Exploration of shared gene signatures and molecular mechanisms between type 2 diabetes and osteoporosis.

Type 2 diabetes mellitus (T2D) and osteoporosis (OP) are systemic metabolic diseases and often coexist. The mechanism underlying this interrelationship remains unclear. We downloaded microarray data for T2D and OP from the Gene Expression Omnibus (GEO) database. Using weighted gene co-expression network analysis (WGCNA), we identified co-expression modules linked to both T2D and OP. To further investigate the functional implications of these associated genes, we evaluated enrichment using ClueGO software. Additionally, we performed a biological process analysis of the genes unique in T2D and OP. We constructed a comprehensive miRNA-mRNA network by incorporating target genes and overlapping genes from the shared pool. Through the implementation of WGCNA, we successfully identified four modules that propose a plausible model that elucidates the disease pathway based on the associated and distinct gene profiles of T2D and OP. The miRNA-mRNA network analysis revealed co-expression of PDIA6 and SLC16A1; their expression was upregulated in patients with T2D and islet ß-cell lines. Remarkably, PDIA6 and SLC16A1 were observed to inhibit the proliferation of pancreatic ß cells and promote apoptosis in vitro, while downregulation of PDIA6 and SLC16A1 expression led to enhanced insulin secretion. This is the first study to reveal the significant roles of PDIA6 and SLC16A1 in the pathogenesis of T2D and OP, thereby identifying additional genes that hold potential as indicators or targets for therapy.

m6A-related lncRNAs as potential biomarkers and the lncRNA ELFN1-AS1/miR-182-5p/BCL-2 regulatory axis in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid subtype. However, unsatisfactory survival outcomes remain a major challenge, and the underlying mechanisms are poorly understood. N6-methyladenosine (m6A), the most common internal modification of eukaryotic mRNA, participates in cancer pathogenesis. In this study, m6A-associated long non-coding RNAs (lncRNA) were retrieved from publicly available databases. Univariate, LASSO, and multivariate Cox regression analyses were performed to establish an m6A-associated lncRNA model specific to DLBCL. Kaplan-Meier curves, principal component analysis, functional enrichment analyses and nomographs were used to study the risk model. The underlying clinicopathological characteristics and drug sensitivity predictions against the model were identified. Risk modelling based on the three m6A-associated lncRNAs was an independent prognostic factor. By regrouping patients using our model-based method, we could differentiate patients more accurately for their response to immunotherapy. In addition, prospective compounds that can target DLBCL subtypes have been identified. The m6A-associated lncRNA risk-scoring model developed herein holds implications for DLBCL prognosis and clinical response prediction to immunotherapy. In addition, we used bioinformatic tools to identify and verify the ceRNA of the m6A-associated lncRNA ELFN1-AS1/miR-182-5p/BCL-2 regulatory axis. ELFN1-AS1 was highly expressed in DLBCL and DLBCL cell lines. ELFN1-AS1 inhibition significantly reduced the proliferation of DLBCL cells and promoted apoptosis. ABT-263 inhibits proliferation and promotes apoptosis in DLBCL cells. In vitro and in vivo studies have shown that ABT-263 combined with si-ELFN1-AS1 can inhibit DLBCL progression.

Dyslipidemia in the First 100 days and the Association with Acute Graft-versus-host Disease after Allogeneic Stem Cell Transplantation: A Single-center Retrospective Study in China.

Dyslipidemia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The interaction between post-transplant hyperlipidemia and acute graft-versus-host disease (aGVHD) is uncertain. In this study, we performed a retrospective study to explore the relationship between dyslipidemia and aGVHD and the potential mechanism of aGVHD on dyslipidemia in 147 recipients who underwent allo-HSCT. The lipid profiles, transplantation details, and other laboratory data of the subjects were collected in the first 100 days post-transplantation. Our results indicated 63 patients with new-onset hypertriglyceridemia and 39 patients with new-onset hypercholesterolemia. A total of 57 (38.8%) patients developed aGVHD after transplantation. In a multifactorial analysis, aGVHD was an independent factor in the development of dyslipidemia in recipients (P < 0.05). After transplantation, the median LDL-C level of patients with aGVHD was 3.04 mmol/L (standard deviation value (SD): 1.36 mmol/L, 95% confidence interval (CI): 2.62, 3.45 mmol/L), and the LDL-C level in patients without aGVHD was 2.51 mmol/L (SD: 1.38 mmol/L, CI: 2.67, 3.40 mmol/L) (P < 0.05). Female recipients had higher lipid levels than males (P < 0.05). LDL levels (≥ 3.4 mmol/L) post-transplant were an independent risk factor for the development of aGVHD (OR = 0.311, P < 0.05). In conclusion, larger sample studies are anticipated to confirm our preliminary result, and an accurate mechanism between lipid metabolism and aGVHD needs to be determined in the future.

