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.

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.

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.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

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). METHODS: A total of 181 patients who underwent CE for OGIB were included in this study. Based on clinical records, laboratory data such as hemoglobin levels, major symptoms, underlying diseases, the types and duration of LDA and NSAID use, and endoscopic characteristics of CE were reviewed.RESULTS: Out of a total of 45 cases of erosive lesions, 27 cases were taking LDA or NSAIDs(7 were on NSAIDs, 9 were on LDA alone, 9 were on LDA and thienopyridine, and 2 were on LDA and warfarin).The prevalence of ulcers or erosion during chronic use of LDA, LDA and the anti-platelet drug thienopyridine (clopidogrel or ticlopidine), and NSAIDs were 64.3%, 80.0%, and 75.0%, respectively. Erosive lesions were observed predominantly in chronic LDA users, while ulcerative lesions were detected mainly in NSAID users. However, concomitant use of thienopyridine such as clopidogrel with LDA increased the proportion of ulcers. The erosive lesions were located in the whole of the small intestine(jejunum and ileum), whereas ulcerative lesions were mainly observed in the ileum(P < 0.05). CONCLUSION: Our CE findings indicate that chronic LDA users and NSAID users show different types and locations of small-bowel mucosal injuries. The concomitant use of anti-platelet drugs with LDA tends to exacerbate the injuries from LDA-type to NSAID-type injuries.

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

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

Effect of low-dose aspirin administration on long-term survival of cirrhotic patients after splenectomy: A retrospective single-center study

BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.

Esophageal mucosal lesion with low-dose aspirin and prasugrel mimics malignancy: A case report

Dual antiplatelet therapy consisting of low-dose aspirin (LDA) and other antiplatelet medications is recommended in patients with coronary heart disease, but it may increase the risk of esophageal lesion and bleeding. We describe a case of esophageal mucosal lesion that was difficult to distinguish from malignancy in a patient with a history of ingesting LDA and prasugrel after implantation of a drug-eluting stent. Multiple auxiliary examinations were performed to make a definite diagnosis. The patient recovered completely after concomitant acid-suppressive therapy. Based on these findings, we strongly argue for the evaluation of the risk of gastrointestinal mucosal injury and hemorrhage if LDA therapy is required, and we stress the paramount importance of using drug combinations in individual patients.

Combined Low-dose Aspirin and Warfarin Anticoagulant Therapy of Postoperative Atrial Fibrillation Following Mechanical Heart Valve Replacement

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients （620 females, mean age of 36.8-4-7.7 years） admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study （warfarin plus 75-100 mg aspirin） or control （warfarin only） groups. International normalized ratio （INR） and prothrombin time were main- tained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respec- tively （P〉0.05）. The incidence of overall thromboembolic events in study group was lower than that in control group （2.16% vs. 4.35%, P=0.049）. No statistically significant differences were found in hem- orrhage events （3.53% vs. 3.95%, P=-0.722） or mortality （0.20% vs. 0.40%, P=0.559） between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Clinical use of low-dose aspirin for elders and sensitive subjects

The use of low-dose aspirin(LDA)has been a common preventive measure to reduce the risk of cardiovascular events.This is attributed to aspirin’s ability to inhibit platelet activation.On the other hand,the use of LDA in human subjects has been associated with the development of gastrointestinal injuries like ulcer and bleeding,especially for those sensitive subjects such as elder human subjects.This opinion review will summarize the recent clinical reports regarding the use of LDA and the development of gastrointestinal conditions in China.Based on these reports,it seems that the use of LDA is commonly associated with gastrointestinal injuries,and stopping its use leads to recovery in elderly subjects.Therefore,we would like to suggest that gastroduodenal health and conditions should be seriously taken into consideration when LDA is recommended to the elderly,or other alternative means to reduce the risk of cardiovascular events such as nutritional interventions should be suggested.

