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Stimuli-evoked NOergic molecules and neuropeptides at acupuncture points and the gracile nucleus contribute to signal transduction of propagated sensation along the meridian through the dorsal medulla-thalamic pathways

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Journal of Integrative Medicine 2024年第5期22卷 515-522页

作者： Sheng-xing Ma Lundquist institute for biomedical Innovation Harbor-University of California at Los Angeles (UCLA) Medical Center department of obstetrics and gynecology David Geffen School of Medicine at UCLA and Harbor-UCLA Medical Center

Numerous studies from different international groups have demonstrated that sensations can be propagated along acupuncture channel pathways. The propagated sensation along the channel pathway(PSCP)can be elicited by electroacupuncture(EA), transcutaneous electrical nerve stimulation(TENS), manual acupuncture(MA), and heat applied to distal acupuncture points(acupoints). Nitric oxide(NO) levels were reported to be elevated in the gracile nucleus and skin regions near to the EA sites, with higher levels at acupoints associated with an enhanced expression of NO synthase and transient receptor potential vanilloid type 1. The stimuli, EA, MA, TENS, and heat, have been used to elicit axonal reflexes, which increase local release of NO and neuropeptides such as calcitonin gene related peptide. Furthermore, the sensation of PSCP along the body surface occurs only ipsilaterally to the stimulated acupoints in various human studies, which does not support the involvement of the spinal-thalamic pathway, which would involve cross over transmission of the signals. The gracile nucleus receives ascending input from the sciatic nerve and responds to somatosensory stimulation mainly on the ipsilateral side via the dorsal column pathway. EA at Zusanli(ST36) increases NO release and expression of NO synthase mainly in the ipsilateral side of the gracile nucleus, while the cardiovascular effects and analgesic responses to EA at ST36 are changed by influences of L-arginine-derived NO synthesis in the ipsilateral gracile nucleus in rats. The stimuli-induced release of NOergic molecules and neuropeptides exist high levels in the acupoints, which contain rich neuronal components and blood vessels. Enhanced NOergic molecules at acupoints cause axon reflexes during the stimuli, which elevate cutaneous blood flow. Elevated NOergic molecules and local blood flow may spread over acupoints one after another along the meridian lines differing from nerve pathways following the stimuli to induce PSC

关键词： Axon reflex Biophysical approaches Calcitonin related polypeptide Dorsal funiculus tract Meridian system Nitric oxide

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Nitric Oxide Signaling Molecules in Acupoints:Toward Mechanisms of Acupuncture

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Chinese Journal of Integrative Medicine 2017年第11期23卷 812-815页

作者： MA Sheng-xing los angeles biomedical research institute at harbor-uclamedical center and department of obstetrics and gynecology David Geffen School of MedicineUniversity of California at Los Angeles and Harbor-UCLA Medical CenterTorranceCA(90502)United States

Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupoints and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide（NO） level is elevated in the acupoints/meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx–（total nitrite and nitrate） and cyclic guanosine monophosphate（c GMP） concentrations are consistently increased over skin acupoints compared to non-meridian control regions（NMCR） in humans. Dermal microdialysis in humans showed that NO-c GMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture（EA）. Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints,

关键词： acupoint nitric oxide electroacupuncture manual acupuncture reinforcement methods

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Low Electrical Resistance Properties of Acupoints:Roles of NOergic Signaling Molecules and Neuropeptides in Skin Electrical Conductance

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Chinese Journal of Integrative Medicine 2021年第8期27卷 563-569页

作者： MA Sheng-xing Lundquist institute for biomedical Innovation at harbor University of California at los angeles(UCLA)Medical center and department of obstetrics and gynecology David Geffen School of Medicine at UCLA and Harbor-UCLA Medical CenterTorranceCA 90502United States

Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical *** devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness,skin thickness,size of the sensing electrode,pressure applied on the electrode,interelectrode distance,room temperature,and *** studies have identified that blood vessels,hair follicles,and nervous components are enhanced in the meridians/acupoints,which represent areas of potentially high neuronal *** evidence shows that nitric oxide(NO)concentrations are enhanced in skin acupoints/meridians.L-arginine-derived NO synthesis modifies skin norepinephrine(NE)synthesis/release in acupoints/meridians,and NO-NE activations play an important role in mediating the skin conductance responses to electrical *** signaling molecules interact with gap junction and transient receptor potential vanilloid *** studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain *** body conditions caused considerable changes in skin conductance or impedance at *** systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field,the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components,and NOergic signaling molecules and neuropeptides involved in the skin low resistance at *** increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system,which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.

