Objective:To investigate the effects of Sishen pill on the expression of type I interferon(IFN)and type III interferon and their receptors in colonic tissues of mice with acute ulcerative colitis(UC).Methods:Male C57B...Objective:To investigate the effects of Sishen pill on the expression of type I interferon(IFN)and type III interferon and their receptors in colonic tissues of mice with acute ulcerative colitis(UC).Methods:Male C57BL/6Cnc mice were randomly divided into control group,model group,sishenwan group and salazosulfapyridine group.The model was made with 0.2 mL 4%dextran sodium sulfate(DSS)for 5 days,and the control group was given 0.2mL normal saline by gavage.On the second day of modeling,sishen pill group was given 0.2mL 1.5 g·kg^(-1) sishen pill,and SASP group was given 0.2mL 0.25 g·kg^(-1) sulfasalazine,twice a day,for 7 days.During the administration period,the disease activity index(DAI)of mice was calculated every day.After administration,the histopathological changes of colon tissues of mice in each group were observed by hematoxylin eosin(HE)staining,and the histological scores were calculated.The expression of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 mRNAs in colon tissues of mice in each group were detected by qRT-PCR.The expression levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 in colon tissues of mice in each group were detected by ELISA.Western blot was used to detect the expression of interferon receptors IFNAR1,IFNAR2 and IFNLR1 in colon tissues of mice in each group.Results:Compared with the control group,the DAI of mice increased significantly(P<0.001)in the model group.The inflammatory cells in colonic tissues infiltrated heavily,lymph nodes enlarged,colonic mucosal structure destroyed,crypt structure lost,inflammation involved a wide range,and the histological score increased significantly(P<0.001).The levels of IFN-α,IFN-βand IFNλ2 mRNA were significantly decreased(P<0.05,P<0.05,P<0.01).The expression levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 were significantly decreased(P<0.01,P<0.01,P<0.001,P<0.001).The levels of IFNAR1,IFNAR2 and IFNLR1 were significantly decreased(P<0.01,P<0.05,P<0.01).Compared with the model group,the DAI decreased significantly(P<0.001)in Sishen pill group,the infiltration of inflammatory cells in colon tissue were significantly reduced,the structural regeneration of colon mucosa was significantly recovered,the crypt structure was significantly recovered,the lymph nodes were significantly reduced,the range of inflammation involvement was reduced,and the histological score was significantly reduced(P<0.001).The levels of IFN-α,IFN-βand IFN-λ2 mRNA were significantly increased(P<0.01,P<0.001,P<0.001).The levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 were significantly increased(P<0.01,P<0.001,P<0.01,P<0.001).The levels of IFNAR1,IFNAR2 and IFNLR1 were significantly increased(P<0.05,P<0.001,P<0.05).Conclusion:Sishen pill may alleviate the symptoms and signs of mice with acute ulcerative colitis by regulating the expression of type I and type III interferon and their receptors in colon tissues.展开更多
BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still...BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
目的探讨成人骨型Ⅲ类患者矫治前后上下前牙区牙槽高度和宽度变化以及前牙区牙根位置变化。方法选取2020年5月—2022年11月在中山市小榄人民医院口腔科正畸掩饰治疗的成人骨型Ⅲ类患者50例,比较正畸治疗前后患者上下颌前牙牙槽骨厚度和...目的探讨成人骨型Ⅲ类患者矫治前后上下前牙区牙槽高度和宽度变化以及前牙区牙根位置变化。方法选取2020年5月—2022年11月在中山市小榄人民医院口腔科正畸掩饰治疗的成人骨型Ⅲ类患者50例,比较正畸治疗前后患者上下颌前牙牙槽骨厚度和高度,其中包括上前牙槽骨厚度(upper anterior alveolar bonethickness,UA)、上后牙槽骨厚度(upper posterior alveolar bone thickness,UP)、上牙槽骨总厚度(upper alveolar bone width,UW)、下前牙槽骨厚度(lower anterior alveolar bone thickness,LA)、下后牙槽骨厚度(lower posterior alveolar bone thickness,LP)、下牙槽骨总厚度(lower alveolar bone width,LW)、根中水平上前牙槽骨厚度(upper anterior alveolar bone thickness at the mid-root level,UA-m)、根中水平上后牙槽骨厚度(upper posterior alveolar bone thickness at the mid-root level,UP-m)、根中水平上牙槽骨总厚度(upper alveolar bone thickness at the mid-root level,UW-m)、根中水平下前牙槽骨厚度(lower anterior alveolar bone thickness at the mid-root level,LA-m)、根中水平下后牙槽骨厚度(lower posterior alveolar bone thickness at the mid-root level,LP-m)、根中水平下牙槽骨总厚度(lower alveolar bone thickness at the mid-root level,LW-m)以及上前牙槽骨高度(upper anterior alveolar bone height,UAH)和下前牙槽骨高度(lower anterior alveolarbone height,LAH)。结果正畸治疗前后患者UA、UP-m测量值比较,差异无统计学意义(P>0.05)。与正畸治疗前比较,正畸治疗后患者UP、UW、UA-m、UW-m测量值均显著降低(P<0.05)。正畸治疗后患者LP、LA-m测量值与正畸治疗前比较,差异无统计学意义(P>0.05)。与正畸治疗前比较,正畸治疗后患者LA、LW、LP-m、LW-m测量值均降低(P<0.05)。与正畸治疗前比较,正畸治疗后患者UAH、LAH测量值均显著降低(P<0.05)。正畸治疗后,患者上下颌前牙解剖牙根长度分别为(10.62±0.57)mm、(9.65±0.48)mm,正畸治疗前患者上下颌前牙解剖牙根长度分别为(11.01±0.58)mm、(10.37±0.48)mm,与正畸治疗前比较,患者上下颌前牙解剖牙根长度明显减小(P<0.05)。结论成人骨型Ⅲ类患者进行正畸掩饰治疗后,牙槽形态会发生相应改变,患者上下前牙牙槽骨厚度和高度会一定程度地减少。因此,在矫治过程中应当对患者牙槽形态的变化给予密切关注,尽量避免上下前牙发生代偿性移动,从而降低不良反应情况发生的风险。展开更多
