BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

OBJECTIVE: To investigate the association between long-term glycemic control and cerebral infarction risk in patients with diabetes through a large-scale cohort study. METHODS: This prospective, community-based cohort study included 12,054 patients with diabetes. From 2006 to 2012, 38,272 fasting blood glucose (FBG) measurements were obtained from these participants. FBG trajectory patterns were generated using latent mixture modelling. Cox proportional hazards models were applied to assess the subsequent risk of cerebral infarction associated with different FBG trajectory patterns. RESULTS: At baseline, the mean age of the participants was 55.2 years. Four distinct FBG trajectories were identified based on FBG concentrations and their changes over the 6-year follow-up period. After a median follow-up of 6.9 years, 786 cerebral infarction events were recorded. Different trajectory patterns were associated with significantly varied outcome risks (Log-Rank P < 0.001). Compared with the low-stability group, Hazard Ratio ( HR) adjusted for potential confounders were 1.37 for the moderate-increasing group, 1.23 for the elevated-decreasing group, and 2.08 for the elevated-stable group. CONCLUSION Sustained high FBG levels were found to play a critical role in the development of ischemic stroke among patients with diabetes. Controlling FBG levels may reduce the risk of cerebral infarction.
Humans ; Cerebral Infarction/blood* ; Middle Aged ; Male ; Female ; Blood Glucose/analysis* ; Fasting/blood* ; Aged ; Prospective Studies ; Risk Factors ; Diabetes Mellitus/blood* ; Adult ; Proportional Hazards Models

BackgroundGenetic factor plays an important role in the pathogenesis of panic disorder. Previous studies have revealed that immune system dysregulation is closely related to mental disorders such as panic disorder， while the relationship between panic disorder and immune-related gene expression remains unclear. ObjectiveTo explore the relationship between the expression of CXCL8， IL6R， JUN， PTGS2， TGFBR1， TLR2， CCR4 genes and panic disorder， providing references for the diagnosis and treatment of panic disorder. MethodsA total of 52 patients who met the diagnostic criteria for panic disorder according to the Diagnosed and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Psychosomatic Medicine Center of Sichuan Provincial People's Hospital from January 2020 to March 2021. Another 72 healthy individuals matched for age and gender from Chengdu were concurrently recruited as control group. The Panic Disorder Severity Scale （PDSS） was used to assess the severity of symptoms in panic disorder patients. Quantitative real-time polymerase chain reaction （PCR） was used to detect gene expression levels in two groups. Spearman correlation analysis was adopted to determine the correlation between PDSS score and immune-related gene expression in research group. ResultsThe expression of the JUN， PTGS2 and TGFBR1 genes were significant higher in panic disorder patients than those in control group （Z=-4.172， -2.086， -3.018， P<0.05 or 0.01）. After false discovery rate （FDR） correction for multiple testing， the differential expression of JUN and TGFBR1 genes remained statistically significant between two groups （P<0.05）. There was no significant difference in the expression of CCR4， CXCL8， IL6R and TLR2 genes between two groups （P>0.05）. Correlation analysis revealed that the expression of the JUN gene in panic disorder patients was positively correlated with PDSS score （r=0.360， P<0.01）， while the CCR4， CXCL8， IL6R， PTGS2， TGFBR1 and TLR2 genes showed no statistically significant correlation with the PDSS score （P>0.05）. ConclusionThe expression of the JUN and TGFBR1 genes may be associated with panic disorder， and the expression of the JUN gene correlated with the severity of panic disorder. ［Funded by Science and Technology Plan Project of Sichuan Provincial Department of Science and Technology （number， 2021YJ0440）］

Objective To explore the risk factors for premature delivery after transvaginal cervical cerclage,construct and validate a predictive model.Methods A total of 209 single-tonsus cervicitis patients who underwent McDonald cervical ring ligation at the Third Affiliated Hospital of Zhengzhou University from January 2022 to December 2024 were selected as subjects,and they were divided into preterm group(n=86)and full-term group(n=123)according to the postoperative pregnancy outcomes.LASSO regression analysis was used to screen variables,and the prediction model was constructed by multivariate Logistic regression.The performance of the model was evaluated by receiver operating characteristic curve,calibration curve and decision curve.Results Body mass index,amniotic sac protrusion,preoperative white blood cell,and cervical length before cerclage＜25mm were identified as independent risk factors for preterm birth(P＜0.05).The prediction model demonstrated an area under the curve of 0.823(95％CI:0.765-0.881),with sensitivity of 77.91％and specificity of 77.24％.Both the calibration curve and decision analysis confirmed the model's strong consistency and clinical net benefit.Conclusion The predictive model constructed in this study has a good predictive effect and can be used as a reference for the stratification of preterm risk after cervical cerclage.

