BACKGROUND:Obesity-induced adipose tissue expansion is characterized by capillary rarefaction and hypoxia, which disrupts angiogenesis and impairs beige adipogenesis. While angiogenesis is known to be crucial for beiging, the functional link between impaired vascularization and defective browning remains poorly understood. How natural compounds like berberine (BBR) links angiogenesis with beige adipogenesis remains unexplored. METHODS:Using both diet-induced obese (DIO) C57BL/6 J and leptin-deficient (ob/ob) murine models, we administered intraperitoneal BBR for 4 weeks. Adipose tissue remodeling was evaluated through histomorphometry, immunofluorescence, and flow cytometry. RNA sequencing of adipose tissue was performed to identify the potential targets. Chemical hypoxia was induced using CoCl₂ in preadipocytes to examine its effects on browning. RESULTS:BBR improved adipose tissue dysfunction in both the DIO model and the ob/ob model. It increased CD34+CD31+ endothelial progenitor cells and enhanced protein levels of VEGF/VEGFR2, PRDM16, PPAR-γ, and UCP-1, indicating simultaneous promotion of angiogenesis and adipose browning. Transcriptomic analysis revealed glutathione peroxidase 3 (GPx3) as a novel target through which BBR alleviates adipose dysfunction. GPX3 knockdown in vivo impaired angiogenesis and suppressed browning markers. BBR reversed chemical hypoxia-induced impairment of beige adipocyte differentiation independently of UCP-1 upregulation by inhibiting HIF-1α activation. CONCLUSIONS:This study unveils that BBR counteracts obesity-associated adipose tissue dysfunction: it upregulates GPx3 to reduce oxidative stress, which in turn normalizes HIF-1α levels and activates the PRDM16 signaling, thereby concurrently restoring adipose angiogenesis and promoting beige adipogenesis. This breaks the vicious cycle of hypoxia-impaired angiogenesis and suppressed thermogenesis, positioning BBR as a promising multi-target therapy for obesity.

Objectives: Parkinson’s disease (PD), the second most prevalent neurodegenerative disease, is closely linked to aging and immune system dysfunction. This study aims to explore potential aging-related biomarkers of PD and examine their diagnostic value, in addition to their relationship with immune cell infiltration, to identify novel therapeutic targets. Methods: Gene expression profiles from the gene expression omnibus (GEO) database (GSE20163, GSE20164, and GSE8397) were analyzed. Aging-related genes associated with PD were screened using weighted gene co-expression network analysis. Subsequent functional enrichment analysis, protein‒protein interaction (PPI) network mapping, and least absolute shrinkage and selection operator regression were used to identify key biomarker candidates. A receiver operating characteristic (ROC) curve analysis was applied to evaluate diagnostic efficacy. Immune cell infiltration was assessed through Spearman correlation analysis, and the expression of key biomarkers was validated in both cellular and animal PD models. Results: Eighteen aging-related genes were identified through a PPI network analysis. Seven genes, including forkhead box O3 (FOXO3) and the proto-oncogene tyrosine-protein kinase receptor rearranged during transfection (RET), showed potential as diagnostic biomarkers for PD. Gene set enrichment analysis revealed that these biomarkers correlated with immune cell infiltration patterns in PD patients. The ROC curve analysis indicated high diagnostic accuracy for these genes across multiple datasets (area under the curve = 96.3158). In vivo and in vitro validation confirmed significant changes in the expression of RET and FOXO3 in PD samples, highlighting their relevance as biomarkers. Conclusion: Our findings suggest that RET and FOXO3 are promising aging-related biomarkers for PD, potentially providing new insights into the early diagnosis and targeted treatment of PD. These biomarkers also reflect the complex interplay between aging, immunity, and PD pathogenesis.

