Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer:a randomized phase Ⅲ ARTIST trial

The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.

Quadruple primary malignancy patient with survival time more than 20 years

Multiple primary carcinoma (MPC) is defined as two or more carcinomas without subordinate relationship detected in the same or other organs of an individual patient. The diagnosis of MPC must comply with the following standards: each of the tumors must present a definite picture of malignancy, each tumor must be histologically distinct, and the probability of one being a metastasis of the other must be excluded. MPC often occurs in the digestive system, but its pathogenesis remains unclear involving genetic susceptibility, tumor immunity and iatrogenic factors, including radiotherapy and chemotherapy. Most MPC patients are double primary malignancy; the occurrence of quadruple primary malignancy is below 0.1%. Here we present a rare case of quadruple primary malignancy involving the small intestine, descending colon, renal pelvis and pancreas. Due to its rarity, the relevant literature is also reviewed. In general, the incidence of MPC is rising, so prevention, early diagnosis and treatment will become necessary and important. Therefore, further research should focus on the etiology and mechanism of MPC.

Transvaginal cholecystectomy vs conventional laparoscopic cholecystectomy for gallbladder disease:A meta-analysis

AIM:To compare the results of transvaginal cholecystectomy(TVC) and conventional laparoscopic cholecystectomy(CLC) for gallbladder disease.METHODS:We performed a literature search of Pub Med,EMBASE,Ovid,Web of Science,Cochrane Library,Google Scholar,Meta Register of Controlled Trials,Chinese Medical Journal database and Wanfang Data for trials comparing outcomes between TVC and CLC.Data were extracted by two authors.Mean difference (MD), standardized mean difference(SMD),odds ratios and risk rate with 95%CIs were calculated using fixed- or random-effects models.Statistical heterogeneity was evaluated with the χ2 test.The fixed-effects model was used in the absence of statistically significant heterogeneity.The randomeffects model was chosen when heterogeneity was found.RESULTS:There were 730 patients in nine controlled clinical trials.No significant difference was found regarding demographic characteristics(P > 0.5),including anesthetic risk score,age,body mass index,and abdominal surgical history between the TVC and CLC groups.Both groups had similar mortality,morbidity,and return to work after surgery.Patients in the TVC group had a lower pain score on postoperative day 1(SMD:-0.957,95%CI:-1.488 to-0.426,P < 0.001),needed less postoperative analgesic medication(SMD:-0.574,95%CI:-0.807 to-0.341,P < 0.001) and stayed for a shorter time in hospital(MD:-1.004 d,95%CI:-1.779 to 0.228,P = 0.011),but had longer operative time(MD:17.307 min,95%CI:6.789 to 27.826,P = 0.001).TVC had no significant influence on postoperative sexual function and quality of life.Better cosmetic results and satisfaction were achieved in the TVC group.CONCLUSION:TVC is safe and effective for gallbladder disease.However,vaginal injury might occur,and further trials are needed to compare TVC with CLC.

Interaction models of CYP1A1, GSTMl polymorphisms and tobacco smoking in intestinal gastric cancer

AIM： To explore the interaction models of the cytochrome P-450 （CYP） 1A1 Valvariant and glutathione S-transferase （GST） M1 null polymorphisms with tobacco smoking in the occurrence of intestinal gastric cancer. METHODS： A community-based case-control study was conducted in Yangzhong. Subjects included 114 intestinal types of gastric cancer with endoscopic and pathological diagnosis during January 1997 and December 1998, and 693 controls selected from their spouse, siblings or siblingsin-law who had no history of digestive system cancer. Logistic regression was used to estimate the interaction models. RESULTS： The frequency of the CYPIA1 Valvariant allele in cases did not differ from that in controls. The OR of GSTM1 null genotype was 2.0 （95% confidence interval [95%CI]： 1.2-3.1, P〈0.01）. It showed a significant type 2 form of interaction model when both CYPIA1 Valvariant allele and former tobacco smoking existed （i.e., among the multiplicative effects, the disease risk is increased by the tobacco exposure alone but not by the CYPIA1 variant alone）. The interaction index y was 2.8, and OReg （95%CI） was 5.0 （1.9-13.4）. GSTM1 null genctype and former tobacco smoking were significant in a type 4 interaction model （i.e., the disease risk is increased by GSTM1 null genotype or tobacco exposure alone among the multiplicative effects）. The interaction index y and OReg （95%CI） were 3.4 and 8.4 （3.4-20.9）, respectively.CONCLUSION： Different interaction models of CYPIA1 Valvariant allele and GSTM1 null genotype with tobacco smoking will contribute to understanding carcinogenic mechanism, but there is a need to further investigate in larger scale studies.

