Xilei san (XLS), a herbal preparation widely used in China for erosive and ulcerative diseases, has been shown to be effective in ulcerative colitis (UC). The present experiments were conducted to ...assess its efficacy and determine its mechanism of action in a rat model that resembles human UC. The model was induced by adding 4% dextran sulfate sodium (DSS) to the rats’ drinking water for 7 days. XLS was administered daily by retention enema from day 2 to day 7; the rats were sacrificed on day 8. The colon tissues were obtained for further experiments. A histological damage score and the activity of tissue myeloperoxidase were used to evaluate the severity of the colitis. The colonic cytokine levels were detected in a suspension array, and epithelial proliferation was assessed using Ki-67 immunohistochemistry. Intrarectal administration of XLS attenuated the DSS-induced colitis, as evidenced by a reduction in both the histological damage score and myeloperoxidase activity. It also decreased the levels of proinflammatory cytokines, but increased the mucosal repair-related cytokines. In addition, the epithelial Ki-67 expression was upregulated by XLS. These results suggest that XLS attenuates DSS-induced colitis by degrading proinflammatory mediators and promoting mucosal repair. XLS could be a potential topical treatment for human UC.
This study was performed to evaluate surgical outcomes in octogenarian patients undergoing valve surgery. Sixty patients (mean age 82.3 ± 1.9 years) who underwent valve surgery were reviewed. Aortic ...valve disease was found in 65% of the patients. Preoperatively, 20% of the patients were in NYHA class IV. An urgent operation and concomitant coronary artery bypass grafting were performed in ten patients each. A bioprosthetic valve was exclusively used for valve replacement except in two patients. Mitral valve repair was done in seven patients. Operative mortality was 13.3% for the period. No risk factors for operative mortality were detected by multivariate analysis; however, urgent operation, preoperative NYHA class IV, preoperative renal dysfunction, perioperative use of an intra-aortic balloon pumping, and prolonged cardiopulmonary bypass time had significant effects on operative mortality. The actuarial survival rate at 1 and 3 years after surgery was 82.6 and 71.5%, respectively, and 97.6% of late survivors reported that their activity level was equal to or better than the preoperative level. Valve surgery can be performed in octogenarian patients with acceptable mortality, good long-term results, and good quality of life. Early referral to surgery should be important to obtain a better postoperative outcome.
We present a case of coronary artery disease with intermediate stenosis in the proximal left anterior descending artery, which was evaluated using multiple functional modalities. FFR
CT
demonstrated ...a significant perfusion abnormality in the LAD, and the value of FFR
CT
(0.68) was similar to the value measured by invasive FFR (0.67). However, the other modalities gave discrepant results. In particular, perfusion scintigraphy with thallium showed no evidence of an inducible perfusion abnormality in the LAD territory. The patient was treated by PCI for two tandem lesions in the LAD. FFR
CT
may have potential as a default noninvasive method for assessment of coronary anatomy and physiology.
Hypophosphatasia (HPP), caused by mutations in the gene ALPL encoding tissue-nonspecific alkaline phosphatase (TNALP), is an inherited systemic skeletal disease characterized by mineralization ...defects of bones and teeth. The clinical severity of HPP varies widely, from a lethal perinatal form to mild odontohypophosphatasia showing only dental manifestations. HPP model mice (Akp2(-/-)) phenotypically mimic the severe infantile form of human HPP; they appear normal at birth but die by 2 weeks of age because of growth failure, hypomineralization, and epileptic seizures. In the present study, we investigated the feasibility of fetal gene therapy using the lethal HPP model mice. On day 15 of gestation, the fetuses of HPP model mice underwent transuterine intraperitoneal injection of adeno-associated virus serotype 9 (AAV9) expressing bone-targeted TNALP. Treated and delivered mice showed normal weight gain and seizure-free survival for at least 8 weeks. Vector sequence was detected in systemic organs including bone at 14 days of age. ALP activities in plasma and bone were consistently high. Enhanced mineralization was demonstrated on X-ray images of the chest and forepaw. Our data clearly demonstrate that systemic injection of AAV9 in utero is an effective strategy for the treatment of lethal HPP mice. Fetal gene therapy may be an important choice after prenatal diagnosis of life-threatening HPP.
