目的 评估重组人Ⅱ型肿瘤坏死因子受体抗体融合蛋白（rhTNRF：Fc）治疗难治性慢性痛风性关节炎的临床疗效及安全性。方法 选取2022年1月一2023年12月广州中医药大学顺德医院风湿科门诊收治的46例难治性痛风性关节炎患者,分为观察组和对照组两组,对照组规范使用降尿酸药物治疗,观察组在对照组治疗的基础上联合使用rhTNRF：Fc至少12周,在0、12、24、48周观察两组的血尿酸（sUA）、肿瘤坏死因子-α（TNF-α）、关节肌肉骨骼超声变化、痛风发作例数、肝肾功能等指标。结果 观察组与对照组sUA无明显差别（P>0.05）,TNF-α水平明显下降（P<0.05）,滑膜炎、关节积液影像表现减少（P<0.05）,痛风发作例数明显减少（P<0.05）,观察期间肝肾功能正常,无患者因不良反应退出研究。结论 rhTNRF：Fc对难治性慢性痛风性关节炎安全有效。

Objective To explore the efficacy and safety of recombinant human type II tumor necrosis factor receptor-antibody fusion protein（rhTNRF：Fc）in refractory chronic gouty arthritis. Methods From January 2022 to December 2023, 46 cases of refractory chronic gouty arthritis in the Rheumatology Outpatient Department,Shunde Hospital Guangzhou University of Chinese Medicine were selected and divided into an observation group and a control group. The control group received routine treatment,while the observation group received rhTNRF：Fc treatment additionally for at least 12 weeks, two groups of indicators such as serum urine acid（sUA）, TNF-α, changes in musculoskeletal ultrasound,number of gout attacks,hepatic and renal function at 0, 12, 24, and 48 weeks were observed. Results There was no significant difference in sUA between the observation group and the control group（P>0. 05）, TNF-α significantly decreased（P<0. 05）, synovitis and joint effusion imaging manifestations reduced（P<0. 05）, number of gout attacks decreased（P<0. 05）. During the observation period, liver and kidney function were normal, and no patients withdrew from the study due to adverse reactions. Conclusions Using rhTNRF：Fc is safe and effective in treating refractory chronic gouty arthritis.

与正常组织细胞微环境相比,肿瘤微环境具有一定的异质性,包括偏酸性、氧化还原状态失衡、存在高浓度活性氧以及酶过量表达等。根据以上肿瘤微环境特点,可设计出一系列通过各种特殊微环境响应型连接臂相连的小分子或聚合物前药纳米粒。其中,多柔比星阿霉素作为一类最常见的广谱抗肿瘤药物在治疗肿瘤的过程中发挥重要作用。文章探讨了在肿瘤微环境特异性的生理状态下针对不同微环境所设计的多柔比星前药及其释放特性等,归纳总结了肿瘤微环境响应型多柔比星前药的研究进展。

Compared with normal tissue cell microenvironment, there is some differences in tumor microenvironment, such as partial acidity, imbalance of redox state, high concentration of reactive oxygen species and cathepsin. According to the above characteristics of tumor microenvironment, a series of small molecule or polymer prodrug nanoparticles connected by various special microenvironment responsive structures can be designed. Doxorubicin, as one of the most common broad-spectrum antitumor drugs, plays an important role in the treatment of tumors. This review discusses the doxorubicin prodrug designed for different tumor microenvironments under the physiological state of tumor microenvironment specificity and their release characteristics, and summarizes the research progress of tumor microenvironment-responsive doxorubicin prodrug.

       肿瘤治疗仍然是生物医学研究的一个突出领域。围绕各种化学治疗（化疗）药物和其他治疗药物的不良反应和靶向疗效的研究推动了各种药物载体的发展。这些载体聚焦于提高肿瘤部位的药物浓度，最大限度地减少全身不良反应，并改善治疗效果。在已报道的递送系统中，可注射水凝胶由于其微创的药物递送特性，已成为化疗药物体内递送的重要载体形式。文章系统地总结了可注射水凝胶的类型和特征，并进一步概括了可注射水凝胶装载药物的方式，同时深入讨论可注射水凝胶在治疗肿瘤的各种药物的递送应用。文章对原位注射水凝胶在治疗肿瘤方面存在的潜在性挑战和可能的解决方案提供了动态前瞻性的参考。可注射的水凝胶作为药物传递系统用于肿瘤治疗具有良好的发展前景。

