ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

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:Dexamethasone and hindlimb suspension are commonly used methods for modeling sarcopenia in animal experiments due to their short modeling time,ease of operation,and low cost.OBJECTIVE:To compare the differences in muscle mass,strength and functional phenotypes and molecular mechanisms between two mouse sarcopenia models induced by dexamethasone and hindlimb suspension.METHODS:Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group).The normal control group received no intervention.The dexamethasone group received daily intraperitoneal injections of 1 mg/kg/d dexamethasone sodium phosphate solution for 6 continuous days to establish sarcopenia models in mice,while mice in the hindlimb suspension group were suspended by tail harness for 16 hours,once per day,to establish sarcopenia models.Within 6 weeks after modeling,changes in body mass were monitored.After 6 weeks of modeling,mice were tested for limb grip strength,mobility(swimming test),skeletal muscle wet mass,and skeletal muscle pathological morphology.Expressions of skeletal muscle protein synthesis and catabolism indexes as well as the AMPK/FoXO3α signaling pathway were detected by RT-PCR and western blot.RESULTS AND CONCLUSION:(1)Two weeks after modeling,both dexamethasone and hindlimb suspension groups showed a significant decrease in body mass compared with the normal control group(P<0.001).After 6 weeks of modeling,grip strength of mice in both dexamethasone and hindlimb suspension groups was lower than that in the normal control group(P<0.001).The wet mass of gastrocnemius and extensor digitorum longus muscles and the cross-sectional area of gastrocnemius and soleus muscles in the dexamethasone group were lower than those in the normal control group(P<0.05).Compared with the hindlimb suspension group,the cross-sectional area of gastrocnemius muscle was significantly smaller in the dexamethasone group(P<0.05),while the cross-sectional area of soleus muscle was larger in the dexamethasone group(P<0.05).Mice in the dexamethasone group had reduced mobility when compared with those in the normal control group and the hindlimb suspension group(P<0.05).(3)Compared with the normal control group,PI3K,mTOR,AMPK,and PGC-1α mRNA expression and P-AMPK/AMPK protein were decreased in the two modeling groups(P<0.05),and FoXO3α mRNA expression and PGC-1α and FoXO3 protein expression were elevated(P<0.05);in the dexamethasone group,Akt1 mRNA expression was decreased(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was elevated(P<0.05);in the hindlimb suspension group,Akt1 mRNA expression was elevated(P<0.05).(4)Compared with the dexamethasone group,mTOR,Akt1,and FoXO3α mRNA expression was elevated in the hindlimb suspension group(P<0.05),while Atrogin-1 and MuRF-1 mRNA expression was decreased(P<0.05).To conclude,both modeling methods could decrease the levels of mitochondrial energy metabolism in skeletal muscle,with the dexamethasone group mediating atrophy of skeletal muscle through the dual action of ubiquitin proteasome and energy metabolism pathways,and the hindlimb suspension group inducing atrophy of skeletal muscle by mediating the energy metabolism pathway through the AMPK/FoXO3α signaling pathway,subsequently causing a reduction in mass,strength,and function of skeletal muscle.

Objective To investigate the relationship between vertical laminar fracture(VLF)in thoracolumbar burst fractures and both neurological injury and dural tear.Methods A retrospective analysis was conducted on the clinical data and multi spiral computed tomography(MSCT)coronal images of 255 patients of thoracolumbar burst fractures.The patients were divided into three groups based on the presence of VLF[Ⅰ group(complete VLF group),Ⅱ group(partial VLF group),and Ⅲ group(normal lamina group)].Statistical analysis was performed using analysis of variance and Fisher's exact test to compare radiological parameters,inci-dence of dural tear,and neurological injury among the groups.Results The Ⅰ group showed significant differences in spinal canal sagittal diameter,pedicle distance,and spinal canal area compared with the other two groups(P<0.05).However,there was no sig-nificant difference in vertebral body compression rate between the Ⅰ group and the Ⅱ group(P>0.05).The Ⅰ group had the high-est incidence of severe neurological injury[American Spinal Injury Association(ASIA)impairment scale grades A and B]and dural tear(P<0.05).Conclusion The severity of VLF is closely related to dural tear and neurological injury.MSCT coronal images can clearly display the extent of VLF,providing an important basis for clinical evaluation and treatment plan.

