Objective To investigate the effects of dapagliflozin on inflammatory factors and prognosis in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction (AMI). Methods In a randomized, double-blind trial, 146 patients with T2DM and AMI (within 7 days of onset) were divided into dapagliflozin (dapagliflozin 10 mg/d combining AMI standard therapy) and control (AMI standard therapy) groups, and were followed up for 12 months. Serum levels of interleukin-1β (IL-1β), IL-6, high-sensitivity C reactive protein (hs-CRP) at baseline, 1, 3, 6, and 12 months, and left ventricular ejection fraction (LVEF), brain natriuretic peptide (BNP), and major adverse cardiovascular events (MACE) rate at 12 months were compared between the two groups. Kaplan-Meier curves were used to analyze the cumulative incidences of MACE in the two groups. Results Three patients were withdrawn or dropped out. At 12 months, IL-1β, IL-6, and hs-CRP levels were significantly lower in dapagliflozin group (n＝71) than those in control group (n＝72, P＜0.01), approaching normal levels. Compared with the control group, LVEF was higher (P＜0.01), BNP was lower (P＜0.01), MACE incidence was lower (P＝0.047) in dapagliflozin group at 12 months. Generalized linear mixed models showed significant group-time interactions in IL-1β, IL-6, and hs-CRP (P＜0.001), and these factors declined faster in the dapagliflozin group. Kaplan-Meier curve showed the cumulative incidences of MACE and heart failure were lower in dapagliflozin group than those in non-dapagliflozin group (P＜0.05). Conclusions For patients with T2DM patients and AMI, dapagliflozin has good anti-inflammatory and cardioprotective effects.

Objective Orosomucoid1 （ORM1） is a novel target in the quest for anti-fatigue pharmacotherapy. Preliminary investigations have illuminated oleuropein （OLE） as a promising candidate molecule, poised to enhance ORM1 expression. To elucidate the influence of OLE on ORM1 protein expression and assess its ramifications on muscle endurance. Methods The impact of OLE on ORM1 protein expressions within hepatocytes and liver tissue was meticulously quantified through Western blotting; the effects of OLE on muscle endurance were evaluated via the rotarod and forced swimming tests; glycogen content within liver and muscle tissues was determined utilizing a specialized kit; and PAS staining was employed to visualize glycogen deposition in the gastrocnemius muscle. Results OLE demonstrated a capacity to elevate ORM1 protein expression in hepatocytes in a time- and dose-dependent manner, concurrently prolonging the duration of swimming and rotarod performance in mice, also in a time- and dose-dependent manner. Furthermore, OLE augmented ORM1 expression in liver tissue, elevated serum ORM1 levels, and enhanced glycogen reserves within the liver and muscle. Conclusion OLE may serve to amplify muscle endurance by elevating ORM1 levels in vivo and augmenting glycogen stores within skeletal muscle.

Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

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.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Gastric precancerous lesions， often presenting as decreased appetite， weight loss， fatigue， epigastric fullness， and upper abdominal pain， pose challenges to treatment and considerably affect patients' quality of life. Pathologically， these lesions are characterized by alterations in the gastric mucosa accompanied by intestinal metaplasia or dysplasia， which markedly elevate the risk of developing gastric cancer. Traditional Chinese medicine （TCM） practitioners have explored various therapeutic approaches focusing on invigorating the spleen， resolving dampness， clearing heat， addressing phlegm accumulation， activating blood， and detoxifying. For contemporary populations suffering from gastric precancerous lesions， our team has innovatively proposed a core pathogenesis theory encompassing deficiency， stagnation， phlegm， stasis， and toxin. Furthermore， our team has developed a comprehensive prevention and treatment framework： Invigorating the spleen and harmonizing the stomach （foundational principles）， balancing and restoring Qi movement （primary objectives）， resolving phlegm and unblocking collaterals （routine practices）， detoxifying and dissipating nodules （critical interventions）， and comprehensive health management （supportive care）. This framework provides a robust theoretical foundation along with practical guidance for preventing and treating diseases related to the spleen-stomach axis. From a pathological perspective， key interventions for managing gastric precancerous lesions include restoring integrity of the gastric mucosae while regulating its microenvironmental conditions and enhancing mucosal circulation， which are integral throughout the entire treatment process. On this basis， a full-course chain of prevention and treatment has been established within clinical practice， encompassing functional gastrointestinal disorders-superficial gastritis-atrophic gastritis-gastric precancerous lesions-prevention and treatment post-endoscopic submucosal dissection. The guiding principles of this treatment approach involve invigorating the spleen， regulating Qi movement， resolving phlegm， unblocking collaterals， and detoxifying. TCM compound formulas such as Jianpi Tongluo Jiedu prescription and Hezhong Xiaopi granules， as well as Chinese patent medicines like Weifuchun and Moluodan， can be used for treating gastric precancerous lesions at different stages. Through medicinal regulation， the state of the gastric mucosa can be improved， and thus the development of gastric precancerous lesions can be curbed from the perspective of full-course prevention and treatment.

