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.

Metabolic dysfunction-associated fatty liver disease （MAFLD） is a chronic liver disease closely related to metabolic dysfunction. Its global prevalence is increasing year by year and shows a trend toward younger onset. It is closely associated with cardiovascular and cerebrovascular diseases， chronic kidney disease， and extrahepatic malignant tumors， and has become a major public health problem affecting the health of the Chinese population. At present， the treatment of MAFLD mainly focuses on lifestyle intervention. When metabolic cardiovascular risk factors and liver injury are present， pharmacological intervention is required. However， there is still no specific drug therapy for MAFLD. In recent years， many studies have found that the pathogenesis of MAFLD involves interactions among multiple factors， including insulin resistance， oxidative stress， endoplasmic reticulum stress， programmed cell death， immune dysregulation， inflammasomes， gut microbiota imbalance， and bile acid metabolism. Traditional Chinese medicine （TCM） has advantages in integrated regulation with multiple components and multiple targets， and shows significant efficacy in the treatment of MAFLD. Active components of Chinese medicinal herbs and Chinese medicine compound formulas exert definite therapeutic effects by regulating multiple signaling pathways to improve lipid metabolism disorders， inhibit inflammatory responses， and regulate the gut microbiota， thereby effectively improving clinical symptoms and delaying the occurrence and development of MAFLD. Therefore， strengthening research on the mechanisms of action of TCM in MAFLD is of crucial importance and significance for its treatment. This article summarizes the mechanisms by which Chinese medicine monomers and compound formulas intervene in MAFLD through the regulation of related signaling pathways， based on the retrieval and analysis of relevant literature from multiple databases， with the aim of providing theoretical support and a reference basis for the clinical application of TCM in the treatment of MAFLD.

ObjectiveTo investigate the efficacy of C-reactive protein （CRP） in predicting the progression to acute-on-chronic liver failure （ACLF） within 90 days after disease onset in patients with acute decompensation （AD） of cirrhosis， and to provide a reference for the early identification of high-risk populations in clinical practice. MethodsA retrospective study was conducted among 906 patients with liver cirrhosis who were hospitalized due to AD in Nanjing Second Hospital from January 1， 2015 to October 31， 2024， and demographic features， AD type， and laboratory markers were collected on admission. The primary endpoint was progression to ACLF within 90 days after admission， and according to the presence or absence of ACLF， the patients were divided into non-ACLF group with 676 patients and ACLF group with 230 patients. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Cox proportional-hazards regression models were used to identify independent predictive factors for ACLF. The receiver operating characteristic （ROC） curve was used to assess the predictive performance of CRP and existing scoring systems （Model for End-Stage Liver Disease ［MELD］， Child-Turcotte-Pugh ［CTP］ score， and Chronic Liver Failure Consortium Acute Decompensation ［CLIF-C AD］ score）， and the restricted cubic spline analysis was used to investigate the nonlinear relationship between CRP and the risk of ACLF. Youden index was used to determine the optimal predictive cut-off value for CRP， and the Kaplan-Meier survival curve was plotted for risk stratification， while the log-rank test was used for survival analysis. ResultsAmong the 906 AD patients， the incidence rate of ACLF was 25.39% within 90 days. The incidence rate of ACLF within 90 days was 45.1% in the 264 patients with bacterial infection and 17.3% in the 642 patients without bacterial infection （χ²=74.791， P<0.001）. Among the 906 patients， 312 patients （34.44%） had acute-on-chronic pre-liver failure （pre-ACLF）， with a significantly higher proportion of patients who progressed to ACLF than those in the non-pre-ACLF group ［60.58% （189/312） vs 6.90% （41/594）， χ²=310.234， P<0.001］. Among the 230 patients with ACLF， there were 102 patients with stable ACLF （44.35%） and 128 patients with unstable ACLF （55.65%）， with a significant difference in CRP between the two groups of patients （U=5 234.500， P<0.001）. The restricted cubic spline analysis showed a significant nonlinear relationship between CRP and the risk of ACLF （P<0.001）. The optimal cut-off value of CRP was determined as 10.16 mg/L based on the Youden index， with a sensitivity of 70.4% and a specificity of 64.5%. The Kaplan-Meier curve analysis showed that the high-risk group with CRP≥10.16 mg/L had a significantly higher event-free survival rate of ACLF within 90 days compared with the low-risk group （P<0.001）. The multivariate Cox regression analysis showed that AD type-hepatic encephalopathy （hazard ratio ［HR］=4.199， 95% confidence interval ［CI］： 3.056 — 5.770， P<0.001）， AD type-bacterial infection （HR=1.826， 95%CI： 1.356 — 2.459， P<0.001）， CRP （≥10.16 mg/L） （HR=2.356， 95%CI： 1.825 — 3.047， P<0.001）， white blood cell count （HR=1.021， 95%CI： 1.002 — 1.041， P=0.035）， hemoglobin （HR=0.994， 95%CI： 0.989 — 0.999， P=0.025）， international normalized ratio （HR=1.657， 95%CI： 1.372 — 2.001， P<0.001）， total bilirubin （HR=1.003， 95%CI： 1.002 — 1.004， P<0.001）， albumin （HR=0.956， 95%CI： 0.926 — 0.986， P=0.004）， creatinine （HR=1.005， 95%CI： 1.004 — 1.006， P<0.001）， serum sodium （HR=0.976， 95%CI： 0.956 — 0.997， P=0.025）， and lactate dehydrogenase （HR=1.001， 95%CI： 1.001 — 1.002， P<0.001） were all independent predictive factors for progression to ACLF within 90 days. The ROC curve analysis showed that CRP alone had an area under the ROC curve （AUC） of 0.724 （95%CI： 0.685 — 0.763） in predicting ACLF， and CRP+MELD score had the best predictive performance （AUC=0.870， 95%CI： 0.843 — 0.898）， while CRP+CTP score and CRP+CLIF-C AD score had an AUC of 0.852 （95%CI： 0.823 — 0.881） and 0.845 （95%CI： 0.812 — 0.877）， respectively. There was a significant increase in model performance after integration （P<0.05）. ConclusionSerum CRP level on admission is an independent predictive factor for progression to ACLF within 90 days in patients with AD of cirrhosis， and a CRP level of ≥10.16 mg/L can be used as a simple threshold for identifying high-risk patients. Incorporating CRP into existing assessment systems may enhance the early identification of patients at a high risk for ACLF， which provides a reference for clinical intervention.

