Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

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.

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.

Leflunomide对实验性IgA肾病大鼠肾脏TGF-β_1、MCP-1表达的影响

目的:分别从基因和蛋白水平研究leflunomide对实验性IgA肾病(IgAN)大鼠肾组织转化生长因子(TGF-β1)、单核细胞趋化因子(MCP-1)水平的影响,了解其作用机制。方法:建立IgAN大鼠模型,随机分成leflunomide组、强的松组、模型对照组,并同时设立正常对照组。用免疫组化、RT-PCR的方法分别检测和比较各组肾组织TGF-β1、MCP-1蛋白和基因的表达水平。结果:Leflunomide组TGF-β1、MCP-1表达均明显低于模型对照组(P<0.05);leflunomide组与激素组相比,TGF-β1、MCP-1表达无明显差异。结论:Leflunomide可通过下调TGF-β1、MCP-1在肾脏的表达,减少局部炎症反应,延缓肾脏纤维化的进程,从而保护肾脏。

Leflunomide对实验性IgA肾病大鼠肾脏病理及MCP-1表达的影响

目的观察leflunomide对实验性IgA肾病(IgAnephropathyIgAN)大鼠肾脏病理及肾组织单核细胞趋化因子(monocytechemoattractivepeptide1,MCP-1)表达的影响,了解其作用机制。方法建立IgAN大鼠模型,随机分成leflunomide组,强的松组,模型对照组,并同时设立正常对照组。行免疫荧光、光镜检查,并用免疫组化和RT-PCR方法分别检测肾组织MCP-1蛋白和基因水平的表达。结果与模型对照组相比,leflunomide组免疫复合物在肾脏的沉积明显减少,系膜区基质增生程度显著减轻(P<0.01);Leflunomide在基因和蛋白水平均能够有效抑制MCP-1在肾组织的表达(P<0.05)。结论Leflunomide能够减少免疫复合物在肾脏的沉积,减轻系膜区基质增生,并且下调MCP-1在肾脏的表达,减少局部炎症反应,减轻肾脏损害,保护肾脏。

Leflunomide对异种肾移植(豚鼠/大白鼠)超急排斥反应的抑制效果

目的：观察Ｌｅｆｌｕｎｏｍｉｄｅ对异种肾移植超急排斥反应的抑制效果。方法：用已经建立的异种异位肾移植超急排斥反应模型。术前１，３，５，７天开始分别给５组受鼠口服Ｌｅｆｌｕｎｏｍｉｄｅ１０ｍｇ／（ｋｇ·ｄ）。观察超急排斥反应发生的时间。结果：术前服药时间少于３天的受鼠，其超急排斥反应发生的时间与对照组相比无明显变化；术前服药５天和７天的受鼠，移植肾的持续泌尿时间分别为９５８±２０９ｍｉｎ和２７２５±７６３ｍｉｎ，显著长于对照组。结论：Ｌｅｆｌｕｎｏｍｉｄｅ作为免疫抑制剂，在异种（豚鼠→大白鼠）肾移植实验研究中，可推迟、但不能消除异种超急排斥反应。

Leflunomide对结肠癌细胞增殖及凋亡的影响

目的:检测Leflunomide对结肠癌细胞增殖和诱导凋亡作用。方法:实验采用结肠癌细胞株SW260,与不同浓度的Leflunomide药物(0、5、10、20、40、80μg/ml)共同培养,以MTT方法和流式细胞仪技术检测细胞的增殖状态,用TUNEL染色和流式细胞仪技术检测细胞的凋亡。结果:Leflunomide在对结肠癌细胞增殖具有双重影响,即在低浓度下(5μg/ml和10μg/ml)有轻度的促进结肠癌细胞SW620增殖的作用,而提高浓度后(>40μg/ml)则表现为明显的抑制细胞的增殖作用,并随着剂量增加和作用时间延长,抑制作用更为明显,即存在着时相性和量-效依赖性。结论:Leflunomide可抑制结肠癌细胞增殖和诱导凋亡。可能对结肠癌病人有潜在的治疗作用。

抗排斥反应的新型免疫抑制剂──Leflunomide

Ｌｅｆｌｕｎｏｍｉｄｅ是一种新型的免疫抑制剂，具有明显的抗急、慢性免疫排斥反应的作用。其作用机制可能与以下三个方面有关：抑制Ｔ、Ｂ淋巴细胞增殖，影响细胞因子及其受体的表达；抑制蛋白酪氨酸激酶的活性；抑制二清乳氢酸脱氢酶的活性。

抗排斥反应的新型免疫抑制剂——Leflunomide

Leflunomide(Lef),又称HWA486,暂译名为雷抑素),是一种新型免疫抑制剂,属异恶唑类衍生物。1979年由德国Hoechst A.G药厂首先合成,初步证实能有效防治MRL小鼠系统性红斑狼疮及慢性移植物抗宿主病和大鼠肾小管间质性肾炎等一系列自身免疫性疾病。此外。

Leflunomide在器官移植中的应用

Leflunomide(Lef)是一种异恶唑类化合物 ,它的应用范围较广 ,目前的研究发现 ,Lef作用于免疫反应的多个环节 ,具有强大的抗排斥反应作用 ,同时Lef具有独特的抗巨细胞病毒感染的作用 ,因此受到移植界的重视。本文对Lef在器官移植抗排斥反应中的应用研究作一综述。

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.

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.

Small-bowel mucosal injuries in low-dose aspirin users with obscure gastrointestinal bleeding

AIM: To investigate the clinical differences between small intestinal injuries in low-dose aspirin (LDA) users and in non-steroidal anti-inflammatory drug (NSAID) users who were examined by capsule endoscopy (CE) for obscure gastrointestinal bleeding (OGIB).

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.

Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLC-UV method for their quantification

Leflunomide （LLM） is subjected to forced degradation under conditions of hydrolysis, oxidation, dry heat, and photolysis as recommended by International Conference on Harmonization guideline Q1A（R2）. In total, four degradation products （I-IV） were formed under different conditions. Products I, II and IV were formed in alkaline hydrolytic, acidic hydrolytic and alkaline photolytic conditions. LLM and all degradation products were optimally resolved by gradient elution over a C18 column. The major degradation product （IV） formed in hydrolytic alkaline conditions was isolated through column chromatography. Based on its IH NMR, IR and mass spectral data, it was characterized as a British Pharmacopoeial impurity B. The HPLC method was found to be linear, accurate, precise, sensitive, specific, rugged and robust for quantification of LLM as well as product IV. Finally, the method was applied to stability testing of the commercially available LLM tablets.