OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells. METHODS The rats were given Sanchong tongluo sanjie formula powder [0.946 g/（kg·d）]， Sanchong tongluo sanjie formula decoction [2.730 g/（kg·d）]， and normal saline intragastrically， and injected with Cisplatin injection （4.2 mg/kg） intra-peritoneally to prepare powder-containing serum， decoction-containing serum， positive control serum and negative control serum. Lewis lung cancer cells were divided into negative control serum group， positive control serum group， and 5%， 10%， 20% drug-containing serum groups. The cell proliferation inhibition rates at 24， 48， and 72 hours post- intervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum. The cell invasion ability， metastasis ability and apoptotic rate were detected in the negative control serum group， positive control serum group， 20% powder-containing serum group， and 20% decoction-containing serum group. Protein expressions of vascular endothelial growth factor （VEGF）， hypoxia-inducible factor-1α （HIF-1α）， prolyl hydroxylase-2 （PHD2）， matrix metalloproteinase-2 （MMP-2）， extracellular regulated protein kinases （ERK），c-Jun N-terminal kinase （JNK） and p38 mitogen-activated protein kinase （p38 MAPK） were detected. RESULTS The cell proliferation inhibition rates for both the 20% powder-containing serum group and the 20% decoction-containing serum group， when intervened for 48 hours， were not less than 50%. Compared with negative control serum group， the number of invasive Lewis lung cancer cells and migration distance were decreased significantly， while the apoptotic rate was increased significantly （P＜0.05）； the apoptotic rate in the 20% powder- containing serum group was significantly higher than 20% decoction-containing serum group （P＜0.05）. The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20% powder-containing serum group （P＜0.05）， while the protein expression of HIF-1α was decreased significantly in the 20% decoction-containing serum group （P＜0.05）. CONCLUSIONS Sanchong tongluo sanjie formula can inhibit the proliferation， invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore， the powder demonstrates superior efficacy compared to the decoction， suggesting that they may possess different mechanisms of action.

Adipose tissue is a critical energy reservoir in animals and humans, with multifaceted roles in endocrine regulation, immune response, and providing mechanical protection. Based on anatomical location and functional characteristics, adipose tissue can be categorized into distinct types, including white adipose tissue (WAT), brown adipose tissue (BAT), beige adipose tissue, and pink adipose tissue. Traditionally, adipose tissue research has centered on its morphological and functional properties as a whole. However, with the advent of single-cell transcriptomics, a new level of complexity in adipose tissue has been unveiled, showing that even under identical conditions, cells of the same type may exhibit significant variation in morphology, structure, function, and gene expression——phenomena collectively referred to as cellular heterogeneity. Single-cell transcriptomics, including techniques like single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq), enables in-depth analysis of the diversity and heterogeneity of adipocytes at the single-cell level. This high-resolution approach has not only deepened our understanding of adipocyte functionality but also facilitated the discovery of previously unidentified cell types and gene expression patterns that may play key roles in adipose tissue function. This review delves into the latest advances in the application of single-cell transcriptomics in elucidating the heterogeneity and diversity within adipose tissue, highlighting how these findings have redefined the understanding of cell subpopulations within different adipose depots. Moreover, the review explores how single-cell transcriptomic technologies have enabled the study of cellular communication pathways and differentiation trajectories among adipose cell subgroups. By mapping these interactions and differentiation processes, researchers gain insights into how distinct cellular subpopulations coordinate within adipose tissues, which is crucial for maintaining tissue homeostasis and function. Understanding these mechanisms is essential, as dysregulation in adipose cell interactions and differentiation underlies a range of metabolic disorders, including obesity and diabetes mellitus type 2. Furthermore, single-cell transcriptomics holds promising implications for identifying therapeutic targets; by pinpointing specific cell types and gene pathways involved in adipose tissue dysfunction, these technologies pave the way for developing targeted interventions aimed at modulating specific adipose subpopulations. In summary, this review provides a comprehensive analysis of the role of single-cell transcriptomic technologies in uncovering the heterogeneity and functional diversity of adipose tissues.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

