With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

With the accelerating aging of the population, the proportion of elderly patients with lung cancer continues to rise, presenting multiple challenges to perioperative management. This paper systematically reviews the clinical characteristics of elderly lung cancer patients. Based on the comprehensive geriatric assessment, it proposes incorporating seven major geriatric syndromes—frailty, delirium, sarcopenia, cognitive impairment, malnutrition, dysphagia, and mood disorders—into the core evaluation system. By integrating multimorbidity management with complication prevention and control, an integrated "geriatric syndrome-multimorbidity-complication" perioperative management model is constructed. Furthermore, this paper outlines stratified intervention strategies for geriatric syndromes, a "five-step" workflow for comorbidity management, and a comprehensive intervention pathway for complications across the preoperative, intraoperative, and postoperative phases. Multidisciplinary team (MDT) collaboration serves as the core mechanism to achieve individualized comprehensive treatment. This paper aims to provide a novel perioperative comprehensive treatment model for elderly lung cancer patients, which is centered on geriatrics, supported by multidisciplinary collaboration, and guided by precision medicine.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNpc), primarily manifesting as motor dysfunctions such as resting tremor, muscle rigidity, and bradykinesia. According to the classical model of basal ganglia motor control, approximately half of the medium spiny neurons (MSNs) in the striatum are D1-MSNs, which constitute the direct pathway. These neurons express D₁-dopamine receptor (D₁R) and substance P, and they mainly participate in the selection, initiation, and execution of movements. The other half are D2-MSNs, which constitute the indirect pathway. These neurons express D₂-dopamine receptor (D₂R) and adenosine 2A receptors and are involved in inhibiting unnecessary movements or terminating ongoing movements, thereby adjusting movement sequences to perform more precise motor behaviors. The direct pathway in the striatum modulates the activity of motor cortex neurons by exciting D1-MSNs through neurotransmitters such as glutamate (Glu), allowing the motor cortex to send signals more freely to the motor system, thus facilitating the generation and execution of specific motor behaviors. Studies using D1-Cre and D2-Cre mice with neurons labeled for D₁R and D₂R have shown that both types of neurons are involved in the execution of movements, with D1-MSNs participating in movement initiation and D2-MSNs in inhibiting actions unrelated to the target movement. These findings suggest that the structural and functional plasticity of D1-MSNs and D2-MSNs in the basal ganglia circuitry enables motor learning and behavioral regulation. Additionally, when SNpc DA neurons begin to degenerate, D1-MSNs are initially affected but do not immediately cause motor impairments. In contrast, when D2-MSNs undergo pathological changes, they are first activated by upstream projecting neurons, leading to the inhibition of most motor behaviors and resulting in motor dysfunction. Therefore, it is hypothesized that motor impairments such as bradykinesia and initiation difficulties are more closely related to the functional activity of D2-MSNs. The extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) signaling pathway has been identified as a critical modulator in the pathophysiology of PD. Recent findings indicate that Erk/MAPK signaling pathway can mediate DA and Glu signaling in the central nervous system, maintaining normal functional activity of striatal MSNs and influencing the transmission of motor control signals. Within this complex regulatory network, the Erk/MAPK signaling pathway plays a key role in transmitting motor information to downstream neurons, regulating normal movements, avoiding unnecessary movements, and finely tuning motor behaviors. Our laboratory’s previous research found that 4 weeks of aerobic exercise intervention improved motor dysfunction in PD mice by inhibiting the Erk1/2 signaling upstream of striatal MSNs, primarily involving the Erk1/2 signaling in D2-MSNs rather than D1-MSNs. This review summarizes the neurobiological mechanisms of Erk/MAPK signaling pathway in D2-MSNs for the prevention and treatment of motor dysfunction in PD. By exploring the role of this signaling pathway in regulating motor abnormalities and preventing motor dysfunction in the central nervous system of PD, this review provides new theoretical perspectives for related mechanistic research and therapeutic strategies.

