Tumor angiogenesis and anti-angiogenic therapy

Anti-angiogenic drugs(AADs),which mainly target the vascular endothelial growth factor-A signaling pathway,have become a therapeutic option for cancer patients for two decades.During this period,tremendous clinical experience of anti-angiogenic therapy has been acquired,new AADs have been developed,and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy.However,improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required.This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development.We revisit the history of concept initiation and AAD discovery,and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Combined modality therapy for stage Ⅰ_B cervical cancer

Objective:To evaluate the current approaches for multimodality therapy for stage ⅠB cervical cancer.Methods:The relevant literature has served as a source for identified high or intermediate risks and management of stage ⅠB cervical cancer.Result:The high risks include pelvic lymph node metastasis(PLNM),positive resection margin(PRM),and the involvement of parametrium(IPM).The intermediate risks include deep stromal invasion(DSI),bulky tumor size(BTS),lymphovascular space invasion(LVSI).Adeno-carcinomatous histotype is the new risk feature relevant to poor prognoses.Both radical hysterectomy plus bilateral pelvic lymph node dissection(PLND) and radical radiotherapy have proven to be equally effective.Surgery is more performed for stage ⅠB1 disease;radiotherapy or chemoradiotherapy is preferable for stage ⅠB2 disease.For patients with one high risk or two of intermediate risks,radical hysterectomy plus PLND followed by concurrent chemoradiotherapy can improve overall survival(OS) and disease-free survival(DFS).Conclusion:The management should be individualized for stage ⅠB cervical cancer.The optimized multidisciplinary therapy can benefit patients with the best cure and minimum morbidity and complications.

Multimodality treatment in hepatocellular carcinoma patients with tumor thrombi in portal vein

AIM: To compare the therapeutic effect and significances of multimodality treatment for hepatocellular carcinoma (HCC) with tumor thrombi in portal vein (PVTT). METHODS: HCC patients (n=147) with tumor thrombi in the main portal vein or the first branch of portal vein were divided into four groups by the several therapeutic methods. There were conservative treatment group in 18 out of patients (group A); and hepatic artery ligation(HAL) and/or hepatic artery infusion (HAI) group in 18 patients (group B), in whom postoperative chemoembolization was done periodically; group of removal of HCC with PVTT in 79 (group C) and group of transcatheter hepatic arterial chemoembolization (TACE) or HAI and/or portal vein infusion (PVI) after operation in 32 (group D). RESULTS: The median survival period was 12 months in our series and the 1-,3-, and 5-year survival rates were 44.3%, 24.5% and 15.2%, respectively. The median survival times were 2, 5, 12 and 16 months in group A, B, C and D, respectively. The 1-, 3- and 5-year survival rates were 5.6%, 0% and 0% in group A; 22.2%, 5.6% and 0% in group B; 53.9%, 26.9% and 16.6% in group C; 79.3%, 38.9% and 26.8% in group D, respectively. Significant difference appeared in the survival rates among the groups (P 【 0.05). CONCLUSION: Hepatic resection with removal of tumor thrombi and HCC should increase the curative effects and be encouraged for the prolongation of life span and quality of life for HCC patients with PVTT, whereas the best therapeutic method for HCC with PVTT is with regional hepatic chemotherapy or chemoembolization after hepatic resection with removal of tumor thrombi.

Treatment of Peripheral Neuropathy: Combination Therapy Using LED Light, Extracorporeal Shockwave Therapy, Platelet Rich Plasma, and an Oral Dietary Supplement

