1.Immune cell-mediated drug delivery system
Chinese Journal of Cancer Biotherapy 2025;32(1):24-29
[摘 要] 免疫细胞介导的药物递送系统是以免疫细胞为载体,利用细胞固有的趋化作用将治疗药物靶向递送至特定病灶部位,因其具有优异的生物相容性、低免疫原性、组织特异性归巢及易穿过生物屏障等多重优势,已成为药物递送和疾病治疗的重要手段。本文系统论述免疫细胞的载药策略和单核细胞、中性粒细胞、间充质干细胞和树突状细胞等作为载体细胞的生物学特性、主要优缺点,以及应用于肿瘤治疗的最新研究进展,为深入研究免疫细胞介导的药物递送系统和临床转化提供重要参考。
2.Effects of KHSRP targeting JAK1/STAT3 signaling pathway on the malignant biological behavior of the adenocarcinoma of esophagogastric junction
ZHANG Haifenga ; WANG Mengyaob△ ; WANG Xiaolonga ; LIU Yangyangb ; LI Lia,b ; WEI Haitaoa
Chinese Journal of Cancer Biotherapy 2025;32(1):38-47
[摘 要] 目的:探讨KH型剪切调节蛋白(KHSRP)靶向调控JAK1/STAT3信号轴对食管胃结合部腺癌(AEG)细胞增殖、迁移和侵袭及移植瘤生长与肺转移的影响。方法:收集2017年1月至2018年12月间在淮河医院确诊的64例AEG组织和癌旁组织标本及临床资料,采用免疫组化法观察AEG组织和癌旁组织中KHSRP的表达水平。qPCR法检测AEG细胞OE-19、TE-7、BIC-1、FLO-1、SK-GT-4、BE-3与正常食管上皮细胞Het-1A中KHSRP的表达差异。通过慢病毒载体对KHSRP进行敲减和过表达处理,分别转染OE-19与TE-7细胞、FLO-1与SK-GT-4细胞,实验分为sh-NC组、sh-KHSRP组和Vector组、KHSRP过表达组(KHSRP组)。采用qPCR法检测敲减或过表达效率,CCK-8法、Transwell小室法分别检测敲减或过表达KHSRP对AEG细胞增殖、迁移和侵袭的影响。构建小鼠异种移植瘤和肺转移模型,观察KHSRP对移植瘤体内生长和转移的作用。WB法验证KHSRP靶向JAK/STAT信号通路。细胞拯救实验验证KHSRP是否通过调节JAK1/STAT3信号通路促进AEG细胞的恶性进程。结果:与癌旁组织相比,AEG组织中KHSRP表达水平显著增高(P < 0.05或P < 0.01)。细胞功能实验分析显示,KHSRP过表达在体外均显著促进AEG细胞增殖、迁移和侵袭(P < 0.05或P < 0.01)。动物实验结果显示,KHSRP在裸鼠体内具有促进AEG细胞移植瘤生长与肺转移的作用(P < 0.05或P < 0.01)。在敲减KHSRP后,JAK/STAT信号通路中JAK1、STAT3磷酸化水平均明显降低,过表达KHSRP后情况则均反之(P < 0.05或P < 0.01)。细胞拯救实验显示,KHSRP可以逆转敲减JAK1/STAT3对细胞增殖、迁移和侵袭的抑制作用(P < 0.05或P < 0.01)。结论:KHSRP通过激活JAK1/STAT3信号通路调控AEG细胞转移的恶性进程,KHSRP有望成为AEG临床治疗的潜在靶点。
3.PTPRD demethylation regulates the proliferation, migration, and chemoresistance of gastric cancer cells through the PI3K/Akt/mTOR pathway
LIU Yanhuia,b ; GAO Ziyua ; REN Pengb ; DU Yuxinb ; LIU Caixiaa ; XING Zhiweia
Chinese Journal of Cancer Biotherapy 2025;32(1):48-55
[摘 要] 目的:探究蛋白酪氨酸磷酸酶D(PTPRD)去甲基化通过PI3K/Akt/mTOR通路对胃癌细胞增殖、迁移及化疗耐药性的影响。方法:体外培养胃癌细胞MKN-74、MKN-45和人胃黏膜上皮细胞GES-1并检测PTPRD表达。常规培养MKN-45细胞及耐药MKN-45/5-FU细胞,分别转染PTPRD空载体(NC组、NC/5-FU组)、PTPRD过表达腺病毒(PTPRD组、PTPRD/5-FU组)、shRNA空载体(sh-NC组、sh-NC/5-FU组)、shRNA-PTPRD慢病毒(sh-PTPRD组、sh-PTPRD/5-FU组)和PTPRD过表达腺病毒 + 10 μmol/L 740Y-P处理(PTPRD + 740Y-P组、PTPRD + 740Y-P/5-FU组)。MTT法、划痕愈合实验检测各组细胞的增殖活力和迁移能力,细胞自噬实验检测细胞的自噬水平,WB法检测细胞中EMT和PI3K/Akt/mTOR通路相关蛋白的表达。采用0、2.5、5、10、20、40 μmol/L的5-aza处理MKN-45细胞,qPCR法、MTT法检测细胞中PTPRD mRNA表达和细胞增殖活力。结果:PTPRD mRNA和蛋白在胃癌细胞中均呈低表达(P < 0.05)。