关键词： acupuncture points skin electric resistance nitric oxide norepinephrine transient receptor potential vanilloid type-1 neuropeptides

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Intervertebral disc degeneration is rescued by TGFβ/BMP signaling modulation in an ex vivo flamin B mouse model

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Bone research 2022年第3期10卷 524-535页

作者： Jennifer Zieba Kimberly N.Forlenza Kelly Heard Jorge H.Martin Michaela Bosakova Daniel H.Cohn Stephen P.Robertson Pavel Krejci Deborah Krakow department of Orthopedic Surgery Los AngelesCA 90095USA department of Biology Faculty of MedicineMasaryk University62500 BrnoCzech Republic International Clinical research center St.Anne’s University Hospital65691 BrnoCzech Republic institute of Animal Physiology and Genetics Czech Academy of Sciences60200 BrnoCzech Republic department of Molecular Cell and Developmental Biology University of CaliforniaLos AngelesLos AngelesCA 90095USA department of Women’s and Children’s Health Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand department of Human Genetics Los AngelesCA 90095USA department of obstetrics and gynecology Los AngelesCA 90095USA department of Pediatrics David Geffen School of Medicine at University of CaliforniaLos AngelesLos AngelesCA 90095USA

Spondylocarpotarsal syndrome(SCT) is a rare musculoskeletal disorder characterized by short stature and vertebral, carpal, and tarsal fusions resulting from biallelic nonsense mutations in the gene encoding filamin B(FLNB). Utilizing a FLNB knockout mouse,we showed that the vertebral fusions in SCT evolved from intervertebral disc(IVD) degeneration and ossification of the annulus fibrosus(AF), eventually leading to full trabecular bone formation. This resulted from alterations in the TGFβ/BMP signaling pathway that included increased canonical TGFβ and noncanonical BMP signaling. In this study, the role of FLNB in the TGFβ/BMP pathway was elucidated using in vitro, in vivo, and ex vivo treatment methodologies. The data demonstrated that FLNB interacts with inhibitory Smads 6 and 7(i-Smads) to regulate TGFβ/BMP signaling and that loss of FLNB produces increased TGFβ receptor activity and decreased Smad 1 ubiquitination. Through the use of small molecule inhibitors in an ex vivo spine model, TGFβ/BMP signaling was modulated to design a targeted treatment for SCT and disc degeneration. Inhibition of canonical and noncanonical TGFβ/BMP pathway activity restored Flnb-/-IVD morphology. These most effective improvements resulted from specific inhibition of TGFβand p38 signaling activation. FLNB acts as a bridge for TGFβ/BMP signaling crosstalk through i-Smads and is key for the critical balance in TGFβ/BMP signaling that maintains the IVD. These findings further our understanding of IVD biology and reveal new molecular targets for disc degeneration as well as congenital vertebral fusion disorders.

关键词： TGFβ vivo BMP treatment

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Comprehensive overview of genotype distribution and prevalence of human papillomavirus in cervical lesions

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gynecology and obstetrics Clinical Medicine 2024年第1期4卷 37-47页

作者： Yuhong Ye Terrel Jones Tiannan Wang Xianxu Zeng Yang Liu Chengquan Zhao department of Pathology the First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina department of Pathology Magee-Womens HospitalUniversity of Pittsburgh Medical CenterPittsburghPennsylvaniaUSA department of Pathology University of Southern CaliforniaLos AngelesCaliforniaUSA department of Pathology The Third Affliated Hospital of Zhengzhou UniversityZhengzhouHenanChina departments of Medicine and Bioengineering University of PittsburghPittsburghPennsylvaniaUSA department of Bioengineering University of Illinois Urbana-ChampaignUrbanaIllinoisUSA

