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

Diabetic sarcopenia (DS) is a common but often ignored skeletal muscle complication in individuals with diabetes mellitus. It is characterized by progressive loss of skeletal muscle mass, reduced muscle strength, and impaired physical performance, which may further increase the risk of falls, disabilities, metabolic disorders, and adverse clinical outcomes. Traditionally, DS has been attributed mainly to hyperglycemia, insulin resistance, aging-related muscle decline, and chronic complications of diabetes. However, increasing evidence suggests that lipid metabolic disturbance and pathological lipid metabolic reprogramming are not merely secondary consequences of diabetes, but may actively participate in the initiation and progression of DS. Under diabetic conditions, impaired fatty acid uptake, transport, oxidation, and storage disrupt skeletal muscle metabolic homeostasis, leading to ectopic lipid deposition and accumulation of lipotoxic intermediates. These lipid-derived metabolites can aggravate insulin resistance, impair mitochondrial energy production, enhance oxidative stress, activate chronic low-grade inflammation, and disturb protein synthesis and degradation balance, thereby accelerating skeletal muscle atrophy and functional decline. Lipid metabolic dysregulation may also interact with multiple pathological processes involved in DS, including mitochondrial dysfunction, inflammatory signaling, oxidative damage, impaired autophagy, and gut microbiota imbalance. These mechanisms do not occur independently; instead, they form a complex bidirectional vicious cycle with diabetes-related metabolic disorders. Specifically, mitochondrial dysfunction reduces fatty acid oxidative capacity, which further promotes lipid accumulation and lipotoxicity. Inflammatory activation can impair insulin signaling and muscle protein metabolism, while lipid overload may in turn amplify inflammatory responses. Similarly, gut microbiota dysbiosis and altered microbial metabolites may influence systemic inflammation, lipid metabolism, and skeletal muscle homeostasis. Therefore, lipid metabolic reprogramming provides an important mechanistic perspective for understanding the progression of DS from metabolic disturbance to structural and functional muscle impairment. Exercise intervention is an effective and clinically feasible non-pharmacological strategy for the prevention and management of DS. Both aerobic exercise and resistance training have been shown to improve insulin sensitivity, enhance fatty acid oxidation, increase mitochondrial biogenesis, reduce ectopic lipid deposition, and attenuate lipotoxic metabolite accumulation. These adaptations not only improved glucose and lipid metabolism, but also increased the preservation of muscle mass, muscle strength, and physical function. Moreover, combined exercise strategies may provide complementary benefits by integrating the metabolic advantages of aerobic exercise with the anabolic and functional effects of resistance training. Based on analyses of publicly available datasets and literature evidences, this review systematically summarizes the role of lipid metabolic disorders in the pathogenesis of DS, with particular attention to the molecular mechanisms linking lipid dysregulation to insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and gut microbiota disturbance. Furthermore, this review discusses the potential mechanisms by which exercise intervention improves DS through the regulation of lipid metabolic reprogramming, and outlines exercise prescription strategies in terms of modality, intensity, frequency, and duration. Understanding the interaction between lipid metabolism and skeletal muscle dysfunction may provide new theoretical evidence for early identification, mechanistic research, and precision exercise therapy in DS. Overall, targeting pathological lipid metabolic reprogramming through exercise intervention represents a promising and clinically actionable approach for improving muscle health and prognosis in individuals with DS.

