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 an...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.展开更多
The role of corticosteroids in the management of severely ill patients with inlfuenza A (H1N1) viral infection is unclear and controversial. Two critically ill cases with influenza A (H1N1) infections complicated with...The role of corticosteroids in the management of severely ill patients with inlfuenza A (H1N1) viral infection is unclear and controversial. Two critically ill cases with influenza A (H1N1) infections complicated with organizing pneumonia (OP) in 2011 successfully treated with low dose corticosteroids were reported here. After initial clinical improvement, the condition of both patients aggravated 20-23 days after the onset of illness. Chest X-ray and computed tomographies (CT) showed an increment of lung infiltrates. Cultures of blood, pleural lfuid and transbronchial aspirate were negative for bacteria and fungi. Organizing pneumonia was diagnosed clinically and both patients were successfully treated with low-dose corticosteroids. Low-dose corticosteroids initiated during convalescence may be beneficial for severe swine-origin influenza A H1N1 pandemic 2009 virus (S-OIV) infections.展开更多
AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma...AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.展开更多
BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute e...BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P<0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P<0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P<0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.展开更多
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 lenva...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.展开更多
Introduction: The severity of Sars-Cov-2 infection is associated with the development of acute respiratory distress syndrome (ARDS). The progression to ARDS appears to be driven by a major inflammatory mechanism poten...Introduction: The severity of Sars-Cov-2 infection is associated with the development of acute respiratory distress syndrome (ARDS). The progression to ARDS appears to be driven by a major inflammatory mechanism potentially sensitive to corticosteroids. Observation: This article describes the case of an elderly patient was admitted to emergency departments for intense asthenia, accompanied by motor diarrhoea, dyspnoea with desaturation in ambient air, in a context of strong suspicion of infection linked to COVID-19. The article also reviews the existing literature on the diagnosis and treatment of this severe form of the disease. Conclusion: Corticosteroids, and in particular dexamethasone, have been shown to be effective in the management of patients with COVID-19, an oxygen-releasing disease.展开更多
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 ...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.展开更多
The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids.Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the...The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids.Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH.However,the data on the efficacy of corticosteroids in these patients have been conflicting.Initial meta-analyses also failed to show beneficial effects of corticosteroids.Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more),led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH.However,corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis,gastrointestinal bleeding,and acute pancreatitis.These patients may be candidates for second line treatment with pentoxifylline.Further,specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids,thus classified as nonresponsive to steroids.The management of these patients is a continuing challenge for physicians.Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH.This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status.Route of administration,dosage,adverse effects,and mechanisms of action of these two drugs are also discussed.Finally,an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described.展开更多
BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids...BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.展开更多
Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical histo...Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.展开更多
Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pa...Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.展开更多
This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology...This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology-Head & Neck Surgery. Despite the increased use of intratympanic corticosteroids for vertigo control in Meniere's disease there is debate as to their effectiveness, particularly compared to gentamicin. Even so,after just a single course of injections, corticosteroids can reliably provide complete vertigo control(Class A) at 2-years in about 50% of cases as indicated in a recent double-blind randomized controlled clinical trial(Patel et al., 2016). But the effectiveness of intratympanic corticosteroids truly increases when treatment is provided 'as-needed', whereby complete vertigo control is established in up to 91% of cases. On the basis of available literature, there is good evidence to recommend the use of intratympanic steroid treatment for vertigo control in Meniere's disease, but patients must be monitored for non-response. The rationale for treating patients as-needed and the possible reasons for corticosteroid nonresponse are discussed.展开更多
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 gast...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.展开更多
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 i...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.展开更多
Background: Pneumonia is the most common cause of community-acquired infection requiring ICU admission. 60-87% of patients with severe community acquired pneumonia (CAP) admitted to the ICU develops respiratory failur...Background: Pneumonia is the most common cause of community-acquired infection requiring ICU admission. 60-87% of patients with severe community acquired pneumonia (CAP) admitted to the ICU develops respiratory failure and require mechanical ventilation (MV). Objectives: To assess the efficacy and safety of adjunctive low dose hydrocortisone infusion treatment in Egyptian ICU patients with CAP. Methods: Hospitalized patients, clinically and radiologically diagnosed with CAP, were randomized to receive hydrocortisone 12.5 mg/h IV infusion for 7 days or placebo, along with antibiotics. The end-points of the study were improvement in PaO2:FIO2 (PaO2:FIO2 > 300 or ≥100 increase from study entry) and SOFA score by study day 8 and the development of delayed septic shock. Results: 80 patients were recruited, 40 of them received hydrocortisone and the remaining 40 received placebo. By study day 8, hydrocortisone treated patients showed a significant improvement in PaO2:FIO2 and chest radiograph score, and a significant reduction in C-reactive protein (CRP) levels, Sepsis-related Organ Failure Assessment (SOFA) score, and delayed septic shock compared to the control group. Hydrocortisone treatment was associated with a significant reduction in the duration of MV. However, hydrocortisone infusion did not show significant difference in the ICU mortality. Conclusions: adjunctive 7-day course of low dose hydrocortisone IV in patients with CAP hastens recovery of pneumonia and prevents the development of sepsis related complications with a significant reduction in duration of the mechanical ventilation.展开更多
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 mitochondri...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展开更多
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 canc...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.展开更多
Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, ...Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluoro- metholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.展开更多
It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein un...It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.展开更多
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 qual...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.展开更多
基金the United Fund of National Natural Science Foundation of China(U2004110)the Leading Talent Fund in Science and Technology Innovation in Henan Province(194200510017)+3 种基金the Science and Technology People-Benefit Project of Zhengzhou(2019KJHM0001)the Special Fund for Young and Middle-Aged Medical Research from China International Medical Foundation(Z-2018-35)the Integrated Thinking Research Fund from China International Medical Foundation(Z-2016-23-2001)the Fund for Mechanism Study on Gabexate Mesilate in Treating Sepsis and Septic Shock(2019-hx-45).