Objectives: Peripheral neuropathy (PN) is a significant contributor to disability in the elderly. It is also one of the most prevalent complications of type 2 diabetes, prediabetes and metabolic syndrome. PN is commonly associated with pain, numbness, tingling, burning, and cramping in the feet and legs. Current treatment options are limited to controlling pain, seizures and use of antidepressant medications. These treatments have undesirable side effects and don’t stop PN progression. Here we utilized a combination of individual-specific modalities to improve local circulation and relieve PN symptoms. Methods: We conducted an open-label, multicenter pilot trial with 34 subjects (19 males and 15 females ranging from 40 - 85 years of age). All of the participants were diagnosed with peripheral neuropathy and had bilateral symptoms in their feet, and many reported the same symptoms (pain, numbness, tingling, burning, and cramping) in their lower legs. The duration of symptoms ranged from four months to over six years. On Day 0, subjects were given a 90-day supply of the oral supplement with dosing instructions and a LED light therapy device. They also received three platelet-rich plasma (PRP) injections in their lower extremities. Subjects also received an extracorporeal shockwave therapy (ESWT) treatment for each foot and subsequently twice per week for the first six weeks, then once weekly for the duration of the study. Subjects filled out the Brief Pain Index (BPI) at weekly intervals. On Day 90, subjects completed the Patient Global Impression of Change (PGIC) survey. Results: There were significant responses to pain, as evidenced by BPI scores at weeks 8, 9, 10 and 11 (p = 0.02, 0.01, 0.02, and 0.003, respectively). Analysis of the final day PGIC survey showed a favorable outcome for 73% of participants (p = 0.003), with the majority reporting Very Much Improved. Conclusions: By utilizing a multi-modality treatment protocol that includes PRP, LED light therapy, ESWT and an oral dietary supplement, we observed significant reductions in BPI scores. Quality of life and their overall impression of change (PGIC) were significantly improved, and there were no significant side effects.

非结核分枝杆菌肺病抗菌素治疗以外的综合治疗研究进展

近年来,非结核分枝杆菌(nontuberculous mycobacteria,NTM)感染引起的肺部疾病发病率和患病率呈快速上升趋势。然而,非结核分枝杆菌肺病(nontuberculous mycobacteria pulmonary disease,NTM-PD)存在治愈率低、病亡率高和复发率高的特点。因而,有学者提出,临床医生在治疗NTM-PD时,应该首先管理患者宿主因素,处理好NTM-PD的可控特性,然后优化抗NTM治疗。笔者就近期有关NTM-PD抗菌素以外综合治疗的现状进行综述,提出在治疗NTM-PD的过程中,强化抗菌素以外的综合治疗,减少或避免接触NTM环境,提高机体的免疫力和改善结构性肺病所引起的肺部内环境,是提高疾病治愈率和降低复发率的重要措施。

神经肌肉电刺激在脑卒中后运动障碍中的研究进展

近年来,中国脑卒中患者的发病率日益增高,且其所致的运动功能障碍往往严重影响了患者的日常生活质量,神经肌肉电刺激(NMES)作为一种新兴康复治疗手段,被广泛应用于治疗脑卒中患者的运动功能障碍。本文就NMES在脑卒中后运动功能康复中作用的参数、机制及其在临床中的运用进行了归纳总结。未来应进一步探讨NMES作用的具体机制及高效安全的治疗方案。

混合小型化波导热疗天线设计

热疗天线由于体积较大,辐射的微波能量范围也较大,天线设计使用较为复杂,不适用于治疗体积较小的肿瘤。针对这一问题设计了一种小型化波导热疗天线来治疗小体积肿瘤,考虑到透热深度与天线体积的兼顾,选用了915 MHz的中心频率,使用混合小型化技术将天线小型化,即通过对天线加脊的同时加入短路探针将天线半径缩小到了19 mm,其高为36 mm。比吸收率仿真时馈入1 W的能量最高点能够达到45 W/kg,温度场仿真时馈入20 W能量加热30分钟后最热的区域温度可达45℃,体模实验结果与仿真实验相吻合,这些实验结果均表明其能够达到治疗乳房内部肿瘤的效果。