与MKN-45组相比,PTPRD组自噬体与自噬溶酶体数量、PTPRD、上皮钙黏素(E-cadherin)、BAX蛋白表达均增加(均P < 0.05),细胞增殖活力、细胞迁移率、p-PI3K、波形蛋白(vimentin)、p-Akt、p-mTOR蛋白表达均降低(均P < 0.05),sh-PTPRD组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达均减少(均P < 0.05);与PTPRD组相比,PTPRD + 740Y-P组细胞增殖活力、细胞迁移率、p-PI3K、vimentin、p-Akt、p-mTOR蛋白表达均增加(均P < 0.05),自噬体与自噬溶酶体数量、PTPRD、E-cadherin、BAX蛋白表达减少(均P < 0.05)。随着5-aza浓度的增加,MKN-45细胞中PTPRD mRNA表达增加、细胞增殖活力均降低(均P < 0.05)。与MKN-45/5-FU组相比,PTPRD/5-FU组细胞迁移率、细胞增殖活力均降低(均P < 0.05),sh-PTPRD/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05);与PTPRD/5-FU组相比,PTPRD + 740Y-P/5-FU组细胞迁移率、细胞增殖活力均增加(均P < 0.05)。结论:PTPRD在胃癌细胞中呈低表达状态,PTPRD去甲基化可能通过抑制PI3K/Akt/mTOR信号通路抑制胃癌细胞增殖、迁移并增强其对化疗的敏感性。
4.The value of iSEND immune score combined with LIPI in assessing the prognosis of non-small cell lung cancer following immunotherapy
JIANG Shan1a ; WANG Lepeng1b ; CHEN Dachuan1a ; YUE Chunya1a ; LAN Nan2
Chinese Journal of Cancer Biotherapy 2025;32(1):79-84
[摘 要] 目的:探讨iSEND免疫评分联合肺癌免疫治疗预后指数(LIPI)在评估非小细胞肺癌(NSCLC)接受免疫治疗预后中的价值。方法:通过回顾性分析2018年2月至2023年2月期间100例接受免疫治疗的晚期NSCLC患者的临床资料,收集并整理患者的iSEND免疫评分和LIPI数据,根据iSEND免疫评分和LIPI分别将患者分为3组(不良组、中等组和良好组),运用Kaplan-Meier方法绘制生存曲线分析所有患者和不同组别患者的无进展生存期(PFS),运用Cox回归分析评估影响患者预后的风险因素。结果:在接受免疫治疗后,NSCLC患者的ORR为42.00%(42/100),DCR为82.00%(82/100)。iSEND免疫评分和LIPI不良组ORR和DCR均最低,良好组均最高,不同组别ORR和DCR比较均有统计学意义(均P < 0.01)。100例NSCLC患者的中位PFS为7.63个月[95% CI(7.23, 8.05)],iSEND免疫评分不良组、中等组和良好组的中位PFS分别为4.69、6.58和8.99个月,iSEND免疫评分良好组的PFS最长,其次为中等组,不良组最短(χ2=125.391,P < 0.000 1)。LIPI不良组、中等组和良好组的中位PFS分别为4.54、6.39和8.49个月,以LIPI良好组的PFS最长,其次为中等组(χ2 = 115.707,P < 0.000 1)。Cox多因素分析提示,ECOG PS > 1、远处转移、iSEND免疫评分≥ 2分和LIPI ≥ 2分是影响患者独立预后的风险因素。结论:iSEND免疫评分和LIPI可作为评估NSCLC免疫治疗预后的良好指标,具有一定的临床价值。
6.Efficacy of N-acetylcysteine plus beta-blocker versus beta-blocker alone in preventing postoperative atrial fibrillation after cardiac surgery: A meta-analysis of randomized controlled trials
Giovanni Vista ; Von Jerick B. Tenorio ; Marivic V. Vestal
Philippine Journal of Cardiology 2025;53(1):73-86
BACKGROUND
Postoperative atrial fibrillation (POAF) is the most common arrythmia to occur after cardiovascular surgery. Inflammation being pivotal in POAF perpetuation has been utilized as a therapeutic target. Owing to their anti-inflammatory and anti-oxidant effects, beta-blockers (BB) and N-acetylcysteine (NAC) became research interests in the pursuit for an effective POAF prevention strategy.
