Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Treat to target in Crohn’s disease:A practical guide for clinicians

A treat-to-target(T2T)approach applies the principles of early intervention and tight disease control to optimise long-term outcomes in Crohn's disease.The Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)-II guidelines specify short,intermediate,and long-term treatment goals,documenting specific treatment targets to be achieved at each of these timepoints.Scheduled appraisal of Crohn’s disease activity against pre-defined treatment targets at these timepoints remains central to determining whether current therapy should be continued or modified.Consensus treatment targets in Crohn’s disease comprise combination clinical and patient-reported outcome remission,in conjunction with biomarker normalisation and endoscopic healing.Although the STRIDE-II guidelines endorse the pursuit of endoscopic healing,clinicians must consider that this may not always be appropriate,acceptable,or achievable in all patients.This underscores the need to engage patients at the outset in an effort to personalise care and individualise treatment targets.The use of non-invasive biomarkers such as faecal calprotectin in conjunction with cross-sectional imaging techniques,particularly intestinal ultrasound,holds great promise;as do emerging treatment targets such as transmural healing.Two randomised clinical trials,namely,CALM and STARDUST,have evaluated the efficacy of a T2T approach in achieving endoscopic endpoints in patients with Crohn’s disease.Findings from these studies reflect that patient subgroups and Crohn’s disease characteristics likely to benefit most from a T2T approach,remain to be clarified.Moreover,outside of clinical trials,data pertaining to the real-world effectiveness of a T2T approach remains scare,highlighting the need for pragmatic real-world studies.Despite the obvious promise of a T2T approach,a lack of guidance to support its integration into real-world clinical practice has the potential to limit its uptake.This highlights the need to describe strategies,processes,and models of care capable of supporting the integration and execution of a T2T approach in real-world clinical practice.Hence,this review seeks to examine the current and emerging literature to provide clinicians with practical guidance on how to incorporate the principles of T2T into routine clinical practice for the management of Crohn’s disease.

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

The seeming paradox of adenosine receptors as targets for the treatment of Alzheimer's disease: agonists or antagonists?

Alzheimer＇s disease （AD） is the most common neurodegenerative disorder, and its incidence is relatively high among elderly people, affecting about 1-2% of the population between 60-65 years old and rising dramatically （about 30%） in people aged 80 years or older （Selkoe, 2002）. Nowadays, considering the increasing mean lifespan of populations in developed countries, the disease is becoming more and more a health concern, and the search for an effective cure has turned into＂a real need＂.

Resistance to targeted therapy in metastatic colorectal cancer:Current status and new developments

Colorectal cancer(CRC)is one of the most lethal and common malignancies in the world.Chemotherapy has been the conventional treatment for metastatic CRC(mCRC)patients.However,the effects of chemotherapy have been unsatisfactory.With the advent of targeted therapy,the survival of patients with CRC have been prolonged.Over the past 20 years,targeted therapy for CRC has achieved substantial progress.However,targeted therapy has the same challenge of drug resistance as chemotherapy.Consequently,exploring the resistance mechanism and finding strategies to address the resistance to targeted therapy,along with searching for novel effective regimens,is a constant challenge in the mCRC treatment,and it is also a hot research topic.In this review,we focus on the current status on resistance to existing targeted therapies in mCRC and discuss future developments.

Preliminary Findings on the Use of Targeted Therapy with Pazopanib and Other Agents in Combination with Sodium Phenylbutyrate in the Treatment of Glioblastoma Multiforme

The most common and aggressive type of brain tumor is glioblastoma multiforme (GBM). The prognosis for GBM remains poor with a five-year survival rate between 1% and 2%. The prospects for patients with recurrent GBM (RGBM) are much worse, with the majority dying within 6 months. This publication provides a brief description of the treatment of 11 GBM patients treated with sodium phenylbutyrate (PB) in combination with pazopanib, m-TOR inhibitors, and other agents. The treatment was associated with tolerable side effects and resulted in objective responses in 54.5% of cases (complete response 18.2%, partial response 36.3%) and 27.3% cases of stable disease. The preferable treatment regimen consisted of PB, pazopanib, dasatinib, everolimus, and bevacizumab (BVZ). For various reasons not all patients were compliant with the treatment regimen. In patients who strictly complied with the treatment plan, all responded as CR or PR. Based on preliminary findings, the authors propose further phase I/II clinical trials with PB in combination with pazopanib, dasatinib, everolimus, and BVZ in patients with RGBM who failed standard surgery, radiation therapy and chemotherapy. With proper dose reductions, the treatment appears to be well-tolerated. Molecular profiling of patient subgroups with favorable genomic signatures may help to select patients for future studies.

