Mitigation of N_(2)O emissions in water-saving paddy fields:Evaluating organic fertilizer substitution and microbial mechanisms

Water-saving irrigation strategies can successfully alleviate methane emissions from rice fields,but significantly stimulate nitrous oxide(N_(2)O)emissions because of variations in soil oxygen level and redox potential.However,the relationship linking soil N_(2)O emissions to nitrogen functional genes during various fertilization treatments in water-saving paddy fields has rarely been investigated.Furthermore,the mitigation potential of organic fertilizer substitution on N_(2)O emissions and the microbial mechanism in rice fields must be further elucidated.Our study examined how soil N_(2)O emissions were affected by related functional microorganisms(ammonia-oxidizing archaea(AOA),ammonia-oxidizing bacteria(AOB),nirS,nirK and nosZ)to various fertilization treatments in a rice field in southeast China over two years.In this study,three fertilization regimes were applied to rice cultivation:a no nitrogen(N)(Control),an inorganic N(Ni),and an inorganic N with partial N substitution with organic manure(N_(i)+N_(o)).Over two rice-growing seasons,cumulative N_(2)O emissions averaged 0.47,4.62 and 4.08 kg ha^(−1)for the Control,Ni and N_(i)+N_(o)treatments,respectively.In comparison to the Ni treatment,the N_(i)+N_(o)fertilization regime considerably reduced soil N_(2)O emissions by 11.6%while maintaining rice yield,with a lower N_(2)O emission factor(EF)from fertilizer N of 0.95%.Nitrogen fertilization considerably raised the AOB,nirS,nirK and nosZ gene abundances,in comparison to the Control treatment.Moreover,the substitution of organic manure for inorganic N fertilizer significantly decreased AOB and nirS gene abundances and increased nosZ gene abundance.The AOB responded to N fertilization more sensitively than the AOA.Total N_(2)O emissions significantly correlated positively with AOB and nirS gene abundances while having a negative correlation with nosZ gene abundance and the nosZ/nirS ratio across N-fertilized plots.In summary,we conclude that organic manure substitution for inorganic N fertilizer decreased soil N_(2)O emissions primarily by changing the soil NO_(3)^(−)-N,pH and DOC levels,thus inhibiting the activities of ammonia oxidation in nitrification and nitrite reduction in denitrification,and strengthening N_(2)O reduction in denitrification from water-saving rice paddies.

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal tract.Traditional Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal therapy.The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR action.The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other constituents.NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice.PR also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin loss.PR treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression levels.The addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of PR.These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

Optimal scheduling of a township integrated-energy system using the adjustable heat-electricity ratio model

With the expansion and implementation of rural revitalization strategies,there is a constant need for new energy sources for the construction of new townships.Consequently,integrated energy systems with the interconnection and interaction of multiple energy sources are developing rapidly.Biomass energy,a renewable green energy source with low pollution and wide distribution,has significant application potential in integrated energy systems.Considering the application of biomass energy in townships,this study established an integrated biomass energy system and proposed a model to optimize its operation.Lowest economic cost and highest clean energy utilization rate were considered as the objective functions.In addition,a plan was suggested to adjust the heat-electricity ratio based on the characteristics of the combined heat and power of the biomass.Finally,a simulation analysis conducted for a town in China was discussed,demonstrating that the construction of a township integrated-energy system and the use of biomass can significantly reduce operating costs and improve the energy utilization rate.Moreover,by adjusting the heat-electricity ratio,the economic cost was further reduced by 6.70%,whereas the clean energy utilization rate was increased by 5.14%.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

Partially-Observed Maximum Principle for Backward Stochastic Differential Delay Equations

Dear Editor,This letter investigates a partially-observed optimal control problem for backward stochastic differential delay equations(BSDDEs).By utilizing Girsanov’s theory and convex variational method,we obtain a maximum principle on the assumption that the state equation contains time delay and the control domain is convex.The adjoint processes can be represented as the solutions of certain time-advanced stochastic differential equations in finite-dimensional spaces.Linear backward stochastic differential equation(BSDE)was first introduced by Bismut in[1],while general BSDE was given by Pardoux and Peng[2].Since then,the theory of BSDEs developed rapidly.The corresponding optimal control problems,whose states are driven by BSDEs,have also been widely studied by some authors,see[3]-[5].

