Objective To study the five-year survival status and influencing factors of elderly patients with lung cancer complicated with chronic obstructive pulmonary disease (COPD). Methods A cohort study was conducted to follow up 450 patients with lung cancer and chronic obstructive pulmonary disease who were hospitalized in our hospital from January 2018 to December 2023. The endpoint of the follow-up was the end of a five-year period or death. The Life Tables method was used to calculate survival rates and plot survival curves. The Cox proportional hazards model was used to analyze the influencing factors of five-year survival. Results The results indicated that the overall five-year survival rate of patients was 4.89%, and it decreased year by year. Cox regression analysis showed that age, gender, family functioning, and psychological status significantly influenced patient survival rate (all P<0.05). Stratified analysis found that the smoking status, family functioning, and psychological status of male patients all had an impact on survival rate (all P<0.05), while the psychological status of female patients had a more significant impact on survival (P=0.008). Conclusion This study provides a scientific basis for comprehensive intervention of elderly lung cancer patients with COPD. It is recommended that clinical attention should be paid to psychological and family factors to improve patient prognosis.

Corneal endothelial cells(CECs), which form the innermost cellular layer of the cornea, play a pivotal role in sustaining corneal transparency and preserving visual acuity. However, CECs are vulnerable to damage induced by a spectrum of pathological conditions or traumatic injuries. Once the density of CECs declines below a critical threshold, corneal endothelial dysfunction is precipitated, ultimately leading to corneal edema and progressive visual impairment. Penetrating keratoplasty and corneal endothelial transplantation remain the first-line therapeutic strategies for managing advanced corneal endothelial dysfunction. Nevertheless, the global shortage of donor corneas severely limits the accessibility and scalability of these surgical interventions. Consequently, regenerative medicine approaches targeting corneal endothelial repair and regeneration have emerged as a major focus of international research in ophthalmology. A key challenge in the in vitro expansion of CECs is their propensity to undergo endothelial-to-mesenchymal transition(EndMT). EndMT is a process of cellular phenotypic transformation, through which endothelial cells lose their intrinsic functions and acquire the characteristic features of mesenchymal cells. The EndMT significantly impedes the clinical translation of in vitro-cultured CECs for regenerative applications. In this review, the risk factors and related signaling pathways involved in EndMT were summarized, aiming to provide references for the basic research and clinical treatment of relevant diseases.

Sleep is an instinctive behavior alternating awakening state, sleep entails many active processes occurring at the cellular, circuit and organismal levels. The function of sleep is to restore cellular energy, enhance immunity, promote growth and development, consolidate learning and memory to ensure normal life activities. However, with the increasing of social pressure involved in work and life, the incidence of sleep disorders (SD) is increasing year by year. In the short term, sleep disorders lead to impaired memory and attention; in the longer term, it produces neurological dysfunction or even death. There are many ways to directly or indirectly contribute to sleep disorder and keep the hormones, including pharmacological alternative treatments, light therapy and stimulus control therapy. Exercise is also an effective and healthy therapeutic strategy for improving sleep. The intensities, time periods, and different types of exercise have different health benefits for sleep, which can be found through indicators such as sleep quality, sleep efficiency and total sleep time. So it is more and more important to analyze the mechanism and find effective regulation targets during sleep disorder through exercise. Dopamine (DA) is an important neurotransmitter in the nervous system, which not only participates in action initiation, movement regulation and emotion regulation, but also plays a key role in the steady-state remodeling of sleep-awakening state transition. Appreciable evidence shows that sleep disorder on humans and rodents evokes anomalies in the dopaminergic signaling, which are also implicated in the development of psychiatric illnesses such as schizophrenia or substance abuse. Experiments have shown that DA in different neural pathways plays different regulatory roles in sleep behavior, we found that increasing evidence from rodent studies revealed a role for ventral tegmental area DA neurons in regulating sleep-wake patterns. DA signal transduction and neurotransmitter release patterns have complex interactions with behavioral regulation. In addition, experiments have shown that exercise causes changes in DA homeostasis in the brain, which may regulate sleep through different mechanisms, including cAMP response element binding protein signal transduction, changes in the circadian rhythm of biological clock genes, and interactions with endogenous substances such as adenosine, which affect neuronal structure and play a neuroprotective role. This review aims to introduce the regulatory effects of exercise on sleep disorder, especially the regulatory mechanism of DA in this process. The analysis of intracerebral DA signals also requires support from neurophysiological and chemical techniques. Our laboratory has established and developed an in vivo brain neurochemical analysis platform, which provides support for future research on the regulation of sleep-wake cycles by movement. We hope it can provide theoretical reference for the formulation of exercise prescription for clinical sleep disorder and give some advice to the combined intervention of drugs and exercise.