Successful Treatment of Recurrent Triple-Negative Breast Cancer with Combination of Targeted Therapies

We present an interesting case of a 56-year-old female diagnosed with invasive high-grade triple-negative breast cancer, who developed diffuse liver metastases following lumpectomy and combination chemotherapy with docetaxel, doxorubicin and cyclophosphamide, re-excision and radiation therapy. Restaging CT and PET scans revealed massive involvement of the liver. She was treated with a combination of gene targeted and cytotoxic chemotherapy including capecitabine, erlotinib, bevacizumab and phenylbutyrate. She tested weakly positive for HER-2 despite prior negative FISH, which prompted us to add trastuzumab to her regimen. Baseline CT revealed five liver tumors—the sum of the products of the two largest perpendicular diameters was 110 cm2. Follow-up CT after three months of treatment revealed 62% decrease in total tumor load. More than 50% decrease in tumor size persisted on two follow-up CT scans, confirming partial response. She developed progressive disease after 15 months of treatment. A group of 16 women, including this patient, diagnosed with triple negative breast cancer with distant metastases were treated by our team with a combination of gene targeted therapy and chemotherapy. Six percent of patients obtained partial response, 25% minor response, 31% stable disease, and 38% progressive disease. The median duration of treatment in patients who relapsed after the second-, third- and fourth- to seventh-lines of chemotherapy was 59 weeks, 22 weeks and 17 weeks, respectively. Comparison of results obtained with cytotoxic chemotherapy revealed that MDT in the second- and third-lines was only nine and four weeks, respectively. In conclusion, this case report indicates that it is possible to obtain durable objective response of recurrent TNBC with a combination of gene targeted agents.

甲状腺功能亢进症的态靶辨治策略

借鉴现代甲状腺功能亢进症的生理病理等医学认识,结合甲状腺功能亢进症的临床诊疗特征等,基于传统中医思维,以态靶辨治理论为指导,重新认识甲状腺功能亢进症,构建现代中医诊疗体系。根据甲亢(瘿气)的疾病发展演变态势,可概括为郁、火、虚三个阶段,治疗以态靶结合,态下分证,随病机变化施以疏肝散郁,或清泄火热,或益气养阴等,重视靶方靶药与现代药理研究的结合应用,精准用药。

Complex Target Volume Delineation and Treatment Planning in Radiotherapy for Malignant Pleural Mesothelioma (MPM)

Introduction: Radiotherapy alone or combined with surgery and/or chemotherapy is being investigated in the treatment of malignant pleural mesothelioma (MPM). This study aimed to simulate a Volumetric Modulated Arc Therapy (VMAT) treatment of a patient with MPM. Materials and Methods: CT images from a patient with intact lungs were imported via DICOM into the Pinnacle3 treatment planning (TP) system (TPS) and used as a model for MPM to delineate organs at risk (OAR) and both clinical and planning target volumes (CTV and PTV) with a margin of 5 mm. Elekta Synergy with 6 MV photons and 80 leafs MLCi2 was employed. VMAT plans were generated using two coplanar arcs with gantry rotation angles of 178° - 182°, the collimator angles of each arc were set to 90°, Octavius® 4D 729 was employed for quality assurance while the calculated and measured doses were compared using VeriSoft. Results: A TP was achieved. The Gamma volume analysis with criteria of 3 mm distance to agreement and 3% dose difference yielded the gamma passing rate = 99.9%. The reference isodose was 42.75 Gy with the coverage constraints for the PTV D95 and V95 = 95.0% of 45 Gy. The remaining dosimetric parameters met the recommendations from the clinically acceptable guidelines for the radiotherapy of MPM. Conclusion: Using well-defined TV and VMAT, a consistent TP compared to similar ones from publications was achieved. We obtained a high agreement between the 3D dose reconstructed and the dose calculated.

