Demyelinating disorders of the nervous system constitute a broad spectrum of neurological conditions characterized by the depletion of myelin sheaths accompanied by inflammatory cell infiltration, manifesting in either the central or peripheral nervous system. The former primarily encompasses conditions such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), while the latter is exemplified predominantly by Guillain-Barre syndrome (GBS). Recent investigations have revealed that dyslipidemia may be related to the occurrence and development of neurological demyelination, but there are fewer analyses and summaries of related advances in China. Consequently, this review aims to comprehensively outline advancements in research concerning the correlation between dyslipidemia and neurological demyelinating disordersand discusses in depth the interrelationship between dyslipidemia and neurological demyelinating diseases, so as to provide reference for the prevention and treatment of neurological demyelinating diseases.

Objective:To evaluate the role of spinal Leucine-rich Repeat Kinase 2 (LRRK2) in neuropathic pain in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6-7 weeks, weighing 210-245 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (C group), neuropathic pain group (NP group), low dose GNE-7915 group (low-dose GNE-7915 group), medium-dose GNE-7915 group (medium-dose GNE-7915 group), and high-dose GNE-7915 group (high-dose GNE-7915 group). Neuropathic pain was induced by the spared nerve injury in anesthetized rats. At 7 days after developing the model, LRRK2 inhibitor GNE-7915 12.5, 25.0 and 50.0 mg/kg were intraperitoneally injected in low-, medium- and high-dose GNE-7915 groups, respectively. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model, at 7 days after developing the model, and at 4 h after injecting the inhibitor. After measurement of the pain threshold, the rats were sacrificed and the spinal cord tissues were taken for determination of the positive expression of ionized calcium-binding adapter molecule 1(Iba-1) (by immunofluorescence staining), contents of interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and IL-18 (by enzyme-linked immunosorbent assay), positive expression of phosphorylated LRRK2 (p-LRRK2) (by immunofluorescence staining), and expression of LRRK2, IL-1β, MCP-1 and IL-18 (by immunoblotting). The ratio of p-LRRK2/LRRK2 was calculated. Results:Compared with C group, the MWT was significantly decreased, the TWL was shortened, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were increased, and the expression of IL-1β, MCP-1 and IL-18 proteins was up-regulated in NP group ( P<0.05). Compared with NP group, the MWT was significantly increased, the TWL was prolonged, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were decreased, and the expression of IL-1β, MCP-1 and IL-18 proteins was down-regulated in low-, medium- and high-dose GNE-7915 groups ( P<0.05). Conclusions:LRRK2 in the spinal cord may be involved in the pathophysiological mechanism of neuropathic pain by activating microglia and inducing inflammatory responses in rats.

