“Hepatic hilum area priority,liver posterior first”:An optimized strategy in laparoscopic resection for type Ⅲ-Ⅳ hilar cholangiocarcinoma

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.

Effect of Sishen pill on expression of type Ⅰ and type Ⅲ interferon in acute ulcerative colitis mice model

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.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

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.

基于上皮细胞-间充质细胞转分化(EMT)理论的艾灸配合化纤Ⅳ号方对实验大鼠Collagen Type Ⅲ和PDGF干预作用实验研究

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。

微针导入重组Ⅲ型人源化胶原蛋白在皮肤屏障功能修复中的应用效果

目的探究微针导入重组Ⅲ型人源化胶原蛋白治疗因皮肤炎性衰老导致的皮肤屏障功能下降的有效性及安全性。方法选取2020年6月至2021年5月在本院接受面部皮肤治疗的30例患者作为研究对象,采用随机数字表法将其分为对照组(重组Ⅲ型人源化胶原蛋白)与治疗组(微针导入重组Ⅲ型人源化胶原蛋白),各15例。治疗后定期对患者进行随访,分别进行主观疗效评价及客观疗效评价。结果治疗后4、8、12周,治疗组的满意度显著高于对照组(P<0.05)。治疗后,治疗组的皮肤皱纹、纹理、红区、毛孔、弹性、皮肤经皮失水及皮肤含水量改善明显(P<0.05);对照组治疗后油脂改善明显(P<0.05)。治疗后12周,治疗组的总症状评分显著低于对照组(P<0.05)。结论微针导入重组Ⅲ型人源化胶原蛋白对皮肤修复有较好的疗效,可增强皮肤屏障功能,为改善皮肤屏障功能、治疗因皮肤屏障受损引起的炎性衰老提供了新选择。

电压模式Buck电路中Type Ⅲ型环路补偿优化方法

设计了以UP1542为电源转换芯片的电压模式Buck电路,提出了一种基于Type Ⅲ型环路补偿中零极点理论的优化方法,引入无补偿时电压模式Buck电路与传统电压模式Buck电路Type Ⅲ型环路补偿方法进行比较。试验测试结果表明:所提优化方法与Buck电路无补偿方法和传统电压模式Buck电路Type Ⅲ环路补偿理论设计方法相比,输出电压超调分别下降33.6%和14.9%,动态响应速度分别提升72.6%和24%,同时保证了品质因素Q附近频率的电路稳定性。该优化方法降低了动态响应误差,同时有效地减小了输出电压动态响应时间,达到了提高电路稳定性的目的,验证了该优化方法的有效性。

Interferon therapy in hepatitis Cleading to chronic type 1 diabetes

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.

Serum hyaluronic acid, procollagen type Ⅲ and Ⅳ in histological diagnosis of liver fibrosis

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.

PLP2, a potent deubiquitinase from murine hepatitis virus, strongly inhibits cellular type I interferon production

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.

The host type I interferon response to viral and bacterial infections

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.

IRF family proteins and type I interferon induction in dendritic cells

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.

An enriched environment increases the expression of fibronectin type Ⅲ domain-containing protein 5 and brain-derived neurotrophic factor in the cerebral cortex of the ischemic mouse brain

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.

Macroscopic appearance of TypeⅣand giant Type Ⅲ is a high risk for a poor prognosis in pathological stage Ⅱ/Ⅲ advanced gastric cancer with postoperative adjuvant chemotherapy

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.

A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes

Type I interferons are critical antiviral cytokines produced following herpes simplex virus type-1 （HSV-1） infection that act to inhibit viral spread. In the present study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the source of interferon-a. We also report mice deficient in the A1 chain of the type I IFN receptor （CDl18-/） are extremely sensitive to ocular infection with low doses （100 PFU） of HSV-1 as seen by significantly elevated viral titers in the cornea Compared to wild type （WT） controls. The enhanced susceptibil- ity correlated with a loss of CD4＋ and CD8＋ T cell recruitment and aberrant chemokine production in the cornea despite mounting an adaptive immune response in the draining mandibular lymph node of CDll8/ mice. Taken together, these results highlight the importance of IFN production in both the innate immune response as well as eliciting chemokine production required to facilitate adaptive immune cell trafficking.