OBJECTIVETo determine the efficacy of NAC plus BB versus BB alone in preventing POAF in cardiac surgery patients.
METHODOLOGYA literature search using the following search engines: PubMed/Medline, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley and Google Scholar for relevant randomized trials were conducted. Published and unpublished studies indexed from inception until 2023 were included. Three independent reviewers evaluated the randomized clinical trials (RCTs) for eligibility. The pooled estimates for POAF prevention as primary outcome and MACE, mortality, myocardial infarction, stroke, ICU LOS and hospital LOS as secondary outcomes were measured using the RStudio statistical software.
RESULTSSeven eligible RCTs allocated 1069 cardiac surgery patients to NAC + BB (n=539) and BB alone (N = 530) treatment arms. The effect estimate using random effect model disclosed significantly reduced POAF events (RR 0.62, 95% CI [0.44, 0.86], p = 0.005) in those on NAC + BB. While no statistical difference between the study arms were demonstrated in reducing mortality (RR 0.63, 95% CI [0.23, 1.73], p = 0.37); myocardial infarction (RR 1.02, 95% CI [0.49, 2.13], p = 0.96); stroke (RR 0.95, 95% CI [0.24, 3.68], p = 0.94); ICU LOS (std. mean difference 0.14, 95% CI [-0.43, 0.70], p = 0.41), and hospital LOS (std. mean difference 0.08, 95% CI [-0.06, 0.21], p = 0.19).
CONCLUSIONAmong cardiac surgery patients, the use of NAC in combination with BB compared with BB alone significantly reduced POAF.
Acetylcysteine ; Arrhythmias, Cardiac ; Atrial Fibrillation ; Myocardial Infarction ; Omega-chloroacetophenone
7.The effect of sulodexide on the incidence of cardiovascular outcomes in patients with vascular disorders
Eugenio B. Reyes ; Paula Victoria Catherine Y. Cheng-bromeo ; Nigel Jeronimo C. Santos
Philippine Journal of Cardiology 2025;53(1):87-97
BACKGROUND AND OBJECTIVES
Among patients with macrovascular and microvascular disease, we investigated the association between sulodexide and cardiovascular (CV) outcomes and adverse events.
METHODSWe conducted a meta-analysis of randomized control trials (RCTs) reporting CV outcomes and adverse events in patients with vascular disease receiving sulodexide for any indication versus control. The following outcomes were investigated: any CV event, myocardial infarction, CV death, bleeding events and gastrointestinal symptoms.
RESULTSTwelve studies with a total of 8,436 patients were included. Sulodexide resulted in a significant reduction in CV events (OR 0.51 [95% confidence interval 0.41-0.73]; pCONCLUSION
Sulodexide has a beneficial effect among patients with macrovascular disease in terms of reducing the risk for MI, overall CV mortality and CV events. Larger RCTs are needed to corroborate these findings.
Human ; Sulodexide ; Glucuronyl Glucosamine Glycan Sulfate
8.Clinical profile and outcome of patients who underwent coronary artery bypass graft surgery under Philhealth Z benefit package in Manila Doctors Hospital
Bienvenido P. Tiu jr. ; Felix Eduardo R. Punzalan ; Noemi S. Pestavo ; Chermaine Love C. Cañ ; averal ; Maria Grethel C. Dimalala-lardizabal ; Rogelio V. Tangco ; Dante D. Morales ; Nelson S. Abelardo ; Eugenio B. Reyes
Philippine Journal of Cardiology 2025;53(1):47-54
OBJECTIVE
This study aims to determine the clinical profile and incidence of in-hospital outcomes of patients who underwent coronary artery bypass graft surgery (CABG) under the Philippine Health Insurance Corporation (Philhealth) Z Benefit Package (PZBP).
METHODSA retrospective descriptive cohort study. A review of medical records was done from July 2017 to October 2023 to collect data and in-hospital outcomes of patients who underwent CABG surgery under Z benefit package.
RESULTSOne hundred twenty-six patients were included in the study. The mean age of patients was 60 years and majority of them were male and came from NCR. Hypertension was the leading cause of comorbidity. The top two most common in-hospital outcomes were hospital-acquired pneumonia and postoperative atrial fibrillation. Most commonly observed caused of increased length in hospitalization was pneumonia. The mean Society of Thoracic Surgeons (STS) (operative mortality) and Euro scores were 1.04 ± 0.82 and 0.88 ± 0.56, respectively. All patients had successful surgical outcome with no mortality and an average length of stay in the hospital of six days.
