Objective To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3(TIM-3)in peripheral blood mononuclear cells and its relationship with non-small cell lung cancer(NSCLC).Methods TIM-3 expression in monocytes from the peripheral blood of 116 NSCLC patients and 37 healthy volunteers was analyzed via flow cytometry.The expression of TIM-3 in macrophages from tissues was detected via multiplex immunohistochemical staining.Transwell migration experiments were used to detect the migration ability of monocytes.Real-time PCR and ELISA were used to detect the mRNA and protein expression of TIM-3 in monocytes.Results Compared with that in healthy volunteers,TIM-3 expression was upregulated in the peripheral blood monocytes of NSCLC patients(P＜0.05).TIM-3 was expressed mainly in macrophages in adjacent tissues and positively correlated with its expression in monocytes in NSCLC patients(P＜0.05).Furthermore,high TIM-3 expression promoted monocyte migration in NSCLC patients(P＜0.05),and high TIM-3 expression in peripheral blood monocytes indicated poor prognosis(P＜0.05).Conclusion TIM-3 expression in peripheral blood monocytes may be a useful indicator of the disease prognosis of NSCLC patients and TIM-3 could be a new target for immunotherapeutic strategies.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

Benzylisoquinoline alkaloids (BIAs) are a structurally diverse group of plant metabolites renowned for their pharmacological properties. However, sustainable sources for these compounds remain limited. Consequently, researchers are focusing on elucidating BIA biosynthetic pathways and genes to explore alternative sources using synthetic biology approaches. CYP80B, a family of cytochrome P450 (CYP450) enzymes, plays a crucial role in BIA biosynthesis. Previously reported CYP80Bs are known to catalyze the 3'-hydroxylation of (S)-N-methylcoclaurine, with the N-methyl group essential for catalytic activity. In this study, we successfully cloned a full-length CYP80B gene (StCYP80B) from Stephania tetrandra (S. tetrandra) and identified its function using a yeast heterologous expression system. Both in vivo yeast feeding and in vitro enzyme analysis demonstrated that StCYP80B could catalyze N-methylcoclaurine and coclaurine into their respective 3'-hydroxylated products. Notably, StCYP80B exhibited an expanded substrate selectivity compared to previously reported wild-type CYP80Bs, as it did not require an N-methyl group for hydroxylase activity. Furthermore, StCYP80B displayed a clear preference for the (S)-configuration. Co-expression of StCYP80B with the CYP450 reductases (CPRs, StCPR1, and StCPR2), also cloned from S. tetrandra, significantly enhanced the catalytic activity towards (S)-coclaurine. Site-directed mutagenesis of StCYP80B revealed that the residue H205 is crucial for coclaurine catalysis. Additionally, StCYP80B exhibited tissue-specific expression in plants. This study provides new genetic resources for the biosynthesis of BIAs and further elucidates their synthetic pathway in natural plant systems.
Cytochrome P-450 Enzyme System/chemistry* ; Benzylisoquinolines/chemistry* ; Hydroxylation ; Plant Proteins/chemistry* ; Alkaloids/metabolism* ; Stephania tetrandra/genetics*

Male factors contribute to 50% of infertility cases, with 20%-30% of cases being solely attributed to male infertility. Helicase for meiosis 1 ( HFM1 ) plays a crucial role in ensuring proper crossover formation and synapsis of homologous chromosomes during meiosis, an essential process in gametogenesis. HFM1 gene mutations are associated with male infertility, particularly in cases of non-obstructive azoospermia and severe oligozoospermia. However, the effects of intracytoplasmic sperm injection (ICSI) in HFM1 -related infertility cases remain inadequately explored. This study identified novel biallelic HFM1 variants through whole-exome sequencing (WES) in a Chinese patient with severe oligozoospermia, which was confirmed by Sanger sequencing. The pathogenicity of these variants was assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunoblotting, which revealed a significant reduction in HFM1 mRNA and protein levels in spermatozoa compared to those in a healthy control. Transmission electron microscopy revealed morphological abnormalities in sperm cells, including defects in the head and flagellum. Despite these abnormalities, ICSI treatment resulted in a favorable fertility outcome for the patient, indicating that assisted reproductive techniques (ART) can be effective in managing HFM1 -related male infertility. These findings offer valuable insights into the management of such cases.
Humans ; Male ; Sperm Injections, Intracytoplasmic ; Oligospermia/therapy* ; Adult ; Spermatozoa/ultrastructure* ; Exome Sequencing ; Mutation

Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".

