Cross-sectional study of therapy-related expectations/concerns of patients with metastatic renal cell carcinoma and physicians in Japan.

OBJECTIVE: To achieve patient-centricity in metastatic renal cell carcinoma (mRCC) treatment, it is essential to clarify the differences in perspectives between patients and physicians. This cross-sectional analysis of a web survey aimed to clarify the differences in expectations and concerns between mRCC patients and physicians regarding systemic mRCC therapy in Japan. METHODS: Surveys from 83 patients and 165 physicians were analyzed. RESULTS: The top three most significant differences in expectations of systemic therapy between patients and physicians (patient-based physician value) were "Chance of achieving treatment-free status" (-30.1%, p < 0.001), "Longer survival" (+25.8%, p < 0.001), and "Chance of eliminating all evidence of disease" (-25.6%, p < 0.001). The top three most significant differences in concerns for systemic therapy between patients and physicians (patient-based physician value) were "Lack of efficacy" (+36.1%, p < 0.001), "Lack of knowledge of treatment" (-28.2%, p < 0.001), and "Daily activities affected by side effects" (+22.3%, p < 0.001). Diarrhea, fatigue/malaise, and nausea/vomiting were patients' most distressing adverse events; 50.6% of patients had difficulty telling their physicians about adverse events such as fatigue, anxiety, and depression. CONCLUSIONS: This study demonstrated a gap between patients with mRCC and physicians in their expectations and concerns for systemic therapy. Japanese patients with mRCC suffer from a number of adverse events, some of which are not shared with physicians. This study highlights the importance of communicating well with patients in clinical practice to achieve patient-centricity in systemic treatment for mRCC.

Financial Toxicity in Japanese Patients with Metastatic Renal Cell Carcinoma: A Cross-Sectional Study.

Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0-36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL.

A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents.

Background: This study aimed to assess the completion rate and postoperative bleeding incidence of endoscopic submucosal dissection (ESD) for gastric tumors under continuous antithrombotic therapy. Methods: A prospective observational study was conducted including 88 patients with 100 gastric lesions who underwent gastric endoscopic submucosal dissection (ESD) and received continuous antithrombotic therapy. Additionally, retrospective data on gastric ESD in 479 patients with 534 lesions who did not receive antithrombotic therapy were collected for comparison. Results: The en bloc resection rates (100% in the continuous antithrombotic therapy group vs. 100% in the non-antithrombotic therapy group) and complete resection rates (97.0% vs. 96.3%, respectively) were high and comparable between the groups. No significant differences were found in the specimen size or procedure time. Perforation rates were low (0% vs. 2.3%, respectively) and were not significantly different between the groups. However, postoperative bleeding occurred significantly more frequently in the continuous antithrombotic therapy group (10.2% vs. 4.2%, respectively) than in the non-antithrombotic therapy group. The subgroup analysis revealed a higher incidence of postoperative bleeding in patients receiving thienopyridine derivatives. Conclusions: Continuous administration of antithrombotic agents, especially thienopyridines, increased the risk of postprocedural hemorrhage following gastric ESD. These findings support the need for careful consideration of pharamcological management before ESD, aligning with the current guidelines.

Vonoprazan versus lansoprazole in the treatment of artificial gastric ulcers after endoscopic submucossal dissection: a randomized, open-label trial.