利用综合康复治疗降低非特异性腰背痛复发率

目的:探讨综合康复治疗方法对慢性非特异性腰背痛患者临床治疗效果,以及对患者腰痛的缓解情况、核心肌群力量的改善情况及腰痛复发率的影响。方法:选取2022年9月—2023年3月在中国人民解放军联勤保障部队第九八九医院门诊治疗的非特异性腰背痛患者共60例,随机分为常规治疗组和综合康复组,常规治疗组采用辅具、服用非甾体类抗炎药物及贴敷膏药进行治疗。综合康复组在常规治疗组治疗方法的基础上通过运动疗法联合物理因子共同治疗。治疗2、4周后对两组患者进行疼痛评估和功能障碍指数评估,6个月后对患者进行回访,分析复发率情况。结果:治疗2周后,综合康复组的视觉模拟评分法(VAS)、腰部疼痛分级指数(PRI)及Oswestry功能障碍指数(ODI)均优于常规治疗组(P<0.05),两组腰痛的疼痛强度(PPI)差异无统计学意义(P>0.05)。治疗4周后,综合康复组观察指标(VAS、PRI、ODI、PPI)均优于常规治疗组,治疗6个月后随访,综合康复组复发率低于常规治疗组(P<0.05)。结论:综合康复治疗对缓解腰部疼痛症状,增强核心肌力,恢复腰椎功能,以及对降低复发率有明显作用。

肺癌化疗患者住院期间体力活动水平和症状群的相关性分析

目的:了解肺癌化疗患者的运动意愿及体力活动水平,并分析患者体力活动水平与症状群的相关性。方法:2022年6—8月,采用一般资料调查表、国际体力活动问卷、中文版安德森症状评估量表、修订版肺癌特异性症状模块对上海市肺科医院住院的232例肺癌化疗患者进行横断面调查。共回收有效问卷229份,有效回收率为98.71%。采用探索性因子分析提取症状群的种类,通过Spearman秩相关分析探讨体力活动水平与症状群的关系。结果:调查显示,肺癌化疗患者存在6个症状群,分别为:呼吸道症状群、睡眠相关症状群、心理症状群、消化道症状群、肺癌特异性症状群和恶病质症状群。中强度体力活动水平与心理症状群及恶病质症状群呈负相关(r=-0.153、-0.159,P值均<0.05);步行体力活动水平与呼吸道症状群、睡眠相关症状群、心理症状群及肺癌特异性症状群呈负相关(r=-0.257、-0.222、-0.284、-0.181,P值均<0.05);总体力活动水平与呼吸道症状群、睡眠相关症状群、心理症状群及恶病质症状群呈负相关(r=-0.252、-0.218、-0.304、-0.132,P值均<0.05)。结论:肺癌化疗患者的体力活动水平与症状群呈负相关,体力活动水平高的患者其症状群负担较轻,建议根据患者的体力活动水平及症状负担进行个性化运动处方设计,健康教育和运动指导,提高患者体力活动水平,从而减轻症状负担。

NMES对脑卒中后上肢失用性肌萎缩的应用效果

目的:观察神经肌肉电刺激对脑卒中后患者上肢失用性肌萎缩的应用效果。方法:采用文献资料法、实验法、数理统计法,选取贵阳市白云区人民医院2023年1月—2024年1月脑卒中后上肢失用性肌萎缩患者20例,依据随机数表法将其分为对照组和实验组,每组10例。对照组给予常规康复治疗,实验组在常规康复治疗的基础上增加神经肌肉电刺激治疗,通过测量肌肉围度,以及采用MMT量表和简化版Fugl-Meyer运动功能能力量表来评估治疗疗效,并对实验数据进行统计分析。结果:治疗中期,实验组和对照组上肢肌肉围度、MMT比较,差异不具有统计学意义(P>0.05);Fugl-Meyer量表比较,差异具有统计学意义(P<0.01)。治疗末期,实验组和对照组上肢肌肉围度、MMT和Fugl-Meyer比较,差异具有统计学意义(P<0.05)。结论:神经肌肉电刺激能改善肌肉功能和有效治疗脑卒中后上肢失用性肌萎缩症状。