[Comparison of Acute Graft-Versus-Host Disease Mouse Models Established by TBI and BU/CY Conditioning Regimens].

OBJECTIVE: To investigate the effect of acute graft-versus-host disease (aGVHD) mouse models established respectively by total body irradiation (TBI) and busulfan combined with cyclophosphamide (BU/CY) conditioning regimens after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Bone marrow cells and splenic mononuclear cells were isolated respectively from femur, tibia, and spleen of C57BL/6 male mice (H-2Kb) which were selected as donors. After TBI pretreatment, BALB/c female mice (H-2Kd) were injected with donor bone marrow cells 1×107/50 µl and splenic mononuclear cells 2×107/100 µl through caudal vein, while CB6F1 female mice (H-2Kd/b) with donor bone marrow cells 2×107/100 µl and splenic mononuclear cells 1×108/500 µl after BU/CY pretreatment. The successful establishment of the aGVHD models were determined by post-transplant manifestations, rate of chimerism, target organ damage, etc. Results: After transplantation, mice of both groups showed listlessness, low activity, continued weight loss, and typical manifestations of aGVHD such as alopecia, hunched posture, diarrhea, and anal swelling. and died within 4 weeks. Flow cytometry detection showed complete chimerism in all the mice. Pathological examination of skin, intestines, liver, lung, and spleen tissues showed obvious aGVHD pathological changes. However, the weight loss, ruffled fur, and alopecia combined with severe scurf on those hair-free areas were significantly apparent in TBI group than BU/CY group, as well as higher aGVHD score, and the differences were statistically significant (P<0.05). CONCLUSION: Both TBI and BU/CY as conditioning regimens can successfully establish stable mouse models of aGVHD after fully allo-HSCT and haploidentical HSCT for further research about mechanism of aGVHD. BU/CY conditioning regimen can more truly simulate physiological status in vivo of patients with chemotherapy based conditioning regimen, while TBI conditioning regimen shows significantly more typical aGVHD symptoms and easier to operate.

Management of dyslipidemia after allogeneic hematopoietic stem cell transplantation.

Dyslipidemia is one of the complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is often underestimated and undertreated. Dyslipidemia in allo-HSCT recipients has been confirmed to be associated with endocrine dysfunction, acute and chronic graft-versus-host disease (aGVHD and cGVHD), immunosuppressive agent application, etc. However, few studies have illustrated the accurate molecular signaling pathways involved in dyslipidemia, and there are no standard guidelines for dyslipidemia management after HSCT. This review will discuss the pathogenesis of dyslipidemia, especially the association with aGVHD and/or cGVHD. Comprehensive treatment methods for dyslipidemia after HSCT will also be summarized.

Factors contributing to comorbid depressive symptoms in adult people with newly diagnosed epilepsy: A 12-month longitudinal study.

OBJECTIVES: We aimed to investigate the point prevalence of comorbid depressive symptoms from the time of newly diagnosed epilepsy to 12 months and to identify the factors contributing to comorbid depressive symptoms over a 12-month period in patients with newly diagnosed epilepsy (PWNDE). METHODS: A consecutive cohort of PWNDE from the First Hospital of Jilin University was recruited. Depressive symptoms were evaluated using the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy scale (C-NDDI-E). Multivariate stepwise logistic regression models were used to confirm the factors contributing to depressive symptoms in patients. RESULTS: The point prevalence of depressive symptoms among PWNDE slightly decreased from 24.8% at baseline to 22.3% at 12 months. A MoCA score < 26 was identified as an independent risk factor contributing to depressive symptoms at baseline (OR = 2.419, 95% CI: 1.093-5.350, P = 0.029) and at 12 months (OR = 3.007, 95% CI: 1.223-7.390, P = 0.016). The adjusted OR for depressive symptoms in female patients was 0.365 (95% CI: 0.171-0.779, P = 0.009) compared with male patients. Depressive symptoms at baseline (OR = 4.539, 95% CI: 1.973-10.445, P < 0.001) were identified as significant predictors of depressive symptoms at 12 months. CONCLUSION: There was a slight decrease in the prevalence of comorbid depressive symptoms in PWNDE over the 12-month period after epilepsy diagnosis. Cognitive impairment and baseline depressive symptoms were independent risk factors for comorbid depressive symptoms at 12 months.

Sex differences in factors associated with quality of life in patients with epilepsy in Northeast China.