Background/Aims: The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify ...characteristics of NAFLD in patients with IBD. Methods: We retrospectively identified and enrolled patients with IBD diagnosed with or without NAFLD by undergoing abdominal computed tomography (CT) at our institution between 2005 and 2020. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of nonobese patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters. Results: Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In nonobese patients (defined as patients with a body mass index <25 kg/㎡), C-reactive protein (CRP; P<0.001) and alanine aminotransferase (P=0.018) levels were higher and the albumin level (P=0.005) and prognostic nutritional index (PNI; P=0.002) values were lower in patients with NAFLD than in those without NAFLD. The PNI value was positively correlated (P<0.001) and the CRP level was negatively correlated (P=0.001) with the hepatosplenic ratio. However, in the NAFLD combined group, PNI (P<0.05) and CRP values (P<0.001) were improved over time after CT imaging by continuing IBD treatment. Conclusions: Worsening nutritional and inflammatory status in IBD patients is associated with complications of NAFLD. Diagnosis of NAFLD in IBD patients using CT imaging might be useful not only for early detection of NAFLD but also in assessing the need for therapeutic intervention for IBD. (Intest Res 2023;21:471-480)
Although Kupffer cells (KCs) play an important role in the liver's immune response, their role in colon cancer metastasis to the liver is unclear. We here analyzed the relationship between KCs and ...tumor cells (TCs) in colon cancer metastasis to the liver. Fischer 344 (F344) rats were divided into control group (KC+ group) and KC elimination group (KC‑ group), in which KC elimination was induced by Cl2MDP liposome injection. RCN‑H4 colon cancer cells were injected into the rats of both groups, and the relationship between the two types of cells was observed by intravital microscopy (IVM) for 6 h. Moreover, to investigate the effect of KCs on liver metastasis formation, KCs were eliminated at different time points before and after the TC injection. The number of metastatic nodules 2 weeks after the injection was evaluated. In the KC‑ group, IVM revealed that the number of adherent TCs had increased 1.5‑fold at 6 h after the TC injection as compared with in the KC+ group. Moreover, in the KC+ group, 74% of the TCs adhered to the KCs, and KC activation and KC phagocytosis of the TCs were observed. Two weeks after the injection, the number of metastatic nodules was significantly increased in rats in which the KCs had been eliminated before the injection, but not in rats in which the KCs had been eliminated after the injection. KC activation and KC phagocytosis of TCs decreased colon cancer cell metastasis to the liver.
Nivolumab is a monoclonal antibody targeting programmed cell death-1 (PD-1) that has been recently shown to exhibit clinical efficacy in patients with gastric cancer. However, various degrees of ...immune-related adverse events (irAEs) have been reported. We report the case of a 71-year-old male patient diagnosed with gastric cancer with peritoneal metastases. He was treated with nivolumab as third-line chemotherapy. On the 10
day after completing seven cycles of nivolumab treatment, he urgently visited the hospital because of mild left cervical lymphadenopathy. We suspected it to be due to inflammation and initiated treatment with levofloxacin hydrate. However, 3 days later, he was admitted to the emergency room due to exacerbation of his lymphadenopathy. A diagnosis of nivolumab-induced lymphadenopathy was made as the antibiotics were ineffective, and the patient was administered prednisolone (PSL) 20 mg. One day after admission, the pain and swelling of the lymph node greatly lessened, and the following day, the pain gradually disappeared; thereafter, the PSL dose was tapered and nivolumab treatment was resumed. The patient again developed cervical lymphadenopathy approximately 4-5 days after nivolumab was reintroduced, which disappeared 1 week later. During each episode of lymphadenopathy, he received a dose of 20 mg of PSL for 4 days, which would be eventually tapered to 10 mg without antibiotics and NSAIDs. After 2 months, cervical lymphadenopathy completely disappeared while 10 mg of PSL was continued, which was also eventually tapered off. To our knowledge, this is the first case report of nivolumab-induced lymphadenopathy in a patient with gastric cancer. This case suggested that we should keep in mind that various irAEs may occur during treatment with immune checkpoint inhibitors. It is necessary to ensure the absence of infection and metastasis before treatment and to promptly administer systemic corticosteroids to address them.
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