Objective To investigate the protective effect and mechanism of heat acclimation(HA)on electromagnetic field(EMF)induced hippocampus neuron injury in mice.Methods Forty healthy BALB/c male mice(18～22 g,7 weeks old)were randomly divided into 4 groups(n=10):Control group(Con),HA group(34℃,30 d),EMF group(2 450 MHz,20 min/d,4 weeks)and HA+EMF group(HA preconditioning+EMF).Sucrose preference test was performed to evaluate sucrose preference levels of mice in each group.Tail suspension test and forced swimming test were utilized to observe the immobility time.Morris water maze test was conducted to determine the learning and memory capabilities.Pathological changes in the hippocampus were observed with HE staining.Immunohistochemical assay for Iba1(marker of microglia),CD68(marker of pro-inflammatory phenotype)and CD206(marker of anti-inflammatory phenotype)were used to detect the number and activation phenotype of microglia in the hippocampus.ELISA was applied to measure the levels of TNF-α,IL-1β,TGF-β and IL-10 in the hippocampus of each group.Western blotting was performed to determine the protein levels of HSP70 in the hippocampus.Results As compared with the Con group,the EMF group showed a decreased preference for sucrose(P<0.05),prolonged immobile time in the tail suspension test(P<0.01)as well as in the forced swimming test(P<0.01),extented escape latency on the 7th day(P<0.01),and a decreased time of crossing the platform(P<0.05).EMF exposure resulted in that the hippocampal neurons were in disordered arrangement,loose structure and irregular morphology,with swollen cytoplasm and condensed nuclei,swollen and more microglial cells in the hippocampus(P<0.01),and enhanced relative fluorescence intensity of CD68(P<0.01),but not in CD206 fluorescence intensity(P=0.885).All these findings suggested that activated microglia predominantly exhibited a pro-inflammatory M1 phenotype during this phase.In the hippocampus,the levels of TNF-α and IL-1β were significantly increased,while the levels of IL-10 and TGF-β were significantly decreased(P<0.01).HA treatment reversed the conditions induced by EMF exposure,including better preference for sucrose(P<0.01),shorten immobile time in tail suspension test(P<0.05)and forced swimming test(P<0.01),less escape latency on the 7th day(P<0.01),and improved hippocampal cell injuries.Compared with the Con group,there were more microglial cells in the hippocampus in the HA+EMF group,with increased relative fluorescence intensity of M2 phenotype marker CD206(P<0.01)and decreased CD68 fluorescence intensity(P<0.01).HA treatment also significantly decreased the expression of TNF-α and IL-1β levels(P<0.01),increased the expression of IL-10 and TGF-β(P<0.01),and elevated the protein level of HSP70(P<0.01)when compared with the EMF group.Conclusion HA may ameliorate EMF-induced hippocampus neurons injury in mice by altering the phenotype of activated microglia and inhibiting inflammatory responses.

Objective To study the relationship between vaginal microecological balance and serum T cell subsets,Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)after hysterectomy.Methods The clinical data of 120 patients who underwent laparoscopic total hysterectomy in Daxing Teaching Hospital of Capital Medical University from June 2020 to June 2022 were retrospectively analyzed.The patients were assigned to normal group(n=50)and unbalanced group(n=70)according to postoperative vaginal microecological changes.General information,such as age,body mass index(BMI),disease type,expression of CD+4,CD+8,CD+4/CD+8,TLR2,and TLR4 were compared between the two groups.The risk factors affecting vaginal microecological balance after hysterectomy were analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of serum T cell subsets,TLR2,and TLR4 in predicting vaginal microecological imbalance after hysterectomy.Results The levels of CD+4 and CD+4/CD+8 in the unbalanced group were significantly lower than those in the normal group,while the levels of CD+8,TLR2 and TLR4 in the unbalanced group were significantly higher than those in the normal group(P<0.05).Multivariable Logistic regression analysis showed that CD+4,CD+8,CD+4/CD+8,TLR2 and TLR4 expression were the influence factors of vaginal microecological imbalance after hysterectomy(P<0.05).ROC analysis confirmed that the expression of CD+4,CD+8 and CD+4/CD+8 and the levels of TLR2 and TLR4 could be used to predict vaginal microecological imbalance after hysterectomy,and the areas under the curve were 0.718,0.813,0.785,0.851,and 0.945,respectively(all P<0.05).Conclusion CD+4,CD+8,CD+4/CD+8,TLR2 and TLR4 expression levels are the influence factors of vaginal microecological imbalance after hysterectomy.They can be used as biological indicators for evaluating vaginal microecological balance after hysterectomy.