糖尿病合并坏死性筋膜炎9例治疗经验

目的总结糖尿病合并坏死性筋膜炎的治疗经验。方法回顾性分析2018年9月至2020年12月贵州医科大学附属医院整形烧伤外科收治的糖尿病合并坏死性筋膜炎患者的临床资料。入院后首先进行血糖控制,经验性应用抗生素抗感染,并进行营养支持治疗;24~72 h内行手术扩创或切开引流,术中收集坏死组织及脓性渗出物行病原微生物培养及药敏试验;扩创术后于创面安装负压封闭引流装置进行引流,联合1.5%过氧化氢溶液冲洗创面,或联合皮下放置多根引流管引流。如果术后感染未得到控制,需再次行扩创处理。在创面清洁、肉芽组织新鲜状态下,采用大腿外侧中厚皮片移植修复。观测坏死性筋膜炎实验室检查风险指标(LRINEC)并评分,包括C反应蛋白、白细胞计数、血红蛋白、血钠、血肌酐、血糖,总分0~13分,评分≥6分应积极怀疑为坏死性筋膜炎;观察创面感染控制情况,统计扩创次数、创面修复方式、截肢情况、住院时间,并对创面愈合情况和坏死性筋膜炎复发情况进行随访。结果共纳入9例患者,其中男7例,女2例;年龄39~81岁;糖尿病病程为0.5~10年;上肢1例,下肢6例,会阴部1例,会阴部合并下肢1例;LRINEC评分≥8分5例,6~7分4例。4例经过1次、3例经过2次、2例经过3次手术扩创后,创面感染得到控制,达到清洁、肉芽组织新鲜状态;7例创面以厚中厚皮片移植修复后愈合,1例创面行薄中厚皮片移植后有散在的点状反复渗液,换药后愈合,1例右小腿中段截肢。微生物培养结果及抗生素应用情况:2例为金黄色葡萄球菌感染,予头孢他啶2000 mg静脉滴注,2次/d;1例为假丝酵母菌感染,予氟康唑400 mg静脉滴注,1次/d;2例为粪肠球菌、2例为屎肠球菌感染,均予哌拉西林他唑巴坦钠4500 mg静脉滴注,3次/d;2例为大肠埃希菌感染,予左氧氟沙星500 mg静脉滴注,1次/d。9例患者住院时间为24~56 d。出院时,LRINEC均较入院时明显改善,LRINEC评分为0~2分。随访3个月至2年,1例随访6个月后患肢创面再次出现感染,经抗感染、换药后愈合;其余病例创面愈合良好,无复发。结论糖尿病合并坏死性筋膜炎采取综合控制血糖的同时进行手术治疗,并联合负压封闭引流和1.5%过氧化氢溶液冲洗创面,以及足量足疗程的抗生素治疗,可控制病情,促进创面愈合,并减少病死率和截肢率。

石墨烯基纳米材料在乳腺癌诊疗中的应用研究进展

乳腺癌是女性最常见的恶性肿瘤,发病率逐年上升。传统的诊治方法仍有不足,因此迫切需要探索新的诊治策略。石墨烯基纳米材料(graphene-based nanomaterials,GBNs)具有靶标选择性、光致发光性、易功能化、化学增敏和高载药量等优点,是一种有前景的药物载体。本文首先总结了GBNs在癌症治疗中的生物特性,然后重点介绍了GBNs在乳腺癌诊疗中的应用,包括化学治疗、光疗、靶向治疗、早期诊断和肿瘤显像、作为联合治疗的平台以及修饰策略。强调了GBNs在减毒增效、多药递送、生物传感、分子成像和联合治疗等方面的优势。最后阐明了GBNs在乳腺癌诊疗领域亟待解决的问题与挑战,旨在为研究者们指明方向并提供新的思路。

