ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Objective:To explore potential risk factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC).Methods:The clinicopathological data of 304 PTMC patients admitted to Baotou Cancer Hospital from Oct 2021 to Mar 2023 were retrospectively analyzed. The risk factors of CLNM were analyzed using unifactorial and multifactorial regression.Results:The rate of central regional lymph node metastasis in 304 patients with PTMC was 46.7% (142/304). Univariate analysis showed that male, age <45 years, maximum cancerous lesion diameter ≥5 mm, total cancerous lesion diameter ≥9.5 mm, anterior-posterior lesion diameter ≥5 mm, anterior-posterior lesion diameter ratio of cancerous lesions ≥0.48, breaching of thyroid capsule, number of lymph nodes on the side of cancerous lesions ≥5, and antithyroid peroxidase antibody ≤34 IU/ml were associated with CLNM (all P<0.05); Logistic multivariate regression analysis showed that. male, age <45 years, total diameter of cancer foci ≥9.5 mm ( OR=2.052, 95% CI: 1.176-3.581, P=0.011), anteroposterior diameter ratio of cancer foci ≥0.48 ( OR=2.076, 95% CI: 1.161-3.711, P=0.014), number of lymph nodes on the side of cancer foci ≥5, and anti-thyroid peroxidase antibody ≤34 IU/ml were independent risk factors for CLNM. Conclusion:Male, age ,total diameter of cancer foci, anterior-posterior diameter ratio of cancer foci, number of lymph nodes on the side of cancer foci, and anti-thyroid peroxidase antibody level are all independent risk factors for CLNM in patients with PTMC.

Objective:To evaluate the role and molecular mechanism of laminin β1(LAMB1)in cortical neurons in regulation of glutamate receptors.Methods:Recombinant lentivirus(LV-shLamb1)-mediated knockdown of LAMB1 expression in mouse primary cortical neurons was performed,followed by immunofluorescence staining and Western blot to detect changes in F-actin,glutamate receptor subtypes(AMPA receptors GluR1/GluR2,NMDA receptors NR1/NR2A),and ERK-related protein expression in cortical neurons.Results:LV-shLamb1 significantly inhibited LAMB1 expression in mouse cortical neurons.Concurrently,LV-shLamb1 markedly increased F-actin polymerization,as well as the expression of AMPA receptor subunits GluR1 and GluR2,and NMDA receptor subunits NR1 and NR2A.Further,Western blot detection showed that the phosphorylation level of ERK was significantly increased after LV-shLamb1 infec-tion.Conclusion:LAMB1 is expressed in cortical neurons.Suppression of LAMB1 expression in mouse cortical neu-rons activates the ERK pathway,which in turn promotes the polymerization of the cytoskeletal protein F-actin and the expression of glutamate receptors.This suggests that LAMB1 may regulate F-actin homeostasis and glutamate receptor levels through the ERK pathway,thereby playing a potentially important role in neuronal function.

Middle compartment defects,a common subtype of pelvic floor dysfunction(PFD),are primarily characterized by the prolapse of the uterus or vaginal vault.Magnetic resonance imaging(MRI)has emerged as a valuable diagnostic tool for PFD,offering superior soft tissue resolution while eliminating exposure to ionizing radiation.This review comprehensive summarizes current applications of MRI in the diagnosis and treatment of PFD,covering measurement methods,manifestations of three-level structural defects,postoperative efficacy evaluation,vaginal axial assessment,and evaluation of the mesh status.The authors suggest that MRI enables precise preoperative evaluation of three-level defects,thereby facilitating the development of personalized treatment plans.Additionally,MRI provides an accurate postoperative assessment of surgical outcomes and mesh status,offering a new basis for postoperative assessment.MRI demonstrates unique value in the diagnosis and treatment of middle compartment defects.