Most patients with differentiated thyroid cancer benefit from surgery,radioactive iodine-131 therapy and TSH suppression therapy,resulting in a favorable prognosis.However,once radioactive iodine refractory thyroid cancer(RAIR-DTC)develops,the prognosis becomes significantly poorer,treatment options are limited,and therapeutic efficacy is constrained.This has emerged as a research focus in recent years.With advancements in understanding tumor mechanisms and rapid developments in diagnostic and therapeutic technologies,significant progress has been made in new drugs and new treatments for RAIR-DTC.The development of novel targeted therapies has revolutionized the management.Notably,multi-target tyrosine kinase inhibitor(mTKI)such as sorafenib and lenvatinib has demonstrated significant improvements in progression-free survival,thereby establishing targeted therapy as a viable option for RAIR-DTC.Cabozantinib has also shown promising results as a second-line treatment following TKI failure.Other TKIs like apatinib and anlotinib have also arnered attention due to efficacy and safety.Additionally,specific TKI targeting BRAF V600E mutations,RET fusions and NTRK fusion genes have ushered in an era of precision medicine for RAIR-DTC.Thus,for patients with RET or NTRK fusions,guidelines recommend prioritizing specific target TKI over pan-target kinase inhibitors.If no such gene mutations are present,pan-target kinase inhibitors are considered as the standard first-line treatments.MEK inhibitors(selumetinib)may induce redifferentiation,potentially restoring iodine uptake.Consequently,the combination of targeted therapy and iodine-131 therapy represents a promising strategy.While immune checkpoint inhibitors only have not yielded optimistic results in RAIR-DTC,combination with TKIs has shown certain safety and efficacy,warranting further exploration.However,given issues of drug resistance and intolerable side effects,it is imperative to explore new treatments.Radionuclide therapy guided by nuclear medicine molecular imaging offers potential hope for RAIR-DTC patients.Targeted radioligand/receptor therapies,such as PSMA,SSTR and FAPi,exhibit characteristics of targeting,visualization and integration of diagnosis and treatment.Initial trials of them in RAIR-DTC patients with TKIs treatment failure have been confirmed feasibility.This review summarized recent advances in new drugs and new technologies for RAIR-DTC treatment,aiming to guide clinical practice and anticipate more personalized and precise treatment options to improve quality of life and survival.

The phenomenon that the listener's reception,perception,and understanding of a sound are dis-turbed by an irrelevant sound is called the auditory masking effect.In the auditory masking effect,the human audi-tory nervous system is able to screen and extract target sounds from different sound sources based on different cues,and filter out unwanted masked sounds.The auditory masking effect is not a simple processing from separation to integration however it is,with a complex internal mechanism.Under energetic masking,acoustic information such as frequency and intensity of target and masher generates coding competition in the auditory periphery.Under infor-mational masking,target sound and masher competes with perceptive and cognitive information in the auditory cen-ter.Informational masking is the focus of masking research,but its mechanism is still controversial.This study studies the neural mechanism of informational masking effect from three factors,including similarity,uncertainty and intelligibility.

Disorders of mitochondrial dynamics are closely re-lated to the development of neurodegenerative diseases(NDDs),which are characterized by the loss of neurons in brain and spinal cord cells.Diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease,and so on are in-volved in NDDs,which are often accompanied by disorders of mi-tochondrial dynamics during the development of these diseases.Recently,the researches on mitochondrial dynamics to study the pathogenesis of neurodegenerative diseases and related medica-tion innovation have garnered significant attention.This review focuses on the fundamental molecular processes of mitochondrial dynamics,such as mitochondrial transport,mitochondrial autoph-agy,and mitochondrial fission-fusion,and their molecular mecha-nisms in the pathogenesis of NDDs.It also outlines the recent research progress on Chinese materia medica and natural prod-ucts in ameliorating NDDs by modulating mitochondrial dynam-ics.The aim is to establish a foundation for researching innova-tive traditional Chinese medicine for NDDs-related diseases by focusing on mitochondrial dynamics.