Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer

Objective:The choice of chemotherapeutic regimen for triple-negative breast cancer(TNBC)remains controversial.Homologous recombination deficiency(HRD)has attracted increasing attention in informing chemotherapy treatment.This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.Methods:Chinese patients with TNBC who received chemotherapy between May 1,2008 and March 31,2020 were retrospectively analyzed with a customized 3D-HRD panel.HRD positivity was defined by an HRD score≥30 or deleterious BRCA1/2 mutation.A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort(NCT01150513)and a metastatic cohort,and 189 patients with available clinical and tumor sequencing data were included.Results:In the entire cohort,49.2%(93/189)of patients were identified as HRD positive(40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of≥30).In the first-line metastatic setting,platinum therapy was associated with longer median progression-free survival(mPFS)than platinum-free therapy[9.1 vs.3.0 months;hazard ratio(HR),0.43;95%confidence interval 0.22–0.84;P=0.01].Among HRD-positive patients,the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy(13.6 vs.2.0 months;HR,0.11;P=0.001).Among patients administered a platinum-free regimen,HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients(P=0.02;treatment-biomarker P-interaction=0.001).Similar results were observed in the BRCA1/2-intact subset.In the adjuvant setting,HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy(P=0.05,P-interaction=0.02).Conclusions:HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

基于openFDA对地加瑞克安全信号的挖掘与分析

目的挖掘和评价前列腺癌治疗药物地加瑞克上市后的安全信号,为临床安全用药提供参考。方法检索美国食品药品管理局公共数据开放项目(openFDA)2004年1月1日—2021年11月4日收录的地加瑞克不良事件(ADE)报告,采用报告比值比法和信息成分法对ADE信号进行检测,利用国际医学用语词典对ADE进行系统归类和安全评估。结果在限定的检索时间段内,共提取到以地加瑞克为怀疑药物的ADE报告4663份,其中严重ADE占51.30%。挖掘出阳性风险信号35个,共涉及9个系统/器官。基于系统/器官分类,全身性及给药部位ADE产生的阳性信号最多,占57.14%。比例失衡测量法显示,全身性及给药部位,各类检查以及各类肌肉骨骼和结缔组织疾病相关ADE产生的信号强度均较高。结论应用地加瑞克时,应警惕严重ADE的发生,重点关注给药部位ADE,同时还应关注前列腺特异性抗原及ALT升高,肌肉骨骼疼痛以及心血管事件的发生。

智能分光电子染色内镜联合小探头超声在食管浅表性病变诊治中的应用价值

目的研究智能分光电子染色(FICE)内镜联合小探头超声内镜(EUS)在诊断食管浅表性病变中的临床价值。方法选取2013年1月-2016年6月该院消化内镜中心行普通白光胃镜检查可疑食管黏膜病变患者为研究对象,共292例,将患者按随机数字法分为观察组和对照组,各146例,对照组采用普通白光放大内镜进行检查,观察组在对照组检查基础上应用FICE放大内镜及小探头EUS,观察病变处食管上皮乳头内毛细血管袢(IPCL)的改变及病变深度,并推测病理类型,将两组内镜诊断结果与病理组织学诊断结果进行对比分析。结果 FICE放大内镜可清晰观察食管IPCL形态并分型,FICE内镜对食管炎性病变诊断的符合率为82.69%,轻中度不典型增生符合率为82.22%,重度不典型增生符合率为86.96%,食管癌符合率为100.00%。观察组与对照组准确率分别为91.78%和76.02%;灵敏度分别为85.71%和44.44%,前者明显优于后者。FICE内镜发现5处白光内镜漏诊的平坦型病变。结论 FICE模式与普通白光内镜相比,可增强病变的可识别性,能清楚显示病变轮廓和形态,能有效提高活检的准确性,操作方便。FICE联合小探头EUS在食管浅表性病变诊断治疗方面有一定的临床应用价值。

COVID-19合并肿瘤患者的免疫状态及治疗策略

近期2019新型冠状病毒变异毒株奥密克戎BA.2亚型在全球大流行,对人民的生命安全造成了较大的影响。肿瘤患者因疾病自身或治疗的原因处于免疫失衡状态,更易罹患2019冠状病毒病(coronavirus disease 2019,COVID-19),并且感染后病死率高于正常人群。肿瘤患者和正常人群在感染病毒后免疫状态有所不同,主要表现为两个方面,一方面是各类细胞因子不受调节的过度释放,另一方面是体液免疫和细胞免疫的后继无力,故抗肿瘤治疗策略也应进行相应的调整。现对相关的研究进展做一综述,为这类特殊人群的治疗提供参考。