强迫症创新性系统化综合治疗疗效分析

目的探讨低成本、系统的综合治疗模式快速有效改善患者强迫症的严重程度。方法选取诊断强迫症患者89例,分为药物治疗组64例和综合治疗组25例。药物治疗组接受常规药物治疗;综合治疗组接受经颅直流电治疗(tDCS)+药物治疗+心理治疗综合组,均治疗2周。治疗前后均采用耶鲁布朗强迫症状量表(Y-BOCS)、24项汉密尔顿抑郁量表(HAMD-24)及汉密尔顿焦虑量表(HAMA)进行评定。结果治疗2周后,两组患者Y-BOCS总分及因子分均较治疗前降低(P<0.05),综合治疗组Y-BOCS总分(Z=-3.112,P=0.002)及因子分[思维分(Z=-2.13,P=0.033),行为分(Z=-3.334,P=0.001)]、HAMD总分(Z=-2.819,P=0.005)、HAMA总分(Z=-2.002,P=0.045)均低于药物治疗组,Y-BOCS减分率高于药物治疗组(Z=-3.658,P<0.001)。2周后,综合治疗组有效率高于药物治疗组(Z=11.063,P<0.001)。两组HAMD、HAMA总分均较治疗前降低(P<0.05)。结论系统的tDCS综合治疗模式可短期内显著改善患者强迫症严重程度。

双模态成像仿生纳米粒对甲状腺髓样癌的声动力治疗

背景:声动力疗法作为一种新型抗肿瘤治疗手段具有非侵入性和时空可控性的特点,在甲状腺髓样癌无创性治疗中具有广阔的应用前景。目的:制备具有双模态成像能力的仿生癌细胞膜涂层脂质纳米粒,检测纳米粒的理化性质、靶向能力、成像效果、细胞毒性和抗迁移能力。方法:以二棕榈酰磷脂酰胆碱、二棕榈酰磷脂酰甘油、二硬脂酰磷脂酰乙醇胺-聚乙二醇2000、胆固醇、血卟啉单甲醚、全氟己烷为原料,通过薄膜水合-超声振荡法制备脂质纳米粒HP@LNP,其中血卟啉单甲醚装载于脂质纳米结构的疏水层,全氟己烷装载于脂质纳米结构的亲水核心层内;将甲状腺髓样癌细胞膜包覆于脂质纳米粒HP@LNP表面,构建具有主动靶向甲状腺髓样癌细胞能力的仿生脂质纳米粒MHP@LNP。表征纳米粒MHP@LNP的理化性质、靶向能力、免疫逃逸能力、成像效果、细胞毒性和抗迁移能力。结果与结论:①脂质纳米粒MHP@LNP呈现典型的核壳结构,粒径为131.06 nm,平均电位为-30.59 mV,凝胶电泳结果显示脂质纳米粒MHP@LNP与癌细胞膜蛋白图谱相符合,荧光共定位结果显示脂质纳米粒MHP@LNP与癌细胞膜的荧光信号显著重合。脂质纳米粒MHP@LNP纳米粒内血卟啉单甲醚的包封率为87.8%,载药率为14.6%。在低强度聚焦超声刺激下,脂质纳米粒MHP@LNP可发生相变产生微泡,在4 min时超声信号强度达到最大值。在激光照射下,脂质纳米粒MHP@LNP的光声信号强度与其质量浓度呈现线性相关。脂质纳米粒MHP@LNP具有同源细胞靶向能力和免疫逃逸能力。未经低强度聚焦超声照射前的脂质纳米粒MHP@LNP具有良好的生物相容性,而经低强度聚焦超声照射后产生具有细胞毒性的活性氧,有效杀伤甲状腺髓样癌细胞,并抑制甲状腺髓样癌细胞的迁移能力。②结果表明,脂质纳米粒MHP@LNP能够在超声和光声双模态成像引导下实现声动力治疗,用于治疗甲状腺髓样癌。

Coronary atherosclerosis is already ongoing in pre-diabetic status: Insight from intravascular imaging modalities