目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方...目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。展开更多
AIM: To review the prevalence,clinical data and course of interferon-associated type 1 diabetes in chronic hepatitis C virus(HCV) infection.METHODS: Search of all interferon(INF)-related type 1diabetes mellitus(T1DM) ...AIM: To review the prevalence,clinical data and course of interferon-associated type 1 diabetes in chronic hepatitis C virus(HCV) infection.METHODS: Search of all interferon(INF)-related type 1diabetes mellitus(T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection,diabetes mellitus type 1,insulin dependent diabetes mellitus,and interferon treatment.We found 107 cases and analyzed their clinical and laboratory data and long-term followup.Due to the predominance of cases described in Japanese literature,we analyzed separately cases of Caucasian and Japanese origin.In addition we describe a representative case with HCV who developed INFrelated T1 DM.RESULTS: Our data show that INF treatment increases the risk of developing T1 DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years(range: 24-66 years) in Caucasians and 52 years(range: 45-63 years) in Japanese.Most patients developed T1 DM during INF treatment,after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups,respectively.The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis,a high titer of anti-islet autoantibodies and almost all patients(105/107) permanently required insulin therapy with a follow-up of up to 4 years.A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases(25% and 31% in Caucasian and Japanese groups,respectively).CONCLUSION: INF-associated T1 DM in HCV has a fulminant course,often associated with other autoimmune diseases,and results almost inevitably in permanent insulin therapy requirement.展开更多
OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, C...OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.展开更多
Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, w...Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.展开更多
Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading ...Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN productionwere largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infectionsby recognizing various viral components. Furthermore, much progress has been made in defining the signaling path-ways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally importantin inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellularviral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also inducethe up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type IIFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. Thisreview will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.展开更多
Dendritic cells （DC）, although a minor population in hematopoietic cells, produce type I interferons （IFN） and other cytokines and are essential for innate immunity. They are also potent antigen presenters and reg...Dendritic cells （DC）, although a minor population in hematopoietic cells, produce type I interferons （IFN） and other cytokines and are essential for innate immunity. They are also potent antigen presenters and regulate adaptive immunity. Among DC subtypes plasmacytoid DC （pDC） produce the highest amounts of type I IFN. In addition, pro- and anti-inflammatory cytokines such as IL-12 and IL-10 are induced in DC in response to Toll like receptor （TLR） signaling and upon viral infection. Proteins in the IRF family control many aspects of DC activity. IRF-8 and IRF-4 are essential for DC development. They differentially control the development of four DC subsets. IRF-8^-/- mice are largely devoid of pDC and CD8α^＋ DC, while