ObjectiveTo evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for muscle atrophy in patients with immobilization after surgical fixation of foot and ankle fractures.MethodsThis was a two-arm randomized controlled trial wherein 80 patients were recruited and divided into control (n = 40) and intervention (n = 40) groups. The control group received conventional orthopedic treatment, whereas the intervention group received TEAS and conventional treatment. The intervention group received TEAS 3 times a week for 30 min each time for 8 weeks. The primary outcomes were muscle thickness (MT) and cross-sectional area (CSA) of the rectus femoris and gastrocnemius muscles, whereas the secondary outcome measure was echo intensity (EI). Data were collected before the fixation operations (baseline assessment) and 4 and 8 weeks after intervention.ResultsCompared with baseline, the MT and CSA were reduced in both groups by the end of treatment, whereas EI increased in both groups. At week 4, the reduction in the rectus femoris CSA in the intervention group was significantly lower than that in the control group (P = .02); however, the between-group differences in the MT and EI (all P .05) were not significant. No serious adverse events were observed in either group.ConclusionOur study showed that TEAS can improve muscle atrophy by attenuating the decline in the muscle CSA. Because this was only a pilot trial, subsequent studies will need longer follow-ups and larger sample sizes.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes.Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder.However,its therapeutic dosage closely approaches toxic levels.Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L,typically giving rise to gastrointestinal and central nervous system reactions.Cardiac toxicity is rare but serious in cases of lithium poisoning.The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers.This resulted in symptoms such as arrhythmia,shock,impaired consciousness,and coarse tremors.Following symptomatic supportive treatment,including blood dialysis,the patient's physical symptoms gradually improved.It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.

Objective To investigate carboxyl terminus of Hsc70-interacting protein(CHIP)and FAT a-typical cadherin 4(FAT4)expression in colorectal cancer(CRC)tissue and their clinical significance.Methods A total of 92 CRC patients treated in a hospital from May 2018 to May 2020 were selected as the study objects.The expressions of CHIP and FAT4 in CRC tissues and adjacent tissues were detected by im-munohistochemistry.Spearman rank correlation analysis showed the correlation between CHIP and FAT4 ex-pression in CRC tissues.Kaplan-Meier curve was used to analyze the relationship between CHIP and FAT4 expression and survival prognosis of CRC patients.Cox proportional risk model was used to analyze the prog-nostic factors of CRC patients.Results Compared with adjacent tissue,the positive rate of CHIP in CRC tis-sue was higher[65.22％(60/92)vs.10.87％(8/92)]and the positive rate of FAT4 was lower[28.26％(26/92)vs.89.13％(82/92)].The difference was statistically significant(X2=63.075,70.300,P＜0.001).There was a negative correlation between CHIP and FAT4 expression in CRC(r=-0.781,P＜0.001).The positive rates of CHIP and FAT4 were higher in CRC tissues with TNM stage Ⅰ to Ⅱ,high school differenti-ation and no lymph node metastasis,and the positive rates of CHIP and FAT4 were lower in CRC tissues with TNM stage Ⅲ,low differentiation and lymph node metastasis,and the difference was statistically significant(P＜0.05).The 3-year survival rates of CHIP positive and CHIP negative patients were 48.33％(29/60)and 78.13％(25/32),respectively,and the difference was statistically significant(Log-rank X2=6.709,P=0.010).The 3-year survival rates of FAT4-positive and FAT4-negative patients were 81.25％(13/16)and 53.95％(41/76),respectively,with statistical significance(Log-rank X2=5.124,P=0.032).TNM stage Ⅲ,low differentiation,lymph node metastasis and positive CHIP were risk factors for the prognosis of CRC pa-tients,while positive FAT4 was protective factor.Conclusion CHIP expression is increased and FAT4 ex-pression is decreased in CRC tissues.Both expressions are associated with poor clinicopathological features of CRC,which is helpful to evaluate the survival prognosis of CRC patients.

