Objective To investigate the expression levels of T cell receptor(TCR)ζchain and Zeta-chain-associated protein kinase 70(ZAP70)in peripheral blood of patients with primary Sj?gren syndrome(PSS).Methods Thirty-six patients with PSS who were treated at Jiujiang NO.1 People's Hospital from January to June 2024 were enrolled in observation group,and 30 healthy subjects during the same period were enrolled in control group.Real-time fluorescent quantitative polymerase chain reaction was used to detect the expression levels of TCRζ chain and ZAP70 in peripheral blood mononuclear cells,and flow cytometry was used to detect peripheral blood T cell subsets.Pearson correlation was used to analyze the correlation between TCRζ chain,ZAP70 and other detection indicators.Results The relative expression levels of TCRζ chain and ZAP70 in observation group were significantly lower than those in control group(P＜0.05),while CD8+and interleukin-6(IL-6)were significantly higher than those in control group(P＜0.05).Pearson correlation analysis showed that TCRζ chain was positively correlated with CD4+,and negatively correlated with CD8+and IL-6(P＜0.05).ZAP70 was negatively correlated with CD8+and IL-6(P＜0.05).Conclusion The expressions of TCRζ chain and ZAP70 are down-regulated in PSS patients,which may exacerbate the immune disorder of PSS through abnormal T cell signal transduction.

Small intestinal bacterial overgrowth（SIBO）is a clinically common but poorly recognized disease with clinical symptoms that overlap with those of functional gastrointestinal disorders（FGID）. FGID is a common risk factor for the occurrence of SIBO，and its SIBO incidence rate is significantly higher than that of healthy people，and has a certain correlation. Intestinal microbiota dysbiosis（including SIBO）plays an important role in the pathophysiology of FGID. At present，the diagnosis and treatment of SIBO still face challenges，and the treatment plan of FGID is gradually introduced into the treatment of SIBO. SIBO and FGID are closely related in clinical manifestations，incidence rate，pathophysiology，treatment and other aspects，but there is little research on the relationship between them. Prospective and large-scale clinical research is still needed to improve understanding and diagnostic accuracy.This article reviews the research progress on the relationship between SIBO and FGID.

Objective To investigate the expression and prognostic value of uncoupling protein 2(UCP2)and ubiquitin associated protein 2-like(UBAP2L)in non-small cell lung cancer(NSCLC).Methods A total of 94 patients with NSCLC who received surgical treatment in a hospital from March 2019 to March 2021 were selected as the study objects.The expressions of UCP2 protein,UBAP2L protein,UCP2 mRNA and UBAP2L mRNA in cancer tissues and adjacent tissues of NSCLC patients were detected by real-time fluorescence quan-titative polymerase chain reaction and immunohistochemistry.The correlation between UCP2 mRNA and UBAP2L mRNA in NSCLC was analyzed by Pearson correlation.Kaplan-Meier curve was used to analyze the differences in survival rates of NSCLC patients with different UCP2 mRNA and UBAP2L mRNA expres-sions,and multivariate Cox regression was used to analyze the prognostic factors of NSCLC patients.Results The positive rate of UCP2 protein and UBAP2L protein in cancer tissues of NSCLC patients was higher than that in adjacent tissues,and the difference was statistically significant(P＜0.05).The expressions of UCP2 mRNA and UBAP2L mRNA in cancer tissues of NSCLC patients were significantly higher than those in adjacent tissues,and the differences were statistically significant(P＜0.05).There was a positive cor-relation between UCP2 mRNA and UBAP2L mRNA expression in NSCLC patients(r=0.721,P＜0.001).The expression of UCP2 mRNA and UBAP2L mRNA in cancer tissues of NSCLC patients was related to TNM stage and lymph node metastasis.There was significant difference in 3-year survival rate between UCP2 mRNA high expression group and UCP2 mRNA low expression group(P＜0.05).There was significant difference in 3-year survival rate between UBAP2L mRNA high expression group and UBAP2L mRNA low expression group(P＜0.05).TNM stage Ⅲ A,lymph node metastasis,UCP2 mRNA high expression and UBAP2L mRNA high expression were risk factors for prognosis of NSCLC patients(P＜0.05).Conclusion UCP2 protein,UBAP2L protein,UCP2 mRNA and UBAP2L mRNA are up-regulated in NSCLC patients,and UCP2 mRNA and UBAP2L mRNA are helpful to evaluate the survival prognosis of NSCLC patients.