Background and purpose:Melanoma is a highly invasive malignant tumor originating from melanocytes,which poses a great threat to human life and health around the world,and its morbidity and mortality have been rising continuously in recent years.Telomerase and autophagy play crucial roles in cell proliferation,survival and stress response.Telomerase maintains the replication ability of cells by prolonging telomeres at the ends of chromosomes,and autophagy,as a self-degradation mechanism of cells,can not only help cells remove damaged components to promote survival,but also induce cell death under certain conditions.In the tumor environment,they are often abnormally activated or out of balance,and participate in the occurrence and development of many cancers,including melanoma.This study investigated the roles of telomerase and autophagy in melanoma progression and evaluated the potential synergistic therapeutic effects of combined application of telomerase inhibitor BIBR1532 and autophagy inhibitor chloroquine(CQ)in melanoma treatment.Methods:Malignant melanoma cells A375 were treated with telomerase inhibitor BIBR1532.The cell viability was assessed using the cell counting kit-8(CCK-8)assay,and the cell apoptosis was detected using the Annexin Ⅴ/propidium iodide(PI)double staining method.Additionally,the expressions of autophagy-related proteins LC3-Ⅱand p62 were detected by Western blot,and the changes in autophagy flux were observed using dual-tagged adenovirus transfection technology.Based on these studies,BIBR1532 and the autophagy inhibitor CQ were further applied in combination to analyze cell proliferation,apoptotic rate,changes in mitochondrial membrane potential,and cell cycle distribution,and the cloning formation experiment was used to verify the cell's proliferative capacity,thereby comprehensively evaluating the efficacy of this combined treatment strategy.Results:Telomerase inhibitor BIBR1532 at a concentration of 50 μmol/L significantly inhibited the growth of malignant melanoma cells A375 and induced apoptosis.At the same concentration,BIBR1532 upregulated the expression of the autophagy-related protein LC3-Ⅱ in A375 cells,while downregulating the expression of p62 protein.By transducing A375 cells with a dual-tagged adenovirus,it was observed that autophagy flux was significantly enhanced after treatment with BIBR1532.Furthermore,the combined application of BIBR1532(50 μmol/L)and the autophagy inhibitor CQ(20 μmol/L)significantly promoted the death of A375 cells,induced apoptosis and destruction of mitochondrial membrane potential,caused cell cycle arrest at the G2/M phase,and significantly inhibited the cell's clonogenic ability.Conclusion:Telomerase inhibitor BIBR1532 not only inhibits the proliferation of malignant melanoma cells but also activates the autophagy process in these cells,and inhibition of the autophagy response by autophagy inhibitor CQ can enhance the sensitivity of malignant melanoma cells to telomerase inhibitor BIBR1532.

Objective To explore the mediating effect of coping styles on the early postoperative cognitive appraisal of health and stigma in patients with radical prostatectomy,so as to provide a reference for an early intervention in postoperative stigma.Methods Convenience sampling was used to select 223 patients who received radical prostatectomy at 5 Tier-ⅢA hospitals in Guangzhou from November 2022 to December 2023.Data were collected using the demographic data questionnaire,social impact scale,brief health cognition appraisal scale and medical coping style scale.Pearson correlation analysis was performed to examine the correlations between the stigma,health cognition appraisal and coping styles.Structural equation modelling was employed to analyse the mediating effect of coping styles on the health cognition appraisals and stigma.Results A total of 210 patients completed the study.The score of stigma for the patients after the radical prostatectomy was(49.46±13.56).Stigma exhibited positive correlations with negative cognitive appraisals(threat and harm)and negative coping styles(avoidance and submission)(both P<0.01).There were negative correlations between stigma and challenging cognitive appraisal and confrontation coping style(both P<0.01).Submission coping style played a mediating role between the cognitive appraisal of health(harm,threat and challenge)and stigma(β=0.072,0.075,-0.121,all P<0.01),accounting for 14.06％,23.15％and 100.00％,respectively,of the total effect.Conclusion Submission coping style is the mediator between the early postoperative cognitive appraisals and stigma in patients with radical prostatectomy.Negative cognitive appraisal positively predicts stigma through the submission coping style,while challenging cognitive appraisal negatively predicts stigma through the submission coping style.Caregivers should assess the early coping styles of patients after surgery,guide patients to correctly cope with the disease,and help them to avoid submissive responses to the postoperative stress hence to reduce the sense of stigma.

