ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

AIM:To investigate the protective ef-fect of sinomenine hydrochloride(SIN)on adjuvant arthritis(AA)rats by regulating the NLRP3/Gasder-min D/Caspase-1/Interleukin-1β pyroptosis path-way.METHODS:Sixty rats were randomly divided into 6 groups,10 rats in each group:Con group(normal rats),AA group(AA rat model),L-SIN group(AA rats were intragastrically administered with 100 mg/kg SIN),M-SIN group(AA rats were intra-gastrically administered with 200 mg/kg SIN),H-SIN group(AA rats were intragastrically administered with 400 mg/kg SIN),ACG group(positive drug group:AA rats were intragastrically administered with 150 mg/kg Wantong Jingu Tablets).Observe the degree of joint swelling and arthritis index.HE was used to observe the pathological changes of the right ankle joint tissue of rats.The levels of in-flammatory factors and oxidative stress-related in-dicators in synovial tissue were detected.Western Blot was used to detect the expression levels of NL-RP3/Gasdermin D/Caspase-1/Interleukin-1β pyrop-tosis pathway-related proteins.RESULTS:Com-pared with Con group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in AA group were signifi-cantly increased(P<0.05).Compared with AA group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NL-RP3,GSDMD,Caspase-1 and IL-1β protein expres-sion levels were significantly decreased in SIN treat-ment group with the increase of treatment dose(P<0.05).Compared with AA group and L-SIN group,the degree of joint swelling,arthritis index,inflam-matory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in ACG group were significantly decreased(P<0.05).Compared with H-SIN group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Cas-pase-1 and IL-1β protein expression levels in ACG group were significantly increased(P<0.05).CON-CLUSION:SIN can alleviate the inflammatory injury of AA rats and reduce the levels of inflammatory factors and oxidative stress,thus exerting a protec-tive effect on AA rats.The mechanism may be based on the NLRP3/Gasdermin D/Caspase-1/Inter-leukin-1β pyroptosis pathway.

AIM:To investigate the protective ef-fect of sinomenine hydrochloride(SIN)on adjuvant arthritis(AA)rats by regulating the NLRP3/Gasder-min D/Caspase-1/Interleukin-1β pyroptosis path-way.METHODS:Sixty rats were randomly divided into 6 groups,10 rats in each group:Con group(normal rats),AA group(AA rat model),L-SIN group(AA rats were intragastrically administered with 100 mg/kg SIN),M-SIN group(AA rats were intra-gastrically administered with 200 mg/kg SIN),H-SIN group(AA rats were intragastrically administered with 400 mg/kg SIN),ACG group(positive drug group:AA rats were intragastrically administered with 150 mg/kg Wantong Jingu Tablets).Observe the degree of joint swelling and arthritis index.HE was used to observe the pathological changes of the right ankle joint tissue of rats.The levels of in-flammatory factors and oxidative stress-related in-dicators in synovial tissue were detected.Western Blot was used to detect the expression levels of NL-RP3/Gasdermin D/Caspase-1/Interleukin-1β pyrop-tosis pathway-related proteins.RESULTS:Com-pared with Con group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in AA group were signifi-cantly increased(P<0.05).Compared with AA group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NL-RP3,GSDMD,Caspase-1 and IL-1β protein expres-sion levels were significantly decreased in SIN treat-ment group with the increase of treatment dose(P<0.05).Compared with AA group and L-SIN group,the degree of joint swelling,arthritis index,inflam-matory factors and oxidative stress levels,NLRP3,GSDMD,Caspase-1 and IL-1β protein expression levels in ACG group were significantly decreased(P<0.05).Compared with H-SIN group,the degree of joint swelling,arthritis index,inflammatory factors and oxidative stress levels,NLRP3,GSDMD,Cas-pase-1 and IL-1β protein expression levels in ACG group were significantly increased(P<0.05).CON-CLUSION:SIN can alleviate the inflammatory injury of AA rats and reduce the levels of inflammatory factors and oxidative stress,thus exerting a protec-tive effect on AA rats.The mechanism may be based on the NLRP3/Gasdermin D/Caspase-1/Inter-leukin-1β pyroptosis pathway.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Based on high-resolution magnetic resonance tube wall imaging,reverse medical engineering modeling techniques are used to obtain individualized intracranial artery models of high prevalence in ischemic stroke.Three types of intracranial artery models,including Newtonian fluid model,non-Newtonian fluid model and non-Newtonian fluid with two-phase flow model,are established for transient numerical simulations using computational fluid dynamics method.The hemodynamic parameters such as blood flow field,wall shear stress distribution and erythrocyte volume distribution are analyzed to investigate the possible mechanisms involved in the formation and progression of intracranial atherosclerosis.It is found that blood flow velocity increased significantly at the end of the internal carotid artery and the middle cerebral artery.Low-speed vortex flow and disturbed flow appear in the local vessels.The difference in blood flow velocity between the center and the edge of the wall is large,with an obvious low-flow velocity area on the outer side.A clear central core area is formed in the stenotic wall under the action of high-speed blood flow,resulting in thinner edge layer and lower erythrocyte volume fraction.The combination of low erythrocyte distribution in the edge layer and low flow velocity on the outer side of the wall exacerbates endothelial cell necrosis,hypoxia,endothelial dysfunction,and leads to atherosclerosis.Compared with Newtonian and non-Newtonian fluid models,non-Newtonian fluid with two-phase flow model has greater variability for hemodynamic parameters and shows higher fidelity in simulating blood flow,which provides a reference for clinical diagnosis and treatment of cerebrovascular diseases.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.