目的 探讨鳞状上皮细胞抗原（SCCA）、人乳头瘤病毒（HPV）-DNA联合阴道镜检查在宫颈鳞状细胞癌（SCC）筛查中的应用价值。方法 选择2019年1月1日—2021年12月31日在中山市博爱医院就诊并确诊为SCC的妇女作为研究对象,共纳入100例SCC患者（SCC组）,同时选择200例经活检确诊为宫颈慢性炎症的患者（宫颈慢性炎症组）作为阴性对照。采用阴道镜观察研究对象的宫颈情况,并采集研究对象的宫颈组织标本进行HPV-DNA检测。采集研究对象的静脉血,采用化学发光免疫法测定研究对象SCCA的水平。以病理检查结果为金标准,分别对HPV-DNA检测、外周血SCCA两者联用以及阴道镜、HPV-DNA检测、外周血SCCA三者联用进行筛查效果的评价。结果 SCC组研究对象的年龄≥40岁者、出血者、性生活开始年龄≤20岁者比例均高于宫颈慢性炎症患者组;而宫颈慢性炎症患者组疼痛的比例高于SCC患者组,差异均有统计学意义（P<0.01）。χ²检验结果显示,SCC组研究对象的SCCA阳性率高于宫颈慢性炎症组（P<0.001）。阴道镜结合SCCA、HPV-DNA检测筛查SCC的灵敏度和特异度均高于单独使用SCCA和HPV-DNA,并取得较好的约登系数（75%）和Kappa值（0.730）。结论 采用阴道镜结合HPV-DNA、SCCA可有效提高SCC疾病的约登系数与Kappa值,其联合诊断的效能高于单独使用阴道镜、HPV-DNA或SCCA诊断SCC。

Objective To study the application value of squamus cell carcinoma antigen（SCCA）and human papillomavirus（HPV）-DNA combined with colposcope in cervical squamous cell carcinoma（SCC）screening．Methods Women diagnosed with SCC who visited Boai Hospital of Zhongshan city from January 1,2019 to December 31,2021 were selected as research subjects,including 100 patients with SCC（SCC group）and 200 patients with chronic cervical inflammation confirmed by biopsy（chronic cervical inflammation group）．The cervix of the subjects was observed by colposcope,and cervical tissue samples were collected for HPV-DNA testing．Venous blood of subjects was collected and SCCA levels were determined by chemiluminescence immunoassay．Using pathological examination results as the gold standard,the screening effect of combination HPV-DNA test and peripheral blood SCCA test,combination colposcope,HPV-DNA test and peripheral blood SCCA were evaluated respectively．Results In SCC group,the proportion of age≥40 years old,bleeding,sexual life age ≤20 years old were higher than those in chronic cervical inflammation group,but chronic cervical inflammation group had higher rate of pain than those in SCC group（P<0.01）by Chi-square test．SCCA positive rate in SCC group was higher than that in chronic cervical inflammation group（P<0.001）by Chi-square test．The sensitivity and specificity of colposcope combined with SCCA and HPV-DNA were higher than those of SCCA and HPV-DNA alone,and better Youden’s coefficient（75%）and Kappa value（0.730）were obtained．Conclusions Colposcope combined with HPV-DNA and SCCA can effectively improve the Youden’s coefficient and Kappa value of SCC disease,and its combined diagnosis efficiency was higher than that of colposcope,HPV-DNA and SCCA alone in the diagnosis of SCC,which has high clinical promotion significance．

肿瘤免疫治疗是指利用人体的免疫机制,通过主动或被动的方法增强患者免疫功能,达到杀伤肿瘤细胞的目的。嵌合抗原受体T细胞（CAR-T）作为肿瘤免疫治疗的新型精准靶向疗法,近几年通过优化和改良已成功应用于多种血液肿瘤的治疗,是目前恶性肿瘤治疗中最有潜力的疗法之一。但由于实体瘤中存在显著的异质性和复杂的肿瘤免疫微环境,CAR-T在实体瘤中的应用仍面临诸多挑战。本文将对目前 CAR-T 细胞治疗实体瘤的研究成果、现存挑战及相应的优化策略进行综述,以期为后续 CAR-T 细胞治疗实体肿瘤研究提供参考。