IRF-4^-/- mice lack CD4^＋ DC. IRF-8^-/-, IRF4^-/-, double knock-out mice have only few CD8α CD4^-DC that lack MHC Ⅱ. IRF proteins also control type Ⅰ IFN induction in DC. IRF-7, activated upon TLR signaling is required for IFN induction not only in pDC, but also in conventional DC （cDC） and non-DC cell types. IRF-3, although contributes to IFN induction in fibroblasts, is dispensable in IFN induction in DC. Our recent evidence reveals that type Ⅰ IFN induction in DC is critically dependent on IRF-8, which acts in the feedback phase of IFN gene induction in DC. Type Ⅰ IFN induction in pDC is mediated by MyD88 dependent signaling pathway, and differs from pathways employed in other cells, which mostly rely on TLR3 and RIG-Ⅰ family proteins. Other pro-inflammatory cytokines are produced in an IRF-5 dependent manner. However, IRF-5 is not required for IFN induction, suggesting the presence of separate mechanisms for induction of type Ⅰ IFN and other pro-inflammatory cytokines. IFN and other cytokines produced by activated DC in turn advance DC maturation and change the phenotype and function of DC. These processes are also likely to be governed by IRF family proteins.展开更多
Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological sta...AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.展开更多
基金National Natural Science Foundation of China(No.82160835)。
文摘Objective:To investigate the effects of Sishen pill on the expression of type I interferon(IFN)and type III interferon and their receptors in colonic tissues of mice with acute ulcerative colitis(UC).Methods:Male C57BL/6Cnc mice were randomly divided into control group,model group,sishenwan group and salazosulfapyridine group.The model was made with 0.2 mL 4%dextran sodium sulfate(DSS)for 5 days,and the control group was given 0.2mL normal saline by gavage.On the second day of modeling,sishen pill group was given 0.2mL 1.5 g·kg^(-1) sishen pill,and SASP group was given 0.2mL 0.25 g·kg^(-1) sulfasalazine,twice a day,for 7 days.During the administration period,the disease activity index(DAI)of mice was calculated every day.After administration,the histopathological changes of colon tissues of mice in each group were observed by hematoxylin eosin(HE)staining,and the histological scores were calculated.The expression of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 mRNAs in colon tissues of mice in each group were detected by qRT-PCR.The expression levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 in colon tissues of mice in each group were detected by ELISA.Western blot was used to detect the expression of interferon receptors IFNAR1,IFNAR2 and IFNLR1 in colon tissues of mice in each group.Results:Compared with the control group,the DAI of mice increased significantly(P<0.001)in the model group.The inflammatory cells in colonic tissues infiltrated heavily,lymph nodes enlarged,colonic mucosal structure destroyed,crypt structure lost,inflammation involved a wide range,and the histological score increased significantly(P<0.001).The levels of IFN-α,IFN-βand IFNλ2 mRNA were significantly decreased(P<0.05,P<0.05,P<0.01).The expression levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 were significantly decreased(P<0.01,P<0.01,P<0.001,P<0.001).The levels of IFNAR1,IFNAR2 and IFNLR1 were significantly decreased(P<0.01,P<0.05,P<0.01).Compared with the model group,the DAI decreased significantly(P<0.001)in Sishen pill group,the infiltration of inflammatory cells in colon tissue were significantly reduced,the structural regeneration of colon mucosa was significantly recovered,the crypt structure was significantly recovered,the lymph nodes were significantly reduced,the range of inflammation involvement was reduced,and the histological score was significantly reduced(P<0.001).The levels of IFN-α,IFN-βand IFN-λ2 mRNA were significantly increased(P<0.01,P<0.001,P<0.001).The levels of IFN-α,IFN-β,IFN-λ2 and IFN-λ3 were significantly increased(P<0.01,P<0.001,P<0.01,P<0.001).The levels of IFNAR1,IFNAR2 and IFNLR1 were significantly increased(P<0.05,P<0.001,P<0.05).Conclusion:Sishen pill may alleviate the symptoms and signs of mice with acute ulcerative colitis by regulating the expression of type I and type III interferon and their receptors in colon tissues.