文摘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.
基金supported by a grant from the National Natural Science Foundation of China(81070005/H0104)Program for New Century Excellent Talents in University(NCET-10-0006)
文摘The role of corticosteroids in the management of severely ill patients with inlfuenza A (H1N1) viral infection is unclear and controversial. Two critically ill cases with influenza A (H1N1) infections complicated with organizing pneumonia (OP) in 2011 successfully treated with low dose corticosteroids were reported here. After initial clinical improvement, the condition of both patients aggravated 20-23 days after the onset of illness. Chest X-ray and computed tomographies (CT) showed an increment of lung infiltrates. Cultures of blood, pleural lfuid and transbronchial aspirate were negative for bacteria and fungi. Organizing pneumonia was diagnosed clinically and both patients were successfully treated with low-dose corticosteroids. Low-dose corticosteroids initiated during convalescence may be beneficial for severe swine-origin influenza A H1N1 pandemic 2009 virus (S-OIV) infections.
基金Supported by the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012)Development Projects of Zhejiang Province(No.2022C03112)Innovation Team Program of Wenzhou.
文摘AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.
文摘BACKGROUND: This study aimed to investigate the prevalence rate of critical illness-related corticosteroid insuffi ciency(CIRCI) and the effect of low-dose glucocorticoid on prognosis of CIRCI in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).METHODS: Since January 2010 to December 2012, 385 patients, who met the criteria of AECOPD, were enrolled in the Intensive Care Unit(ICU) of the First People's Hospital and Municipal Central Hospital of Xiangtan City. The AECOPD patients complicated with CIRCI screened by an adrenalcorticotrophic hormone test within 12 hours after admission to ICU were divided into a treatment group(n=32) and a control group(n=31) for a prospective, randomized and controlled clinical trial. Hydrocortisone(150 mg/d) or normal saline was injected intravenously for 7 days. The patients were followed up for 28 days after injection. The endpoint included 28-day survival time, non-shock time, ICU stay and the period of non-mechanical ventilation. The markers ofinfl ammation C-reactive protein, tumor necrosis factor-α, interleukin 6 and procalcitonin were measured at baseline and 7 days after treatment. The variables were analyzed by Student's t test, the non-parametric statistical test, the Chi-square test or the Kaplan-Meier method with SPSS18.0 statistic software. A P value <0.05 was considered statistically signifi cant.RESULTS: Totally 63 patients were diagnosed with CIRCI by an adrenalcorticotrophic hormone test and the prevalence rate was 16.4%. The shock rate of the AECOPD patients complicated with CIRCI was higher than that of the AECOPD patients without CIRCI(23.8% vs. 8.7%, P<0.01). KaplanMeier analysis revealed that the 28-day survival time of the treatment group was obviously longer than that of the control group(P<0.05). Compared with the control group, shock-free days within 28 days was longer in the treatment group(18.2±9.5 vs. 25.8±4.1, P<0.05). Treatment with low-dose glucocorticoid obviously decreased the markers ofinfection and inflammation(P<0.01), such as C-reactive protein(13.2±5.5 mg/L vs. 8.3±3.1 mg/L for the control group; 13.5±5.9 mg/L vs. 5.1±2.3 mg/L for the treatment group), tumor necrosis factor-α(26.1±16.2 g/L vs. 17.5±11.7 g/L for the control group; 25.0±14.8 g/L vs. 10.4±7.8 g/L for the treatment group) and procalcitonin(3.88 g/L vs. 2.03 g/L for the control group; 3.77 g/L vs. 1.26 g/L for the treatment group). Furthermore, the markers in the treatment group decreased more obviously than those in the control group(P<0.01).CONCLUSION: The prevalence rate of CIRCI was higher in the patients with AECOPD in the department of critical medicine, and low-dose glucocorticoid treatment for one week reduced the 28-day mortality, shock time and markers ofinfection and infl ammation.