BackgroundSepsis-induced acute lung injury (ALI) represents the earliest and most severe complication of sepsis, with extraordinarily high mortality rates. Baihe Gujin decoction (BHGJD), a classical traditional Chinese medicine formula, has demonstrated protective effects against various pulmonary diseases, yet its therapeutic potential in sepsis-induced ALI remains unexplored.MethodsThe chemical constituents of BHGJD were characterized by mass spectrometry, and potential protective mechanisms were predicted using network pharmacology. In vivo, a cecal ligation and puncture (CLP) mouse model was established to evaluate BHGJD’s protective effects through histopathological assessment and serum inflammatory cytokine analysis. Lung tissue RNA sequencing and untargeted metabolomics were performed to explore underlying molecular mechanisms, followed by validation of key proteins (HO-1, GPX4, PPARα, CPT1A, mTOR, and p-mTOR) by Western blot, immunohistochemistry, and immunofluorescence. Lung-deposited bioactive components were subsequently identified by mass spectrometry. In vitro, (+)-catechin, a representative lung-exposed constituent detected in lung tissue, was used to treat lipopolysaccharide-induced MLE-12 cells. Cellular levels of adenosine triphosphate, reactive oxygen species, and ferrous iron were measured. Mitochondrial ultrastructure was assessed by transmission electron microscopy, and fatty acid oxidation capacity was evaluated using the Seahorse palmitate oxidation assay, followed by validation of key proteins by Western blot.ResultsBHGJD significantly ameliorated CLP-induced ALI, as evidenced by improved histological architecture and reduced inflammatory cytokine levels. Integrated multi-omics analysis and experimental validation revealed three interconnected protective mechanisms: 1) activation of an Nrf2/GPX4-associated antioxidant response, initially suggested by glutathione pathway enrichment, reduced lipid peroxidation-related metabolites, and restoration of redox and mitochondrial homeostasis; 2) PPARα/CPT1A-associated metabolic remodeling toward fatty acid utilization, supported by fatty acid transport/metabolism enrichment, coordinated changes in multiple acylcarnitine species, increased PPARα/CPT1A expression, and improved palmitate-supported mitochondrial respiration in vitro; and 3) reduction of inflammatory lipid mediators. Altered mTOR signaling accompanied these changes and may represent a convergent regulatory pathway.ConclusionBHGJD alleviates sepsis-induced ALI through coordinated enhancement of Nrf2/GPX4-associated antioxidant defense, PPARα/CPT1A-linked metabolic reprogramming toward fatty acid utilization, and suppression of inflammatory lipid mediators. These findings provide an integrated mechanistic framework for the protective actions of BHGJD.

The therapeutic landscape for Parkinson's disease (PD) is fraught with challenges, primarily due to the intertwined pathogenic cycles of oxidative stress and ferroptosis that perpetuate neuronal loss. While conventional antioxidants fail to address the iron-mediated root of reactive oxygen species (ROS) generation, existing ferroptosis inhibitors suffer from poor blood-brain barrier (BBB) permeability, rely on physical chelation and lack intrinsic ROS-scavenging ability. Here, we report the one-pot synthesis of bifunctional carbon dots (DFCDs) from dragon fruit, a sustainable biomass, as a novel nanotherapeutic agent that concurrently disrupts both pathways. Distinct from conventional strategies that rely on physical iron chelation, the DFCDs exhibit a unique dual functionality: they possess potent antioxidant activity to neutralize downstream ROS and, most notably, function as endogenous pathway modulators that inhibit ferroptosis by upregulating the endogenous cytoprotective SLC7A11/GPX4 axis. Their ultrasmall size (similar to 4.1 nm) facilitates exceptional BBB penetration without requiring complex surface functionalization. In a murine PD model, DFCDs administration significantly mitigates neuroinflammation, reduces dopaminergic neuron degeneration, and suppresses ferroptosis, culminating in the substantial restoration of motor functions. This work pioneers the use of biologically-active carbon dots as a standalone therapeutic and presents a simplified, biomass-derived strategy offering a potent and translatable approach for synergistic PD treatment.

