dysfunction(P<0.05).Regarding inflammatory markers,the levels of C-reactive protein(CRP),procalcitonin(PCT),and lactate dehydrogenase(LDH)were notably elevated in the RMPP group(P<0.05),whereas the level of albumin(Alb)was lower(P=0.001).In the RMPP group,the levels of interleukin-2(IL-2),interleukin-5(IL-5),interleukin-8(IL-8),interleukin-1β(IL-1β),and D-Dimer were increased,while the levels of interleukin-6(IL-6)and interleukin-17(IL-17)were decreased(P<0.05).Chest computed tomography(CT)scans revealed a higher proportion of lung consolidation,pleural effusion,and atelectasis in the RMPP group(P<0.05).Multivariate logistic regression analysis demonstrated that CRP,total bilirubin(T-BIL),LDH,IL-17,and prothrombin time(PT)were independent risk factors for RMPP(P<0.05).The receiver operating characteristic(ROC)predictive model established based on these factors had an area under the curve(AUC)of 0.787(95%confidence interval[CI]:0.693～0.880),with a cutoff value of 0.421,a sensitivity of 0.786,and a specificity of 0.660.The calibration curve indicated that the predicted probability matched well with the reference probability,and there was no statistical difference in the results of the Hosmer-Lemeshow test(P>0.05).Conclusions The clinical features of children with RMPP are predominantly characterized by prolonged fever,moderate lung lesions,other organ injuries,and high inflammatory markers.CRP,T-BIL,LDH,IL-17,and PT can act as independent risk factors for RMPP.

Objective To comprehensively analyze the clinical characteristics and risk factors of children with refractory mycoplasma pneumonia(RMPP),precisely identify the joint predictors in these children,and construct a prediction model.This aims to offer a scientific foundation for the early identification of RMPP and the formulation of accurate treatment and medication strategies.Methods A retrospective analysis was performed on the clinical data of 282 children diagnosed with mycoplasma pneumoniae pneumonia(MPP)who were admitted to the Pediatric Department of the Seventh Medical Center of the Chinese People's Liberation Army General Hospital between August 1,2023,and February 29,2024.Among these children,119 with RMPP were classified into the RMPP group,while the remaining 163 with general MPP(GMPP)were assigned to the GMPP group.The clinical data of both groups,encompassing age,gender,duration of fever,symptoms,laboratory test indices,chest imaging data,complications,etc.,were compared.A logistic probability model(LogP model)for joint application was constructed.The discriminatory ability of the model was evaluated using the area under the receiver operating characteristic(ROC)curve,and the calibration of the model was assessed by means of a calibration curve.Results In comparison with the GMPP group,children in the RMPP group exhibited a significantly longer duration of fever(P=0.002).Moreover,they had a higher incidence of complications,including myocardial damage and coagulation dysfunction(P<0.05).Regarding inflammatory markers,the levels of C-reactive protein(CRP),procalcitonin(PCT),and lactate dehydrogenase(LDH)were notably elevated in the RMPP group(P<0.05),whereas the level of albumin(Alb)was lower(P=0.001).In the RMPP group,the levels of interleukin-2(IL-2),interleukin-5(IL-5),interleukin-8(IL-8),interleukin-1β(IL-1β),and D-Dimer were increased,while the levels of interleukin-6(IL-6)and interleukin-17(IL-17)were decreased(P<0.05).Chest computed tomography(CT)scans revealed a higher proportion of lung consolidation,pleural effusion,and atelectasis in the RMPP group(P<0.05).Multivariate logistic regression analysis demonstrated that CRP,total bilirubin(T-BIL),LDH,IL-17,and prothrombin time(PT)were independent risk factors for RMPP(P<0.05).The receiver operating characteristic(ROC)predictive model established based on these factors had an area under the curve(AUC)of 0.787(95%confidence interval[CI]:0.693～0.880),with a cutoff value of 0.421,a sensitivity of 0.786,and a specificity of 0.660.The calibration curve indicated that the predicted probability matched well with the reference probability,and there was no statistical difference in the results of the Hosmer-Lemeshow test(P>0.05).Conclusions The clinical features of children with RMPP are predominantly characterized by prolonged fever,moderate lung lesions,other organ injuries,and high inflammatory markers.CRP,T-BIL,LDH,IL-17,and PT can act as independent risk factors for RMPP.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Fetuin-B (FETUB) is a glycoprotein mainly synthesized and secreted by the liver. It is involved in many physiological and pathological processes including glucose metabolism, inflammatory response, nonalcoholic fatty liver disease, myocardial infarction, tumor and so on. In recent years, FETUB has also been confirmed to play roles in the female reproductive system. FETUB may affect follicular development and play an important role in in vivo and in vitro fertilization. In addition, serum FETUB level is elevated significantly during pregnancy and labor. FETUB expression is changed in a variety of reproductive diseases (polycystic ovary syndrome, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy). In this review, we summarize FETUB related studies in female reproduction, and focus on the roles of FETUB in female reproductive physiology and pathology, in order to provide information for the pathogenesis of reproductive disorders.
Humans ; Female ; Pregnancy ; Polycystic Ovary Syndrome/physiopathology* ; Fetuin-B/physiology* ; Pregnancy Complications/metabolism* ; Animals ; Diabetes, Gestational/physiopathology* ; Cholestasis, Intrahepatic/metabolism* ; Reproduction/physiology* ; Ovarian Follicle/physiology*

Aim To explore the effects of putative receptor protein related to ATI (APJ) homodimer on the behaviors-the proliferation, migration and tube formation of human umbilical vein endothelial cells (HU-VECs). Methods HUVECs at logarithmic growth stage were randomly divided into PBS, Apelin-13 + TM1 (APJ monomer group) and Apelin-13 + PBS group (APJ homodimer group). Western blot and Matrix-Assisted Laser Desorption/Ionization Time of Fligh Mass Spectrometry (MALDI-TOF MS) were used to detect the expression of APJ and APJ homodimer in HUVECs, respectively. Real-Time Cell Analyzers (RT-CA) was used to detect the concentration of the maximum effect of Apelin-13. Cell viability was detected by CCK-8. The cell migration ability was detected by scratch test, and the number of tubes formed on matri-gel that made artificial basement membrane was counted. Results Western blot and MALDI-TOF MS showed that APJ and APJ homodimer were expressed in HUVECs. The EC50 of Apelin-13 was 2.26 x 10

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing