BACKGROUND:The immune-related pathogenesis of Alzheimer's disease is still unclear.Exploring the correlation between natural killer cells and cuproptosis mechanism in Alzheimer's disease patients through bioinformatics can provide a new direction for the study of the occurrence and development of Alzheimer's disease. OBJECTIVE:To screen the key genes related to cuproptosis of natural killer cells in peripheral blood of patients with Alzheimer's disease by bioinformatics analysis and verify them in clinical specimens. METHODS:The GEO online database was used to screen the transcriptome differentially expressed genes and natural killer cell related genes in the peripheral blood of patients with Alzheimer's disease,and intersected with the reported cuproptosis factors.Differentially expressed cuproptosis-related genes were obtained.Then RT-qPCR technology was used to verify the relative gene expression levels.The experimental samples were all from peripheral blood of hospitalized patients in the Department of Neurology of Anhui Provincial Hospital from 2021 to 2023,and 30 patients in the disease group and 20 in the control group were included according to the inclusion and exclusion criteria.The protein-protein interaction network was further constructed using the online GeneMANIA website.R language was used for immune infiltration analysis.Transcription factor prediction was conducted based on ENCODE database. RESULTS AND CONCLUSION:(1)The differential expression genes of peripheral blood transcriptome of Alzheimer's disease patients in GSE63060 data set,natural killer cell related genes in GSE168522 data set,and reported cuproptosis genes were used to screen and obtain four differentially expressed cuproptosis-related genes by using online Venn diagram tool,LASSO algorithm,and random forest machine learning methods:ferredoxin 1(FDX1),ATPase Cu2+transporting alpha polypeptide(ATP7A),pyruvate dehydrogenase El subunit beta(PDHB),and dihydrolipoamide succinyltransferase(DLST).(2)Clinical sample experiments showed that FDX1 and ATP7A were up-regulated in peripheral blood of patients with Alzheimer's disease(P<0.001),and were differentially expressed in different genotypes of apolipoprotein E4(P<0.01,P<0.001).The expression of PDHB and DLST in peripheral blood of patients with Alzheimer's disease was down-regulated(P<0.001),and there was no difference in apolipoprotein E4 genotypes(P>0.05).(3)Protein-protein interaction network found that 20 functional proteins were associated with key genes,and immunoinfiltration analysis showed that key genes were significantly associated with 12 immune cells(P<0.05 was considered to be relevant).(4)Bioinformatics analysis and experimental verification results suggest that FDX1,ATP7A,PDHB,and DLST are differentially expressed in Alzheimer's disease,may participate in the occurrence and development of Alzheimer's disease through the cuproptosis mechanism in peripheral blood natural killer cells,and also provide potential targets for the diagnosis and treatment of Alzheimer's disease.

Objective: To investigate the sleep quality in patients with burning mouth syndrome (BMS) and its influencing factors, providing a basis for developing sleep intervention measures to reduce the impact of BMS symptoms. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. A total of 150 patients with BMS and 150 healthy volunteers were enrolled as subjects in this study. The Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of patients with BMS. Visual analog scale (VAS) was used to assess the degree of oral mucosal pain, generalized anxiety disorder 7-item scale (GAD-7) was used to assess the frequency of anxiety symptoms, and the patient health questionnaire depression questionnaire (PHQ-9) was used to assess the frequency of depression symptoms. Univariate analysis was performed to identify potential influencing factors affecting sleep quality in patients with BMS, and multiple linear regression analysis was employed to determine independent risk factors. Results: The PSQI score for patients with BMS was 7.61 ± 4.29, which was significantly higher than that of healthy controls (P = 0.016). In the PSQI subscale analysis, patients with BMS exhibited increased sleep latency, decreased sleep duration, and lower sleep efficiency compared to healthy controls (P<0.05). Patients with BMS and comorbid sleep difficulties had significantly higher scores on GAD-7 and PHQ-9 compared to the patients with BMS without sleep difficulties (P<0.001), but there was no significant difference in pain VAS scores between the two (P = 0.068). Multiple linear regression analysis revealed that longer disease duration (>6 months), the presence of systemic concomitant symptoms (such as headache and mental stress), and higher depression scores were identified as independent risk factors affecting sleep quality in patients with BMS. Conclusion For patients with BMS, long course of illness, presence of headaches, high mental stress, and depressive symptoms may be independent factors affecting their sleep quality.

Pyroptosis, a form of inflammatory cell death mediated by the Gasdermins family, promotes the release of inflammatory mediators and activates immune cell populations such as NK cells, T cells and macrophages in the tumor microenvironment(TME) to exert immune-regulating and anti-tumor effects. Glioblastoma(GBM) is the most serious and malignant glioma, and the median survival of patients diagnosed with GBM is less than 2 years, and the presence of the blood-brain barrier makes it difficult to deliver drugs to the brain, thus affecting the effect of drugs against GBM. Therefore, it is important to explore new measures and mechanisms to treat GBM, which has a complex TME with a large number of immune cell populations that are often immunosuppressed by GBM. Cellular pyroptosis as a mode of cell death capable of activating immunity, has the effect of activating the body’s immunity to help reverse TME immunosuppression. This review will focus on the relationship between cell pyroptosis and the immune system, how cell pyroptosis affects the immune cell population of TME in GBM, and the new progress in drug research on cell pyroptosis pathways in GBM treatment, providing new directions and strategies for future clinical treatment of GBM.