       Tumor treatment remains a prominent area of biomedical research．The  researches surrounding the adverse 

reactions and targeted efficacy of various chemotherapy drugs and other therapeutic drugs have driven the development of various drug carriers．These carriers focus on increasing drug concentration at tumor site，minimizing systemic adverse reactions，and improving treatment outcomes．In the reported delivery systems，injectable hydrogels have become an important carrier for the delivery of chemotherapeutic drugs in vivo due to their minimally invasive characteristics．This review systematically summarized the types and characteristics of injectable hydrogels，and further summarized their drug loading methods．At the same time，the application of injectable hydrogels in the delivery of various drugs for tumor treatment was discussed in depth．This  review provides dynamic and prospective reference for the potential challenges and possible solutions of the in situ injectable hydrogels for tumor therapy．Injectable hydrogels as drug delivery systems are with good prospects for tumor treatment．

      长链非编码RNA（lncRNA）是一类长度大于200个核苷酸转录本，通过调控DNA、RNA及蛋白质的表达和功能，参与肿瘤发生、发展并发挥重要作用的RNA，近年来lncRNA成为恶性肿瘤早期诊断和预后标志物研究新的关注方向。Linc-UBC1作为一种新发现的lncRNA，在多种恶性肿瘤如肺癌、胃癌、结直肠癌、宫颈癌、卵巢癌、食管鳞癌等中异常高表达，可通过作为竞争性RNA（ceRNA）、参与信号通路等促进肿瘤细胞的增殖、迁移、侵袭、细胞周期进展、细胞凋亡和上皮间充质转化（EMT）等过程；高表达的linc-UBC1能够增加恶性肿瘤的耐药性，其表达水平与肿瘤分期、淋巴结转移和原发肿瘤远处转移呈正相关；linc-UBC1有望成为许多恶性肿瘤的新型的生物标志物、预后预测因子和治疗靶点，但其具体的调控机制仍处于研究的早期阶段，有待进一步深入研究。文章就目前linc-UBC1在恶性肿瘤发生和发展中的作用研究进展进行综述。

       Long non-coding RNA（lncRNA）is a class of transcripts with a length of more than 200 nucleotides．It is 

involved in the occurrence and development of tumors and plays an important role by regulating the expression and function of DNA，RNA and protein．In recent years，lncRNA has become a new research direction for early diagnosis and prognosis of malignant tumors．As a newly discovered lncRNA，linc-UBC1 is abnormally highly expressed in a variety of malignant tumors such as lung cancer，gastric cancer，colorectal cancer，cervical cancer，ovarian cancer，and esophageal squamous cell carcinoma．It can  promote the proliferation，migration，invasion，cell cycle progression，cell apoptosis and EMT of tumor cells by acting as a competing endogenous RNA（ceRNA）and participating in signaling pathways．High expression of linc-UBC1 can increase the drug resistance of malignant tumors，and its expression level is positively correlated with tumor stage，lymph node metastasis and distant metastasis of primary tumors．linc-UBC1 is expected to become a new biomarker，prognostic predictor and therapeutic target for many malignant tumors，while its specific regulatory mechanism is still in the early stage of research and needs further in-depth study．This article reviews the current research progress of linc-UBC1 in the occurrence and development of malignant tumors．

       目的   总结女性生殖系统中恶性中胚叶混合瘤（MMMT）的临床病理特征及预后，分析P53及错配修复蛋白与MMMT发病之间的关系。方法   收集大理大学第一附属医院2015年9月—2022年9月15例经手术切除病理诊断为MMMT的病例，总结临床病理特点、免疫表型（P53、错配修复蛋白等）、治疗方案并随访。结果  15例MMMT原发于子宫10例，卵巢5例。发病年龄范围49~76岁，平均年龄60岁，中位年龄58岁。临床表现为阴道流血或流液，伴或不伴腹痛或盆腔包块。镜下肿瘤均由不同比例的恶性上皮和间叶源性肿瘤构成，P53野生型12例，突变型3例；错配修复蛋白（MSH6、MSH2、MLH1、PMS2）检测存在缺失的有4例。15例患者中均行手术治疗，12例行盆腔淋巴结清扫术，术后辅以放化疗。随访失访2例，死亡4例，复发6例，3例术后无复发和转移。结论   恶性中胚叶混合瘤临床少见，恶性程度高，病理诊断上存在困难，需要辅以免疫组织化学染色，P53及错配修复蛋白缺失与MMMT的发生存在一定关系。治疗上需要手术切除，辅以放化疗。