单眼和双眼三焦点IOL植入术后视觉相关生活质量的比较

目的:对比分析双眼三焦点IOL(AT LISA tri 839MP IOL)植入与一眼植入AT LISA tri 839MP IOL而另一眼植入非球面单焦点IOL患者术后视觉相关生活质量。方法:前瞻性临床研究。收集2018-05/2019-08在我院行白内障超声乳化联合三焦点AT LISA tri 839MP IOL植入的患者45例,按是否双眼植入AT LISA tri 839MP IOL分为两组,双眼植入者24例纳入双眼三焦点组;一眼植入AT LISA tri 839MP IOL而另一眼植入非球面单焦点IOL者21例纳入单眼三焦点组。术后3mo,检测两组患者裸眼视力及等效球镜度,并通过中国版视功能指数量表(VF-14-CN)评价视觉相关生活质量,评估日常生活脱镜率及满意度。结果:术后3mo,双眼三焦点组和单眼三焦点组患者双眼裸眼远、中、近视力均无明显差异(P>0.05),两组患者VF-14-CN问卷得分(96.2±0.50、92.43±1.32分)、日常生活脱镜率(96%、90%)及患者主观满意度(96%、95%)均无差异(P>0.05)。结论:双眼植入AT LISA tri 839MP IOL和一眼植入AT LISA tri 839MP IOL而另一眼植入非球面单焦点IOL的患者术后均具有良好的双眼裸眼远、中、近视力,术后视觉相关生活质量、脱镜率、满意度无明显差异。对一眼不适合植入三焦点IOL或既往一眼已植入非球面单焦点IOL的患者,可考虑另一眼行三焦点IOL植入以满足患者双眼全程视力的要求。

中期18F-FDG PET-CT两种图像判读法在弥漫性大B细胞淋巴瘤预后评估中的应用

目的:探讨中期正电子发射型计算机断层显像(positron emission tomography-computed tomography,PET-CT)Deauville五分法(Deauville five-point scale,5-PS)与最大标准摄取值缩减率(maximum standard uptake value variation,△SUVmax)两种图像判读法在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者预后评估中的应用价值。方法:回顾性分析2012年10月至2018年6月重庆医科大学附属第一医院收治的94例DLBCL患者资料。采用Kaplan-Meier法及Cox比例风险回归模型进行生存资料分析,计算并采用χ2检验比较5-PS和△SUVmax对DLBCL患者预后预测的能力。结果:5-PS和△SUVmax分别以4分、86%进行分组。5-PS<4分组、△SUVmax≥86%组的患者无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS)均优于5-PS≥4分组、△SUVmax<86%组的患者(P<0.05)。△SUVmax与5-PS对患者PFS和OS均有影响,较高的阴性预测值(89.4%,93.6%;76.1%,85.9%),较低的阳性预测值(48.9%,31.9%;47.8%,34.8%),并且△SUVmax对于患者的敏感性优于5-PS(82.1%,83.3%vs.39.3%,44.4%)。单因素分析中国际预后指数(international prognostic index,IPI)(P=0.007)、△SUVmax(P<0.001)、5-PS(P=0.014)及基线全身肿瘤代谢体积(total metabolic tumor volume,TMTV)(P=0.001)与PFS相关,△SUVmax(P=0.014)、5-PS(P=0.033)、TMTV(P=0.004)与OS相关;多因素分析显示TMTV是OS的独立预测因子(P=0.005),△SUVmax和TMTV是PFS的独立预测因子(P=0.002,P=0.020),并且△SUVmax<86%且高水平TMTV患者较低TMTV患者的PFS明显缩短(P=0.001)。结论:5-PS和△SUVmax均能初步评估DLBCL患者预后,但△SUVmax具有更高的预测价值,并且联合基线TMTV可以对DLBCL患者进行再次危险度分层。

Therapeutic potential of natural compounds from Chinese medicine in acute and subacute phases of ischemic stroke

Stroke is one of the leading causes of death and disability in adults worldwide,resulting in huge social and financial burdens.Extracts from herbs,especially those used in Chinese medicine,have emerged as new pharmaceuticals for stroke treatment.Here we review the evidence from preclinical studies investigating neuroprotective properties of Chinese medicinal compounds through their application in acute and subacute phases of ischemic stroke,and highlight potential mechanisms underlying their therapeutic effects.It is noteworthy that many herbal compounds have been shown to target multiple mechanisms and in combinations may exert synergistic effects on signaling pathways,thereby attenuating multiple aspects of ischemic pathology.We conclude the paper with a general discussion of the prospects for novel natural compound-based regimens against stroke.

