Objective: To investigate the effect of different surface treatment protocols on the surface properties and immediate shear bond strength (SBS) between 3D-printed zirconia and resin cement to provide a reference for clinical practice. Methods: Disc-shaped zirconia specimens (Ø 14 mm× 1.2 mm) with two different surface designs were fabricated using 3D printing technology: a smooth surface (Group S) and microporous surface (Group M), with 40 specimens in each group. Each group was further randomly divided into four subgroups according to surface treatment: untreated (Subgroup U), alumina sandblasting (Subgroup ST), alumina sandblasting + Z-Prime ceramic primer (Subgroup ZP), and alumina sandblasting + Monobond N ceramic primer (Subgroup MN). The surface morphology was examined, roughness was measured, and wettability was evaluated via contact-angle testing. Composite resin cylinders (Ø 3.5 mm× 2.0 mm) were bonded to the zirconia surfaces with resin cement. Immediate SBS was determined by shear testing, and failure modes were analyzed. Results: Scanning electron microscopy revealed clear micro-grooves (2-5 μm wide) in Subgroup S-U and micropores (approximately 400 μm in diameter) in Subgroup M-U. After sandblasting, the micro-grooves in Subgroup S-ST were partially destroyed with some micro-cracks, while the microporous structure in Subgroup M-ST remained clear. Compared with Subgroups S-U and M-U, sandblasted zirconia specimens (Subgroups S-ST, S-ZP, S-MN, M-ST, M-ZP, M-MN) showed significantly increased roughness and decreased contact angles. Different surface treatments significantly affected SBS between 3D-printed zirconia and resin. Sandblasted groups (Subgroups S-ST and M-ST) had significantly higher SBS than untreated groups (Subgroups S-U and M-U). The application of ceramic primers after sandblasting (Subgroups S-ZP, S-MN, M-ZP, M-MN) further increased SBS; however, there was no statistically significant difference in SBS between the two primers used after sandblasting (Subgroup S-ZP vs. S-MN, Subgroup M-ZP vs. M-MN). Under the same surface treatment, microporous surface groups (Subgroups M-U, M-ST, M-MN, M-ZP) all exhibited significantly higher SBS than smooth surface groups (Subgroups S-U, S-ST, S-MN, S-ZP). Conclusion Fabricating a microporous surface using 3D printing technology can improve resin bonding effectiveness. Sandblasting combined with a ceramic primer yields the highest immediate SBS.

ObjectiveTo investigate the mechanisms of Tongnao decoction （TND） in mice with acute ischemic stroke （AIS）. MethodsFifty male C57BL/6J mice were randomly divided into a sham operation group， model group， TND low-dose group （1.86 g·kg^-1）， TND high-dose group （3.72 g·kg^-1）， and butylphthalide （NBP） group （10 mg·kg^-1）， with 10 mice in each group. A mouse model of cerebral ischemic injury was established using photochemical thrombosis （PT）. The sham operation group and model group were administered an equal volume of normal saline by gavage. All five groups were treated once daily for 14 consecutive days. Behavioral tests were performed before modeling and at the end of administration. T₂-weighted imaging （T₂WI） was performed 3 days after modeling to evaluate the extent of injury. Hematoxylin-eosin （HE） staining was used to observe histological changes in the cerebral cortex， and Nissl staining was used to observe neuronal morphology. Cerebral blood flow in mice was detected using a laser speckle contrast imaging （LSCI） system. Immunofluorescence staining was used to detect the cell proliferation marker bromodeoxyuridine （BrdU） and the highly glycosylated type I transmembrane glycoprotein CD34. Western blot analysis was used to detect the expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， glycogen synthase kinase-3β （GSK-3β）， and their phosphorylation levels， as well as tight junction-related proteins zonula occludens-1 （ZO-1）， Occludin， and Claudin-5 in the peri-infarct tissue. Thirty-five zebrafish were randomly divided into normal control group， model group， TND low and high dose groups （0.16， 0.32 g·L^-1） and NBP group （10 μmol·L^-1）， with 7 in each group. A stereoscopic fluorescence microscope was used to observe vascular growth in zebrafish. ResultsImaging showed that PT caused ischemia in the right cortical region. Behavioral tests indicated that， compared with the model group， the drug-treated groups reduced the error rate of irregular balance ladder climbing on the affected side and shortened the tape removal time （P<0.05）. HE staining and Nissl staining showed that， compared with the model group， the drug-treated groups exhibited reduced brain tissue damage， fewer scars， and improved neuronal morphology. LSCI results showed that the drug-treated groups partially restored cerebral blood perfusion and promoted the establishment of collateral circulation compared with the model group. Immunofluorescence staining indicated that the drug-treated groups increased the positive rates of BrdU and CD34 compared with the model group （P<0.01）， promoting angiogenesis. Meanwhile， compared with the model group， the drug-treated groups upregulated the expression levels of p-PI3K， p-Akt， p-GSK-3β， and tight junction proteins ZO-1， Occludin， and Claudin-5 （P<0.05，P<0.01）， and increased the number of intersegmental vessels in zebrafish （P<0.05，P<0.01）. ConclusionTND can promote angiogenesis around the infarct in PT model mice by regulating the PI3K/Akt/GSK-3β signaling pathway， thereby improving cerebral ischemic injury.

Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

Objective: To investigate the role of ferroptosis in transfusion-related acute lung injury (TRALI) and evaluate the efficacy of the specific inhibitor Ferrostatin-1 (Fer-1), thereby to provide a basis for the prevention and treatment of TRALI. Methods: This study utilized a ”2-hit” model to induce TRALI in mice. The mouse model of TRALI was validated through survival curve analysis, lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) activity, and total protein concentration in lung tissue. Samples from the TRALI model group, LPS group, and control group (n=6) were collected. The occurrence of ferroptosis in TRALI was confirmed by measuring key ferroptosis indicators, including iron concentration in lung tissue, malondialdehyde (MDA) level, lipid peroxidation products (LPO) level, and expression levels of related proteins (GPX4, ACSL4). Additionally, a Fer-1 intervention group was added to evaluate its preventive and therapeutic effects. The survival rates and clinical symptoms of the four groups (n=6) were dynamically monitored, and the degrees of lung injury were assessed. Ferroptosis-related indicators were also measured to elucidate the protective mechanism of Fer-1. Results: A mouse model of TRALI was successfully established. Compared to the control and LPS groups, the TRALI group showed significantly higher levels of ferrous iron [(18.32±1.11) nmol/well, MDA [(14.68±0.96) μmol/L], and LPO [(1.60±0.02) μmol/L] in lung tissue (all P<0.01), along with a downregulation of GPX4 and an upregulation of ACSL4. Fer-1 pretreatment significantly reversed these abnormalities: the W/D ratio decreased to 4.01±0.43, and MPO activity significantly decreased [Fer-1 group: (21 606±4 235) pg/mL vs TRALI group: (30 724±2 616) pg/mL], the total protein concentration in lung tissue of the Fer-1 group decreased by approximately 40.8% compared to the TRALI group (all P<0.01). These changes indicate that the lung injury in mice was alleviated after treatment. Following Fer-1 intervention, ferrous iron concentration [(7.46±1.83) nmol/well] was restored to a level close to that of the control group [(5.48±0.70) nmol/well]. Lipid peroxidation tests further revealed that Fer-1 intervention reduced MDA and LPO levels by 35.8% and 29.4%, respectively (P<0.001). Additionally, the expression levels of GPX4 and ACSL4 proteins returned to near-normal levels in the treated mice (both P>0.05). Conclusion: The progression of TRALI is closely related to the activation of ferroptosis, characterized by iron overload, lipid peroxidation accumulation, and the imbalance of GPX4/ACSL4. Ferrostatin-1 significantly alleviates pulmonary edema and inflammatory damage by inhibiting the ferroptosis pathway, suggesting that targeting ferroptosis may provide a new therapeutic strategy for TRALI.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Gastric cancer （GC） has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present， the treatment plans are optimized mainly in terms of surgery， radiotherapy， and intervention， while the endpoints of clinical trials， such as patients' overall survival， progression-free survival， and disease-free survival， are still unsatisfactory. Therefore， effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s， Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then， the abnormal metabolic network inside tumor cells has gradually entered into researchers' view， and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years， traditional Chinese medicine （TCM） is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore， linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically， while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer （PLGC） in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor （HIF）-1α， cancer-Myc （c-Myc）， apolipoprotein E （APOE） and pyruvate kinase M2 （PKM2） were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized， with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.

Ulcerative colitis （UC） is a chronic intestinal autoimmune disease， with clinical manifestations including abdominal pain， diarrhea， mucus and bloody stools， and its pathogenesis is complex. The classic prescription Xianglian pills （XLP） has been widely used in the clinical treatment of UC in recent years. It has few adverse reactions， good patient tolerance， and shows significant potential for clinical application. However， there is currently no comprehensive integration of evidence on its clinical research and molecular mechanisms. Through a systematic review of the clinical research and molecular mechanisms of XLP in the treatment of UC， it is found that XLP and its modified formulas， when used in combination with chemical drugs， can significantly improve the symptoms of UC patients and reduce intestinal inflammation， with superior efficacy compared to chemical drugs alone. Its mechanism of action involves regulating pan-apoptosis， immune response， signaling pathways （hypoxia-inducible factor-1α， nuclear factor-κB， etc.）， intestinal flora， and repairing the intestinal mucosal barrier. Its medicinal materials， monomers and active components can also prevent the differentiation of helper T cells 17 and restore the balance of M1/M2 cells through regulating multiple pathways such as Wnt/β -catenin and Janus kinase/signal transducer and activator of transcription， thereby reducing intestinal damage in UC.

The Huangdi Neijing proposes the " using bitter herbs to nourish or purge" theory to guide clinical prescription and formulation of herbal remedies based on the physiological characteristics and functions of the five zang viscera, along with the properties and flavors of medicinal herbs. This study explored diabetic kidney disease pathogenesis and treatment based on the " using bitter herbs to nourish or purge" theory. Kidney dryness is a key pathological factor in diabetic kidney disease, and the disharmony of kidney dryness is an essential aspect of its pathogenesis. Strengthening is the primary therapeutic principle, and kidney dryness is a persistent factor throughout the occurrence and progression of diabetic kidney disease. In the early stage, the pathogenesis involves heat-consuming qi and injuring yin, leading to kidney dryness. In the middle stage, the pathogenesis manifests as qi deficiency and blood stasis in the collaterals, resulting in turbidity owing to kidney dryness. In the late stage, the pathogenesis involves yin and yang deficiency, with kidney dryness and disharmony. This study proposes the staging-based treatment based on the " need for firmness" characteristic of the kidney. The aim is to provide new insights for clinical diagnosis and treatment in traditional Chinese medicine by rationally using pungent, bitter, and salty medicinal herbs to nourish and moisturize the kidney. This approach seeks to promote precise syndrome differentiation and personalized treatment for different stages of diabetic kidney disease, thereby enhancing clinical efficacy.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.