Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.

PI3K/Akt, Wnt/β-catenin, TGF-β, Nrf2 and Notch signaling pathways are mainly involved in the TCM treatment of chronic refractory wounds (CRW). Chinese materia medica monomers and compound preparations can inhibit protein kinases related to signaling pathways in wound tissue and promote wound healing; reduce the expression of inflammatory factors and inhibit the occurrence of inflammatory response; promote the proliferation and differentiation of growth factors and epidermal stem cells, accelerate the regeneration of granulation tissue, and play a role in repairing wound regeneration.

Objective To explore the value of cranial CT perfusion imaging(CTP)parameters combined with head and neck CT angiography(CTA)in assessing collateral circulation status and predicting prognosis in acute ischemic stroke(AIS).Methods A retrospective analysis was carried out on 83 AIS patients who were treated in Taikang Xianlin Drum Tower Hospital from June 2018 to June 2023.CTP and head and neck CTA examinations were performed within 24 hours after admission.Digital subtraction angiography is the gold standard for assessing collateral circulation status in AIS patients.The general information of these patients was collected,and the patient's prognosis was evaluated using the modified Rankin scale through telephone or outpatient follow-up 90 days after the occurrence of AIS.Pearson or Spearman correlation was used to analyze the correlation between collateral circulation assessment and CTP parameters and head and neck CTA scores.The value of CTP parameters and head and neck CTA scores in predicting the prognosis of AIS patients was discussed using multivariate Logistic regression.Moreover,the receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTP parameters,head and neck CTA,and the combination for the prognosis of AIS patients.Results The cerebral blood volume(CBV),cerebral blood flow(CBF),and CTA score were higher,while mean transit time(MTT)and time to peak(TTP)were shorter in the good collateral circulation group than in poor collateral circulation group(P<0.05).The collateral circulation status in AIS patients was negatively correlated with CBV,CBF,and CTA score,while positively correlated with MTT and TTP(P<0.05).Compared with poor prognosis group,good prognosis group had higher CBV,CBF,CTA,and shorter MTT and TTP(P<0.05).Multivariate Logistic regression analysis identified MTT and TTP as risk factors for poor prognosis,and CBV,CBF,and CTA scores as protective factors for poor prognosis in AIS patients(P<0.05).The ROC results showed that the area under the curve(AUC)of CBV,MTT,CBF,TTP,CTA score and the combination to predict the prognosis of AIS patients were 0.897,0.864,0.835,0.920,0.918,and 0.979,respectively,showing better predictive performance of the combination than single index alone(Z=2.194,2.910,2.521,2.229,2.171;P<0.05).Conclusion CTP parameters combined with CTA may effectively assess collateral circulation in patients with AIS and is significant for prognosis prediction.

Objective To explore the value of cranial CT perfusion imaging(CTP)parameters combined with head and neck CT angiography(CTA)in assessing collateral circulation status and predicting prognosis in acute ischemic stroke(AIS).Methods A retrospective analysis was carried out on 83 AIS patients who were treated in Taikang Xianlin Drum Tower Hospital from June 2018 to June 2023.CTP and head and neck CTA examinations were performed within 24 hours after admission.Digital subtraction angiography is the gold standard for assessing collateral circulation status in AIS patients.The general information of these patients was collected,and the patient's prognosis was evaluated using the modified Rankin scale through telephone or outpatient follow-up 90 days after the occurrence of AIS.Pearson or Spearman correlation was used to analyze the correlation between collateral circulation assessment and CTP parameters and head and neck CTA scores.The value of CTP parameters and head and neck CTA scores in predicting the prognosis of AIS patients was discussed using multivariate Logistic regression.Moreover,the receiver operating characteristic(ROC)curve was used to analyze the predictive value of CTP parameters,head and neck CTA,and the combination for the prognosis of AIS patients.Results The cerebral blood volume(CBV),cerebral blood flow(CBF),and CTA score were higher,while mean transit time(MTT)and time to peak(TTP)were shorter in the good collateral circulation group than in poor collateral circulation group(P<0.05).The collateral circulation status in AIS patients was negatively correlated with CBV,CBF,and CTA score,while positively correlated with MTT and TTP(P<0.05).Compared with poor prognosis group,good prognosis group had higher CBV,CBF,CTA,and shorter MTT and TTP(P<0.05).Multivariate Logistic regression analysis identified MTT and TTP as risk factors for poor prognosis,and CBV,CBF,and CTA scores as protective factors for poor prognosis in AIS patients(P<0.05).The ROC results showed that the area under the curve(AUC)of CBV,MTT,CBF,TTP,CTA score and the combination to predict the prognosis of AIS patients were 0.897,0.864,0.835,0.920,0.918,and 0.979,respectively,showing better predictive performance of the combination than single index alone(Z=2.194,2.910,2.521,2.229,2.171;P<0.05).Conclusion CTP parameters combined with CTA may effectively assess collateral circulation in patients with AIS and is significant for prognosis prediction.