Notch signaling mediated by TGF-β/Smad pathway in concanavalin A-induced liver fibrosis in rats

AIM To explore the exact interaction between Notch and transforming growth factor(TGF)-β signaling in liver fibrosis. METHODS We established a rat model of liver fibrosis induced by concanavalin A. Peripheral blood mononuclear cells(PBMCs) were isolated from the modeled rats, and cultured with γ-secretase inhibitor DAPT and TGF-β inhibitor for 24 h. The m RNA levels of Notch and TGF-β signaling were detected by quantitative real-time polymerase chain reaction. Expression of Notch and TGF-β proteins was analyzed by western blotting.RESULTS Compared to control rats, Notch and TGF-β signaling was activated in PBMCs of model rats. Administration of DAPT and TGF-β inhibitor suppressed Notch and TGF-β signal transducer in PBMCs of model rats. DAPT reduced m RNA and protein expression of TGF-β signaling, such as TGF-β1 and Smad3. TGF-β inhibitor also downregulated Notch1, Hes1 and Hes5, and m RNA and protein expression of the Notch signaling pathway.CONCLUSION Notch and TGF-β signaling play a role in liver fibrosis. TGF-β signaling upregulates Notch signaling, which promotes TGF-β signaling.

Relationship between traditional Chinese medicine syndrome differentiation and imaging characterization to the radiosensitivity of nasopharyngeal carcinoma

Background and Objective: Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC. Methods: Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures. Results: Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P < 0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P < 0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P < 0.05). Conclusions: Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.

Polyurea coating for foamed concrete panel:An efficient way to resist explosion

Autoclaved aerated concrete(AAC) panels have ultra-light weight,excellent thermal insulation and energy absorption,so it is an ideal building material for protective structures.To improve the blast resistance of the AAC panels,three schemes are applied to strengthen the AAC panels through spraying 4 mm thick polyurea coating from top,bottom and double-sides.In three-point bending tests,the polyurea-coated AAC panels have much higher ultimate loads than the un-coated panels,but slightly lower than those strengthened by the carbon fiber reinforced plastics(CEFRPs).Close-in explosion experiments reveal the dynamic strengthening effect of the polyurea coating.Critical scaled distances of the strengthened AAC panels are acquired,which are valuable for the engineering application of the AAC panels in the extreme loading conditions.Polyurea coatings efficiently enhance the blast resistance of the bottom and double-sided polyurea-coated AAC panels.It is interesting that the polyurea-coated AAC panels have much more excellent blast resistance than the CFRP reinforced AAC panels,although the latter have better static mechanical properties.

Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

Motor function impairment is a common outcome of stroke.Constraint-induced movement therapy(CIMT)involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of‘learned non-use’and improve limb function after stroke.However,the underlying mechanism of CIMT remains unclear.In the present study,rats were randomly divided into a middle cerebral artery occlusion(model)group,a CIMT+model(CIMT)group,or a sham group.Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups.Compared with the model group,CIMT significantly improved the forelimb functional performance in rats.By western blot assay,the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group,and was similar to sham group levels.These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

Palliative primary tumor resection provides survival beneits for the patients with metastatic colorectal cancer and low circulating levels of dehydrogenase and carcinoembryonic antigen

Background: It remains controversial whether palliative primary tumor resection(PPTR) can provide survival benefits to the patients with metastatic colorectal cancer(m CRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with m CRC.Methods: We conducted a retrospective study on consecutive m CRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival(OS) and progression?free survival(PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient groups.Results: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months(P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months(P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group(219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group(95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase(LDH) levels and with carcinoembryonic antigen(CEA) levels <70 ng/m L benefited from PPTR(median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001).Conclusions: For m CRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/m L.