Objective:This study analyzed the expression of CD24 antigen on bone marrow plasma cells (BMPC) of patients with multiple myeloma (MM) and the predictive value of induction therapy.Methods:This clinical observational study utilized 258 MM patients samples treated at the Hematology Department of Beijing Jishuitan Hospital who met the inclusion criteria in the Department of Hematology, Capital Medical University, from August 12th, 2022 to February 1st, 2024. According to the different stages of the disease, patients were divided into three groups: 78 cases of Newly Diagnosed Multiple Myeloma(NDMM) (42 males and 36 females, aged 62±11), 56 cases of the relapse refractory group (34 males and 22 females, aged 64±9), and 124 cases of the disease remission group (68 males and 56 females, aged 62±10). Multiparameter flow cytometry (MFC) was used to detect the expression level of CD24 antigen on BMPC and the relationship between CD24 and MM disease status. The clinical data and test results of 78 NDMM patients at initial diagnosis were retrospectively analyzed, including gender, age, MFC detection of the positive expression rate of antigens (CD19, CD20, CD24, CD27, CD56), the results of efficacy evaluation after induction therapy, ISS staging, R-ISS staging, blood hemoglobin, β2-microglobulin, human serum albumin, serum creatinine, lactate dehydrogenas, correction of calcium, BMPC ratio, and the results of FISH. The patients were divided into a deep remission group [including complete remission (CR) and very good partial remission (VGPR)] with 43 cases and a non-deep remission group (non CR and VGPR) with 17 cases according to the difference of antigen positive expression rate after induction therapy. The differences of antigen expression on BMPC between the two groups were compared. Binary logistic regression was used to analyze the relationship between the expression of each antigen and the efficacy after induction therapy in patients, and the results showed that CD24 was more correlated with the achievement of deep remission after induction therapy than other antigens. Therefore, taking the positive expression rate of CD24 in NDMM patients at the initial diagnosis and deep remission after induction therapy as the research objects, the predictive value of CD24 for NDMM patients reaching deep remission after induction therapy was analyzed by using receiver operating characteristic curve (ROC), and the optimal cutoff value was obtained. NDMM was divided into two groups according to the cut-off value, and the differences between the two groups in clinical baseline data and prognostic indicators were compared.Results:The positive rates of plasma cell CD24 expression in the NDMM group, the relapse refractory group and the disease remission group were 2.18 (95% CI 0.08-81.85)%, 3.81 (95% CI 0.10-64.56)%, 8.74 (95% CI 0.79-95.55)% respectively. Compared with the disease remission group, the NDMM and relapse refractory group was lower ( Z=-7.889, -5.282, respectively, P<0.001). Univariate analysis showed that there was a significant difference in the positive expression rate of CD24 at initial diagnosis between the deep remission group and the non-deep remission group ( Z=-3.265, P<0.001), while there was no significant difference in CD19 ( Z=-0.271, P=0.787), CD20 ( Z=-0.205, P=0.837), CD27 ( Z=-0.582, P=0.560), and CD56 ( Z=-0.328, P=0.743) between the two groups. Binary logistic regression analysis showed that compared with other antigens [CD19 ( OR=1.045, 95% CI 0.975-1.120, P=0.217), CD20 ( OR=1.000, 95% CI 0.971-1.030, P=0.976), CD27 ( OR=0.997, 95% CI 0.977-1.016, P=0.734), CD56 ( OR=1.006, 95% CI 0.990-1.006, P=0.449)], the expression of CD24 ( OR=0.423, 95% CI 0.990-1.006, P=0.449) on BMPC in NDMM patients was most closely related to the achievement of deep remission was achieved after induction therapy. The lower the proportion of CD24 at the initial diagnosis was, the lower the probability of achieving deep remission after induction therapy was. The area under the curve (AUC) of CD24 in predicting deep remission after induction therapy was 0.772 (95% CI 0.655-0.889, P=0.001), with a sensitivity of 60.50%, a specificity of 85.00%, and the optimal critical value was 2.21%. Compared with the group with plasma CD24 positive rate>2.21%, the group with plasma CD24 positive rate<2.21% had a higher proportion of male (39.47%vs 65.00%, χ2=5.092, P=0.024), ISS stagingⅢ (41.67% vs 58.33%, χ2=6.175, P=0.046), β2 microglobulin (3.19 mg/L vs 4.14 mg/L, Z=-2.257, P=0.024), and BMPC [(8.672±1.827)% vs (19.530±3.188)%, t=-2.963, P=0.004] detected by MFC, and the differences were statistically significant. Conclusions:The low positive rate of plasma cell CD24 is closely related to the higher tumor burden and the worse disease status of MM patients. In addition, the positive expression rate of CD24 is at initial diagnosis can predict the efficacy achieved after induction therapy, and the lower positive rate of CD24 is, the worse the efficacy achieved after induction therapy. At the same time, MFC detection of CD24 is convenient and efficient in the evaluation and prediction of MM.

Objective To compare the efficacy and safety of three kinds of endoscopic minimally invasive treatment of internal hemorrhoids.Methods The clinical data of 222 patients with internal hemorrhoids who underwent endoscopic treatment in Shangyu People's Hospital of Shaoxing from January 2020 to June 2023 were retrospectively analyzed.According to the treatment method,the patients were divided into simple sclerotherapy group(40 cases),simple ligation group(114 cases)and combined group(68 cases).The perioperative indexes,postoperative adverse events,effective rate and satisfaction of three groups were compared.Results There was significant difference in operation time among three groups(P＜0.05),and the operation time of simple ligation group was the shortest.There was no significant difference in postoperative hospital stay among three groups(P＞0.05).The incidences of anal distention,postoperative pain and dysuria in simple ligation group and combined group were significantly higher than those in simple sclerotherapy group(P＜0.05).The incidence of postoperative bleeding in simple ligation group was significantly higher than that in simple sclerotherapy group and combined group(P＜0.05).There was significant difference in treatment effectiveness among three groups(P＜0.05),and combined treatment had the best effect.The satisfaction of three groups was higher,and the difference was not statistically significant(P＞0.05).Conclusion The three endoscopic minimally invasive treatment methods for internal hemorrhoids are safe and effective.Ligation combined with sclerotherapy can effectively improve symptoms,and the postoperative delayed bleeding are low,which is a safe and efficient treatment method.