OBJECTIVE: We aimed to investigate sex differences in factors associated with poor quality of life (QOL) in a cohort of patients with epilepsy (PWE) in Northeast China. METHODS: A consecutive cohort of 221 PWE from the First Hospital of Jilin University was recruited. The Chinese versions of the Patient Health Questionnaire-9 (PHQ-9), the Beck Anxiety Inventory (BAI), and the Quality of Life in Epilepsy Inventory (QOLIE-31) were used to measure depressive symptoms, anxiety symptoms, and the QOL. RESULTS: A total of 221 adult PWE participated in this study. In the multivariate regression model, three independent factors were found to be significantly associated with the total QOLIE-31 score in men: epilepsy duration (p = 0.007), the PHQ-9 score (p < 0.001), and the BAI score (p < 0.001). As for the subscale domain of QOL, marital status showed a relationship with cognitive function (p = 0.047), and residence was related with medication effects (p = 0.034). Two independent factors were found to be significantly associated with the total QOLIE-31 score in women: the PHQ-9 score (p < 0.001) and the BAI score (p < 0.001). The education level of women was positively associated with three subdomain scores of QOL, including overall QOL (p < 0.001), emotional well-being (p = 0.028), and energy/fatigue (p = 0.025). CONCLUSION: We found that high levels of depressive and anxiety symptoms are strong predictors of a poor QOL in both men and women. Sex differences also occur in several demographic and clinical factors influencing the overall QOL or subscale domain scores such as epilepsy duration, marital status, and educational level. Timely diagnosis and treatment of psychiatric comorbidities might be crucial for improving the QOL in both men and women.

Clinical features of anti-leucine-rich glioma-inactivated 1 encephalitis in northeast China.

AIM: To examine the clinical characteristics, laboratory tests, imaging and electroencephalography presentation, treatment, and prognosis of anti-leucine-rich glioma-inactivated 1 (anti-LGI1) encephalitis and improve the awareness of this disease. METHOD: We performed a retrospective analysis of the clinical data of 41 patients who were diagnosed with anti-LGI1 encephalitis. Their clinical characteristics, laboratory tests, and imaging and electroencephalography data were collected, and the treatment results and prognosis were evaluated. The modified Rankin Scale (mRS) was used to evaluate neurological function. RESULTS: A total of 41 patients were included in the study, the average follow-up time is 33.0 months.The initial symptoms included cognitive impairment (n = 16, 39.0%),faciobrachial dystonic seizures (FBDS) (n = 12, 29.3%), grand mal seizures (n = 5, 12.2%) hallucinations (n = 4, 9.8%), loss of consciousness (n = 2, 4.9%), nausea and vomiting (n = 1, 2.4%),and head discharge-like sensation and radiate one limb (n = 1, 2.4%). There were 20 and 21 patients in the good (mRS ≤ 2) and poor (mRS > 2) prognosis groups, respectively. In the good prognosis group, the initial symptoms included faciobrachial dystonic seizures (FBDS) (n = 6, 30.0%), cognitive impairment (n = 6, 30.0%), hallucinations (n = 4, 20.0%), grand mal seizures (n = 3, 15.0%), loss of consciousness (n = 2, 10.0%), and nausea and vomiting (n = 1, 5.0%). There were 10 patients with hyponatremia. Magnetic resonance imaging (MRI) showed limbic system involvement in 12 patients (60.0%).17 patients (85.0%) recovered, 2 (10.0%) showed significant improvement, and 1 (5.0%) died after a mean follow-up period of 36.9 months. In the poor prognosis group, the initial symptoms included FBDS (n = 6, 28.5%), cognitive impairment (n = 10, 47.6%), grand mal seizures (n = 2, 9.5%), and electric shock-like sensation in the left limbs (n = 1, 4.7%). There were 20 patients with hyponatremia. MRI showed limbic system involvement in 11 patients (52.4%). 11 patients (52.4%) recovered, 8 (38.1%) showed significant improvement, and 2 (9.5%) died after a mean follow-up period of 29.0 months. CONCLUSIONS: The clinical characteristics of anti-LGI1 encephalitis include hyponatremia, FBDS, epileptic seizures, hallucinations, cognitive impairment, and loss of consciousness, while the rarely seen characteristics are nausea, vomiting, and other autonomic dysfunctions and electric shock-like sensation. The appearance of hallucinations often indicates a good prognosis.Hyponatremia and elevated cerebrospinal fluid protein levels can be used as indicators that affect the prognosis of patients.Limbic system involvement has nothing to do with prognosis.Attention should be paid to early diagnosis and timely first-line immunotherapy.

