All cancers develop from malignant transformation of normal cells, while it is challenging to identify these cells-of-origin since it is impossible to witness the dynamic changes in human cancers. Retinoblastoma (Rb), an intraocular malignant cancer, is a typical model for study the molecular and cellular mechanisms of cancers. Although the maturing cone precursors (CPs) are proposed as the cellular origin of human Rb, it is unknow whether other retinal cells are also sensitive to RB1 inactivation. Here we developed RB1-deficient human retinal organoids (ROs) models from RB1-/- or RB1+/- human induced pluripotent stem cells (hiPSCs). RB1-/- hiPSCs developed into Rb tumors which recapitulated the features of human native Rb and had the ability to form consecutive orthotopic xenografts in mice. Importantly, RB1 loss induced the overproliferation of ATOH7+ neurogenic retinal progenitor cells (nRPCs), which disrupted the retinal development by generating proliferative, nascent retinal cells including retinal ganglion cells and CPs. scRNA-seq analysis verified the ATOH7+/RXRγ+ nascent CPs survived and finally drove Rb development. In contrast, monoallelic RB1 inactivation with low pRB expression did not induce nascent CPs proliferation, but only induced nRPCs overproliferation which caused retinocytoma-like phenotype. Finally, a potential therapeutic agent for Rb was identified from multi-omics data. Our findings firstly indicate that nRPCs are the most sensitive cells to RB1 loss inducing nascent retinal cells abnormal proliferation, and ATOH7+ nascent CPs are the earliest cellular origin of human Rb, facilitating drug development for Rb. ### Competing Interest Statement The authors have declared no competing interest.

月骨无菌性坏死又称为Kienb?ck病,被描述至今已有 110多年.然而,对月骨无菌性坏死的病因、发病机制、分期及治疗等方面尚未达成共识.目前月骨无菌性坏死分期主要有Lichtman分期、Schmitt分期、Bain分期,以及基于年龄、月骨状态及腕部状态的新分期和基于术后MRI定量分析的新分期,临床上最常用的是Lichtman分期.尽管已有十几种术式用于治疗月骨无菌性坏死,但各个阶段选择最佳治疗方案对临床医生来说仍然是棘手的问题.该文就月骨无菌性坏死分型及治疗进展进行综述.

三角纤维软骨复合体(TFCC)作为腕关节重要的解剖结构,承担着不可替代的生物力学作用,损伤后如果不治疗可能会导致腕部尺侧慢性疼痛和不稳定.经保守治疗后症状仍未缓解的TFCC损伤患者需要行进一步的手术治疗.然而,目前对于TFCC损伤的分型和治疗方法仍没有统一的标准,这给其诊治带来了一系列难题.该文以TFCC损伤的Palmer及Atzei分型为基础,在关节镜技术发展的前提下,详细阐述了各类型损伤的治疗方式及预后结果,为TFCC损伤提供了临床诊疗思路及参考依据.

尺骨撞击综合征是导致腕部尺侧疼痛的重要原因之一,其病因多为尺骨阳性变异,诊断依靠症状、查体、影像学检查及腕关节镜检查.X线检查可观察到尺骨阳性变异,月骨和三角骨硬化、囊变等;MRI检查可以早期发现骨髓及软骨改变如水肿、囊变,以及三角纤维软骨复合体损伤等,灵敏度及特异度较高;腕关节镜可以直接观察到腕关节月骨偏尺侧软骨软化或损伤,发现MRI等影像学检查难以发现的早期细微病变,是诊断尺骨撞击综合征的金标准,同时镜下可进行治疗性操作.尺骨撞击综合征通常保守治疗效果有限,以手术治疗为主,手术方法主要有尺骨短缩截骨术、Wafer术、腕关节镜下清理术、桡骨截骨矫形术等.该文就尺骨撞击综合征诊断及治疗进展进行综述.

VerdanⅠ区伸肌腱解剖结构窄而薄,韧性差,位置表浅,很容易发生撕裂或从止点处撕脱骨折,导致远端指间关节主动伸展功能障碍,如不能及时给予适当干预,可能会引发锤状指畸形,甚至造成晚期创伤性关节炎或鹅颈指畸形,既影响伸指功能,又影响美观.该文就伸肌腱Ⅰ区的解剖结构、损伤机制以及锤状指畸形诊断、分型及治疗的研究进展进行综述.

目的:分析各种病因摘除眼球的患儿中视网膜母细胞瘤(retinoblastoma,RB)的误诊率,并总结其临床和病理特点.方法:回顾性分析2003年以来在中山眼科中心因临床诊断为RB并接受眼球摘除的患者563例(577眼),比较术前临床诊断和术后病理诊断,从中筛选出误诊病例,分析这些病例的临床和病理特点,包括患者年龄、性别、治疗过程、临床影像学、肿瘤病理分期、病理诊断以及分化程度.结果:共发现误诊病例22例(22眼),误诊率3.91％,所有误诊病例均为单眼摘除患者.常见的临床误诊类型为:与Coats病相混淆12例(12眼),与眼内炎症反应混淆5例(5眼),以及与眼内其他肿瘤混淆5例(5眼).所有患者中,>4岁者55例,其中误诊12例,误诊率21.82％.结论:与RB相关的临床误诊并不罕见,其中最常见的误诊病因是Coats病,>4岁患者是误诊的主要人群.