Gastric cancer (GC) is characterized by a complex tumor microenvironment (TME) with substantial cellular heterogeneity. Tumor-associated macrophages (TAMs) represent the most abundant immune cell population in the TME and exhibit remarkable functional plasticity. This study integrated single-cell RNA-sequencing (scRNA-seq) data, bulk transcriptomics, and spatial transcriptomics to systematically characterize TAM heterogeneity and identify prognostic biomarkers in GC. ScRNA-seq analysis revealed nine major cell types (T cells, plasma cells, epithelial cells, fibroblasts, macrophages, endothelial cells, B cells, smooth muscle cells, and mast cells) and distinct macrophage subpopulations with tumor-specific expansion patterns. High-dimensional weighted gene coexpression network analysis identified coexpression modules enriched in GC-associated macrophages. Machine learning algorithms were employed to construct a prognostic signature, and the CoxBoost model demonstrated superior predictive performance across multiple cohorts. The seven-gene signature, including UPP1, VCAN, ELL2, ABCA1, TUBA1A, MX2, and TSPO, showed robust prognostic value in survival prediction. Spatial transcriptomic analysis further revealed distinct metabolic profiles and extensive cellular interaction networks mediated by UPP1-expressing TAMs. These findings provide a comprehensive atlas of TAM heterogeneity and establish novel prognostic biomarkers with potential therapeutic implications in GC.

Sonodynamic therapy (SDT) offers a promising non-antibiotic strategy for intracranial bacterial infections, but its efficacy is limited by the blood–brain barrier (BBB), lesion hypoxia, and potential systemic toxicity of conventional sonosensitizers. Here, we develop multifunctional manganese-doped carbon dots (Mn-CDs) through precursor engineering by hydrothermally carbonizing methylene blue (MB, a sonosensitive moiety), manganese gluconate (a coordinated catalytic source), and dragon fruit powder (a biocompatible carbon matrix). This design integrates MB-derived sonosensitive motifs and Mn-related catalase (CAT)-like catalytic sites into an ultrasmall carbon framework. Mn-CDs efficiently decompose pathological hydrogen peroxide (H2O2) into oxygen (O2), thereby relieving hypoxia and fueling ultrasound-triggered SDT to generate singlet oxygen. The resulting oxidative stress disrupts bacterial membranes, impairs metabolic activity, and achieves 98% antibacterial efficiency against methicillin-resistant Staphylococcus aureus (MRSA) in vitro. Owing to their ultrasmall size (around 4.84 nm) and good Mn retention, Mn-CDs cross the BBB and efficiently accumulate in infected brain tissue with favorable biosafety. In an MRSA-induced meningitis mouse model, Mn-CDs-mediated SDT markedly reduces cerebral bacterial burden, attenuates neuroinflammation by regulating TNF-α and IL-10, decreases neuronal apoptosis, and improves behavioral recovery. This microenvironment-adaptive Mn-CDs platform provides an intelligent strategy for treating drug-resistant central nervous system infections.

ETHNOPHARMACOLOGICAL RELEVANCE:Alzheimer's disease (AD) is an incurable and irreversible type of dementia. Existing drugs cannot meet clinical needs; thus, developing new treatments is necessary. Traditional Chinese medicine (TCM) has been used in the prevention and treatment of AD. TCM holds the theory that "the kidney support brain function" and believes that dementia can be addressed from a kidney-based perspective. Kidney-tonifying herbs are a class of medicines that have the effect of tonifying the kidney and benefiting the brain. Some of these herbs have been shown to have anti-AD effects. Iridoid glycosides (IGs), which are important components of kidney-tonifying herbs, may have the potential to prevent and treat AD. However, their effects on AD have not yet been reviewed. AIM OF THE REVIEW:This literature review provides a comprehensive summary of the potential of IGs in the prevention and treatment of AD. It also sets the foundation for future studies that will make the use of such drugs in clinical practice possible. MATERIAL AND METHODS:Kidney-tonifying Chinese herbs were selected with reference to the Chinese Pharmacopoeia (2020 edition) and the textbook of Chinese Materia Medica (5th edition). Literature survey was conducted using PubMed, Web of Science, Google Scholar, and CNKI, with "Alzheimer's disease," "kidney-tonifying Chinese medicinal herbs," and "Iridoid Glycosides" as the primary keywords. RESULTS:Kidney-tonifying herbal IGs include loganin, morroniside, verbenalin, cornuside, catalpol, rehmannioside A, geniposidic acid, and aucubin. These IGs have shown multiple pharmacological effects, including anti-AD effects. The effective mechanisms of IGs for AD treatment include anti-oxidative stress, inhibiting neuronal apoptosis, antagonizing amyloid neurotoxicity and tau protein hyperphosphorylation, regulating immune function, anti-inflammation, normalizing the function of the cholinergic nervous system, recuperating neurobiochemical, and regulating AD-related genes. Consequently, IGs can combat AD by modulating multiple targets and pathways. CONCLUSION:Kidney-tonifying herbal IGs have great potential to combat AD.

