Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and protection.Methods Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first immunization.Additionally,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death status.In a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first immunization.Results A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P<0.05).The groups 0-3-7-14,0-3-7-21,and 0-3-7-28 showed no statistically significant difference(P>0.05)in RVNAs levels at any time point.The post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malignancies;however,despite being efficacious in various instances,negative consequences have also been recorded.Multiple conditioning regimens were extracted from various literature searches from databases like PubMed,Google scholar,EMBASE,and Cochrane.Conditioning regimens for each disease were compared by using various end points such as overall survival(OS),progression free survival(PFS),and leukemia free survival(LFS).Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen.In multiple myeloma,the most effective regimen was high dose melphalan(MEL)given at a dose of 200/mg/m2.The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan(BU)+MEL regarding OS and BU+VP16 regarding LFS.In case of acute lymphoblastic leukemia(ALL),BU,fludarabine,and etoposide(BuFluVP)conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence.However,for ALL,chimeric antigen receptor(CAR)T cell therapy was preferred in the context of better OS and LFS.With respect to Hodgkin’s lymphoma,mitoxantrone(MITO)/MEL overtook carmustine,VP16,cytarabine,and MEL in view of PFS and vice versa regarding OS.Non-Hodgkin’s lymphoma patients were administered MITO(60 mg/m2)and MEL(180 mg/m2)which showed promising results.Lastly,amyloidosis was considered,and the regimen that proved to be competent was MEL 200(200 mg/m2).This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma(aGC),it may lead to an adverse prognosis.Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients.AIM To determine the efficacy and safety of cetuximab(CET)combined with the FOLFOX4 regimen(infusional fluorouracil,folinic acid,and oxaliplatin)as firstline therapy for patients with aGC,who received evidence-based care(EBC).METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled.Of these,60 in the research group(RG)received CET+FOLFOX4 as first-line therapy,whereas 57 in the control group(CG)received FOLFOX4.The efficacy[clinical response rate(RR)and disease control rate(DCR)],safety(liver and kidney dysfunction,leukopenia,thrombocytopenia,rash,and diarrhea),serum tumor marker expression[STMs;carbohydrate antigen(CA)19-9,CA72-4,and carcinoembryonic antigen(CEA)],inflammatory indicators[interleukin(IL)-2 and IL-10],and quality of life(QOL)of the two groups were compared.RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG,with an equivalent safety profile between the two groups.RG exhibited notably reduced CA19-9,CA72-4,CEA,and IL-2 levels following treatment,which were lower than the pre-treatment levels and those in the CG.Post-treatment IL-10 was statistically increased in RG,higher than the pre-treatment level and the CG.Moreover,a significantly improved QOL was evident in the RG.CONCLUSION The CET+FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC.It facilitates the suppression of STMs,ameliorates the serum inflammatory microenvironment,and enhances QOL,without increased adverse drug effects.

Correlation between postoperative chemotherapy regimen and survival in patients with resectable gastric adenocarcinoma accompanied with vascular cancer thrombus

BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.

Clinical Effects of the Follicular Phase Long Regimen and Luteal Phase Long Regimen on Ovulation Induction in IVF-ET Treatment: A Meta-Analysis