Acrosscervical squamousandgl and ular lesions,a spectrum of human papillomavirus(HPV)genotypes has been *** review aims to provide a comprehensive summary detailing the distribution and profile of HPV genotypes detected in cervical lesions,leveraging insights from histological and cytological ***-risk HPV(HR-HPV)genotypes exhibit varying degrees of oncogenic potential,with HPV16 and HPV18 identified as the most prevalent and oncogenic *** of HR-HPVgenotypes varies among different degrees of the cervical lesions and varies between squamous andglandular ***16 is predominantly associated with severe lesions(precancers and carcinomas),while HPV18 demonstrates a significantly higher prevalence in endocervical as compared with squamous *** distribution of HR-HPV in severe squamous lesions is complex,involving many HR-HPV genotypes in addition to HPV16,while the distribution of HR-HPV genotypes in endocervical glandular lesions is mainly limited in HPV18 and *** datasets from China have identified the three mostcommon HR-HPVgenotypes in this population as stratified by diagnostic category:HPV52,HPV16,HPV58 in histologically negative cases and cervical intraepithelial neoplasia 1(CIN1);HPV16,HPV52,HPV58 in CIN2/3;HPV16,HPV58,HPV52 or HPV18 in squamous cell carcinoma(SCC);HPV16,HPV18 and HPV52 in endocervical adenocarcinoma in situ(AIS),invasiveadenocarcinoma,as well asmixedsquamous and glandular ***33 is the fourth most common HPVtype in CIN2/3and SCC,whileHPV45occursmore commonly in AIS and adenocarcinoma,compared with squamous *** prevalence and distribution of multiple HR-HPV coinfections vary across different cervical *** clinical significance and pathogenesis of these multiple HR-HPV infections remain uncertain,although recent two large studies demonstrate that multiple HR-HPV infections are not associated with cumulatively higher risk of high-grade cervical squamous lesiondeve

关键词： cervical lesions prevalence

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Women’s preconception health patterns in traditional Chinese medicine as a predictor of fertility outcomes

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Journal of Integrative Medicine 2020年第3期18卷 222-228页

作者： Xia-qiu Wu Wendy Satmary Jin Peng Ka-kit Hui School of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053Zhejiang ProvinceChina center for East-West Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCA 90024USA department of obstetrics&gynecology David Geffen School of MedicineUniversity of CaliforniaLos AngelesCA 90024USA institute of Basic research in Clinical Medicine China Academy of Chinese Medical SciencesBeijing 100700China

Objective: To examine the association between traditional Chinese medicine(TCM), preconception health patterns and fertility ***: A community-based prospective cohort study was conducted in China. A total of 3012 newly married women who were willing to conceive within 2 years were enrolled in the study and took National Free Prepregnancy Checkups(NFPC). A reliably structured self-rating scale was used to measure the TCM preconception health patterns of the enrolled women. A 3-year follow-up was conducted to obtain the fertility outcomes, including pregnancy rate, time to pregnancy, spontaneous miscarriage and newborn status. Statistical analyses were conducted using Chi-square or Fisher’s exact tests, logistic regression models, general linear models and the Cox proportional hazard ***: The fertility outcomes showed no statistic correlations to the terms of NFPC in this *** a half of the women(46.66%) had unhealthy patterns. Women with qi & blood-deficiency(odds ratio [OR] = 35.19, 95% confidence interval [CI] = 1.55–801.15) or qi-stagnation(OR = 4.55, 95% CI =0.90–23.06) pattern took a longer time to get pregnant, and those with qi-stagnation(OR = 2.05, 95% CI =1.1–3.82) or yang-deficiency(OR = 1.91, 95% CI = 1.12–3.25) pattern had a higher risk of spontaneous ***: Three unhealthy TCM patterns during the preconception period might be risk factors for low fecundity or poor pregnancy outcomes. The TCM preconception pattern identification may provide a convenient and effective way to screen for potential pregnancy risks beyond the NFPC. Further, appropriate interventions based on the TCM preconception health patterns are needed to improve quality in women’s fecundability and birth outcomes.