Objective To explore the risk factors for premature delivery after transvaginal cervical cerclage,construct and validate a predictive model.Methods A total of 209 single-tonsus cervicitis patients who underwent McDonald cervical ring ligation at the Third Affiliated Hospital of Zhengzhou University from January 2022 to December 2024 were selected as subjects,and they were divided into preterm group(n=86)and full-term group(n=123)according to the postoperative pregnancy outcomes.LASSO regression analysis was used to screen variables,and the prediction model was constructed by multivariate Logistic regression.The performance of the model was evaluated by receiver operating characteristic curve,calibration curve and decision curve.Results Body mass index,amniotic sac protrusion,preoperative white blood cell,and cervical length before cerclage＜25mm were identified as independent risk factors for preterm birth(P＜0.05).The prediction model demonstrated an area under the curve of 0.823(95％CI:0.765-0.881),with sensitivity of 77.91％and specificity of 77.24％.Both the calibration curve and decision analysis confirmed the model's strong consistency and clinical net benefit.Conclusion The predictive model constructed in this study has a good predictive effect and can be used as a reference for the stratification of preterm risk after cervical cerclage.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

OBJECTIVE: To re-evaluate the systematic review/Meta-analysis of acupuncture and moxibustion for childhood autism (CA), aiming to provide decision-making basis for clinical diagnosis and treatment. METHODS: The systematic review and/or Meta-analysis of acupuncture and moxibustion for CA were searched in PubMed, EMbase, Cochrane Library, SinoMed, CNKI and Wanfang databases. The retrieval time was from the database establishment to May 5th, 2022. PRISMA (preferred reporting items for systematic reviews and Meta-analyses) was used to evaluate the report quality, and AMSTAR 2 (a measurement tool to assess systematic reviews 2) was used to evaluate the methodological quality, bubble map was used to construct the evidence map and GRADE was used to evaluate the quality of evidence. RESULTS: A total of 9 systematic reviews were included. The PRISMA scores ranged from 13 to 26. The report quality was low, and there was a serious lack in the aspects of program and registration, search, other analysis and funding. The main problems in methodology included not making prespecified protocol, incomplete retrieval strategy, not providing a list of excluded literatures, and incomplete explanation on heterogeneity analysis and bias risk. The evidence map showed that 6 conclusions were valid, 2 conclusions were possible valid and 1 conclusion was uncertain valid. The overall quality of evidence was low, and the main factors leading to the downgrade were limitations, followed by inconsistency, imprecision and publication bias. CONCLUSION Acupuncture and moxibustion has a certain effect for CA, but the quality of reporting, methodology and evidence in included literature need to be improved. It is suggested to perform high-quality and standardized research in the future to provide evidence-based basis.
Child ; Humans ; Acupuncture Therapy/methods* ; Autistic Disorder ; Moxibustion/methods* ; Publication Bias ; Research Design ; Systematic Reviews as Topic ; Meta-Analysis as Topic

Objective:To evaluate the diagnostic value of 1, 3-β-D glucan (BDG), mannan IgM antibody (Mn-IgM) and mannan IgG antibody (Mn-IgG) in invasive candidiasis and to compare the differences in the diagnostic capability of serological markers used alone or in combination.Methods:Serum samples of 126 patients with invasive candidiasis and 104 healthy people who took physical examination during the same period were collected. BDG was detected by dynamic chromogenic method, and Mn-IgM and Mn-IgG were detected by ELISA. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, coincidence rate and Kappa value of the three serological markers used alone or in combination in the diagnosis of invasive candidiasis were analyzed and compared. The receiver operating characteristic (ROC) curves were drawn and the areas under the curves (AUCs) were calculated.Results:The levels of BDG, Mn-IgM and Mn-IgG in patients with invasive candidiasis were significantly higher than those in healthy people ( P<0.01). The sensitivity, specificity, Kappa value and AUC of BDG were 48.41%, 92.31%, 0.389 and 0.842. The sensitivity, specificity, Kappa value and AUC of Mn-IgM were 64.29%, 91.35%, 0.540 and 0.829. The sensitivity, specificity, Kappa value and AUC of Mn-IgG were 27.78%, 95.19%, 0.214 and 0.737. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM were 76.19%, 88.46%, 0.637 and 0.921. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgG were 59.52%, 91.35%, 0.491 and 0.856. The sensitivity, specificity, Kappa value and AUC of Mn-IgM+ Mn-IgG were 69.84%, 90.38%, 0.588 and 0.891. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM+ Mn-IgG were 80.16%, 88.46%, 0.679 and 0.922. Conclusions:The sensitivity of Mn-IgM was higher than that of BDG and Mn-IgG in the diagnosis of invasive candidiasis. When the serological biomarkers were used in combination, BDG+ Mn-IgM and BDG+ Mn-IgM+ Mn-IgG had relatively high Kappa value and AUC, showing high accuracy. The clinical diagnostic value of multiple serological biomarkers used in combination was significantly higher than that of any serological biomarkers used alone. Early combined detection and continuous monitoring of multiple serological biomarkers in patients with high risk of invasive candidiasis could be used clinically to adjust antifungal treatment strategies timely.

