Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

Analysis of the Efficacy of Low-Dose Betaloc Combined with Amiodarone in Treating Ventricular Arrhythmia

Objective:To explore and analyze the clinical effect of low-dose Betaloc combined with amiodarone in treating ventricular arrhythmia.Methods:70 patients with ventricular arrhythmia who were admitted to the Department of Cardiology of our hospital between August 2022 and August 2023 were selected as research subjects.They were divided into two groups using the coin-tossing method:the combination group(n=35)and the reference group(n=35).The combination group was treated with low-dose Betaloc and amiodarone,and the control group was treated with low-dose Betaloc alone.The treatment efficacy,cardiac function indicators,and related tested indicators of the two groups were compared.Results:The total efficacy of the treatment received by the combination group was much higher than that of the control group(P<0.05).Besides,after treatment,the cardiac function indicators such as left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV),and cardiac index(CI)of the patients in the combination group were significantly better than those of the reference group(P<0.05).Furthermore,the high-sensitivity C-reactive protein(Hs-CRP),N-terminal prohormone of brain natriuretic peptide(NT-proBNP),adiponectin(APN),and other related test indicators of the patients in the combination group were significantly better than those of the reference group(P<0.05).Conclusion:Low-dose Betaloc combined with amiodarone has a noticeable effect in treating ventricular arrhythmia and deserves to be widely promoted.

Successful treatment of patients with refractory idiopathic membranous nephropathy with low-dose Rituximab:A single-center experience

BACKGROUND The recognition of idiopathic membranous nephropathy(IMN)as an autoimmune disease has paved the way for the use of B-cell-depleting agents,such as Rituximab(RTX),which is now a first-line drug for treating IMN with proven safety and efficacy.Nevertheless,the usage of RTX for the treatment of refractory IMN remains controversial and challenging.AIM To evaluate the efficacy and safety of a new low-dose RTX regimen for the treatment of patients with refractory IMN.METHODS A retrospective study was performed on refractory IMN patients that accepted a low-dose RTX regimen(RTX,200 mg,once a month for five months)in the Xiyuan Hospital of Chinese Academy of Chinese Medical Sciences’Department of Nephrology from October 2019 to December 2021.To assess the clinical and immune remission data,we performed a 24 h urinary protein quantification(UTP)test and measured the serum albumin(ALB)and serum creatinine(SCr)levels,phospholipase A2 receptor(PLA2R)antibody titer,and CD19+B-cell count every three months.RESULTS A total of nine refractory IMN patients were analyzed.During follow-up conducted twelve months later,the results from the 24 h UTP decreased from baseline[8.14±6.05 g/d to 1.24±1.34 g/d(P<0.05)]and the ALB levels increased from baseline[28.06±8.42 g/L to 40.93±5.85 g/L(P<0.01)].Notably,after administering RTX for six months,the SCr decreased from 78.13±16.49μmol/L to 109.67±40.87μmol/L(P<0.05).All of the nine patients were positive for serum anti-PLA2R at the beginning,and four patients had normal anti-PLA2R titer levels at six months.The level of CD19+B-cells decreased to 0 at three months,and CD19+B-cell count remained at 0 up until six months of follow-up.CONCLUSION Our low-dose RTX regimen appears to be a promising treatment strategy for refractory IMN.

Hformer:highly efficient vision transformer for low-dose CT denoising

In this paper,we propose Hformer,a novel supervised learning model for low-dose computer tomography(LDCT)denoising.Hformer combines the strengths of convolutional neural networks for local feature extraction and transformer models for global feature capture.The performance of Hformer was verified and evaluated based on the AAPM-Mayo Clinic LDCT Grand Challenge Dataset.Compared with the former representative state-of-the-art(SOTA)model designs under different architectures,Hformer achieved optimal metrics without requiring a large number of learning parameters,with metrics of33.4405 PSNR,8.6956 RMSE,and 0.9163 SSIM.The experiments demonstrated designed Hformer is a SOTA model for noise suppression,structure preservation,and lesion detection.

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.

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.

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

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.

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.

Effi cacy and safety of low-dose corticosteroids for acute respiratory distress syndrome:A systematic review and meta-analysis

BACKGROUND:There are confl icting results regarding whether corticosteroids have better effi cacy than placebo in acute respiratory distress syndrome(ARDS)patients.Therefore,we aim to further evaluate the effi cacy and safety of corticosteroids in adult ARDS patients.METHODS:The databases,including Medline,EMBASE,and Cochrane Central Register of Controlled Trials(CENTRAL)in the Cochrane Library,were searched from their inception to May 2,2020.Randomized controlled trials(RCTs)and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients.The quality of the results was judged by the Grading of Recommendations Assessment,Development,and Evaluation(GRADE)methodology.The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio(OR),standardized mean diff erence(SMD),and their 95%confi dence interval(CI).RESULTS:Eight eligible RCTs and six cohort studies were included.The use of corticosteroids was associated with reduced mortality(OR 0.57,95%CI 0.43-0.76,I2=35.1%,P=0.148)in ARDS patients,and the result was confirmed in the included cohort studies(OR 0.51,95%CI 0.27-0.95,I2=66.7%,P=0.010).The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had signifi cant survival benefits in the RCTs.The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients.CONCLUSIONS:The low-dose corticosteroid therapy may be safe and reduce mortality,especially in patients with prolonged treatment and early ARDS.

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.

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.