基金Supported by the Health Research Program of Anhui,No.AHWJ2022b032 and No.AHWJ2023A30034.
文摘BACKGROUND In recent years,pure laparoscopic radical surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma(HCCA)has been preliminarily explored and applied,but the surgical strategy and safety are still worthy of further improvement and attention.AIM To summarize and share the application experience of the emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types Ⅲ and IV.METHODS The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed.RESULTS Among the 6 patients,4 were males and 2 were females.The average age was 62.2±11.0 years,and the median body mass index was 20.7(19.2-24.1)kg/m^(2).The preoperative median total bilirubin was 57.7(16.0-155.7)μmol/L.One patient had Bismuth-Corlette type Ⅲa,4 patients had Bismuth-Corlette type Ⅲb,and 1 patient had Bismuth-Corlette type Ⅳ.All patients successfully underwent pure laparoscopic radical resection following the strategy of“hepatic hilum area dissection priority,liver posterior separation first”.The operation time was 358.3±85.0 minutes,and the intraoperative blood loss volume was 195.0±108.4 mL.None of the patients received blood transfusions during the perioperative period.The median length of stay was 8.3(7.0-10.0)days.Mild bile leakage occurred in 2 patients,and all patients were discharged without serious surgery-related complications.CONCLUSION The emerging strategy of“hepatic hilum area dissection priority,liver posterior separation first”is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types Ⅲ and Ⅳ.This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA,shortens the learning curve,and is worthy of further clinical application.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
文摘目的探讨成人骨型Ⅲ类患者矫治前后上下前牙区牙槽高度和宽度变化以及前牙区牙根位置变化。方法选取2020年5月—2022年11月在中山市小榄人民医院口腔科正畸掩饰治疗的成人骨型Ⅲ类患者50例,比较正畸治疗前后患者上下颌前牙牙槽骨厚度和高度,其中包括上前牙槽骨厚度(upper anterior alveolar bonethickness,UA)、上后牙槽骨厚度(upper posterior alveolar bone thickness,UP)、上牙槽骨总厚度(upper alveolar bone width,UW)、下前牙槽骨厚度(lower anterior alveolar bone thickness,LA)、下后牙槽骨厚度(lower posterior alveolar bone thickness,LP)、下牙槽骨总厚度(lower alveolar bone width,LW)、根中水平上前牙槽骨厚度(upper anterior alveolar bone thickness at the mid-root level,UA-m)、根中水平上后牙槽骨厚度(upper posterior alveolar bone thickness at the mid-root level,UP-m)、根中水平上牙槽骨总厚度(upper alveolar bone thickness at the mid-root level,UW-m)、根中水平下前牙槽骨厚度(lower anterior alveolar bone thickness at the mid-root level,LA-m)、根中水平下后牙槽骨厚度(lower posterior alveolar bone thickness at the mid-root level,LP-m)、根中水平下牙槽骨总厚度(lower alveolar bone thickness at the mid-root level,LW-m)以及上前牙槽骨高度(upper anterior alveolar bone height,UAH)和下前牙槽骨高度(lower anterior alveolarbone height,LAH)。结果正畸治疗前后患者UA、UP-m测量值比较,差异无统计学意义(P>0.05)。与正畸治疗前比较,正畸治疗后患者UP、UW、UA-m、UW-m测量值均显著降低(P<0.05)。正畸治疗后患者LP、LA-m测量值与正畸治疗前比较,差异无统计学意义(P>0.05)。与正畸治疗前比较,正畸治疗后患者LA、LW、LP-m、LW-m测量值均降低(P<0.05)。与正畸治疗前比较,正畸治疗后患者UAH、LAH测量值均显著降低(P<0.05)。正畸治疗后,患者上下颌前牙解剖牙根长度分别为(10.62±0.57)mm、(9.65±0.48)mm,正畸治疗前患者上下颌前牙解剖牙根长度分别为(11.01±0.58)mm、(10.37±0.48)mm,与正畸治疗前比较,患者上下颌前牙解剖牙根长度明显减小(P<0.05)。结论成人骨型Ⅲ类患者进行正畸掩饰治疗后,牙槽形态会发生相应改变,患者上下前牙牙槽骨厚度和高度会一定程度地减少。因此,在矫治过程中应当对患者牙槽形态的变化给予密切关注,尽量避免上下前牙发生代偿性移动,从而降低不良反应情况发生的风险。