Combined treatment promotes the long-range axon regeneration to right brain targets

Axons in the peripheral nervous system(PNS)can regenerate after injury.However,the adult mammalian central nervous system(CNS)loses the intrinsic regrowth ability.No robust axon regeneration occurs spontaneously after nerve injury,which was clearly observed by Ramon y Cajal in the early 20^(th) century(1,2).Due to lack

采用Cell-SELEX技术的核酸适配体在肿瘤靶向治疗的研究进展

阐述细胞-配体指数富集系统进化(Cell-SELEX)技术特点,以及通过该技术筛选得到的核酸适配体在肿瘤靶向治疗中的应用进展和挑战,通过查阅近年的相关文献,综述核酸适配体作为药物及药物载体在肿瘤靶向治疗中的应用研究进展。结果表明:基于Cell-SELEX技术筛选得到的核酸适配体在肿瘤靶向治疗中的疗效显著,可开发成为肿瘤靶向治疗的潜力药物及良好的药物载体。

三维斑点追踪显像监测靶向治疗HER2阳性乳腺癌患者心肌损伤的临床价值

目的探讨三维斑点追踪成像(3D-STI)监测HER2阳性乳腺癌患者靶向治疗后心功能变化的临床价值,以及评估早期心肌损害的有效方法。方法选择2018年3月至2021年2月于解放军总医院第七医学中心首次接受曲妥珠单抗靶向治疗的HER2阳性乳腺癌患者65例。根据年龄分组,<60岁为A组(n=34),≥60岁为B组(n=31)。检测两组患者治疗前及治疗3月、6月、12月和治疗结束后6月的三维斑点追踪显像参数左室整体纵向应变(LVGLS)、二维超声心动图左室射血分数(LVEF),血清心肌损伤指标心肌肌钙蛋白Ⅰ(cTnI),N末端脑钠肽前体(NT-pro BNP)和肌酸激酶同工酶(CK-MB)质量。分别比较组间及组内不同时间的参数,采用Pearson检验评估LVGLS与cTnI的相关性。结果治疗前,两组患者的LVGLS、LVEF及cTnI、NT-proBNP和CK-MB水平比较,差异无统计学意义(P>0.05)。治疗12月,B组LVEF值较治疗前减低。治疗3月、6月、12月,B组LVGLS值较治疗前逐渐减低;B组LVGLS水平低于A组。治疗3月、6月、12月,B组cTnI、NT-proBNP、CK-MB水平较治疗前逐渐增高;B组cTnI、NT-pro BNP、CK-MB水平高于A组。与治疗12月的参数比较,治疗后6月,两组LVGLS增高,cTnI、NT-proBNP、CK-MB水平均减低。三维斑点追踪参数LVGLS与血清心肌损伤指标cTnI呈负相关(r=-0.82,P<0.05)。结论三维斑点追踪参数LVGLS能早期检测HER2阳性乳腺癌患者靶向治疗后的心肌损伤,客观反映心肌损伤程度,与血清心肌损伤指标水平相关。3D-STI在监测靶向药物治疗HER2阳性乳腺癌患者的早期心脏毒性具有临床价值。

基于态靶辨治代谢疾病智能辅助诊疗系统的研究与设计

目的:基于“态靶辨证”中医诊疗思维,利用人工智能技术为代谢病中医辅助诊疗提供智能化支持。方法:通过自然语言处理技术,对医学文献和专家经验进行信息抽取和实体识别,构建包含疾病状态、治疗靶点及相关辨证规则的术语知识库。在此基础上,利用图数据库和深度学习算法,构建态靶辨证知识图谱,表达不同疾病状态与治疗靶点之间的复杂关系。结果:通过模型训练和知识推理,结合病例的具体症状和体质,推荐相应的中医治疗方案,提高了代谢病辅助诊疗的准确性和效率。结论:本研究为中医辨证施治提供了新的方法和思路,不断迭代优化算法,拓展临床应用,推动中医药辅助诊疗的发展和完善,为中医药传承创新奠定良好的技术基础。

纳米金材料在肿瘤诊治领域中的应用研究进展

在肿瘤的预防与控制方面,实施“三早”策略——即早期发现、早期诊断、早期治疗——被认为是实现一级预防效果的最有效途径。尽管如此,当前肿瘤早期诊断的技术和能力仍然遭遇着重大挑战。另一方面,传统的抗肿瘤药物由于其高毒性和缺乏针对特定组织的特异性,导致在实际治疗中的应用受到了显著限制。纳米金材料因其独特的优势而脱颖而出,包括表面易于改性、出色的生物相容性、小尺寸带来的特殊效应、光学性质以及量子效应等,使其在肿瘤细胞的诊断和治疗方面显示出巨大的应用潜力。近年来,纳米金在肿瘤的临床诊断和治疗领域受到了广泛的关注和研究,并已取得了令人鼓舞的进展。该文旨在对纳米金材料在肿瘤诊治领域中的最新研究进展进行全面的综述,以期为肿瘤患者提供更加有效和个性化的诊疗方案,推动其在临床实践中的广泛应用。

Long-term acupuncture treatment has a multitargeting regulation on multiple brain regions in rats with Alzheimer＇s disease：a positron emission tomography study

The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.