Chikungunya virus (CHIKV), which is primarily transmitted by Aedes aegypti and Ae. albopictus, has recently rapidly spread across the world, which poses a huge threat to public health. Chikungunya fever (CHIKF), caused by CHIKV infection, typically manifests as acute febrile illness with severe polyarthralgia that may persist for months to years. A few severe CHIKF cases may be accompanied by serious neurological complications, even resulting in death. The accelerating global expansion of CHIKV is closely associated with genetic variations of the virus, and mutated genes in CHIKV may augment the virus adaptability to Aedes vectors and transmission efficiency. Currently, the diagnosis of the CHIKV infection primarily relies on molecular and serological assays; however, there are still multiple challenges for early and differential diagnosis of CHIKV infections due to co-infections with arboviruses and nonspecific early symptoms. The first prophylactic vaccine for CHIKF has been recently approved in the United States; however, the large-scale application still awaits further validations. More importantly, there are no licensed antiviral therapies against CHIKV until now. This review describes the structure and pathogenesis of CHIKV, summarizes the latest epidemiology and advances in the diagnosis of CHIKV infections, and depicts the current status and prospects of antiviral agents and vaccine development, so as to inform evidence-based prevention and control strategies.

Objective:To explore the value of paediatric age-adjusted shock index（SIPA）in early identification of septic shock in children，and to evaluate the relationship between SIPA and disease severity and prognosis.Methods:The infected children admitted to the department of critical care medicine of the Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2023 to July 2024 were collected. Dynamic assessment was performed 0 to 6 hours after admission. Patients diagnosed with sepsis without septic shock were classified as the sepsis group and those diagnosed with sepsis with septic shock were classified as the septic shock group. According to whether the blood pressure of the children decreased，they were divided into two groups：compensated septic shock group and decompensated septic shock group. The difference of SIPA among the three groups was analyzed，and the predictive value of SIPA on case fatality rate，lactate level，pediatric critical illness score，ventilator utilization rate and length of hospital stay were analyzed.Results:Among 203 children with sepsis，112 were males and 91 were females. There were 146 cases in the sepsis group，37 cases in the compensated septic shock group and 20 cases in the decompensated septic shock group. There was no significant difference between the three groups in gender（ P>0.05），but there was a statistically significant difference in age（ χ 2=32.905， P<0.001）. There was no significant difference in age between the sepsis group and the compensated septic shock group（ P>0.05）. The age of sepsis group and decompensated septic shock group，compensated septic shock group and decompensated septic shock group were statistically significant（ χ 2=29.431， P<0.001； χ 2=19.764， P=0.001）. The proportion of increased SIPA was statistically different among the three groups，with both the compensated septic shock group and the decompensated septic shock group being higher than the sepsis group（ χ2=20.383， P<0.001； χ2=33.600， P<0.001）. The decompensated septic shock group was higher than the compensated septic shock group（ χ2=6.555， P=0.01）. SIPA was correlated with case fatality rate，lactate level，pediatric critical illness score，ventilator use rate and length of stay of the children，with statistically significant differences（ P<0.05）. Conclusion:The increase of SIPA can be used for the early identification of septic shock in children，and it has a certain early warning value for the prognosis assessment of sepsis and septic shock.

Percutaneous renal denervation(RDN)is a minimally invasive interventional treatment for hypertension that has been used in clinics at home and abroad,primarily for patients with resistant hypertension or who cannot tolerate antihypertensive drugs.Current clinical studies have confirmed the safety and efficacy of this technique.As RDN is still in its promotional and popularization stage,the expert group has written this clinical pathway to promote the orderly implementation of this technology,standardize the operating process,and standardize diagnostic and therapeutic behaviors.The pathway describes the clinical assessment of patients in detail(including indications,contraindications,and the patient screening process),the standardized operating process for RDN(including perioperative medication,anaesthesia,ablation,and management of complications),and the postoperative follow-up plan(including follow-up content,methods,and timing).It is hoped that this will serve as a reference for physicians involved in RDN clinical work,standardize diagnostic and therapeutic behaviors,and promote the standardized,precise,and sustainable development of the RDN discipline.