This study aims to investigate the mechanism of Linderae Radix water extract(LRWE) in the prevention and treatment of diarrhea-predominant irritable bowel syndrome(IBS-D) based on serum metabolomics. Eighteen 2-week-old male SD rats were randomized into control, IBS-D model, and LRWE groups. The rats in other groups except the control group received gavage of senna concentrate combined with restraint stress for the modeling of IBS-D. The rats in the LRWE group were administrated with LRWE(5.4 g·kg~(-1)) by gavage, and those in the control and IBS-D model groups with an equal volume of distilled water for a total of 14 days. The visceral sensitivity was evaluated by the abdominal withdrawal reflex(AWR) score, and the degree of diarrhea was assessed by the fecal water content(FWC). The morphological changes of the colon and the morphology and number of goblet cells were observed by hematoxylin-eosin(HE) and periodic acid-schiff(PAS) staining, respectively. Ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) was used for the screening of the potential biomarkers in the rat serum and their related metabolic pathways. The results showed that LRWE reduced the AWR score, decreased FWC, and alleviated visceral sensitivity and diarrhea symptoms in IBS-D rats. HE and PAS staining showed that LRWE mitigated low-grade intestinal inflammation and increased the number of mature secretory goblet cells in the colonic epithelium of IBS-D rats. A total of 25 potential biomarkers of LRWE in treating IBS-D were screened out in this study, which were mainly involved in riboflavin, tryptophan, glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, and cysteine and methionine metabolism. The regulatory effects were the most significant on the riboflavin and tryptophan metabolism pathways. LRWE may alleviate the visceral hypersensitivity by promoting energy metabolism and amino acid metabolism, enhancing intestinal barrier function, and improving intestinal immune function in IBS-D rats.
Rats ; Male ; Animals ; Irritable Bowel Syndrome/metabolism* ; Water ; Chromatography, Liquid ; Tryptophan ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Diarrhea/drug therapy* ; Biomarkers ; Riboflavin

ObjectiveTo investigate the intervention effect of Danggui Buxuetang on oxidative stress and inflammatory response in diabetic kidney disease （DKD） rats from its improvement of podocyte mitochondrial dysfunction. MethodSD rats were randomly divided into the control group and modeling group， and the ones in the latter group rats were fed a high-glucose and high-fat diet and then intraperitoneally injected with a small dose of streptozotocin （STZ） for inducing type 2 diabetes. The successfully modeled rats were randomized into the model group， high- and low-dose （1.44 and 0.72 g·kg^-1） Danggui Buxuetang groups， and irbesartan （0.017 g·kg^-1）group and gavaged with the corresponding drugs， while those in the normal and model groups with an equal volume of normal saline. After 20 weeks of drug intervention， the urinary microalbumin-to-urine creatinine ratio （UACR） and serum malondialdehyde （MDA） content and manganese superoxide dismutase （MnSOD） activity in each group were measured. The pathological changes in renal tissue were observed by Masson trichrome staining， and periodic acid-silver metheramine （PASM） staining， followed by the observation of ultrastructural changes in podocytes under the transmission electron microscope （TEM）. The expression level of reactive oxygen species （ROS） in rat kidney tissue was detected using a fluorescent probe dihydroethidium （DHE）. The protein expression levels of peroxisome proliferator-activated receptor γ -coactivator -1α （PGC-1α）， nucleotide-binding domain like receptor protein 3 （NLRP3）， and Wilms tumor protein-1 （WT-1） were measured by immunohistochemistry （IHC）， and the expression levels of NLRP3， interleukin-1β （IL-1β），and WT-1 in podocytes by immunofluorescence （IF） assay. The mRNA expression levels of PGC-1α and NLRP3 in the renal tissues were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of PGC-1α， MnSOD， NLRP3， and IL-1β were assayed by Western blot. ResultCompared with the normal group， the model group exhibited elevated UACR and MDA content， weakened MnSOD activity （P<0.01）， glomerular hypertrophy， thickened basement membrane， mesangial hyperplasia， increased extracellular matrix， K-W nodules， podocyte mitochondrial swelling， disordered mitochondrial cristae， foot process fusion or loss， vacuolization， increased ROS （P<0.01）， enhanced NLRP3 and IL-1β but diminished WT-1 expression in podocytes， down-regulated PGC-1α mRNA expression （P<0.01） and PGC-1α and MnSOD protein expression （P<0.01）， and up-regulated NLRP3 mRNA expression and NLRP3 and IL-1β protein expression （P<0.01）. Compared with the model group， Danggui Buxuetang high-dose group significantly decreased UACR and MDA， enhanced MnSOD activity （P<0.05， P<0.01）， improved renal histopathology and podocyte mitochondrial ultrastructure， decreased ROS （P<0.05， P<0.01） and NLRP3 and IL-1β expression in podocytes， enhanced WT-1 expression in podocytes， up-regulated the mRNA and protein levels of PGC-1α and MnSOD， and down-regulated the mRNA and protein levels of NLRP3 and IL-1β （P<0.05， P<0.01）. ConclusionDanggui Buxuetang alleviates oxidative stress， reduces inflammatory response， protects kidney， and delays the progression of DKD possibly by improving the mitochondrial dysfunction in podocytes of DKD rats.