OBJECTIVE To study the quality standard of the ethnic medicine Diplazium lanceum， and to provide reference for its quality control.METHODS The medicinal material of D. lanceum was identified by properties， microscopy， and thin-layer chromatography（TLC）， and its moisture， ash， and extract contents were determined. The contents of chlorogenic acid and rutin in 10 batches of D. lanceum were determined by high-performance liquid chromatography . RESULTS The rhizome of D. lanceum is slender and creeping， the leaf is leathery and shriveled， and yellow sporangia are borne on the abaxial surface of the leaf. The transverse section of the leaf shows inclusions， sclerenchyma， phloem cells， etc.； the transverse section of the petiole shows ground tissue， sclerenchyma， endodermis， etc.； the transverse section of the rhizome shows ground tissue， tracheids， vascular bundles， etc.； and the powder shows spiral vessels and brown inclusions. The TLC identification results showed that the chromatogram of the test sample exhibited spots of the same color at the corresponding positions as the chromatogram of the chlorogenic acid reference substance. The content ranges of moisture， total ash， acid-insoluble ash， extract， chlorogenic acid， and rutin in the 10 batches of samples were 10.18%-12.43%， 7.08%-19.12%， 0.95%-10.62%， 14.13%-26.05%， 0.113 1-1.015 9 mg/g， and 0.009 9-0.208 9 mg/g， respectively. CONCLUSIONS In the quality standard of D. lanceum， the moisture content should be ≤12.5%， total ash content should be ≤20.0%， acid-insoluble ash content should be ≤11.0%， extract content should be ≥14.0%， and chlorogenic acid content should be ≥0.11 mg/g. The established method is simple， specific， and reproducible， and can provide a scientific basis for the quality control of D. lanceum.

During habitation on low-Earth-orbit (LEO) space stations, astronauts are exposed to a combination of orbital microgravity, space radiation, an enclosed and artificially controlled cabin environment, altered sleep-wake rhythms, and sustained operational and psychosocial demands. These factors can modify sensorimotor inputs, body-fluid distribution, arousal state, and task-related neural processing, thereby affecting brain function and behavior. Because evidence from real spaceflight remains limited by small samples, heterogeneous mission durations, and different measurement time points, this review integrates findings from real human spaceflight with relevant ground-based analog studies while treating real orbital studies as the primary source of evidence. We focus on electroencephalography (EEG) and event-related potentials (ERPs), structural and functional neuroimaging, and sensorimotor and cognitive outcomes, with particular attention to the direction, anatomical distribution, temporal course, and possible physiological significance of the reported changes. EEG studies indicate that long-duration spaceflight is associated with increased resting-state beta activity, particularly in sensorimotor and frontotemporal regions, together with state-dependent alterations in beta-band functional connectivity. In contrast, alpha source power and functional connectivity associated with the default mode network are reduced during long-duration missions, and some of these effects may persist into the early postflight period. Task-related electrophysiological findings further suggest that sustained mental workload can weaken frontocentral theta-temporoparietal gamma phase-amplitude coupling, whereas in-flight decision-making is accompanied by reduced P300 amplitude and reorganization of feedback-related potentials. Short-duration missions, however, have shown relative preservation of posterior dominant rhythms and some ERP measures, indicating that mission duration, recording state, and task demands substantially influence the observed electrophysiological phenotype. Neuroimaging provides complementary evidence at structural and network levels. Long-duration spaceflight has been associated with upward brain displacement, ventricular and cerebrospinal fluid expansion, regional gray- and white-matter remodeling, and alterations in white-matter structural connectivity. Functional magnetic resonance imaging (fMRI) studies further indicate reorganization of vestibular-sensorimotor, visual, and default mode networks. Some network changes recover after return to Earth, whereas others may remain detectable for months. Importantly, most MRI measurements are obtained after landing rather than in orbit; therefore, postflight findings may reflect a mixture of in-flight adaptation, the rapid transition back to 1 g, and subsequent readaptation rather than a single spaceflight effect. Behavioral evidence is most consistent for sensorimotor function. Early after return, astronauts frequently show impaired postural control, gait, spatial orientation, and coordination, consistent with reweighting among vestibular, visual, and proprioceptive information. By comparison, simple cognition and some critical operational tasks are often preserved. More subtle or high-load processes-including sustained attention, feedback evaluation, temporal processing, error monitoring, and metacognitive calibration may be more sensitive than global cognitive performance. This dissociation between neural change and preserved behavior suggests that altered brain activity should not automatically be interpreted as functional deterioration. Integrating the available modalities, we propose that LEO space-station habitation is better characterized by system-specific and stage-dependent neural adaptation than by a generalized increase or decline in brain function. The most coherent cross-modal pattern involves sensorimotor reorganization: reduced gravitational reference and weight-bearing feedback under microgravity may drive reweighting of vestibular, visual, and proprioceptive inputs, accompanied by changes in beta activity and