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

Objective:To establish a genomic nucleic acid mass spectrometry detection platform for allelic risk associated with Alzheimer's disease.Methods:Whole blood samples of 61 patients diagnosed as Alzheimer's disease in the Affiliated Brain Hospital of Guangzhou Medical University from December 28th, 2023 to 31st, March 2024 were collected and deoxynucleic acid (DNA) was extracted, including 22 males and 39 females, aged (67.36 ± 8.18) years old. After screening out 17 risk gene loci in Chinese population, multiplex polymerase chain reaction primers, single-base extension primers and Sanger sequencing primers were designed. Ten samples were used for primer optimization and debugging through Sanger sequencing and time-of-flight mass spectrometry to establish a detection system. The remaining samples were genotyped using a time-of-flight mass spectrometer and verified by Sanger sequencing for accuracy evaluation. Five samples were selected for gradient dilution and then subjected to time-of-flight mass spectrometry detection to evaluate the detection limit. Three clinical samples, one case of Escherichia coli and one case of Staphylococcus aureus genomic DNA samples were selected for cross-reaction research. The anti-interference ability of the detection system was evaluated against hemolysis, chylous substances and conventional anticoagulants in the samples. Two samples, one wild and one homozygous mutation sample with representative peak shapes, were selected to evaluate the anti-interference ability. Four samples containing the common genotypes of all gene loci in the system were selected and repeated 10 times to evaluate the precision.Results:The minimum intensity of single-base extension primers on mass spectrometry is greater than half of the maximum intensity. All 17 risk gene loci screened were successfully typed. The time-of-flight mass spectrometry detection results of 1,037 loci from 61 samples showed that the genotyping detection rate was 100%. The genotypes of the 20 DNA samples were completely consistent with the results of Sanger sequencing, with an accuracy rate of 100%. The mass spectrometry detection results of five samples after gradient dilution indicated that the low detection limit was 5 ng of DNA. The reaction system has a strong anti-interference ability against hemolysis of samples, chylous substances, conventional anticoagulants and DNA cross-contamination. Homologous allele interference and no cross-reaction between the bacterial genome and 17 gene loci do not affect the risk genome detection results. The results of 10 repeated mass spectrometry tests on 4 samples showed that the precision was 100%.Conclusion:The genomic detection system of Alzheimer's disease risk has been successfully established to provide an auxiliary mean for disease diagnosis and risk assessment.

Objective:To quantitatively evaluate the effects of left bundle branch block（LBBB）on left ventricular structure，function and myocardial perfusion using left ventricular pressure-strain loop and single photon emission computed tomography（SPECT），and to investigate the relationship between myocardial work，myocardial perfusion and pathological changes of left ventricular remodeling in left bundle branch block induced cardiomyopathy（LBBB-CM）.Methods:Fourteen male beagle dogs were selected，and the main trunk of the left bundle branch was ablated to create an LBBB dog model. Electrocardiogram（ECG），transesophageal echocardiography and arterial blood pressure data of LBBB dogs were collected before and 12 months after the ablation of left bundle branch trunk. Global and segmental myocardial work parameters were obtained by left ventricular pressure-strain loop. The differences of above parameters between baseline and 12 months after the ablation of left bundle branch were compared. SPECT was performed in LBBB dogs 12 months after the creation of LBBB. The hearts were harvested for anatomy observation and histopathological analysis in LBBB dogs and another 7 male beagle dogs（normal control group）matched by age and weight. The correlation between myocardial perfusion（percentage of regional tracer uptake）and myocardial work parameters，myocardial fibrosis in LBBB dogs were analyzed.Results:Compared with baseline，the left ventricular end-diastolic volume of 12 months after the ablation increased［（20.78 ± 5.32）ml vs（26.71 ± 7.94）ml， P = 0.003］，left ventricular ejection fraction decreased［（59.17 ± 5.67）% vs（47.69 ± 5.45）%， P<0.001］；left ventricular global/segmental longitudinal strain，global/segmental constructive work and global/segmental work efficiency decreased（all P<0.05），left ventricular global/segmental wasted work increased（all P<0.001）. Heterogenous perfusion defect was observed in LBBB dogs by SPECT，compared with lateral wall segments，the percentage of regional tracer uptake of septum was decreased（all P<0.05）. Gross anatomical and myocardial pathological changes were manifested as cardiomegaly，flaky or focal grayish thickening of endocardium，cardiomyocyte degeneration and fibrosis. Compared with normal control group，the collagen fiber volume fraction（CVF）in all segmental endocardium and partial segmental myocardium of LBBB dogs were significantly increased（all P<0.05）. Percentage of regional tracer uptake was positively correlated with segmental myocardial work（SMW）and segmental myocardial efficiency（SWE）（ r s = 0.49，0.31；both P<0.001），and negatively correlated with CVF and segmental wasted work（SWW）（ r s = -0.51，-0.49；both P<0.001）. Conclusions:Isolated LBBB is not benign，which can result in left ventricular remodeling，decreased cardiac constructive function，abnormal myocardial perfusion，endocardial fibrosis and myocardial fibrosis.The parameters of myocardial work assecsed by echocardiograpgy and myocardial perfusion，as non-invasive examination，can to some extent reflect the degree of left ventricular remodeling in LBBB-CM.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.