CD137L,a driver of harmful inflammation in the nervous system

CD137 (TNFRSF9,4-1BB) is a member of the tumor necrosis factor (TNF) receptor family and a potent costimulatory molecule.High levels of CD137 are expressed on T cells upon activation.CD137 signaling in T cells,either by cognate interaction with antigen-presenting cells (APC)or by agonistic anti-CD137 antibodies,strongly enhances proliferation,interferon-y secretion,and cytolytic activity of T cells.Thus,CD137 signaling is a main driver of cellular,type 1 helper T cells (Th1)and type 1 cytolytic T cells (Tc1) polarised immune responses.

Dental trauma in endoscopy:A systematic review and experience of a tertiary endoscopy centre

BACKGROUND Dental injury is the leading cause of litigation in anaesthesia but an underrecognized preventable complication of endoscopy.AIM To determine frequency and effects of dental injury in endoscopy,we present findings from an audit of outpatient endoscopy procedures conducted at a tertiary university hospital and a systematic review of literature.METHODS Retrospective review of 11265 outpatient upper endoscopy procedures over the period of 1 June 2019 to 31 May 2021 identified dental related complications in 0.284%of procedures.Review of literature identified a similar rate of 0.33%.RESULTS Pre-existing dental pathology or the presence of prostheses makes damage more likely but sound teeth may be affected.Pre-endoscopic history and tooth examination are key for risk stratification and may be conducted succinctly with limited time outlay.Tooth retrieval should be prioritized in the event of dental injury to minimize aspiration and be followed by prompt dental consultation for specific management.CONCLUSION Dental complications occur in approximately 1 in 300 of upper endoscopy cases.These are easily preventable by pre-endoscopy screening.Protocols to mitigate dental injury are also suggested.

Wearable Smart Sensor System for Medical Monitoring with an Assessment of the Level of Blood Loss and Pain Shock Because of Trauma or Injury

Blood loss in peacetime is mainly due to the normal menstrual cycle in women or diseases with surgical intervention. In wartime, blood loss in military personnel is a characteristic sign of a closed or open injury of the body during internal or external bleeding. Access to clinical care for wounded military personnel injured on the battlefield is limited and has long delays compared to patients in peacetime. Most of the deaths of wounded military personnel on the battlefield occur within the first hour after being wounded. The most common causes are delay in providing medical care, loss of time for diagnosis, delay in stabilization of pain shock and large blood loss. Some help in overcoming these problems is provided by the data in the individual capsule, which each soldier of the modern army possesses;however, data in an individual capsule is not sufficient to provide emergency medical care in field and hospital conditions. This paper considers a project for development of a smart real-time monitoring wearable system for blood loss and level of shock stress in wounded persons on the battlefield, which provides medical staff in field and hospital conditions with the necessary information to give timely medical care. Although the hospital will require additional information, the basic information about the victims will already be known before he enters the hospital. It is important to emphasize that the key term in this approach is monitoring. It is tracking, and not a one-time measurement of indicators, that is crucial in a valid definition of bleeding.

Genetic risk stratification of inflammatory bowel disease-associated venous thromboembolism:An Asian perspective

The utilisation of polygenic scoring models may enhance the clinician’s ability to risk stratify an inflammatory bowel disease patient’s individual risk for venous thromboembolism(VTE)and guide the appropriate usage of VTE thromboprophylaxis,yet there is a need to validate such models in ethnically diverse populations.

Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review

BACKGROUND Acute liver failure(ALF)and acute-on-chronic liver(ACLF)carry high short-term mortality rate,and may result from a wide variety of causes.Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant.Other cohort studies demonstrated potential improvement in survival in patients with ACLF.AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.METHODS Databases MEDLINE via PubMed,and EMBASE were searched and relevant publications up to 30 March,2019 were assessed.Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange,with or without another alternative non-bioartificial liver assist device.RESULTS Three hundred twenty four records were reviewed,of which 62 studies were found to be duplicates.Of the 262 records screened,211 studies were excluded.Fifty-one articles were assessed for eligibility,for which 7 were excluded.Twenty-nine studies were included for ALF only,and 9 studies for ACLF only.Six studies included both ALF and ACLF patients.A total of 44 publications were included.Of the included publications,2 were randomized controlled trials,14 cohort studies,12 case series,16 case reports.All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange.In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment(SMT)for ACLF,a biochemical improvement was seen.Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT.Using the aforementioned studies,plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60(95%CI 0.46-0.77,P<0.01).CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high.Plasma exchange in ACLF improves survival at 30-and 90-d in nontransplanted patients.Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.

