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.

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.

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 investigate the predictive value of sphinor kinase 1 (sphk1), D-lactic acid, and intestinal fatty acid binding protein (I-FABP) for gastrointestinal injury in patients with sepsis. METHODS: A prospective observational study was conducted. Sixty-eight patients with sepsis and gastrointestinal dysfunction admitted to the department of critical care medicine of the First Affiliated Hospital of Baotou Medical College Inner Mongolia University of Science and Technology from May 2024 to March 2025 were enrolled (sepsis group), and they were divided into acute gastrointestinal injury (AGI) I-IV groups according to the definition and grading criteria of AGI proposed by the European Society of Intensive Care Medicine in 2012. Twenty non-sepsis patients without AGI admitted to the intensive care unit during the same period were enrolled as the control group (non-sepsis group). Within 30 minutes of patient enrollment, plasma sphk1, D-lactic acid, and I-FABP levels were determined by enzyme linked immunosorbent assay (ELISA). General data such as gender, age were recorded, and levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), lactic acid (Lac), and acute physiology and chronic health evaluation II (APACHEII), sequential organ failure assessment (SOFA) were measured. Spearman method was used to analyze the correlation between sphk1, I-FABP, D-lactic acid and other indicators. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive value of sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score for gastrointestinal injury in patients with sepsis. RESULTS: Among the 68 sepsis patients, 13 were classified as AGI grade I, 16 as AGI grade II, 23 as AGI grade III, and 16 had AGI grade IV. There were no statistically significant differences in gender, age, and abdominal infection rate among the groups. The SOFA score and APACHEII score of the sepsis group were significantly higher than those of the non-sepsis group; and the APACHEII score of the AGI IV group was significantly higher than that of the AGI I and AGI II groups. The levels of sphk1, D-lactic acid, I-FABP, PCT, Lac and hs-CRP in the sepsis group were significantly higher than those in the non-sepsis group, and each indicator gradually increased with the increase of AGI grade. Correlation analysis showed that plasma sphk1, D-lactic acid, and I-FABP in patients with sepsis-induced gastrointestinal injury were positively correlated with PCT, Lac, APACHEII score, and AGI grade (all P < 0.05), and sphk1 was positively correlated with I-FABP and D-lactic acid (r values were 0.773 and 0.782, respectively, both P < 0.05). ROC curve analysis showed that sphk1, D-lactic acid, I-FABP, APACHEII score, and SOFA score had high predictive value for gastrointestinal injury in patients with sepsis, with area under the curve (AUC) of 0.996, 0.987, 0.976, 0.901, and 0.934 (all P < 0.05). When the optimal cut-off value of sphk1 was 60.46 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of D-lactic acid was 1 454.3 μg/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of I-FABP was 0.91 ng/L, the sensitivity and specificity were 95.6% and 100%, respectively; when the optimal cut-off value of APACHEII score was 14.5, the sensitivity and specificity were 80.9% and 85.0%, respectively; when the optimal cut-off value of SOFA score was 3.5, the sensitivity and specificity were 85.3% and 95.0%, respectively. CONCLUSIONS The levels of plasma sphk1, I-FABP, and D-lactic acid were significantly elevated in patients with sepsis and gastrointestinal injury. These indicators can serve as sensitive and relatively specific serological markers for early prediction of intestinal mucosal damage.
Humans ; Lactic Acid/blood* ; Fatty Acid-Binding Proteins/blood* ; Sepsis/complications* ; Prospective Studies ; Male ; Female ; Middle Aged ; Predictive Value of Tests ; Adult ; Aged ; Gastrointestinal Diseases/blood* ; Prognosis

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

BACKGROUND:Patch surgery by tension-free repair has become the first choice for treatment of abdominal hernias in recent years because of its effectiveness in reducing postoperative pain and recurrence rates compared to traditional suturing.OBJECTIVE:To summarize the advantages and disadvantages associated with the application of different hernia repair patch materials.METHODS:CNKI,Google Scholar,and PubMed databases were searched using Chinese and English search terms"abdominal wall defect,hernia patches,hernia treatment"for articles published from January 2018 to February 2024.A few classic early-onset articles were used to express the development of hernia repair.After preliminary screening by reading titles and abstracts,those with low relevance to hernia repair materials were excluded.Finally,90 articles were included for summarization.RESULTS AND CONCLUSION:Hernia repair patches can be divided into non-absorbable synthetic patches,absorbable synthetic patches,natural polymer patches,and composite patches based on different materials used.Non-absorbable patches have high mechanical strength and are beneficial for tissue healing in hernia areas,but long-term presence of patches in the body may trigger immune responses,leading to inflammation and pain.Absorbable synthetic patches and natural polymer patches have good tissue compatibility and degradability,but their mechanical strength is unstable.Composite material patches inherit the excellent mechanical properties of traditional non-absorbable patches and reduce the risk of complications through the design of absorbable parts.In subsequent studies of hernia repair patch materials,researchers should focus on how to combine novel technologies with composite patches to form multifunctionalized hernia repair materials.

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.

Good endometrial receptivity is an essential factor for embryo implantation,and gene expression in endometrial tissue during the window of implantation(WOI)is closely related to receptivity.Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases,as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression.Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism.Moreover,gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure,thereby guiding individualized embryo transfer strategies.This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions.This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level,in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.