BACKGROUND:Nobiletin, a major component derived from the natural product Citrus reticulata Blanco, has been shown to exhibit potent anti-cancer activity across various cancer types. However, the mechanisms underlying its anti-breast cancer effects, particularly in triple-negative breast cancer (TNBC), remain poorly understood. PURPOSE:The study aims to explore the role of nobiletin in promoting ferroptosis in TNBC by targeting aldo-keto reductase family 1 member C1 (AKR1C1) to facilitate ubiquitination and degradation of glutathione peroxidase 4 (GPX4). METHODS:Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assay were conducted to evaluate the effect of nobiletin on TNBC cell proliferation. Transmission electron microscopy and mitochondrial membrane potential assays were used to observe mitochondrial changes. A ferrous ion detection kit was used to assess intracellular ferrous ion levels. Malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), and dihydroethidium (DHE) and BODIPY 581/591 C11 detection kits were used to measure changes in redox-related molecules. Western blot analysis was performed to detect alterations in ferroptosis-related proteins following nobiletin treatment. Further, RNA sequencing was conducted to identify target genes and pathways affected by nobiletin treatment. Molecular docking, surface plasmon resonance (SPR), and cellular thermal shift assay (CETSA) were used to determine the interaction sites between nobiletin and AKR1C1. Plasmid construction, viral transfection, co-immunoprecipitation (co-IP), and in vitro ubiquitination assays were employed to investigate the effect of the nobiletin-AKR1C1 interaction on GPX4 ubiquitination. Immunohistochemistry of breast cancer patient tumour tissues was performed to analyse AKR1C1 expression in tumour and adjacent normal tissues. In addition, an orthotopic breast tumour mouse model was established to explore the in vivo effects of nobiletin on tumour growth and ferroptosis. Swiss ADME analysis was conducted to predict the pharmacokinetic properties of nobiletin. RESULTS:In our research, we demonstrate that nobiletin effectively suppresses proliferation and induces ferroptosis in TNBC cell liness, accompanied by the release of ROS, iron accumulation, production of MDA, and depletion of GSH, changes that can be reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1) and the ROS scavenger N-acetylcysteine (NAC). Furthermore, RNA sequencing analyses revealed that nobiletin significantly upregulates the expression of AKR1C1 which correlates with improved patient survival, suggesting its potential as a prognostic marker. Using SPR, molecular docking techniques, and CETSA, we identified AKR1C1 as a direct binding target of nobiletin, with the likely binding sites being HIS117A, LYS207A, and SER217A. Subsequently, through co-IP and in vitro ubiquitination experiments, we demonstrated that the nobiletin-AKR1C1 complex promotes the degradation of GPX4 by enhancing its ubiquitination. CONCLUSION:Our study demonstrates that nobiletin induces ferroptosis through a direct and previously unrecognised molecular mechanism: targeting AKR1C1 to promote GPX4 ubiquitination and degradation. These results emphasise the promising role of nobiletin as an effective therapeutic approach for TNBC.

Gastric cancer (GC), a life-threatening malignancy with profound global health impacts, remains a cardinal focus of biomedical research. Recently, astragaloside IV (AS-IV), a bioactive triterpenoid saponin derived from Astragalus mongholicus Bunge, has garnered substantial attention for its multifaceted anticancer properties in preclinical investigations. This review systematically synthesizes current evidence on the molecular mechanisms underlying AS-IV’s inhibitory effects against GC, encompassing programmed cell death pathways (apoptosis, autophagy, pyroptosis, ferroptosis), tumor angiogenesis, tumor microenvironment modulation, Helicobacter pylori and inflammatory signaling networks. Many studies demonstrate that AS-IV can inhibit the development of GC through multi-target and multi-pathway mechanisms, making it a well-deserved nemesis of GC. Notably, although AS-IV has emerged as a potential candidate for GC therapy, it suffers from problems such as single research model, unclear toxic and side effects, and poor bioavailability. These seriously hinder the efficiency of AS-IV in the treatment of GC. In the future, we can design and implement a series of in vivo and in vitro experiments to further explore and clarify the mechanism of action of AS-IV in the treatment of GC. It is encouraged to carry out a number of high-quality clinical controlled studies to further prove the effectiveness and safety of AS-IV. In addition, we can also use emerging technologies (such as nanotechnology) to improve the bioavailability of AS-IV, bringing more hope to GC patients.