Sinogram denoising via attention residual dense convolutional neural network for low-dose computed tomography

The widespread use of computed tomography(CT)in clinical practice has made the public focus on the cumulative radiation dose delivered to patients.Low-dose CT(LDCT)reduces the X-ray radiation dose,yet compromises quality and decreases diagnostic performance.Researchers have made great efforts to develop various algorithms for LDCT and introduced deep-learning techniques,which have achieved impressive results.However,most of these methods are directly performed on reconstructed LDCT images,in which some subtle structures and details are readily lost during the reconstruction procedure,and convolutional neural network(CNN)-based methods for raw LDCT projection data are rarely reported.To address this problem,we adopted an attention residual dense CNN,referred to as AttRDN,for LDCT sinogram denoising.First,it was aided by the attention mechanism,in which the advantages of both feature fusion and global residual learning were used to extract noise from the contaminated LDCT sinograms.Then,the denoised sinogram was restored by subtracting the noise obtained from the input noisy sinogram.Finally,the CT image was reconstructed using filtered back-projection.The experimental results qualitatively and quantitatively demonstrate that the proposed AttRDN can achieve a better performance than state-of-the-art methods.Importantly,it can prevent the loss of detailed information and has the potential for clinical application.

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.

Effect of low-dose radiation on thyroid function and the gut microbiota

BACKGROUND The thyroid-gut axis has a great influence on the maintenance of human health;however,we know very little about the effects of low-dose ionizing radiation(LDR) on thyroid hormone levels and gut microbiota composition.AIM To investigate the potential effects of low-dose X-ray radiation to male C57BL/6J mice.METHODS Peripheral blood was collected for enzyme-linked immunosorbent assay(ELISA),and stool samples were taken for 16S ribosomal RNA(rRNA) gene sequencing after irradiation.RESULTS We found that LDR caused changes in thyroid stimulating hormone(TSH) levels in the irradiated mice,suggesting a dose-dependent response in thyroid function to ionizing radiation.No changes in the diversity and richness of the gut microbiota were observed in the LDR-exposed group in comparison to the controls.The abundance of Moraxellaceae and Enterobacteriaceae decreased in the LDR-exposed groups compared with the controls,and the Lachnospiraceae abundance increased in a dose-dependent manner in the radiated groups.And the abundances of uncultured_bacterium_g_Acinetobacter,uncultured_bacterium_o_Mollicutes_RF39,uncultured_bacterium_g_Citrobacter,and uncultured_bacterium_g_Lactococcus decreased in the radiated groups at the genus level,which showed a correlation with radiation exposure and diagnostic efficacy.Analysis of functional metabolic pathways revealed that biological metabolism was predicted to have an effect on functional activities,such as nucleotide metabolism,carbohydrate metabolism,and glycan biosynthesis and metabolism.Furthermore,Kyoto Encyclopedia of Genes and Genomes pathway annotation also suggested that changes in the gut microbiota were related to processing functions,including translation,replication and repair.CONCLUSION LDR can change thyroid function and the gut microbiota,and changes in the abundances of bacteria are correlated with the radiation dose.

Low-dose lipopolysaccharide as an immune regulator for homeostasis maintenance in the central nervous system through transformation to neuroprotective microglia

Microglia,which are tissue-resident macrophages in the brain,play a central role in the brain innate immunity and contribute to the maintenance of brain homeostasis.Lipopolysaccharide is a component of the outer membrane of gram-negative bacteria,and activates immune cells including microglia via Toll-like receptor 4 signaling.Lipopolysaccharide is generally known as an endotoxin,as administration of highdose lipopolysaccharide induces potent systemic inflammation.Also,it has long been recognized that lipopolysaccharide exacerbates neuroinflammation.In contrast,our study revealed that oral administration of lipopolysaccharide ameliorates Alzheimer’s disease pathology and suggested that neuroprotective microglia are involved in this phenomenon.Additionally,other recent studies have accumulated evidence demonstrating that controlled immune training with low-dose lipopolysaccharide prevents neuronal damage by transforming the microglia into a neuroprotective phenotype.Therefore,lipopolysaccharide may not a mere inflammatory inducer,but an immunomodulator that can lead to neuroprotective effects in the brain.In this review,we summarized current studies regarding neuroprotective microglia transformed by immune training with lipopolysaccharide.We state that microglia transformed by lipopolysaccharide preconditioning cannot simply be characterized by their general suppression of proinflammatory mediators and general promotion of anti-inflammatory mediators,but instead must be described by their complex profile comprising various molecules related to inflammatory regulation,phagocytosis,neuroprotection,anti-apoptosis,and antioxidation.In addition,microglial transformation seems to depend on the dose of lipopolysaccharide used during immune training.Immune training of neuroprotective microglia using lowdose lipopolysaccharide,especially through oral lipopolysaccharide administration,may represent an innovative prevention or treatment for neurological diseases;however more vigorous studies are still required to properly modulate these treatments.

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.

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 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.

Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents,such as vitamin D compounds,is a potential regimen to treat acute myeloid leukemia（AML） patients who are unfit for high-intensity chemotherapy.The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3（1,25-D3）.Here,firstly,c Bio Portal database was used and we found out that vitamin D receptor（VDR） was highly expressed in acute monocytic leukemia（M5） and high VDR expression was associated with a poor survival of AML patients.Then,we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines（U937,MOLM-13,THP-1） and blasts from M5 patients than in non-monocytic cell lines（KG1 a and K562） and blasts from M2 patient.Finally,it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate,growth inhibition and G0/G1 arrest,while mild changes were found in the apoptosis in acute monocytic leukemia cell lines.Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia,especially for elderly and frail ones.