Following extensive interdisciplinary research and development over several years,mechanical circulatory support devices(MCSD),including ventricular assist device(VAD)and total artificial heart(TAH),are now established as vital treatment options for patients with advanced heart failure.These devices have proven to be crucial in assisting or replacing a failing heart,offering patients a new lease of life and improving their quality of life.Currently,mechanical circulatory support(MCS)has become a well-recognised,long-term treatment option for patients who are unable to undergo heart transplantation due to donor organ shortages or contraindications.Given their continuous availability independent of donor organ limitations,these devices are poised to play an increasingly vital role in the future of medicine.This article aims to summarize the evolution,clinical applications,categorization,and potential complications of MCSD.

Neuroscience,a cutting-edge field in interdisciplinary research,consistently draws considerable research interest,of which quantitatively probing the neurochemical dynamics is essential for brain science research.In vivoelectrochemical analysis,featuring with high sensitivity,high spatiotemporal resolution,free from transfection,and designable electrode/solution interfaces,provides important tools for in vivo neurochemicals sensing.Fast scan cyclic voltammetry combined with microelectrodes can not only enable precise detection of dopamine but also is compatible with existing neurosurgical equipment.This offers new opportunities for the clinical application of in vivo electrochemical analysis and paves new avenues for the diagnosis and treatment of neurological diseases.This review summarized recent progress of in vivo electrochemical techniques for brain neurochemistry and addressed key clinical challenges and their potential solutions.

Objective To construct an aptamer-functionalized carboxylated graphene oxide(CGO)fluo-rescent sensor to achieve highly sensitive and specific detection of ketamine(KET)and its metabolite norketamine(NK)using an aptamer capable of simultaneously recognizing KET and NK.Methods A specific aptamer for simultaneous recognition of KET and NK was screened using graphene oxide-sys-tematic evolution of ligand by exponential enrichment(GO-SELEX)and molecular docking tech-niques.The aptamer,labeled with Cy5 fluorescence,was chemically conjugated to CGO to construct an aptamer-functionalized CGO fluorescent sensor.By optimizing detection conditions,including the mass concentration of CGO,aptamer concentration,reaction temperature,and incubation time,quantita-tive analysis of the target analytes was achieved using the ratio of fluorescence intensity changes be-fore and after target addition.The stability of the sensor in biological matrices was evaluated by moni-toring fluorescence intensity changes over incubation time in blank blood and urine,in comparison with the traditional physical adsorption-based CGO fluorescent sensor.Spiked recovery experiments in blank blood and urine were conducted to compare performance with that of HPLC-MS/MS.Results A specific aptamer A5 was selected and chemically conjugated with CGO to construct the aptamer-functionalized CGO fluorescent sensor.Under optimized conditions,the proposed fluorescent sensor ex-hibited a linear detection range of 1.0-5.0 ng/mL for KET,with a limit of detection(LOD)of 0.86 ng/mL;while for NK,the linear detection range was 1.0-5.0 ng/mL,with an LOD of 0.70 ng/mL.Com-pared with the CGO fluorescent sensor constructed via physical adsorption,this sensor demonstrated greater stability in blood and urine.The spiked recovery rates of KET and NK in blank blood and urine ranged from 81.50%to 110.03%,exhibiting detection performance comparable to that of HPLC-MS/MS.Conclusion The aptamer screening method offers a novel approach for selecting aptamers tar-geting drugs and their metabolites.The constructed aptamer-functionalized CGO fluorescent sensor pro-vides an efficient and reliable strategy for the high-performance detection of KET and NK.

Objective:To analyze the long-term trends in cause-specific mortality across different sexes and age groups in China from 1990 to 2021, and quantitatively assess the impact of population aging on cause-specific deaths by sex.Methods:Based on data from the Global Burden of Disease Study 2021, this study extracted the number of deaths, crude mortality rates and age-standardized mortality rates (ASMRs) for all causes, Level 1 causes (communicable, maternal, neonatal, and nutritional diseases; non-communicable diseases; injuries) and Level 3 causes in China from 1990 to 2021, stratified by sex and age group. This study analyzed the current situation and long-term trends in mortality in China, applying decomposition analysis to quantify the impact of population aging on the number of deaths.Results:In 2021, the ASMRs of all-cause death and the three primary causes of death in Level 1 in China were 644.68, 26.59, 575.55, and 41.82 per 100 000, respectively. The ASMRs of the three primary causes continued to decline, with the smallest decrease observed in non-communicable diseases [EAPC=-1.79%, 95% CI (-1.92%, -1.66%)] and the largest in communicable, maternal, neonatal, and nutritional diseases (CMNND) [EAPC=-5.86%, 95% CI (-6.06%, -5.65%)]. The ASMRs were higher in males than females, with a smaller decline. Mortality was higher in the elderly. CMNND deaths mainly occurred in children under 5 and the elderly; non-communicable disease deaths were concentrated in the elderly; injury deaths were relatively evenly distributed across age groups. The proportion of CMNND deaths decreased annually, while the proportion of non-communicable disease deaths increased. From 1990 to 2021, population aging contributed to an increase of 8.11 million all-cause deaths, 167 464.42 CMNND deaths, 7.74 million non-communicable diseases deaths, and 196 287.78 injury deaths. The impact of population aging differed by sex and disease, with male and female aging-related deaths increasing by 4.47 million and 3.70 million, respectively. Compared to 1990, the age-specific mortality rate contributions in 2021 were -72.82% for males and -93.87% for females, with variations by sex and disease. Conclusion:The composition of disease-related deaths in China has changed notably. Population aging is linked to the sharp rise in deaths, with varying impacts across sexes and diseases. Reducing disease mortality can help lessen the negative effects of population aging.