    Objective  To summarize the clinical and pathological characteristics and prognosis of malignant mesodermal mixed tumor（MMMT）in the female reproductive system，and analyze the relationship between P53 and mismatch  repair proteins and the onset of MMMT．Methods  A total of 15 cases diagnosed with MMMT after surgical resection at the First Affiliated Hospital of Dali University from September 2015 to September 2022 were collected．The clinical and pathological characteristics，immune phenotype（P53，mismatch repair protein，etc. ），treatment plan were summarized．And the patients were followed-up．Results  Ten of 15 cases of MMMT were primary in the uterus and 5 of 10 in the ovaries．The age range of onset was 49 to 76 years old，with an average age of 60 and a median age of 58．Clinical manifestations included vaginal bleeding or fluid discharge，with or without abdominal pain or pelvic masses．Under the microscope，all tumors were composed of malignant epithelial and mesenchymal tumors in different proportions，with 12 cases of P53 wild-type and 3 cases of mutant type．There were 4 cases of missing mismatch repair proteins（MSH6，MSH2，MLH1，PMS2）detected．Among the 15 patients，all underwent surgical treatment，and 12 underwent pelvic lymph node dissection with postoperative adjuvant chemotherapy and radiotherapy．Two cases were lost to follow-up，four cases died，six cases recurred，and three cases had no recurrence or metastasis after surgery．Conclusions  MMMT are rare in clinical practice，with high malignancy and poor prognosis．Pathological diagnosis is difficult，and immunohistochemical staining is needed．The absence of P53 and mismatch repair protein is related to the occurrence of MMMT. Surgical  resection is required for treatment，supplemented by radiotherapy and chemotherapy．

       实体瘤对免疫治疗应答非常有限，因此，如何有效提升肿瘤免疫治疗的疗效，已成为当前肿瘤免疫治疗领域亟待解决的关键难题与挑战。髓系来源抑制性细胞（MDSCs）的趋化募集及其所介导的肿瘤免疫逃逸机制，是制约实体瘤免疫治疗效果的核心因素之一。文章深入探讨了MDSCs的起源、表型特征、其介导肿瘤免疫逃逸的具体机制，以及当前针对MDSCs的靶向治疗策略与将MDSCs靶向疗法与肿瘤免疫治疗相结合的最新研究进展。此外，文章还系统性地分析了靶向MDSCs联合免疫治疗策略所面临的关键挑战，并据此提出了MDSCs的精准靶向策略。这一策略旨在精确激活抗肿瘤免疫反应，为癌症患者提供更为个性化、高效的治疗方案，从而开启肿瘤免疫治疗领域的新纪元，为癌症治疗策略的创新与发展贡献力量。

  Solid tumors exhibit a very limited response to immunotherapy．Consequently，effectively enhancing the therapeutic efficacy of tumor immunotherapy has emerged as a critical challenge and problem that urgently needs to be addressed in tumor immunotherapy．The chemotaxis and recruitment of myeloid-derived suppressor cells（MDSCs）and the tumor immune evasionmechanisms mediated by them are one of the core factors that significantly restrict the efficacy of immunotherapy for solid tumors．In this review，we discuss the origins and phenotypic characteristics of MDSCs，the specific mechanisms by which they mediate tumor immune evasion，as well as current targeted therapeuticstrategies for MDSCs and the latest research progress in combining MDSC-targeted therapy with tumor immunotherapy．Furthermore，we  have  systematically analyzed the  key challenges faced by the combination of MDSC-targeted and immunotherapy strategies，and accordingly proposed a precise targeting strategyfor MDSCs．This strategy aims to precisely activate anti-tumor immune responses，providing more personalized and efficienttreatment options for cancer patients，thereby opening a new era in tumor immunotherapy and contributing to the innovation anddevelopment of cancer treatment strategies．

乳酸以往被视为不具备生物学功能的代谢废物。随着人们对乳酸的深入研究,发现乳酸有多种作用。乳酸化修饰是近期发现一种与乳酸有关的蛋白质翻译后修饰过程。乳酸化修饰主要有两种,一种是与乳酸相关的直接修饰,另外一种是与丙酮酸相关的间接修饰。这两种乳酸化修饰均可能受到糖酵解、乳酸转运与堆积、蛋白质串扰以及神经系统等多方面的调控。乳酸化修饰可以通过直接或间接修饰组蛋白或非组蛋白,从而在肿瘤组织的代谢重编程、增殖、迁移及免疫逃逸中发挥着重要作用。乳酸化修饰的深入研究,有望为肿瘤的诊断和治疗开辟新的路径。因此,为了明确乳酸化修饰在肿瘤方面的研究进展,本文就蛋白乳酸化修饰的分子机制及其在肿瘤中作用的研究进展作一综述。

       Lactic acid was previously regarded as a metabolic waste product with no biological function. As lactic acid has been intensively studied, it has been found to have multiple roles. Lactation modification is a recently discovered protein post-translational modification process related to lactic acid. There are two main types of lactation modification：one is direct modification related to lactic acid and the other is indirect modification related to pyruvate. Both types of lactation modification may be regulated by various aspects such as glycolysis, lactate transport and accumulation, protein crosstalk, and the nervous system. Lactation modification can play an important role in metabolic reprogramming, proliferation, migration, and immune escape of tumor tissues by directly or indirectly modifying histones or non-histone proteins. The in-depth study of lactation modification is expected to find new pathways for tumor diagnosis and treatment. Therefore, in order to clarify the research progress of lactation modification in tumors, this paper presents a review on the molecular mechanism of protein lactation modification and the research progress of its role in tumors.