Feasibility of Integrating Leprosy Post-Exposure Prophylaxis with Single-Dose Rifampicin (LPEP) into Routine Leprosy Control Program in Bukedi and Teso Regions in Uganda

Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.

A Bioequivalence Study of Empagliflozin/Metformin Fixed-Dose Combination in Healthy Subjects under Fasting Conditions

Background: This study evaluated the bioequivalence of empagliflozin 12.5 mg/metformin 1000 mg tablets compared to Synjardy® (Empagliflozin 12.5 mg/metformin 1000 mg) tablets in healthy male subjects under fasting conditions. Methods: This was a phase I, randomized, single-dose, two-period, two-sequence, crossover study to evaluate the bioequivalence (BE) profiles of two fixed-dose combinations (FDCs) of empagliflozin/metformin. Cmax, AUC0-t and AUC0-∞ from test and reference formulations were evaluated to access BE. The plasma concentrations were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) method. Of the 24 subjects enrolled, 23 completed both periods of the study. The two formulations test and reference were considered bioequivalent if 90% confidence interval (CI) fell within 80.00% - 125.00% for Cmax, AUC0-t and AUC0-∞. Tolerability and safety were assessed throughout the study. Results: The pharmacokinetic (PK) parameters were similar between the test product (T) and reference product (R) Synjardy®. The 90% CI of the test/reference ratios of log-transformed PK parameters point estimates was Cmax: 89.87% (85.68% - 94.27%), AUC0-t: 87.91% (83.65% - 92.39%) and AUC0-∞: 87.16% (82.80% - 91.75%) to empagliflozin and Cmax: 92.19% (87.95% - 96.65%), AUC0-t: 91.38% (84.42% - 98.91%) and AUC0-∞: 93.78% (83.82% - 104.93%) to metformin respectively (90% CI for all PK parameters fell within 80.00% - 125.00%). Conclusion: Our results demonstrated BE between the test and reference formulations of oral tablets of empagliflozin 12.5 mg/metformin 1000 mg (FDC) in healthy male subjects under fasting conditions.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Nitrate Leaching from Maize Intercropping Systems with N Fertilizer Over-Dose

A 2-yr field experiment was conducted on a calcareous alluvial soil with four summer maize intercropping systems at Shangzhuang Experiment Station （116.3°E, 39.9°N） in the North China Plain. The objective was to determine nitrate leaching from intercropping systems involving maize （Zea mays L.）： sole maize （CK）, maize ＋ soybean （CST）, maize ＋ groundnut （CGT）, maize ＋ ryegrass （CHM）, and maize ＋ alfalfa （CMX）. Intercropping greatly reduced nitrate accumulation in the 100-200 cm soil layers compared with maize monoculture. Nitrate accumulation under intercropping systems decreased significantly at the 140-200 cm soil depth; the accumulation varied in the order CK〉CST〉CMX〉CHM〉CGT. However, compared to the CK treatment, nitrate leaching losses during the maize growing period were reduced by 20.9- 174.8 （CGT）, 35.2-130.8 （CHM）, 60.4-122.0 （CMX）, and 30.6-82.4 kg ha-1 （CST）. The results also suggested that intereropping is an effective way to reduce nitrogen leaching in fields with N fertilizer over-dose.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin(LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society.On the other hand,a very low dose of aspirin(10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage.The incidence of LDAinduced gastrointestinal mucosal injury and bleeding has increased.It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug(NSAID)-induced lesions.The pathogenesis related to inhibition of cyclooxygenase(COX)-1 includes reduced mucosal flow,reduced mucus and bicarbonate secretion,and impaired platelet aggregation.The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence.The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation.The factors associated with an increased risk of upper gastrointestinal(GI) complications in subjects taking LDA are aspirin dose,history of ulcer or upper GI bleeding,age > 70 years,concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs,and Helicobacter pylori(H.pylori) infection.Moreover,no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea,acid regurgitation,heartburn,and bloating.It has been shown that the ratios of ulcers located in the body,fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA.Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers.In contrast to NSAIDinduced gastrointestinal ulcers,a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers.The eradication of H.pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding.Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates,as stopping aspirin therapy is associated with higher mortality rates.It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding,and every effort should be exercised to prevent the bleeding complications.