Colorectal cancer (CRC) is a prevalent and lethal malignancy necessitating new treatments. Sclareol, the primary active component of Salvia sclarea L., exhibits diverse pharmacological properties, making it a promising anti-cancer drug warranting further investigation. To evaluate Sclareol's action in CRC cell death, various methods were performed, including cell viability and colony formation assays, EdU assay, flow cytometry for cell cycle analysis and apoptosis, as well as TUNEL staining, transmission electron microscopy (TEM), reactive oxygen species (ROS) detection, and Fe2+ fluorometric assay. RNA sequencing and pathway analysis, combined with in silico molecular docking, and immunoblotting, were conducted to determine the mechanism of action of Sclareol. A CRC xenograft model in immunocompetent mice was used to evaluate Sclareol's in vivo efficacy and toxicity, with immunohistochemistry confirming its mechanism of action. Sclareol significantly suppressed CRC cell proliferation and induced cell cycle arrest in vitro without significantly inducing apoptosis. Ferroptosis as a promising mechanism of action was validated through TEM, ROS detection, and Fe2+ staining. RNA sequencing analysis revealed enrichment in metal ion-transporter activity. Molecular docking analysis showed direct binding of Sclareol to the key ferroptosis-related target solute carrier family 7 member 11 (SLC7A11). Additionally, Sclareol downregulated the expression of SLC7A11, nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4) proteins, indicating ferroptosis induction in vitro. Significant tumor growth inhibition was observed without hepatic or renal toxicities, with immunohistochemistry confirming the suppression of ferroptosis- and proliferation-related markers in vivo. Sclareol inhibits CRC growth by modulating the ferroptosis pathway through the SLC7A11/GPX4 axis. Sclareol shows promise as a therapeutic agent in CRC, warranting further pre-clinical studies to confirm its efficacy and safety.

Background:Atrial fibrillation (AF) represents a major risk factor of ischemic stroke recurrence with serious management implications. However, it often remains undiagnosed due to lack of standard or prolonged cardiac rhythm monitoring. We aim to create a novel end-to-end artificial intelligence (AI) model that uses MRI data to rapidly identify high AF risk in patients who suffer from an acute ischemic stroke. Methods:This study comprises an internal retrospective cohort and a prospective cohort from Shanghai sixth people's hospital to train and validate an MRI-based AI model. Between January 1, 2018 and December 31, 2021, 510 patients were retrospectively enrolled for algorithm development and performance was measured using fivefold cross-validation. Patients from this trial were registered with http://www.chictr.org.cn, ChiCTR2200056385. Between September 1, 2022 and July 31, 2023, 73 patients were prospectively enrolled for algorithm test. An external cohort of 175 patients from Huashan Hospital, Minhang Hospital, and Shanghai Tenth People's Hospital was also enrolled retrospectively for further model validation. A combined classifier leveraging pre-defined radiomics features and de novo features extracted by convolutional neural network (CNN) was proposed to identify underlying AF in acute ischemic stroke patients. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated for model evaluation. Findings:The top-performing combined classifier achieved an AUC of 0.94 (95% CI, 0.90-0.98) in the internal retrospective validation group, 0.85 (95% CI, 0.79-0.91) in the external validation group, and 0.87 (95% CI, 0.90-0.98) in the prospective test group. Based on subgroup analysis, the AI model performed well in female patients, patients with NIHSS > 4 or CHA2DS2-VASc ≤ 3, with the AUC of 0.91, 0.94, and 0.90, respectively. More importantly, our proposed model identified all the AF patients that were diagnosed with Holter monitoring during index stroke admission. Interpretation:Our work suggested a potential association between brain ischemic lesion pattern on MR images and underlying AF. Furthermore, with additional validation, the AI model we developed may serve as a rapid screening tool for AF in clinical practice of stroke units. Funding:This work was supported by grants from the National Natural Science Foundation of China (NSFC, Grant Number: 81871102 and 82172068); Shanghai Jiao Tong University School of Medicine, Two-Hundred Talent Program as Research Doctor (Grant Number: SBR202204); Municipal Science and Technology Commission Medical Innovation Project of Shanghai, (Grant/Award Number: 20Y11910200); Research Physician Program of Shanghai Shen Kang Hospital Development Center (Grant Number: SHD2022CRD039) to Dr. Dong Huang and the SJTU Trans-med Awards Research (No. 20220101) to Dahong Qian.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2 , PARS2 , ETHE1 , LRPPRC , TMEM70 , AARS2 , ACAD9 , VARS2 , and ATP8A2 . The high-RS group had more inflamed immune features, including T and CD4 + memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