Objective To observe the value of habitat model based on lung CT for predicting brain metastasis(BM)of lung adenocarcinoma with epidermal growth factor receptor(EGFR)mutation.Methods Data of plain lung CT of 198 lung adenocarcinoma patients with EGFR-mutant were retrospectively analyzed.The patients were divided into training set(n=138)and test set(n=60)at the ratio of 7∶3,and further divided into BM subgroup and non-BM subgroup in each set.Then a logistic regression(LR)clinical model was constructed using variables being statistically different between subgroups in training set.For features extracted from tumor and subregion of tumor,radiomics models and habitat models were constructed based on random forest,Gaussian process(GP)and support vector machine(SVM)algorithms,and the best radiomics and habitat models with generalization ability were screened.LR combined model was constructed based on the predicted values of the best radiomics and habitat models with generalization ability,as well as the clinical model.Then receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting BM of lung adenocarcinoma with EGFR-mutant.Spearman correlation analysis was performed to observe the correlations between Ki-67 and habitat features of lung adenocarcinoma with EGFR-mutant.Results AUC of LR clinical model,GP radiomics model,SVM habitat model and LR combined model for predicting BM of lung adenocarcinoma with EGFR-mutant was 0.700,0.726,0.801 and 0.834 in training set,0.754,0.600,0.715 and 0.848 in test set,respectively.AUC of LR combined model was higher than that of LR clinical model in training set(P＜0.001),also higher than that of GP radiomics model in test set(P=0.010).Compared with GP radiomics model and SVM habitat model,the performance of LR combined model was significantly and positively improved in training set(integrated discrimination improvement index[IDI]=8.60%,8.55%,both P＜0.001).Ki-67 level of EGFR-mutant lung adenocarcinoma was lowly and positively correlated with habitatmap_original_glszm_lalgle extracted from habitat map(│rs│=0.201,P=0.004).Conclusion The habitat model based on lung CT could be used to predict BM of lung adenocarcinoma with EGFR-mutant effectively.

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts,often misdiagnosed due to its similarity to many infectious and non-infectious diseases.This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics,including methotrexate,leflunomide,and infliximab,leading to recurrent joint pain,poorly controlled rheumatoid arthritis activity,and persistent elevation of white blood cell counts.Abdominal CT revealed a pelvic mass and right ureteral dilation.Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules,indicating actinomycosis.The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide,hydroxychloroquine sulfate,and tofacitinib,resulting in improved joint symptoms and normalized white blood cell counts.After 2 years of follow-up,the patient remained stable with no recurrence.This case highlights the importance of clinicians being vigilant for infections,particularly chronic,occult infections from rare pathogens,in rheumatoid arthritis patients on potent immunosuppressants and biologics,advocating for early screening and diagnosis.

Demyelinating disorders of the nervous system constitute a broad spectrum of neurological conditions characterized by the depletion of myelin sheaths accompanied by inflammatory cell infiltration, manifesting in either the central or peripheral nervous system. The former primarily encompasses conditions such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), while the latter is exemplified predominantly by Guillain-Barre syndrome (GBS). Recent investigations have revealed that dyslipidemia may be related to the occurrence and development of neurological demyelination, but there are fewer analyses and summaries of related advances in China. Consequently, this review aims to comprehensively outline advancements in research concerning the correlation between dyslipidemia and neurological demyelinating disordersand discusses in depth the interrelationship between dyslipidemia and neurological demyelinating diseases, so as to provide reference for the prevention and treatment of neurological demyelinating diseases.

Female ; Humans ; Pregnancy ; Septate Uterus ; Uterus/surgery* ; Hysteroscopy/methods* ; Estrogens ; Tissue Adhesions/surgery* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. METHODS: Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. RESULTS: A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. CONCLUSIONS This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; Adenocarcinoma ; Cancer-Associated Fibroblasts ; Prognosis ; Tumor Microenvironment ; Sulfotransferases