关键词： Preconception care Fertility Traditional Chinese medicine Women’s health Risk assessment

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Umbilical cord artery-derived perivascular stem cells for treatment of ovarian failure through CD146 signaling

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Signal Transduction and Targeted Therapy 2022年第8期7卷 2694-2697页

作者： Lu Xu Yanjun Yang Lingling Zhang Guijun Yan Shiyuan Li Yifan Li Yali Hu Lijun Ding Bruno Péault Haixiang Sun center for Reproductive Medicine and obstetrics and gynecology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China center for Molecular Reproductive Medicine Nanjing UniversityNanjing 210093China department of obstetrics and gynecology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China NHC Key Lab of Reproduction Regulation Shanghai Institute of Planned Parenthood ResearchPharmacy SchoolFudan UniversityShanghai 200032China Clinical center for Stem Cell research the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Orthopedic Hospital research center and Broad Stem Cell center David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210008China

Dear Editor,Chemotherapy-induced ovarian failure significantly diminishes ovarian blood flow,ovarian size,and follicular *** plays a vital role in repairing ovarian damage.1 Perivascular stem cells(PSCs),known as mural cells covering the vasculature,are essential for blood vessel formation and postulated as progenitors of mesenchymal stem cells(MSCs).2,3 We previously established umbilical cord artery-derived PSCs(UCA-PSCs)and Wharton’s jelly-derived MSCs(WJ-MSCs)and UCAPSCs display optimal angiogenic capacity in vitro.4 Therefore,we explored the angiogenesis and pro-angiogenesis mechanisms of UCA-PSCs and provided them as an efficient treatment strategy for ovarian failure.

关键词： CD146 treatment artery damage

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Enhanced physician prompts in prenatal electronic medical records impact documentation on smoking cessation

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Open Journal of obstetrics and gynecology 2013年第10期3卷 717-721页

作者： Lisa D. Levine Jitsen Chang Irwin R. Merkatz Peter S. Bernstein department of obstetrics and gynecology and Women’s Health Albert Einstein College of Medicine Montefiore Medical Center Bronx USA department of obstetrics and gynecology Cedar Sinai Medical Center Los Angeles USA department of obstetrics and gynecology Maternal and Child Health Research Program University of Pennsylvania Perelman School of Medicine Philadelphia USA

Objective: Smoking cessation during pregnancy is a modifiable intervention that can improve maternal and neonatal outcomes. Encouraging smoking cessation is an assessed measure of the Meaningful Use incentives to ensure best practices with the increased use of the electronic medical record (EMR). Physician EMR prompts have been used shown to be successful with preventive care but there is a paucity of data evaluating prompts within obstetrics. The objective of this study is to determine the effectiveness of enhanced smoking cessation prompts in a prenatal EMR. Methods: A retrospective cohort study of an enhanced smoking cessation prompting system within our prenatal EMR was performed. Pregnant women who reported tobacco use at first prenatal visit were included. The number of times a smoking cessation method was offered and documented, the number of documented attempts at smoking cessation, and the final number of cigarettes smoked were compared pre and post the enhancement of the smoking cessation prompting system. Results: 95 patients were included (48 pre-enhancement;47 post-enhancement). Post-enhancement, the documentation of smoking cessation method offered increased (0 vs. 1, p = 0.03) and documentation of smoking cessation attempts increased (1 vs. 2, p = 0.006). There was no change in the final number of cigarettes smoked (p = 0.9). Conclusions: Enhanced prompting systems increase documentation related to smoking cessation with no change in number of cigarettes smoked. In the era of Meaningful Use guidelines which focus on documentation in the EMR, continued research must be done to assure that software enhancements and improved documentation truly result in improved patient care.