Objective:To investigate the relationship between positive asthma prediction index (API) and single nucleotide polymorphisms (SNPs) of interleukin (IL-13), IL-4, β 2 adrenergic receptor (ADRB2), and type I Fc ε receptor β (FcER1B) genes in asthmatic children.Methods:A prospective study was conducted on 102 asthmatic children under 5 years old admitted to Zhongshan Boai Hospital and Foshan First People′s Hospital (51 cases were API positive and 51 cases were API negative) from January 2020 to August 2023. Oral and buccal mucosal exfoliated cells were collected from the children, and genomic DNA was extracted using magnetic bead method. Four gene loci (IL-13 rs20541, IL-4 rs2243250, ADRB2 rs1042713, FcER1B rs569108) were genotyped using a matrix assisted laser desorption ionization time-of-flight mass spectrometer. Logistic regression analysis was used to evaluate the correlation between SNP typing at these four gene loci and API positivity in asthmatic children.Results:There was a statistically significant difference in the SNP typing and allele distribution frequency of IL-13 rs20541, IL-4 rs2243250, ADRB2 rs1042713, FcER1B rs569108 between the API positive and API negative groups of wheezing children (all P<0.05). Among API positive children, the proportion of IL-13 rs20541 site was higher in GG type, the proportion of IL-4 rs2243250 site was higher in TT type, the proportion of ADRB2 rs1042713 site was higher in AG type, and the proportion of FcER1B rs569108 site was higher in AA type; The results of logistic regression analysis showed that IL-13 rs20541 GG type, IL-4 rs2243250 TT type, FcER1B rs569108 AA type were associated with the risk of API positivity in asthmatic children (all P<0.05). Conclusions:IL-13, IL-4, and FcER1B genes are risk genes for the development of API positive wheezing in children under 5 years old. SNP typing of these genes can be used to evaluate the risk of API positivity in clinical practice.

Objective To investigate the distribution and antimicrobial resistance of clinical isolates in the First Affiliated Hospital of Xi'an Jiaotong University in 2022 for rational use of antibiotics in clinical practice.Methods Nonduplicate clinical isolates were collected from January 1,2022 to December 31,2022.Antimicrobial susceptibility testing was carried out using Kirby-Bauer method and automated systems.The data were analyzed using WHONET 5.6 software and interpreted according to the Clinical and Laboratory Standards Institute(CLSI)breakpoints(2021 Edition).Results Of the 8 638 clinical isolates,gram negative bacteria and gram positive bacteria accounted for 60.8％(5 253/8 638)and 39.2％(3 385/8 638),respectively.The prevalence of methicillin-resistant strains was 33.0％in S.aureus(MRSA),75.8％in S.epidermidis(MRSE),and 51.9％in other coagulase-negative Staphylococcus(MRCNS).No staphylococcal strains were found resistant to vancomycin.The prevalence of vancomycin-resistant E.faecium was 0.6％,and no vancomycin-resistant E.faecalis was found.E.faecalis strains showed higher resistance rate to linezolid(5.2％)than E.faecium(0.7％).The prevalence of carbapenem-resistant Enterobacterales(CRE)was 7.9％,specifically 12.1％for carbapenem-resistant K.pneumoniae(CRKP)and 1.6％for carbapenem-resistant E.coli(CREC).The prevalence of carbapenem-resistant P.aeruginosa(CRPA)and carbapenem-resistant A.baumannii(CRAB)was 30.9％and 77.0％,respectively.Conclusions Clinical microbiology laboratories should strengthen the collection and testing of clinical specimens from the sites of infection in order to improve pathogenic diagnosis and antimicrobial resistance surveillance.This is conducive to the rational use of antibiotics and reduce the further spread of multidrug-resistant bacteria.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*