Objective:To explore potential risk factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC).Methods:The clinicopathological data of 304 PTMC patients admitted to Baotou Cancer Hospital from Oct 2021 to Mar 2023 were retrospectively analyzed. The risk factors of CLNM were analyzed using unifactorial and multifactorial regression.Results:The rate of central regional lymph node metastasis in 304 patients with PTMC was 46.7% (142/304). Univariate analysis showed that male, age <45 years, maximum cancerous lesion diameter ≥5 mm, total cancerous lesion diameter ≥9.5 mm, anterior-posterior lesion diameter ≥5 mm, anterior-posterior lesion diameter ratio of cancerous lesions ≥0.48, breaching of thyroid capsule, number of lymph nodes on the side of cancerous lesions ≥5, and antithyroid peroxidase antibody ≤34 IU/ml were associated with CLNM (all P<0.05); Logistic multivariate regression analysis showed that. male, age <45 years, total diameter of cancer foci ≥9.5 mm ( OR=2.052, 95% CI: 1.176-3.581, P=0.011), anteroposterior diameter ratio of cancer foci ≥0.48 ( OR=2.076, 95% CI: 1.161-3.711, P=0.014), number of lymph nodes on the side of cancer foci ≥5, and anti-thyroid peroxidase antibody ≤34 IU/ml were independent risk factors for CLNM. Conclusion:Male, age ,total diameter of cancer foci, anterior-posterior diameter ratio of cancer foci, number of lymph nodes on the side of cancer foci, and anti-thyroid peroxidase antibody level are all independent risk factors for CLNM in patients with PTMC.

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective:To investigate the changes of melanin concentration hormone receptor 1(MCHR1)in dorsal root ganglion(DRG)of mice with neuropathic pain.Methods:The expression profile of MCHR1 in the DRG of mice were observed by immunofluorescent staining.Neuropathic pain model was established by spared nerve injury(SNI)in mice.Male mice(C57BL/6)were randomly divided into 2 groups:Sham-operated group and SNI group.The paw withdrawal threshold(PWT)and paw withdrawal latency(PWL)were observed by von Frey fibers and thermal radiation stimulation.The mRNA and protein levels of MCHR1 in DRG were detected by real time RT-PCR and West-ern Blot,respectively.Results:MCHR1 was widely distributed in mouse DRG and co-labeled with small and medium-sized neuronal markers calcitonin gene-related peptide(CGRP)and isolectin B4(IB4),as well as large diameter neu-ronal marker NF200.Stable mechanical hyperalgesia and heat hyperalgesia were observed in the ipsilateral hindpaw of mice at 7 days post-SNI.Real time RT-PCR and Western Blot experiments showed that mRNA and protein expression levels in DRG were both significantly up-regulated in SNI-treated mice,as compared with Sham group.Conclusion:MCHR1 was widely distributed in large,medium and small neurons of DRG.After the SNI model mice presented a sta-ble phenomenon of hyperalgesia,the transcription and protein level of MCHR1 in DRG were significantly elevated in SNI mice.These data suggest that MCHR1 in DRG may be involved in the occurrence and development of neuropathic pain.

Objective To observe the value of clinical and CT radiomics features for predicting microsatellite instability-high(MSI-H)status of gastric cancer.Methods Totally 150 gastric cancer patients including 30 cases of MSI-H positive and 120 cases of MSI-H negative were enrolled and divided into training set(n=105)or validation set(n=45)at the ratio of 7∶3.Based on abdominal vein phase enhanced CT images,lesions radiomics features were extracted and screened,and radiomics scores(Radscore)was calculated.Clinical data and Radscores were compared between MSI-H positive and negative patients in training set and validation set.Based on clinical factors and Radscores being significant different between MSI-H positive and negative ones,clinical model,CT radiomics model and clinical-CT radiomics combination model were constructed,and their predictive value for MSI-H status of gastric cancer were observed.Results Significant differences of tumor location and Radscore were found between MSI-H positive and negative patients in both training and validation sets(all P＜0.05).The area under the curve(AUC)of clinical model,CT radiomics model and combination model for evaluating MSI-H status of gastric cancer in training set was 0.760,0.799 and 0.864,respectively,of that in validation set was 0.735,0.812 and 0.849,respectively.AUC of clinical-CT radiomics combination model was greater than that of the other 2 single models(all P＜0.05).Conclusion Clinical-CT radiomics combination model based on tumor location and Radscore could effectively predict MSI-H status of gastric cancer.

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.