AIM:To investigate the protective effects of Dendrobium officinale polysaccharide(DOP)on high glucose-induced apoptosis in retinal capillary pericytes and its potential mechanism involving mitochondrial function.METHODS:Retinal capillary pericytes were allocated into five groups: normal control(NC), high glucose(HG), and three DOP treatment groups(low, DOP-L; medium, DOP-M; high, DOP-H). Pericyte ultrastructure was analyzed using transmission electron microscopy(TEM). Apoptotic rate was quantified via Annexin V-FITC staining. Mitochondrial transmembrane potential was assessed using the JC-1 probe. Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot were employed to measure expression levels of cytochrome C(Cyt C), B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), Caspase-9, and Caspase-3, respectively.RESULTS:Compared to the NC group, pericytes exposed to HG exhibited significant mitochondrial damage, elevated apoptotic rate, increased mRNA and protein expression of Cyt C, Bax, Caspase-9, and Caspase-3(all P<0.01), alongside a marked reduction in mitochondrial transmembrane potential and expression of Bcl-2 mRNA and protein(all P<0.01). In contrast, DOP treatment groups(DOP-M,DOP-H)dose-dependently ameliorated mitochondrial damage, reduced apoptotic rate, downregulated Cyt C, Bax, Caspase-9, and Caspase-3 expression, enhanced mitochondrial transmembrane potential, and upregulated Bcl-2 expression relative to the HG group(all P<0.05).CONCLUSION:DOP attenuates high glucose-induced apoptosis and mitochondrial injury in retinal capillary pericytes. The underlying mechanism may involve the restoration of mitochondrial transmembrane potential.

This paper summarizes professor TU Jinwen's clinical experience in treating cancer-related insomnia （CRI） based on different qi and fire. It is believed that the pathogenesis of CRI can be divided into three stages. At the initial stage， qi movement is constrained， while the strong fire begins to stir， and the sovereign fire is unsettled， when qi is abundant， but the fire is not excessive. For this， Sanhua Jieyu Anshen Decoction （三花解郁安神汤） is suggested， which can move qi and vent constraint， clear and diffuse strong fire， calm the heart and spirit. At the progressive stage， strong fire becomes intense and burning， and qi transformation weakens， with toxin fire harassing the spirit. This is the stage where both qi and fire are excessive， for which Huanglian Jiedu Anshen Decoction （黄连解毒安神汤） can be used to clear and dissipate strong fire， drain fire and resolve toxin， clear heart and calm spirit. At the terminal stage， strong fire subsides， and consumption of qi damages healthy qi， with failure of nourishment of heart spirit， when both qi and fire deplete. Correspondingly， Erren Yangxin Anshen Decoction （二仁养心安神汤） is used to boost qi and nourish yin， restore interaction between the heart and the kidney， nourish the heart and calm spirit.

Chemical constituents of n-butanol fraction of ethanol extract from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja were studied. Ten compounds were purified by silica gel, MCI, ODS, Sephadex LH-20 column chromatography and semi-preparative high-performance liquid chromatography. Based on the physicochemical properties and spectroscopic data, these compounds were identified as (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(3′′,5′′-dimethoxy-(E)-p-coumaroyl)]-β-D-glucopyranoside (1), (4S)-4,8-dihydroxy-α-tetralone-5-[6′-(E)-feruloyl]-β-D-glucopyranoside (2), (1S,3R,4S,5R)-4,5-di-O-caffeoyl quinic acid methyl ester (3), (1R,3R,4S,5R)-3,4-di-O-caffeoyl quinic acid methyl ester (4), (3R,5R)-3,4,5-tri-O-caffeoylquinic acid methyl ester (5), (1R,3R,4S,5R)-3-O-caffeoyl-5-O-p-coumaroyl quinic acid methyl ester (6), (1R,3R,4S,5R)-3-O-p-coumaroy-4-O-caffeoyl quinic acid methyl ester (7), (1R,3R,4S,5R)-3-O-caffeoyl-4-O-p-coumaroy quinic acid methyl ester (8), (3R,5R)-3,5-di-O-caffeoyl quinic acid methyl ester (9) and (1S,3R,4R,5R)-4-O-caffeoyl-5-O-feruloyl quinic acid methyl ester (10). Among them, compound 1 was a new compound, and compounds 3–10 were isolated from the genus Cyclocarya for the first time.

This article provides a systematic review of the research progress in the mechanisms related to lung cancer and ferroptosis， ferroptosis-related lung cancer biomarkers and gene mutation targets， and ferroptosis-targeted regulation of Chinese medicine in treating lung cancer in the past five years， providing a feasible and effective basis for the prevention and treatment of lung cancer with Chinese medicine and the development of new drugs. According to the available studies， ferroptosis is widely suppressed in lung cancer， while the specific regulatory mechanisms have not been fully elucidated. The suppression is related to lipid metabolism， iron metabolism， cystine/glutamate antiporter system Xc^- （System Xc^-）/glutathione （GSH）/glutathione peroxidase 4 （GPX4）， ferroptosis suppressor protein 1 （FSP1）/coenzyme Q10 （CoQ10）/nicotinamide adenine dinucleotide phosphate ［NAD（P）H］， long non-coding RNA （lncRNA）， nuclear factor E₂-related factor 2 （Nrf2）， and p53. In modern times， traditional Chinese medicine is widely used in the comprehensive treatment of lung cancer， and it has gradually become a hot research topic due to its obvious advantages of anti-tumor activity， high efficacy， and low toxicity. Traditional Chinese medicine plays an important role in the treatment of lung cancer. Studies have shown that the active components， extracts， and prescriptions of Chinese medicine can induce ferroptosis in lung cancer cells through targeted regulation of iron metabolism， lipid metabolism， and p53， Nrf2， LncRNA， and GPX4 pathways to inhibit the growth and proliferation of lung cancer， thus exerting anti-tumor effects. Therefore， regulating ferroptosis is expected to become a new direction for preventing lung cancer. Basic research has shown that Chinese medicine can regulate ferroptosis via multiple targets and pathways in the treatment of lung cancer. At present， Chinese medicine demonstrates great research prospects in regulating ferroptosis to treat lung cancer， which， howeve， still faces challenges to achieve clinical transformation.