BACKGROUND: Vonoprazan is more potent and longer acting than traditional proton pump inhibitor. Although vonoprazan is expected to be superior to proton pump inhibitor, its efficacy in the treatment of gastric ulcers following endoscopic submucosal dissection (ESD) is not fully understood. The aim of this study was to evaluate the effectiveness of vonoprazan in artificial ulcer healing following ESD. METHODS: Patients with gastric tumors were randomly assigned to the vonoprazan group (group V) or lansoprazole group (group L) after ESD. Patients received intravenous lansoprazole (30 mg) twice on the day of ESD. Thereafter, patients were treated with vonoprazan (20 mg/day) in group V or lansoprazole (30 mg/day) in group L. Esophagogastroduodenoscopy was performed 4 and 8 weeks after the ESD. RESULTS: A total of 168 patients were analyzed. The 4-week healing rate for artificial ulcer was not significantly higher in group V versus group L (17/85, 20.0% vs. 14/83, 16.9%, respectively). In addition, there were no significant differences between the 4-week shrinkage rates between the two groups. Postoperative bleeding occurred in none of the patients in group V and three in group L. One patient in group V presented delayed perforation 2 days after ESD. CONCLUSIONS: Vonoprazan might not be superior to lansoprazole in the healing of artificial gastric ulcer after ESD. TRIAL REGISTRATION: University hospital Medical Information Network (registration number: UMIN000016642), Registered 27 February 2015, https://www.umin.ac.jp/ctr/index-j.htm.

A Japanese Patient with Gastric Cancer and Dihydropyrimidine Dehydrogenase Deficiency Presenting with DPYD Variants.

A 63-year-old Japanese male with stomach adenocarcinoma received oral 5-fluorouracil derivative, cisplatin and trastuzumab chemotherapy. On day 8, severe diarrhea and mucositis developed; chemotherapy was stopped. On day 14, the patient developed renal dysfunction and febrile neutropenia. He also suffered from pneumonia due to Candida albicans. Systemic symptoms improved after intensive conservative treatment. Best supportive care was continued until the patient died from gastric cancer. The dihydropyrimidine dehydroge-nase protein level was low at 3.18 U/mg protein. The result of DPYD genotyping revealed three variants at posi-tions 1615 (G > A), 1627 (A > G), and 1896 (T > C) in exons 13, 13, and 14, respectively.

A multicenter observational study on the clinicopathological features of gastric cancer in young patients.

BACKGROUND: The details of gastric cancer in young patients remain unclear because of the low prevalence of the disease. This study aimed to clarify the clinicopathological features and prognosis of gastric cancer in young patients. METHODS: From January 2007 to January 2016, patients in their 20s and 30s who were diagnosed with primary gastric cancer at 4 hospitals were enrolled. Their clinical characteristics and prognosis were evaluated. RESULTS: The total number of patients was 72. The median age was 36 years, and the ratio of males to females was 1:1. The dominant histological type was undifferentiated type (66/72, 92%). Helicobacter pylori (H. pylori) was positive in 81% (54/67). Although there were some asymptomatic patients in stages I-III, all stage IV patients had some clinical symptoms at the diagnosis. The percentage of stage IV was significantly higher in patients in their 20s than in those in their 30s (75% vs. 25%, P < 0.001). The Kaplan-Meier method showed that the overall survival of patients in their 20s was significantly lower than that of patients in their 30s (P = 0.037). CONCLUSIONS: A high rate of H. pylori infection was revealed in young gastric cancer patients. The patients in their 20s had a worse prognosis than those in their 30s. We should consider examining the H. pylori infection status for young patients as well as older patients to identify high-risk populations.

Multi-institutional comparison of secondary check of treatment planning using computer-based independent dose calculation for non-C-arm linear accelerators.

PURPOSE: This report covers the first multi-institutional study of independent monitor unit (MU)/dose calculation verification for the CyberKnife, Vero4DRT, and TomoTherapy radiotherapy delivery systems. METHODS: A total of 973 clinical treatment plans were collected from 12 institutions. Commercial software employing the Clarkson algorithm was used for verification after a measurement validation study, and the doses from the treatment planning systems (TPSs) and verification programs were compared on the basis of the mean value ±â€¯two standard deviations. The impact of heterogeneous conditions was assessed in two types of sites: non-lung and lung. RESULTS: The dose difference for all locations was 0.5 ±â€¯7.2%. There was a statistically significant difference (P < 0.01) in dose difference between non-lung (-0.3 ±â€¯4.4%) and lung sites (3.5 ±â€¯6.7%). Inter-institutional comparisons showed that various systematic differences were associated with the proportion of different treatment sites and heterogeneity correction. CONCLUSIONS: This multi-institutional comparison should help to determine the departmental action levels for CyberKnife, Vero4DRT, and TomoTherapy, as patient populations and treatment sites may vary between the modalities. An action level of ±5% could be considered for intensity-modulated radiation therapy (IMRT), non-IMRT, and volumetric modulated arc radiotherapy using these modalities in homogenous and heterogeneous conditions with a large treatment field applied to a large region of homogeneous media. There were larger systematic differences in heterogeneous conditions with a small treatment field because of differences in heterogeneity correction with the different dose calculation algorithms of the primary TPS and verification program.