Comparative study and systematic review of laparoscopic liver resection for hepatocellular carcinoma

AIM: To compare the surgical outcomes between laparoscopic liver resection(LLR) and open liver resection(OLR) as a curative treatment in patients with hepatocellular carcinoma(HCC). METHODS: A Pub Med database search was performed systematically to identify comparative studies of LLR vs OLR for HCC from 2000 to 2014. An extensive text word search was conducted, using combinations of search headings such as "laparoscopy", "hepatectomy", and "hepatocellular carcinoma". A comparative study was also performed in our institution where we analysed surgical outcomes of 152 patients who underwent liver resection between January 2005 to December 2012, of which 42 underwent laparoscopic or hand-assisted laparoscopic resection and 110 underwent open resection. RESULTS: Analysis of our own series and a review of 17 high-quality studies showed that LLR was superior to OLR in terms of short-term outcomes, as patients in the laparoscopic arm were found to have less intraoperative blood loss, less blood transfusions, and a shorter length of hospital stay. In our own series, both LLR and OLR groups were found to have similar overall survival(OS) rates, but disease-free survival(DFS) rates were higher in the laparoscopic arm. CONCLUSION: LLR is associated with better short-term outcomes compared to OLR as a curative treatment for HCC. Long-term oncologic outcomes with regards to OS and DFS rates were found to be comparable in both groups. LLR is hence a safe and viable option for curative resection of HCC.

Multinational survey on the preferred approach to management of Barrett’s esophagus in the Asia-Pacific region

BACKGROUND Major societies provide differing guidance on management of Barrett’s esophagus(BE),making standardization challenging.AIM To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists.METHODS Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis,surveillance and management of BE.RESULTS Five hundred sixty-nine of 1016(56.0%)respondents completed the survey,with most respondents from Japan(n=310,54.5%)and China(n=129,22.7%).Overall,the preferred endoscopic landmark of the esophagogastric junction was squamocolumnar junction(42.0%).Distal palisade vessels was preferred in Japan(59.0%vs 10.0%,P<0.001)while outside Japan,squamo-columnar junction was preferred(59.5%vs 27.4%,P<0.001).Only 16.3%of respondents used Prague C and M criteria all the time.It was never used by 46.1%of Japanese,whereas 84.2%outside Japan,endoscopists used it to varying extents(P<0.001).Most Asian endoscopists(70.8%)would survey long-segment BE without dysplasia every two years.Adherence to Seattle protocol was poor with only 6.3%always performing it.73.2%of Japanese never did it,compared to 19.3%outside Japan(P<0.001).The most preferred(74.0%)treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis.For BE with low-grade dysplasia,6-monthly surveillance was preferred in 61.9%within Japan vs 47.9%outside Japan(P<0.001).CONCLUSION Diagnosis and management of BE varied within Asia,with stark contrast between Japan and outside Japan.Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction,which is incorrect.Most also did not consistently use Prague criteria,and Seattle protocol.Lack of standardization,education and research are possible reasons.

Collagen 1 signaling at the central nervous system injury site and astrogliosis

Central nervous system （CNS） injuries are often devastating as func- tional recovery via axonal regrowth over the lesion site is very minimal.

