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Microbiome subsets determine tumor prognosis and molecular characteristics of clear-cell renal cell carcinoma:a multi-center integrated analysis of microbiome,metabolome,and transcriptome data

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Frontiers of Medicine 2024年第2期18卷 399-402页

作者： Wenjin Chen Xiuwu Pan Wang Zhou da xu Jiaxin Chen Keqin Dong Weijie Chen Brian Rini Xingang Cui Department of Urology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai200092China Department of Urology Third Affiliated Hospital of the Second Military Medical UniversityShanghai201805China Division of Hematology Oncology Vanderbilt University Medical CenterNashvilleTN37232USA

Dear editor,Patients with clear-cell renal cell carcinoma(ccRCC)potentially have a high recurrence rate of more than 40%[1].Patients receive radical or partial nephrectomy,sometimes assisted by targeted therapies or/and immune checkpoint inhibitors(ICIs),to improve overall survival(OS)[2].Large-cohort studies and large-scale human tissue sequencing have provided a series of molecular subtyping methods for precision medicine-based ccRCC risk stratification and therapeutic regimens,such as ClearCode34,the prognostic risk predictor[3],and seven subsets for ICI and angiogenesis blockade outcomes[4].However,these subtyping results are all based on human genomes without including the host microbiota,which may be non-negligible genome components.

关键词： editor negligible characteristics

Nonlinear Extrapolation Estimates of π

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 91-108页

作者： Wen-qing xu Sha-sha Wang da-chuan xu Beijing Institute for Scientific and Engineering Computing Beijing University of TechnologyBeijing100124China Department of Mathematics and Statistics California State UniversityLong BeachCalifornia90840USA Department of Mathematics and Physics Shijiazhuang Tiedao UniversityShijiazhuang050043China

The classical Archimedean approximation of π uses the semiperimeter or area of regular polygons inscribed in or circumscribed about a unit circle in R~2 and it is well-known that by using linear combinations of these basic estimates,modern extrapolation techniques can greatly speed up the approximation process.Similarly,when n vertices are randomly selected on the circle,the semiperimeter and area of the corresponding random inscribed and circumscribing polygons are known to converge to π almost surely as n→∞,and by further applying extrapolation processes,faster convergence rates can also be achieved through similar linear combinations of the semiperimeter and area of these random polygons.In this paper,we further develop nonlinear extrapolation methods for approximating π through certain nonlinear functions of the semiperimeter and area of such polygons.We focus on two types of extrapolation estimates of the forms χ_n=S_n~αA_n~β and Y_n(p)=(αS_n~p+βA_n~p)~(1/p) where α+β=1,p≠0,and Sn and An respectively represents the semiperimeter and area of a random n-gon inscribed in the unit circle in R~2,and Xn may be viewed as the limit of Y_n(p) when p→0.By deriving probabilistic asymptotic expansions with carefully controlled error estimates for Xn and Y_n(p),we show that the choice α=4/3,β=-1/3 minimizes the approximation error in both cases,and their distributions are also asymptotically normal.

关键词： Archimedean polygons random polygons approximations ofπ extrapolation processes asymptotic convergence

From Acupoints to Mylohyoid: Revealing the Neural Circuitry Basis of Electroacupuncture for Dysphagia

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Neuroscience Bulletin 2024年第1期40卷 139-142页

作者： Xiaoli da xuhong Jiang Lihong Li Cenglin xu Zhong Chen Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of Neurology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310003China Department of Acupuncture the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310000China

Acupuncturea representative and historical treatment in traditional Chinese medicine(TCM),has been used to cure diseases for Chinese people in the past centuries.Since the late 1990s,acupuncture has been further accepted worldwide.The World Health Organization(WHO)proposed Clinical Research Specification for acupuncture in 1995 and the US Food and Drug Administration(Fda)approved acupuncture as a complementary and alternative therapy for various kinds of diseases in 1996,with clinical advantages such as convenience and effectiveness[1].Cumulative evidence has proved that acupuncture could produce different degrees of efficacy for treating various kinds of diseases(such as neuropathic pain,migraine,Parkinson's disease et al.)and alleviate symptoms[2-4].However,unlike its evidence-based efficacies.

