Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.

Textbook Outcome as a measure of surgical quality assessment and prognosis in gastric neuroendocrine carcinoma:A large multicenter sample analysis

Objective:Quality assurance is crucial for oncological surgical treatment assessment.For rare diseases,singlequality indicators are not enough.We aim to develop a comprehensive and reproducible measurement,called the"Textbook Outcome"(TO),to assess the quality of surgical treatment and prognosis of gastric neuroendocrine carcinoma(G-NEC)patients.Methods:Data from patients with primary diagnosed G-NEC included in 24 high-volume Chinese hospitals from October 2005 to September 2018 were analyzed.TO included receiving a curative resection,≥15 lymph nodes examined,no severe postoperative complications,hospital stay≤21 d,and no hospital readmission≤30 d after discharge.Hospital variation in TO was analyzed using a case mix-adjusted funnel plot.Prognostic factors of survival and risk factors for non-Textbook Outcome(non-TO)were analyzed using Cox and logistic models,respectively.Results:TO was achieved in 56.6%of 860 G-NEC patients.TO patients had better overall survival(OS),disease-free survival(DFS),and recurrence-free survival(RFS)than non-TO patients(P<0.05).Moreover,TO patients accounted for 60.3%of patients without recurrence.Multivariate Cox analysis revealed non-TO as an independent risk factor for OS,DFS,and RFS of G-NEC patients(P<0.05).Increasing TO rates were associated with improved OS for G-NEC patients,but not hospital volume.Multivariate logistic regression revealed that nonlower tumors,open surgery,and>200 mL blood loss were independent risk factors for non-TO patients(P<0.05).Conclusions:TO is strongly associated with multicenter surgical quality and prognosis for G-NEC patients.Factors predicting non-TO are identified,which may help guide strategies to optimize G-NEC outcomes.

Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions

Alternative splicing(AS)is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs(mRNAs),extremely improving the richness of transcriptome and proteome.Both mammal hosts and pathogens require AS to maintain their life activities,and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS.Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA(named cis-splicing).Parasites also use spliceosomes to splice,but this splicing can occur among different mRNAs(named trans-splicing).Bacteria and viruses directly hijack the host’s splicing machinery to accomplish this process.Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators(abundance,modification,distribution,movement speed,and conformation),which further radiate to alterations in the global splicing profiles.Genes with splicing changes are enriched in immune-,growth-,or metabolism-related pathways,highlighting approaches through which hosts crosstalk with pathogens.Based on these infection-specific regulators or AS events,several targeted agents have been developed to fight against pathogens.Here,we summarized recent findings in the field of infection-related splicing,including splicing mechanisms of pathogens and hosts,splicing regulation and aberrant AS events,as well as emerging targeted drugs.We aimed to systemically decode host–pathogen interactions from a perspective of splicing.We further discussed the current strategies of drug development,detection methods,analysis algorithms,and database construction,facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.

Magnetic-field-induced electronic instability of Weyl-like fermions in compressed black phosphorus

Revealing the role of Coulomb interaction in topological semimetals with Dirac/Weyl-like band dispersion shapes a new frontier in condensed matter physics.Topological node-line semimetals(TNLSMs),anticipated as a fertile ground for exploring electronic correlation effects due to the anisotropy associated with their node-line structure,have recently attracted considerable attention.In this study,we report an experimental observation for correlation effects in TNLSMs realized by black phosphorus(BP)under hydrostatic pressure.By performing a combination of nuclear magnetic resonance measurements and band calculations on compressed BP,a magnetic-field-induced electronic instability of Weyl-like fermions is identified under an external magnetic field parallel to the so-called nodal ring in the reciprocal space.Anomalous spin fluctuations serving as the fingerprint of electronic instability are observed at low temperatures,and they are observed to maximize at approximately 1.0 GPa.This study presents compressed BP as a realistic material platform for exploring the rich physics in strongly coupled Weyl-like fermions.

From tuberculosis bedside to bench:UBE2B splicing as a potential biomarker and its regulatory mechanism

Alternative splicing(AS)is an important approach for pathogens and hosts to remodel transcriptome.However,tuberculosis(TB)-related AS has not been sufficiently explored.Here we presented the first landscape of TB-related AS by long-read sequencing,and screened four AS events(S100A8-intron1-retention intron,RPS20-exon1-alternaitve promoter,KIF13B-exon4-skipping exon(SE)and UBE2B-exon7-SE)as potential biomarkers in an in-house cohort-1.The validations in an in-house cohort-2(2274 samples)and public datasets(1557 samples)indicated that the latter three AS events are potential promising biomarkers for TB diagnosis,but not for TB progression and prognosis.The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers.Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance.The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression.After heat-killed mycobacterium tuberculosis stimulation,231 ubiquitination proteins in macrophages were differentially expressed,and most of them are apoptosis-related proteins.Taken together,we depicted a global TB-associated splicing profile,developed TB-related AS biomarkers,demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing,offering a novel insight into the pathophysiology of TB.

A precision medicine approach to managing 2019 novel coronavirus pneumonia

In December 2019,several patients with pneumonia of an unknown cause were detected in Wuhan,China.On 7 January 2020,the causal organism was identified as a new coronavirus,later named as the 2019 novel coronavirus(2019-nCoV).Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus.As of 29 January 2020,the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries.It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact.This finding has caused a great concern about the prevention of illness spread.The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections,making it difficult to diagnose.Given that the virus has a strong ability to spread between individuals,it is of top priority to identify potential or suspected patients as soon as possible—or the virus may cause a serious pandemic.Therefore,a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus.In this article,we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu,China.