[Results of Palliative Stent Insertion for Malignant Colorectal Obstruction].

We compared the utility of self-expandable metallic stents (SEMS) to that of colostomy in palliative care patients with malignant colorectal obstruction. The SEMS-related morbidity and mortality rates were 15.4% and 7.7% in 13 patients, respectively. The median time to first diet was significantly shorter after SEMS insertion than that after colostomy, (2 vs 6 days, respectively, p=0.0102). The postprocedure median length of hospital stay of the palliative care patients without followed chemotherapy was shorter after SEMS insertion than after colostomy (10 vs 23 days, respectively). The median time to chemotherapy administration was shorter after SEMS insertion than after colostomy (13 vs 29 days, respectively); however, this difference was not statistically significant. Insertion of SEMS should be considered as the first-line treatment for palliative care patients with malignant colorectal obstruction.

A multi-institutional study of secondary check of treatment planning using Clarkson-based dose calculation for three-dimensional radiotherapy.

PURPOSE: As there have been few reports on quantitative analysis of inter-institutional results for independent monitor unit (MU) verification, we performed a multi-institutional study of verification to show the feasibility of applying the 3-5% action levels used in the U.S. and Europe, and also to show the results of inter-institutional comparisons. METHODS: A total of 5936 fields were collected from 12 institutions. We used commercial software employing the Clarkson algorithm for verification after a validation study of measurement and software comparisons was performed. The doses generated by the treatment planning systems (TPSs) were retrospectively analyzed using the verification software. RESULTS: Mean ±â€¯two standard deviations of all locations were 1.0 ±â€¯3.6%. There were larger differences for breast (4.0 ±â€¯4.0%) and for lung (2.5 ±â€¯5.8%). A total of 80% of the fields with differences over 5% of the action level involved breast and lung targets, with 7.2 ±â€¯5.4%. Inter-institutional comparisons showed various systematic differences for field shape for breast and differences in the fields were attributable to differences in reference point placement for lung. The large differences for breast and lung are partially attributable to differences in the methods used to correct for heterogeneity. CONCLUSIONS: The 5% action level may be feasible for verification; however, an understanding of larger differences in breast and lung plans is important in clinical practice. Based on the inter-institutional comparisons, care must be taken when determining an institution-specific action level from plans with different field shape settings and incorrectly placed reference points.

Multi-institutional comparison of computer-based independent dose calculation for intensity modulated radiation therapy and volumetric modulated arc therapy.

PURPOSE: No multi-institutional studies of computer-based independent dose calculation have addressed the discrepancies among radiotherapy treatment planning systems (TPSs) and the verification programs for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). We conducted a multi-institutional study to investigate whether ±5% is a reasonable action level for independent dose calculation for IMRT/VMAT. METHODS: In total, 477 IMRT/VMAT plans for prostate or head and neck (H&N) malignancies were retrospectively analyzed using a modified Clarkson-based commercial verification program. The doses from the TPSs and verification programs were compared using the mean ±1 standard deviation (SD). RESULTS: In the TPS-calculated dose comparisons for prostate and H&N malignancies, the sliding window (SW) technique (-2.5 ±â€¯1.8% and -5.3 ±â€¯2.6%) showed greater negative systematic differences than the step-and-shoot (S&S) technique (-0.3 ±â€¯2.2% and -0.8 ±â€¯2.2%). The VMAT dose differences for prostate and H&N malignancies were 0.9 ±â€¯1.8% and 1.1 ±â€¯3.3%, respectively. The SDs were larger for the H&N plans than for the prostate plans in both IMRT and VMAT. Such plans including more out-of-field control points showed greater systematic differences and SDs. CONCLUSIONS: This study will help individual institutions to establish an action level for agreement between primary calculations and verification for IMRT/VMAT. A local dose difference of ±5% at a point within the planning target volume (above -350 HU) may be a reasonable action level.