关键词： medicine(TCM) acupuncture Acupuncture

Cancer organoids:A platform in basic and translational research

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Genes & Diseases 2024年第2期11卷 614-632页

作者： Xin Ma Qin Wang Guozheng Li Hui Li Shouping xu da Pang Department of Breast Surgery Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Sino-Russian Medical Research Center Harbin Medical University Cancer HospitalHarbinHeilongjiang 150081China Heilongjiang Academy of Medical Sciences HarbinHeilongjiang 150086China Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China) College of Pharmacy of Harbin Medical UniversityHarbinHeilongjiang 150086China

An accumulation of previous work has established organoids as good preclinical models of human tumors,facilitating translation from basic research to clinical practice.They are changing the paradigm of preclinical cancer research because they can recapitulate the heterogeneity and pathophysiology of human cancers and more closely approximate the complex tissue environment and structure found in clinical tumors than in vitro cell lines and animal models.However,the potential applications of cancer organoids remain to be comprehensively summarized.In the review,we firstly describe what is currently known about cancer organoid culture and then discuss in depth the basic mechanisms,including tumorigenesis and tumor metastasis,and describe recent advances in patient-derived tumor organoids(PDOs)for drug screening and immunological studies.Finally,the present challenges faced by organoid technology in clinical practice and its prospects are discussed.This review highlights that organoids may offer a novel therapeutic strategy for cancer research.

关键词： Drug assays Immunotherapy Mechanism research Organoids Precision medicine

Satellite glial cells in sensory ganglia play a wider role in chronic pain via multiple mechanisms

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Neural Regeneration Research 2024年第5期19卷 1056-1063页

作者： Xiaoyun Qiu Yuanzhi Yang Xiaoli da Yi Wang Zhong Chen Cenglin xu Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina

Satellite glial cells are unique glial cells that surround the cell body of primary sensory neurons.An increasing body of evidence suggests that in the presence of inflammation and nerve damage,a significant number of satellite glial cells become activated,thus triggering a series of functional changes.This suggests that satellite glial cells are closely related to the occurrence of chronic pain.In this review,we first summarize the morphological structure,molecular markers,and physiological functions of satellite glial cells.Then,we clarify the multiple key roles of satellite glial cells in chronic pain,including gap junction hemichannel Cx43,membrane channel Pannexin1,K channel subunit 4.1,ATP,purinergic P2 receptors,and a series of additional factors and their receptors,including tumor necrosis factor,glutamate,endothelin,and bradykinin.Finally,we propose that future research should focus on the specific sorting of satellite glial cells,and identify genomic differences between physiological and pathological conditions.This review provides an important perspective for clarifying mechanisms underlying the peripheral regulation of chronic pain and will facilitate the formulation of new treatment plans for chronic pain.

关键词： chronic pain primary sensory neurons satellite glial cells sensory ganglia

Associations between remnant cholesterol levels and mortality in patients with diabetes

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World Journal of Diabetes 2024年第4期15卷 712-723页

作者： Deng Pan Lin xu Li-Xiao Zhang da-Zhuo Shi Ming Guo Department of Cardiovascular Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China Graduate School Beijing University of Chinese MedicineBeijing 100020China National Clinical Research Center for Chinese Medicine Cardiology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing 100091China Gynecological Department of Traditional Chinese Medicine China-Japan Friendship HospitalBeijing 100020China