Molecular analyses display the increasing diversity of Podostemaceae in China

Podostemaceae(riverweed family),one of the largest aquatic plant families in the world,comprises about 350 species in 51 genera placed in three subfamilies,Podostemoideae,Weddellinoideae,and Tristichoideae(Koi et al.,2022).Most Podostemaceae genera(~38)are monotypic or oligotypic,with a high level of endemism(Koi et al.,2018,2022).Members of Podostemaceae adhere to rocks in fast-flowing rivers,streams,or waterfalls in the subtropics and tropics(Koi et al.,2018).As an adaptation to fastrunning currents,the morphological structure of river-weeds tends to be extremely reduced,including a loss or reduction of primary shoots or roots(Koi and Kato,2007).The vegetative mass of these plants resembles lichens or bryophytes,and are thus known commonly as“dream bryophytes”(Philbrick and Retana,1998).Podostemaceae plants flower when the water level drops during the dry season.In recent years,anthropogenic factors and climate change have severely affected river weed habitats,decreasing populations of these plants.

Research progress in spasmodic torticollis rehabilitation treatment

Spasmodic torticollis(ST)is a focal dystonia that affects adults,causing limited muscle control and impacting daily activities and quality of life.The etiology and curative methods for ST remain unclear.Botulinum toxin is widely used as a firstline treatment,but long-term usage can result in reduced tolerance and adverse effects.Rehabilitation therapy,with its minimal side effects and low potential for harm,holds significant clinical value.This article explores the effectiveness of adjunctive therapies,including exercise therapy,transcranial magnetic stimulation,shockwave therapy,neuromuscular electrical stimulation,vibration therapy,electromyographic biofeedback,and acupuncture,in the treatment of ST.The aim is to provide clinicians with additional treatment options and to discuss the efficacy of rehabilitation therapy for ST.

Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

Oral fruquintinib combined with tegafur-gimeracil-oteracil potassium for advanced colorectal cancer to obtain longer progression-free survival:A case report

BACKGROUND After the failure of second-line standard therapy,effective treatment options for metastatic colorectal cancer are limited,and the duration of remission cannot meet clinical needs.In addition,associated drug toxicity may lead to treatment interruption that may affect patient outcomes.Therefore,more safe,effective and convenient treatments are urgently needed.CASE SUMMARY Here,we describe a patient with advanced colorectal cancer with multiple metastases in both lungs.Oxaliplatin combined with 5-fluorouracil or capecitabine was given as the first-line treatment,and bevacizumab combined with irinotecan was given as the second-line treatment after disease progression.However,treatment was interrupted due to recurrent grade 2 nausea and grade 1 diarrhea.He received targeted therapy with fruquintinib starting on August 26,2020 and responded well for 12 mo.After slow progression of the lung metastases,progression-free survival was again achieved over 13.5 mo by continued treatment of fruquintinib in combination with tegafur-gimeracil-oteracil potassium chemotherapy.Overall treatment duration was more than 25.5 mo.The treatments delayed tumor progression,reduced drug side effects,maintained a good quality of life,and further extended overall survival.CONCLUSION This case report detailed preliminary evidence showing that the combination of fruquintinib with tegafur-gimeracil-oteracil potassium chemotherapy double oral therapy may result in longer progression-free survival in patients with advanced colorectal cancer.

Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence

Metastasis-associated processes are the predominant instigator of fatalities linked to cancer,wherein the pivotal role of circulating tumor cells lies in the resurgence of malignant growth.In recent epochs,exosomes,constituents of the extracellular vesicle cohort,have garnered attention within the field of tumor theranostics owing to their inherent attributes encompassing biocompatibility,modifiability,payload capacity,stability,and therapeutic suitability.Nonetheless,the rudimentary functionalities and limited efficacy of unmodified exosomes curtail their prospective utility.In an effort to surmount these shortcomings,intricate methodologies amalgamating nanotechnology with genetic manipulation,chemotherapy,immunotherapy,and optical intervention present themselves as enhanced avenues to surveil and intercede in tumor metastasis and relapse.This review delves into the manifold techniques currently employed to engineer exosomes,with a specific focus on elucidating the interplay between exosomes and the metastatic cascade,alongside the implementation of tailored exosomes in abating tumor metastasis and recurrence.This review not only advances comprehension of the evolving landscape within this domain but also steers the trajectory of forthcoming investigations.

伴有SORL1基因突变的阿尔茨海默病1例报道

目的:阿尔茨海默病(AD)是一种神经变性疾病,近年来分拣蛋白相关受体基因(SORL1)作为其风险基因越来越得到重视,现将1例伴有SORL1基因突变的早发型阿尔茨海默病(EOAD)进行报道。方法:收集1例伴有SORL1基因突变的AD患者临床资料,包括病史特点、神经系统查体、神经心理学检查、常规检验、MRI、PET-CT及基因检测,并复习相关文献。结果:该患者49岁起病,以记忆力减退为主,之后计算力等各项认知功能持续性下降,伴肌张力增高、运动迟缓,缺乏联带运动等锥体外系症状,日常生活不能自理;头颅MRI显示脑萎缩,以颞叶、海马萎缩为著;基因检测显示SORL1基因43号外显子c.5744A>G杂合突变(p.Y1915C)。结论:本患者发病年龄,临床表现,影像和脑脊液异常,存在SORL1基因突变,诊断符合SORL1基因突变的EOAD,该病例锥体外系症状有助于丰富SORL1突变相关的EOAD临床特征,对临床诊疗工作具有提示作用。

经黏膜下隧道内镜切除术治疗食管固有肌层肿物效果分析

目的通过对比经黏膜下隧道内镜切除术(submucosal tunnelingendoscopicresection,STER)与其他治疗方式在治疗食管固有肌层平滑肌瘤的结果差异,探讨STER的安全性及适应症.方法回顾2012-11-01/2018-03-01期间,因食管固有肌层平滑肌瘤行切除治疗的121名患者,收集并分析其临床特点及治疗结果.结果胸腔镜切除(thoracoscopic enucleation, TE)组与内镜切除(endoscopic resection, ER)组在肿瘤的生长部位和大小、手术时间、整块切除率、患者平均住院日和平均住院费用方面的差异具有统计学意义(P<0.05);STER组与TE组在整块切除率、手术时间、患者平均住院日和费用方面的差异具有统计学意义(P<0.05),尽管STER组肿瘤直径(2-40 mm,平均17.68mm)比TE组肿瘤直径(5-80 mm,平均20.33 mm)小,但差异并无统计学意义(P=0.229);而STER组与内镜黏膜下剥离术(endoscopic submucosal dissection, ESD)组的对比中发现,两组在肿瘤直径、整块切除率和患者住院费用方面的差异具有统计学意义(P<0.05).尽管研究过程中我们发现STER组的整块切除率低于外科组和ESD组,但平均随访22.4 mo(3-60 mo),三个组均未见肿瘤复发及转移.结论 STER是一种安全、有效的内镜下治疗手段,对于≤4cm的食管固有肌层平滑肌瘤,我们推荐优先考虑STER切除.