OBJECTIVE To evaluate the influence of pharmaceutical quality control on the efficiency and outcomes of standardized medication therapy management （MTM） services for patients with coronary heart disease by using Economic， Clinical and Humanistic Outcomes （ECHO） model. METHODS This study collected case data of coronary heart disease patients who received MTM services during January-March 2023 （pre-quality control implementation group， n＝96） and June-August 2023 （post-quality control implementation group， n＝164）. Using propensity score matching analysis， 80 patients were selected from each group. The study subsequently compared the economic， clinical， and humanistic outcome indicators of pharmaceutical services between the two matched groups. RESULTS There were no statistically significant differences in baseline data between the two groups after matching （P＞0.05）. Compared with pre-quality control implementation group， the daily treatment cost （16.26 yuan vs. 24.40 yuan， P＜0.001）， cost-effectiveness ratio [23.12 yuan/quality-adjusted life year （QALY） vs. 32.32 yuan/QALY， P＜0.001]， and the incidence of general adverse drug reactions （2.50% vs. 10.00%， P＝0.049） of post-quality control implementation group were decreased significantly； the utility value of the EuroQol Five-Dimensional Questionnaire （0.74± 0.06 vs. 0.71±0.07， P＝0.003）， the reduction in the number of medication related problems （1.0 vs. 0.5， P＜0.001）， the medication adherence score （[ 6.32±0.48） points vs. （6.10±0.37） points， P＝0.001]， and the satisfaction score （[ 92.56±1.52） points vs. （91.95±1.56） points， P＝0.013] all showed significant improvements. Neither group experienced serious adverse drug reactions. There was no statistically significant difference in the incidence of new adverse reactions between the two groups （1.25% vs. 3.75%， P＝0.310）. CONCLUSIONS Pharmaceutical quality control can improve the quality of pharmaceutical care， and the ECHO model can quantitatively evaluate the effect of MTM services， making pharmaceutical care better priced and more adaptable to social needs， thus being worthy of promotion.

Objective To investigate risk factors for short-term residual symptoms after resolution of benign paroxysmal positional vertigo （BPPV） through logistic regression analysis. Methods A total of 110 patients with BPPV in our hospital from July 2020 to January 2023 were enrolled. The patients were grouped according to whether they were cured or had residual symptoms at 8 weeks after repositioning maneuvers. A logistic regression analysis was used to analyze the risk factors for short-term residual symptoms after treatment. Results Forty-nine of the 110 patients had short-term residual symptoms. The univariable logistic regression analyses showed that age， the duration of vertigo before treatment， recurrence， medical history （hypertension， diabetes， and ischemic cerebrovascular disease）， anxiety， depression， sleep quality， and vestibular evoked myogenic potential were risk factors for short-term residual symptoms in patients with BPPV. The multivariable logistic regression analysis revealed that age （OR=0.942，95%CI 0.913-0.972，P<0.001）， the duration of vertigo before treatment（OR=0.333，95%CI 1.015~1.019，P=0.002），recurrence（OR=0.777，95%CI 0.726-0.832，P<0.001）， a history of hypertension（OR=0.682，95%CI 0.624-0.745，P<0.001）， a history of diabetes（OR=0.854，95%CI 0.791-0.922，P<0.001），a history of ischemic cerebrovascular disease（OR=0.876，95%CI 0.806-0.953，P=0.002）， anxiety（OR=1.158，95%CI 1.046-1.283，P=0.005），depression（OR=1.178，95%CI 1.033-1.344，P=0.014），sleep quality（OR=1.164，95%CI 1.009-1.343，P=0.037）， and vestibular evoked myogenic potential（OR=1.196，95%CI 1.068-1.340，P=0.002） were independent risk factors for short-term residual symptoms in patients with BPPV. Conclusion Patients with BPPV are more likely to have short-term residual symptoms if they have a history of hypertension， diabetes， or cerebrovascular diseases， advanced age， a long duration of vertigo before treatment， and the presence of emotional disorders （anxiety， depression， sleep deficiency， vestibular evoked myogenic potential abnormalities）.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective: To investigate the mental health status and related factors among primary and secondary school students in western Yunnan Province, so ao to provide scientific evidences for advancing mental health education. Methods: In June 2024, a stratified cluster sampling method was employed to select 4 584 students from 18 schools across Diqing Tibetan Autonomous Prefecture, Lincang City and Baoshan City three regions in western Yunnan Province. The Mental Health Test (MHT) was used for assessment. Latent class analysis (LCA) and Logistic regression were applied for data classification and related factor analysis respectively. Results: The overall positive detection rate of MHT was 11.81%, with a mean total score of 40.50±19.25. The predominant issues were learning anxiety (58.4%), hypersensitivity tendency (31.1%), and self blame tendency (23.1%). LCA categorized students into four groups:severe psychological problems group (74.4% detection rate), learning anxiety hypersensitivity group ( 16.4 %), learning anxiety physical symptoms group (9.2%), and healthy group (0). Logistic regression revealed that compared with the healthy group, the severe problems group showed higher risks among females ( OR =3.01), junior/senior high school students ( OR =1.88/4.02), and those with authoritarian parenting ( OR =3.54); the anxiety hypersensitivity group had higher risks for females ( OR =1.87), senior high students ( OR =1.54), boarders ( OR =1.31), and authoritarian parenting recipients ( OR = 1.85 ); the anxiety physical symptoms group demonstrated increased risks among females ( OR =2.22), senior high students ( OR =2.58), and authoritarian parenting recipients ( OR =2.74), while lower risks were observed for students with parent/grandparent guardians ( OR =0.38) and non only children ( OR =0.58) (all P <0.05). Conclusions Mental health problems are prominent among students in western Yunnan, with gender, grade level, boarding status, guardian type, and parenting style being key determinants. Recommendations include strengthening mental health education, prioritizing left behind children s psychological well being and promoting healthy development.