A Japanese Case of Esophageal Lichen Planus that Was Successfully Treated with Systemic Corticosteroids.

Esophageal lichen planus (ELP) is rare and only about 80 cases have been reported in the literature. An 85-year-old woman presented with dysphagia and odynophagia. Endoscopy revealed a severe stricture in the proximal esophagus. Oral examinations at two years after the first endoscopy revealed erosions around the gingiva, and an examination of biopsy specimens taken from the site of erosion led to a diagnosis of oral lichen planus. Esophageal endoscopy was performed again, and biopsy specimens showed spongiosis and necrotic keratinocytes in the epithelium (civatte bodies). The patient was diagnosed with ELP and was treated with systemic corticosteroids, which resulted in clinical relief.

Linked color imaging (LCI), a novel image-enhanced endoscopy technology, emphasizes the color of early gastric cancer.

BACKGROUND AND STUDY AIMS: Linked color imaging (LCI) and blue laser imaging (BLI) are novel image-enhanced endoscopy technologies with strong, unique color enhancement. We investigated the efficacy of LCI and BLI-bright compared to conventional white light imaging (WLI) by measuring the color difference between early gastric cancer lesions and the surrounding mucosa. PATIENTS AND METHODS: Images of early gastric cancer scheduled for endoscopic submucosal dissection were captured by LCI, BLI-bright, and WLI under the same conditions. Color values of the lesion and surrounding mucosa were defined as the average of the color value in each region of interest. Color differences between the lesion and surrounding mucosa (ΔE) were examined in each mode. The color value was assessed using the CIE L*a*b* color space (CIE: Commission Internationale d'Eclairage). RESULTS: We collected images of 43 lesions from 42 patients. Average ΔE values with LCI, BLI-bright, and WLI were 11.02, 5.04, and 5.99, respectively. The ΔE was significantly higher with LCI than with WLI ( P  < 0.001). Limited to cases of small ΔE with WLI, the ΔE was approximately 3 times higher with LCI than with WLI (7.18 vs. 2.25). The ΔE with LCI was larger when the surrounding mucosa had severe intestinal metaplasia ( P  = 0.04). The average color value of a lesion and the surrounding mucosa differed. This value did not have a sufficient cut-off point between the lesion and surrounding mucosa to distinguish them, even with LCI. CONCLUSION: LCI had a larger ΔE than WLI. It may allow easy recognition and early detection of gastric cancer, even for inexperienced endoscopists.

Preoperative Pulmonary Function Tests Predict Aspiration Pneumonia After Gastric Endoscopic Submucosal Dissection.