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 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.

Objective:To explore the correlation between quantitative parameters based on SUV acquired by dynamic SPECT/CT imaging of parotid glands and pathological grading of labial gland in patients with primary Sj?gren syndrome (pSS).Methods:Seventy-two patients (6 males, 66 females, age (51.5±13.8) years) with confirmed pSS diagnosed at Hebei General Hospital between August 2022 and March 2024 were prospectively included. The clinical data and pathological grading information from labial gland biopsies were analyzed. Dynamic SPECT/CT imaging of the parotid glands was performed, and quantitative parameters based on SUV were obtained using Q-metrix software: SUV max, SUV mean, uptake volume of parotid glands (UVP) and total parotid uptake (TPU) pre/post-acid stimulation, as well as the differences in quantitative parameters before and after acid stimulation (ΔSUV max, ΔSUV mean, ΔUVP, and ΔTPU). The independent-sample t test or Mann-Whitney U test was performed to evaluate the differences in parameters between patients with pathological grade 1-2 and those with pathological grade 3-4. Spearman rank correlation was used to analyze the correlation between quantitative parameters and pathological grading. The performance of quantitative parameters in distinguishing pathological grade 1-2 from grade 3-4 was assessed using ROC curve analysis with Delong test. Results:The SUV max pre/post-acid stimulation in patients with pathological grade 1-2 ( n=30) were higher than those in patients with grade 3-4 ( n=42) (36.38(27.81, 44.17) vs 15.45(10.77, 24.51), Z=-5.51, P<0.001(pre-acid stimulation); 21.53(16.93, 26.21) vs 11.33(7.32, 15.89), Z=-5.27, P<0.001 (post-acid stimulation)). SUV mean, UVP and TPU pre/post-acid stimulation in patients with pathological grade 1-2, as well as ΔSUV max, ΔSUV mean and ΔTPU, were all significantly higher ( Z values: from -4.73 to -3.04, t values: 6.39, 4.50, all P<0.01). Moreover, these parameters were negatively correlated with the pathological grading ( rs values: from -0.66 to -0.36, all P<0.05). No significant difference in ΔUVP was observed between patients with pathological grade 1-2 and those with grade 3-4 ( Z=-1.05, P=0.293), and ΔUVP showed no correlation with pathological grading ( rs=-0.13, P=0.297). Among all parameters, SUV max pre/post-acid stimulation and TPU pre-acid stimulation exhibited better diagnostic performance in differentiating pathological grade 1-2 from grade 3-4, with AUC values of 0.883, 0.866, and 0.888, respectively. Delong test showed that those 3 AUC values were all higher than AUC values of SUV mean, UVP post-acid stimulation and ΔUVP (all AUC<0.800; Z values: 2.09-4.65, all P<0.05). Conclusion:The quantitative parameters of parotid glands based on SUV acquired by dynamic SPECT/CT can reflect the damage degree of parotid glands in patients with pSS, providing novel quantitative analytical tools for the functional diagnosis and assessment of pSS.