Objective:To investigate the anti-inflammatory action and mechanism of action of rosmarinic acid(RA),a Chi-nese monomeric herbal compound based on the NF-κB/NLRP3 pathway in a rat model of acute gouty arthritis(AGA).Methods:Forty healthy male SD rats were randomly assigned to five groups,and the model and drug administration groups were established a rat model of AGA by injecting a suspension of sodium urate crystals(MSU)into the joint cavity of the right paw of the rats.The degree of ankle joint swelling was measured using vernier calipers and stained with hematoxylin-eosin(HE).The inflammatory infiltration of the ankle joint and chondrocyte shedding was observed by staining with Safranine O-fast green(SOFG)and Mankin's score.The levels of IL-6,IL-1β and TNF-α in the right ankle joint of rats were determined by ELISA and the expression of NF-κB/NLRP3 pathway-associated proteins in the ankle joint were measured by Western blot.Results:Injection of MSU suspension into the ankle successfully induced AGA in rats.Compared with control group,the rats in model group showed significantly increased ankle swelling(P<0.01),greater in-flammatory infiltration,significant chondrocyte detachment,significantly increased secretion of IL-1β,IL-6 and TNF-α(P<0.01)and increased expressions of NF-κB/NLRP3 pathway-related proteins.Compared with model group,RA showed greater anti-inflamma-tory effects,dose-dependently inhibiting the development of ankle swelling in rats(P<0.01,P<0.001)and inhibited inflammatory cy-tokine infiltration.RA inhibited the secretion of inflammatory cytokines IL-6,IL-1β,TNF-α(P<0.01)and inhibited the expressions of proteins associated with the NF-κB/NLRP3 pathway(P<0.01).Conclusion:RA shows potent anti-inflammatory effects in a mouse model of AGA,and the mechanism is associated with regulation of the NF-κB/NLRP3 pathway.