ObjectiveTo investigate the effect of Hezhongxiaopi granules （HZXPG） on methylnitronitrosoguanidine （MNNG）-mediated gastric mucosal cell apoptosis and the regulatory effects on the Nicalin （Ncln）-C/EBP homologous protein （CHOP） axis and endoplasmic reticulum stress （ERS）. MethodsThe cell counting kit-8 （CCK-8） assay was employed to examine the inhibitory effect of MNNG on the proliferation of GES-1 cells， and the optimal effective dose of MNNG was selected. Human gastric mucosal GES-1 cells were allocated into the control， model （MNNG， 1.562 5 mmol·L^-1）， and low/high-dose HZXPG （5% and 10% HZXPG-containing serum） groups. Phalloidin staining was employed to detect MNNG-induced morphological changes in human gastric mucosal cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was adopted to assess cell apoptosis. Annexin Ⅴ/propidium iodide （Annexin Ⅴ/PI） flow cytometry was utilized to measure the alterations in the apoptotic cycle of human gastric mucosal cells. Western blot was performed to determine the expression levels of proteins related to apoptosis， ERS， and the Ncln/CHOP axis. ResultsCompared with the control group， the model group exhibited a reduction in the surface area of GES-1 cells， endoplasmic reticulum （ER） dilation， increased early and late apoptosis rates of gastric mucosal cells， upregulated protein levels of truncated Bid （tBid）， Bcl-2-associated X protein （Bax）， cleaved-cysteinyl aspartate-specific proteinase （Caspase）-3， and cleaved-Caspase-8， and downregulated protein level of B-cell lymphoma-2 （Bcl-2） （P<0.01）. In addition， the expression levels of binding immunoglobulin protein （BiP）， Ncln， and CHOP were upregulated （P<0.01）， with enhanced Ncln expression in the ER and elevated CHOP expression in the nucleus. Compared with the model group， the high-dose HZXPG group showed a significant increase in the surface area of gastric mucosal cells. Both dose groups exhibited inhibited ER dilation and reduced early and late apoptosis rates of gastric mucosal cells （P<0.01）. Low-dose HZXPG decreased the expression of tBid and Bax （P<0.05， P<0.01） and promoted Bcl-2 expression （P<0.01）. High-dose HZXPG reduced the expression levels of tBid， Bax， cleaved-Caspase-3， and cleaved-Caspase-8 （P<0.05， P<0.01） and increased the Bcl-2 expression level （P<0.05）. Furthermore， high-dose HZXPG downregulated the expression levels of BiP， Ncln， and CHOP （P<0.05， P<0.01）， while decreasing the nuclear translocation of CHOP. ConclusionHZXPG alleviates MNNG-induced ERR-mediated apoptosis of gastric mucosal cells by inhibiting the Ncln-CHOP axis， thereby relieving gastric mucosal cell damage caused by precancerous gastric lesions.

Senile chronic atrophic gastritis （SCAG） is a condition characterized by high prevalence， prolonged duration， and difficulty in treatment， along with a significant risk of carcinogenesis. This severely impacts the quality of life among the elderly population in China. The prevention and management of SCAG represent one of the most urgent and prominent needs within the current health care and elderly care sectors. However， existing treatment options are limited， with insufficient mucosal repair following Helicobacter pylori eradication， as well as a lack of effective methods to reverse atrophy or intestinal metaplasia. The primary objectives in treating chronic gastritis in older adults are symptom relief and alleviation of mucosal histological abnormalities. Traditional Chinese medicine （TCM） offers unique advantages for managing patients with SCAG. Therefore， utilizing TCM methodologies underpinned by TCM theory to prevent and treat the progression of SCAG holds considerable clinical significance. Our research team has been dedicated to theoretical， clinical， and fundamental investigations into gastric precancerous lesions and SCAG for an extended period. This article systematically reviews the intricate causal relationship between the spleen-stomach system and aging while elucidating TCM pathogenesis of SCAG as internal deficiency coupled with excess in manifestations. It explores evolutionary patterns of dampness， stagnation， stasis， toxicity， and deficiency and proposes a progressive pathogenic evolution chain： Aging-deficiency of spleen and kidney-imbalance of Qi and blood-phlegm turbidity accompanied by Qi stagnation-accumulation of phlegm， stasis， and toxicity-weakness of stomach collaterals. The core treatment principle emphasizes simultaneous treatment targeting both spleen and kidney as its foundation while employing strategies such as promoting Qi movement to resolve dampness， alongside efforts aimed at removing stasis and detoxifying as primary approaches. Finally， this article summarizes current research achievements in TCM interventions for SCAG， aiming to provide new insights for clinical practice and scientific research in TCM interventions for SCAG.