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To investigate the clinical application value of expanded non-invasive prenatal testing(NIPT-plus)in screening for fetal chromosome copy number variations(CNV).Methods:From January 2021 to December 2023,141 pregnant women who voluntarily underwent amniocentesis at the Prenatal Diagnostic Centre of Urumqi Maternal and Child Health Hospital due to NIPT-plus suggesting a high risk of fetal CNV were selected.Amniotic fluid samples were collected for fetal chromosome karyotyping and chromosome microarray analysis(CMA).Pregnant women who underwent the above tests signed an informed consent form,and all cases were followed up forpregnancy outcome.Results:Among 141 NIPT-plus screen positive pregnant women,41 true posi-tive cases were detected by chromosomal karyotype analysis and CMA.The positive predictive value(PPV)for NIPT-plus screening for CNV was 29.08％(41/141).There was no statistically significant difference(P＞0.05)in the PPV of CNV detected by NIPT plus among different ages,indications and variant types.However,the PPV of CNV size＜10 Mb was significantly higher than that of CNV size≥ 10 Mb,and the difference was statistically signif-icant(39.62％vs.22.73％,P＜0.05).Among the 41 true positive cases,in addition to CNV,the CMA also detec-ted 7 cases of regions of Homozygosity(ROH),accounting for 17.07％(7/41)of the cases,two of which involved imprinted genes located on chromosomes 6 and 7.All continued pregnancy after genetic counselling and no signif-icant abnormalities were seen at neonatal follow-up after birth.Conclusions:NIPT-plus screening for fetal CNV has some clinical value,especially for CNV with fragment size＜10Mb,but accuracy needs to be further improved;CMA as a molecular diagnostic technique can detect ROH in cases where NIPT-plus suggests CNV abnormali-ties,and the combined use of the two techniques also opens new avenues for screening and diagnosis of prenatal imprinted diseases.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

The glymphatic system(GS)is a unique toxic sub-stance clearance system in brain,which is very important for maintaining the microenvironment stability of the central nervous system.The polarization distribution of aquaporin 4(AQP4)lo-cated in the terminal foot of astrocytes affects the function of GS and participates in the pathological progress of many neurodegen-erative diseases,but the detailed regulation mechanism of AQP4 polarization distribution has not been systematically summarized.Therefore,this paper systematically combs the mechanism of reg-ulating the polarization distribution of AQP4 from the perspective of the composition integrity of dystrophin-glycoprotein complex(DGC)and basement membrane foot complex,and summarizes the potential drug and non-drug therapies for targeted regulation of AQP4 polarization distribution at present,aiming at providing new target reference and theoretical basis for targeted regulation of AQP4 polarization to prevent and treat neurodegenerative dis-eases.

Objective:To investigate the value of coarse calcification ultrasound feature for the differential diagnosis of benign and malignant thyroid nodules and the China Thyroid Imaging Reporting and Data System (C-TIRADS) classification.Methods:A retrospective case series study was conducted. Two hundred and twenty solid thyroid nodules with coarse calcification confirmed by surgical pathology in 210 patients from January 2023 to February 2024 in Shanxi Province Cancer Hospital were selected. Using the postoperative pathological results as the gold standard, the nodules were divided into benign and malignant groups, and the ultrasound characteristics and specific features of coarse calcification of the nodules were compared between the two groups. Binary logistic regression analysis was used to screen for independent predictors of nodal malignancy in the coarse calcification features, and the independent predictors were assigned scores based on the C-TIRADS classification. The efficacy of C-TIRADS classification combined with independent predictors of nodal malignancy in the coarse calcification features for diagnosing malignant nodules was analyzed using receiver operating characteristic (ROC) curve.Results:The postoperative pathological findings of 220 thyroid nodules showed 70 (31.82%) were benign and 150 (68.18%) were malignant. The echogenicity, maximum diameter, orientation, margins of nodules and the location, number, promiscuity, peripheral soft tissue shadow of coarse calcification were compared between the benign and malignant groups, and the differences were statistically significant (all P < 0.05). Logistic regression analysis showed that the presence of coarse and irregular calcification ( OR = 7.20, 95% CI: 3.16-16.37, P < 0.001) and coarse calcification with peripheral soft tissue shadow ( OR = 7.87, 95% CI: 3.74-16.57, P < 0.001) were independent predictors for nodule malignancy. The area under the curve (AUC), sensitivity, specificity, and accuracy for diagnosing malignant nodules by C-TIRADS classification were 0.75, 66.67%, 81.43%, and 71.36%, respectively; the AUC, sensitivity, specificity, and accuracy for diagnosing malignant nodules by C-TIRADS classification combined with coarse and irregular calcification and peripheral soft tissue shadow were 0.88, 84.00%, 80.00%, and 82.73%, respectively; the difference in AUC for diagnosing malignant nodules with C-TIRADS classification alone and in combination with coarse calcification features was statistically significant ( Z = 4.69, P < 0.001). Conclusions:Coarse and irregular calcification and peripheral soft tissue shadow are risk factors for malignancy of thyroid nodules, and the diagnostic accuracy of the two in combination with C-TIRADS classification is high.