Evaluation of small bowel blood flow in healthy subjects receiving low-dose aspirin

AIM:To investigate the relationship between low-dose aspirin-induced small bowel mucosal damage and blood flow,and the effect of rebamipide. METHODS:Ten healthy volunteers were enrolled in this study.The subjects were divided into two groups:a placebo group given low-dose aspirin plus placebo and a rebamipide group given low-dose aspirin plus rebamipide for a period of 14 d.Capsule endoscopy and contrast-enhanced ultrasonography were performed before and after administration of drugs.Areas under the curves and peak value of time-intensity curve were calculated. RESULTS:Absolute differences in areas under the curves were-1102.5(95%CI:-1980.3 to-224.7,P=0.0194) in the placebo group and-152.7(95%CI:-1604.2 to 641.6,P=0.8172) in the rebamipide group. Peak values of time intensity curves were-148.0(95% CI:-269.4 to-26.2,P=0.0225) in the placebo group and 28.3(95%CI:-269.0 to 325.6,P=0.8343) in the rebamipide group.Capsule endoscopy showed mucosal breaks only in the placebo group. CONCLUSION:Short-term administration of low-dose aspirin is associated with small bowel injuries and blood flow.

Effect of low-dose aspirin and Danshen injection on hemorheology, vascular endothelial function and oxidative stress in pregnancy-induced hypertension

Objective:To investigate the effect of low dose aspirin and salvia miltiorrhiza injection on hemorrheology, endothelial function and oxidative stress in patients with pregnancy induced hypertension.Methods: One hundred and eighty pregnancy-induced hypertension patients treated in our hospital from April 2015 to November 2016 were selected as study subjects and randomly divided into control group and observation group with 90 cases in each group. The control group was given routine treatment. The observation group was treated with low-dose aspirin plus Salvia miltiorrhiza in the control group. After treatment, blood rheology, vascular endothelial function and oxidative stress were measured in two groups.Results: The levels of MAP and 24 h Upro in both groups were significantly lower than those before treatment. After treatment, the MAP and 24 h Upro levels in the observation group were significantly lower than those in the control group. After treatment, the level of PT was significantly higher than that before treatment, while the level of DD and Fg was significantly lower than that before treatment. Comparing the two groups after treatment showed that the PT level, and the levels of DD and Fg were significantly lower than those in the control group;After treatment, NO levels in both groups were significantly higher than those before treatment, ET-1 and ET-1/NO levels were significantly lower than before treatment, after treatment, ET-1, NO and ET The NO level in the observation group was significantly higher than that in the control group, while ET-1 and ET-1/NO levels were significantly lower than those in the control group;Compared with those before treatment, the levels of SOD in the two groups were significantly increased and MDA significantly decreased after treatment. The SOD and MDA levels in the two groups after treatment showed that the SOD level in the observation group was significantly higher than that in the control group, while MDA level was significantly lower than that of the control group.Conclusion: The combination of low-dose aspirin and Salvia miltiorrhiza injection has significant therapeutic effect on gestational hypertension, and can effectively improve the hemorheological parameters and endothelial function of patients and reduce the oxidative stress injury in patients. It is worth further clinical promotion.

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.

Efficacy and safety of low-dose aspirin on preventing transplant renal artery stenosis: a prospective randomized controlled trial

Background:Transplant renal artery stenosis(TRAS)is a vascular complication after kidney transplantation associated with poor outcomes.This study aimed to analyze the efficacy and safety of low-dose aspirin for preventing TRAS.Methods:After kidney transplantation,patients were enrolled from January 2018 to December 2020 in Henan Provincial People’s Hospital.A total of 351 enrolled recipients were randomized to an aspirin group with low-dose intake of aspirin in addition to standard treatment(n=178),or a control group with only standard treatment(n=173).The patients was initially diagnosed as TRAS(id-TRAS)by Doppler ultrasound,and confirmed cases were diagnosed by DSA(c-TRAS).Results:In the aspirin and control groups,15.7%(28/178)and 22.0%(38/173)of the recipients developed id-TRAS,respectively,with no statistical difference.However,for c-TRAS,the difference of incidence and cumulative incidence was statistically significant.The incidence of c-TRAS was lower in the aspirin group compared with the control group(2.8%[5/178]vs.11.6%[20/173],P=0.001).Kaplan–Meier estimates and Cox regression model identified the cumulative incidence and hazard ratio(HR)of TRAS over time in two groups,showing that recipients treated with aspirin had a significantly lower risk of c-TRAS than those who were not treated(log-rank P=0.001,HR=0.23,95%confidence interval[CI]:0.09–0.62).The levels of platelet aggregation rate(P<0.001),cholesterol(P=0.028),and low-density lipoprotein cholesterol(P=0.003)in the aspirin group were decreased compared with the control group in the third-month post-transplantation.For the incidence of adverse events,there was no statistical difference.Conclusion:Clinical application of low-dose aspirin after renal transplant could prevent the development of TRAS with no significant increase in adverse effects.Trial Registration:Clinicaltrials.gov,NCT04260828.