文摘目的:基于上皮细胞-间充质细胞转分化(EMT)学说观察化纤Ⅳ号方、艾灸以及二者相配合治疗肺纤维化大鼠Collagen TypeⅢ(Ⅲ-C)和PDGF的变化,探讨其治疗效应及生物学机制。方法:将鼠龄约为6周的SD大鼠随机分为空白组、模型组、化纤Ⅳ号方组、艾灸组、化纤Ⅳ号方与艾灸配合治疗组(简称为"灸药组"),治疗30 d后处死观察其肺组织病理改变,并检测其Collagen TypeⅢ、PDGF的基因和蛋白表达情况。结果:实时荧光定量结果显示:与空白组相比,各组Ⅲ-C和PDGF m RNA表达增高(P<0.05)。与模型组相比,各组的Ⅲ-C和PDGF m RNA表达有明显降低(P<0.01)。而各组中,灸药组疗效最明显,Ⅲ-C和PDGF的表达最低。蛋白免疫印迹法检测结果显示:与模型组相比各组的Ⅲ-C蛋白表达有差异。结论:1艾灸、化纤Ⅳ号方均可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度。2艾灸配合化纤Ⅳ号方可减轻博莱霉素诱导肺纤维化大鼠的肺纤维化程度,且其效果优于单用艾灸或单用化纤Ⅳ号方。3艾灸、化纤Ⅳ号方及其二者配合使用不同程度阻抑博莱霉素诱导肺纤维化大鼠肺纤维化进程的效应机制,可能与通过调控其EMT过程中的Ⅲ-C和PDGF表达环节紧密相关。
文摘AIM: To review the prevalence,clinical data and course of interferon-associated type 1 diabetes in chronic hepatitis C virus(HCV) infection.METHODS: Search of all interferon(INF)-related type 1diabetes mellitus(T1DM) cases published in the English literature from 1992 to December 2013 according to the key words: chronic hepatitis C infection,diabetes mellitus type 1,insulin dependent diabetes mellitus,and interferon treatment.We found 107 cases and analyzed their clinical and laboratory data and long-term followup.Due to the predominance of cases described in Japanese literature,we analyzed separately cases of Caucasian and Japanese origin.In addition we describe a representative case with HCV who developed INFrelated T1 DM.RESULTS: Our data show that INF treatment increases the risk of developing T1 DM by 10-18 fold compared with the corresponding general population and the median age of onset was 43 years(range: 24-66 years) in Caucasians and 52 years(range: 45-63 years) in Japanese.Most patients developed T1 DM during INF treatment,after a median time-period of 4.2 and 5.7 mo in Caucasian and Japanese groups,respectively.The clinical course was characterized by a fulminant course with abrupt severe hyperglycemia or ketoacidosis,a high titer of anti-islet autoantibodies and almost all patients(105/107) permanently required insulin therapy with a follow-up of up to 4 years.A substantial number of patients had evidence for other autoimmune disorders mainly thyroid diseases(25% and 31% in Caucasian and Japanese groups,respectively).CONCLUSION: INF-associated T1 DM in HCV has a fulminant course,often associated with other autoimmune diseases,and results almost inevitably in permanent insulin therapy requirement.
基金This study was supported by the grant from the Guangdong Provincial Science and Technology Foundation (No. A 1999--198).
文摘OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.
基金These authors contributed equally to this work. We thank Drs S Vaidya and E Chow （University of California Los Angeles, USA） for their help in setting up critical experimental systems. We greatly thank Dr K Holmes （University of Colorado Health Sciences Center, USA） for sharing with us 17C1-1 cell line and helping to optimize the protocol to produce high titered MHV-A59 virus stock. We also thank Drs R Baric and L Su （University of North Carolina, USA） for the gift of MHV-A59 and guidance of virus infection. We thank Dr K Lim （National Neuroscience Institute, Singapore） for the gift of Ubi plasmids. We thank Dr M Wathelet （University of Cincinnati College of Medicine, USA） for sharing the nsp3 construct. Also we thank Dr G Gao （Institute of Biophysics, CAS） for providing us with VSV. This research was partly supported by grants from the National Natural Science Foundation of China （30728006） to Genhong Cheng and the National Basic Research Program of MOST （2004BA519A61, 2006CB504300, 2007DFC30190） to Hong Tang.