Diabetes mellitus is a powerful risk factor of coronary artery disease(CAD), leading to death and disability. In recent years, given the accumulating evidence that prediabetes is also related to increasing risk of CAD including cardiovascular events, a new guideline has been proposed for the treatment of blood cholesterolfor primary prevention of cardiovascular events. This guideline recommends aggressive lipid-lowering statin therapy for primary prevention in diabetes and other patients. The ultimate goal of patient management is to inhibit progression of systemic atherosclerosis and prevent fatal cardiovascular events such as acute coronary syndrome(ACS). Because disruption of atherosclerotic coronary plaques is a trigger of ACS, the high-risk atheroma is called a vulnerable plaque. Several types of novel diagnostic imaging technologies have been developed for identifying the characteristics of coronary atherosclerosis before the onset of ACS, especially vulnerable plaques. According to coronary angioscopic evaluation, atherosclerosis severity and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable to that in diabetic patients. In addition, pharmacological intervention by statin therapy changed plaque color and complexity, and the dynamic changes in plaque features are considered plaque stabilization. In this article, we review the findings of atherosclerosis in prediabetes, detected by intravascular imaging modalities, and the therapeutic implications.

Adjuvant therapy in pancreatic cancer

The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic cancer, leading to a dramatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone. The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

Effects of Electro-Acupuncture on Immune Function After Chemotherapy in 28 Cases

PURPOSE: To observe the effects of electroacupuncture therapy on T cells and activity of NK cell in the patient of Chemotherapy. METHOD: Electro-acupuncture therapy was simultaneously applied during chemotherapy, T cells and activity of NK cell of patients were determined before electroacupuncture treatment (before chemotherapy) and after 4-course electro-acupuncture treatments. RESULTS: Before chemotherapy, CD3 was low within the normal range, CD4 was much lower than the normal range, and CD8, CD4/CD8 and activity of NK cell were within the normal range. After one month of chemotherapy combined with electro-acupuncture, no decline of all the indices was found (P > 0.05). CONCLUSION: Electro-acupuncture can really increase the immune function of patients of chemotherapy.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

AIM:rAAV mediated endostatin gene therapy has been examined as a new method for treating cancer.However, a sustained and high protein delivery is required to achieve the desired therapeutic effects.We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model. METHODS:rAAV containing endostatin expression cassettes were transduced into hepatoma cell lines.To test whether the topoisomerase inhibitor pretreatment increased the expression of endostatin,Western blotting and ELISA were performed.The biologic activity of endostatin was confirmed by endothelial cell proliferation and tube formation assays. The anti-tumor effects of the rAAV-endostatin vector combined with a topoisomerase inhibitor,etoposide,were evaluated in a mouse liver tumor model. RESULTS:Topoisomerase inhibitors,including camptothecin and etoposide,were found to increase the endostatin exPression level in vitro.The over-expressed endostatin, as a result of pretreatment with a topoisomerase inhibitor, was also biologically active.In animal experiments,the combined therapy of topoisomerase inhibitor,etoposide with the rAAV-endostatin vector had the best tumor- suppressive effect and tumor foci were barely observed in livers of the treated mice.Pretreatment with an etoposide increased the level of endostatin in the liver and serum of rAAV-endostatin treated mice.Finally,the mice treated With rAAV-endostatin in combination with etoposide showed the longest survival among the experimental models. CONCLUSION:rAAV delivered endostatin gene therapy in combination with a topoisomerase inhibitor pretreatment is an effective modality for anticancer gene therapy.

Forty-three Cases of Acute Lumbar Sprain Treated by Acupuncture Plus Kinesitherapy

Acute lumbar sprain is commonly encountered among the young and middle-aged. It often occurs at the lower part of the back, which seriously hinders the daily life and work of the patients because of the severe pain. The author has treated 43 cases of acute lumbar sprain by needling Weizhong (BL 40), Houxi (SI 3) and Yaotongdian (EX-UE7) plus kinesitherapy and obtained satisfactory therapeutic results. A report follows.