This study aimed to investigate the protective effects of Huangqi Guizhi Wuwu decoction (HGWD) against cerebral ischemic injury and the underlying mechanisms. A middle cerebral artery occlusion (MCAO) model was established in C57BL/6 mice to evaluate the effects of HGWD on neurobehavioral scores, cerebral infarction rate, brain water content, and oxidative stress and inflammatory markers. The mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in brain tissue were assessed. In addition, Nrf2 knockout mice were used to verify the role of Nrf2 in the protective effects of HGWD against MCAO-induced injury. Additionally, an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary neuronal cells was employed to further confirm the pharmacological effects of HGWD in vitro. The results showed that HGWD significantly ameliorated cerebral ischemic injury in MCAO mice, alleviated oxidative stress, suppressed the release of inflammatory factors, and markedly upregulated the expression of Nrf2, HO-1, and Bcl-2 while downregulating Bax expression, with consistent trends being observed at both mRNA and protein levels. The protective effects of HGWD were significantly attenuated in Nrf2 knockout mice, indicating the pivotal role of Nrf2 in HGWD-mediated protection against cerebral ischemic injury. In vitro experiments revealed that HGWD significantly increased neuronal cell viability, reduced lactate dehydrogenase(LDH) leakage, and decreased apoptosis in OGD/R-treated cells, accompanied by upregulation of Nrf2, HO-1, and Bcl-2 and downregulation of Bax. In conclusion, HGWD protects against cerebral ischemic injury by activating the Nrf2/HO-1 pathway to enhance antioxidant capacity and modulating the Bcl-2/Bax signaling pathway to inhibit apoptosis, thereby protecting brain cells from ischemic damage.

This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

The crystalline lens of the eye is recognized as one of the most radiosensitive tissues in the human body. While the International Commission on Radiological Protection (ICRP) has classified ionizing radiation (IR)-induced cataracts as a tissue reaction (deterministic effect) and subsequently reduced the occupational equivalent dose limit for the lens, significant uncertainties remain regarding the precise dose threshold and the complex biological pathways driving lens opacification. This review provides a comprehensive synthesis of current knowledge concerning radiation-induced lens damage, integrating epidemiological exposure characteristics with dose-response modeling and mechanistic molecular insights. First, we analyze exposure characteristics through four epidemiological dimensions: dose, time, space, and population. Clinical evidence suggests that radiation cataracts—particularly posterior subcapsular opacities—exhibit a distinct latency period that is inversely correlated with dose. We highlight that risk is not confined to acute high-dose scenarios (such as in atomic bomb survivors) but is increasingly relevant in chronic low-dose occupational settings (e.g., interventional radiology) and medical diagnostics (e.g., CT scans). Crucially, individual susceptibility is modified by genetic background, age, and environmental co-factors, complicating risk assessment. Second, we critically examine the dose-effect relationship. Although the ICRP suggests a threshold of 0.5 Gy, emerging data challenge the traditional threshold model, with some studies advocating for a linear non-threshold (LNT) relationship. We further discuss the critical roles of radiation quality and dose rate. High linear energy transfer (LET) radiation demonstrates a significantly higher relative biological effectiveness (RBE) for cataractogenesis compared to low-LET radiation. Paradoxically, and unlike many other tissues, the lens may exhibit an “inverse dose-rate effect,” where fractionated or protracted exposures potentially enhance biological damage—a finding that challenges classical radiobiological paradigms. Third, drawing upon the “cataractogenic load” hypothesis and the unique physiological constraints of the lens, this review elucidates the multidimensional molecular mechanisms driving radiation-induced opacification. Key mechanisms include four aspects. (1) DNA damage and repair: IR induces DNA double-strand breaks (DSBs) that, due to the lens’ limited repair capacity (modulated by genes such as ATM, Ptch1, and Ercc2), lead to the accumulation of damage. (2) Antioxidant defense system: dysfunction of the Nrf2/HO-1 antioxidant axis results in redox imbalances, triggering NF-κB-mediated inflammation and protein aggregation. (3) Cell proliferation and senescence: IR disrupts cell cycle regulation, causing a dichotomy of effects—driving premature senescence in some cell populations (evidenced by ATM nuclear foci) while inducing aberrant proliferation via growth factor upregulation (FGF2, TGFβ) in others. (4) Cell migration and adhesion: activation of the Wnt/β‑catenin pathway and alterations in the E-cadherin complex promote the abnormal migration of epithelial cells to the posterior capsule, a hallmark of radiation-induced cataracts. In conclusion, radiation-induced cataractogenesis is a multifactorial process in which genetic susceptibility and environmental stressors converge to overwhelm the lens’ homeostatic thresholds. Future research must prioritize longitudinal cohort studies to refine dose thresholds and employ multi-omics approaches to map the crosstalk between DNA damage responses and matrix remodeling. Establishing a robust mechanistic model is essential for developing targeted radioprotective strategies and optimizing radiation protection standards for occupational and medical safety.