文摘Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.
基金A. K. Perry is supported by the Howard Hughes Medi-cal Institute predoctoral fellowship (Grant No. 59003787).Part of this work was also supported by National Insti-tutes of Health research grants RO1 CA87924, RO1AI056154, and R37 AI47868 to G. Cheng and from the MajorResearch Plan (30170461, 30430640) +1 种基金Natural ScienceFoundation of China, and the National Basic ResearchProgram of MOST (2002CB513001, 2001CB-510002)H. Tang. H. Tang is also a fellow of Outstanding YoungInvestigators of National Naturual Science Foundation ofChina (30025010).
文摘Type I interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type I IFNsare produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN productionwere largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type I IFN during viral infectionsby recognizing various viral components. Furthermore, much progress has been made in defining the signaling path-ways downstream of TLRs for type I IFN production. TLR7 and TLR9 have become apparent as universally importantin inducing type I IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellularviral pattern recognition receptors leading to type I IFN production have been identified. Many bacteria can also inducethe up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type IIFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. Thisreview will discuss the recent advances made in defining the signaling pathways leading to type I IFN production.
文摘Dendritic cells （DC）, although a minor population in hematopoietic cells, produce type I interferons （IFN） and other cytokines and are essential for innate immunity. They are also potent antigen presenters and regulate adaptive immunity. Among DC subtypes plasmacytoid DC （pDC） produce the highest amounts of type I IFN. In addition, pro- and anti-inflammatory cytokines such as IL-12 and IL-10 are induced in DC in response to Toll like receptor （TLR） signaling and upon viral infection. Proteins in the IRF family control many aspects of DC activity. IRF-8 and IRF-4 are essential for DC development. They differentially control the development of four DC subsets. IRF-8^-/- mice are largely devoid of pDC and CD8α^＋ DC, while IRF-4^-/- mice lack CD4^＋ DC. IRF-8^-/-, IRF4^-/-, double knock-out mice have only few CD8α CD4^-DC that lack MHC Ⅱ. IRF proteins also control type Ⅰ IFN induction in DC. IRF-7, activated upon TLR signaling is required for IFN induction not only in pDC, but also in conventional DC （cDC） and non-DC cell types. IRF-3, although contributes to IFN induction in fibroblasts, is dispensable in IFN induction in DC. Our recent evidence reveals that type Ⅰ IFN induction in DC is critically dependent on IRF-8, which acts in the feedback phase of IFN gene induction in DC. Type Ⅰ IFN induction in pDC is mediated by MyD88 dependent signaling pathway, and differs from pathways employed in other cells, which mostly rely on TLR3 and RIG-Ⅰ family proteins. Other pro-inflammatory cytokines are produced in an IRF-5 dependent manner. However, IRF-5 is not required for IFN induction, suggesting the presence of separate mechanisms for induction of type Ⅰ IFN and other pro-inflammatory cytokines. IFN and other cytokines produced by activated DC in turn advance DC maturation and change the phenotype and function of DC. These processes are also likely to be governed by IRF family proteins.
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
文摘AIM To evaluate whether a high risk macroscopic appearance(Type Ⅳ and giant Type Ⅲ) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage Ⅱ/Ⅲ(p Stage Ⅱ/Ⅲ) gastric cancer.METHODS One hundred and seventy-two advanced gastric cancer(defined as pT2 or beyond) patients with p Stage Ⅱ/Ⅲ who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival(RFS)(35.7%) and overall survival(OS)(34%) than an average risk appearance(P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13^(th) Japanese Gastric Cancer Association(JGCA) pT(P = 0.01), but not with the 13^(th) JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13^(th) JGCA p Stage(P < 0.0001)and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified highrisk macroscopic appearance(P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13^(th) JGCA stage in p Stage Ⅱ/Ⅲ advanced gastric cancer.