Objective:To systematically evaluate the clinical effects of the follicular phase long regimen and the luteal phase long regimen on ovulation induction in IVF-ET treatment.Methods:Databases including PubMed,Embase,Cochrane Library,CNKI,Chinese Biomedical Literature(CBM),VIP,Wanfang,and others were searched up to January 2021.Clinical studies on ovulation induction using the follicular phase long regimen and luteal phase long regimen in IVF-ET treatment were identified.Literature screening,data extraction,and quality evaluation were conducted based on inclusion and exclusion criteria.Meta-analysis was performed using RevMan 5.3 software.Results:After screening,a total of 11 studies were included,comprising 21,544 patients:9,974 in the follicular phase long regimen group and 11,570 in the luteal phase long regimen group.The meta-analysis results were as follows:(1)The number of Gn days and the total amount of Gn in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05);(2)The number of eggs obtained in the follicular phase long regimen was higher than that in the luteal phase long regimen(P<0.05).There were no significant differences in the rate of embryo optimization and cycle cancellation between the two groups(P>0.05);(3)The embryo implantation rate and clinical pregnancy rate in the follicular phase long regimen were higher than those in the luteal phase long regimen(P<0.05),while the abortion rate in the follicular phase long regimen was lower than that in the luteal phase long regimen(P<0.05).Conclusion:Compared to the luteal phase long regimen,the follicular phase long regimen involves more Gn days and a higher total amount of Gn.The optimal embryo rate and cycle cancellation rate were similar between the regimens,but the follicular phase long regimen resulted in more eggs,significantly improved the implantation and clinical pregnancy rates,and reduced the abortion rate.However,these conclusions require further validation through more multicenter,large-sample RCT studies.

超重/肥胖不孕症患者早卵泡期长效长方案中添加重组黄体生成素可行性及新鲜周期妊娠结局的分析

目的 探讨超重/肥胖不孕症患者采用早卵泡期长方案促排卵过程中,在不同时机添加重组黄体生成素(rLH)对新鲜周期助孕结局的影响。方法 回顾性分析2021年1月至2023年6月于南京医科大学第一附属医院生殖医学中心行早卵泡期长方案促排卵治疗的1 181例超重/肥胖患者的临床资料,根据是否添加rLH及添加时机分为3组:未添加rLH组(A组,n=584),促排卵全程添加rLH组(B组,n=526),促排卵中期添加rLH组(C组,n=71)。比较3组患者的基本资料、代谢水平、促排卵情况以及新鲜胚胎移植周期的妊娠结局。结果 3组患者间年龄、抗苗勒管激素(AMH)、体质量指数(BMI)比较均无统计学差异(P>0.05),但A组患者糖耐量异常比例显著低于B组患者(P=0.001)。促排卵过程中,A组获卵数、可移植胚胎数、优质胚胎数均显著高于B组(P<0.05),A组2PN率也显著高于其他两组(P<0.05),C组优质胚胎数显著高于B组(P<0.05);但3组患者间Gn使用天数、FSH用量比较均无统计学差异(P>0.05)。3组患者的平均移植胚胎数、胚胎种植率、早期流产率、临床妊娠率、活产率比较均无统计学差异(P>0.05)。结论 超重/肥胖、卵巢功能正常的患者在早卵泡期长方案中添加rLH不能显著降低FSH用量以及促排卵时间,对胚胎质量以及妊娠结局无显著影响,高BMI不能作为早卵泡期长方案促排卵时rLH的应用指征。

E-CHOP方案治疗中高度恶性非霍奇金淋巴瘤的疗效观察

目的:观察E-CHOP方案对中高度恶性非霍奇金淋巴瘤的治疗效果。方法:应用E-CHOP方案治疗28例中高度恶性非霍奇金淋巴瘤。E-CHOP方案:环磷酰胺750mg/m2,d1;长春新碱1.4mg/m2,d1;表阿霉素50mg/m2,d1;强的松60mg/(m2.d),d1～d5;足叶乙甙100mg/d,3～5d。每21天为1周期,共进行6～8个周期。结果:CR率为68%(19/28),PR率为17%(5/28),NC率为7%(2/28),PD率为7%(2/28),总有效率(CR+PR)为85%。主要毒副作用为骨髓抑制,其次为恶心呕吐,脱发,较少的是口腔粘膜损害,全部病例无化疗相关死亡。结论:E-CHOP方案有较高的有效率,且耐受性良好,可以作为中高度淋巴瘤患者的一线治疗方案。

