Language：English   Publisher：John Wiley & Sons Australia, Ltd  

小腸カプセル内視鏡(CE)画像読影を補助するためのモデリング問題について検討するデータセットおよび対象検出CE人工知能(AI)モデルの作成を試みた。2014年9月から2021年6月までの間に施行した523回の小腸CEから18481枚の画像を抽出した。23033病変の12320枚の画像に対して注解を行い、6161枚の正常画像と組み合わせてデータセットとして、その特徴を解析した。このデータセットに基づいてYOLO v5を用いた対象検出AIモデルを作成し、その検証を行った。データセットで用いた注解項目は12種類で、同一画像に対して複数の注解項目を適用した。1396枚の画像を用いてAIモデルを検証し、全12種類の注解項目の感度は91%で、1375画像が真陽性、659画像が偽陽性、120画像が偽陰性であった。各注解項目のうち、最も感度が高かったのは97%で、受信者動作特性曲線下面積は0.98であったが、注解項目により診断能は異なっていた。以上より、YOLO v5を用いた小腸CEにおける対象検出AIモデルは効果的かつ理解が容易な読影補助となる可能性があることが示唆された。

Language：English  

DOI： 10.1002/deo2.258

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PubMed

Language：English   Publisher：The Japanese Society of Internal Medicine  

<p><b>Objective </b>T helper (Th) cells play a central role in the pathogenesis of ulcerative colitis (UC). The present study analyzed the changes in circulating T cells by administration of ustekinumab (UST), an interleukin-12/23p40 antibody. </p><p><b>Methods </b>CD4 T cells were isolated from peripheral blood at 0 and 8 weeks after UST treatment, and we analyzed the proportion of CD4 T cells by flow cytometry. Clinical information and laboratory data were obtained at 0, 8, and 16 weeks. </p><p><b>Patients </b>We evaluated 13 patients with UC who received UST for the induction of remission between July 2020 and August 2021. </p><p><b>Results </b>The median partial Mayo score improved from 4 (1-7) to 0 (0-6) (p<0.001) with UST. Among serological parameters, albumin concentrations, C-reactive protein concentrations, the sedimentation rate, and leucine-rich alpha 2 glycoprotein concentrations showed significant improvement with UST. A flow cytometric analysis of circulating CD4 T cells showed that the percentage of Th17 cells was significantly decreased by UST treatment in all patients (1.85% to 0.98%, p<0.0001). Th1 cells were significantly increased by UST treatment (9.52% to 10.4%, p<0.05), but Th2 and regulatory T cells were not significantly different. The high-Th17 subgroup had a significantly better partial Mayo score than the low-Th17 subgroup at 16 weeks after UST treatment (0 vs. 1, p=0.028). </p><p><b>Conclusion </b>Treatment with UST decreases circulating Th17 cells, suggesting that this change may be related to the anti-inflammatory effect of UC. </p>

DOI： 10.2169/internalmedicine.1724-23

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CiNii Research

Language：English   Publisher：(一社)日本内科学会  

2020年7月～2021年8月に寛解導入目的でウステキヌマブ(UST)が投与された潰瘍性大腸炎(UC)患者13例(男性3例、女性10例、中央値42歳)を対象に、循環T細胞分画の変化を評価した。UST治療の0週目と8週目に末梢血からCD4 T細胞を分離し、フローサイトメトリーによりCD4 T細胞率を解析した。UST治療により、部分的Mayoスコア中央値が有意に改善し(4→0)、血清パラメータのうちアルブミン値、C反応性タンパク質値、沈降速度、ロイシンリッチα2グリコプロテイン値が有意に改善した。循環CD4 T細胞のフローサイトメトリー解析では、全患者でUST治療によりヘルパーT(Th)17細胞率が有意に低下し、Th1細胞率が有意に上昇したが、Th2細胞率と制御性T細胞率には有意な変化を認めなかった。治療開始前のTh17細胞率が2%超の患者は2%未満の患者に比べて16週時の部分的Mayoスコアが有意に良好であった(0 vs 1)。UC患者において、UST治療により循環Th17細胞が減少することが示された。