Objective:This study aimed to systematically evaluate the efficacy of glucagon-like peptide-1(GLP-1) receptor agonists and multi-target analogs on weight reduction and cardiometabolic outcomes in non-diabetic individuals with obesity, and to compare the efficacy and safety across different GLP-1 receptor agonists.Methods:Randomized controlled trials(RCTs) published between January 2000 and March 2025 were identified through a systematic search of CNKI, Wanfang, Web of Science, PubMed, and Cochrane databases. Two reviewers independently screened the studies, extracted data, and assessed methodological quality. Meta-analysis was performed using RevMan 5.4.1 software. Results:A total of 16 RCTs involving 11 032 non-diabetic individuals with obesity were included. Meta-analysis showed that GLP-1 receptor agonists significantly reduced body weight(ΔWeight=-8.71 kg, 95% CI -10.68 to -6.74, P<0.001) and BMI(ΔBMI=-3.01 kg/m 2, 95% CI -3.77 to -2.25, P<0.001), as well as improved systolic blood pressure(ΔSBP=-4.13 mmHg, 1 mmHg=0.133 kPa, 95% CI -4.87 to -3.39, I2=60%) and diastolic blood pressure(ΔDBP=-1.39 mmHg, 95% CI -2.32 to -0.46, I2=95%). Tirzepatide showed the most pronounced effects on both weight and blood pressure reduction. In addition, GLP-1 receptor agonists significantly lowered LDL-C, TC, and TG, while moderately increasing HDL-C levels. In terms of safety, GLP-1 receptor agonists were associated with an increased risk of gastrointestinal adverse events, but did not significantly increase the risk of hypoglycemia. Conclusion:GLP-1 receptor agonists are effective in reducing weight, BMI, and blood pressure, and in improving lipid profiles in non-diabetic individuals with obesity. However, gastrointestinal side effects should be closely monitored. Given the variability in efficacy and safety among various GLP-1 receptor agonists, personalized treatment approaches are recommended.

Spleen-stomach damp-heat syndrome is currently the most prevalent TCM pattern in patients with chronic atrophic gastritis (CAG), with internal damp-heat accumulation regarded as a key factor contributing to its prolonged and refractory course. This syndrome represents a critical stage in the progressive pathogenesis of CAG, characterized by a deepening pathological evolution. Modern TCM practitioners generally agree that its core pathogenesis lies in "deficiency in root and excess in superficiality, with internal damp-heat retention", and emphasize a treatment strategy that combines eliminating pathogenic factors and reinforcing the body's healthy qi through dynamic syndrome differentiation. Chinese materia medica used in treating CAG with spleen-stomach damp-heat syndrome can effectively relieve clinical symptoms, improve the internal damp-heat environment, mitigate gastric mucosal atrophy and intestinal metaplasia, and delay the inflammation-to-cancer transformation. Its mechanisms may involve eradication of Helicobacter pylori, repair of gastric mucosal injury, regulation of immune inflammatory response and other aspects, which has the advantages of multi-channel and multi-target.