多发性骨髓瘤患者CTX或E-CHOP化疗联合G-CSF动员采集外周血造血干细胞的成功率及影响因素分析

目的:分析多发性骨髓瘤患者环磷酰胺(CTX)或E-CHOP化疗联合粒细胞集落刺激因子(G-CSF)动员采集外周血造血干细胞(HSC)成功率及影响因素。方法:收集本院75例多发性骨髓瘤患者的临床资料,进行回顾性分析,对患者均行CTX或E-CHOP化疗联合G-CSF动员采集HSC,对其成功率(CD34^+细胞≥2×10~6/kg)及其影响因素进行统计学分析。结果:对全组75例患者共行86次动员采集,平均采集CD34^+细胞数为3.22(0.12-22.28)×10~6/kg,采集成功率为70.67%(53/75)。单因素分析结果发现,采集前化疗疗程数和疾病状态与HSC采集成功率均存在显著相关性(P<0.05),而与不同性别、年龄、疾病分型、ISS分期和动员方案均无显著关系(P>0.05)。多因素Logistic回归分析结果发现,采集前化疗疗程数与HSC采集成功率呈正相关(OR=2.95,95%CI:1.60-5.41,P<0.01),而与采集前疾病状态并无显著关系(OR=1.01,95%CI:0.88-1.16,P=0.89)。结论:多发性骨髓瘤患者性别、疾病分型、ISS分期和动员方案对HSC采集成功率均无明显影响,并且采集前化疗疗程数较少(<5)的患者HSC采集成功率较高。

孕产妇血流感染病原菌特点与抗感染方案分析

目的为制订血流感染孕产妇的药物治疗方案提供参考。方法回顾性分析徐州医科大学附属医院产科2017年1月至2022年6月收治的57例血流感染孕产妇的临床资料,分析患者的临床特征、抗菌药物治疗方案、血培养分离菌株分布及主要致病菌的药物敏感性试验结果。结果均采用抗菌药物治疗;住院期间静脉使用抗菌药物疗程3~30 d,中位疗程9(7,12)d;联合用药42例(73.68%);57例患者的体温及炎性因子水平指标均有升高;血培养分离菌株62株,大肠埃希菌占比最高(59.68%),其次为肠球菌属(17.74%)和链球菌属(11.29%)。药物敏感性试验结果显示,大肠埃希菌对哌拉西林他唑巴坦、头孢哌酮舒巴坦、亚胺培南、美罗培南的敏感率为100.00%,肠球菌对氨苄西林的敏感率为81.82%。结论孕产妇血流感染以大肠埃希菌较常见,结合药物适应证可选择哌拉西林他唑巴坦、头孢哌酮舒巴坦或碳青霉烯类抗菌药物单药治疗,必要时可联合用药。

运动干预脑卒中患者心肺功能的Meta分析

目的:临床上脑卒中患者在康复期间会经历显著的心肺功能障碍,这增加了复发性脑卒中的概率,而通过运动干预则可以有效改善脑卒中患者的心肺功能。此文通过Meta分析方法对国内外关于运动干预改善脑卒中患者心肺功能的研究进行综合定量评价,检验不同运动方式对脑卒中患者心肺功能的影响,探索最佳运动方案。方法:检索中国知网、万方、维普、Web of Science、Cochrane图书馆、PubMed、EBSCO数据库建库至2024-05-15发表的相关文章,主要纳入运动干预改善脑卒中患者心肺功能的随机对照试验,采用Review Manager 5.4和Stata 17软件进行统计分析。结果:(1)共纳入符合标准的文献32篇,包括脑卒中患者1 826例;(2)结果显示,运动干预能够显著改善脑卒中患者的摄氧能力[MD=2.10,95%CI(1.57,2.63),P <0.000 01],采用高强度间歇训练的干预方式,每周干预五六次,每次干预41-60 min,持续干预12周以上是改善脑卒中患者摄氧能力的最佳运动方案;(3)运动干预可以明显提高脑卒中患者有氧运动耐力[MD=38.00,95%CI(29.55,46.45),P <0.000 01],采用高强度间歇训练的干预方式,每周干预两三次,每次干预41-60 min,持续干预12周以上是改善脑卒中患者有氧运动耐力的最佳运动方案。结论:运动干预可以显著改善脑卒中患者心肺功能,高强度间歇训练是最具潜力的运动干预方式。所以采用高强度间歇训练,每次干预41-60 min,初始干预频率每周2次,根据耐受情况逐渐增加干预频率,并持续干预12周以上是改善脑卒中患者心肺功能的最佳运动方案;未来应收集更多高质量、多项目的临床研究和证据来验证上述结论,尤其是探索高强度间歇训练改善脑卒中患者心肺功能的最佳运动——间歇比值。