Tumor immunotherapy is the process of enhancing patients’ immune system through active or passive methods to achieve the goal of eliminating tumor cells．Through optimization and modification,chimeric antigen receptor T cells（CAR-T）,a novel precise targeted therapy of cancer immunotherapy,have been successfully used in the treatment of several hematological malignancies in recent years．CAR-T is considered as one of the most promising therapies for the treatment of malignant tumors at the moment．However,application of CAR-T in solid tumors still confronts several difficulties due to the high heterogeneity and intricate tumor immune microenvironment．To serve as a reference for future CAR-T cell therapy for solid tumors,the present research findings,current difficulties and associated optimization techniques are reviewed in this paper．

目的 分析早、中期肝细胞癌（HCC）切除术后早期（≤2年）复发的危险因素并探讨术前系统免疫炎症指数（SII）对早、中期HCC术后早期复发的预测价值。方法 回顾性研究2017年10月—2020年10月于我院接受肝癌根治性切除术的238例早中期HCC患者,收集基线资料,通过1∶1倾向性评分匹配（PSM）均衡组间协变量获取早期复发组及未复发组各69例;单因素和多因素Logistic回归分析影响术后早期HCC复发的相关因素,构建列线图模型,临床决策曲线（DCA）评估列线图预测模型在临床的应用效果;受试者操作特征（ROC）曲线评价预测效能,根据最高约登指数确定截断点。结果 单因素及多因素Logistic回归分析结果均提示微血管侵犯（MVI）及术前系统免疫炎症指数（SII）高水平是术后早期复发的独立危险因素;列线图模型有较好的预测效能;ROC曲线计算出SII最佳临界值为696.85×10⁹／L。结论 术前高水平SII可能对预测HCC患者术后早期复发具有潜在价值。

目的 采用体外试验的方法,研究弱酸性培养对人正常食管内皮细胞（HEEC）活力的影响及潜在的调控机制。方法 细胞培养液的pH值分别设为（6.0~6.5）和（7.0~7.4）。以中性培养组为对照。利用CCK8实验,检测弱酸培养条件下,不同时间点食管内皮细胞活力的变化。采用蛋白免疫印迹法检测p38和磷酸化p38（p-p38）的表达。利用酶联免疫吸附剂测定法检测培养基上清液中IL-1β和IL-8的表达水平,并检测加入p38激酶活性抑制剂SBS 203580后两者浓度的变化。结果 弱酸环境下,细胞活力下降。培养1 h时,弱酸组细胞活力为（96.4±8.0）%,培养3 h和6 h时分别为（88.7±6.2）%和（87.7±7.4）%。细胞中p38的水平与培养基的pH值无关。弱酸培养可以促使细胞内p-p38的含量增加。基线时,弱酸组p-p38的灰度值比值为（0.37±0.02）,在培养2 h和6 h时分别为（0.64±0.09）、（0.84±0.11）,差异显著（P<0.01）。弱酸刺激诱导食管内皮细胞表达更多的IL-8和IL-1β。基线时弱酸组上清液中IL-8和IL-1β的浓度分别为（8.64±1.31）pg/mL,（3.35±0.49）pg/mL。培养6 h后,二者的浓度分别上升至（36.85±2.02）pg/mL和（19.19±1.60）pg/mL,差异显著（P<0.01）。加入SBS 203580后,IL-8和IL-1β的浓度明显下降（P<0.05）。结论 弱酸刺激可以降低食管内皮细胞的活力。p38 MAPK可能通过调控IL-8和IL-1β的表达参与该调节过程。