Microbiota regulation in constipation and colorectal cancer

The relevance of constipation to the development and progression of colorectal cancer(CRC)is currently a controversial issue.Studies have shown that changes in the composition of the gut microbiota,a condition known as ecological imbalance,are correlated with an increasing number of common human diseases,including CRC and constipation.CRC is the second leading cause of cancerrelated deaths worldwide,and constipation has been receiving widespread attention as a risk factor for CRC.Early colonoscopy screening of constipated patients,with regular follow-ups and timely intervention,can help detect early intestinal lesions and reduce the risks of developing colorectal polyps and CRC.As an important regulator of the intestinal microenvironment,the gut microbiota plays a critical role in the onset and progression of CRC.An increasing amount of evidence supports the thought that gut microbial composition and function are key determinants of CRC development and progression,with alterations inducing changes in the expression of host genes,metabolic regulation,and local and systemic immunological responses.Furthermore,constipation greatly affects the composition of the gut microbiota,which in turn influences the susceptibility to intestinal diseases such as CRC.However,the crosstalk between the gut microbiota,constipation,and CRC is still unclear.

Zero-shot Fine-grained Classification by Deep Feature Learning with Semantics

Fine-grained image classification, which aims to distinguish images with subtle distinctions, is a challenging task for two main reasons: lack of sufficient training data for every class and difficulty in learning discriminative features for representation. In this paper, to address the two issues, we propose a two-phase framework for recognizing images from unseen fine-grained classes, i.e., zeroshot fine-grained classification. In the first feature learning phase, we finetune deep convolutional neural networks using hierarchical semantic structure among fine-grained classes to extract discriminative deep visual features. Meanwhile, a domain adaptation structure is induced into deep convolutional neural networks to avoid domain shift from training data to test data. In the second label inference phase, a semantic directed graph is constructed over attributes of fine-grained classes. Based on this graph, we develop a label propagation algorithm to infer the labels of images in the unseen classes. Experimental results on two benchmark datasets demonstrate that our model outperforms the state-of-the-art zero-shot learning models. In addition, the features obtained by our feature learning model also yield significant gains when they are used by other zero-shot learning models, which shows the flexility of our model in zero-shot finegrained classification.

In-situ Corrosion Characterization of API X80 Steel and Its Corresponding HAZ Microstructures in an Acidic Environment

During heat treatment processing, microstructures of heat affected zone （HAZ） were formed in X80 pipe- line steel. After observation by optical microscopy, scanning electron microscopy and transmission electron microsco- py, microstructure of the as-received X80 steel was confirmed to be acicular ferrite, while the microstructures of quenched, normalized and annealed X80 steels were lath bainite, granular ferrite and quasi-polygonal ferrite, respec- tively. After immersion in the simulated acidic soil solution for 48 h, corrosion rates of these four steels were deter- mined by mass loss measurements and corrosion products were examined by Raman spectroscopy and X-ray photoe lectron spectroscopy. Scanning vibrating electrode technique was used to characterize the micro-galvanic corrosion be- haviors of the synthetic bimetallic electrodes which were formed by coupling each of the simulated HAZ microstruc- tures with the as-received steel in direct physical and electric contact. It is demonstrated that the as-received steel acts as cathode in the as-received/quenched and as-received/normalized couples, while the annealed steel acts as cathode when coupling with the as received steel. The distinction of current density between the galvanic couples reduces with prolonging the immersion time.

Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer,a comparison with GEMOX regimen

Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX(mFOLFIRINOX)and gemcitabine plus oxaliplatin(GEMOX)as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.Methods:The data of patients with unresectable locally advanced or metastatic GBC,who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine,were retrieved.This retrospective study evaluated the clinical characteristics,survival outcomes and adverse events.Results:A total of 44 patients(n=25 in mFOLFIRINOX,n=19 in GEMOX)were included.There were no significant differences between groups in baseline characteristics.The median progression free survival(mPFS)was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group[P=0.021;hazard ratio(HR),0.499;95%CI,0.266 to 0.937].The median overall survival(mOS)was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group(P=0.019;HR,0.471;95%CI,0.239 to 0.929).Disease control rate(DCR)was 76.0%in the mFOLFIRINOX group and 47.4%in the GEMOX group(P=0.051).The rate of grade 3-4 adverse events was 48%in the mFOLFIRINOX group and 36.8%in the GEMOX group(P=0.459).The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group,while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.Conclusions:mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC,and the results need to be further verified by prospective clinical studies.

Chloride channels are involved in sperm motility and are downregulated in spermatozoa from patients with asthenozoospermia

Human spermatozoa encounter an osmotic decrease from 330 to 290 mOsm I-z when passing through the female reproductive tract. We aimed to evaluate the role of chloride channels in volume regulation and sperm motility from patients with asthenozoospermia. Spermatozoa were purified using Percoll density gradients. Sperm volume was measured as the forward scatter signal using flow cytometry. Sperm motility was analyzed using computer-aided sperm analysis （CASA）. When transferred from an isotonic solution （330 mOsm I-z） to a hypotonic solution （290 mOsm I-Z）, cell volume was not changed in spermatozoa from normozoospermic men; but increased in those from asthenozoospermic samples. The addition of the chloride channel blockers, 4,4＇-diisothiocyanatostilbene-2,2＇- isulfonic acid （DIDS） or 5-nitro-2-（3-phenylpropylamino） benzoic acid （NPPB） to the hypotonic solution caused the normal spermatozoa to swell but did not increase the volume of those from the asthenozoospermic semen. DIDS and NPPB decreased sperm motility in both sets of semen samples. The inhibitory effect of NPPB on normal sperm motility was much stronger than on spermatozoa from the asthenozoospermic samples. Both sperm types expressed CIC-3 chloride channels, but the expression levels in the asthenozoospermic samples were much lower, especially in the neck and mid-piece areas. Spermatozoa from men with asthenozoospermia demonstrated lower volume regulating capacity, mobility, and CIC-3 expression levels （especially in the neck） than did normal spermatozoa. Thus, chloride channels play important roles in the regulation of sperm volume and motility and are downregulated in cases of asthenozoospermia.

Nonlinear Dimensionality Reduction by Local Orthogonality Preserving Alignment

We present a new manifold learning algorithm called Local Orthogonality Preserving Alignment （LOPA）. Our algorithm is inspired by the Local Tangent Space Alignment （LTSA） method that aims to align multiple local neighborhoods into a global coordinate system using affine transformations. However, LTSA often fails to preserve original geometric quantities such as distances and angles. Although an iterative alignment procedure for preserving orthogonality was suggested by the authors of LTSA, neither the corresponding initialization nor the experiments were given. Procrustes Subspaces Alignment （PSA） implements the orthogonality preserving idea by estimating each rotation transformation separately with simulated annealing. However, the optimization in PSA is complicated and multiple separated local rotations may produce globally contradictive results. To address these difficulties, we first use the pseudo-inverse trick of LTSA to represent each local orthogonal transformation with the unified global coordinates. Second the orthogonality constraints are relaxed to be an instance of semi-definite programming （SDP）. Finally a two-step iterative procedure is employed to further reduce the errors in orthogonal constraints. Extensive experiments products, and neighborhoods of the original datasets. In that of PSA and comparable to that of state-of-the-art significantly faster than that of PSA, MVU and MVE. show that LOPA can faithfully preserve distances, angles, inner comparison, the embedding performance of LOPA is better than algorithms like MVU and MVE, while the runtime of LOPA is