Hospital-Based Phenotypic Features and Treatment Outcomes of Chinese Women with Polycystic Ovary Syndrome: The Effect of Body Mass Index and Geographic Distribution

Genetic,lifestyle,and environmental factors contribute to the etiology of polycystic ovary syndrome(PCOS).Increased body mass index(BMI)exacerbates the reproductive and metabolic parameters and reduces the fecundity of women with PCOS.This is a secondary analysis of a large-sample,multicenter,randomized controlled trial conducted at 21 sites in Chinese mainland.A total of 1000 women diagnosed with PCOS were enrolled in this trial.Of these,998 women with PCOS were included in the analysis.Increased BMI was associated with more severe menstrual irregularities,elevated testosterone level,higher prevalence of metabolic syndrome,and poorer quality of life.The rates of ovulation per woman for the normal,overweight,and obese BMI groups were 83.0%,78.2%,and 63.6%,respectively(P<0.001),and the rates of live birth were 23.6%,18.1%,and 15.3%(P=0.030).Northern PCOS patients showed more severe reproductive,glucose,and lipid profiles;less exercise;and lower total ovulation rates compared with PCOS patients from Southern China(74.8%vs 81.2%,absolute difference 6.4%,95%confidence interval 1.2%–11.5%).The results show the typical phenotypic features of Han women with PCOS in Northern and Southern China.The women living in Northern China showed a higher BMI,more severe glycolipid metabolism profiles,and subsequently worse clinical outcomes by the same interventions than those living in Southern China.The difference in phenotypic features can be explained mostly by differences in BMI and the resulting difference in ovulation.

Therapeutic implications of advanced age at time of spinal cord injury

A recent demographic shift towards increased age at time of spinal cord injury (SCI), as well as decreased functional recovery following SCI in older populations, create the need to investigate how age effects SCI pathology and repair (Scivoletto et al., 2003). While decreased neuroplasticity or physical strength with age may contribute to functional deficits, work from our lab and others have identified exacerbated acute inflammatory events as contributors to age-dependent secondary injury. Specifically, our recent paper identified that increased production of reactive oxygen species (ROS) from macrophage nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) with age exacerbates secondary injury after SCI (Zhang et al., 2019).

On numerical earthquake prediction

Can earthquakes be predicted? How should people overcome the difficulties encountered in the study of earthquake prediction? This issue can take inspiration from the experiences of weather forecast.Although weather forecasting took a period of about half a century to advance from empirical to numerical forecast,it has achieved significant success.A consensus has been reached among the Chinese seismological community that earthquake prediction must also develop from empirical forecasting to physical prediction.However,it is seldom mentioned that physical prediction is characterized by quantitatively numerical predictions based on physical laws.This article discusses five key components for numerical earthquake prediction and their current status.We conclude that numerical earthquake prediction should now be put on the planning agenda and its roadmap designed,seismic stations should be deployed and observations made according to the needs of numerical prediction,and theoretical research should be carried out.

Face and object visual working memory deficits in first-episode schizophrenia correlate with multiple neurocognitive performances

Background Working memory(WM)deficit is considered a core feature and cognitive biomarker in patients with schizophrenia.Several studies have reported prominent object WM deficits in patients with schizophrenia,suggesting that visual WM in these patients extends to non-spatial domains.However,whether non-spatial WM is similarly affected remains unclear.Aim This study primarily aimed to identify the processing of visual object WM in patients with first-episode schizophrenia.Methods The study included 36 patients with first-episode schizophrenia and 35 healthy controls.Visual object WM capacity,including face and house WM capacity,was assessed by means of delayed matching-to sample visual WM tasks,in which participants must distribute memory so that they can discriminate a target sample.We specifically examined their anhedonia experience by the Temporal Experience of Pleasure Scale and the Snaith-Hamilton Pleasure Scale.Cognitive performance was measured by the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS).Results Both face and house WM capacity was significantly impaired in patients with schizophrenia.For both tasks,the performance of all the subjects was worse under the high-load condition than under the low-load condition.We found that WM capacity was highly positively correlated with the performance on RBANS total scores(r=−0.528,p=0.005),RBANS delayed memory scores(r=−0.470,p=0.013),RBANS attention scores(r=−0.584,p=0.001),RBANS language scores(r=−0.448,p=0.019),Trail-Making Test:Part A raw scores(r=0.465,p=0.015)and simple IQ total scores(r=−0.538,p=0.005),and correlated with scores of the vocabulary test(r=−0.490,p=0.011)and scores of the Block Diagram Test(r=−0.426,p=0.027)in schizophrenia.No significant correlations were observed between WM capacity and Positive and Negative Syndrome Scale symptoms.Conclusions Our research found that visual object WM capacity is dramatically impaired in patients with schizophrenia and is strongly correlated with other measures of cognition,suggesting a mechanism that is critical in explaining a portion of the broad cognitive deficits observed in schizophrenia.