糖尿病患者白内障术后视功能与术前HbA1c值的相关性研究

目的:探究糖尿病患者白内障术后黄斑区视网膜结构、脉络膜结构及最佳矫正视力与术前HbA1c值的相关性。方法:临床病例对照研究。选择2016-10/2017-12在青岛市市立医院眼科中心符合入组条件的超声乳化白内障患者82例87眼,分为非糖尿病组和糖尿病组。依据术前HbA1c水平,将糖尿病组分为高HbA1c值组(HbA1c>7.0%)和正常HbA1c值组(HbA1c≤7.0%)。其中非糖尿病组(4%≤HbA1c≤6.0%)28例30眼,高HbA1c组28例29眼和正常HbA1c组26例28眼。运用频域光相干断层扫描(SD-OCT)检查各组患者术前1d,术后1d,1wk,1、3mo时黄斑中心凹视网膜厚度(CST)、黄斑总容积(CV)和黄斑中心凹脉络膜厚度(SFCT),采用多因素重复测量方差分析其变化,Pearson相关分析探究其与HbA1c值的相关性;同时比较各组患者术后黄斑水肿(PCME)发生率;进一步分析糖尿病患者HbA1c值与术后最佳矫正视力(CDVA)的关联性。结果:非糖尿病组、高HbA1c组和正常HbA1c组患者白内障术后1wk时CST分别为239.03±11.55、254.38±26.44、247.07±19.51μm,术后1mo时CST分别为241.00±11.15、271.55±61.05、248.64±38.28μm(F=3.001,P=0.048);其中高HbA1c值组和正常HbA1c值组比较有差异(P<0.05),且两组患者术后1wk,1mo时HbA1c值与CST之间在P=0.01水平上呈正相关关系(r术后1wk=0.338,r术后1mo=0.297)。三组患者术后发生PCME分别为0例、5眼(17%)和1眼(4%)。非糖尿病组、高HbA1c组和正常HbA1c组患者术后1wk时CDVA分别为0.07±0.06、0.12±0.10、0.09±0.08,术后1mo时CDVA分别为0.03±0.06、0.11±0.15、0.11±0.09,术后3mo时CDVA分别为0.02±0.04、0.08±0.12、0.06±0.06(F=3.272,P=0.045);其中高HbA1c值组和正常HbA1c值组比较无差异(P>0.05),两组患者HbA1c值与术后1wk,1、3mo(r术后1wk=0.425,r术后1mo=0.235,r术后3mo=0.332)CDVA(LogMAR)在P=0.01水平上两者显著相关且呈正相关关系。三组患者白内障术后CV、SFCT的组间变化趋势大致相同,其变化程度的组间无差异。结论:糖尿病患者术前HbA1c水平与超声乳化白内障术后黄斑区视网膜和脉络膜结构有一定的相关性;术前HbA1c>7.0%的患者术后发生黄斑水肿的风险增加。同时,糖尿病患者术前HbA1c水平与白内障术后最佳矫正视力密切相关;术前HbA1c值越高的患者术后视力提高越欠佳。

胃肠胰神经内分泌肿瘤药物治疗进展

随着胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine tumors,GEP-NETs)发病率的增高,对GEP-NETs的治疗越来越受到关注。根据2010年第4版世界卫生组织(WHO)消化系统肿瘤病理的最新分类方法,将神经内分泌肿瘤(neuroendocrine neoplasms,NENs)分为3级:G1、G2、G3级,其中G1、G2级为神经内分泌瘤(neuroendocrime tumor,NETs),G3级为神经内分泌癌(neuroendocrine carcinoma,NECs)。对于G1、G2级NETs现有的药物治疗方案主要包括生长抑素类似物(somatostatin analogs,SSAs)、靶向治疗、干扰素、化疗,而对于G3级NECs一般以铂类为基础的化疗为主。免疫因素可能是NENs的发病因素之一,现关于NENs免疫治疗的临床试验正在开展。本文将对GEP-NETs的药物治疗进行综述。

