OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral(Dem)in ulcerative colitis(UC)and collagen-induced arthritis(CIA),focusing on its regulation of Th17 cell differentiation and associated signaling pathways.METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium(DSS),and Dem was administered by gavage at low(1 mg·kg-1)or high(2 mg·kg-1)doses.Disease severity was assessed by body weight loss,colon length,and stool consisten-cy.Serum cytokines(TNF-α,IL-1β,IL-6)were quantified by ELISA,and Th17 cell ratio in mesenteric lymph nodes was deter-mined by flow cytometry.The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model.The efficacy of Dem was further verified in the CIA model,and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.RESULTS Dem-treated mice showed reduced weight loss and colon shortening,and decreases in ser-um TNF-α,IL-1β,and IL-6 levels(P<0.01)and Th17 cell proportion(P<0.01).Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 path-way.Dem also significantly alleviated arthritis symptoms and related markers in the CIA model,confirming its anti-inflammatory effects.CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway,inhibi-ting Th17 cell differentiation and pro-inflammatory cytokine expression,suggesting its potential therapeutic value in immune-related diseases.

Background::Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.Methods::A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.Discussion::This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.Trial Registration::Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.

Background::Statins are the first line of treatment for dyslipidemia, but their side effects often reduce medication compliance. Natto and red yeast rice are natural ingredients with lipid-lowering effects. However, the efficacy of Natto Red Yeast Rice (NRYR) supplement in combination with statins in regulating blood lipid levels has not been fully evaluated.Methods::A multicenter, double-blinded, randomized-controlled trial was conducted among individuals with low-density lipoprotein cholesterol (LDL-C) of 3.4 to 5.0 mmol/L at six sites in China, of those at moderate risk of cardiovascular disease (CVD) are prioritized. Participants are enrolled and randomly assigned into four groups by a combination of NRYR (or its placebo) and Simvastatin (or its placebo) in a ratio of 1:1:1:1. After examination at baseline, all participants underwent intervention for 3 months and two follow-up visits at 1 month and 3 months after the intervention. The primary outcome is the change in LDL-C level at 3 months, and secondary outcomes include changes in levels of other lipid profiles and biomarkers, as well as calculated 10-year CVD risk. A total of 1136 participants were randomly assigned, of whom 1110 received the intervention.Discussion::This study may provide new evidence for the efficacy of NRYR supplement in combination with statins to regulate lipid levels and optimize lipid management.Trial Registration::Chinese Clinical Trial Registry database: registration nos. ChiCTR2200064214, ChiCTR2200064215.

Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P＜0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P＜0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.

OBJECTIVE To investigate the anti-inflammatory mechanisms of demethylzeylasteral(Dem)in ulcerative colitis(UC)and collagen-induced arthritis(CIA),focusing on its regulation of Th17 cell differentiation and associated signaling pathways.METHODS UC was induced in C57BL/6 mice using dextran sulfate sodium(DSS),and Dem was administered by gavage at low(1 mg·kg-1)or high(2 mg·kg-1)doses.Disease severity was assessed by body weight loss,colon length,and stool consisten-cy.Serum cytokines(TNF-α,IL-1β,IL-6)were quantified by ELISA,and Th17 cell ratio in mesenteric lymph nodes was deter-mined by flow cytometry.The anti-inflammatory efficacy of Dem was further validated using a CIA mouse model.The efficacy of Dem was further verified in the CIA model,and the expression of JAK2 and STAT3 was intervened by siRNA to investigate its mechanism of action in Th17 differentiation.RESULTS Dem-treated mice showed reduced weight loss and colon shortening,and decreases in ser-um TNF-α,IL-1β,and IL-6 levels(P<0.01)and Th17 cell proportion(P<0.01).Western blot and siRNA assays showed that Dem significantly inhibited the differentiation and activation of Th17 cells by suppressing the phosphorylation of the JAK2-STAT3 path-way.Dem also significantly alleviated arthritis symptoms and related markers in the CIA model,confirming its anti-inflammatory effects.CONCLUSION Dem improves UC and rheumatoid arthritis by downregulating the JAK2-STAT3 signaling pathway,inhibi-ting Th17 cell differentiation and pro-inflammatory cytokine expression,suggesting its potential therapeutic value in immune-related diseases.

Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P＜0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P＜0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.

Objective In recent decades,China has implemented a series of policies to address air pollution.We aimed to assess the health effects of these policies on stroke burden attributable to ambient fine particulate matter(PM2.5). Methods Joinpoint regression was applied to explore the temporal tendency of stroke burden based on data from the Global Burden of Disease 2019 study. Results The age-standardized rates of disability-adjusted life year(DALY)for stroke attributable to ambient PM2.5 in China,increased dramatically during 1990-2012,subsequently decreased at an annual percentage change(APC)of-1.98[95%confidence interval(CI):-2.26,-1.71]during 2012-2019.For ischemic stroke(IS),the age-standardized DALY rates doubled from 1990 to 2014,and decreased at an APC of-0.83(95%CI:-1.33,-0.33)during 2014-2019.Intracerebral hemorrhage(ICH)showed a substantial increase in age-standardized DALY rates from 1990 to 2003,followed by declining trends,with APCs of-1.46(95%CI:-2.74,-0.16)during 2003-2007 and-3.33(95%CI:-3.61,-3.06)during 2011-2019,respectively.Conversely,the age-standardized DALY rates for subarachnoid hemorrhage(SAH)generally declined during 1990-2019. Conclusion Our results clarified the dynamic changes of the ambient PM2.5-attributable stroke burden in China during 1990-2019,highlighting the health effects of air quality improvement policies.

Objective To investigate the imaging features of papillary tumor of the pineal region(PTPR).Methods The ima-ging data of 10 patients with PTPR confirmed by operation and pathology were analyzed retrospectively.Results All lesions were located in the posterior commissure area of the posterior inferior wall of the third ventricle.All lesions were heterogeneously hyper-intensity on T1WI and hyperintensity on T2WI.Multiple small cysts or microcapsules signal intensity were observed within the tumor.Of all 10 lesions,there were 9 lesions with high signal intensity within or at the edge of the lesion on T1WI.All lesions showed restricted diffusion.All 10 cases showed uneven and obvious enhancement patterns.Midbrain tectum was compressed and moved backward in 5 cases,moved downward in 2 cases,moved forward and downward in 1 case,and was not clearly displayed in other 2 cases.One case was disseminated and 1 case was hyperperfusion.There were all 10 cases with obstructive hydrocephalus and equal or slightly high density on CT imaging,and 4 cases with calcification.Conclusion Imaging characteristics of PTPR included the lesions centered on the posterior commissure,compressed tectum with backward and downward,multiple small cysts or micro-capsules components within the tumor,hyperintensity on T1WI,and uneven and obvious enhancement patterns.

Objective To establish a method for qualitative detection of the presence or absence of all KIR genes by quantitative polymerase chain reaction(Q-PCR).Methods Based on the polymorphism of high-resolution level KIR alleles in Chinese population and the IPD-KIR database,KIR gene-specific primers were designed to amplify all the 16 KIR genes and 2DS4-Normal and 2DS4-Deleted subtypes by Q-PCR.Meanwhile,one negative control and one positive control specific amplifying human growth hormone(HGH)gene fragment were set to monitor the false positive and false negative results in PCR amplification,respectively.A total of 302 samples with known KIR genotype previously identified by KIR PCR-SSP commercial kit were randomly selected for blind inspection to verify the reliability of KIR Q-PCR method established by au-thors.Results The results of 300 samples detected by our KIR Q-PCR method were consistent with the known results,but two samples showed inconsistent results.One sample was negative for 2DS5 by Q-PCR but positive by PCR-SSP,another sample was positive for 2DS1 by Q-PCR but negative by PCR-SSP.The two doubtful samples were genotyped by sequencing-based typing(PCR-SBT)for 2DS5and2DS1,respectively.PCR-SBT results confirmed that the results of Q-PCR test was correct.Conclusion The KIR Q-PCR method established in this paper can provide accurate and reliable results for testing the presence or absence of KIR genes.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.