BACKGROUND: ESD allows higher rates of en-bloc and R0 resections, but has occasionally complications such as aspiration pneumonia. Factors associated with aspiration pneumonia are not completely understood. AIMS: To analyze the relationship between aspiration pneumonia and preoperative factors including pulmonary function tests. METHODS: A total of 978 patients with gastric tumors who had received pulmonary function tests were treated by ESD between June 2006 and May 2014. Pulmonary function tests were assessed using a spirometer. The patients were categorized into four groups according to the predicted vital capacity (%VC) and forced expiratory volume in 1 s as a percentage of forced vital capacity (FEV1.0%): normal; restrictive pulmonary dysfunction; obstructive; and mixed. The factors associated with aspiration pneumonia were retrospectively analyzed. RESULTS: Among the 268 cases with abnormal pulmonary function, 10 cases (3.7%) developed aspiration pneumonia. On the other hand, 7 cases (1.0%) with normal pulmonary function developed pneumonia. There was a significant correlation between pulmonary function and aspiration pneumonia (p = 0.010). When the pulmonary function cases were stratified into subgroups, 2.5% of cases with obstructive pulmonary dysfunction developed pneumonia, 5.5% with restrictive and 5.3% with mixed. By logistic regression analysis, pulmonary function, the presence of cerebral vascular disease, and procedure time were identified as significant independent risk factors associated with aspiration pneumonia. The odds ratios for pulmonary function, cerebral vascular disease, and procedure time were 3.6, 5.1, and 5.2, respectively. CONCLUSIONS: Preoperative pulmonary function tests may be useful markers to evaluate the risk for aspiration pneumonia after gastric ESD.

Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study.

AIM: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy. METHODS: Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS: Although NaP showed better tolerability in terms of taste, volume and overall impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION: Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.

Precision in Wedge Off-axis Using Independent Dose Verification.

It is essential for quality assurance to verify the safety of each individual patient's plan in radiation therapy. The tolerance level for independent verification of monitor unit calculations for non-IMRT clinical radiotherapy has been shown in the AAPM TG114. Thus, we investigated the precision of independent MU (dose) verification considering a wedge off-axis calculation and we conducted a study at twelve institutes for independent verification with the wedge off-axis calculation. The results obtained with the wedge off-axis calculation showed better agreement with the treatment planning system calculation results than those without the former calculation in a phantom study and in the patient retrospective study. The confidence limits with the wedge off-axis calculation were 2.2±3.4% and 2.0±4.3% for the plans with a physical wedge and a non-physical wedge in the patient study, respectively. However, the confidence limits were over 5% without the off-axis calculation. From our multi-institutional study, the results suggested that the tolerance level for the wedge off-axis plan would be 5% when considering the wedge off-axis calculation and the level was similar to that of the treatment planning system using other conventional irradiation techniques.

Variation of the prescription dose using the analytical anisotropic algorithm in lung stereotactic body radiation therapy.

PURPOSE: The aim of the present investigation was to evaluate the dosimetric variation regarding the analytical anisotropic algorithm (AAA) relative to other algorithms in lung stereotactic body radiation therapy (SBRT). We conducted a multi-institutional study involving six institutions using a secondary check program and compared the AAA to the Acuros XB (AXB) in two institutions. METHODS: All lung SBRT plans (128 patients) were generated using the AAA, pencil beam convolution with the Batho (PBC-B) and adaptive convolve (AC). All institutions used the same secondary check program (simple MU analysis [SMU]) implemented by a Clarkson-based dose calculation algorithm. Measurement was performed in a heterogeneous phantom to compare doses using the three different algorithms and the SMU for the measurements. A retrospective analysis was performed to compute the confidence limit (CL; mean±2SD) for the dose deviation between the AAA, PBC, AC and SMU. The variations between the AAA and AXB were evaluated in two institutions, then the CL was acquired. RESULTS: In comparing the measurements, the AAA showed the largest systematic dose error (3%). In calculation comparisons, the CLs of the dose deviation were 8.7±9.9% (AAA), 4.2±3.9% (PBC-B) and 5.7±4.9% (AC). The CLs of the dose deviation between the AXB and the AAA were 1.8±1.5% and -0.1±4.4%, respectively, in the two institutions. CONCLUSIONS: The CL of the AAA showed much larger variation than the other algorithms. Relative to the AXB, larger systematic and random deviations still appeared. Thus, care should be taken in the use of AAA for lung SBRT.

Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs.