Objective: To explore the effect of different obesity indicators in predicting cardiovascular and cerebrovascular diseases (CVD) risk among patients with type 2 diabetes mellitus (T2DM), so as to provide the evidence for the early identification of CVD risk among T2DM patients. Methods: The patients with T2DM under community management in Qingpu District, Shanghai Municipality were selected as the study subjects in January 2025. Basic information such as gender, age, and blood glucose control status were collected through the Shanghai Chronic Disease Information Management System, while history of CVD were obtained from residents' electronic health records and the Shanghai Disease Control Information Platform. Obesity was assessed using body mass index (BMI), waist circumference (WC), BMI combined with WC, waist-to-height ratio (WHtR), and triglyceride (TG) combined with WC indicators. The association between obesity and CVD was analyzed using multivariable logistic regression models. The predictive effect of each obesity indicators for CVD was evaluated using the area under the receiver operating characteristic curve (AUC). Results: A total of 4 367 patients with T2DM were included, including 2 121 males (48.57%) and 2 246 females (51.43%). The average age was (68.71±8.05) years. The prevalence of CVD was 44.49%. Multivariable logistic regression analysis showed that after adjusting for age, education level, history of hypertension, duration of T2DM, use of glucose-lowering medications, renal function, and blood glucose control status, obese T2DM patients had a 389.4% increased risk of CVD compared to those with normal BMI; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WC; T2DM patients with isolated general obesity and compound obesity had 161.0% and 241.1% increased risks of CVD, respectively, compared to those with normal BMI and WC; centrally obese T2DM patients had a 100.4% increased risk compared to those with normal WHtR; T2DM patients with normal TG-high WC and high TG-high WC phenotypes had 83.1% and 68.8% increased risks of CVD, respectively, compared to those with normal TG and normal WC (all P<0.05). BMI had the highest AUC, at 0.714, with sensitivity and specificity of 0.675 and 0.642, respectively. This was followed by BMI combined with WC, which had an AUC of 0.707, with sensitivity and specificity of 0.635 and 0.679, respectively. Conclusions Obesity defined by BMI, WC, BMI combined with WC, WHtR, and TG combined with WC increases the risk of CVD among patients with T2DM. BMI and BMI combined with WC have better predictive effect in predicting CVD risk among patients with T2DM, and can be used as the primary obesity indicators for CVD risk screening.

ObjectiveIn the realm of forensic science, dust is a valuable type of trace evidence with immense potential for intricate investigations. With the development of DNA sequencing technologies, there is a heightened interest among researchers in unraveling the complex tapestry of microbial communities found within dust samples. Furthermore, striking disparities in the microbial community composition have been noted among dust samples from diverse geographical regions, heralding new possibilities for geographical inference based on microbial DNA analysis. The pivotal role of microbial community data from dust in geographical inference is significant, underscoring its critical importance within the field of forensic science. This study aims to delve deeply into the nuances of fungal community composition across the urban landscapes of Beijing, Fuzhou, Kunming, and Urumqi in China. It evaluates the accuracy of biogeographic inference facilitated by the internal transcribed spacer 2 (ITS2) fungal sequencing while concurrently laying a robust foundation for the operational integration of environmental DNA into geographical inference mechanisms. MethodsITS2 region of the fungal genomes was amplified using universal primers known as 5.8S-Fun/ITS4-Fun, and the resulting DNA fragments were sequenced on the Illumina MiSeq FGx platform. Non-metric multidimensional scaling analysis (NMDS) was employed to visually represent the differences between samples, while analysis of similarities (ANOSIM) and permutational multivariate analysis of variance (PERMANOVA) were utilized to statistically evaluate the dissimilarities in community composition across samples. Furthermore, using Linear Discriminant Analysis Effect Size (LEfSe) analysis to identify and filter out species that exhibit significant differences between various cities. In addition, we leveraged SourceTracker to predict the geographic origins of the dust samples. ResultsAmong the four cities of Beijing, Fuzhou, Kunming and Urumqi, Beijing has the highest species richness. The results of species annotation showed that there were significant differences in the species composition and relative abundance of fungal communities in the four cities. NMDS analysis revealed distinct clustering patterns of samples based on their biogeographic origins in multidimensional space. Samples from the same city exhibited clear clustering, while samples from different cities showed separation along the first axis. The results from ANOSIM and PERMANOVA confirmed the significant differences in fungal community composition between the four cities, with the most pronounced distinctions observed between Fuzhou and Urumqi. Notably, the biogeographic origins of all known dust samples were successfully predicted. ConclusionSignificant differences are observed in the fungal species composition and relative abundance among the cities of Beijing, Fuzhou, Kunming, and Urumqi. Employing fungal ITS2 sequencing on dust samples from these urban areas enables accurate inference of biogeographical locations. The high feasibility of utilizing fungal community data in dust for biogeographical inferences holds particular promise in the field of forensic science.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.