Objective:To analyze the changes in serum levels of neurofilament light chain(NFL),binding protein S100 β(S100 β),and C-reactive protein(CRP)in patients with cognitive impairment after cardiac surgery,and to analyze the correlation between these indicators and patient prognosis.Methods:124 patients with heart disease who underwent surgical treatment from January 2022 to January 2025 were selected.One week after surgery,the patients were evaluated using the Montreal Cognitive Assessment Scale(MoCA).60 patients with MoCA scores＜26 were divided into the cognitive impairment group,and 64 patients with MoCA scores ≥ 26 were divided into the non cognitive impairment group.Compare the general information of two groups,including changes in serum NFL,S100 β,and CRP levels before and after surgery.Using logistic regression to analyze the influencing factors of cognitive impairment after cardiac surgery.Following a 4-month postoperative follow-up,the cognitive impairment group was assessed using the MoCA score.Patients with a MoCA score＜26 were categorized as having a poor prognosis,while the remaining patients were classified as having a good prognosis.The NfL,S100β,and CRP levels in both groups were compared,and the ROC curve was used to evaluate the predictive value of serum NFL,S100β,and CRP for poor prognosis in patients with postoperative cognitive impairment.Results:There was no significant difference in gender,BMI,education level,comorbidities(hypertension,diabetes),disease type,ASA classification,intraoperative blood loss,intraoperative fluid replacement,and cardiopulmonary bypass time between cognitive impairment group and non-cognitive impairment group(P＞0.05).The cognitive impairment group had a higher incidence of age,anesthesia maintenance time during surgery,no analgesia after operation and agitation during awakening than the non-cognitive impairment group(P＜0.05);There was no significant difference in the levels of serum NFL,S100β,and CRP between the two groups of patients before surgery(P＞0.05).On postoperative day 3,the levels of serum NFL,S100β,and CRP increased in both groups,with the cognitive impairment group being higher than the non cognitive impairment group(P＜0.05);Using cognitive impairment(occurrence=1,no occurrence=0)as the dependent variable,logistic regression analysis showed that age,intraoperative anesthesia maintenance time,agitation during the recovery period,postoperative 3-day NFL,S100 β,CRP were independent influencing factors of cognitive impairment after cardiac surgery(P＜0.05);The serum levels of NFL,S100β,and CRP in the good prognosis group and poor prognosis group were higher than those before surgery,and the NFL,S100 β,and CRP levels in the poor prognosis group were higher than those in the good prognosis group before and after surgery(P＜0.05);Using poor prognosis as positive samples and good prognosis as negative samples,a ROC curve was plotted.The results showed that the sensitivity and specificity of the combined prediction of three indicators before and after surgery for poor prognosis of cognitive impairment in cardiac surgery were higher than those of a single indicator(P＜0.05).Conclusion:The serum levels of NFL,S100β,and CRP are significantly elevated in patients with cognitive impairment after cardiac surgery,and the early postoperative elevation of NFL,S100β,and CRP is a contributing factor to the occurrence of cognitive impairment.Preoperative and early postoperative detection of these indicators can predict the prognosis of patients with cognitive impairment after cardiac surgery.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

OBJECTIVES: To evaluate and integrate evidence on the management of sleep disorders in children with attention deficit hyperactivity disorder (ADHD). METHODS: Literature was retrieved based on the 6S model, and evidence related to sleep disorder management in children with ADHD was extracted from the included references. RESULTS: A total of 17 studies were included, from which 16 pieces of evidence were extracted. Of these, 6 were classified as Level 1 evidence and 10 as Level 5. The evidence covered screening, assessment, non-pharmacological interventions, pharmacological interventions, follow-up, and multidisciplinary collaboration. CONCLUSIONS This study integrated evidence on the management of sleep disorders in children with ADHD using an evidence-based approach, providing an evidence-based foundation for managing sleep disorders in this population.
Humans ; Attention Deficit Disorder with Hyperactivity/complications* ; Sleep Wake Disorders/etiology* ; Child ; Evidence-Based Medicine

Episodic memory, our ability to recall past experiences, is supported by structures in the medial temporal lobe (MTL) particularly the hippocampus, and its interactions with fronto-parietal brain regions. Understanding how these brain regions coordinate to encode, consolidate, and retrieve episodic memories remains a fundamental question in cognitive neuroscience. Non-invasive brain stimulation (NIBS) methods, especially transcranial magnetic stimulation (TMS), have advanced episodic memory research beyond traditional lesion studies and neuroimaging by enabling causal investigations through targeted magnetic stimulation to specific brain regions. This review begins by delineating the evolving understanding of episodic memory from both psychological and neurobiological perspectives and discusses the brain networks supporting episodic memory processes. Then, we review studies that employed TMS to modulate episodic memory, with the aim of identifying potential cortical regions that could be used as stimulation sites to modulate episodic memory networks. We conclude with the implications and prospects of using NIBS to understand episodic memory mechanisms.
Humans ; Memory, Episodic ; Transcranial Magnetic Stimulation/methods* ; Brain/physiology* ; Nerve Net/physiology* ; Mental Recall/physiology* ; Neural Pathways/physiology*