ObjectiveTo investigate differential metabolites associated with browning in the post-harvest processing of Pinelliae Rhizoma， providing data support for elucidating the key metabolites and metabolic pathways involved in browning， and developing safe and efficient sulfur-free processing techniques. MethodsUltra-performance liquid chromatography-triple quadrupole/linear ion trap mass spectrometry（UPLC-QTRAP-MS/MS） was used to detect the metabolites of Pinelliae Rhizoma at different browning stages（0， 8， 16 h） for widely targeted metabolomics. Subsequently， Multivariate statistical analysis of metabolites was conducted using principal component analysis（PCA）， hierarchical cluster analysis（HCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， and K-means cluster analysis. Differential metabolites at different browning stages were screened based on variable importance in the projection（VIP） value>1 and |log₂fold change（FC）|≥1， and metabolic pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. ResultsA total of 1 416 metabolites were identified across the three browning stages of Pinelliae Rhizoma， predominantly comprising amino acids and their derivatives（239）， lipids（219）， alkaloids（156）， phenolic acids（121）， terpenoids（113）， and flavonoids（111）. A two-by-two comparison of the three browning phases， yielded 622 differential metabolites that were significantly enriched in the phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolic pathway. Further analysis revealed that carbohydrates such as D-mannose and turanose， phenolic acids such as 1-O-caffeoyl-6-O-glucosyl-β-D-glucose， dicaffeoylshikimic acid， and flavonoids such as epigallocatechin gallate， vitexin-7-O-rutinoside， luteolin-7-O-（6″-malonyl）glucoside-5-O-arabinoside， catechin gallate， epicatechin gallate， isovitexin-7-O-glucoside-2″-O-rhamnoside， apigenin-7-O-rutinoside-4ʹ-O-sophoroside， 3，5，3ʹ，4ʹ，5ʹ-penta-hydroxyflavan-7-gallate may act as browning substrates and play important roles in the browning process. ConclusionCarbohydrates， phenolic acids， and flavonoids may serve as key substrates in the browning process of Pinelliae Rhizoma， involving pathways such as phenylpropanoid biosynthesis， flavone and flavonol biosynthesis， and purine metabolism， which can provide a theoretical basis for further exploration of the browning mechanism.

Objective: To observe the distribution characteristics of sex differences in physical growth among children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024, so as to provide clues for improving growth assessment standards and promoting the health of children and adolescents. Methods: Using publicly available height and weight data for children and adolescents aged 6-15 years in Taiwan, China from 2007 to 2024 released by the statistics agency of the Taiwan education authorities, sex difference indices were analyzed. Growth curve charts and Pearson correlation were used to analyze the correlation between height/weight and year, as well as trends of change with age and year. These were compared with data from the 8th National Survey on Students Constitution and Health in 2019, covering Han and ethnic minority groups aged 6-15 years in mainland China. Results: The sex difference index for height among children and adolescents in Taiwan, China ranged from -1.20% to 6.67%, showed a trend of decreasing first and then increasing with age. The sex difference index for weight ranged from 3.76% to 19.15%, exhibited an age related trend of a slight initial increase, followed by a decrease, and then an increase. The sex difference indices for height in the 12-15 age groups and for weight in the 15-year-old group were positively correlated with the year ( r =0.74, 0.66, 0.61, 0.92 ; 0.63), while the sex difference indices for weight in the 6-8 age groups were negatively correlated with the year ( r =-0.71, -0.77, -0.53) (all P <0.05). In 2024, the height of children and adolescents in Taiwan, China increased gradually with age, but the growth rate for girls slowed down after age 12. A "two crossover" was observed in height between boys and girls, with boys being taller than girls in the 6-9 age range and after age 12. Weight for both sexes gradually increases with age, but boys have greater weight than girls at all ages. In 2019, the sexual differences in body size among children and adolescents in the Taiwan region, China (the sex difference indices for height:-0.96% to 6.49%；the sex difference indices for weight:4.69%-17.89%) fell within the variation ranges of counterparts in mainland China (the sex difference indices for height:-5.43% to 7.69%；the sex difference indices for weight:-10.12% to 21.56%). Conclusion The sex differences in physical growth among children and adolescents in Taiwan, China are dynamically changing with age and over the long term.