ObjectiveThis study aimed to provide a scientific basis for the safety management of drinking water by assessing the contamination levels of 21 per- and polyfluoroalkyl substances (PFASs) in water samples collected from the Yangtze River Delta region. MethodsSolid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to determine 21 PFASs in 6 source water samples, 20 treated water samples, and 60 tap water samples collected from 5 administrative districts in the Yangtze River Delta region across four seasons in 2023. The Kruskal-Wallis H test was used to compare differences in PFAS concentrations among the three types of water samples, followed by post hoc pairwise comparisons with Bonferroni correction. Removal efficiencies of target compounds were also calculated. ResultsAmong the 86 samples, 14 PFASs were detected, with 7 compounds detected in 100% of samples. The total concentrations of PFASs in source water, treated water, and tap water ranged from 63.85 to 190.54 ng·L^-¹, 55.75 to 774.36 ng·L^-¹, and 40.72 to 689.80 ng·L^-¹, respectively. The compounds with the highest median concentrations were perfluorobutanoic acid (PFBA) (40.19, 15.20, and 14.05 ng·L^-¹), perfluorohexanoic acid (PFHxA) (29.69, 32.62, and 34.24 ng·L^-¹), perfluorooctanoic acid (PFOA) (17.65, 39.45, and 36.83 ng·L^-¹), and potassium perfluorobutanesulfonic acid (PFBS) (16.99, 24.38, and 23.89 ng·L^-¹). Notably, concentrations of PFOA (7.71‒71.63 ng·L^-¹) and PFOS (-¹) in tap water were below the regulatory limits specified in GB 5749‒2022 Standards for Drinking Water Quality (PFOA: 0.000 08 mg·L^-1, PFOS: 0.000 04 mg·L^-1). Significant seasonal variations in PFAS concentrations were observed, with total PFAS levels in March being higher than those in September and November (adjusted P<0.001, and P=0.006), and levels in May being higher than those in September (adjusted P=0.037). The removal efficiencies of PFASs in the water treatment plants ranged from -14% to 34%. ConclusionPFAS contamination is widespread in source water, treated water, and tap water in the Yangtze River Delta region, and concentrations of PFOA and PFOS in all tested water samples comply with the Chinese national standards for drinking water quality (GB 5749‒2022). The use of PFASs should be continuously regulated to ensure water safety.

Specification for Quality Control in Traditional Chinese Medicine Clinical Trials（GB/T 47336-2026） is the first national standard in the field of clinical research on traditional Chinese medicine （TCM）， aims to address the core issue that the quality shortcomings of current TCM clinical research restrict the transformation of achievements and international recognition. Through the interpretation of the core contents of this standard， including its scope of application， graded quality control system， TCM-specific quality control requirements， implementation and responsible entities， responsibilities of quality control personnel， formulation of quality control plans， critical nodes of quality control， and quality control archive management， it is believed that the promotion and implementation of this standard are of great significance for improving the standard system of TCM clinical research， enhancing research quality， optimizing the quality management model， and promoting the internationalization process of TCM. Meanwhile， the implementation paths for the standard are discussed， including carrying out pilot applications in institutions， establishing publicity， implementation， and training mechanisms， encouraging multi-party collaborative supervision， and setting up implementation feedback mechanisms. On this basis， the challenges that may be encountered during implementation， such as resource input pressure， difficulties in implementing TCM-specific quality control， and a relative shortage of interdisciplinary composite talents， are sorted out， and corresponding strategies are proposed， which can provide references for relevant researchers and practitioners.

Objective To determine the effect of baicalein on high glucose-induced cardiac fibro-blast pyroptosis based on the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)pathway.Methods Rat cardiac fibroblasts were grouped into control,high glucose group,low-,medium-and high-dose baicalein(H-,M-and L-baicalein)groups,and H-baicalein+NLRP3 agonist(BMS-986299)group.Except for the control group,all other groups were cultured in DMEM medium containing 40 mmol/L glucose,then 12.5,25 and 50 μmol/L baicalein was added into the medium correspondingly,and 1 μmol/L BMS-986299 was used to treat the H-baicalein+NLRP3 agonist group.Lactate dehydrogenase(LDH)cytotoxicity assay were employed to detect cell cytotoxicity.qRT-PCR and Western blotting were performed to determine the expression of NLRP3,Caspase-1,and GSDMD at mRNA and protein levels.Results High glucose treatment induced more EdU positive cells,higher pyroptotic rate,stronger cytotoxicity,higher Col-Ⅰ and Col-Ⅲ contents,and enhanced mRNA and protein levels of NLRP3,Caspase-1 and GSDMD in comparison to the control group(P＜0.05).The H-baicalein+NLRP3 agonist group had more EdU positive cells(26.85±2.95 cells vs 15.43±1.82 cells,P＜0.05),higher pyroptotic rate[(33.45±4.02)％vs(17.34±2.15)％,P＜0.05],stronger cytotoxicity[(27.94±2.93)％vs(14.13±1.87)％,P＜0.05],and increased contents of Col-Ⅰ(107.58±13.39 ng/ml vs 58.73±8.36 ng/ml,P＜0.05)and Col-Ⅲ(118.43±13.95 ng/ml vs 68.74±8.57 ng/ml,P＜0.05),and enhanced expression of NLRP3,Caspase-1 and GSDMD at both mRNA and protein levels(P＜0.05)when compared with the H-baicalein group.Conclusion Baicalein inhibits high glucose-induced cardiac fibroblast pyroptosis by suppressing NLRP3/Caspase-1/GSDMD pathway.