Language：English   Publisher：Journal of Gastroenterology  

DOI： 10.1007/s00535-023-02064-w

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Language：English   Publisher：Laboratory Investigation  

Acute kidney injury (AKI) is a complex clinical syndrome with a rapid decrease in renal function caused by several different etiologies, including sepsis, ischemia, and the administration of nephrotoxic drugs. Tubular arginase 2 (ARG2), an arginine-metabolic enzyme, is a potential therapeutic target for AKI, but it has not been confirmed under various AKI conditions. The aim of this study was to investigate ARG2 as a therapeutic target for cisplatin-induced AKI. Cisplatin-treated mice with a genetic deficiency in Arg2 had significant amelioration of renal dysfunction, characterized by decreased acute tubular damage and apoptosis. In contrast, cisplatin-induced tubular toxicity was not ameliorated in proximal tubule cells derived from Arg2-deficient mice. Immunohistochemical analysis demonstrated the increased infiltration of ARG2-positive macrophages in kidneys damaged by cisplatin. Importantly, cisplatin-treated Arg2 knockout mice exhibited a significant reduction in kidney inflammation, characterized by the decreased infiltration of inflammatory macrophages and reduced gene expression of interleukin (IL)-6 and IL-1β. The secretion of IL-6 and IL-1β induced by lipopolysaccharides was decreased in bone marrow–derived macrophages isolated from Arg2-deficient mice. Furthermore, the lipopolysaccharide-induced elevation of mitochondrial membrane potential and production of reactive oxygen species were reduced in bone marrow–derived macrophages lacking Arg2. These findings indicate that ARG2 promotes the inflammatory responses of macrophages through mitochondrial reactive oxygen species, resulting in the exacerbation of AKI. Therefore, targeting ARG2 in macrophages may constitute a promising therapeutic approach for AKI.

DOI： 10.1016/j.labinv.2023.100227

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PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

青黛の潰瘍性大腸炎への効果から、フェロトーシスと潰瘍性大腸炎発症との関連について解析した。遺伝子解析では、青黛治療により潰瘍性大腸炎患者の粘膜における抗酸化遺伝子の上昇が観察された。in vitro分析では、NRF2関連遺伝子発現が青黛によって上方制御された。青黛処理によって細胞のフェロトーシスに対する耐性が得られた。メタボロミクス分析では、青黛によって還元型グルタチオンの上昇が示唆された。青黛による治療により、直腸でCYP1A1とGPX4の蛋白質発現が上昇した。青黛の主成分のインジルビンとインディゴはフェロトーシスを阻害した。青黛で治療している潰瘍性大腸炎患者の直腸粘膜で、インジルビンが検出された。青黛による腸管上皮でのフェロトーシス抑制が潰瘍性大腸炎の治療の標的であり、青黛の主要な活性成分はインジルビンと考えられた。

Language：English   Publisher：Journal of Gastroenterology  

Background: Ferroptosis, a type of programmed cell death triggered by oxidative stress, was suspected to play a role in ulcerative colitis. Indigo naturalis is highly effective against ulcerative colitis, but its mechanism is unclear. This study found that indigo naturalis treatment suppressed ferroptosis. Methods: We analyzed 770 mRNA expressions of patients with ulcerative colitis. Suppression of ferroptosis by indigo naturalis treatment was shown using a cell death assay. Malondialdehyde levels and reactive oxygen species were analyzed in CaCo-2 cells treated with indigo naturalis. Glutathione metabolism was shown by metabolomic analysis. Extraction of the ingredients indigo naturalis from the rectal mucosa was performed using liquid chromatograph—mass spectrometry. Results: Gene expression profiling showed that indigo naturalis treatment increased antioxidant genes in the mucosa of patients with ulcerative colitis. In vitro analysis showed that nuclear factor erythroid-2-related factor 2-related antioxidant gene expression was upregulated by indigo naturalis. Indigo naturalis treatment rendered cells resistant to ferroptosis. Metabolomic analysis suggested that an increase in reduced glutathione by indigo naturalis. The protein expression of CYP1A1 and GPX4 was increased in the rectum by treatment with indigo naturalis. The main ingredients of indigo naturalis, indirubin and indigo inhibited ferroptosis. Indirubin was detected in the rectal mucosa of patients with ulcerative colitis who were treated with indigo naturalis. Conclusions: Suppression of ferroptosis by indigo naturalis in the intestinal epithelium could be therapeutic target for ulcerative colitis. The main active ingredient of indigo naturalis may be indirubin.