Study of Gong tone matching to five colors based on event-related potential

Objective:To investigate the neural mechanism of Gong tone matching to the five colors.Methods:The experiment was designed using event-related potential technique,following the S1 →S2 paradigm,and dividing into two arms according to the Gong tone being played in harmonics or open strings.For each arm,S1 was the playing of the Gong tone,followed by S2,where subjects,based on their first reaction,were required to make a yes/no judgement to whether the tone matches to a randomly-picked color out of the five colors.During this process,the event-related potentials were recorded.Results:Gong tone played in harmonics,most participants matched it with black and cyan;while in the open strings arm,most matched it with black.The average amplitudes of P300 at PZ,FZ,and CZ points were compared.For the Gong tone played in harmonics,there was a significant difference between those who matched it with black and those who did otherwise (P <.01).There was also a significant difference between those who matched it with cyan and those who did otherwise (P <.01).For the open strings arm,there was a significant difference between those who matched it with black and those who did otherwise (P <.01).Conclusion:Our comparison of the average amplitudes of P300 suggests a commonality in the neural mechanism underlying categorical thinking that is not fundamentally altered by playing style.However,behavioral theory suggests that playing style does have an influence on categorization.The Gong tone can be matched with any of the five colors,which accords with the thought of central Earth in the five-element theory.This provides evidence of the similarity within five elements correspondences existing alongside the indirect matching between five tones and five colors.

中国男性乳腺癌患者临床特征:公开发表文章的总结(英文)

Objective:The extremely low incidence of male breast cancer (MBC) leads to lack of prospective randomized phase III studies worldwide. Especially in China,all studies on Chinese patients with MBC were based on small sample size and single institute experience. The aim of this study was to provide overall view of characteristics of Chinese patients with MBC by means of summarizing all related papers published in Chinese journals. Methods: An online search was made in CBM,VIP,CNKI,and CBA databases to find all published articles of interest on Chinese patients with MBC. And eight subjects including the proportion of MBC in all breast cancer,age,tumor location,clinical stages,pathological subtypes,treatment modalities,ER/PR expression,and 5-year survival rate were selected to calculate the proportion and their 95% interval confidence. Results: There were 122 papers with 2584 patients enrolled. The basic features of Chinese patients with MBC included:(1) MBC only with a proportion of 1.06% of all the breast cancer; (2) The mean age at diagnosis was 57.6 years old; (3) Tumor mainly located in the areolar region (74.83%) with obvious nipple and/or skin involvement; (4) Nearly 62.62% patients were in early stage before accepting treatment; (5) Infiltrating ductal carcinoma accounted for 79.05% of all pathological subtypes; (6) ER/PR expression rate was 65.86%; (7) Radical resection was up to 86.06% in all surgical modalities; (8) The 5-year survival rate was 57.33%. Conclusion: The results showed in this study were an overall view of Chinese patients with MBC whose characteristics were similar to that reported in the West. Though this study provided a little bit stronger confidence than a single study collected in this paper,studies with more powerful evidence are urgently demanding in China.

MyD88 exacerbates immunological pathology in experimental viral fulminant hepatitis

Objective To explore the role of MyD88 signaling in MHV-3 virus-mediated fulminant hepatitis. Methods We evaluated liver lesion status, the expression of multiple pro-inflammatory cytokines and HMGB1, the recruitment of inflammatory ILC3, and mortality in MyD88-/-and WT mice. Results The expression of multiple pro-inflammatory cytokines that recruit inflammatory ILC3 to the liver was severely impaired in MyD88-/-mice resulting in reduced liver pathology, viral replication, and mortality post-infection. Additionally, MHV-3 markedly increased the expression of high-mobility group box 1(HMGB1) in infected hepatocytes/macrophages and induced HMGB1 protein migration from the nucleus to the extracellular milieu, where it activates MyD88-dependent inflammation. Conclusion Our findings indicate that MyD88 exacerbates immunological pathology in experimental viral fulminant hepatitis.

Synthesis of multi-hydroxyl and sulfonyl dual-functionalized room temperature ionic liquids

Starting from the hydroxylamine (dimethyl amino ethanol, triethanolamine) and 1,3-propane sultone, a series of hydroxyl and sulfonyl dual-functionalized zwitterionic salts and corresponding acidic room temperature ionic liquids have been synthesized. The hydroxyl groups of the synthesized substances were confirmed by the 1H NMR measurement. These zwitterionic salts and ionic liquids may be used for synthesizing other functionalized ionic liquids or ionic liquid-polymer (polyelectrolyte).