Objective : To investigate the role of early inhibition of Toll⁃like receptor 4 (TLR4) in regulating hippampal neuroimmune responseto adolescent ratsafter neonatal hypoxic⁃ischemic brain damage(HIBD) . Methods: Postnatal day 7 rats were randomized into controlgroup , hypoxic ischemia (HI) group , and HI + TAK⁃242( the specific inhibitor of TLR4)(TAK⁃242) group. The expression of TLR4 in rat hippocampus was detected by immunohistochemistry at 3 days after HI. Immunofluorescence were used to determine the number of Iba⁃1 + , GFAP + , CD161 + , MPO + and CD3 + cells in the hippocampus at 21 days after HI. Immunohistochemistry was used to detect ICAM⁃1 and C3a expression in the hippocampal CA1 region ; and Western blot was used to detect tumor necrosis factor interleukin IL⁃1β , TNF⁃α and IL⁃10 expression. Results : Compared with control group , significantly raised TLR4 expression was observed in the left hippocampal CA1 , CA3 and DG regions(P < 0. 01 or P < 0. 05) , while the expression in the TAK⁃242 group lowered compared to the HI group (P < 0. 05) . The number of GFAP + cells in the CA1 area of the hippocampus in the TAK⁃242 group of neonatal rats decreased compared to which in the HI group at 21 days after HI(P < 0. 05) , but the number of CD3 + T lymphocytes in the hippocampal CA1 area of new born rats in the HI group increased compared to which in the Control group (P < 0. 05) , but the difference between TAK⁃242 and the Control group was not statistically significant. The number of Iba⁃1 + cells , MPO + cells , CD161 + cells , the expression of ICAM⁃1 and C3a in hippocampal CA1 region , and the expression of TNF⁃α , IL⁃1β and IL⁃10 in hippocampus of rats were not different among groups at 21 days after HIBD. Conclusion Early inhibition of TLR4 may ameliorate adolescent neuroimmune disorders by reducing the increase of hippocampal astrocytesafter neonatal HIBD.

Burning mouth syndrome (BMS) is a chronic oral and facial pain disorder characterized by burning pain in the oral mucosa, with multiple pathogenic factors including psychosocial, neuropathological, endocrine, and immune factors. There is still a lack of effective treatment options that have been demonstrated to work. With the development of research on the pathogenesis and treatment of BMS, multidisciplinary comprehensive treatment has gradually been introduced and become a new trend of diagnosis and treatment. Before multidisciplinary treatment, it is necessary to go through a full and comprehensive diagnosis and analysis, select the best comprehensive treatment plan, take the diagnosis and treatment of stomatology as the basis and premise, and apply other multidisciplinary combined treatment, including the treatment of concurrent diseases, psychological interventions, correction of bad habits, etc. A combination of laser therapy and psychological intervention is a more effective treatment method among the current treatment methods, with high comfort and good acceptance by patients. If necessary, mecobalamin tablets, clonazepam α-lipoic acid and other drugs can be used to nourish nerves and provide symptomatic treatment. The comprehensive multidisciplinary treatment of BMS is expected to become a new trend and provide a new strategy for improving the therapeutic effect.

Humans ; Female ; Fumarate Hydratase/genetics* ; Kidney Neoplasms ; Carcinoma, Renal Cell ; Leiomyomatosis ; Uterine Neoplasms

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Celastrol(Cel) is a active ingredient extracted from the natural compound Tripterygium wilfordii, which has good anti-tumor activity and other pharmacological effects. In recent years, studies have found that Cel has good anti-tumor activity and the ability to penetrate the blood-brain barrier(BBB), which is a potential drug for treating brain tumors. However, due to its severe liver toxicity, its clinical application prospects are questioned. Glioma(GMA) is a high incidence tumor in the brain, with a survival rate of<5% after diagnosis. Currently, there are few drugs available in clinical practice, so it is urgent to explore new drugs or drug delivery strategies to treat neuro GMA. Some studies have found that Cel has good anti-tumor activity and also has a good inhibitory effect on GMA, but the relevant mechanisms have not yet been systematically summarized and expanded. Since Cel still faces many problems in its clinical application in GBA, it is necessary to further consider what means to use in the future to enable Cel to efficiently pass through BBB and deliver it to the GMA site for Targeted therapy while reducing its hepatotoxicity. This article summarizes and expands the mechanisms and research results of Cel in various tumors and GMA in recent years. This article also reviews the new applications of Cel combined with nanocarriers in enhancing efficacy and reducing toxicity in recent years, in order to more clearly summarize the role of Cel in the treatment of GMA and how to systematically summarize the delivery methods of Cel through BBB, providing new treatment methods for clinical treatment of GMA.

Objective To analyze the detection level and distribution characteristics of occupational contraindications in pre-employment occupational health examination, and to provide a reference for relevant management departments to strengthen the control of personnel exposed to occupational hazards. Methods The data of pre-employment occupational health examination of 2 626 workers in a vehicle manufacturing enterprise from September 2018 to December 2020 were collected. The detection rate of occupational contraindications was calculated according to the judgement standard, and the distribution of occupational contraindications in different gender, length of service and age was analyzed. Results The detection rate of occupational contraindications was 13.71%, and there was no significant difference between the genders. The detection rate in the 40-45 years old group was the highest (31.75%), and the difference among the different age groups was statistically significant (χ²=30.16, P<0.01). Among the workers with different length of occupational employment, the detection rate was the highest in the group with 20-25 working years (30.65%), and the difference was statistically significant (χ²=30.20, P<0.01). Conclusion Relevant departments should strengthen the occupational health supervision and management of vehicle manufacturing enterprises and urge enterprises to pay attention to the pre-job occupational health examination as well as the health of workers.