Orbital ordering and fluctuations in a kagome superconductor CsV_(3)Sb_(5)

Recently,competing electronic instabilities,including superconductivity and density-wave-like order,have been discovered in vanadium-based kagome metals AV_(3)Sb_(5)(A=K,Rb,Cs)with a nontrivial band topology.This finding stimulates considerable interest to study the interplay of these competing electronic orders and possible exotic excitations in the superconducting state.Here,we performed51V and133Cs nuclear magnetic resonance(NMR)measurements on a CsV_(3)Sb_(5)single crystal to clarify the nature of density-wave-like transition in these kagome superconductors.A first-order structural transition is unambiguously revealed below T_(s)~94 K by observing the sudden splitting of Knight shift in^(51)V NMR spectrum.Moreover,combined with^(133)Cs NMR spectrum,the present result confirms a three-dimensional structural modulation.By further analyzing the anisotropy of Knight shift and 1/T_(1)T at^(51)V nuclei,we proposed that the orbital order is the primary electronic order induced by the firstorder structural transition,which is supported by further analysis on electric field gradient at^(51)V nuclei.In addition,the evidence for possible orbital fluctuations is also revealed above T_(s).The present work sheds light on a rich orbital physics in kagome superconductors AV_(3)Sb_(5).

Identification of Abnormal 51 CTA/CTG Expansion as Probably the Shortest Pathogenic Allele for Spinocerebellar Ataxia-8 in China

Spinocerebellar ataxias （SCAs） are a group of genetic disorders characterized by slowly progressive incoordina- tion of gait and are often associated with poor coordination of the hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. The genetic forms of ataxia are diagnosed by family history, physical examina- tion, neuroimaging, and molecular genetic testing. At present, 36 SCA subtypes including 27 pathogenic genes have been identified [1]. Different subtypes of SCAs have clear distribution differences among ethnic populations, and SCA8 is an infrequent entity worldwide, which has mostly been reported in Japanese, but has never been reported in Chinese [2]. SCAB involves bidirectional expression based on the total number of both the （CTA）n and （CTG）n expansion transcripts in ATXN8OS. The pathogenesis of this disorder is complex and the spectrum of clinical presentations is broad. It is predominantly characterized by drawn-out slowness of speech and gait instability, followed by slowly progressive ataxia, with disease onset typically occurring in adulthood [3]. How- ever, the lowest full-penetrance allele for SCA8 onset remains elusive and the current understanding of the phenotypic and genotypic features of SCA8 is limited. Since SCA8 has not yet been reported in the Chinese population and is scantily reported in a small proportion of pedigrees so far, clinical knowledge is still developing. Moreover, the boundary between the normal and patho- genic alleles of SCA8 is uncertain. Here we report the clinical and molecular genetic characteristics of 3 Chinese SCA8 families and have identified 51 CTA/CTG repeats within ATXN8OS, probably the shortest pathogenic allele for SCA8.

Mechanism regulating the inhibition of lung cancer A549 cell proliferation and structural analysis of the polysaccharide Lycium barbarum

The water-soluble polysaccharide LBP-1 was isolated and characterized from Lycium barbarum L.LBP-1 was mainly composed of arabinose,galactose,glucose,xylose,mannose at a molar ratio of 37.53:28.08:14.72:7.83:4.50,respectively.Based on nuclear magnetic resonance(NMR)and methylation analysis,the backbone of LBP-1 was speculated in theα-L-Ara(1→[5-α-L-Ara(1→3)-β-D-Galp-(1→]n→4)-α-D-Galp-(1[→5-α-L-Ara(1]n[→6)-β-D-Galp-(1→4)-β-D-Galp-(1→]n,and the side chains of LBP-1 were in theα-L-Ara(1→3)-β-D-Galp-(1→6 position.These results showed that LBP-1 inhibited the growth of cancer A549 cells through cell cycle arrest and apoptosis,with an IC50 value of 42.5μg/mL.In addition,LBP-1 altered the expression of Cyclin D1,Cyclin D3,and CDK 2,thus blocking the cell cycle in G0/G1 phase,reducing cell migration,and regulating the PI3K/Akt/mTOR signaling pathway to induce apoptosis.

Applications of laboratory findings in the prevention,diagnosis,treatment,and monitoring of COVID-19

The worldwide pandemic of coronavirus disease 2019(COVID-19)presents us with a serious public health crisis.To combat the virus and slow its spread,wider testing is essential.There is a need for more sensitive,specific,and convenient detection methods of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Advanced detection can greatly improve the ability and accuracy of the clinical diagnosis of COVID-19,which is conducive to the early suitable treatment and supports precise prophylaxis.In this article,we combine and present the latest laboratory diagnostic technologies and methods for SARS-CoV-2 to identify the technical characteristics,considerations,biosafety requirements,common problems with testing and interpretation of results,and coping strategies of commonly used testing methods.We highlight the gaps in current diagnostic capacity and propose potential solutions to provide cutting-edge technical support to achieve a more precise diagnosis,treatment,and prevention of COVID-19 and to overcome the difficulties with the normalization of epidemic prevention and control.