糖尿病眼肌麻痹的相关危险因素分析

目的:研究糖尿病眼肌麻痹发生的相关危险因素。方法:回顾性分析2008-06/2017-06就诊于青岛市市立医院眼科的糖尿病眼肌麻痹患者120例120眼的临床资料,根据颅神经受累部位分为动眼神经麻痹组(Ⅲ组,66例)、外展神经麻痹组(Ⅵ组,41例)、复合神经麻痹组(Ⅲ+Ⅵ组,13例)。收集所有患者的临床资料并进行统计分析,筛选糖尿病眼肌麻痹的相关危险因素。结果:年龄、性别、糖尿病病程、糖化血红蛋白(HbA1c)水平、合并糖尿病视网膜病变(DR)和高血压情况与糖尿病眼肌麻痹的发生相关,其中年龄≥45岁,男性,糖尿病病程≥10a,合并DR,HbA1c>7%是糖尿病眼肌麻痹发生的独立危险因素。结论:糖尿病眼肌麻痹的发生与糖尿病患者的年龄、性别、糖尿病病程、是否合并DR及HbA1c水平相关。

Neuroprotective effects of ginsenoside Rb1 on hippocampal neuronal injury and neurite outgrowth

Ginsenoside Rb1 has been reported to exert anti-aging and anti-neurodegenerative effects. In the present study, we investigate whether ginsenoside Rb1 is involved in neurite outgrowth and neuroprotection against damage induced by amyloid beta（25–35） in cultured hippocampal neurons, and explore the underlying mechanisms. Ginsenoside Rb1 significantly increased neurite outgrowth in hippocampal neurons, and increased the expression of phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2. These effects were abrogated by API-2 and PD98059, inhibitors of the signaling proteins Akt and MEK. Additionally, cultured hippocampal neurons were exposed to amyloid beta（25–35） for 30 minutes; ginsenoside Rb1 prevented apoptosis induced by amyloid beta（25–35）, and this effect was blocked by API-2 and PD98059. Furthermore, ginsenoside Rb1 significantly reversed the reduction in phosphorylated-Akt and phosphorylated extracellular signal-regulated kinase 1/2 levels induced by amyloid beta（25–35）, and API-2 neutralized the effect of ginsenoside Rb1. The present results indicate that ginsenoside Rb1 enhances neurite outgrowth and protects against neurotoxicity induced by amyloid beta（25–35） via a mechanism involving Akt and extracellular signal-regulated kinase 1/2 signaling.

Hepatitis C virus NS5A inhibitors and drug resistance mutations

Some direct-acting antiviral agents for hepatitis C virus (HCV), such as telaprevir and boceprevir have been available since 2011. It was reported that HCV NS5A is associated with interferon signaling related to HCV replication and hepatocarcinogenesis. HCV NS5A inhibitors efficiently inhibited HCV replication in vitro. Human studies showed that dual, triple and quad regimens with HCV NS5A inhibitors, such as daclatasvir and ledipasvir, in combination with other direct-acting antiviral agents against other regions of HCV with or without peginterferon/ribavirin, could efficiently inhibit HCV replication according to HCV genotypes. These combinations might be a powerful tool for &#x0201c;difficult-to-treat&#x0201d; HCV-infected patients. &#x0201c;First generation&#x0201d; HCV NS5A inhibitors such as daclatasvir, ledipasvir and ABT-267, which are now in phase III clinical trials, could result in resistance mutations. &#x0201c;Second generation&#x0201d; NS5A inhibitors such as GS-5816, ACH-3102, and MK-8742, have displayed improvements in the genetic barrier while maintaining potency. HCV NS5A inhibitors are safe at low concentrations, which make them attractive for use despite low genetic barriers, although, in fact, HCV NS5A inhibitors should be used with HCV NS3/4A inhibitors, HCV NS5B inhibitors or peginterferon plus ribavirin. This review article describes HCV NS5A inhibitor resistance mutations and recommends that HCV NS5A inhibitors be used in combination regimens potent enough to prevent the emergence of resistant variants.

Regulation of microRNA by hepatitis B virus infection and their possible association with control of innate immunity

Hepatitis B virus(HBV)chronically infects more than350 million people worldwide.HBV causes acute and chronic hepatitis,and is one of the major causes of cirrhosis and hepatocellular carcinoma.There exist complex interactions between HBV and the immune system including adaptive and innate immunity.Tolllike receptors(TLRs)and TLR-signaling pathways are important parts of the innate immune response in HBV infections.It is well known that TLR-ligands could suppress HBV replication and that TLRs play important roles in anti-viral defense.Previous immunological studies demonstrated that HBV e antigen(HBeAg)is more efficient at eliciting T-cell tolerance,including production of specific cytokines IL-2 and interferon gamma,than HBV core antigen.HBeAg downregulates cytokine production in hepatocytes by the inhibition of MAPK or NF-κB activation through the interaction with receptor-interacting serine/threonine protein kinase.MicroRNAs(miRNAs)are also able to regulate various biological processes such as the innate immune response.When the expressions of approximately 1000 miRNAs were compared between human hepatoma cells HepG2 and HepG2.2.15,which could produce HBV virion that infects chimpanzees,using real-time RT-PCR,we observed several different expression levels in miRNAs related to TLRs.Although we and others have shown that HBV modulates the host immune response,several of the miRNAs seem to be involved in the TLR signaling pathways.The possibility that alteration of these miRNAs during HBV infection might play a critical role in innate immunity against HBV infection should be considered.This article is intended to comprehensively review the association between HBV and innate immunity,and to discuss the role of miRNAs in the innate immune response to HBV infection.

Gastrocolic fistula in Crohn’s disease detected by oral agent contrast-enhanced ultrasound: A case report of a novel ultrasound modality

BACKGROUND Fistulas are common complications of Crohn’s disease(CD).Gastrocolic fistulas(GFs)are rare,occult and potentially life-threatening complications.Few cases of GFs have been reported.Oral agent contrast-enhanced ultrasound(OA-CEUS)is a novel technique of ultrasound(US)for gut.Contrast agent made by Chinese yam is taken orally to dilate the lumen of the upper gastrointestinal tract.Thus,the impediment of gas inside gastrointestinal tract is removed and a good acoustic window is provided for gastroin-testinal tract scanning.This paper describes a case of GF secondary to CD detected by OA-CEUS when it was missed by endoscopy and computed tomography(CT).To our knowledge,this is the first report of GF secondary to CD detected by OA-CEUS up to date.CASE SUMMARY A 29-year-old woman with a 6-year history of CD was admitted to our hospital for abdominal pain and diarrhea for 5 months without obvious predisposing causes.Initial gastroscopy failed to show any evidence of lesions.Colonoscopy revealed multiple erosions,mucosal nodularity,linear ulcers and a cobblestone appearance.A CT scan of her abdomen showed a complex multilocular structure adherent to the greater curvature of the stomach in her left lower abdomen,with fluid,gas and significant surrounding inflammation.CT also demonstrated an abdominal abscess,which was later treated with US-guided drainage.Colonoscopy,gastroscopy and CT missed the presence of a GF.OA-CEUS was performed.A contrast agent made from Chinese yam was taken orally to dilate the lumen of the gastrointestinal tract.A good acoustic window was provided for gastrointestinal tract scanning and the impediment of gas inside the gastrointestinal tract was removed.With the aid of the“window”,a canal with hypoechoic wall was identified connecting the greater curvature of stomach to the splenic colon flexure in free sections.We also observed the hyperechoic gas flowing dynamically inside the canal.Thus,a GF was suspected.US is the first imaging modality taking GF into account.At the same time,OA-CEUS identified the site of the fistula and its two orifices.Gastroscopy was performed again,revealing a small ulcer approximately 5 mm in diameter,which was considered as an orifice.On the basis of OA-CEUS and other examinations,the patient was diagnosed with a GF secondary to CD.Then,laparoscopic exploration,partial stomach resection,transverse colostomy and abdominal abscess drainage were performed.The patient recovered uneventfully.CONCLUSION GFs are rare,occult and potentially life-threatening complications in CD.US is one of the first-line modalities to evaluate CD and its complications.OA-CEUS,a novel technique of US for gut,may be helpful in reducing the possibility of a missed diagnosis of GF.

Hepatitis C virus protease inhibitor-resistance mutations: Our experience and review

Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.