Mental Health Literacy and the Belief in the Supernatural

Objective: Mental health literacy affects treatment seeking. We compare literacy levels of psychiatric outpatients and a control group of outpatients seeking treatment for non-psychiatric disorders in the same hospital. We hypothesized higher levels of mental health literacy among psychiatric patients than controls, with younger age and higher educational levels associated with better literacy. We also hypothesized that there would be an inverse relationship between educational level and the belief in the supernatural causality of mental disorders. Methods: Literacy was estimated by showing psychiatric outpatients and a control group of non-psychiatric patients vignettes depicting a case of major depression and a case of generalised anxiety disorder. Their opinions regarding diagnosis, etiology, treatment, and attitudes towards mental health services were ascertained by structured questionnaires. Results: Psychiatric patients did not demonstrate superior mental health literacy compared to controls, with the exception of knowing where to obtain a psychiatric referral. Lower age and higher education levels of psychiatric patients were associated with better literacy. The higher the education level is, the less likely to attribute the causality of mental disorders to supernatural elements. Conclusion: This study highlights the need for a program of psycho-education targeting patients, their relatives, and the public.

Precision medicine in inflammatory bowel disease:Individualizing the use of biologics and small molecule therapies

The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

Paediatric gastrointestinal endoscopy in the Asian-Pacific region:Recent advances in diagnostic and therapeutic techniques

There has been a rapid expansion in the knowledge of paediatric gastroenterology over the recent decade,with a fast-growing repertoire of diagnostic techniques and management strategies for a wide spectrum of childhood gastrointestinal(GI)diseases.Paediatric GI endoscopy is a core competency every paediatric gastroenterologist should possess,and represents one of the most common procedures performed in children for both diagnostic and therapeutic purposes.Yet there remains a dearth of literature on the utility and outcomes of paediatric GI endoscopy in the Asia-Pacific region.Data on the diagnostic value of paediatric GI endoscopy would be an important aspect of discussion,with the emergence of inflammatory bowel disease(IBD)and eosinophilic GI disease as increasingly common endoscopic diagnoses.Time-based trends in paediatric GI endoscopy do point towards more IBD and gastroesophageal reflux disease-related complications being diagnosed,with a declining incidence of GI bleeding.However,the real-world diagnostic value of endoscopy in Asia must be contextualised to the region-specific prevalence of paediatric GI diseases.Helicobacter pylori infection,particularly that of multidrug-resistant strains,remains a highly prevalent problem in specific regions.Paediatric functional GI disorders still account for the majority of childhood GI complaints in most centres,hence the diagnostic yield of endoscopy should be critically evaluated in the absence of alarm symptoms.GI therapeutic endoscopy is also occasionally required for children with ingested foreign bodies,intestinal polyposis or oesophageal strictures requiring dilation.Endoscopic haemostasis is a potentially life-saving skill in cases of massive GI bleeding typically from varices or peptic ulcers.Advanced endoscopic techniques such as capsule endoscopy and balloon-assisted enteroscopy have found traction,particularly in East Asian centres,as invaluable diagnostic and therapeutic tools in the management of IBD,obscure GI bleeding and intestinal polyposis.State of the art endoscopic diagnostics and therapeutics,including the use of artificial intelligence-aided endoscopy algorithms,real-time confocal laser endomicroscopy and peroral endoscopic myotomy,are expected to gain more utility in paediatrics.As paediatric gastroenterology matures as a subspecialty in Asia,it is essential current paediatric endoscopists and future trainees adhere to minimum practice standards,and keep abreast of the evolving trends in the diagnostic and therapeutic value of endoscopy.This review discusses the available published literature on the utility of paediatric GI endoscopy in Asia Pacific,with the relevant clinical outcomes.

亚太地区慢性乙型肝炎治疗共识(2012最新版)

自2008年至今,有大量关于慢性HBV感染的自然史和治疗的最新数据不断涌现。其中包括慢性HBV感染的无症状感染者,以社区为基础的队列研究,HBV基因型的作用,非药物诱导的自然HBV变异型毒株,无创性肝纤维化评估方法的应用,HBsAg定量在临床中的应用,更有效的新治疗药物和新治疗方案等等。来自亚太地区的专家审查和评估了相关数据,并共同商讨了近年来报道的最有意义的发现,基于此,对2008年版的亚太地区慢性乙型肝炎治疗共识进行修订,同时对2008年版治疗指南定义的关键词组进行了修订。修订后的指南包括以下几方面内容:一般治疗,肝纤维化评价适应证,何时开始治疗或停药,初始抗病毒治疗药物的选择,如何监测治疗中和治疗后的患者。关于特殊人群的治疗建议中包括了对妊娠妇女,已发生耐药,合并其他病毒感染,肝功能失代偿,接受免疫抑制治疗、化疗,肝移植或肝细胞癌患者的具体治疗建议。