Objective To study the effect of weak acidic culture on the viability of normal human esophageal endothelial cells(HEEC)and the potential regulatory mechanisms. Methods The pH values of cell culture medium were set at(6. 0-6. 5)and(7. 0-7. 4),respectively. The group in neutral medium was set as control. CCK8 experiment was used to detect the change of cell viability at different time points. The expressions of p38 and phosphorylated p38(p-p38)were detected by Western Blot experiment. Enzyme linked immunosorbent assay was used to detect IL-1β and IL-8 concentration in the medium supernatant before and after adding p38 activity inhibitor(SBS 203580). Results HEEC viability was decreased under weak acidic conditions. After 1 hour of cultivation,the HEEC viability was(96. 4±8. 0)%,after 3 and 6 hours,it decreased to(88. 7±6. 2)% and(87. 7±7. 4)%,respectively. The level of p38 in cells was independent of culture medium pH values. Weak acidic stimulation could promote an increase of p-p38 in HEEC. At baseline,the gray value ratio of p-p38 in the weak acidic group was(0. 37±0. 02),and after 2 and 6 hours of culturing,it increased to(0. 64±0. 09)and(0. 84±0. 11),respectively,which differences were significant(P<0. 01). More IL-8 and IL-1β were expressed after weak acidic stimulation. At baseline,the concentrations of IL-8 and IL-1β in the medium supernatant of weak acidic group were(8. 64±1. 31)pg/mL and(3. 35±0. 49)pg/mL. After 6 hours of culturing,they increased significantly to(36. 85±2. 02)pg/mL and(19. 19±1. 60)pg/mL(P<0. 01),while the concentrations were decreased after adding SBS 203580(P<0. 05). Conclusions The HEEC viability was reduced by weak acidic stimulation,p38 MAPK may participate in the process by regulating the expression of IL-8 and IL-1β.

目的 构建尺寸可变纳米递送系统PAMAM/DOX-pep并进行表征,检测其理化性质并评价其体外抗肿瘤效果与靶向性。方法 将阿霉素（DOX）物理包埋在阳离子聚合物PAMAM的疏水空腔内,以4-（N-马来酰亚胺基甲基）环己烷羧酸N-羟基琥珀酰亚胺酯（SMCC）作为交联剂,采用金属基质蛋白酶（MMP-2）敏感的多肽pep（CPLGVRGC）串联小粒径纳米颗粒形成大尺寸纳米递送系统（PAMAM/DOX-pep）,对各纳米颗粒的粒径、电位、理化性质以及对小鼠乳腺癌细胞（4T1）的抑制作用、细胞摄取效果和核靶向作用进行检测。结果 PAMAM/DOX粒径约为10 nm,载药率为23%,多肽pep交联后形成的PAMAM/DOX-pep粒径约为200 nm,可在低pH下缓释DOX,7天内体外保持稳定且溶血率低、安全无毒,其与MMP-2共孵育后细胞摄取量与核靶向性显著增加。结论 尺寸可变纳米颗粒有助于克服尺寸所引发的递送障碍,将药物靶向递送至乳腺癌细胞核内并发挥作用,为纳米递送系统的设计提供了新策略。

Objective To construct and characterize the size-variable nano-delivery system PAMAM/DOX-pep,examine its physicochemical properties and evaluate its antitumor and targeting effects in vitro. Methods Small particle size PAMAM/DOX was obtained by physically encapsulating DOX within the hydrophobic cavity of the cationic polymer PAMAM. The large size nano-delivery system(PAMAM/DOX-pep)was formed by tandem linking small size nanoparticles by MMP-2 sensitive peptide pep(CPLGVRGC)using SMCC as a cross-linker. The particle size,potential,physical and chemical properties,inhibitory effect,cell uptake and nuclear targeting effect of each nanoparticle on mouse breast cancer cells(4T1)were detected. Results The particle size of PAMAM/DOX was about 10 nm,and the drug loading rate was 23%. PAMAMAM/DOX-pep,formed after cross-linking of peptide,had a particle size of about 200 nm,which could release DOX slowly at low pH,and remained stable,safe and non-toxic in vitro for 7 days with low hemolysis rate,and its cellular uptake amount and nuclear targeting rate increased significantly after co-incubation with MMP. Conclusions Size-variable nanoparticles overcome size-induced delivery barriers to target and deliver drugs to the 4T1 nucleus,providing a new strategy for the design of nano delivery systems.