Yersinia type Ⅲ effectors perturb host innate immune responses

The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system(T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp.(Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gramnegative bacteria that share in common a 70 kb virulence plasmid which encodes the T3 SS. Translocation of the Yersinia effector proteins(YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.

Vitamin D deficiency: Correlation to interleukin-17, interleukin-23 and PⅢNP in hepatitis C virus genotype 4

AIM: To assess vitamin D (Vit D) abnormalities in hepatitis C infected patients and their relationship with interleukin (IL)-17, IL-23 and N-terminal propeptide of type Ⅲ pro-collagen (PⅢNP) as immune response mediators. METHODS: The study was conducted on 50 Egyptian patients (36 male, 14 female) with hepatitis C virus (HCV) infection, who visited the Hepatology Outpatient Clinic in the Endemic Disease Hospital at Cairo University. Patients were compared with 25 ageand sexmatched healthy individuals. Inclusion criteria were based on a history of liver disease with HCV genotype 4 (HCV-4) infection (as new patients or under followup). Based on ultrasonography, patients were classified into four subgroups; 14 with bright hepatomegaly; 11 with perihepatic fibrosis; 11 with hepatic cirrhosis; and 14 with cirrhosis and hepatocellular carcinoma (HCC).Total Vit D (i.e., 25-OH-Vit D) and active Vit D [i.e., 1,25-(OH) 2 -Vit D] assays were carried out using commercial kits. IL-17, IL-23 and PⅢNP levels were assayed using enzyme linked immunosorbent assay kits, while HCV virus was measured by quantitative and qualitative polymerase chain reaction. RESULTS: Levels of Vit D and its active form were significantly lower in advanced liver disease (hepatic cirrhosis and/or carcinoma) patients, compared to those with bright hepatomegaly and perihepatic fibrosis. IL-17, IL-23 and PⅢNP levels were markedly increased in HCV patients and correlated with the progression of hepatic damage. The decrease in Vit D and active Vit D was concomitant with an increase in viral load, as well as levels of IL-17, IL-23 and PⅢNP among all subgroups of HCV-infected patients, compared to normal healthy controls. A significant negative correlation was evident between active Vit D and each of IL-17, IL-23 and PⅢNP (r = -0.679, -0.801 and -0.920 at P < 0.001, respectively). HCV-infected men and women showed no differences with respect to Vit D levels. The viral load was negatively correlated with Vit D and active Vit D (r = -0.084 and -0.846 at P < 0.001, respectively), and positively correlated with IL-17, IL-23 and PⅢNP (r = 0.951, 0.922 and 0.94 at P < 0.001, respectively). Whether the deficiency in Vit D was related to HCVinduced chronic liver disease or was a predisposing factor for a higher viral load remains to be elucidated. CONCLUSION: The negative correlations between Vit D and IL-17, IL-23 and PⅢNP highlight their involvement in the immune response in patients with HCV-4related liver diseases in Egypt.

Microscopic removal of type Ⅲ dens invaginatus and preparation of apical barrier with mineral trioxide aggregate in a maxillary lateral incisor:A case report and review of literature

BACKGROUND Invaginated teeth pose greater challenges in clinical management because of their complex configuration.With advancements in equipment and materials,such as the dental operation microscope,cone-beam computed tomography and mineral trioxide aggregate,the preservation rate of type Ⅲ dens invaginatus could be greatly increased.CASE SUMMARY This case report presented a 31-year-old woman with complaints of spontaneous swelling and pain in the right maxillary lateral tooth.With the aid of cone-beam computed tomography,type Ⅲ dens invaginatus with apical periodontitis was diagnosed and confirmed.Three-visit endodontic treatment was performed.In the first visit,the invagination was carefully removed under the dental operation microscope,and chemomechanical preparation was done.In the second visit,mineral trioxide aggregate apical barrier surgery was performed in this tooth.In the third visit,the canal was finally obturated with thermoplastic gutta-percha to recover the crown morphology.A 26-mo follow-up revealed a satisfied outcome both in the radiographic and oral examinations.CONCLUSION In this case,removal of the entire abnormal structure provided great convenience for the follow-up treatment.When confronted with the same clinical case in the future,we can take a similar approach to address it.