Effectiveness of RESET care program: A real-world-evidence on managing non-alcoholic fatty liver disease through digital health interventions

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)management requires sustainable lifestyle modifications.This study aimed to evaluate the effectiveness of the RESET care plan,a comprehensive program that is an integrated personalized diet,exercise,and cognitive behavior therapy,delivered via MyTatva’s digital health application enabled through a body composition analyzer(BCA)and smartwatch.AIM To evaluates the effectiveness of the comprehensive program delivered via My-Tatva’s digital health app enabled through internet of thing devices.METHODS This retrospective observational study analyzed deidentified data from 22 par-ticipants enrolled in the MyTatva RESET care program.Participants were divided into three groups:Group A,diet plan;Group B,diet+exercise plan;and Group C,diet+exercise+cognitive behavioral therapy plan.Participants were provided with a BCA and smartwatch for continuous monitoring of anthropometric para-meters.Statistical analysis,including one-way ANOVA and post-hoc Tukey’s Honest Significant Difference test,was conducted to compare mean changes in anthropometric parameters across the groups.INTRODUCTION Non-alcoholic fatty liver disease(NAFLD)has emerged as a global health burden,affecting approximately 1 in 4 in-dividuals worldwide.NAFLD ranges from simple steatosis(fat accumulation)to non-alcoholic steatohepatitis(NASH),and its global prevalence in the general population is estimated between 6.3%and 33%,with NASH affecting 3-5%[1,2].Obesity is a major risk factor of NAFLD,with studies showing that the likelihood of developing NAFLD increases 5-fold at a body mass index(BMI)of 30-32.5 kg/m²and up to 14-fold at BMI of 37.5-40 kg/m²compared to a BMI of 20-22.5 kg/m²[3,4].Effective NAFLD management requires both dietary and physical activity modifications.Healthy weight loss with sustained muscle mass plays a pivotal role,with a reduction of 3%-5%decreasing hepatic steatosis,5%-7%improving NASH conditions,and 10%or more needed to reverse hepatic fibrosis[5].Management also normalizes elevated liver enzymes(aspartate aminotransferase and alanine aminotransferase),enhances insulin sensitivity,and thereby reduces cardiovascular risk by improving endothelial function and increasing cardiorespiratory fitness[6].However,diet or exercise alone is often not as effective as a combined approach.Integrating both balanced dietary changes and increased physical activity yields more sustainable improvements in NAFLD and overall metabolic health[1,7].Traditional intervention methods usually involve in-person consultations,which often lack real-time and continuous patient monitoring.The recommendation of drastic changes in diet and exercise can also be overwhelming for patients,leading to low adherence rates.Many patients struggle to maintain these changes in the long-term due to a lack of con-tinuous motivational support[8,9].In recent years,the health ecosystem has witnessed a significant shift toward digital health platforms,which complement pharmacological treatments in chronic disease management,and increase scala-bility.These platforms provide continuous monitoring and personalized support,helping to bridge the gap between health care setups and patients[10].Recent digital advances enable internet of things(IoT)devices to be integrated into such management plans to track health metrics,to address the limitations of traditional methods[11,12].The MyTatva digital health application offers the RESET plan,a novel comprehensive approach for NAFLD mana-gement by integrating personalized support from nutrition,physiotherapy,and cognitive behavioral therapy(CBT)coaches.We aimed to evaluate the effectiveness of the RESET plan by analyzing the reduction in anthropometric para-meters across three different digital intervention groups.