BACKGROUND:More than 60% of paroxysmal kinesigenic dyskinesia (PKD) cases are of uncertain variants. OBJECTIVE:The aim was to elucidate novel genetic contribution to PKD. METHODS:A total of 476 probands with uncertain genetic causes were enrolled for whole-exome sequencing. A method of case-control analysis was applied to identify the candidate genes. Whole-cell patch-clamp recording was applied to verify the electrophysiological impact of the identified variants. A mouse model with cerebellar heterozygous knockout of the candidate gene was developed via adeno-associated virus injection, and dystonia-like phenotype inducement and rotarod tests were performed. In vivo multiunit electrical recording was applied to investigate the change in neural excitability in knockout mice. RESULTS:Heterozygous variants of potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) clustered in PKD patients were compared with those in the control groups. Fifteen variants were detected in 16 of 522 probands (frequency = 3.07%). Patients with KCNJ10 variants tended to have a milder manifestation compared to those with PRRT2 (proline-rich transmembrane protein 2) variants. KCNJ10 variants partially altered the transmembrane location of inwardly rectifying potassium channel 4.1 (Kir4.1). The Kcnj10 expression is consistent with the natural course of PKD. Variants resulted in different degrees of reduction in cell Kir4.1 currents, and mice with heterozygous conditional knockout of Kcnj10 in the cerebellum presented dystonic posture, together with poor motor coordination and motor learning ability in rotarod tests. The firing rate of deep cerebellar nuclei was significantly elevated in Kcnj10-cKO mice. CONCLUSION:We identified heterozygous variants of KCNJ10 in PKD. Impaired function of Kir4.1 might lead to abnormal neuronal excitability, which attributed to PKD. © 2024 International Parkinson and Movement Disorder Society.

Background:Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored.Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration.Methods: A comprehensive set of methodologies was employed to assess CPAE’s impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE’s in vivo anti-cancer potential.Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-β1/Smad2/3 pathway. In vivo experiments underscored CPAE’s ability to inhibit tumor proliferation.Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-β1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE’s therapeutic potential in pancreatic cancer.

目的:探讨中西药结合的肿瘤临床药学监护模式.方法:临床药师对 1 例转移性肠癌患者使用曲氟尿苷/替匹嘧啶化疗后Ⅳ度骨髓抑制的治疗过程进行分析总结,并探讨Ⅳ度骨髓抑制发生的影响因素.结果:在配合临床医生进行中西医结合治疗的过程中,临床药师提出合理性建议,对患者进行药学监护并提供用药教育,使患者骨髓抑制情况明显改善后出院.结论:临床药师通过参与药学监护,使中西药治疗更合理,并提高患者用药依从性,保证患者用药安全和有效,体现了临床药师的服务价值.

腹腔间隔室综合征易导致多器官功能衰竭,而感染新型冠状病毒会加剧患者肺功能下降甚至死亡.治疗1例新型冠状病毒肺炎合并腹腔间隔室综合征患者,现代医学治疗手段有限,根据患者临床表现中医辨证属于本虚标实、脾虚气滞之证,以益气扶正、通腑泄浊为治法.针药结合治疗2周后,患者病情显著好转.