严重烧伤后患者免疫功能的失调,易导致创面感染、全身炎症反应综合征、脓毒症、感染性休克等并发症,增加患者病死率。免疫细胞功能适度的活化将有助于烧伤患者抵御外界病原体的侵袭、促进创面的愈合,但功能过度激活或者功能低下,则会引发一系列严重的后果。本文旨在归纳严重烧伤后中性粒细胞、单核/巨噬细胞、肥大细胞、NK细胞及T淋巴细胞等免疫细胞的功能变化与炎症反应之间的关系,为完善烧伤患者诊疗、减少并发症、改善预后提供新的思路。

The imbalance of immune function in severely burned patients can easily lead to wound infection,systemic inflammatory response syndrome,sepsis,septic shock and other complications,which increase the mortality of patients. Moderate activation of immune cell function will help burned patients to resist the invasion of external pathogens and promote wound healing,but excessive activation or low function can lead to a series of serious consequences. The purpose of this paper is to summarize the relationship between the functional changes of immune cells such as neutrophils,monocytes/macrophages,mast cells,NK cells,T lymphocytes and inflammatory reaction after severe burns,and to provide new ideas for improving the diagnosis and treatment of burned patients,reducing complications and improving the prognosis.

目的 探讨柚皮素对人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1的作用机制。方法 选择人乳腺癌细胞株MCF-7和小鼠乳腺癌细胞系4T1为实验对象,设置对照组和柚皮素组,其中柚皮素组分为20、40、80 和120 μmol/L 4个浓度,利用CCK-8、平板克隆形成实验检测柚皮素对乳腺癌细胞的增殖作用,应用流式细胞术检测柚皮素对乳腺癌细胞的凋亡作用。建立乳腺癌移植瘤模型,应用柚皮素作用于模型小鼠,探讨柚皮素在体内抗肿瘤作用。通过荧光定量PCR和蛋白免疫印迹实验检测自噬相关基因,分析其作用机制。结果 经柚皮素处理后,乳腺癌细胞的增殖明显受到抑制,正常乳腺癌细胞增殖情况变化不大,MCF-7乳腺癌细胞和小鼠乳腺癌4T1均出现明显的凋亡（P<0.001）。结论 柚皮素可以抑制乳腺癌细胞的增殖,且对正常乳腺细胞无明显毒副作用。柚皮素通过凋亡和自噬方式促进乳腺癌细胞的死亡,体内实验结果显示柚皮素具有抗肿瘤作用,并可促进其坏死。

目的 探讨外周血CD34阳性（CD34⁺）细胞计数对普乐沙福自体干细胞动员效果的预测价值。方法 回顾性分析2021年5月—2023年7月中山大学附属第七医院使用人粒细胞集落刺激因子（G-CSF）联合普乐沙福进行自体干细胞动员的13例患者临床资料,分析普乐沙福动员前后外周血CD34⁺细胞计数的变化及干细胞采集情况。结果 共有13例患者纳入研究,包括淋巴瘤10例和多发性骨髓瘤3例。多发性骨髓瘤患者中1例为新诊断,另2例为复发患者;淋巴瘤患者中3例为套细胞淋巴瘤,6例为弥漫大B细胞淋巴瘤（包括1例复发）,1例为B细胞淋巴瘤（不能明确类型）。本研究纳入的患者均使用G-CSF动员,在使用普乐沙福后CD34⁺细胞计数均升高,使用普乐沙福前中位CD34⁺细胞计数为13.3（2.5~76.1）/μL,使用普乐沙福后中位CD34⁺细胞计数为73.6（10.4~208.70）/μL,升高4.18（1.99~13.60）倍。13例患者中有2例患者在使用普乐沙福前外周血CD34⁺细胞计数<5 /μL,均动员失败。Spearman相关分析结果显示,使用普乐沙福后CD34⁺细胞计数与使用普乐沙福前CD34⁺细胞数呈正相关（r_s=0.769,P=0.003）。多元线性回归分析显示,使用普乐沙福后CD34⁺细胞计数能较好地预测采集结果（P=0.004）。结论 监测外周血CD34⁺细胞计数可预测普乐沙福自体干细胞动员效果,使用普乐沙福后CD34⁺细胞计数越多,CD34⁺细胞采集量越大。