信迪利单抗联合伊立替康方案治疗晚期食管鳞癌患者的临床观察

目的探讨信迪利单抗联合伊立替康方案治疗晚期食管鳞癌(ESCC)的疗效。方法选取2019年3月至2021年3月新蔡县人民医院收治的102例晚期ESCC患者,使用随机数字表法分为研究组(伊立替康+替吉奥+信迪利单抗)和对照组(伊立替康+替吉奥)各51例。持续治疗2个周期后观察效果,随访1年观察随访期间生存情况。结果研究组客观缓解率(37.25%)、疾病控制率(70.59%)均高于对照组(17.65%,49.02%),差异均有统计学意义(P<0.05)。治疗后,研究组癌胚抗原(CEA)、细胞角蛋白19片段抗原21-1(CYFRA21-1)、鳞状细胞癌抗原(SCCA)水平均低于对照组,差异有统计学意义(P<0.05)。两组不良反应情况比较,差异无统计学意义(P>0.05)。随访1年,研究组和对照组各失访1、2例,各存活41、31例,两组生存曲线比较,经Log-rank检验,研究组生存曲线优于对照组,差异具有统计学意义(χ2=4.427,P=0.035)。结论信迪利单抗联合伊立替康方案治疗晚期ESCC疗效显著,可降低患者肿瘤标志物水平、延长患者近期生存率,安全性较好。

益肺清化颗粒联合含铂两药化疗方案及卡瑞利珠单抗治疗晚期非小细胞肺癌疗效观察及对细胞毒T细胞的影响

目的:观察益肺清化颗粒联合含铂两药化疗方案及卡瑞利珠单抗治疗晚期非小细胞肺癌(NSCLC)的临床疗效及对细胞毒T(Tc)细胞的影响。方法:将110例2021年1月—2023年8月郑州大学附属肿瘤医院收治的晚期NSCLC患者按随机数字表法分为对照组、观察组各55例。对照组采用含铂两药化疗方案及卡瑞利珠单抗治疗,观察组在对照组的基础上加用益肺清化颗粒。比较2组中医证候评分、免疫功能相关指标[Tc细胞、自然杀伤(NK)细胞和调节性T(Treg)细胞]、不良反应和临床疗效。结果:观察组客观缓解率、疾病控制率分别为65.45%(36/55)、94.55%(52/55),对照组分别为36.36%(20/55)、80.00%(44/55),2组比较,差异均有统计学意义(P<0.05)。治疗后,2组中医证候评分均较治疗前降低(P<0.05),且观察组评分低于对照组(P<0.05)。2组Tc、NK细胞占比较治疗前增加(P<0.05),Treg细胞占比较治疗前降低(P<0.05);且观察组Tc、NK细胞占比高于对照组(P<0.05),Treg细胞占比低于对照组(P<0.05)。观察组不良反应发生率为21.82%(12/55),对照组为41.82%(23/55),2组比较,差异有统计学意义(P<0.05)。结论:益肺清化颗粒联合含铂两药化疗方案及卡瑞利珠单抗治疗晚期NSCLC可提高临床疗效,有效改善中医证候及免疫功能,减轻化疗的毒副反应。

The Adverse Effect of the 2-1-1 Regimen for Rabies PEP in Preschool Children

Post-exposure prophylaxis（PEP） has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children（aged 0-6）. We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014. We find that, in preschool children, the febrile reaction after the first 2-dose injection in the 2-1-1 regimen was significantly higher than that induced by the first 1-dose in the Essen procedure. Thus, we recommend that the Essen regimen should still be used for rabies PEP in preschool children.