Wilms tumor gent 1 (WT1)-specific adoptive immunotherapy in hematologic diseases.

As an attractive tumor-associated antigen (TAA), Wilms tumor gene 1 (WT1) is usually overexpressed in malignant hematological diseases. In recent years, WT1-specific adoptive immunotherapy has been the "hot spot" for tumor treatment. The main immunotherapeutic techniques associated with WT1 include WT1-specific cytotoxic T lymphocytes (CTLs), vaccine, and T cell receptor (TCR) gene therapy. WT1-based adoptive immunotherapy exhibited promising anti-tumorous effect with tolerable safety. There are still many limitations needed to be improved including the weak immunogenetics of WT1, immune tolerance, and short persistence of the immune response. In this review, we summarized the progress of productive technologies and the clinical or preclinical investigations of WT1-specific immunotherapy in hematological diseases.

Social anxiety is associated with poor quality of life in adults with epilepsy in Northeast China: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the factors influencing the level of social anxiety in patients with epilepsy (PWE) in Northeast China. We also identified the effect of social anxiety on the quality of life in these patients. METHODS: A consecutive cohort of 148 adult PWE from The First Hospital of Jilin University were recruited. In this sample, 116 patients had focal epilepsy, 20 had generalized epilepsy, and 12 had unclassified epilepsy. Depressive symptoms, social anxiety, and quality of life were evaluated using the Chinese version of the Patient Health Questionnaire 9 (PHQ-9), 20-item Social Phobia Scale (SPS), 20-item Social Interaction Anxiety Scale (SIAS), and Quality-of-Life Inventory in Epilepsy-31 (QOLIE-31), respectively. Multivariate linear regression analyses were employed to identify independent factors influencing SPS scores and SIAS scores. RESULTS: Correlation analysis suggested that sex, age at onset, seizure frequency over the last year, AED treatment model, >50% nocturnal seizures, PHQ-9 score, and QOLIE-31 score had a significant correlation with the SPS score. The age at onset, seizure frequency over the last year, AED treatment model, PHQ-9 score, and QOLIE-31 score correlated with the SIAS score. Multiple linear regression analysis showed that the total QOLIE-31 score (ß = - 0.481; p = 0.001) was inversely associated with the SPS score in PWE. Additionally, earlier age of onset (ß = -0.156; p = 0.022) and low total QOLIE-31 score (ß = -0.457; p = 0.001) were risk factors for high SIAS scores. CONCLUSION: We found that social anxiety was independently associated with poor quality of life. Earlier age of onset was also a risk factor for social anxiety. Future studies with large sample sizes are required to confirm our findings.

One-Year Analysis of Risk Factors Associated With Cognitive Impairment in Newly Diagnosed Epilepsy in Adults.

Cognitive impairment (CI) occurs in people with epilepsy, affecting their quality of life. This study aimed to identify factors associated with CI in adult patients with newly diagnosed epilepsy. Additionally, we sought to determine whether any particular cognitive function is impaired predominantly by anti-seizure medications or by other factors. We enrolled 229 patients with newly diagnosed epilepsy and 191 participants were followed up for 1 y. We used the Montreal Cognitive Assessment as a tool to quantify CI. The sub-item scores were also collected to assess whether any aspects of CI are predominantly affected by anti-seizure medication treatment. Subjective memory decline due to anti-seizure medications was also recorded. One-hundred-and-two participants (44.5%) had CI onset before anti-seizure medication treatment. Aging, low education level, stroke or brain surgery etiology, and anxious symptoms were identified as risk factors for CI before anti-seizure medications use. Brain surgery for the young, anxious status for the middle-aged, and depressive status for the elderly were risk factors for CI at different ages. The elderly PWE had worse memory than the others. PWE with TLE had worse cognition, especially in memory and naming. The overall impact of anti-seizure medications on cognition was mild. Refractory epilepsy was a predictor of cognitive decline. Subjective memory decline was predicted by high-risk treatment and by a finding of refractory epilepsy. Clarifying the risk factors for CI can help the physician to assess the probable risk of CI for each individual before the start of anti-seizure medication treatment, which may lead to better compliance.

Sex differences in marital status of people with epilepsy in Northeast China: An observational study.