Lung cancer is the most common malignant tumor worldwide, ranking first in both incidence and mortality rates. According to the latest statistics from the International Agency for Research on Cancer (IARC), approximately 2.5 million new cases and around 1.8 million deaths from lung cancer occurred in 2022, placing a tremendous burden on global healthcare systems. The high mortality rate of lung cancer is closely linked to its subtle early symptoms, which often lead to diagnosis at advanced stages. This not only complicates treatment but also results in substantial economic losses. Current treatment options for lung cancer include surgery, radiotherapy, chemotherapy, targeted drug therapy, and immunotherapy. Among these, immunotherapy has emerged as the most groundbreaking advancement in recent years, owing to its unique antitumor mechanisms and impressive clinical benefits. Unlike traditional therapies such as radiotherapy and chemotherapy, immunotherapy activates or enhances the patient’s immune system to recognize and eliminate tumor cells. It offers advantages such as more durable therapeutic effects and relatively fewer toxic side effects. The main approaches to lung cancer immunotherapy include immune checkpoint inhibitors, tumor-specific antigen-targeted therapies, adoptive cell therapies, cancer vaccines, and oncolytic virus therapies. Among these, immune checkpoint inhibitors and tumor-specific antigen-targeted therapies have received approval from the U.S. Food and Drug Administration (FDA) for clinical use in lung cancer, significantly improving outcomes for patients with advanced non-small cell lung cancer. Although other immunotherapy strategies are still in clinical trials, they show great potential in improving treatment precision and efficacy. This article systematically reviews the latest research progress in lung cancer immunotherapy, including the development of novel immune checkpoint molecules, optimization of treatment strategies, identification of predictive biomarkers, and findings from recent clinical trials. It also discusses the current challenges in the field and outlines future directions, such as the development of next-generation immunotherapeutic agents, exploration of more effective combination regimens, and the establishment of precise efficacy prediction systems. The aim is to provide a valuable reference for the continued advancement of lung cancer immunotherapy.

ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

ObjectiveAs the central hub of the classical visual pathway, the primary visual cortex not only encodes and processes visual information but also establishes dense neural circuit connections with higher-order cognitive brain regions. Numerous studies have shown that 40 Hz flicker stimulation can induce γ oscillations in the brain and significantly improve learning and cognitive impairments in patients with neurodegenerative diseases. Moreover, flickering light phenomena naturally occur in daily environments. Given that the primary visual cortex serves as the brain’s first cortical hub for receiving visual input, it is essential to comprehensively understand how non-invasive light flicker stimulation modulates its information processing mechanisms. This study systematically investigates the effects of non-invasive light flicker stimulation at different frequencies on the functional properties of neurons in the primary visual cortex of adult mice, aiming to uncover how such stimulation modulates this region and, consequently, affects overall brain function. MethodsThree groups of adult mice (approximately 12 weeks old) were exposed to light flicker stimulation at frequencies of 20 Hz, 40 Hz, and 60 Hz, respectively, for a duration of two months. A control group was exposed to the same light intensity without flickering. Following the stimulation period, in vivo multi-channel electrophysiological recordings were conducted. During these recordings, anesthetized mice were presented with various types of moving sinusoidal light gratings to assess the effects of different flicker frequencies on the functional properties of neurons in the primary visual cortex. ResultsThe experimental results demonstrate that two months of light flicker stimulation at 20 Hz, 40 Hz, and 60 Hz enhances the orientation tuning capabilities of neurons in the primary visual cortex. Specifically, 40 Hz and 60 Hz stimulation improved contrast sensitivity, whereas 20 Hz had no significant effect. Further analysis revealed that all three frequencies reduced neuronal response variability (as measured by the Fano factor), increased the signal-to-noise ratio, and decreased noise correlation (r_sc) between neurons. ConclusionNon-invasive light flicker stimulation enhances orientation tuning (e.g., orientation bias index) and contrast sensitivity (e.g., contrast threshold and C₅₀) in neurons of the primary visual cortex. This enhancement is likely due to improved information processing efficiency, characterized by reduced neuronal variability and increased signal-to-noise ratio. These findings suggest that the primary visual cortex can achieve precise and efficient information encoding in complex lighting environments by selectively adapting to different flicker frequencies and optimizing receptive field properties. This study provides new experimental evidence on how various types of light flicker influence visual perception and offers insights into the mechanisms through which specific frequencies enhance brain function.