AIM To investigate the effects of Qifu Yixin Granules on cardiac inflammation in a rat model of heart failure.METHODS The rats were induced into chronic heart failure(CHF)models by 6-week intraperitoneal injection of doxorubicin followed by the random assignment of the successful rat models into the model group,the captopril group(22.5 mg/kg),and the low-dose,medium-dose,and high-dose Qifu Yixin Granules groups(2.84,5.67,11.34 g/kg),in contrast to the normal rats of the blank group.The rats had their body weight monitored;their cardiac function assessed by echocardiography;their serum levels of NT-proBNP,TNF-α,IL-6,IL-1 and CRP measured by ELISA;their cardiac morphological alterations observed by HE and Masson staining;their cardiac protein expressions of TLR4,MyD88 and NF-κB detected by immunohistochemistry and Western blot;and their cardiac mRNA expressions of TLR4,MyD88 and NF-κB measured by RT-qPCR.RESULTS Compared to the blank group,the model group exhibited significantly reduced body weight,LVEF and LVFS(P＜0.01),alongside significantly elevated LVEDD,LVESD,and serum concentrations of NT-proBNP,TNF-α,IL-6,IL-1 and CRP(P＜0.01).Additionally,the model group displayed greater myocardial inflammatory cell aggregation,increased collagen deposition(P＜0.01);and upregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.01).Compared to the model group,the groups intervened with captopril or medium/high dose Qifu Yixin Granules demonstrated significantly increased body weight,LVEF and LVFS(P＜0.05,P＜0.01);significantly reduced LVEDD,LVESD,and serum levels of the aforementioned indicators(P＜0.05,P＜0.01);mitigated inflammation and collagen deposition(P＜0.05,P＜0.01);and downregulated myocardial protein and mRNA expressions of TLR4,MyD88 and NF-κB(P＜0.05,P＜0.01).CONCLUSION Qifu Yixin Granules attenuate cardiac inflammation and improve cardiac function in doxorubicin-induced CHF rats;this therapeutic effect is mediated by inhibiting the activation of the TLR4/MyD88/NF-κB signaling pathway.

In this study,a sensitive lateral flow immunoassay(LFIA)platform based on carbon dots-mesoporous silica nanocomposite(CD-MSNs)fluorescent probes was constructed for high-performance detection of inflammatory marker interleukin-6(IL-6).Green fluorescent carbon dots(CDs)were prepared by hydrothermal method with 3,9-perylenic acid and 3-aminopropyltriethoxysilane(APTES)as raw materials,and highly fluorescent CD-MSNs composites were then constructed by encapsulating the prepared CDs in mesoporous silica nanoparticles(MSNs).Fluorescent probes were prepared by covalent coupling of CD-MSNs with IL-6 antibody.Fluorescent immunochromatographic test strips were constructed by spraying IL-6 capture antibody and goat anti-mouse IgG on nitrocellulose membrane as detection line(T-line)and quality control line(C-line),respectively.The fluorescence immunoassay analyzer was used to quantitatively detect the fluorescence intensity of T-line,and the experimental results showed that the LFIA platform based on this probe had a good linear relationship in IL-6 concentration range of 102-106 pg/mL,and the detection limit was 64 pg/mL,which was two orders of magnitude more sensitive than that of the traditional colloidal gold test strips.This method effectively solved the issue of insufficient sensitivity of traditional LFIA technique,and provided a rapid and highly sensitive detection method for early diagnosis of inflammatory diseases.