Comparison of two different treatment regimens’ efficacy in neovascular age-related macular degeneration in Turkish population—based on real life data-Bosphorus RWE Study Group

AIM: To compare two different anti-vascular endothelial growth factor(anti-VEGF) treatment regimens'-a priori pro re nata(PRN) and PRN regimen following^(th)e loading phaseanatomical and functional results in neovascular agerelated macular degeneration(n AMD) patients. METHODS: Totally 544 n AMD patients followed and treated with aflibercept(n=135) and ranibizumab(n=409)at 9 different centers between 2013 and 2015 were enrolled into^(th)is retrospective multicenter study. Patients with initial best corrected visual acuity(BCVA) interval of 1.3-0.3(log MAR) and a minimum follow-up of 12 mo were included. Patients under two different regimens-a priori pro re nata(1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen(3+PRN)-were compared in BCVA at 3^(th), 6^(th) and 12^(th) months, and in central macular^(th)ickness(CMT) at 6^(th) and 12^(th) months. The total study group, intravitreal ranibizumab(IVR) and intravitreal aflibercept(IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in^(th)e 1+PRN(n=101) regimen from 407 to 358 and 340 μm and in^(th)e 3+PRN(n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically,^(th)e CMT reduction at 6^(th) month(48.5 vs 76.4;P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75;in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3^(th) month(-0.01 vs 0.12;P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6^(th)(44 vs 72) and 12^(th) month(61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3^(th) month(-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction(61 vs 89, 6^(th) month;85 vs 97, 12^(th) month) and visual gain(0.02 vs 0.16;0.02 vs 0.14;0.05 vs 0.11) was found in favor of 3+PRN group at all visits.CONCLUSION: The loading dose of anti-VEGF treatments in n AMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

The Optimum Dosage Regimen of Intravenous Infusion for Drugs Obeying Parallel First-order and Michaelis-Menten Elimination Kinetics

For drugs obeying parallel first-order and Michaelis-Menten elimination kinetics,mathematical analysis concerning the optimum dosage regimen of intravenous infusion is conducted and following equations are derived:where Xo is the intravenous loading dose,Cb the plasma concentration level desired in clinical therapy,V the apparent distribution volume,k0 the rate constant of intravenouns infusion,K the first－order elimination rate constant,Vm the theoretical maximum rate of the Michaelis－Menten elimination process,Km the Michaelis constant.From this dosage regimen,plasma level maintains a constant Cb during the administration period.When K=0 the dosage regimen above is also suitable for drugs obeying Michaelis-Menten elimination kinetics.

Is a split-dose regimen of 2 L polyethylene glycol plus ascorbic acid tolerable for colonoscopy in an early morning visit to a comprehensive medical check-up?

To evaluate the effectiveness and tolerability of a split-dose 2 L polyethylene glycol (PEG)/ascorbic acid (AA) regimen for healthy examinees who visited for comprehensive medical check-up in the early morning.METHODSFrom February 2015 to March 2015, examinees of average risk who were scheduled for a colonoscopy in the morning were retrospectively enrolled.RESULTSThe 189 examinees were divided into split-dose and non-split-dose groups. The adequacy of bowel preparation for the split-dose group vs the non-split-dose group was 96.8% vs 85.2%, respectively, P < 0.001, and the compliance of the last meal restriction was 74.6% vs 58.2%, respectively, P < 0.001. The sleep disturbance (P < 0.001) was more prevalent in the split-dose group, however the willingness to repeat the same preparation method (P = 0.243) was not different in both groups. The split-dose regimen was the most important factor influencing adequate bowel preparation in multivariate analysis (HR = 10.89, 95%CI: 6.53-18.17, P < 0.001).CONCLUSIONA split-dose regimen of 2 L PEG/AA for an early morning colonoscopy was more effective and showed better compliance for diet restriction without any difference in satisfaction and discomfort. Introducing a split-dose regimen of 2 L PEG/AA to morning colonoscopy examinees is effective and tolerable in a comprehensive medical check-up setting.