Objective:To explore the alterations in functional connectivity density (FCD) resulted from mild cognitive impairment (MCI) and their correlations with cognitive scores in various cognitive domains in patients with Parkinson's disease (PD).Methods:Forty-three PD patients admitted to Department of Neurology, Sixth Affiliated Hospital of Nantong University from January 2022 to April 2024 were selected and divided into PD-MCI group (MoCA scores<26) and PD with normal cognition (PD-NC) group (MoCA scores≥26) according to Montreal Cognitive Assessment (MoCA). Another 23 middle-aged and elderly healthy volunteers (HC group) matched with PD patients in age, gender and education level were recruited at the same period. Resting-state functional MRI (rs-fMRI) data were collected and whole brain FCD was calculated. Differences of clinical data, whole brain FCD, and FCD in brain regions with significantly different FCD among the 3 groups were compared. Efficiency of FCD in brain regions with significantly different FCD between PD-MCI group and PD-NC group in differentially diagnosing PD-MCI and PD-NC was analyzed by receiver operating characteristic (ROC) curve. Pearson correlation was used to the analyze the correlations of FCD in brain regions with significantly different FCD with MoCA score and cognitive scores in various cognitive domains.Results:Among the 43 patients, 23 were into the PD-MCI group and 20 into the PD-NC group. PD-MCI group had significantly lower scores in the visuospatial and executive function, abstraction, and delayed memory cognitive domains than PD-NC group ( P<0.05). Brain regions with significantly different FCD among the 3 groups were the right parahippocampal gyrus, left gyrus rectus, right rolandic operculum, left middle occipital gyrus, right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. Compared with the HC group, the PD-MCI group and PD-NC group had significantly increased FCD at the right parahippocampal gyrus, left gyrus rectus and right rolandic operculum, statistically decreased FCD at the right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus ( P<0.05). Compared with the HC group, the PD-MCI group had significantly increased FCD at the left middle occipital gyrus ( P<0.05). Compared with the PD-NC group, the PD-MCI group had significantly decreased FCD at the right parahippocampal gyrus, and statistically increased FCD at the left middle occipital gyrus and left middle frontal gyrus ( P<0.05). Area under ROC curve (AUC) of FCD in brain regions with significantly different FCD in discriminating PD-MCI and PD-NC was 0.878, with sensitivity of 90.0% and specificity of 91.3%. FCD at right parahippocampal gyrus, left middle occipital gyrus and left middle frontal gyrus was negatively correlated with MoCA score ( P<0.05); FCD at right parahippocampal gyrus was positively correlated with cognitive scores in the visuospatial and executive function, and delayed memory domains ( P<0.05); FCD at left middle occipital gyrus was negatively correlated with cognitive scores in the executive function and visual-spatial skills, and abstraction domains ( P<0.05); FCD at the left medial frontal gyrus was negatively correlated with cognitive scores in the visuospatial and executive function, abstraction and delayed memory domains ( P<0.05). Conclusions:Abnormal FCD can be noted in some brain regions of PD patients, enjoying differences between PD-MCI patients and PD-NC patients. Combined FCD in brain regions with significantly different FCD has high value in differentially diagnosing PD-MCI and PD-NC, and FCD in brain regions with significantly different FCD is correlated with cognitive function changes in PD patients.

Objective:To investigate the correlation between pulmonary ultrasound on pulmonary consolidation and T lymphocytes,cytokines in predicting the progression of neonatal pneumonia.Methods:A total of 80 pediatric patients with pulmonary consolidation,who admitted to neonatal ward of Beijing Chao-yang Hospital and were confirmed by the first ultrasound examination on lung from February 2021 to February 2023,were divided into study group,and 50 children,who underwent physical examination during the same period,were divided into control group.The cell subsets and cytokines between two groups were compared.The study group was further divided into mitigation group and progression group according to the disease conditions of pediatric patients of study group after they received 3 d treatment.Multifactor logistic regression was adopted to analyze the correlation among the T lymphocytes,cytokines and the progression of disease.Results:The CD3+,CD8+,CD4+/CD8+cell subsets of T lymphocytes and cytokines such as IL-17-A,TNF-α and ICAM-1 of study group were significantly higher than those of control group(t=16.483,4.933,4.113,22.933,22.433,19.525,P<0.05),respectively,and the CD4+level was significantly lower than that of control group(t=7.773,P<0.05).The CD3+cell subsets and cytokine levels such as IL-17A,TNF-α and ICAM-1 of progression group were significantly higher than those of mitigation group(t=6.815,4.631,4.307,P<0.05),however the CD4+level was significantly lower than that of mitigation group(t=3.044,P<0.05).The results of the multivariate Logistic regression analysis showed that the decrease of CD3+expression,the increase of IL-17A expression and the increase of the area of pulmonary consolidation were the risk factors of the progress of neonatal pneumonia(β=-0.176,0.777,0.931,P<0.05),respectively.The results of the Pearson-correlation analysis showed that CD3+was negative correlation with the progression of neonatal pneumonia(r=-0.295,P<0.001),however,the IL-17A and the area of pulmonary consolidation showed a positive correlation with the progression of neonatal pneumonia(r=0.677,0.517,P<0.001).Conclusion:The CD3+expression,IL-17A of peripheral blood and the area of pulmonary consolidation are significantly predictive factors of pneumonia progression,and are closely related to the progression of pneumonia.