Objective:To investigate the changes of the epidemiology and clinical characteristics of human metapneumovirus (hMPV) among children with acute lower respiratory tract infection (ALRTI) before and after the discontinuation of non-pharmaceutical interventions (NPI) during coronavirus disease 2019 epidemic.Methods:This was a retrospective cohort study. Children hospitalized at The Second Affiliated Hospital and Yuying Children′s Hospital of Wenzhou Medical University between January 2021 and December 2023, who were diagnosed with ALRTI by nasopharyngeal secretion testing for respiratory pathogens nucleic acid were enrolled. Clinical and laboratory data were collected. Children admitted between January 1, 2021 and January 7, 2023 were classified as the pre-NPI withdrawal group (abbreviated as pre-withdrawal group), while those admitted from January 8, 2023 afterward were classified as the post-NPI withdrawal group (abbreviated as post-withdrawal group). Nasopharyngeal secretions from the enrolled children were tested for 13 respiratory pathogens using polymerase chain reaction-capillary electrophoresis fragment analysis, and bacterial cultures were also performed. Statistical analyses were performed using the Mann-Whitney U test or chi-square test. Results:A total of 30 855 ALRTI cases were enrolled, with 1 679 of hMPV-positive. In the pre-withdrawal group, there were 861 cases with an age of onset of 2.0(1.0, 3.0) years, and the highest proportion was in the 1 to <3 years age group, accounting for 35.3%(304/861). In the post-withdrawal group, there were 818 cases with an age of onset of 3.0(2.0, 4.0) years, and the highest proportion was in the 3 to <5 years age group, accounting for 39.2%(321/818).The age of onset in the post-withdrawal group was significantly older than that in the pre-withdrawal group ( Z=7.69, P<0.001) .The hMPV detection rate was higher in the pre-withdrawal group than that in post-withdrawal group (5.75%(861/14 984) vs 5.15%(818/15 871); χ2=5.25, P=0.022). In the pre-withdrawal group, the epidemic peaks occurred in winter and spring, with the highest rates in January 2022(25.2%(224/890)) and March 2022 (21.6%(186/860)). In the post-withdrawal group, the epidemic peak shifted to spring and summer, and the detection rate became increased since April 2023(10.8%(136/1 258)). The post-withdrawal group showed lower rates of wheezing, shortness of breath, cyanosis, respiratory support, severe pneumonia, intensive care unit admission, and shorter hospital stays compared to the pre-withdrawal group ( χ2=69.09, 31.63, 12.97, 57.96, 55.73, 5.48 and Z=7.11, respectively, all P< 0.05).In the pre-withdrawal group, 412 cases (47.9%(412/861)) had other pathogens detected, compared to 445 cases (54.4%(445/181)) in the post-withdrawal group, indicating a significantly higher rate of co-infections in the post-withdrawal group ( χ2=7.20, P<0.05). The most commonly detected pathogens in both groups were Mycoplasma pneumoniae (MP), rhinovirus, and Streptococcus pneumoniae. However, the post-withdrawal group showed significantly higher detection rates of MP and influenza virus, but lower bacterial detection rates compared to the pre-withdrawal group ( χ2=39.41, 9.70, 5.63, respectively, all P<0.05). The detection rate of Haemophilus influenzae was 2.1%(17/818) in the post-withdrawal group which lower than that (6.7%(58/861)) in the pre-withdrawal group, and the difference was statistically significant ( χ2=21.32, P<0.001). Conclusions:In 2023, following the withdrawal of NPI, the epidemic peak of hMPV in Wenzhou area is delayed to spring and summer. The age of children with hMPV-associated ALRTI increases, with the majority being 3 to <5 years old. The overall severity of the disease decreases. However, the detection of mixed pathogens increases, with MP being the most common, while bacterial detection decreases.