特瑞普利单抗辅助FOLFOX治疗对进展期胃癌患者血管新生和PD-1/PD-L1信号通路的影响

目的探讨特瑞普利单抗联合FOLFOX方案治疗进展期胃癌的效果及其免疫调节机制。方法选取2021年6月至2023年6月驻马店市中心医院收治的97例进展期胃癌患者纳入研究,按随机数表法分为观察组49例和对照组48例,其中对照组采用FOLFOX方案治疗者,观察组采用FOLFOX方案+特瑞普利单抗治疗,21 d为一个疗程,持续治疗6个疗程。比较两组患者治疗6个疗程后的治疗效果,以及治疗前、治疗3个疗程和6个疗程后的程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)信号通路(PD-1蛋白、PD-1 m RNA、PD-L1蛋白、PD-L1 m RNA)、血管新生指标[低氧诱导因子1α(HIF-1α)、血管内皮生长因子(VEGF)、促血管生成素-2(Ang-2)、环氧合酶-2(COX-2)],同时比较两组患者治疗期间的毒副反应以及随访6个月的生存率。结果治疗6个疗程后,观察组患者的疾病控制率为63.27%,明显高于对照组的41.67%,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的PD-1蛋白分别为5.83±1.12、5.77±1.26,明显低于对照组的6.84±1.25、7.11±1.36,PD-1m RNA分别为6.12±1.33、6.01±1.34,明显低于对照组的6.91±1.34、7.20±1.30,PD-L1蛋白分别为6.30±1.05、6.19±1.11,明显低于对照组的7.02±1.33、6.88±1.40,PD-1 mRNA分别为6.41±1.24、6.33±1.25,明显低于对照组的7.19±1.36、7.10±1.38,差异有统计学意义(P<0.05)。治疗3个疗程、6个疗程后,观察组患者的VEGF分别为(224.46±25.25)ng/mL、(150.10±14.14)ng/mL,明显低于对照组的(279.79±30.44)ng/mL、(191.65±16.63)ng/mL,HIF-1α分别为(135.51±16.67)μg/L、(100.10±12.28)μg/L,明显低于对照组的(175.53±18.48)μg/L、(153.53±14.88)μg/L,Ang-2分别为(68.98±7.36)ng/mL、(46.68±5.13)ng/mL,明显低于对照组的(75.51±7.95)ng/mL、(56.64±6.11)ng/mL,COX-2分别为(31.48±4.12)ng/mL、(20.24±3.38)ng/mL,明显低于对照组的(36.64±4.20)ng/mL、(25.74±3.59)ng/mL;差异均有统计学意义(P<0.05)。两组患者治疗6个疗程后的毒副反应发生率与随访期间生存率比较差异均无统计学意义(P>0.05)。结论特瑞普利单抗联合FOLFOX方案治疗进展期胃癌,可阻断PD-1/PD-L1信号通路,增强肿瘤控制效果,且具有较好的安全性。

Effect of Nitrogen and Phosphorus Starvations on <i>Chlorella vulgaris</i>Lipids Productivity and Quality under Different Trophic Regimens for Biodiesel Production

In this work the effects of nutrients starvations on Chlorella vulgaris were investigated in different trophic regimens. For all the tested conditions, the cellular response to nutrient starvation and trophic regimen was evaluated on specific growth rate, biomass and lipids productivity, lipids content and quality. These parameters are all crucial for microalgae biodiesel production, but in literature the lipids quality, in terms of polar and nonpolar lipids, is often neglected. Thus the typical high content of polar lipids, a class of molecules that negatively affects the biodiesel production process, of microalgae crude oil is generally not analyzed. In the tested conditions the triggering effect of nitrogen starvation on total lipids productivity is confirmed only in autotrophic regimen, while in mixotrophic and heterotrophic conditions the total lipids productivity is reduced, as a consequence of the lowered biomass productivity, but with an evident compositional shift towards nonpolar lipids production (from 0.5 mg/Ld to 41.6 mg/Ld in mixotrophic regimen). Nitrogen and phosphorus co-starvation induced the highest nonpolar lipids productivity in all trophic regimens. Maximum nonpolar lipids productivity was obtained in nitrogen limited and phosphorus deprived condition during mixotrophic growth, equal to 118.2 mg/Ld, representing the 80% of produced lipids. On the basis of the obtained results, the possibility of a short pre-harvesting cultural step to maximize the nonpolar lipids yield of the crop could be envisaged.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.