ObjectiveTo analyze the epidemiological trends and characteristics of brucellosis in humans (hereinafter referred to as brucellosis) in Tangshan City, Hebei Province from 2016 to 2023, and to provide a scientific basis for formulating brucellosis prevention and control strategies in the region. MethodsThe incidence data of human brucellosis in Tangshan City from 2016 to 2023 were collected from the China Disease Prevention and Control Information System. The diagnosis time, infection route, and clinical characteristics of the cases were obtained from the case investigation reports. Descriptive epidemiological methods were used to analyze the temporal, spatial, demographic distributions, and clinical characteristics of human brucellosis. Brucella species were identified using agglutination tests with bacterial suspension and A/M antigen-positive serum. ResultsA total of 2 193 cases of human brucellosis were confirmed and clinically diagnosed in Tangshan City from 2016 to 2023, with the peak incidence occured from March to August, and which exhibited distinct geographic distribution patterns. The highest incidence rate was found in people aged 60‒<70 years. The occupation of cases were primarily farmers. The incidence rate in males (528/100 000) was higher than that in females (184/100 000). All cases had confirmed exposure to infected animals or contaminated animal products. ConclusionThe epidemic of human brucellosis in Tangshan exhibited an overall steady downward trend from 2016 to 2023, except for a slight increase in 2016 and 2021, with the incidence rate controlled at 289/100 000‒335/100 000. The prevention and control situation of human brucellosis still remains severe, with the highest incidence rate in the eastern region of Tangshan, which are characterized by the breeding, slaughtering, and processing of cattle and sheep. Therefore, it it is necessary to enhance the prevention and control of human brucellosis among the personnel engaged in these industries in the eastern areas.

Based on the traditional Chinese medicine(TCM) theory of "kidney-brain interaction", a two-sample Mendelian randomization(MR) analysis was conducted to investigate the causal effects of chronic kidney disease(CKD) on Alzheimer's disease(AD) and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD. From the perspective that CKD is closely related to the core pathogenesis of AD, namely "kidney deficiency, essence loss, and marrow reduction", genome-wide association study(GWAS) data was used, with the inverse variance weighting(IVW) method as the main approach to reveal the causal association between CKD and AD. Sensitivity analysis was conducted to evaluate the robustness of the results. To further investigate the causal effects of CKD on AD, two different AD datasets were used as outcomes, and the urinary albumin-to-creatinine ratio(UACR) data was used as the exposure for a supplementary analysis. On this basis, the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored. The IVW analysis show that CKD(ieu-b-2: OR=1.084, 95%CI[1.011, 1.163], P=0.024; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.001], P=0.002) and UACR(ieu-b-2: OR=1.247, 95%CI[1.021, 1.522], P=0.031; ieu-b-5067: OR=1.001, 95%CI[1.000, 1.003], P=0.015) both have significant causal effects on AD in different datasets, with CKD increasing the risk of AD. The sensitivity analysis further confirmed the reliability of the results. Genetic studies have shown that CKD has a significant causal effect on AD, suggesting that controlling CKD is an important intervention measure for preventing and treating AD. Therefore, further research on CKD's role in AD is crucial in clinical practice. The research enriches the theoretical implication of "kidney-brain interaction", deepens the understanding of AD' etiology, and provides further insights and directions for the prevention and treatment of AD with TCM, specifically from a kidney-based perspective.
Humans ; Alzheimer Disease/genetics* ; Renal Insufficiency, Chronic/genetics* ; Kidney/metabolism* ; Brain/physiopathology* ; Genome-Wide Association Study ; Medicine, Chinese Traditional ; Mendelian Randomization Analysis

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

Objective To prepare monoclonal antibodies against bovine CD4 and identify their basic biological characteristics. Methods Recombinant bovine CD4 (rHis-BoCD4 and rGST-BoCD4) was successfully expressed and purified by constructing a prokaryotic plasmid of bovine CD4 gene. The bovine CD4 monoclonal antibody was produced using hybridoma technology. The subtype and potency of the monoclonal antibody were identified and analyzed by ELISA, while specificity was analyzed through indirect immunofluorescence assay (IFA) and Western-blot. Results Four hybridoma cell lines, namely, 1H4, 6A10, 3F9 and 4G10, stably secreting monoclonal antibodies against BoCD4 were successfully obtained. The subclasses of the monoclonal antibodies subclass 6A10 was IgG2b and the rest of the monoclonal antibodies were of IgM type. Western-blot results showed that the four anti-bovine CD4 mAb strains were able to specifically bind to the bovine CD4 protein expressed in vitro. Indirect immunofluorescence assay showed that four monoclonal antibodies were able to specifically recognize the natural bovine CD4 protein. Flow cytometry assay showed that 3F9 was best to recognize bovine natural CD4 molecules. Conclusion Four monoclonal antibody strains with high specificity to natural bovine CD4 protein were successfully prepared, which lays the foundation for the subsequent studies on the function of bovine CD4 and diagnosis and treatment of bovine T-lymphocyte diseases.
Animals ; Antibodies, Monoclonal/isolation & purification* ; Cattle ; CD4 Antigens/genetics* ; Hybridomas/immunology* ; Antibody Specificity/immunology* ; Mice ; Mice, Inbred BALB C ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect

OBJECTIVE: To analyze the significance of total vitamin D (tVD), total procollagen type I amino-terminal propeptide (tPINP) and β-CrossLaps (β-CTx) in the staging and prognosis of patients with multiple myeloma (MM). METHODS: A total of 54 patients with newly diagnosed MM admitted to the Second Affiliated Hospital of Fujian Medical University from 2020 to 2022 were selected as the observation group (MM group), and 50 healthy persons who underwent physical examinations in our hospital were selected as the control group. The expression levels of tVD, tPINP and β-CTx in the two groups were detected by chemiluminescence method. The differences in the expression levels of tVD, tPINP and β-CTx among MM patients at different ISS stages were analyzed. The expression levels of tVD, tPINP and β-CTx in MM patients with different levels of hemoglobin (Hb), serum calcium (Ca), creatinine (Crea), albumin (ALB), β₂-microglobulin (β₂-MG) and lactate dehydrogenase (LDH) were compared. The correlations between the expression levels of tVD, tPINP, β-CTx and the aforementioned clinical parameters were analyzed, respectively. The relationship between the expression levels of tVD, tPINP, β-CTx and the progression-free survival (PFS) of MM patients was analyzed. RESULTS: The expression level of tVD in the MM group was significantly lower than that in the control group (21.73±14.45 ng/ml vs 30.78±9.94 ng/ml, P =0.022). The expression level of β-CTx in the MM group was significantly higher than that in the control group (1.43±0.99 ng/ml vs 0.53±0.29 ng/ml, P =0.013). The tVD level in MM patients with ISS stage I-II was significantly higher than that of MM patients with ISS stage III (29.50±14.59 ng/ml vs 12.62±7.73 ng/ml, P =0.028), indicating that the higher the ISS stage, the lower the tVD level. The tPINP and β-CTx levels in MM patients with high Ca levels (>2.65 mmol/L) were significantly higher than those in patients with low Ca levels (≤2.65 mmol/L) (P =0.016, P =0.021). The tVD level of MM patients was positively correlated with the ALB level (r =0.570), tPINP was positively correlated with Ca and β₂-MG levels (r =0.791,r =0.673), and β-CTx was positively correlated with tPINP level (r =0.616). The PFS of the low tVD expression group was significantly lower than that of the high tVD expression group (P =0.041). CONCLUSION The expression level of tVD is decreased in MM patients, which can be used as an indicator to evaluate the disease stage and prognosis of the patients. The β-CTx expression level is increased in MM patients. tPINP and β-CTx may be correlated with clinical symptoms such as osteolytic lesions and renal function changes in MM patients.
Humans ; Multiple Myeloma/pathology* ; Procollagen/blood* ; Vitamin D/blood* ; Prognosis ; Peptide Fragments/blood* ; Collagen Type I/blood* ; Female ; Male ; Middle Aged ; Aged ; Neoplasm Staging

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Long non-coding RNA(lncRNA)can affect the occurrence and development of diseases by directly or indirectly regulating target genes and their signal pathways.With the deepening of research,more and more lncRNA have been found to be involved in regulating the occurrence,development and drug resistance of multiple myeloma(MM).Therefore,it is necessary to study the role and molecular mechanism of abnormal expression of lncRNA in MM,which can provide theoretical basis for clinical diagnosis and targeted therapy.

Objective:To evaluate the efficacy of ultrasound-guided semispinalis capitis plane (SCP) block for treatment of occipital neuralgia (ON).Methods:This was a prospective study. Ninety patients of both sexes, aged 29-66 yr, suffering ON for 3 months-6 yr in Zibo Municipal Hospital from January 2022 to December 2023, were divided into 3 groups ( n=30 each) using a random number table method: combination of greater occipital nerve (GON) block and the third occipital nerve (TON) block group (group GT), SCP block via the medial head of semispinalis capitis muscle (SCM) group (group Sm), and SCP block via the space between obliquus capitis inferior and C 2, 3 facet joint (OCI-C 2, 3) group (group OC). In GT group, the analgesic and anti-inflammatory compound solution 2.5 ml was injected around GON in the SCM-OCI space at the C 2 level of the cervical vertebra and at the lateral surface of C 2, 3 facet joint. In Sm group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the medial head of SCM at the level of C 1. In OC group, the analgesic and anti-inflammatory compound solution 5 ml was injected into the OCI-C 2, 3 space in the deep part of SCM. The Visual Analogue Scale (VAS) score and Pittsburgh Sleep Quality Index (PSQI) score were recorded before treatment (T 1) and at 1, 3, 7, 10 and 14 days after treatment (T 2-6), and then the rates of pain relief and improvement in sleep quality were calculated. The time spent in blocking, onset time of blocking, completion time of blocking, duration of block, and occurrence of adverse reactions within 24 h after block were recorded. Results:There were no significant differences in VAS scores and PSQI scores at T 1-3 and T 5-6 among the three groups ( P>0.05), and VAS and PSQI scores were significantly higher at T 4 in Sm group than in OC and GT groups ( P<0.05). Compared with GT group, the time spent in blocking was significantly shortened, the onset time and completion time of block was prolonged, and the duration of block was shortened in Sm group, and the time spent in blocking was significantly shortened, the onset time and completion time of block was shortened ( P<0.05), and no significant change was found in the duration of block in OC group ( P>0.05). No severe complications were observed in the three groups. Conclusions:Compared with the combination of GON and TON blocks, ultrasound-guided SCP block for treating ON is simple and highly safe, SCP block via the OCI-C 2, 3 space has rapid onset and long duration, leading to significant improvements in pain and sleep quality, and it can be used as the first-choice block method for treating ON.