BACKGROUND AND AIM: Video-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model. METHODS: A total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group). RESULTS: Serum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P < 0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P < 0.01). Serum d-ROM levels were lower in NC and NE than N (P < 0.01), and OXY levels were higher in NC than N and NE (P < 0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N. CONCLUSIONS: Non-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

Molecular mechanisms and new treatment strategies for non-alcoholic steatohepatitis (NASH).

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), in which most patients exhibit non-progressive, non-alcoholic fatty liver (NAFL) attributable to simple steatosis. Multiple hits, including genetic differences, fat accumulation, insulin resistance and intestinal microbiota changes, account for the progression of NASH. NAFLD is strongly associated with obesity, which induces adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level, which in turn induces hepatic steatosis, inflammation and fibrosis. Among these factors, gut microbiota are acknowledged as having an important role in initiating this multifactorial disease. Oxidative stress is considered to be a key contributor in the progression from NAFL to NASH. Macrophage infiltration is apparent in NAFL and NASH, while T-cell infiltration is apparent in NASH. Although several clinical trials have shown that antioxidative therapy with vitamin E can effectively control hepatitis pathology in the short term, the long-term effects remain obscure and have often proved to be ineffective in many other diseases. Several long-term antioxidant protocols have failed to reduce mortality. New treatment modalities that incorporate current understanding of NAFLD molecular pathogenesis must be considered.

Effect of N-doping of single-walled carbon nanotubes on bioelectrocatalysis of laccase.

Nondoped and N-doped SWCNTs (N-SWCNTs) were used to clarify the effect of N-doping on a direct electron transfer (DET) reaction of laccase (Lac, from Trametes sp.). The level of N-doping in the carbon phase of the N-SWCNTs, which were synthesized by a CVD method, was determined to be 0.1, 2.4, and 4.1% from X-ray photoelectron spectroscopy measurements. The N-SWCNTs were also carefully characterized using electron microscopy, Brunauer-Emmett-Teller (BET) specific surface area measurements, Raman spectroscopy, and electrochemistry. The bioelectrocatalytic current for the DET reaction of Lac immobilized onto the N-SWCNTs tended to decrease with increasing N dopant ratio, whereas the amount of Lac adsorbed per BET surface area of the N-SWCNTs did not depend on the N dopant ratio. There were two main explanations for this behavior. First, an electrostatic interaction between the positively charged interface of the N-SWCNTs due to nitrogen species surface functional groups and the negative charges of carboxylate residues surrounding the T1 site. Second, the surface potential of the N-SWCNTs during Lac modification, because the slope value of the surface potential versus N dopant ratio of the N-SWCNTs was about 53 mV/N%. From additional investigations into the surface potential effect and thermodynamic investigations, we carefully concluded that the above behaviors may be due to denaturation and/or decreasing of the DET reaction rate caused by the strong electrostatic interaction between Lac and the N-SWCNTs surface.

Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH).

Multiple parallel hits, including genetic differences, insulin resistance and intestinal microbiota, account for the progression of non-alcoholic steatohepatitis (NASH). Multiple hits induce adipokine secretion, endoplasmic reticulum (ER) and oxidative stress at the cellular level that subsequently induce hepatic steatosis, inflammation and fibrosis, among which oxidative stress is considered a key contributor to progression from simple fatty liver to NASH. Although several clinical trials have shown that anti-oxidative therapy can effectively control hepatitis activities in the short term, the long-term effect remains obscure. Several trials of long-term anti-oxidant protocols aimed at treating cerebrovascular diseases or cancer development have failed to produce a benefit. This might be explained by the non-selective anti-oxidative properties of these drugs. Molecular hydrogen is an effective antioxidant that reduces only cytotoxic reactive oxygen species (ROS) and several diseases associated with oxidative stress are sensitive to hydrogen. The progress of NASH to hepatocellular carcinoma can be controlled using hydrogen-rich water. Thus, targeting mitochondrial oxidative stress might be a good candidate for NASH treatment. Long term clinical intervention is needed to control this complex lifestyle-related disease.