以CD54为评价指标的THP-1细胞光致敏体外评价方法的确定和验证

目的 确定并验证以细胞表面标志物CD54作为评价指标的光致敏体外评价方法。方法 将THP-1细胞与多种光致敏剂、光刺激剂、皮肤致敏剂、皮肤刺激剂和阴性受试物分别孵育,在光照射或避光处理后,用流式细胞仪测定细胞表面标志物CD54和CD86的表达水平并统计分析,进一步确定具体的评价指标,并对该方法的准确性、特异性、灵敏度、重复性进行验证。结果 19种光致敏剂中有15种引起照射组THP-1细胞表达CD54的平均荧光强度（MFI）较非照射组显著增加（P<0.05、0.01） ,且照射组细胞表达CD54的相对荧光强度（RFI）值均在1.5以上。光刺激剂经光照射后也可引起细胞表达CD54的MFI显著增加（P<0.01） ,但经过预照射处理后,CD54的表达水平较直接照射组显著下降（P<0.01）。未经光照射条件下,皮肤致敏剂即可引起THP-1细胞表达CD54和CD86的MFI比对照组显著增加（P<0.01） ,光照后CD54的表达反而略有下降。在光照和避光条件下,皮肤刺激剂、阴性受试物（乳酸）均未引起细胞表达CD54或CD86的显著性变化。以CD54为评价指标的THP-1细胞光致敏评价方法检测光致敏剂的准确性、特异性和灵敏度分别是85.2%、100%和78.9%,具有良好的重复性。结论 确定了THP-1细胞光致敏评价方法的细胞表面标志物评价指标为CD54,判定标准为：（1）光照后THP-1细胞表达CD54的MFI较照射前显著性增加;（2）光照后THP-1细胞表达CD54的RFI≥1.5;（3）当上述条件均满足时,对受试物进行预照射处理,结果仍然满足前2条标准。     

A questionnaire about radiation safety management of the draining-water system at nuclear medicine facilities

We conducted a questionnaire survey about radiation-safety management condition in Japanese nuclear medicine facilities to make materials of proposition for more reasonable management of medical radioactive waste. We distributed a questionnaire to institutions equipped with Nuclear Medicine facilities. Of 1,125 institutions, 642 institutes (52.8%) returned effective answers. The questionnaire covered the following areas: 1) scale of an institution, 2) presence of enforcement of radiotherapy, 3) system of a tank, 4) size and number of each tank, 5) a form of draining-water system, 6) a displacement in a radioactive rays management area, 7) a measurement method of the concentration of medical radioactive waste in draining water system, 8) planned and used quantity of radioisotopes for medical examination and treatment, 9) an average displacement of hospital for one month. In most institutions, a ratio of dose limitation of radioisotope in draining-water system was less than 1.0, defined as an upper limitation in ordinance. In 499 hospitals without facilities of hospitalization for unsealed radioisotope therapy, 473 hospitals reported that sum of ratios of dose limits in a draining-water system was less than 1.0. It was calculated by used dose of radioisotope and monthly displacement from hospital, on the premise that all used radioisotope entered in the general draining-water system. When a drainage including radioactivity from a controlled area join with that from other area before it flows out of a institution, it may be diluted and its radioactive concentration should be less than its upper limitation defined in the rule. Especially, in all institutions with a monthly displacement of more than 25,000 m3, the sum of ratio of the concentration of each radionuclide to the concentration limit dose calculated by used dose of radioisotope, indicated less than 1.0.     

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer     

Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava

We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.     

Studies on percutaneous transvenous mitral commissurotomy using a modified transseptal approach

Summary A modified version of Brockenbrough's trans-septal catheterization technique was carried out in 11 patients indicated for percutaneous transvenous mitral commissurotomy (PTMC). In 8/11 (72.7%), a coiled guide-wire was successfully inserted through theforamen ovale without atrial septal puncture. The Brockenbrough needle was used merely to maintain stiffness and the orientation of the dilator. PTMC was performed with an Inoue single balloon without incident.Patent foramen ovale was found by transesophageal echocardiography prior to the operation in only 1/11 patients (9.0%); nonetheless, it proved not to be a critical factor for the success of the procedure. This procedure seems to have much potential to enable the treatment of mitral stenosis with a lowered risk to the patient, as long as it is performed with precision and caution.     

Intraductal papillary adenoma: Usefulness of magnetic resonance cholangiopancreatography in the diagnosis of cystic branch-duct dilatation of the pancreas

A 70-year-old woman with gastric cancer was referred to our hospital for further evaluation of a cystic mass in the head of the pancreas. Endoscopic ultrasonography (EUS) showed a mural nodule in the cystic mass. Endoscopic retrograde cholangio pancreatography (ERCP) revealed a cystic lesion with a filling defect caused by obstruction with mucus. Magnetic resonance cholangiopancreatography (MRCP) allowed visualization of the entire configuration of the cystic lesion despite the presence of mucus. Pancreatic juice was positive for K-ras point mutation. Pancreatoduodenectomy was performed, with a diagnosis of intraductal papillary adenoma or adenocarcinoma with gastric cancer. Pancreatography of the resected specimen showed a cystic lesion in the uncinate process, consistent with the MRCP findings. Histological examination revealed an intraductal papillary adenoma. MRCP is very useful for demonstrating the total configuration of cystic lesions and is not impeded by impacted mucin. Nevertheless, because of its lower spatial resolution, this noninvasive modality is of limited value in detecting mural nodules. At present, therefore, surgical indications for cystic lesion of the pancreas should be determined by comprehensively analyzing: size and sequential changes in size of the cyst; presence of mural nodules, cytologic examination for presence of malignant cells, and/or K-ras point mutation in pure pancreatic juice.     

Utility of a simplified ultrasonography scoring system among patients with rheumatoid arthritis: A multicenter cohort study

We aimed to evaluate the utility of a simplified ultrasonography (US) scoring system, which is desired in daily clinical practice, among patients with rheumatoid arthritis (RA) receiving biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs).A total of 289 Japanese patients with RA who were started on tumor necrosis factor inhibitors, abatacept, tocilizumab, or Janus kinase inhibitors between June 2013 and April 2019 at one of the 15 participating rheumatology centers were reviewed. We performed US assessment of articular synovia over 22 joints among bilateral wrist and finger joints, and the 22-joint (22j)-GS and 22-joint (22j)-PD scores were evaluated as an indicator of US activity using the sum of the GS and PD scores, respectively.The top 6 most affected joints included the bilateral wrist and second/third metacarpophalangeal joints. Therefore, 6-joint (6j)-GS and -PD scores were defined as the sum of the GS and PD scores from the 6 synovial sites over the aforementioned 6 joints, respectively. Although the 22j- or 6j-US scores were significantly correlated with DAS28-ESR or -CRP scores, the correlations were weak. Conversely, 6j-US scores were significantly and strongly correlated with 22j-US scores not only at baseline but also after therapy initiation.Using a multicenter cohort data, our results indicated that a simplified US scoring system could be adequately tolerated during any disease course among patients with RA receiving biological/targeted synthetic DMARDs.