2023年度非小细胞肺癌外科治疗进展

肺癌是当前世界各地最普遍和最致命的癌症,严重威胁人们的生命健康。外科手术切除是最早治疗肺癌的手段,也是目前肺癌最主要的治疗手段。随着医学技术的进步,外科手术方法和辅助治疗策略不断革新,这为肺癌患者带来了新的希望。因此总结肺癌外科治疗领域的最新研究进展具有重要意义。本文旨在综述2023年度非小细胞肺癌(non-small cell lung cancer,NSCLC)外科治疗的主要进展,包括手术技术的创新、微创手术、辅助分子靶向治疗及免疫治疗在NSCLC围手术期的应用等。

巨噬细胞靶向的纳米载药平台治疗RA滑膜炎研究新进展

类风湿关节炎(RA)是一种以慢性侵蚀性多关节炎为特征的全身性自身免疫性疾病。其核心病理改变是关节滑膜的持续炎症和血管翳形成,进而引起关节软骨和骨的破坏。RA的病因和发病机制仍不明确且复杂,尽管在过去的几十年里已经积累了大量关于RA的治疗证据和经验,但目前尚没有明确的方法可以逆转RA关节组织损伤。纳米载药平台作为一种基于纳米材料的药物递送系统,旨在改善药物分布、增强疗效及减少药物不良反应。该文重点分析RA滑膜炎的发病机制,并探讨巨噬细胞靶向的纳米载药平台在RA的预防和治疗中的应用和潜力。

中晚期原发性肝细胞癌的临床治疗现状与展望

鉴于我国肝细胞癌的高发率和中晚期肝癌的高检出率,患者就诊时已失去手术切除癌组织的机会,而临床上对于不可手术切除的肝癌患者进行单一的治疗往往无法获得良好的预后效果,且5年生存率低。因此,急需规范的综合治疗手段提高晚期肝癌患者的总生存期。通过复习国内外开展的针对中晚期肝癌患者治疗的临床实验,发现阿替利珠单抗联合贝伐株单抗用于不可手术切除的晚期肝癌患者在总生存期、无病进展期和药物不良反应发生率方面明显优于单药纳武力尤单抗和派姆单抗,同时,瑞戈非尼靶向治疗索拉菲尼耐药的肝癌患者也取得了更长时间的中位生存期。由于单独应用免疫治疗或靶向治疗不能达到晚期肝癌患者无瘤生存的要求,因此介入手术治疗联合免疫治疗或靶向治疗可明显缩短患者总治疗时间,且药物不良反应分级更低,增加了患者的依从性。通过对现有临床药物试验结果的总结和分析,在提高肝癌患者药物获益率和降低不良反应等方面具有重要意义。

NLRP3炎症小体在动脉粥样硬化中的作用机制和靶向炎症治疗的研究进展

动脉粥样硬化(As)是由一系列复杂因素引起的病理过程,包括内皮功能障碍、动脉血管壁中脂质沉积、巨噬细胞浸润、平滑肌细胞功能失调、泡沫细胞形成等,炎症反应在这一过程中发挥了重要的作用。NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体是炎症细胞的传导器,其激活后介导炎症反应,激活下游的白细胞介素18、白细胞介素1β,从而参与As的发生和发展。因此,针对NLRP3炎症小体和下游炎症因子的特异性抑制剂是目前临床药物研究的潜在靶点,有望成为治疗As的一种新的治疗措施。文章对NLRP3炎症小体的结构和激活机制及与As的关系进行了讨论,同时对靶向NLRP3炎症小体和下游炎症因子的药物进行了介绍。

基于“态靶辨治”理论的甲状腺功能亢进症临证诊疗思路

甲状腺功能亢进症是内分泌系统常见病,其临床表现复杂多变,发病率较高。单纯依靠传统中医学的辨证论治甲状腺功能亢进症,往往只能改善症状。仝小林院士提出“态靶辨治”理论,此方略对于本病的治疗亦大有可为。通过中医思维四诊合参,借助临床指标对疾病进行诊断,“郁、火、虚”三态定位疾病阶段,病靶、症靶、标靶合参精准辨证论治,并通过归纳核心病因病机,审查甲状腺功能亢进症“郁态”之“因态”,兼顾“虚态”之“果态”,以确定理法方药量,病证合参,态靶结合,不仅能够改善临床症状,同时兼顾疾病本身的治疗,以达到扶正固本、标本同治的效果。