Mortality outcomes of low-dose computed tomography screening for lung cancer in urban China:a decision analysis and implications for practice

Background: Mortality outcomes in trials of low-dose computed tomography(CT) screening for lung cancer are inconsistent. This study aimed to evaluate whether CT screening in urban areas of China could reduce lung cancer mortality and to investigate the factors that associate with the screening effect.Methods: A decision tree model with three scenarios(low-dose CT screening, chest X-ray screening, and no screening) was developed to compare screening results in a simulated Chinese urban cohort(100,000 smokers aged45-80 years). Data of participant characteristics were obtained from national registries and epidemiological surveys for estimating lung cancer prevalence. The selection of other tree variables such as sensitivities and specificities of low-dose CT and chest X-ray screening were based on literature research. Differences in lung cancer mortality(primary outcome), false diagnoses, and deaths due to false diagnosis were calculated. Sensitivity analyses were performed to identify the factors that associate with the screening results and to ascertain worst and optimal screening effects considering possible ranges of the variables.Results: Among the 100,000 subjects, there were 448,541, and 591 lung cancer deaths in the low-dose CT, chest X-ray, and no screening scenarios, respectively(17.2% reduction in low-dose CT screening over chest X-ray screening and 24.2% over no screening). The costs of the two screening scenarios were 9387 and 2497 false diagnoses and 7and 2 deaths due to false diagnosis among the 100,000 persons, respectively. The factors that most influenced death reduction with low-dose CT screening over no screening were lung cancer prevalence in the screened cohort, lowdose CT sensitivity, and proportion of early-stage cancers among low-dose CT detected lung cancers. Considering all possibilities, reduction in deaths(relative numbers) with low-dose CT screening in the worst and optimal cases were16(5.4%) and 288(40.2%) over no screening, respectively.Conclusions: In terms of mortality outcomes, our findings favor conducting low-dose CT screening in urban China.However, approaches to reducing false diagnoses and optimizing important screening conditions such as enrollment criteria for screening are highly needed.

Mitochondrial Modulation of Apoptosis Induced by Low-dose Radiation in Mouse Testicular Cells

Objective To investigate whether apoptosis induced by low-dose radiation （LDR） is regulated by mitochondrial pathways in testicular cells. Methods Male mice were exposed to whole-body LDR, and changes in mitochondrial function and in expression of apoptotic factors were analyzed in the testicular cells as follows. Total nitric-oxide synthase （T-NOS） and Na＋/K＋ ATPase activities were biochemically assayed. Reactive oxygen species （ROS） and mitochondrial membrane potential （Adjm） were determined by flow cytometry using fluorescent probes. Levels of mRNAs encoding cytochrome c （Cyt c） and apoptosis-inducing factor （AIF） were quantified by real-time reverse-transcription PCR （RT-PCR）. Expression of Cyt c, AIF, caspase-9, and caspase-3 at the protein level was assessed by western blotting and immunohistochemistry. Results LDR induced an increase in T-NOS activity and ROS levels, and a decrease in Na＋/K~ ATPase activity and mitochondrial A^m, in the testicular cells. The intensity of these effects increased with time after irradiation and with dose. The cells showed remarkable swelling and vacuolization of mitochondria, and displayed a time- and dose-dependent increase in the expression of Cyt c, AIF, procaspase-9, and procaspase-3. Activation of the two procaspases was confirmed by detection of the cleaved caspases. The changes in expression of the four apoptotic factors were mostly limited to spermatogonia and spermatocytes. Conclusion LDR can induce testicular cell apoptosis through mitochondrial signaling pathways

Split-dose vs same-day reduced-volume polyethylene glycol electrolyte lavage solution for morning colonoscopy

AIM: To compare same-day whole-dose vs split-dose of 2-litre polyethylene glycol electrolyte lavage solution (PEG-ELS) plus bisacodyl for colon cleansing for morning colonoscopy.

Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy

BACKGROUND Endoscopic submucosal dissection(ESD) for gastric neoplasms during continuous low-dose aspirin(LDA) administration is generally acceptable according to recent guidelines. This retrospective study aimed to investigate the effect of continuous LDA on the postoperative bleeding after gastric ESD in patients receiving dual antiplatelet therapy(DAPT).AIM To investigate the feasibility of gastric ESD with continuous LDA in patients with DAPT.METHODS A total of 597 patients with gastric neoplasms treated with ESD between January2010 and June 2017 were enrolled. The patients were categorized according to type of antiplatelet therapy(APT).RESULTS The postoperative bleeding rate was 6.9%(41/597) in all patients. Patients were divided into the following two groups: no APT(n = 443) and APT(n = 154). APT included single-LDA(n = 95) and DAPT(LDA plus clopidogrel, n = 59)subgroups. In the single-LDA and DAPT subgroups, 56 and 39 patients were received continuous LDA, respectively. The bleeding rate with continuous singleLDA(10.7%) was similar to that with discontinuous single-LDA(10.3%)(P >0.99). Although the bleeding rate with continuous LDA in patients receiving DAPT(23.1%) was higher than that with discontinuous LDA in patients receiving DAPT(5.0%), no significant difference was observed(P = 0.141).CONCLUSION The bleeding rate with continuous LDA in patients receiving DAPT was not statistically different from that with discontinuous LDA in patients receiving DAPT. Therefore, continuous LDA administration may be acceptable for ESD in patients receiving DAPT, although patients should be carefully monitored for possible bleeding.