vestibular-sensorimotor networks and followed by transient postflight sensorimotor deficits. A second major process involves fluid-related structural remodeling, in which cephalad fluid shifts and altered hydrostatic gradients may contribute to changes in cerebrospinal fluid spaces, ventricular volume, and brain tissue configuration. Resting-state and cognitive electrophysiological changes likely represent additional adjustments in network regulation and resource allocation, but their functional interpretation remains more dependent on sleep, workload, recording conditions, and individual differences. Future studies should move beyond isolated pre-post comparisons and group averages toward standardized longitudinal designs spanning preflight, multiple in-flight time points, and postflight recovery. Synchronized assessment of brain function, behavior, sleep, and key environmental parameters should be used to characterize individual adaptation trajectories and determine which neural changes reflect successful compensation, which predict delayed recovery, and which have genuine value for brain-health risk prediction and individualized countermeasures.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the leading cause of dementia in the elderly, is characterized by severe cognitive decline, loss of daily living abilities, and neuropsychiatric symptoms. This condition imposes a substantial burden on patients, families, and society. Despite extensive research efforts, the complex pathogenesis of AD, particularly the early mechanisms underlying cognitive dysfunction, remains incompletely understood, posing significant challenges for timely diagnosis and effective therapeutic intervention. Among the various cellular components implicated in AD, GABAergic interneurons have emerged as critical players in the pathological cascade, playing a pivotal role in maintaining neural network integrity and function in key brain regions affected by the disease. GABAergic interneurons represent a heterogeneous population of inhibitory neurons essential for sustaining neural network homeostasis. They achieve this by precisely modulating rhythmic oscillatory activity (e.g., theta and gamma oscillations), which are crucial for cognitive processes such as learning and memory. These interneurons synthesize and release the inhibitory neurotransmitter GABA, exerting potent control over excitatory pyramidal neurons through intricate local circuits. Their primary mechanism involves synaptic inhibition, thereby modulating the excitability and synchrony of neural populations. Emerging evidence highlights the significant involvement of GABAergic interneuron dysfunction in AD pathogenesis. Contrary to earlier assumptions of their resistance to the disease, specific subtypes exhibit vulnerability or altered function early in the disease process. Critically, this impairment is not merely a consequence but appears to be a key driver of network hyperexcitability, a hallmark feature of AD models and potentially a core mechanism underlying cognitive deficits. For instance, parvalbumin-positive (PV⁺) interneurons display biphasic alterations in activity. Both suppressing early hyperactivity or enhancing late activity can rescue cognitive deficits, underscoring their causal role. Somatostatin-positive (SST⁺) neurons are highly sensitive to amyloid β-protein (Aβ) dysfunction. Their functional impairment drives AD progression via a dual pathway: compensatory hyperexcitability promotes Aβ generation, while released SST-14 forms toxic oligomers with Aβ, collectively accelerating neuronal loss and amyloid deposition, forming a vicious cycle. Vasoactive intestinal peptide-positive (VIP⁺) neurons, although potentially spared in number early in the disease, exhibit altered firing properties (e.g., broader spikes, lower frequency), contributing to network dysfunction (e.g., in CA1). Furthermore, VIP release induced by 40 Hz sensory stimulation (GENUS) enhances glymphatic clearance of Aβ, demonstrating a direct link between VIP neuron function and modulation of amyloid pathology. Given their central role in network stability and their demonstrable dysfunction in AD, GABAergic interneurons represent promising therapeutic targets. Current research primarily explores three approaches: increasing interneuron numbers (e.g., improving cortical PV⁺ interneuron counts and behavior in APP/PS1 mice with the antidepressant citalopram; transplanting stem cells differentiated into functional GABAergic neurons to enhance cognition), enhancing neuronal activity (e.g., using low-dose levetiracetam or targeted activation of specific molecules to boost PV⁺ interneuron excitability, restoring neural network γ‑oscillations and memory; non-invasive neuromodulation techniques like 40 Hz repetitive transcranial magnetic stimulation (rTMS), GENUS, and minimally invasive electroacupuncture to improve inhibitory regulation, promote memory, and reduce Aβ), and direct GABA system intervention (clinical and animal studies reveal reduced GABA levels in AD-affected brain regions; early GABA supplementation improves cognition in APP/PS1 mice, suggesting a therapeutic time window). Collectively, these findings establish GABAergic interneuron intervention as a foundational rationale and distinct pathway for AD therapy. In conclusion, GABAergic interneurons, particularly the PV⁺, SST⁺, and VIP⁺ subtypes, play critical and subtype-specific roles in the initiation and progression of AD pathology. Their dysfunction significantly contributes to network hyperexcitability, oscillatory deficits, and cognitive decline. Understanding the heterogeneity in their vulnerability and response mechanisms provides crucial insights into AD pathogenesis. Targeting these interneurons through pharmacological, neuromodulatory, or cellular approaches offers promising avenues for developing novel, potentially disease-modifying therapies.