DOI： 10.1007/s00535-023-02016-4

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Language：English   Publisher：Communications Biology  

Kidney metabolism may be greatly altered in chronic kidney disease. Here we report that arginine metabolism is the most altered in unilateral ureteral obstruction (UUO)-induced fibrosis of the kidneys in metabolomic analysis. Spermidine is the most increased metabolite of arginine. In human glomerulonephritis, the amount of spermidine shown by immunostaining is associated with the amount of fibrosis. In human proximal tubule cells, spermidine induces nuclear factor erythroid 2-related factor 2 (Nrf2). Subsequently, fibrotic signals, such as transforming growth factor β1 secretion, collagen 1 mRNA, and oxidative stress, represented by a decrease in the mitochondrial membrane potential is suppressed by spermidine. UUO kidneys of Arg2 knockout mice show less spermidine and significantly exacerbated fibrosis compared with wild-type mice. Nrf2 activation is reduced in Arg2 knockout UUO kidneys. Spermidine treatment prevents significant fibrotic progression in Arg2 knockout mice. Spermidine is increased in kidney fibrosis, but further increases in spermidine may reduce fibrosis.

DOI： 10.1038/s42003-023-05057-w

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PubMed

Publisher：株式会社医学書院  

DOI： 10.11477/mf.1403203120

CiNii Research

Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞患者は50歳代,男性.20XX年8月より心窩部痛,嘔気,体重減少が出現し,当院へ紹介となった.上部消化管X線造影検査では前庭部から胃体部に辺縁の毛羽立ちと粗そうな粘膜像を認め,EGDでは前庭部から胃体部に不整形のびらんや潰瘍が多発していた.当初は胃MALTリンパ腫を疑ったが,風俗店の利用歴と梅毒血清反応陽性であったため胃生検組織の抗T. pallidum抗体染色を行い,胃梅毒と診断した.ペニシリン,アモキシシリンによる駆梅療法を行った結果,速やかに軽快した.近年,梅毒感染症の増加が報告されており,消化器領域の日常診療でも胃梅毒に注意すべきである.

Language：Japanese   Publisher：(一社)日本消化器内視鏡学会  

クエン酸マグネシウム(Mg)製剤による大腸内視鏡前処置後に著明な高Mg血症を生じた2例を経験した.両症例とも前処置前には腎障害を認めず,大腸癌による腸管切除歴を有していた.発症時,症例1は直腸吻合部付近の便塊貯留による糞便性腸閉塞を,症例2はS状結腸に吻合部狭窄による通過障害を認めていた.それぞれ全身管理のもとで用手摘便とバルーン拡張にて閉塞を解除することで病状の改善が得られた.潜在的に腸管通過障害を有する被験者では,腎機能に関わらずMg製剤を用いた前処置による高Mg血症の出現に十分注意する必要があると考えられた.(著者抄録)

Language：Japanese   Publisher：Japan Gastroenterological Endoscopy Society  

<p>Two cases of extreme hypermagnesemia occurred after administration of bowel preparation with magnesium citrate for colonoscopy. Neither patient had renal dysfunction but both had a history of bowel resection for treatment of colorectal cancer. Each patient presented with bowel obstruction secondary to fecal impaction at the rectal anastomosis or severe anastomotic stricture at the sigmoid colon. The hypermagnesemia improved in each with the successful release of the bowel obstruction by digital disimpaction or balloon dilation under systemic management. In a patient with a possible intestinal obstruction, the risk of hypermagnesemia incidence with bowel preparation with magnesium products should be considered regardless of renal function.</p>

DOI： 10.11280/gee.64.1564

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