Objective:To explore the diagnostic value of quantitative analysis of contrast-enhanced ultrasound for the Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) thyroid nodules 4.Methods:A retrospective case series study was conducted. A total of 87 patients with thyroid nodules from Shanxi Province Cancer Hospital between October 2018 and July 2022 were selected. All patients were diagnosed as C-TIRADS 4 thyroid nodules by routine ultrasound and had DICOM storage format ultrasound contrast dynamic data. All 96 thyroid nodules in 87 patients had clear surgical and pathological results. Based on the contrast-enhanced ultrasound features of the nodules, the nodules were reclassified by using C-TIRADS according to 3 different criteria. VueBox analysis software was used to obtain dynamic contrast-enhanced ultrasound (DCE-US) quantitative parameters, the most effective quantitative parameters for diagnosing thyroid malignant nodules were obtained by using receiver operating characteristic (ROC) curves, and their optimal cut-off values were obtained. Based on ultrasound contrast and DCE-US quantitative parameters, the nodules were reclassified by using C-TIRADS. Based on pathological results, the malignancy rates of nodules classified by C-TIRADS based on the conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters were calculated. ROC curves were drawn to compare the diagnostic efficacy of conventional ultrasound, contrast-enhanced ultrasound, and contrast-enhanced ultrasound combined with DCE-US quantitative parameters for thyroid malignant nodules.Results:Among the 96 thyroid nodules, the malignancy rates of C-TIRADS 4a, 4b, and 4c nodules evaluated by conventional ultrasound were 50.0% (17/34), 72.1% (31/43) and 100.0% (19/19), respectively, which were not within the reference range provided by the C-TIRADS guideline. After reclassifying the nodules according to the contrast-enhanced ultrasound standards, the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/2), 25.0% (2/8), 31.3% (5/16), 71.9% (23/32), and 97.4% (37/38), respectively. Among them, the malignancy rate of the 4a type nodule was still relatively high, which was not within the reference range given by the C-TIRADS guideline. The area under the curve of DCE-US quantitative parameter peak intensity (PE) for diagnosing thyroid malignant nodules according to ROC curves was the largest with the optimal cut-off value of 2080.7a.u. Based on contrast-enhanced ultrasound and combined with PE, the nodules were classified again, and the malignancy rates of C-TIRADS 3, 4a, 4b, 4c, 5 of nodules were 0 (0/7), 9.1% (1/11), 27.3% (3/11), 83.3% (11/13), and 98.1% (53/54), respectively, all were within the reference range provided by the C-TIRADS guideline. ROC curve analysis showed that the AUC of contrast-enhanced ultrasound combined with DCE-US quantitative parameter PE for diagnosing thyroid malignant nodules was greater than that of conventional ultrasound and contrast-enhanced ultrasound (both P < 0.05); the optimal cut-off value was type 4b, with the sensitivity of 94.0%, the specificity of 89.7%, and the accuracy of 92.7%. Conclusions:The combination of contrast-enhanced ultrasound and DCE-US quantitative parameter PE is helpful for more accurate classification of C-TIRADS 4 thyroid nodules and improves the diagnostic efficiency of thyroid malignant nodules.

Alzheimer's disease(AD)presents a notable gender disparity in prevalence among elderly individuals, with elderly women being a high-risk group for AD onset.Researches have confirmed the effects of estrogen on the nervous system and cognitive function through in vitro and animal models.Throughout their reproductive years, women undergo various life events such as menarche, menopause, pregnancy, childbirth, miscarriage, relevant surgeries, and medication, all of which can impact their endocrine status and subsequently influence brain function.As a result, there is a growing body of epidemiological evidence investigating the relationship between women's menstrual and reproductive factors and AD.Despite some controversies, this article offers a thorough review of current epidemiological research on the link between different menstrual and fertility factors in women and AD.