Objective: To characterize the traditional Chinese medicine（TCM） syndromes of mild corona virus disease 2019（COVID-19） cases infected with Omicron variant for better prevention and treatment of COVID-19 infection.Methods A total of 188 mild covid-19 patients infected with Omicron variant infection in the northern section of Ruijin Hospital affiliated to Shanghai Jiao Tong university school of medicine and Jiahe Xinyuan shelter from March 24 through April 24, 2022 were enrolled, the tongue manifestation features, basic information, TCM syndrome and the time of negative turning were collected by the questionnaires. Results The mild cases were generally in good health status, with less than20% patients having other major diseases. There was statistical significance in the median time of turning negative among different tongue shapes. The tongue coating indicated that the syndrome of cold-dampness stagnating, of evil-heat accumulating and dampness blocking in the lung pattern accounted for 38.8%, 34.5% and 23.4% of all cases. The syndrome of cold-dampness stagnating in the lung pattern and the syndrome of evil-heat accumulating in the lung pattern were found in majority of patient investigated. It took similar time for patients with different syndrome types to become COVID-19 virus negative（P＞0.05）. Conclusions The cold dampness was most common among mild COVID-19 patients with Omicron infection, who predominately presented syndrome of cold-dampness stagnating in the lung pattern.

目的 观察血府逐瘀汤对血瘀证的结直肠癌伴抑郁、焦虑患者的临床疗效及肠道代谢产物的影响.方法 将2019年1月～ 2022年1月上海交通大学医学院附属瑞金医院收治的120例血瘀证型Ⅲ期结直肠癌伴抑郁、焦虑患者,随机分为治疗组和对照组,每组60例.治疗组给予血府逐瘀汤口服,对照组给予安慰剂口服.3个月后比较分析两组心理量表(包括SDS、SAS、HAMD、HAMA)、中医症状评分、无疾病生存期(disease free survival,DFS)及代谢组学.结果 治疗后,组内比较,治疗组的乏力得分较前增加(P＜0.05),量表(SDS、SAS、HAMD、HAMA)、不寐、脘腹胀满、心烦易怒得分较前明显下降(P＜0.01);对照组HAMD、HAMA、不寐、乏力得分较前明显下降(P＜0.01).两组间比较,治疗组SDS、HAMD、不寐、心烦易怒得分均低于对照组(P＜0.05),HAMA、脘腹胀满得分明显低于对照组(P＜0.01).治疗组DFS为38.72±2.22个月,较对照组延长2个月(P＞0.05).两组肠道代谢产物差异分析主要为脯氨酸、6-羟基烟酸、丝氨酸、肌醇、丙二酸、阿魏酸、吲哚丁酸、丁酸等.结论 中药血府逐瘀汤可改善结直肠癌的抑郁、焦虑,调节肠道代谢,延长无疾病生存期.

目的:探讨新型小分子抗病毒药物临床使用的药学监护模式.方法:临床药师对 2例肺部感染患者使用不同的小分子抗病毒药物后发生不良反应的治疗过程进行分析总结.探讨小分子抗病毒药物引发不良反应发生的影响因素,协助医师评价可疑药物和处理不良反应.结果:通过与临床医生协同处理不良反应,患者不良反应情况明显改善后出院.结论:临床药师通过参与药学监护,体现了临床药师的服务价值,保障了临床用药的有效性安全性.

新型冠状病毒(新冠)感染属于中医瘟疫,并非由外感"六淫"之邪诱发,而是天地疫厉之气所化.疫气由口鼻侵入,《瘟疫论》开篇即指出"夫瘟疫之为病,非风非寒,非暑非湿,乃天地间别有一种疫气所感"[1].回顾3年的新冠感染抗疫之路,不难发现该病毒的多变、狡猾,令人捉摸不透,所以在治疗时很难用一套固定的组方治疗所有新冠感染患者.在疫情放开后,发现自己核酸/抗原阳性,在家用药需要注意什么呢?