Evaluation of antiviral activities of Houttuynia cordata Thunb.extract,quercetin,quercetrin and cinanserin on murine coronavirus and dengue virus infection

Objective:To evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(H.cordata) Thunb.(Saururaceae) and three of its constituent flavonoids(quercetin.quercitrin and rutin) against murine coronavirus and dengue virus(DENV).Methods:The antiviral activities of various concentrations of the EA fraction of H.cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus(MHV) and DENV type 2(DENV-2).Cinanserin hydrochloride was also tested against MHV.The EA fraction of H.cordata was tested for acute oral toxicity in C57BL/6 mice.Results:The EA fraction of H.cordata inhibited viral infectivity up to 6 d.Cinanserin hydrochloride was able to inhibit MHV for only 2 d.The 50%inhibitory concentrations(IC_(50)) of the EA fraction of H.cordata added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2with absence of cytotoxicity.The mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity,with normal histological features of major organs.Certain flavonoids exhibited comparatively weaker antiviral activity,notably quercetin which could inhibit both MHV and DENV-2.This was followed by quercitrin which could inhibit DENV-2but not MHV,whereas rutin did not exert any inhibitory effect on either virus.When quercetin was combined with quercitrin,enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed.However,the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction.Conclusions:The compounds in H.cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vim.H.cordata has much potential for the development of antiviral agents against coronavirus and dengue infections.

Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers

Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide,due to late detection and high recurrence rates.Today,these cancers have a heavy socioeconomic burden,for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets.Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers.Over the past decade,emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers,indicating its potential as an independent prognostic indicator in such patients.Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo .Furthermore,OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment,in which many details need further exploration.OPN signaling results in various functions,including prevention of apoptosis,modulation of angiogenesis,malfunction of tumor-associated macrophages,degradation of extracellular matrix,activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways,which lead to tumor formation and progression,particularly in gastric and liver cancers.This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression,its potential as a therapeutic target,and putative mechanisms in gastric and liver cancers.Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.

Role of LPS/CD14/TLR4-mediated inflammation in necrotizing enterocolitis:Pathogenesis and therapeutic implications

AIM:To establish the roles of lipopolysaccharide (LPS)/CD14/toll-like receptor 4 (TLR4)-mediated inflammation in a rat model of human necrotizing enterocolitis (NEC).METHODS: Six pairs of intestinal samples from human NEC were collected before and after recovery for histological and molecular analysis of inflammatory cytokines and signaling components. In the rat NEC model, we isolated 10-cm jejunum segments and divided them into six groups (n=6) for sham operation, treatment with LPS, bowel distension, combined bowel distension and LPS stimulation, and two therapeutic groups. The potential eff icacy of a recombinant CD18 peptide and a monoclonal CD14 antibody was evaluated in the latter two groups. The serum and tissue levels of several inflammatory mediators were quantified by real-time polymerase chain reaction, ELISA and immunoblotting.RESULTS: Human acute phase NEC tissues displayed significant increases (P<0.05) in levels of TLR4, CD14, myeloid differentiation protein (MD)-2, tumor necrosis factor (TNF)-α and nuclear factor-κB when compared to those after recovery. The histological and inflammatory picture of human NEC was reproduced in rats that were treated with combined bowel distension and LPS, but not in the sham-operated and other control rats. Serum levels of interleukin-6 and TNF-α were also elevated. The NEC pathology was attenuated by treating the NEC rats with a monoclonal CD14 antibody or an LPS-neutralizing peptide.CONCLUSION:LPS and distension are required to produce the histological and inflammatory features of NEC. A potential treatment option is blocking LPS activation and leukocyte infi ltration.