Objective To explore the predictive value of peripheral blood CD34⁺ cell count for the stem cell mobilization effect of plerixafor．Methods The clinical data of 13 patients who used granulocyte colony-stimulating factor + plerixafor for stem cell mobilization in the Seventh Affiliated Hospital of Sun Yat-sen University from May 2021 to July 2023 were retrospectively analyzed．The changes of peripheral blood CD34⁺ cell count in all patients before and after the mobilization of plerixafor were analyzed．Results In 13 enrolled patients,there were 10 lymphoma patients and 3 multiple myeloma（MM）patients．One patient was newly diagnosed with MM,and the other two were recurrent patients．The lymphoma cases included 3 mantle cell lymphoma,6 diffuse large B cell lymphoma and 1 B cell non-Hodgkin's lymphoma（type cannot be specified）．The CD34⁺ cell counts were increased in all patients when mobilized with granulocyte colony-stimulating factor before plerixafor．The CD34⁺ cell count was 13.3（2.5~76.1）/μL and 73.6（10.4~208.70）/μL before and after the use of plerixafor,between which the difference was statistically significant（Z=0.578,P<0.05）,and the median increased of 4.18（1.99~13.6）times．There were 2 patients failed in mobilizing whose CD34⁺ cell count was less than 5 /μL before using plerixafor．Spearman analysis showed that there was a positive correlation in peripheral blood CD34⁺ cell count before and after the use of plerixafor（r_s=0.80,P=0.032）．The CD34⁺ cell count after using plerixafor was a good predictor of the collection results（P=0.002）．Conclusions Monitoring the CD34⁺ cell count in peripheral blood has a certain predictive value for the stem cell mobilization effect of plerixafor．The higher of CD34⁺ cell count after the use of plerixafor,the higher of CD34⁺ collection．

帕金森病（PD）是一种常见的与年龄相关的神经退行性疾病,其特点是黑质致密部内多巴胺能神经元的进行性丢失以及路易小体的积累。多巴胺能神经元的退化导致纹状体的多巴胺水平降低,最终出现静息性震颤、运动迟缓、肌肉僵硬和姿势不稳等运动症状,以及认知能力下降、嗅觉功能受损、精神异常和睡眠障碍等非运动症状。由于人口结构转变和全球老龄化,PD的不断增加对患者、家庭和社会构成重大负担。尽管广泛的研究已阐明了PD的病因学和潜在机制,但现有治疗主要集中在症状管理,无法阻止疾病的进展。小胶质细胞作为脑内重要的免疫细胞,对维持中枢神经系统的稳态具有关键作用。本文综述了PD研究,包括其病因学因素、分子机制和现有治疗策略。此外,审视了在PD样模型中涉及小胶质细胞的研究,深入探讨了小胶质细胞在疾病进展中的动态,并探究了小胶质细胞在促进或减轻疾病进展方面所扮演的错综角色。通过这样的探讨,本综述旨在为PD复杂的发病机制提供新的洞见和观点,激发出针对性治疗干预的创新思路。

Parkinson's disease（PD）,a prevalent age-related neurodegenerative disorder,is characterized by the progressive loss of dopaminergic neurons within the substantia nigra compacta（SNc）and the accumulation of Lewy bodies．The degeneration of dopaminergic neurons leads to diminished striatal dopamine levels,culminating in motor symptoms such as resting tremors,bradykinesia,muscle rigidity and postural instability,alongside non-motor manifestations encompassing cognitive decline,impaired olfactory function,psychological abnormalities and sleep disturbances．The escalating incidence of PD due to shifting demographics and global aging poses substantial burdens on patients,families and society．Although extensive research has elucidated the etiology and underlying mechanisms of PD,available treatments largely focus on symptom management and lack the capacity to halt disease progression．Microglia,as integral immune cells within the brain,wield pivotal influence over central nervous system homeostasis．This review presents a comprehensive synthesis of PD,encompassing its etiological factors,molecular mechanisms,and existing therapeutic strategies．Furthermore,we scrutinized research involving microglia in PD-like models,delving into the dynamics of microglia in disease progression and probing into the intricate roles that microglia assume in either fostering or mitigating disease advancement．By doing so,this review aims to furnish novel insights and perspectives that shed light on the intricate pathogenesis of PD,potentially sparking innovative concepts for targeted therapeutic interventions．

目的 探讨负性调节细胞CD4⁺CD25⁺T及其相关细胞因子在慢性阻塞性肺病(COPD)患者外周血中的表达与合并细菌感染的相关性。方法 纳入2018年1月—2019年12月间收治的66例COPD患者作为研究对象,其中急性加重期COPD患者(AECOPD)36例、稳定期患者30例,并纳入同期体检健康者30例作为对照组。对所有纳入的研究对象外周血标本中的CD4⁺CD25⁺T调节性T细胞及其相关细胞因子[白介素-4(IL-4)、白介素-10(IL-10)、干扰素-γ(IFN-γ)]表达水平进行检测,分析相关指标水平与COPD是否合并细菌感染的关系,及预测细菌感染的效能。结果 AECOPD和稳定期COPD患者CD4⁺、CD4⁺CD25⁺、IFN-γ/IL-4水平均低于对照组(P<0.05),IL-4、IL-10水均高于对照组(P<0.05);AECOPD患者IFN-γ水平高于对照组(P<0.05);AECOPD患者CD4⁺、CD4⁺CD25⁺水平低于稳定期COPD患者(P<0.05),IL-4、IL-10、IFN-γ均高于稳定期COPD患者(P<0.05);CD4⁺、CD4⁺CD25⁺水平与IL4、IFN-γ均呈负相关关系(P<0.05),CD4⁺水平与IL-10呈负相关关系(P<0.05);COPD合并感染者CD4⁺水平低于未合并感染者(P<0.05),IL-4、IFN-γ水平均高于未合并感染者(P<0.05);COPD合并革兰氏阴性菌感染者CD4⁺CD25⁺水平低于未合并感染者(P<0.05),IL-10水平均高于未合并感染者(P<0.05);CD4⁺、IL-4、IL-10、IFN-γ均是预测COPD患者合并细菌感染的有效指标(P<0.05),其中IL-4和IFN-γ效能较高。结论 CD4⁺、CD4⁺CD25⁺Treg细胞及其相关细胞因子参与COPD发生发展和患者细菌感染,监测其水平变化有利于为临床诊治提供信息。

Objective To investigate the correlation between the expressions of negative regulatory cell CD4⁺CD25⁺T and its related cytokines in peripheral blood and bacterial infection of patients with chronic obstructive pulmonary disease (COPD). Methods Sixty-six COPD patients admitted between January 2018 and December 2019 were included as the research subjects, including 36 patients with acute exacerbation of COPD (AECOPD) and 30 patients with stable COPD. Another 30 healthy people undergoing physical examination during the same period were included in control group. The expression levels of CD4⁺CD25⁺ regulatory T cell and its related cytokines [interleukin-4 (IL-4), interleukin-10 (IL-10), interferon-γ (IFN-γ)] in the peripheral blood samples were detected among the included subjects. The relationship between levels of related indicators and presence or absence of bacterial infection in COPD and the efficacy of predicting infection were analyzed. Results The levels of CD4⁺, CD4⁺CD25⁺ and IFN-γ/IL-4 in patients with AECOPD and patients with stable COPD were lower than those in control group (P<0.05), while the levels of IL-4 and IL-10 were higher than those in control group (P<0.05). The IFN-γ level of AECOPD patients was higher than that of control group (P<0.05). The levels of CD4⁺ and CD4⁺CD25⁺of AECOPD patients were lower than those of stable COPD patients (P<0.05), while the levels of IL-4, IL-10 and IFN-γ were all higher than those of stable COPD patients (P<0.05). The levels of CD4⁺ and CD4⁺CD25⁺were negatively correlated with IL-4 and IFN-γ (P<0.05), and the CD4⁺level was negatively correlated with IL-10 (P<0.05). The CD4⁺ level in COPD patients with infection was lower than that in patients without infection (P<0.05), while the levels of IL-4 and IFN-γ were higher than those in patients without infection (P<0.05). The CD4⁺CD25⁺level of COPD patients with Gram-negative bacteria infection was lower than that of patients without infection (P<0.05), while the IL-10 level was higher than that of patients without infection (P<0.05). CD4⁺, IL-4, IL-10 and IFN-γ were effective indicators in predicting bacterial infection in COPD patients (P<0.05), and IL-4 and IFN-γ had higher efficacy. Conclusions CD4⁺, CD4⁺CD25⁺ T cell and related cytokines are involved in the occurrence and development of COPD and bacterial infection in patients. Monitoring changes of those levels is helpful to provide information for clinical diagnosis and treatment.