ObjectivesTo investigate the molecular epidemiological characteristics of HIV-1 infection among men who had sex with men (MSM) in Taizhou City, Zhejiang Province, and to provide a scientific reference for acquired immune deficiency syndrome prevention and control efforts. MethodsThe research subjects were all newly reported MSM population in Taizhou City from 2020 to 2023. Blood samples without antiviral therapy were collected. The HIV-1 pol gene was amplified and sequenced, and the sequences were submitted to the Stanford University drug resistance database to identify the mutation sites and drug resistance. MEGA 11.0 software was used to analyze the nucleic acid sequences, construct phylogenetic tree, and calculate genetic distance of gene sequences. The molecular transmission network diagram of HIV-1 was constructed using Cytoscape_v3.10.1, and the influencing factors of network entry were analyzed by logistic regression. ResultsA total of 363 newly reported HIV-infected MSM patients were included, with a median age [M (P₂₅, P₇₅)] of 34 (26,47) years old. The majority had an educational level of junior high school or below (55.65%). A total of eight subtypes were found, mainly CRF07_BC and CRF01_AE. The primary drug resistance rate was 10.47% (38/363). The optimal molecular network gene distance was 0.019, with a network access rate of 42.70% (155/363), and a total of 47 molecular clusters were formed. Multivariate logistic analyses showed that compared with the CRF01_AE subtype, the clustering risk of CRF07_BC subtype was higher (OR=1.916, 95%CI: 1.191‒3.109), cases with drug resistance had a higher risk of cluster formation than those without drug resistance (OR=2.011, 95%CI: 1.006‒4.080), and recent infected patients had a lower risk of entering the largest molecular cluster than long-term infected patients (OR=0.376, 95%CI: 0.137‒0.928). ConclusionThe newly diagnosed infections among the MSM population are active in Taizhou City, Zhejiang Province, with a high level of primary drug resistance. Individuals carrying drug-resistant strains are more likely to cluster. Drug resistance monitoring should be strengthened to prevent further spread of drug-resistant strains in the network.

OBJECTIVES: To explore the lipidomic characteristics of children with bronchial asthma (hereafter referred to as asthma) and identify potential biomarkers for asthma. METHODS: A total of 26 asthmatic children were prospectively enrolled as the asthma group, and 20 healthy children served as the healthy control group. The asthma group was further divided into atopic (n=13) and non-atopic (n=13) subgroups based on IgE levels. Serum lipid metabolites were analyzed using liquid chromatography-mass spectrometry, followed by statistical analysis and data visualization. RESULTS: A total of 1 435 lipids were detected in the 46 children, primarily glycerophospholipids (625/1 435, 43.55%). Significant differences were observed in serum lipid profiles between the asthma and control groups. Twelve significantly differential lipids were identified, with receiver operating characteristic curve analysis showing that phosphatidylserine (PS)(18:0/20:4) and ceramide (Cer)(c16:0) exhibited the highest diagnostic value for asthma. The relative abundances of PS(18:0/20:4) and PS(18:0/22:6) were higher in the atopic subgroup than in the non-atopic subgroup (P<0.05) and positively correlated with total IgE levels in asthmatic children (r=0.675 and 0.740, respectively; P<0.05). CONCLUSIONS Asthmatic children exhibit significant lipid metabolic disturbances, primarily characterized by abnormal glycerophospholipid metabolism. Among these, PS(18:0/20:4) and Cer(c16:0) demonstrate specific alterations and may serve as potential diagnostic biomarkers for asthma. Furthermore, the positive correlation between PS(18:0/20:4) and PS(18:0/22:6) levels and serum total IgE suggests their possible involvement in immune regulation in asthma.
Humans ; Asthma/metabolism* ; Male ; Child ; Female ; Prospective Studies ; Mass Spectrometry/methods* ; Lipids/blood* ; Chromatography, Liquid/methods* ; Child, Preschool ; Immunoglobulin E/blood* ; Biomarkers/blood* ; Adolescent ; Liquid Chromatography-Mass Spectrometry

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR＜0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95％CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P＜0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.