Objective To assess renal oxygen metabolism and iron deposition in type 2 diabetes mellitus(T2DM)patients using a combination of blood oxygen level-dependent(BOLD)and mDixon Quant techniques.Methods Clinical data of 58 T2DM patients from Tianjin First Central Hospital(September 2022-December 2023)were prospectively collected.According to urinary albumin-to-creation ratio(ACR),patients were divided into the normal albuminuria(NAU,ACR＜30 mg/g,n=35)group and the microalbuminuria(MAU,30 mg/g≤ACR＜300 mg/g,n=23)group.Thirty-three healthy volunteers were included as the control group during the same period.All participants underwent renal BOLD and mDixon Quant MRI to obtain cortical and medullary apparent relaxation rate(R2*)values.The differences of general data and image parameter values were compared between groups.Receiver operating characteristic(ROC)curves were used to analyze the diagnostic efficacy of relevant parameters for early renal function changes.Results There were significant differences in body weight,estimated glomerular filtration rate(eGFR)and ACR between the control group,the NAU group and the MAU group(P＜0.01).The R2* value in renal cortex was lower than that in renal medulla(P＜0.01)in the same group.Apart from R2* value of BOLD renal cortex,which showed no significant difference between the three groups(P＜0.05),and the differences in the other parameters were statistically significant(P<0.05).When distinguishing between the control group and the NAU group,the NAU group and the MAU group,as well as between the control group and the early-stage T2DM(NAU+MAU)group,the combined two-sequence approach demonstrated higher area under the curve(AUCs)than any single sequence alone,with AUC value of 0.892(95%CI:0.809-0.975),0.785(95%CI:0.666-0.904)and 0.841(95%CI:0.756-0.926),respectively.Conclusion The combination of BOLD imaging with mDixon Quant enables noninvasive and quantitative assessment of alterations in renal oxygen metabolism and iron content in early-stage T2DM patients.The diagnostic performance of this combined approach surpasses that of individual methods.

Objective:To explore applications of adjusting timing of nebulization and analgesic usage in patients after lung cancer surgery, to provide reference for postoperative rehabilitation of lung cancer.Methods:Adopting a prospective randomized controlled study design, a total of 84 patients with lung cancer who underwent surgery in affiliated hospital of Jining Medical University from September 2020 to June 2023 were enrolled by a convenience sampling method, they were randomly divided into experimental group and control group according to random number table method. Two groups was given routine perioperative care, on this basis, the control group received lip and abdomen contraction breathing training according to the conventional process, and the experimental group adjusted timing of nebulization and analgesic usage and received respiratory function training when nebulization and analgesics were at the peak of blood drug concentration. Pain level and exercise self-efficacy of two groups were compared.Results:There were 27 males and 15 females in the control group, aged (54.52 ± 14.06) years; and 24 males and 18 females in the experimental group, aged (53.33 ± 12.02) years. At one day, two days and three days after operation, the scores of Numerical Rating Scale (NRS) were (5.07 ± 0.84), (3.40 ± 0.49), (2.93 ± 0.87) in the experimental group, lower than (5.86 ± 1.05), (4.09 ± 0.88), (3.33 ± 0.65) in the control group, the differences were statistically significant ( t=3.79, 4.44.2.42, all P<0.05), and for both groups, the differences in the time effect, between-group effect, and the interaction effect were all statistically significant ( F=582.92, 44.65, 3.82, all P<0.05). Three days after operation, the dimensions of efficacy expectation, outcome expectation and total self-efficacy scores were (28.62 ± 6.75), (33.71 ± 7.04) and (62.33 ± 9.07) in the experimental group, and (25.52 ± 6.66), (30.43 ± 6.80) and (55.95 ± 9.34) in the control group, the differences were statically significant ( t=2.12, 2.18, 3.18, all P<0.05). Conclusions:Adjusting timing of nebulization and analgesic usage and giving respiratory function training for lung cancer surgery when nebulization and analgesics at the peak of blood drug concentration can effectively alleviate the pain caused by respiratory exercise and improve training self-efficacy of patients after lung cancer surgery.