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.

Low-dose aspirin in the prevention of pre-eclampsia in China: postpartum hemorrhage in subgroups of women according to their characteristics and potential bleeding risk

Background:The APPEC study is a large-population randomized controlled trial in China evaluating the role of low-dose aspirin prophylactic treatment for pre-eclampsia.There was no statistically significant difference in postpartum hemorrhage(PPH)incidence between the aspirin and control groups.This study aimed to evaluate the potential bleeding risk of 100 mg aspirin in high-risk pregnant women and the difference in the incidence of PPH according to maternal characteristics.Methods:This is a secondary data analysis of the APPEC study.Platelet counts and coagulation test results were collected at five follow-up visits.Subgroups defined by maternal age(<35 years and≥35 years),pre-pregnancy body mass index(pre-BMI,<28 kg/m 2 and≥28 kg/m 2),parity,gestational age at enrollment,and medical history,including pre-eclampsia,chronic hypertension,and diabetes mellitus,were analyzed.Logistic regression analysis was used to determine the statistical significance of the difference in the incidence of PPH after aspirin administration in pregnant women in each subgroup.Adjustment using multiple logistic regression models followed these analyses.Binary logistic regression was used to determine the relationship between pre-BMI and PPH.Results:There was no significant difference between the aspirin and control groups in bleeding risk(3.4%[16/464]vs.3.0%[13/434],T=0.147,P=0.701).No significant difference was found in the incidence of PPH in total(relative risk=1.220,95%confidence interval[CI]=0.720–2.067,P=0.459;aspirin group vs.control group,6.5%[30/464]vs.5.3%[23/434],P=0.459)or in subgroup analysis.A significant correlation between pre-BMI and PPH was found in the aspirin group,while in the control group there was no significant correlation(aspirin group,odds ratio[OR]=1.086,95%CI=1.004–1.175,P=0.040;control group,OR=1.060,95%CI=0.968–1.161,P=0.209).Conclusions:A dosage of 100 mg of aspirin per day,initiated from 12 to 20 gestational weeks until 34 weeks of gestation,did not increase the risk of potential bleeding and PPH regardless of the maternal characteristic.In the aspirin group,the positive correlation between BMI and PPH was significant.Trial Registration:ClinicalTrials.gov,NCT01979627.

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

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

Prevention of Osteopenia and Dyslipidemia in Rats after Ovariectomy with Combined Aspirin and Low-dose Diethylstilbestrol

Objective To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia. Methods Thirty-eight 4-month-old female SD rats were divided into baseline （BAS） group （n=6）, sham operation group （n=8） and ovariectomy （OVX） group （n=24）. The OVX group was further divided into vehicle treatment group （n=8）, diethylstilbestrol （30 ug/kg.d） treatment group （OVX＋D30 group, n=8）, and aspirin （9 mg/kg.d） plus diethylstilbestrol （10 ug/kg.d） treatment group （OVX＋A-D10 group, n=8）. Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement. Results The body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats. Conclusion Aspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.

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

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

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity

BACKGROUND Hepatocellular carcinoma(HCC)is the most common malignant liver disease in the world.Platelets(PLTs)are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases.Aspirin is the most classic antiplatelet agent.However,the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study.AIM To explore the impact of the antiplatelet effect of aspirin on the development of HCC.METHODS Platelet-rich plasma,platelet plasma,pure platelet,and platelet lysate were prepared,and a coculture model of PLTs and HCC cells was established.CCK-8 analysis,apoptosis analysis,Transwell analysis,and real-time polymerase chain reaction(RT-PCR)were used to analyze the effects of PLTs on the growth,metastasis,and inflammatory microenvironment of HCC.RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways.Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo,and the effect of PLTs on the progression of HCC RESULTS PLTs significantly promoted the growth,invasion,epithelial-mesenchymal transition,and formation of an inflammatory microenvironment in HCC cells.Activated PLTs promoted HCC progression by activating the mitogenactivated protein kinase/protein kinase B/signal transducer and activator of transcription three(MAPK/AKT/STAT3)signaling axis.Additionally,aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation.CONCLUSION PLTs play an important role in the pathogenesis of HCC,and aspirin can affect HCC progression by inhibiting platelet activity.These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.