Gender differences of low-dose aspirin-associated gastroduodenal ulcer in Japanese patients

AIM:To clarify the gender differences about the clini-cal features and risk factors of low-dose aspirin (LDA) (81-100 mg daily)-associated peptic ulcer in Japanese patients.METHODS: There were 453 patients under treatment with LDA (298 males, 155 females) who underwent esophagogastroduodenoscopy at the Department of Gastroenterology and Hepatology of Hiratsuka City Hospital between January 2003 and December 2007. They had kept taking the LDA or started treatmentduring the study period and kept taking LDA during the whole period of observation. Of these, 119 patients (87 males, 32 females) were diagnosed as having LDA-associated peptic ulcer. We examined the clinical factors associated with LDA-associated peptic ulcer in both sexes.RESULTS: A history of peptic ulcer was found to be the risk factor for LDA-associated peptic ulcer common to both sexes. In female patients, age greater than 70 years (prevalence ORs 8.441, 95% CI: 1.797-33.649, P = 0.0069) was found to be another significant risk fac-tor, and the time to diagnosis as having LDA-associat-ed peptic ulcer by endoscopy was significantly shorter than that in the male patients (P = 0.0050). CONCLUSION: We demonstrated gender differences about the clinical features and risk factors of LDA-asso-ciated peptic ulcer. Special attention should be paid to aged female patients taking LDA.

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Low-dose computed tomography with 4th-generation iterative reconstruction algorithm in assessment of oncologic patients

AIM To compare radiation dose and image quality of lowdose computed tomography(CT) protocol combined with hybrid-iterative reconstruction algorithm with standarddose CT examinations for follow-up of oncologic patients. METHODS Fifty-one patients with known malignant diseases which underwent, during clinical follow-up, both standarddose and low-dose whole-body CT scans were enrolled. Low-dose CT was performed on 256-row scanner, with 120 kV and automated m A modulation, and iterative reconstruction algorithm. Standard-dose CT was performed on 16-rows scanner, with 120 kV, 200-400 m As(depending on patient weight). We evaluated density values and signal-to-noise ratio, along with image noise(SD), sharpness and diagnostic quality with 4-point scale.RESULTS Density values in liver, spleen and aorta were higher in lowdose images(liver 112.55 HU vs 103.90 HU, P < 0.001), as SD values in liver and spleen(liver 16.81 vs 14.41). Volumetric-Computed-Tomographic-Dose-Index(CTDIvol) and Dose-Length-Product(DLP) were significantly lower in low-dose CT as compared to standard-dose(DLP 1025.6 m Gy*cm vs 1429.2 m Gy*cm, P < 0.001) with overall dose reduction of 28.9%. Qualitative analysis did not reveal significant differences in image noise and diagnostic quality.CONCLUSION Automatic tube-current modulation combined with hybriditerative algorithm allows radiation dose reduction of 28.9% without loss of diagnostic quality, being useful in reducing dose exposure in oncologic patients.

Low-dose CT coronary angiography using iterative reconstruction with a 256-slice CT scanner

AIM:To explore whether computer tomography coronary angiography(CTCA) using iterative reconstruction(IR) leads to significant radiation dose reduction without a significant loss in image interpretability compared to conventional filtered back projection(FBP).METHODS:A consecutive series of 200 patients referred to our institution to undergo CTCA constituted the study population.Patients were sequentially assigned to FBP or IR.All studies were acquired with a 256-slice CT scanner.A coronary segment was considered interpretable if image quality was adequate for evaluation of coronary lesions in all segments ≥ 1.5 mm.RESULTS:The mean age was 56.3±9.6 years and165(83%) were male,with no significant differences between groups.Most scans were acquired using prospective ECG triggering,without differences between groups(FBP 84%vs IR 82%;P=0.71).A total of 3198(94%) coronary segments were deemed of diagnostic quality.The percent assessable coronary segments was similar between groups(FBP 91.7%±4.0% vs IR92.5% ± 2.8%; P=0.12).Radiation dose was significantly lower in the IR group(2.8±1.4 mSvvs 4.6±3.0mSv;P<0.0001).Image noise(37.8±1.4 HUvs 38.2±2.4 HU; P=0.20) and signal density(461.7±51.9HU vs 462.2±51.2 HU; P=0.54) levels did not differ between FBP and IR groups,respectively.The IR group was associated to significant effective dose reductions,irrespective of the acquisition mode.CONCLUSION:Application of IR in CTCA preserves image interpretability despite a significant reduction in radiation dose.