关键词： Prenatal EMR Physician Prompts Smoking Cessation

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Type III interferon-induced CBFβinhibits HBV replication by hijacking HBx

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Cellular & Molecular Immunology 2019年第4期16卷 357-366页

作者： Fengchao Xu Hongxiao Song Qingfei Xiao Na Li Hong Zhang Genhong Cheng Guangyun Tan department of Immunology Institute of Translational MedicineThe First Hospital of Jilin UniversityChangchunJilin 130061China department of Nephrology The First HospitalJilin UniversityChangchunJilin 130021China department of obstetrics The First Hospital of Jilin UniversityChangchunJilin 130021China Phase I Clinical research center The First Hospital of Jilin UniversityJilin 130021China department of Microbiology Immunology and Molecular GeneticsUniversity of CaliforniaLos AngelesCA 90095USA center of Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005 Suzhou institute of Systems Medicine SuzhouJiangsu 215123China

Hepatitis B virus(HBV)and its associated chronic infection remain serious health threats ***,there is still no impactful approach for clinical treatment of hepatitis B ***,developing a better understanding of the interactions between HBV and its host is particularly *** infection has been reported to induce type-III but not type-I or type-II interferon(IFN).In this study,we identified CBFβ,an HIV enhancer,as an HBV restriction factor that is specifically induced by type-III IFN in the early stages of HBV ***-III IFN-induced IL-10 played an important role in the production of CBFβ.Interestingly,the interaction between CBFβ-and HBV-encoded regulatory protein X(HBx)enhanced the stability of CBFβ,but notably blocked HBx-mediated promotion of HBV ***βexpression was lower in HBV patients than in healthy persons,and the addition of serum from HBV patients inhibited CBFβexpression in HepG2 *** the contrary,HBV via HBsAg inhibited type-III IFN-induced CBFβexpression and decreased the anti-HBV activity of type-III IFN,suggesting that HBV inhibits antiviral interferon-stimulated gene(ISG)expression and induces IFN ***,our results demonstrate that type-III IFN-triggered and IL-10-induced CBFβare crucial factors for inhibiting HBV replication,and the HBx–CBFβ–HBsAg axis reveals a new molecular mechanism of interaction between HBV and its hosts.

关键词： inhibited interferon CBF

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Serum semaphorin 4C as a diagnostic biomarker in breast cancer:A multicenter retrospective study

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Cancer Communications 2021年第12期41卷 1373-1386页

作者： Ya Wang Long Qiao Jie Yang Xiong Li Yaqi Duan Jiahao Liu Shaoqi Chen Huayi Li Dan Liu Tian Fang Jingjing Ma Xiaoting Li Fei Ye Junxiang Wan Juncheng Wei Qin Xu Ensong Guo Ping Jin Mingfu Wu Lin Zhang Yun Xia Yaqun Wu Jun Shao Yaojun Feng Qing Zhang Zongyuan Yang Gang Chen Qinghua Zhang Xingrui Li Shixuan Wang Junbo Hu Xiaoyun Wang Mona P.Tan Kazuaki Takabe Beihua Kong Qifeng Yang Ding Ma Qinglei Gao department of obstetrics and gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China Cancer Biology research center(Key Laboratory of the Ministry of Education) Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China department of obstetrics and gynecology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450000P.R.China department of gynecology and obstetrics The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430014P.R.China department of Pathology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China department of obstetrics and gynecology Wuhan Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China Leonard Davis School of Gerontology University of Southern CaliforniaLos AngelesCalifornia 90001USA department of Thyroid and Breast Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China department of Breast Surgery Hubei Cancer HospitalWuhanHubei 430079P.R.China department of gynecology and obstetrics Qilu Hospital of Shandong UniversityJinanShandong 250012P.R.China Yidu Cloud(Beijing)Technology Co. Beijing 100000P.R.China MammoCare The Breast Clinic&SurgerySingapore 329563Singapore department of Surgery and the Massey Cancer Centre Virginia Commonwealth University School of MedicineRichmondVirginia 23298USA department of Breast Surgery Qilu Hospital of Shandong UniversityNo.107Jinan Culture RoadJinanShandong 250012P.R.China

Background:To date,there is no approved blood-based biomarker for breast cancer ***,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic ***:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer *** cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid *** cancer patients who underwent mass excision prior to modified radical mastectomy were also *** hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast *** endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and ***-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM *** was no restriction on disease stage for ***:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy ***,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation *** AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),*** SEMA4C levels significantly decreased after surgery,and the reduction was more str

关键词： breast cancer semaphorin 4C serum biomarker diagnosis early detection ductal carcinoma in situ pan-cancer analysis enzyme-linked immunosorbent assay

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