Reactive poly(divinyl benzene-co-maleic anhydride) nanoparticles:Preparation and characterization

Polymeric nanoparticles（NPs）have drawn great interest in the past few years due to their potential applications in the felds of biomedical and optical technologies.However,it is still a challenge to prepare functional polymeric NPs,especially for particle diameters smaller than 50 nm.In this work,we demonstrate a one-pot method to fabricate reactive poly（divinyl benzene-co-maleic anhydride）NPs（PDVBMAH NPs）through a self-stable precipitation polymerization process.The size and morphology of these PDVBMAH NPs were characterized in detail by scanning electronic microscopy,and their chemical structure was determined by IR.The results showed that these NPs were highly cross-linked and their diameter was about 30 nm with narrow distribution.Additionally,the DVB and MAH endow the NPs with reactive surface anhydride and pendant vinyl groups,and these particles could be further functionalized through reaction of these groups.A plausible pathway was proposed for the formation of PDVBMAH NPs.

Passivation Behavior of 2507 Super Duplex Stainless Steel in Hot Concentrated Seawater:Influence of Temperature and Seawater Concentration

The electrochemical behavior and passivation properties of 2507 super duplex stainless steel(SDSS)in the hot concentrated seawater with different concentrations at different temperatures are characterized by electrochemical methods and X-ray photoelectron spectroscopy.The passive film formed on 2507 SDSS belongs to n-type semiconductor and mainly composed of hydroxides and oxides of Fe and Cr under all circumstances.The protectiveness of the passive film decreases with the increase in temperature mainly because of the increase in defect density in the passive film.The corrosion resistance of 2507 decreases with the increase in seawater concentration,and the critical pitting temperature also decreases.

Correction

Correction to:Zero-shot Fine-grained Classification by Deep Feature Learning with Semantics DOI:10.1007/s11633-019-1177-8 Authors:Ao-Xue Li,Ke-Xin Zhang,Li-Wei Wang The article Zero-shot Fine-grained Classification by Deep Feature Learning with Semantics written by Ao-Xue Li,Ke-Xin Zhang and Li-Wei Wang,was originally published on vol.16,no.5 of International Journal of Automation and Computing without Open Access.After publication,the authors decided to opt for Open Choice and to make the article an Open Access publication.

Behçet Disease with Generalized Polymorphous Cutaneous Lesions:A Case Report

Introduction:Behçet disease is a chronic multisystem vasculitis disease,however generalized polymorphous cutaneous lesions are uncommon.Here,we reported a case of Behçet disease with multiple parts of the body and complex lesions,which may lead to misjudging in clinical diagnosis.Case report:A 69-year-old man presented with a seven-year history of recurrent generalized polymorphous mucocutaneous lesions(erythematous papules,nodules,ulcers,and necrosis)over his entire body,and the lesions had been painful for the past three years.Based on the past medical history,clinical presentation,histological examination excluded other diseases,and the 2014-amended International Criteria for Behget disease,the patient had a score of 6 points and was diagnosed as Behçet disease.Discussion:The common clinical feature in patients with Behçet syndrome is the presence of recurrent and usually painful mucocutaneous ulcers.Other clinical manifestations of this disorder are more variable among different patients.A diagnosis of generalized polymorphous cutaneous lesions should remain on the list of differential diagnosis of Behçet disease after excluding other diseases.Conclusion:The mucocutaneous lesions of Behçet disease are often preceded by other manifestations,and timely diagnosis may benefit early treatment and prognosis.