基金financially supported by the Science and Technology Plan Project of Guangzhou (No. 202102010171)National Natural Science Foundation Cultivation Project of the Third Affiliated Hospital of Sun Yat-sen University (No. 2020GZRPYMS11)+2 种基金Natural Science Foundation of Guangdong Province (No. 2018A030313641)Natural Science Foundation of Guangdong Province (No. 2016A030313848)Science and Technology Plan Project of Guangzhou (No. 201704020175)。
文摘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.
文摘Introduction: The severity of Sars-Cov-2 infection is associated with the development of acute respiratory distress syndrome (ARDS). The progression to ARDS appears to be driven by a major inflammatory mechanism potentially sensitive to corticosteroids. Observation: This article describes the case of an elderly patient was admitted to emergency departments for intense asthenia, accompanied by motor diarrhoea, dyspnoea with desaturation in ambient air, in a context of strong suspicion of infection linked to COVID-19. The article also reviews the existing literature on the diagnosis and treatment of this severe form of the disease. Conclusion: Corticosteroids, and in particular dexamethasone, have been shown to be effective in the management of patients with COVID-19, an oxygen-releasing disease.
文摘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.
文摘The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids.Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH.However,the data on the efficacy of corticosteroids in these patients have been conflicting.Initial meta-analyses also failed to show beneficial effects of corticosteroids.Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more),led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH.However,corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis,gastrointestinal bleeding,and acute pancreatitis.These patients may be candidates for second line treatment with pentoxifylline.Further,specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids,thus classified as nonresponsive to steroids.The management of these patients is a continuing challenge for physicians.Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH.This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status.Route of administration,dosage,adverse effects,and mechanisms of action of these two drugs are also discussed.Finally,an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described.
基金supported by a grant from the General Project Foundation of the Education Department of Liaoning Province (2009A809)
文摘BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.
文摘Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.
文摘Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.
基金supported by the National Institute for Health Research(NIHR)Imperial Biomedical Research Centre
文摘This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology-Head & Neck Surgery. Despite the increased use of intratympanic corticosteroids for vertigo control in Meniere's disease there is debate as to their effectiveness, particularly compared to gentamicin. Even so,after just a single course of injections, corticosteroids can reliably provide complete vertigo control(Class A) at 2-years in about 50% of cases as indicated in a recent double-blind randomized controlled clinical trial(Patel et al., 2016). But the effectiveness of intratympanic corticosteroids truly increases when treatment is provided 'as-needed', whereby complete vertigo control is established in up to 91% of cases. On the basis of available literature, there is good evidence to recommend the use of intratympanic steroid treatment for vertigo control in Meniere's disease, but patients must be monitored for non-response. The rationale for treating patients as-needed and the possible reasons for corticosteroid nonresponse are discussed.
文摘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.
基金Supported by First Affiliated Hospital,Guangxi Medical University
文摘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.
文摘Background: Pneumonia is the most common cause of community-acquired infection requiring ICU admission. 60-87% of patients with severe community acquired pneumonia (CAP) admitted to the ICU develops respiratory failure and require mechanical ventilation (MV). Objectives: To assess the efficacy and safety of adjunctive low dose hydrocortisone infusion treatment in Egyptian ICU patients with CAP. Methods: Hospitalized patients, clinically and radiologically diagnosed with CAP, were randomized to receive hydrocortisone 12.5 mg/h IV infusion for 7 days or placebo, along with antibiotics. The end-points of the study were improvement in PaO2:FIO2 (PaO2:FIO2 > 300 or ≥100 increase from study entry) and SOFA score by study day 8 and the development of delayed septic shock. Results: 80 patients were recruited, 40 of them received hydrocortisone and the remaining 40 received placebo. By study day 8, hydrocortisone treated patients showed a significant improvement in PaO2:FIO2 and chest radiograph score, and a significant reduction in C-reactive protein (CRP) levels, Sepsis-related Organ Failure Assessment (SOFA) score, and delayed septic shock compared to the control group. Hydrocortisone treatment was associated with a significant reduction in the duration of MV. However, hydrocortisone infusion did not show significant difference in the ICU mortality. Conclusions: adjunctive 7-day course of low dose hydrocortisone IV in patients with CAP hastens recovery of pneumonia and prevents the development of sepsis related complications with a significant reduction in duration of the mechanical ventilation.
基金supported by the National Natural Science Foundation of China (30970681)Basic Research and Operating Expenses of Jilin University (200903116)
文摘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
基金supported by Peking Union Medical College Youth Fund and the Fundamental Research Funds for the Central Universities(No.2017310049)
文摘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.
文摘Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluoro- metholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.
基金supported by a grant from the University of Torino(Ricerca Locale ex-60%,Bando 2015)
文摘It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.
基金This work was supported in part by the National Key R&D Program of China(Nos.2016YFC0104609 and 2019YFC0605203)The Fundamental Research Funds for the Central Universities(Nos.2019CDYGYB019 and 2020CDJ-LHZZ-075)。
文摘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.