With the rapid development of deep learning(DL)technology,its potential applications in the medical field have become increasingly prominent.As a refractory disease,osteonecrosis of the femoral head(ONFH)has certain limitations in traditional diagnostic and therapeutic approaches.The application of DL technology is expected to overcome these limitations and improve diagnosis and treatment outcomes.At present,the applications of DL models-including enhancing image clarity,improving diagnostic accuracy and efficiency,conducting prognostic evaluations,optimizing preoperative planning,assisting intraoperative imaging,and customizing personalized treatment plans-have fully demonstrated their tremendous potential in the diagnosis and treatment of ONFH.This review summarizes the current application status of DL in ONFH diagnosis and treatment,aiming to provide references and insights for future related research.

Objective: To investigate the prevalence levels and trends of overweight and obesity among adult residents in Zhejiang Province from 2015 to 2023, so as to provide a basis for developing regional weight management strategies. Methods: Permanent residents aged ≥18 years from Zhejiang Province who participated in the China Chronic Disease and Risk Factor Surveillance Project in 2015, 2018, and 2023 were selected as survey subjects. Data on sociodemographic information, height, weight and waist circumference were collected through questionnaire surveys and physical examinations. The prevalence of overweight, obesity, and central obesity were calculated and standardized using data from the Seventh National Population Census of Zhejiang Province in 2020. The Cochran-Armitage trend test was employed to analyze the trends in prevalence of overweight, obesity, and central obesity across different genders, ages and regions. Results: A total of 23 902 individuals were surveyed, comprising 10 985 males (45.96%) and 12 917 females (54.04%). Participants were aged ≥60 years, with 13 088 individuals accounting for 54.76%. There were 9 388 urban residents (39.28%) and 14 514 rural residents (60.72%). The standardized prevalence of overweight among residents increased from 30.05% in 2015 to 33.98% in 2023, the standardized prevalence of obesity increased from 7.67% to 15.22%, and the standardized prevalence of central obesity increased from 22.81% to 33.82%, all showed upward trends (all P<0.05). In 2015, 2018, and 2023, the standardized prevalence of overweight was higher in males than in females. In 2018 and 2023, the standardized prevalence of obesity and central obesity were higher in males than in females (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both males and females showed upward trends (all P<0.05). In 2015, 2018 and 2023, the prevalence of central obesity showed an increasing trend with age (all P<0.05). From 2015 to 2023, upward trends were observed in the prevalence of overweight, obesity, and central obesity among residents aged 18-<45 years and aged ≥60 years, as well as in the prevalence of obesity and central obesity among residents aged 45-<60 years (all P<0.05). In 2015, 2018 and 2023, the standardized prevalence of overweight obesity were higher in urban areas than in rural areas, while the standardized prevalence of central obesity was lower in urban areas (all P<0.05). From 2015 to 2023, the standardized prevalence of overweight, obesity, and central obesity among both urban and rural areas showed upward trends (all P<0.05). Conclusion From 2015 to 2023, the prevalence of overweight, obesity, and central obesity among adult residents in Zhejiang Province showed increasing trends, with variations in prevalence levels and trends observed across genders, ages, and urban / rural areas.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

Objective Neurological disorders,constitute the majority of acupuncture-treated ailments.By critically examining a comprehensive selection of high-quality clinical randomized controlled trials(RCTs)from both domestic and international sources,we aimed to uncover the prevailing hot research topic and potential future directions in acupuncture therapy for these conditions.Methods Four databases,including PubMed,Web of science,Cochrane Library and EMBASE were searched.The search period is set from the establishment of each database to November 30,2023.And the search content was RCTs of acupuncture for neurological diseases classified as Ⅰ and Ⅱ by the Chinese Academy of Sciences were extracted.Key aspects extracted included annual publication volume,journals,disease types,outcomes,conclusions,acupuncture methods and control groups.Results A total of 81 high-quality RCTs were identified,revealing a consistent annual publication trend of acupuncture for neurological disorders.Key journals contributing to this research were Cephalalgia,Clinical Rehabilitation and Clinical Journal Of Pain,etc.The studies predominantly focused on migraine and sequela of apoplexy with migraine days/frequency and Ashworth scale and its modifications as commonly used primary outcome indicators,respectively.Overall,there were 73 RCTs that concluded that acupuncture for neurologic disorders were effective,8 were ineffective.The acupuncture methods were diverse,encompassing acupuncture,individualized acupuncture and transcutaneous electrical nerve stimulation,etc.The control measures were also varied,featuring sham acupuncture,sham-acupoint and micro-needle,etc.Conclusion With the development of acupuncture RCTs,their international influence has expanded.Research has shifted from validation of effectiveness to exploration of mechanisms,and despite the expansion of the disease spectrum of acupuncture,acupuncture trials have yet to be regulated and standardized,and the assessment of acupuncture efficacy remains controversial and challenging for the discipline.It is recommended to promote multi-center cooperation and strengthen the training of trialists etc.to provide more high-quality clinical evidence.