Extranodal NK/T cell lymphoma (ENKTL) is a rare subtype of extranodal non-Hodgkin lymphoma (NHL) with strong invasiveness. Although the chemotherapy regimen based on asparaginase is the standard treatment for advanced patients, the prognosis needs to be improved. Moreover, treatment options are limited for recurrent or refractory patients who have failed chemotherapy. In recent years, the research progress of the programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitor has provided a new perspective for ENKTL treatment. This article summarizes the role of PD-1/PD-L1 in the pathogenesis of ENKTL and the regulatory factors of PD-L1 expression. It also explores the differences in the PD-1/PD-L1 expression in ENKTL of different molecular typing systems as well as the application prospects of their inhibitors in the treatment of ENKTL.

ObjectiveTo explore the impacts of material type and loading volume of rigid containers on the hydrogen peroxide low temperature plasma sterilization of thoracoscopic instruments, to identify the best rigid containers and loading volume of thoracoscopic instruments. MethodsThoracoscopic instruments sterilized by STERRAD^® 100NX hydrogen peroxide low temperature plasma in Shanghai Pulmonary Hospital affiliated to Tongji University from August to September 2024 were selected as the research items. According to the material of rigid containers, the instruments were divided into polyethylene case group (A), stainless steel case group (B) and silicone resin case group (C). In terms of the loading volume, the rigid containers were divided into (loading capacity <80%) groups of 8, 10 and 12 instruments. The results of physical monitoring, the first type of chemical indicator card monitoring, and the five types of card luminal chemical process challenge device (PCD) monitoring of the 9 groups of A8, A10, A12, B8, B10, B12, C8, C10 and C12 were compared and evaluated. ResultsCompared to A8, A10 A12, C8, C10 or C12 groups, the thoracoscope instruments in the stainless steel containers in B8, B10 or B12 group had higher hydrogen peroxide concentrations and shorter elapsed time in the pressure check phases 1 and phases 2, with the differences statistically significant (P<0.05), followed by the silicone resin case group and the polyethylene case group. The nine groups of physical parameter monitoring, the first type of chemical indicator monitoring, and the five types of chemical PCD monitoring for lumen sterilization achieved 100% qualification rates, and there were no significant differences in the qualified rates of sterilization among the 9 groups (P>0.05). ConclusionWhen using hydrogen peroxide low temperature plasma to sterilize thoracoscopic instruments, it is recommended to use stainless steel or silicone resin rigid containers with a controlled loading capacity (≤12) to ensure optimal sterilization quality.

ObjectiveTo investigate the modifiable areal unit problem （MAUP） in the spatial pattern of Pseudostellaria heterophylla production regions and reveal the impact of statistical scales on the spatial distribution characteristics of this medicinal plant species. MethodsUsing multi-source data （literature records， field surveys， and statistical data）， we systematically analyzed the spatial patterns across three administrative levels （provincial， prefectural， and county scales）. Spatial autocorrelation （Moran's I） analysis， high-low clustering （Getis-Ord General G）， and hot/cold spot analysis （Getis-Ord Gi*） were employed. ResultsThe literature-based analysis showed that the production regions of P. heterophylla presented random distribution on the provincial scale and significant aggregation on the prefectural scale. The field survey data showed that the production regions displayed random distribution on the provincial scale but significant aggregation on both prefectural and county scales. The statistical data revealed that the production regions lacked spatial autocorrelation on the provincial scale but demonstrated significant aggregation on prefectural and county scales. ConclusionMAUP effects have substantive implications for understanding and decision-making in the arrangement of medicinal plant production regions. The county scale proves to be the most sensitive and explanatory level for analyzing the spatial pattern of P. heterophylla production regions， providing a critical foundation for habitat modeling， suitability evaluation， and ecological cultivation planning of medicinal plants.