CONCLUSIONSThis study will serve as a future reference to enhance screening criteria and improved in-hospital outcomes for those who will undergo CABG under Z benefit package. The study also showed insights on clinical profile and in-hospital outcomes of patients who underwent CABG in our own institution and this may give way to a larger scale of study involving multiple centers who also offer the said program.
Human ; Coronary Artery Bypass ; Atrial Fibrillation ; Insurance, Health
9.Effect of Huoxin pill (concentrated pill) combined with Baduanjin on prognosis after interventional operation of acute myocardial infarction complicated with heart failure
Peng WANG ; Zhengyan ZHANG ; Zonggui WU
Journal of Pharmaceutical Practice and Service 2025;43(7):348-352
<b>Objectiveb> To observe the effect of Huoxin pill (concentrated pill) combined with Baduanjin on the prognosis of patients with acute myocardial infarction complicated by percutaneous coronary intervention (PCI). <b>Methodsb> 120 patients with acute myocardial infarction complicated with heart failure who received emergency interventional treatment in our hospital from January 2022 to January 2023 were randomly divided into western medicine treatment group and Traditional Chinese Medicine (TCM)comprehensive treatment group. Western medicine treatment: standard western medicine treatment + five prescriptions for cardiac rehabilitation; based on western medicine treatment, Huoxin pill (concentrated pill) combined with Baduanjin therapy was added to the TCM comprehensive treatment group, and the follow-up was 6 months. The observed indexes were exertion angina pectoris scale, Chinese Medicine Syndrome Scale, Chinese medicine syndrome treatment effect evaluation, 6-minute walking test (6MWT), left ventricular ejection fraction (LVEF), and brain natriuretic peptide precursor (pro-BNP). <b>Resultsb> Sixty patients were enrolled in the two groups respectively. During the treatment, 2 cases fell off in the western medicine treatment group and 8 cases fell off in the TCM comprehensive treatment group, and a total of 110 cases were enrolled in the group. Compared with the western treatment group, TCM combined therapy significantly improved angina pectoris scale score, TCM Syndrome Scale score, pro-BNP, LVEF and 6MWT (P<0.001). There were no significant differences in blood routine, liver and kidney function, potassium, blood glucose, blood lipids and cardiac Troponin I (cTnI) between the two groups (P>0.05). No adverse cardiovascular events occurred during the entire treatment period in both groups. <b>Conclusionb> Huoxin pill (concentrated pill) combined with Baduanjin was more effective than western therapy in improving LVEF, 6MWT distance, exercise tolerance and cardiac function in patients with acute myocardial infarction complicated with heart failure.
10.Retrospective analysis of clinical efficacy of Nuangong Waifu formula in preventing intrauterine re-adhesion
Xuemei DI ; Wen SHUAI ; Qiqiang ZHANG ; Meixiang YU ; Hai ZHANG ; Yonghong NIE
Journal of Pharmaceutical Practice and Service 2025;43(7):353-356
<b>Objectiveb> The Nuangong Waifu formula (NGWFF) is a traditional Chinese medicine prescription that has been used in gynecology of traditional Chinese medicine in our hospital for many years. It has a certain effect on preventing postoperative intrauterine re-adhesion. To further retrospectively analyze the clinical efficacy of NGWFF. <b>Methodsb> A total of 200 patients who were diagnosed with intrauterine adhesions and underwent intrauterine adhesion separation from January 2018 to December 2020 were retrospectively included. They were divided into control group and observation group according to different drug use for postoperative prevention of re-adhesion, with 100 cases in each group. All patients were given oral estrogen and progesterone (ethinyl estradiol tablets 0.037 5 mg, q12 h, or estradiol valerate tablets 3 mg, q12 h, a total of 21 days, 7 days after estrogen therapy plus dydrogesterone 20 mg, qd or progesterone capsules 200 mg, qd) to promote endometrial growth. In the control group, 100 patients only used estrogen and progesterone after operation. In the observation group, 100 patients were treated with NGWFF at Guanyuan acupoint (four fingers under the navel), once a day. Both groups were evaluated for the degree of intrauterine adhesions under hysteroscopy and the effective rate after 3-5 menstrual cycles of drug treatment. <b>Resultsb> Compared with using estrogen and progesterone alone, combination use of NGWFF significantly decreased in the scores of intrauterine adhesions under hysteroscopy (2.41±1.19 vs 3.31±1.18, P=0.00), and the effective rate was also significantly higher than that in the control group ( 86 % vs 47 %, P<0.000). <b>Conclusionb> The combination use of NGWFF was more effective than using estrogen and progesterone alone in preventing re-adhesion after intrauterine adhesions, which provided a scientific basis for the clinical application of NGWFF.


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