In the development of chemo-immunotherapy, many efforts have been focusing on designing suitable carriers to realize the co-delivery of chemotherapeutic and immunotherapeutic with different physicochemical properties and mechanisms of action. Besides, rapid drug release at the tumor site with minimal drug degradation is also essential to facilitate the antitumor effect in a short time. Here, we reported a cancer cell membrane-coated pH-responsive nanogel (NG@M) to co-deliver chemotherapeutic paclitaxel (PTX) and immunotherapeutic agent interleukin-2 (IL-2) under mild conditions for combinational treatment of triple-negative breast cancer. In the designed nanogels, the synthetic copolymer PDEA-co-HP-β-cyclodextrin-co-Pluronic F127 and charge reversible polymer dimethylmaleic anhydride-modified polyethyleneimine endowed nanogels with excellent drug-loading capacity and rapid responsive drug-releasing behavior under acidic tumor microenvironment. Benefited from tumor homologous targeting capacity, NG@M exhibited 4.59-fold higher accumulation at the homologous tumor site than heterologous cancer cell membrane-coated NG. Rapidly released PTX and IL-2 enhanced the maturation of dendritic cells and quickly activated the antitumor immune response in situ, followed by prompted infiltration of immune effector cells. By the combined chemo-immunotherapy, enhanced antitumor effect and efficient pulmonary metastasis inhibition were achieved with a prolonged median survival rate (39 days).

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

Objective:To compare fibrosis-driving cells in patients with primary myelofibrosis (PMF) and patients with myelodysplastic syndromes (MDS) with myelofibrosis (MF) (MDS-MF) .Methods:Bone marrow biopsy sections of patients with newly diagnosed PMF and MDS (10 each randomly selected for MF-0/1, MF-2, and MF-3) were stained with specific immunofluorescence antibodies to label Gli1, LeptinR, alpha smooth muscle actin (α-SMA) , CD45, and ProcollagenⅠ. Images captured by confocal microscopy were analyzed by Fiji-ImageJ to calculate the cell counts of Gli1 +, LeptinR + cells, and fibrosis-driving cells including α-SMA +, α-SMA +/Gli1 +, α-SMA +/LeptinR +, and ProcollagenⅠ +/CD45 + cells. Results:Patients with PMF and MDS with MF-2/3 had higher LeptinR +, α-SMA +, α-SMA +/Gli1 +, and Procollagen Ⅰ +/CD45 + cell counts compared with those with MF-0/1 (all P values<0.05) . However, patients with PMF with MF-2/3 presented with higher Gli1 + and α-SMA +/LeptinR + cell counts than those with MF-0/1 ( P=0.001 and 0.006) , whereas these cells were similar between patients with MDS with MF-0/1 and MF-2/3 ( P=0.169 and 0.067) . In patients with MF-0/1, all fibrosis-driving cells did not differ between PMF and MDS (all P>0.05) . However, in patients with MF-2/3, Procollagen Ⅰ +/CD45 + cell counts were higher in patients with PMF compared with those with MDS ( P=0.007) , while other fibrosis-driving cell counts were similar between these two groups (all P>0.05) . MF grade and fibrosis-driving cell counts were not correlated with overall survival in patients with either PMF or MDS. Conclusion:α-SMA + cells in patients with PMF originated from both Gli1 + and LeptinR + cells, whereas α-SMA + cells in patients with MDS-MF only originated from Gli1 + cells; patients with PMF had higher ProcollagenⅠ +/CD45 + cell counts than those with MDS-MF.