补益气血祛瘀通络针刺法治疗中风疗效观察

中风后的康复是医学上的一大难题。临床上多采取营养神经细胞、改善血液循环、抗血栓以及中医药治疗。而针刺疗法是中医的一大特色,也是颇具疗效的手段之一。2009-07—2009-10,我们以补益气血、祛瘀通络为治则,采用针刺疗法治疗中风30例,结果如下。

Multi-detector computed tomography in the diagnosis and management of acute aortic syndromes

Acute aortic syndrome(AAS) is a spectrum of conditions, which may ultimately progress to potentially life-threatening aortic rupture. This syndrome encompasses aortic dissection(AD), intramural haematoma, penetrating atherosclerotic ulcer and unstable thoracic aortic aneurysms. Multi-detector CT(MDCT) is crucial for the diagnosis of AAS, especially in the emergency setting due to its speed, accuracy and ready availability. This review attends to the value of appropriate imaging protocols in obtaining good quality images that can permit a confident diagnosis of AAS. AD is the most commonly encountered AAS and also the one with maximum potential to cause catastrophic outcome if not diagnosed and managed promptly. Hence, this review briefly addresses certain relevant clinical perspectives on this condition. Differentiating the false from the true lumen in AD is often essential; a spectrum of CT findings, e.g., "beak sign", aortic "cobwebs" that allows such differentiation have been described with explicit illustrations. The value of non enhanced CT scans, especially useful in the diagnosis of an intramural hematoma has also been illustrated. Overlap in the clinical and imaging features of the various conditions presenting as AAS is not unusual. However, on most instances MDCT enables the rightdiagnosis. On select occasions MRI or trans-esophageal echocardiography may be required as a problem solving tool.

Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

Recent advances in diagnostic upper endoscopy

BACKGROUND Esophageo-gastro-duodenoscopy(EGD)is an important procedure used for detection and diagnosis of esophago-gastric lesions.There exists no consensus on the technique of examination.AIM To identify recent advances in diagnostic EGDs to improve diagnostic yield.METHODS We queried the PubMed database for relevant articles published between January 2001 and August 2019 as well as hand searched references from recently published endoscopy guidelines.Keywords used included free text and MeSH terms addressing quality indicators and technological innovations in EGDs.Factors affecting diagnostic yield and EGD quality were identified and divided into the follow segments:Pre endoscopy preparation,sedation,examination schema,examination time,routine biopsy,image enhanced endoscopy and future developments.RESULTS We identified 120 relevant abstracts of which we utilized 67 of these studies in our review.Adequate pre-endoscopy preparation with simethicone and pronase increases gastric visibility.Proper sedation,especially with propofol,increases patient satisfaction after procedure and may improve detection of superficial gastrointestinal lesions.There is a movement towards mandatory picture documentation during EGD as well as dedicating sufficient time for examination improves diagnostic yield.The use of image enhanced endoscopy and magnifying endoscopy improves detection of squamous cell carcinoma and gastric neoplasm.The magnifying endoscopy simple diagnostic algorithm is useful for diagnosis of early gastric cancer.CONCLUSION There is a steady momentum in the past decade towards improving diagnostic yield,quality and reporting in EGDs.Other interesting innovations,such as Raman spectroscopy,endocytoscopy and artificial intelligence may have widespread endoscopic applications in the near future.

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Liver cancer is the fifth and seventh most common cause of cancer in men and women,respectively.Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma(HCC).Based on the current understanding,this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC.Furthermore,we will discuss the role of dickkopfs(DKKs)in regulating Wnt/β-catenin signalling,which is poorly understood and understudied.DKKs are a family of secreted proteins that comprise at least four members,namely DKK1-DKK4,which act as inhibitors of Wnt/β-catenin signalling.Nevertheless,not all members antagonize Wnt/β-catenin signalling.Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis.Because of the important oncogenic roles,there are an increasing number of therapeutic molecules targetingβ-catenin and the Wnt/β-catenin pathway for potential therapy of HCC.