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 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 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 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.

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.

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*

Objective:To investigate the change in 25-hydroxy vitamin D (25-OHD) levels in hospitalized newborns in the neonatal intensive care unit (NICU) between baseline and vitamin D supplementation, and to explore the effect of different levels of vitamin D on the complications.Method:A prospective study was conducted on the newborns admitted to NICU at Jingzhou Hospital Affiliated to Yangtze University within 72 h after birth from January 2021 to January 2022. Vitamin D supplementation was initiated after the detection of basal 25-OHD levels within 72 h after birth. Serum 25-OHD levels were measured after 2, 4, and 6 weeks of supplementation. Newborns were categorized into four groups according to the basal 25-OHD level: sufficient, insufficient, deficient, and severely deficient groups. The analysis of variants, independent sample t-test, paired sample t-test, Chi-square test, or Fisher's exact probability method were employed to evaluate the differences in basal 25-OHD levels among newborns with different clinical conditions and gestational ages, as well as the variation in 25-OHD levels before and after supplementation among the four groups. Furthermore, differences in the morbidity and mortality among different basal status groups were analyzed. Result:(1) During the study period, 626 cases met the inclusion criteria, and after excluding seven cases, 619 infants were ultimately included in the study with serum 25-OHD level within 72 h being (21.8±10.1) ng/ml. There were 134 cases (21.6%) in the sufficient group, 208 cases (33.6%) in the insufficient group, 186 cases (30.0%) in the deficient group, and 91 cases (14.7%) in the severe deficient group. (2) No statistically significant differences were observed in the basal 25-OHD levels regardless of the genders, gestational age, birth month, number of fetuses or small for gestational age (all P>0.05). (3) Among all infants, 158 cases continued to supplement vitamin D for two weeks, 64 cases continued for four weeks, and 13 cases continued for six weeks, with all of them discharged within eight weeks. Compared with the basal 25-OHD levels, there were no statistically significant differences in the serum 25-OHD levels among the sufficient, insufficient, deficient, and severely deficient groups after two weeks of supplementation [(37.1±9.3) vs. (36.8±4.9) ng/ml, (24.7±7.2) vs. (24.7±2.9) ng/ml, (16.0±7.6) vs. (15.4±2.9) ng/ml, (8.1±5.6) vs. (7.6±1.4) ng/ml; t=0.18, 0.04, 0.65 and 0.48, respectively; all P>0.05]. After four weeks of supplementation, however, the serum 25-OHD levels in the four groups were higher than those before supplementation [(40.0±5.2) vs. (35.8±3.9) ng/ml, (29.7±6.4) vs. (24.5±2.9) ng/ml, (20.3±7.1) vs. (15.6±3.0) ng/ml, (14.9±7.3) vs. (6.5±2.3) ng/ml; t=2.13, 2.66, 5.08 and 7.64, respectively; all P<0.05]. (4) The incidence of hypocalcemia [23.1% (21/91) vs. 9.7% (18/186)] and neonatal respiratory distress syndrome [15.4% (14/91) vs. 3.2% (6/186)] were higher in the severely deficient group than those in the deficient group ( χ2=9.07 and 13.49, both P<0.008). No statistically significant differences were observed in the incidence of neonatal sepsis, neonatal necrotizing enterocolitis, bronchopulmonary dysplasia, retinopathy of prematurity, and mortality among the four groups (all P>0.05). Conclusions:The insufficiency of 25-OHD levels and vitamin D deficiency were prevalent in NICU neonates. Vitamin D status did not significantly differ among newborns with varying gestational ages. A prolonged period of sustained vitamin D supplementation may be required to elevate the serum 25-OHD level. The incidence of hypocalcemia and neonatal respiratory distress syndrome are higher in newborns with severe vitamin D deficiency.

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology* ; Cellular Senescence ; Homeostasis ; Cell Cycle Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; Mitochondria/metabolism* ; Electron Transport Complex III/metabolism* ; Humans ; Cells, Cultured

OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO₂/FiO₂), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO₂/FiO₂ at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.
Humans ; Prevalence ; Critical Care ; Risk Factors ; Sepsis ; Intensive Care Units