Molecular Cloning and Bioinformatics Analysis of TypeⅢSecretion System Effector Protein Va1686 Gene of Vibrio alginolyticus

In this study, Va 1686 gene was cloned from Vibrio alginolyticus . The total length of the gene is 1 164 bp, and it could encode 387 amino acids. The physicochemical properties, protein structure, genetic evolutionary relationship and antigenic characteristics of the effect protein Va1686 of V. alginolyticus HY9901 type Ⅲ secretion system were studied and analyzed by bioinformatics methods and tools. The results showed that Va1686 is a stable hydrophilic and acidic protein without a transmembrane region and a signal peptide, and secondary structure to α-helix. The evolutionary analysis showed that V. alginolyticus HY9901 and V. harveyi were clustered together, which indicated that the genetic relationship between the two species was the closest. Va1686 contains a Fic superfamily conserved domain associated with cell division. Bioinformatics analysis showed that the B-cell preponderant epitopes of Va1686 might be localized in the regions of 48-49, 82-85, 125-126, 150-153, 185-186, 236-237 and so on. The 3D structure model of Va1686 subunit was simulated by SWISS-MODEL software and it was found that the vopS of V. parahaemolyticus was similar and the similarity was 89.46%. In this study, the feasibility of Va1686 as a common antigen of Vibrio was verified from the perspective of bioinformatics, which laid the foundation for the next step in vaccine development.

Uniform persistence of multispecies ecological competition predator-pray system with Holling Ⅲ type functional response

The main purpose of this paper is to study the persistence of the general multispecies competition predator-pray system with Holling Ⅲ type functional response. In this system, the competition among predator species and among prey species are simultaneously considered. By using the comparison theory and qualitative analysis, the sufficient conditions for uniform strong persistence are obtained.

Adjuvant chemoradiotherapy vs adjuvant chemotherapy in locally advanced Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction after D2/R0 resection

BACKGROUND For Siewert type Ⅱ/Ⅲ adenocarcinoma of gastroesophageal junction(AGE), the efficacy of adjuvant chemoradiotherapy(CRT) after D2/R0 resection remains uncertain.AIM To determine whether CRT was superior to chemotherapy(CT) alone after D2/R0 resection for locally advanced Siewert type Ⅱ/Ⅲ AGE.METHODS We identified 316 locally advanced Siewert type Ⅱ/Ⅲ AGE patients who were treated with D2/R0 resection at National Cancer Center from 2011 to 2018.57 patients received adjuvant CRT and 259 patients received adjuvant CT.We followed patients for overall survival(OS), relapse-free survival, and recurrence pattern.RESULTS Five-year OS rates of the CRT group and the CT group for all patients were 66.7% and 41.9%(P = 0.010).Five-year OS rates of the CRT group and the CT group for Siewert type Ⅲ AGE patients were 65.7% and 43.9%(P = 0.006).Among the 195 patients whose recurrence information could be obtained, 18 cases(34.6%) and 61 cases(42.7%) were diagnosed as recurrence in the CRT group and CT group, respectively.The local and regional recurrence rates in the CRT group were lower than that in the CT group(22.2% vs 24.6%, 27.8% vs 39.3%).Multivariable cox regression analysis showed that vascular invasion, nerve invasion, and adjuvant CRT were important prognostic factors for Siewert type Ⅲ AGE.CONCLUSION For locally advanced Siewert type Ⅲ AGE, adjuvant CRT may prolong OS and reduce the regional recurrence rate.