1.Tryptophan Metabolites in Irritable Bowel Syndrome: An Overnight Time-course Study
Robert L BURR ; Haiwei GU ; Kevin CAIN ; Danijel DJUKOVIC ; Xinyu ZHANG ; Claire HAN ; Nini CALLAN ; Daniel RAFTERY ; Margaret HEITKEMPER
Journal of Neurogastroenterology and Motility 2019;25(4):551-562
BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) often report poor sleep quality. Whether poor sleep is associated with tryptophan (Trp) metabolites is unknown. We compared serum Trp metabolites in women with IBS and healthy controls (HCs) using targeted liquid chromatography mass spectrometry (LC-MS)-based profiling. In IBS only, we explored whether Trp metabolites are associated with IBS symptoms and subjective and objective sleep indices, serum cortisol, plasma adrenocorticotropic hormone (ACTH), and cortisol/ACTH levels. METHODS: Blood samples were obtained every 80 minutes in 21 HCs and 38 IBS subjects following an anticipation-of-public-speaking stressor during a sleep laboratory protocol. Subjects completed symptom diaries for 28 days. Adjacent values of metabolites were averaged to represent 4 time-periods: awake, early sleep, mid-sleep, and mid-to-late sleep. Thirteen of 20 targeted Trp metabolites were identified. RESULTS: Ten of 13 Trp metabolites decreased across the night, while nicotinamide increased in both groups. A MANOVA omnibus test performed after principal component analysis showed a significant difference in these 13 principal component (P = 0.014) between groups. Compared to HCs, nicotinamide levels were higher and indole-3-lactic acid levels lower in the IBS group. Melatonin and indole-3-acetic acid levels were associated with several subjective/objective sleep measures; decreased stool consistency/frequency and abdominal pain were positively associated with melatonin and serotonin in the IBS group. The kynurenine and kynurenic acid were associated with ACTH (positively) and cortisol/ACTH (negatively). CONCLUSIONS: Nighttime Trp metabolites may provide clues to poor sleep and stress with IBS. Further study of the mechanism of metabolite action is warranted.
Abdominal Pain
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Adrenocorticotropic Hormone
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Chromatography, Liquid
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Female
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Humans
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Hydrocortisone
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Irritable Bowel Syndrome
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Kynurenic Acid
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Kynurenine
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Mass Spectrometry
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Melatonin
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Niacinamide
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Plasma
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Principal Component Analysis
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Serotonin
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Tryptophan
2.Prospective comparison of hybrid capture 2 and SPF₁₀-LiPA for carcinogenic human papillomavirus detection and risk prediction of cervical cancer: a population-based cohort study in China.
Li DONG ; Rui mei FENG ; Li ZHANG ; Xiao qian XU ; Xue lian ZHAO ; Margaret Zhuoer WANG ; You lin QIAO ; Fang hui ZHAO
Journal of Gynecologic Oncology 2017;28(5):e66-
OBJECTIVE: To investigate the extent of the cross-reactivity of hybrid capture 2 (HC2) assay and evaluate the potential effect of cross-reactivity on the long-term risk for cervical cancer and precancers. METHODS: Based on the Shanxi Province Cervical Cancer Screening Study-I (SPOCCS-I) cohort from 2005 to 2014 in Shanxi, China, SPF₁₀-line probe assay (LiPA) was performed in all 598 HC2 positive and 300 random-selected HC2 negative cervical specimens. Ten-year cumulative incidence rate (CIR) of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) of these two tests was evaluated using Kaplan-Meier methods. Possible human papillomavirus (HPV) types to be cross-reacted by HC2 were also analyzed. RESULTS: The overall agreement between HC2 and SPF₁₀-LiPA for detecting carcinogenic HPV was 73.27%. The highest 10-year cumulative risk of CIN2+ was observed in both HC2 positive and LiPA-carcinogenic HPV positive women (25.70%; 95% confidence interval [CI]=23.55%–27.91%), followed by HC2 positive but LiPA-non-carcinogenic HPV positive women (9.97%; 95% CI=8.57%–11.50%), HC2 negative but LiPA-carcinogenic HPV positive (2.56%; 95% CI=2.44%–2.70%) and HC2 positive but LiPA-HPV negative (1.85%; 95% CI=1.78%–1.92%) women. The proportion of cross-reactivity of HC2 with untargeted carcinogenic types was 8.9%, most of which were attributable to HPV26, 73, 82, 69, 71, 53, 11, 43, and 54. CONCLUSION: The noticeable high risk of CIN2+ in women infected with cross-reacted non-carcinogenic HPV and low risk in those with miss-to-detective carcinogenic HPV supported an overall good clinical performance of HC2 for a general cervical cancer screening.
Cervical Intraepithelial Neoplasia
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China*
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Cohort Studies*
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Female
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Humans*
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Incidence
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Mass Screening
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Prospective Studies*
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Uterine Cervical Neoplasms*
3.Current evidence for endolymphatic sac surgery in the treatment of Meniere's disease: a systematic review.
Ming Yann LIM ; Margaret ZHANG ; Heng Wai YUEN ; Jern-Lin LEONG
Singapore medical journal 2015;56(11):593-598
This paper aims to identify emerging evidence for endolymphatic sac surgery (ESS) in the treatment of Meniere's disease since the landmark study by Thomsen et al, published in 1998 (conducted from 1981 to 1989). Using the MEDLINE database (PubMed), a systematic review of the literature published from January 1990 to June 2014 was performed. We included all English-language, peer-reviewed randomised controlled trials (RCTs) and controlled studies. Single-arm cohort studies were included if the sample size was ≥ 90 with a response rate > 60%. Altogether, 11 studies fulfilled our inclusion criteria; one was an RCT, two were controlled trials and eight were single-arm cohort studies. There currently exists a low level of evidence for the use of ESS in the treatment of Meniere's disease. Further studies, in particular RCTs and/or controlled studies, are required to fully evaluate this modality. However, there are difficulties in designing a valid placebo and achieving adequate blinding of observers and investigators.
Endolymphatic Sac
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surgery
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Humans
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Meniere Disease
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surgery
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Otologic Surgical Procedures
;
methods
4.Targeting tumor-associated macrophages by anti-tumor Chinese materia medica.
Wei-Ling PU ; Li-Kang SUN ; Xiu-Mei GAO ; Curzio RÜEGG ; Muriel CUENDET ; Micheal O HOTTIGER ; Kun ZHOU ; Lin MIAO ; Yun-Sha ZHANG ; Margaret GEBAUER
Chinese journal of integrative medicine 2017;23(10):723-732
Tumor-associated macrophages (TAMs) play a key role in all stages of tumorigenesis and tumor progression. TAMs secrete different kinds of cytokines, chemokines, and enzymes to affect the progression, metastasis, and resistance to therapy depending on their state of reprogramming. Therapeutic benefit in targeting TAMs suggests that macrophages are attractive targets for cancer treatment. Chinese materia medica (CMM) is an important approach for treating cancer in China and in the Asian region. According to the theory of Chinese medicine (CM) and its practice, some prescriptions of CM regulate the body's internal environment possibly including the remodeling the tumor microenvironment (TME). Here we briefly summarize the pivotal effects of TAMs in shaping the TME and promoting tumorigenesis, invasion, metastasis and immunosuppression. Furthermore, we illustrate the effects and mechanisms of CMM targeting TAMs in antitumor therapy. Finally, we reveal the CMM's dual-regulatory and multi-targeting functions on regulating TAMs, and hopefully, provide the theoretical basis for CMM clinical practice related to cancer therapy.