Concepts are the cornerstone of the development of disciplines. The concepts of TCM present that a superior concept contains more subordinate concepts. The superordinate concepts are often used to refer to different subordinate concepts, which can refer to both superior concepts themselves and non-specific subordinate concepts, that is, the characteristics of subordinate coverage and indefinite reference, which cause confusion in concept meaning, concept relationships, reasoning logic, and other problems. Nowadays, the TCM scholars pay little attention to this characteristic. Therefore, this article analyzed this characteristic, discussed its impact on the inheritance and development of TCM, and proposed that starting from the anchoring of concepts and entities to clarify the connotation of concepts, looking forward to provide new ideas for the definition of the concepts of TCM and the development of the discipline.

Objective:To explore the ways and methods to improve the ability of hospital ethical review and ensure the quality and efficiency of ethical review.Methods:By consulting the literature and combining the practical experience of the construction of the ethics committee and the ethical review work in the hospital, analyze the present situation of ethical review in our country, and deeply analyze the main problems existing in the work of ethical review in hospitals.Results:The quality and efficiency of ethical review can be effectively improved by implementing centralized management, optimizing work processes, establishing emergency response systems, opening green channels, optimizing the composition of committee members, strengthening ethical training and assessment, establishing emergency response systems, opening green channels, strengthening pre-review communication, establishing emergency response systems, opening green channels, strengthening formal review, increasing publicity, and improving ethical awareness.Conclusions:Clarifing the division of responsibilities and strengthen multi-department interaction can effectively improve the efficiency of ethics review. Optimizing the structure of ethics committee, strengthen the training and assessment of members, can effectively enhance the ability of ethics committee review. Unifing the list of documents, optimizing the work flow and the way of examination can effectively shorten the period of ethical examination. It is suggested that continuous ethical training and assessment should be carried out, that an information-based platform system should be used to achieve dynamic supervision, and that a certification system and assessment mechanism for ethics committees should be established at the national level, to promote the improvement of the ability of ethical review.

Objective:To observe the effects of kidney-tonifying and mind-calming acupuncture therapy on sleep,mood,sex hormone levels,and traditional Chinese medicine(TCM)symptoms in patients with perimenopausal insomnia(PMI). Methods:A total of 90 patients with PMI were randomly divided into a treatment group and a control group,with 45 cases in each group.Patients in the treatment group were treated with acupuncture at Shenshu(BL23),Taixi(KI3),Baihui(GV20),and Anmian(Extra).The control group was treated with sham acupuncture.Both groups were treated 3 times a week for 4 weeks.Pittsburgh sleep quality index(PSQI)and insomnia severity index(ISI)were used to evaluate the sleep quality of the subjects before treatment,after treatment,and 1 month after treatment(follow-up).Beck depression inventory(BDI)and Beck anxiety inventory(BAI)were used to evaluate the depression and anxiety of the subjects before treatment,after treatment,and at 1-month follow-up.The TCM symptom scale was used to evaluate the TCM symptoms of the subjects before treatment,after treatment,and 1 month after treatment.Serum levels of estradiol(E2),follicle-stimulating hormone(FSH),and luteinizing hormone(LH)were measured before and after treatment. Results:During the study,2 cases dropped out of the treatment group,and no cases dropped out of the control group.The PSQI scores of the treatment group were significantly lower after treatment and at 1-month follow-up compared with those before treatment(P<0.05),and the difference was statistically significant compared with that of the control group(P<0.05).In the control group,the PSQI score was significantly lower after treatment compared with before treatment(P<0.05),and the difference was not statistically significant at 1-month follow-up compared with before treatment(P>0.05).Compared with the pre-treatment,the ISI,BDI,BAI,and TCM symptom scale scores of the treatment group were lower after treatment and at 1-month follow-up(P<0.05),and the differences with the control group at the same time point were statistically significant(P<0.05).The differences in ISI,BDI,BAI,and TCM symptom scale scores of the control group before treatment,after treatment,and at 1-month follow-up were not statistically significant(P>0.05).After treatment,the serum E2 level in the treatment group was significantly higher than that before treatment(P<0.05),and the difference with the control group was statistically significant(P<0.05).The difference in the serum E2 level before and after treatment in the control group was not statistically significant(P>0.05).The differences in the serum FSH and LH levels between before and after treatment were not statistically significant in either group of subjects(P>0.05). Conclusion:Kidney-tonifying and mind-calming acupuncture therapy can improve sleep quality,relieve anxiety and depression,delay the decrease of serum E2 level,and improve related TCM symptoms in patients with PMI.

【Objective】 To compare the diagnostic performance of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB) enhanced magnetic resonance imaging (MRI) and multi-detector computed tomography (MDCT) in detecting liver metastases from metastatic colorectal cancer (mCRC). 【Methods】 We made a retrospective collection of 128 patients diagnosed with mCRC from May 2019 to June 2022 at Haikou Hospital, Xiangya School of Medicine, Central South University and Xijing Hospital, Air Force Military Medical University. All patients underwent Gd-EOB MRI and MDCT imaging. Three radiologists judged the accuracy, sensitivity, specificity, positive predictive value and negative predictive value of the two modalities for colorectal liver metastases, respectively. 【Results】 Of the 128 patients diagnosed with mCRC, a total of 462 lesions were obtained, with 424 positive and 38 negative metastases confirmed by pathology. In the interpretation of physician A, Gd-EOB MRI judged 404 positive and 38 negative liver metastases, with accuracy of 95.67%, sensitivity of 95.28%, specificity of 100.00%, a positive predictive value of 100%, and a negative predictive value of 65.52%. MDCT judged 337 positive and 37 negative liver metastases, with accuracy of 80.95%, sensitivity of 79.48% and specificity of 97.37%, a positive predictive value of 99.70%, and a negative predictive value of 29.84%. In the interpretation of physician B, Gd-EOB MRI judged 403 positive and 36 negative liver metastases, with accuracy of 95.02%, sensitivity of 95.05%, specificity of 94.74%, a positive predictive value of 99.51%, and a negative predictive value of 64.91%. MDCT judged 335 positive and 35 negative liver metastases, with accuracy of 80.09%, sensitivity of 79.01%, specificity of 92.11%, a positive predictive value of 99.11%, and a negative predictive value of 28.23%. In the interpretation of physician C, Gd-EOB MRI judged 406 positive and 38 negative liver metastases, with accuracy of 96.10%, sensitivity of 95.75%, specificity of 100.00%, a positive predictive value of 100.00%, and a negative predictive value of 67.86%. MDCT judged 352 positive and 34 negative liver metastases, with accuracy of 83.55%, sensitivity of 83.02%, specificity of 89.47%, a positive predictive value of 98.88%, and a negative predictive value of 32.08%. Gd-EOB MRI judged the nature of liver metastases with higher accuracy, sensitivity and negative predictive value than MDCT, and had better agreement with pathological examination results in the judgment of physician A and physician C (Kappa=0.770, 0.788). In physician B’s judgment, the agreement with pathological findings was fair (Kappa=0.731), while the agreement between the results of MDCT examination and pathological findings was poor (Kappa=0.379, 0.378 and 0.400). 【Conclusion】 Gd-EOB MRI has higher accuracy, sensitivity and positive predictive rate than MDCT in diagnosing colorectal liver metastasis, and has higher diagnostic performance. Therefore, it can provide more valuable reference information for clinical differential diagnosis. Subcapsular lesions, peribiliary metastases and hepatic steatosis can reduce the diagnostic performance of MDCT, while Gd-EOB MRI detection can provide more accurate results than MDCT.