Geographic differences in low-dose aspirin-associated gastroduodenal mucosal injury

Aspirin, even at low doses, has been known to cause upper gastro-intestinal complications, such as gastroduodenal ulcers, despite the definite benefits from its antithrombotic effects. Helicobacter pylori(H. pylori) is major pathogen responsible for gastroduodenal ulcerformation. There have been conflicting results about the potential interaction between these two ulcerogenic factors and the geographic areas involved. In Western countries, the prevalence of gastroduodenal ulcers is consistently higher in H. pylori-positive low-dose aspirin(LDA) users than in H. pylori-negative ones, suggesting that H. pylori infection exacerbates LDA-induced gastroduodenal mucosal injury in these geographic areas. Meanwhile, previous studies from Japan have generally reported a similar prevalence of LDA-induced gastroduodenal mucosal injury regardless of the presence of H. pylori infection, indicating that the infection is not an overall exacerbating factor for drug-induced injury. H. pylori infection could have a synergistic or antagonistic interaction with LDA use in adverse gastroduodenal events depending on gastric acid secretion. It is wellrecognized that the net effect of H. pylori infection on gastric acid secretion shows considerable geographic variation at the population level. While gastric acid secretion levels were not decreased and were wellpreserved in most patients with H. pylori infection from Western countries, the majority of Japanese patients with H. pylori infection exhibited decreased gastric acid secretion. Such large geographic differences in the net effect of H. pylori infection on gastric acid secretion could be at least partly responsible for the geographically distinct interaction between LDA use and H. pylori infection on adverse gastroduodenal lesions.

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound （HIFU） combined with （＋） low-dose external beam radiotherapy （LRT） as supplemental therapy for advanced prostate cancer （PCa） following hormonal therapy （HT）. Our definition of HIFU＋LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy （CRT）. We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU＋LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU ＋LRT treatment. There were significant differences among four groups with regard to overall survival （OS） and disease-specific survival （DSS） curves （P=0.018 and 0.015）. Further comparison between each pair of groups suggested that the long-term DSS of the H IFU ＋ LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU＋LRT group and the CRT group. Multivariable Cox＇s proportional hazard model showed that both HIFU＋LRT and CRT were independently associated with DSS （P=0.001 and 0.035） and had protective effects with regard to the risk of death. Compared with CRT, HIFU ＋LRT significantly decreased incidences of radiation-related late gastrointestinal （GI） and genitourinary （GU） toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and reRional lymph node metastases after HT. As an alternative to CRT, HIFU＋LRT showed Rood efficacy and better safety.

Low-Dose Metronomic Chemotherapy in Metastatic Breast Cancer: A Retrospective Analysis of 40 Patients

Purpose: Low-dose metronomic chemotherapy is an emergent treatment schedule in which low doses of cytotoxic agents are given orally continuously, with no or short drug-free intervals. In general, it provides better tolerance, especially in patients who have been previously exposed to other oncologic treatments, with a favorable cost-effectiveness profile. It is well known that all these low-dose schedules have a favorable safety profile and may provide an adequate tumor control in patients with metastatic breast cancer. However, there are no data in literature reporting the patient’s tolerance and response to subsequent lines of chemotherapy after receiving metronomic regimens. Methods: We retrospectively analyzed 40 patients with metastatic breast cancer treated with low doses of Cyclophosphamide and/or Methotrexate and/or Capecitabine in a single center from June 2009 to April 2014. The following data were collected: age, hormone and epidermal growth factor receptor 2 (HER-2) status, number of lines of chemotherapy prior to and after low-dose metronomic treatment, duration of metronomic treatment, toxicity reason for treatment discontinuation. Duration of low-dose metronomic chemotherapy was also correlated with the variables analyzed and treatment outcomes. Results: The median time on metronomic chemotherapy was 5.4 months. The most frequent drugs administered were cyclophosphamide, methotrexate and capecitabine alone. Asthenia, myelotoxicity, gastrintestinal symptoms and handfoot syndrome were the most commonly recorded treatment related toxicity. Twenty six (65%) patients had the opportunity to receive a classic chemotherapy regimen following metronomic regimen interruption. Although patients who developed toxicity to low-dose metronomic chemotherapy remained less time (<6 months) in subsequent chemotherapy, there was no statistically significant difference among those who received more lines of chemotherapy. Discussion: This is the first report in the literature describing the efficacy of low-dose metronomic regimens and the tolerance to subsequent lines of treatments following a period of metronomic chemotherapy. Most of our patients were able to tolerate conventional chemotherapy regimens administered in full doses. Several patients received as many as three lines of additional chemotherapy for periods that exceeded 6 months of treatment, which suggests that the use of prolonged metronomic treatment does not affect a patient’s ability to tolerate subsequent therapy.