BACKGROUND Dyslipidemia is frequently present in patients with diabetes.The associations of remnant cholesterol and mortality remains unclear in patients with diabetes.AIM To explore the associations of remnant cholesterol with all-cause and cardiovas-cular mortality in patients with diabetes.METHODS This prospective cohort study included 4740 patients with diabetes who par-ticipated in the National Health and Nutrition Examination Survey from 1999 through 2018.Remnant cholesterol was used as the exposure variable,and all-cause and cardiovascular mortality were considered outcome events.Outcome data were obtained from the National Death Index,and all participants were followed from the interview date until death or December 31,2019.Multivariate proportional Cox regression models were used to explore the associations between exposure and outcomes,in which remnant cholesterol was modeled as both a categorical and a continuous variable.Restricted cubic splines(RCSs)were calculated to assess the nonlinearity of associations.Subgroup(stratified by sex,age,body mass index,and duration of diabetes)and a series of sensitivity analyses were performed to evaluate the robustness of the associations.RESULTS During a median follow-up duration of 83 months,1370 all-cause deaths and 389 cardiovascular deaths were documented.Patients with remnant cholesterol levels in the third quartile had a reduced risk of all-cause mortality[hazard ratio(HR)95%confidence interval(CI):0.66(0.52-0.85)];however,when remnant cholesterol was modeled as a continuous variable,it was associated with increased risks of all-cause[HR(95%CI):1.12(1.02-1.21)per SD]and cardiovascular[HR(95%CI):1.16(1.01-1.32),per SD]mortality.The RCS demonstrated nonlinear associations of remnant cholesterol with all-cause and cardiovascular mortality.Subgroup and sensitivity analyses did not reveal significant differences from the above results.CONCLUSION In patients with diabetes,higher remnant cholesterol was associated with increased risks of all-cause and cardiovascul

关键词： Diabetes Remnant cholesterol Mortality Cardiovascular National Health and Nutrition Examination Survey

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance

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中华医学杂志(英文版) 2024年第7期137卷 859-870页

作者： Wang Xianlong Zhao Chuan Lin Jincheng Liu Hongxing Zeng Qiuhong Chen Huadong Wang Ye xu dapeng Chen Wen xu Moping Zhang En Lin da Lin Zhixiong Sanbo Brain Hospital Capital Medical University Beijing 100093 Department of Bioinformatics School of Medical Technology and Engineering Key Laboratory of Medical Bioinformatics Key Laboratory of Ministry of Education for Gastrointestinal Cancer Fujian Medical University Fuzhou Fujian 350122 China Department of Neurosurgery

Background: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively.Results: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/β-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox,P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group (P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB (P = 0.01).Conclusions: ACP comprises three molecular subtypes with disti

关键词： Craniopharyngioma Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf

Recent advances in tip-enhanced Raman spectroscopy probe designs

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Nano Research 2023年第4期16卷 5555-5571页

作者： da xu Boqun Liang Yaodong xu Ming Liu Department of Electrical and Computer Engineering University of California-RiversideRiversideCalifornia 92521USA Materials Science and Engineering program University of California-RiversideRiversideCalifornia 92521USA

Tip-enhanced Raman spectroscopy(TERS)imaging is a super-resolution imaging technique that features the merits of both surface-enhanced Raman spectroscopy(SERS)and scanning probe microscopy(SPM),such as the high chemical sensitivity from the former and the nanoscale spatial resolution from the latter.These advantages make TERS an essential nanospectroscopic characterization technique for chemical analysis,materials science,bio-sensing,etc.TERS probes,the most critical factor determining the TERS imaging quality,are expected to provide a highly confined electromagnetic hotspot with a minimized scattering background for the generation of Raman signals with high spatial resolution.After two decades of development,numerous probe design concepts have been proposed and demonstrated.This review provides a comprehensive overview of the state-of-the-art TERS probe designs,from the working mechanism to the practical performance.We start with reviewing the recent development of TERS configurations and the corresponding working mechanisms,including the SPM platforms,optical excitation/collection techniques,and probe preparation methods.We then review the emerging novel TERS probe designs,including the remote-excitation probes,the waveguide-based nanofocusing probes,the metal-coated nanofocusing probes,the nanowire-assisted selective-coupling probes,and the tapered metal-insulator-metal probes.Our discussion focuses on a few critical aspects,including the surface-plasmon-polariton(SPP)hotspot excitation technique,conversion efficiency,working frequency,and controllability.In the end,we review the latest TERS applications and give a perspective on the future of TERS.

关键词： tip-enhanced Raman spectroscopy plasmonics scanning probe microscopy nanoscale imaging nanophotonics nanofocusing

Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu xu Songrong Ren da Yang Xiaochao Ma Wen Xie Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA Department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor PAPS.The involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been reported.Here,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon cancer.Gut epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)mice.Apc^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory axis.Chondroitin sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal tumorigenesis.In summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin signaling.Chondroitin sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR