Imperative for long-term management and surveillance in Kawasaki disease

Kawasaki disease(KD)is a significant pediatric vasculitis known for its potential to cause severe coronary artery complications.Despite the effectiveness of initial treatments,such as intravenous immunoglobulin,KD patients can experience long-term cardiovascular issues,as evidenced by a recent case report of an adult who suffered a ST-segment elevation myocardial infarction due to previous KD in the World Journal of Clinical Cases.This editorial emphasizes the critical need for long-term management and regular surveillance to prevent such complications.By drawing on recent research and case studies,we advocate for a structured approach to follow-up care that includes routine cardiac evaluations and preventive measures.

基于Clinical Trials数据库的癌性疼痛治疗药物临床试验分析

目的了解近年来癌性疼痛(癌痛)治疗药物临床试验的趋势和特点,为癌痛治疗药物的开发和临床研究提供参考依据。方法从Clinical Trials数据库中检索1987—2022年癌痛治疗药物临床试验的相关信息,从试验类型、备案时间、申报地区、癌痛类型、癌痛治疗药物等角度进行描述性分析。结果筛选出临床试验376项,由研究者发起的试验(IIT)项目数多于注册类试验(IST),其中北美洲的总项目数、IIT和IST项目数最多;试验总项目数和IST项目数先增长后回落,IIT的试验项目数稳步增长。针对慢性癌痛、爆发性癌痛和重度癌痛的研究相对较多。研究对象以阿片类药物尤其是芬太尼的占比最高。结论癌痛治疗药物临床试验对推进癌痛治疗药物治疗发挥了重要作用,未来有待进一步加强IST在新型癌痛治疗药物的研究和开展更多IIT研究,以更好地优化癌痛治疗效果。

Long-term effect of clopidogrel in patients with and without diabetes: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Previous studies have shown that patients with diabetes mellitus(DM) respond poorly to clopidogrel treatment.AIM To systematically evaluate the efficacy of clopidogrel for the treatment of acute coronary syndromes or ischemic stroke in patients with or without DM.METHODS Pub Med,the Cochrane Central Register of Controlled Trials,and EMBASE were searched from 1980 on 27 June 2019 to identify relevant randomized controlled trials that compared the effect of a combination of clopidogrel and aspirin with aspirin alone.A random-effects meta-analysis was used to estimate the hazard ratio(HR) and its 95% confidence interval(CI).Sensitivity analysis was performed using a fixed-effect model.The I2 statistic was used to evaluate the heterogeneity of the study data.RESULTS Six randomized controlled trials,comprising 43352 participants(13491 with and 29861 without DM) who had received antiplatelet therapy for≥3 mo,were included in the meta-analysis.Compared with aspirin alone,a combination of clopidogrel and aspirin significantly reduced the risk of any cardiovascular event in patients without DM(HR=0.78,95%CI:0.71–0.86,P<0.001;I2=23%,P=0.26).Clopidogrel plus aspirin also significantly reduced cardiovascular risk in patients with DM,although the effect was smaller(HR=0.89,95%CI:0.81–0.99,P=0.030;I2=0%,P=0.74).Nevertheless,there was no significant difference in the efficacy of clopidogrel at reducing the risk of cardiovascular events in patients with DM vs those without(P for interaction=0.062).CONCLUSION Thus,the present study shows that the addition of clopidogrel to aspirin significantly lowers cardiovascular risk in patients with or without DM who have experienced ischemic cardiovascular disease.The beneficial effect of the addition of clopidogrel to aspirin for patients with DM was lower than that in patients without DM,although the modifying effect of DM did not reach significance.

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: An unblinded randomized trial

AIM： To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications. METHODS： One hundred consecutive patients admitted for first-onset ascites were randomized to receive diuretics plus human albumin 25 g/wk in the first year and 25 g every two wk thereafter （group 1） or diuretics alone （group 2）. The primary endpoint was survival without liver transplantation. Secondary endpoints were recurrence of ascites and occurrence of other complications. RESULTS： Median follow-up was 84 （2-120） mo. Albu- min-treated patients had significantly greater cumulative survival rate （Breslow test= 7.05, P= 0.0078） and lower probability of ascites recurrence （51% versus 94%, P〈0.0001）. Chronic albumin infusion resulted in a mean increase in survival of 16 mo. CONCLUSION： Long-term albumin administration after first-onset ascites significantly improves patients＇ survival and decreases the risk of ascites recurrence.

Long-Term Animal Feeding Trial of the Refined Konjac Meal Ⅱ. Effects of the Refined Konjac Meal on the Aging of the Brain, Liver, and Cardiovascular Tissue Cells in Rats

Rats of both sexes were fed on a basal feed containing 1% refined konjac meal (RKM) for 18 months and the effects of RKM on the cell aging were observed. A comparable group fed on the basic feed was used as the control. Results obtained demonstrate that the long-term feeding of RKM to rats can delay the course of cell aging of the gliocyte, cadiomyocyte, and the endothelial cell of the large and medium arteriases, hence it is likely to delay the occurrence of arteriosclerosis and improve the functions of the brain, heart and vascular system.

Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet

BACKGROUND The gluten-free diet(GFD)has limitations,and there is intense research in the development of adjuvant therapies.AIM To examine the effects of orally administered Aspergillus niger prolyl endopeptidase protease(AN-PEP)on inadvertent gluten exposure and symptom prevention in adult celiac disease(CeD)patients following their usual GFD.METHODS This was an exploratory,double-blind,randomized,placebo-controlled trial that enrolled CeD patients on a long-term GFD.After a 4-wk run-in period,patients were randomized to 4 wk of two AN-PEP capsules(GliadinX;AVI Research,LLC,United States)at each of three meals per day or placebo.Outcome endpoints were:(1)Average weekly stool gluten immunogenic peptides(GIP)between the run-in and end of treatments and between AN-PEP and placebo;(2)celiac symptom index(CSI);(3)CeD-specific serology;and(4)quality of life.Stool samples were collected for GIP testing by ELISA every Tuesday and Friday during run-ins and treatments.RESULTS Forty patients were randomized for the intention-to-treat analysis,and three were excluded from the per-protocol assessment.Overall,628/640(98.1%)stool samples were collected.GIP was undetectable(<0.08μg/g)in 65.6%of samples,and no differences between treatment arms were detected.Only 0.5%of samples had GIP concentrations sufficiently high(>0.32μg/g)to potentially cause mucosal damage.Median GIP concentration in the AN-PEP arm was 44.7%lower than in the run-in period.One-third of patients exhibiting GIP>0.08μg/g during run-in had lower or undetectable GIP after AN-PEP treatment.Compared with the run-in period,the proportion of symptomatic patients(CSI>38)in the AN-PEP arm was significantly lower(P<0.03).AN-PEP did not result in changes in specific serologies.CONCLUSION This exploratory study conducted in a real-life setting revealed high adherence to the GFD.The AN-PEP treatment did not significantly reduce the overall GIP stool concentration.However,given the observation of a significantly lower prevalence of patients with severe symptoms in the AN-PEP arm,further clinical research is warranted.

Long-Term Animal Feeding Trial of the Refined Konjac Meal Ⅰ. Effects of the Refined Konjac Meal on the Calcium and Phosphorus Metabolism and the Bone in Rat

Effects of refined konjac meal (RKM) on the calcium and phosphorus metabolism and bone parameters were observed in rats of both sexes fed with food containing 1% of RKM for 18 months. A comparable group of rats fed on basic diet only was used as a control.Results obtained indicate that all the measured parameters (serum calcium and phosphorus level, femur weight and its calcium and phesphorus content, and the osteometry of the tibia) showed no significant difference between the experimental and the control groups.Thus there is no adverse effect either on the calcium and phosphorus metabolism or on the bone after a long-term intake at a moderate dosage.

Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications,which highlights the need for early diagnosis and novel medications.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)placement is a procedure that can effectively treat complications of portal hypertension,such as variceal bleeding and refractory ascites.However,there have been no specific studies on predicting long-term survival after TIPS placement.AIM To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS.METHODS A retrospective analysis was conducted on a cohort of 224 patients who un-derwent TIPS implantation.Through univariate and multivariate Cox regression analyses,various factors were examined for their ability to predict survival at 6 years after TIPS.Consequently,a composite score was formulated,encompassing the indication,shunt reasonability,portal venous pressure gradient(PPG)after TIPS,percentage decrease in portal venous pressure(PVP),indocyanine green retention rate at 15 min(ICGR15)and total bilirubin(Tbil)level.Furthermore,the performance of the newly developed Cox(NDC)model was evaluated in an in-ternal validation cohort and compared with that of a series of existing models.RESULTS The indication(variceal bleeding or ascites),shunt reasonability(reasonable or unreasonable),ICGR15,post-operative PPG,percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement.The NDC model incorporated these parameters and successfully identified patients at high risk,exhibiting a notably elevated mortality rate following the TIPS procedure,as observed in both the training and validation cohorts.Additionally,in terms of predicting the long-term survival rate,the performance of the NDC model was significantly better than that of the other four models[Child-Pugh,model for end-stage liver disease(MELD),MELD-sodium and the Freiburg index of post-TIPS survival].CONCLUSION The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis,help identify high-risk patients and guide follow-up management after TIPS implantation.

Changes in weight and metabolic parameters following long-term iloperidone use: A meta-analysis of data from 9 Phase II and III trials of iloperidone

Objective: To determine the impact of iloperidone treatment on metabolic parameters. Methods: Data were analyzed from 3210 patients who received iloperidone and 587 patients who received placebo for up to 2 years during 9 Phase II and Phase III studies (integrated safety database). Patients were pooled by most frequent iloperidone dose into 3 groups: 4 - 8 mg/d, 10 - 16 mg/d, and 20 - 24 mg/d. Laboratory data from 8 studies were random (fasting and nonfasting) while patients from 1 study (n = 447) were all sampled at fasting. Results: Mean (standard deviation [SD]) weight gain from baseline to endpoint was 2.1 (6.8) kg for all patients on iloperidone. Fasting mean (SD) total cholesterol changes from baseline to end of study were 8.2 (31.6) for iloperidone and -2.2 (35.2) mg/dL for placebo. Fasting mean (SD) triglyceride changes during this period were iloperidone: -0.83 (82.3);placebo: 16.5 (113.1) mg/dL. Fasting mean (SD) glucose changes were iloperidone: 6.6 (24.0);placebo: -0.05 (17.0) mg/dL from baseline to end of study. Glycosylated hemoglobin levels were unchanged following iloperidone treatment. Conclusion: These data suggest a metabolic profile for iloperidone of modest weight gain accompanied by small changes in lipids and glucose that are unlikely to be of clinical concern.

Long-Term Effect of Industrial Waste Water Irrigation on Soil Chemical Properties

A laboratory experiment was conducted in Soil Science Division of BRRI during 2011 aimed to determine the vertical distribution of soil chemical properties under long-term industrial waste water irrigated rice field. Waste water irrigated rice field seemed to create some differences in soil pH profile. The pHW and pHKCl in all soil depth was higher with waste water irrigated rice field. The surface charge of both the soils was considerably negative. Waste water irrigated rice field developed more negative charges in soils. Irrigation with waste water increased Electrical Conductivity （EC） in rice soils profile. The organic carbon content （%） started to decrease sharply with the increase in soil depth. Organic carbon content was higher with waste water irrigated rice soils Total nitrogen （%） was high with underground water irrigated rice soils in surface but at deeper, total N was similar in both soils. Olsen P （mg/kg） was higher with underground water irrigated soil at 0-5 cm depth but at 5-100 cm soils profile, it was higher with waste water irrigated rice soils. Micronutrients （Zn, Fe, Cu and Mn） and heavy metals （Pb, Cd, Ni and Cr） in soils were increased significantly through irrigation with waste water in rice-rice cropping pattern.

Long-term outcomes after endoscopic removal of malignant colorectal polyps:Results from a 10-year cohort

BACKGROUND Choosing an optimal post-polypectomy management strategy of malignant colorectal polyps is challenging,and evidence regarding a surveillance-only strategy is limited.AIM To evaluate long-term outcomes after endoscopic removal of malignant colorectal polyps.METHODS A single-center retrospective cohort study was conducted to evaluate outcomes after endoscopic removal of malignant colorectal polyps between 2010 and 2020.Residual disease rate and nodal metastases after secondary surgery and local and distant recurrence rate for those with at least 1 year of follow-up were invest-igated.Event rates for categorical variables and means for continuous variables with 95%confidence intervals were calculated,and Fisher’s exact test and Mann-Whitney test were performed.Potential risk factors of adverse outcomes were RESULTS In total,135 lesions(mean size:22.1 mm;location:42%rectal)from 129 patients(mean age:67.7 years;56%male)were enrolled.The proportion of pedunculated and non-pedunculated lesions was similar,with en bloc resection in 82%and 47%of lesions,respectively.Tumor differentiation,distance from resection margins,depth of submucosal invasion,lymphovascular invasion,and budding were reported at 89.6%,45.2%,58.5%,31.9%,and 25.2%,respectively.Residual tumor was found in 10 patients,and nodal metastasis was found in 4 of 41 patients who underwent secondary surgical resection.Univariate analysis identified piecemeal resection as a risk factor for residual malignancy(odds ratio:1.74;P=0.042).At least 1 year of follow-up was available for 117 lesions from 111 patients(mean follow-up period:5.59 years).Overall,54%,30%,30%,11%,and 16%of patients presented at the 1-year,3-year,5-year,7-year,and 9-10-year surveillance examinations.Adverse outcomes occurred in 9.0%(local recurrence and dissemination in 4 patients and 9 patients,respectively),with no difference between patients undergoing secondary surgery and surveillance only.CONCLUSION Reporting of histological features and adherence to surveillance colonoscopy needs improvement.Long-term adverse outcome rates might be higher than previously reported,irrespective of whether secondary surgery was performed.

基于ClinicalTrials.gov及WHO ICTRP的中日诱导多能干细胞临床研究现状的比较研究

目的基于ClinicalTrials.gov和WHO ICTRP比较研究中日诱导多能干细胞(iPSC)的临床研究现状。方法检索ClinicalTrials.gov和WHO ICTRP平台,对建库至2024年3月中日iPSC临床试验数据进行采集,利用文献计量学方法,从注册数量、申办机构、疾病分类和研究类型及分期等角度,对中日该领域的临床试验注册现状进行比较研究。结果中国注册iPSC临床试验15项,日本53项;中日临床试验申办者均以高校、医院等科研院所为主,中国企业表现也较为活跃;中国临床试验覆盖的疾病范围小于日本;中日两国临床试验均以实验性研究为主。结论中国的iPSC技术还有较大的发展空间,未来发展需要进一步完善监管政策,建立严格的质量控制体系,合理规划和建设临床级i PS细胞库,综合高校、科研院所、企业三者iPSC研发与应用优势,加强资源合作,促进技术成果转化,推动技术的进步和应用的拓展。

Comparative analysis of breast and lung cancer survival rates and clinical trial enrollments among rural and urban patients in Georgia

Objectives:Rural patients have poor cancer outcomes and clinical trial(CT)enrollment compared to urban patients due to attitudinal,awareness,and healthcare access differential.Knowledge of cancer survival disparities and CT enrollment is important for designing interventions and innovative approaches to address the stated barriers.The study explores the potential disparities in cancer survival rates and clinical trial enrollments in rural and urban breast and lung cancer patients.Our hypotheses are that for both cancer types,urban cancer patients will have longer 5-year survival rates and higher enrollment rates in clinical trials than those in rural counties.Methods:We compared breast and lung cancer patients’survival rates and enrollment ratios in clinical trials between rural(RUCC 4-9)and urban counties in Georgia at a Comprehensive Cancer Center(CCC).To assess these differences,we carried out a series of independent samples t-tests and Chi-Square tests.Results:The outcomes indicate comparable 5-year survival rates across rural and urban counties for breast and lung cancer patients,failing to substantiate our hypothesis.While clinical trial enrollment rates demonstrated a significant difference between breast and lung cancer patients at CCC,no significant variation was observed based on rural or urban classification.Conclusion:These findings underscore the need for further research into the representation of rural patients with diverse cancer types at CCC and other cancer centers.Further,the findings have considerable implications for the initiation of positive social change to improve CT participation and reduce cancer survival disparities.

Tailoring Iron-Ion Release of Cellulose-Based Aerogel-Coated Iron Foam for Long-Term High-Power Microbial Fuel Cells

The presence of iron(Fe) has been found to favor power generation in microbial fuel cells(MFCs). To achieve long-term power production in MFCs, it is crucial to effectively tailor the release of Fe ions over extended operating periods. In this study, we developed a composite anode(A/IF) by coating iron foam with cellulose-based aerogel. The concentration of Fe ions in the anode solution of A/IF anode reaches 0.280 μg/mL(Fe^(2+) vs. Fe^(3+) = 61%:39%) after 720 h of aseptic primary cell operation. This value was significantly higher than that(0.198 μg/mL, Fe^(2+) vs. Fe^(3+) = 92%:8%) on uncoated iron foam(IF), indicating a continuous release of Fe ions over long-term operation. Notably, the resulting MFCs hybrid cell exhibited a 23% reduction in Fe ion concentration(compared to a 47% reduction for the IF anode) during the sixth testing cycle(600-720 h). It achieved a high-power density of 301 ± 55 mW/m^(2) at 720 h, which was 2.62 times higher than that of the IF anode during the same period. Furthermore, a sedimentary microbial fuel cell(SMFCs) was constructed in a marine environment, and the A/IF anode demonstrated a power density of 103 ± 3 mW/m^(2) at 3240 h, representing a 75% improvement over the IF anode. These findings elucidate the significant enhancement in long-term power production performance of MFCs achieved through effective tailoring of Fe ions release during operation.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Efficacy of a Nutritional Cream Intervention to Treat Depression in Rescuers:A Randomized Controlled Trial

Objective To explore the effectiveness of a nutritional intervention in rescuers who screened positive for depression.Methods A randomized controlled trial design was employed.From June to August,2022,4,460 rescuers were screened using the Self-Rating Depression Scale(SDS),and 1,615 positive cases were identified.Thirty-one volunteers were recruited and randomly divided into a nutritional intervention group and a control group.The intervention group received health education and nutritional intervention(a compound paste therapy primarily composed of red roses and Seville orange flowers),while the control group received psychological education.SDS scores were assessed before and after the intervention.Results There was a statistically significant decline in SDS scores in the nutritional intervention group after the intervention(P<0.05).Furthermore,the SDS scores of the intervention group were significantly lower than those of the control group,both before and after the intervention(P<0.05).No severe adverse reactions were observed during safety evaluation.Conclusion The nutritional intervention effectively reduced the depression scores in rescuers.Early nutritional intervention is recommended for rescuers who initially screen positive for depression.

Intravitreal long-term sustained ranibizumab delivery using injectable microgel-embedded hydrogel

Retinal vascular disease is the leading cause of visual impairment.Although intravitreal drug injections are the most suitable approach for addressing retinal disorders,existing clinical treatments necessitate repeated administration,imposing a substantial burden on patients with various intraocular complications.This study introduces an injectable and biodegradable hyaluronan microgel(Hm)-embedded gelatin-PEG-tyramine hydrogel(HmGh)designed for sustained intravitreal ranibizumab(RBZ)delivery to reduce patient burden and minimize the side effects associated with frequent injections.Hm exhibited a controlled RBZ loading capacity and release profile.HmGh effectively controlled the initial burst release and overall release profile.Cytocompatibility and cellular drug efficacy were also demonstrated.In an animal study,HmGh maintained RBZ concentrations in the vitreous and retina for>120 d.Pharmacokinetic studies showed that the half-life of RBZ-loaded HmGh in the vitreous and retina was 2.55 and 2.05 times longer than that of RBZ-loaded Hm and 9.58 and 38.46 times longer than that of RBZ solution.Importantly,the initial RBZ elimination from HmGh to the aqueous humor was significantly reduced compared to that from Hm and RBZ solutions.Intraocular degradation and safety were comprehensively evaluated using fundus imaging and histological analyses.In conclusion,this injectable hydrogel is a promising prolonged drug delivery system for treating various posterior segment eye diseases.

Long-Term Performance and Microstructural Characterization of Dam Concrete in the Three Gorges Project

This study investigates the long-term performance of laboratory dam concrete in different curing environments over ten years and the microstructure of 17-year-old laboratory concrete and actual concrete cores drilled from the Three Gorges Dam.The mechanical properties of the laboratory dam concrete,whether cured in natural or standard environments,continued to improve over time.Furthermore,the laboratory dam concrete exhibited good resistance to diffusion and a refined microstructure after 17 years.However,curing and long-term exposure to the local natural environment reduced the frost resistance.Microstructural analyses of the laboratory concrete samples demonstrated that moderate-heat cement and fine fly ash(FA)particles were almost fully hydrated to form compact micro structures consisting of large quantities of homogeneous calcium(alumino)silicate hydrate(C-(A)-S-H)gels and a few crystals.No obvious interfacial transition zones were observed in the microstructure owing to the longterm pozzolanic reaction.This dense and homogenous microstructure was the crucial reason for the excellent long-term performance of the dam concrete.A high FA volume also played a significant role in the microstructural densification and performance growth of dam concrete at a later age.The concrete drilled from the dam surface exhibited a loose microstructure with higher microporosity,indicating that concrete directly exposed to the actual service environment suffered degradation caused by water and wind attacks.In this study,both macro-performance and microstructural analyses revealed that the application of moderate-heat cement and FA resulted in a dense and homogenous microstructure,which ensured the excellent long-term performance of concrete from the Three Gorges Dam after 17 years.Long-term exposure to an actual service environment may lead to microstructural degradation of the concrete surface.Therefore,the retained long-term dam concrete samples need to be further researched to better understand its microstructural evolution and development of its properties.