PURPOSE: Our aims were to determine (1) whether the marriage rate was different between the sexes and (2) whether the influencing factors of marital status varied by sexes. METHODS: A cross-sectional study was performed among 475 people with epilepsy (PWE) in Northeast China. The demographic information and clinical data were gathered and recorded. Sex differences in the marriage rate of PWE and the related influencing factors were analyzed. Multivariate logistic regression analyses were used to investigate the independent factors influencing marital status in men and women, respectively. RESULTS: Among 475 participants, 219 (79.6%) men with epilepsy (MWE) were married, and 140 (70%) women with epilepsy (WWE) were married. In MWE, age, educational level, age at seizure onset, and disease duration were significantly different between the married men and the single men. In WWE, age, educational level, occupation and age at seizure onset showed significant differences between the married women and the single women. In the multiple logistic regression model, age and age at first seizure onset had an independent effect on the marital status in men with epilepsy. Multiple logistic regression analysis also revealed that age and age at first seizure onset were independent factors that influenced marital status in WWE. CONCLUSION: Men with epilepsy were more likely to marry than WWE. Age and the age of seizure onset independently affected the marital status of men and women.

Association Between SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 Polymorphisms and Responsiveness to Antiepileptic Drugs: A Meta-Analysis.

Background: SCN1A and SCN2A genes have been reported to be associated with the efficacy of single and combined antiepileptic therapy, but the results remain contradictory. Previous meta-analyses on this topic mainly focused on the SCN1A rs3812718 polymorphism. However, meta-analyses focused on SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, or SCN2A rs2304016 polymorphisms are scarce or non-existent. Objective: We aimed to conduct a meta-analysis to determine the effects of SCN1A rs2298771, SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms on resistance to antiepileptic drugs (AEDs). Methods: We searched the PubMed, Embase, Cochrane Library, WANFANG, and CNKI databases up to June 2020 to collect studies on the association of SCN1A and SCN2A polymorphisms with reactivity to AEDs. We calculated the pooled odds ratios (ORs) under the allelic, homozygous, heterozygous, dominant, and recessive genetic models to identify the association between the four single-nucleotide polymorphisms (SNPs) and resistance to AEDs. Results: Our meta-analysis included 19 eligible studies. The results showed that the SCN1A rs2298771 polymorphism was related to AED resistance in the allelic, homozygous, and recessive genetic models (G vs. A: OR = 1.20, 95% CI: 1.012-1.424; GG vs. AA: OR = 1.567, 95% CI: 1.147-2.142; GG vs. AA + AG: OR = 1.408, 95% CI: 1.053-1.882). The homozygous model remained significant after Bonferroni correction (P < 0.0125). Further subgroup analyses demonstrated the significance of the correlation in the dominant model in Caucasians (South Asians) after Bonferroni correction (GG + GA vs. AA: OR = 1.620, 95% CI: 1.165-2.252). However, no association between SCN1A rs2298771 polymorphism and resistance to AEDs was found in Asians or Caucasians (non-South Asians). For SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms, the correlations with responsiveness to AEDs were not significant in the overall population nor in any subgroup after conducting the Bonferroni correction. The results for SCN1A rs2298771, SCN1A rs10188577, and SCN2A rs2304016 polymorphisms were stable and reliable according to sensitivity analysis and Begg and Egger tests. However, the results for SCN2A rs17183814 polymorphism have to be treated cautiously owing to the significant publication bias revealed by Begg and Egger tests. Conclusions: The present meta-analysis indicated that SCN1A rs2298771 polymorphism significantly affects resistance to AEDs in the overall population and Caucasians (South Asians). There were no significant correlations between SCN1A rs10188577, SCN2A rs17183814, and SCN2A rs2304016 polymorphisms and resistance to AEDs.

Familial Hemiplegic Migraine With Progressive Cerebellar Ataxia Caused by a p.Thr666Met CACNA1A Gene Mutation in a Chinese Family.

Here, we describe the first case of familial hemiplegic migraine type 1 (FHM1) resulting from a T666M mutation in the CACNA1A gene of a Chinese individual. A 54-year-old female patient demonstrated extensive clinical manifestations, including transient paropsia, hemianesthesia, logaphasia, hemiplegia, migraine, fever, impaired consciousness, and progressive cerebellar ataxia. At admission, neurological examination showed a fever of 38.6°C, coma, bilateral pupillary constriction, left-sided deviation of both eyes, meningeal irritation, and bilateral positive Chaddock's sign. Brain magnetic resonance imaging (MRI) displayed only cerebellar atrophy. The pressure and white blood cells of the cerebrospinal fluid (CSF) were elevated. Her nine relatives also had similar clinical spectra. To further clarify the diagnosis, we conducted a genetic analysis on the family. The results of genetic testing showed that all seven living affected members carried the T666M mutation in the CACNA1A gene. This case report indicates that the diagnosis of FHM should be taken into account when a patient manifests migraine accompanied with hemiplegia, acute encephalopathy, and abnormal CSF. In addition, genetic testing is indispensable for the identification of some atypical attacks of hemiplegic migraine.