Improvement of total-dose irradiation hardness of silicon-on-insulator materials by modifying the buried oxide layer with ion implantation

The hardening of the buried oxide （BOX） layer of separation by implanted oxygen （SIMOX） silicon-on-insulator （SOI） wafers against total-dose irradiation was investigated by implanting ions into the BOX layers. The tolerance to total-dose irradiation of the BOX layers was characterized by the comparison of the transfer characteristics of SOI NMOS transistors before and after irradiation to a total dose of 2.7 Mrad（SiO2）. The experimental results show that the implantation of silicon ions into the BOX layer can improve the tolerance of the BOX layers to total-dose irradiation. The investigation of the mechanism of the improvement suggests that the deep electron traps introduced by silicon implantation play an important role in the remarkable improvement in radiation hardness of SIMOX SOI wafers.

Suppression of Low-dose Hyper-radiosensitivity in Human Lung Cancer Cell Line A549 by Radiation-induced Autophagy

This study explored the role of radiation-induced autophagy in low-dose hyperradiosensitiv- ity （HRS） in the human lung cancer cell line A549. A549 cells, either treated with an autophagic inhibitor 3-methyladenine （3-MA）, or with a vehicle control, were irradiated at different low doses （〈0.5 Gy）. The generation of autophagy was examined by laser scanning confocal microscopy. Western blot- ting was used to detect the expression ofmicrotubule-associated protein I light chain 3B II （LC3B- II）. Flow cytometry （FCM） and clonogenic assays were used to measure the fraction of surviving cells at the low irradiation doses. Our results showed that there was a greater inhibition of autophagic activity, but a higher degree of low-dose HRS in A549 cells treated with 3-MA than in control group. Our data dem- onstrated that radiation-induced autophagy is correlated with HRS in A549 cells, and is probably one of the mechanisms underlying HRS.

Low-dose fractionated radiation reverses cisplatin resistance in ovarian cancer cells via PI3K/AKT/GSK-3β signaling

Objective To investigate whether low-dose fractionated radiation(LDFRT) could enhance cisplatin sensitivity in drug-resistant human ovarian cancer cells SKOV3/DDP, and to further explore the underlying mechanism.Methods SKOV3/DDP ovarian cancer cells were divided into three groups as follows: control, LDFRT, and conventional-dose radiation groups. Cells from all three groups were treated with different concentrations of cisplatin(0, 1.25, 2.5, 5, 10, and 20 μg/m L) for 48 h. The proliferation inhibition rate was investigated using the cell counting kit 8(CCK8). The rate of apoptosis was determined by flow cytometry(FCM). Protein levels of AKT, P-AKT, GSK-3β, P-GSK-3β, P21, cyclin D1, and P27 were examined by Western blotting. Results As expected, LDFRT significantly reduced the half-maximal inhibitory concentration(IC50) of cisplatin and promoted apoptosis in SKOV3/DDP cells. Moreover, in the LDFRT group, protein levels of P-AKT, P-GSK-3β, and cyclin D1 were markedly decreased, those of P21 and P27 were greatly increased, and total AKT and GSK-3β levels showed no significant difference compared to those in both the control and conventional-dose radiation groups.Conclusion LDFRT sensitizes resistant SKOV3/DDP ovarian cancer cells to cisplatin through inactivation of PI3 K/AKT/GSK-3β signaling.

Granulomatous Mastitis with Erythema Nodosum That Responded to Low-Dose Steroid: Case Report and Literature Review of Nine Patients

A 31-year-old woman was referred with a painful mass in the left breast that was initially treated with antibiotics. Three weeks later, the mass had increased and polyarthritis and erythema nodosum had developed in both legs. A core needle biopsy led to a diagnosis of granulomatous mastitis with arthritis and erythema nodosum. Low-dose prednisolone (10 mg) rapidly improved the arthritis and the erythema nodosum. Granulomatous mastitis is a very rare, chronic inflammatory disease and only nine patients with granulomatous mastitis with erythema nodosum have been described. We reviewed the literature to determine the clinicopathological features and treatment of granulomatous mastitis. Appropriate diagnosis and steroid therapy should result in excellent outcomes.