目的:探索用细胞块制备试剂盒对眼内玻璃体液微量细胞制备细胞块的成功率,苏木素-伊红(hematoxylin-eosin,HE)染色效果及技术要点.方法:收集中山大学中山眼科中心临床病理科2020年9月至2021年1月由临床送检的25例玻璃体液(含玻璃体切割液),应用细胞块制备试剂盒制备细胞块后,常规固定、脱水、包埋、切片,随后进行HE染色,观察染色效果.结果:25例玻璃体细胞蜡块制作成功率达到100％,制片后HE染色效果好,背景干净,细胞形态清晰,核质对比分明.结论:应用细胞块制备试剂盒能将眼内玻璃体液微量细胞制成蜡块,极大提高了标本的利用率,为后续的病理研究提供丰富的材料.

目的:探讨掌板前移术治疗陈旧性近指间关节骨折脱位的疗效。方法:自2005年1月至2020年12月我们对8例陈旧性近指间关节骨折脱位患者，采用掌板前移克氏针内固定术治疗。结果:术后所有患者均获得随访，时间为3~23个月，平均14个月。所有患者均无切口感染、克氏针松动。影像学检查发现7例近指间关节无半脱位，1例在术后3个月复查时近指间关节出现半脱位。末次随访时，患手平均握力为健侧的92%。手功能恢复按手指关节总活动度(total active motion，TAM)评定标准评价：优5例，良3例。结论:掌板前移克氏针内固定术可以重建陈旧性近指间关节骨折脱位的稳定性，术后早期功能锻炼可以较大程度恢复患指屈伸功能，是治疗陈旧性近指间关节骨折脱位的有效方法之一。

目的:探讨眼眶黏膜相关淋巴组织(mucosa-associated lymphoid tissue,MALT)结外边缘区B细胞淋巴瘤的临床表现、影像学特征及病理学特点,以期减少眼眶淋巴瘤的误诊,提高生存率.方法:对2020年1月至2020年12月中山大学中山眼科中心诊治的71例眼眶MALT结外边缘区B细胞淋巴瘤的临床、影像及病理学资料进行回顾性分析.结果:71例患者中,男38例,女33例;左侧眼眶31例,右侧眼眶34例,双侧眼眶6例;原发病例67例,复发病例4例;年龄23～84岁,病程为3个月～15年.最常见的临床表现是眼部肿块和不同程度的眼球活动受限;磁共振成像(magnetic resonance imaging,MRI)检查见密度均匀的软组织影,呈"铸造样",眼球内未见侵犯;组织病理检查可见肿瘤由小至中等大小淋巴样细胞组成,瘤细胞呈弥漫或片状生长,核小到中等、不规则,核仁不明显,部分细胞呈单核样淋巴瘤细胞改变,其中9例可见浆细胞样分化,伴浆细胞分化的病例kappa与lambda的表达不对称.结论:眼眶MALT结外边缘区B细胞淋巴瘤有多种临床表现,影像学检查具有一定的特征,可辅助术前诊断.病理学检查可用于术后的准确诊断及分型,据此制定合适的治疗方案,提高疗效.

三角纤维软骨复合体(TFCC)是腕关节尺侧维持腕关节稳定性的重要结构,腕尺侧疼痛为TFCC损伤最常见的首发症状.经保守治疗后疼痛症状未缓解及腕关节功能差的创伤型TFCC损伤(PalmerⅠ型)应行手术治疗.腕关节镜手术具有创伤小、腕关节功能恢复快、术后并发症少等优点.单纯的浅层TFCC撕裂可于腕关节镜下直接缝合;对于合并止点撕脱及伴远尺桡关节不稳的TFCC损伤,酌情行腕关节镜下缝合锚固定修复或切开行韧带重建;对于陈旧性TFCC损伤,大多伴发远尺桡关节脱位或不稳,多需切开行韧带重建.该文就TFCC的解剖结构、损伤分型、诊断及近年来腕关节镜下治疗TFCC的理念和进展作一综述.

桡骨远端关节内骨折为常见的上肢骨折,治疗难度高,治疗不当容易影响腕关节功能.桡骨远端B型、C型骨折在腕关节镜下复位固定可使关节面台阶小于1 mm,显著降低术后关节炎发生率,同时能在术中镜下诊断并处理合并的腕关节软组织损伤.对于桡骨远端关节内的骨折,可采用腕关节镜下辅助复位联合克氏针或掌侧锁定接骨板固定.该文就腕关节镜下治疗桡骨远端关节内骨折的研究进展作一综述.

Purpose. In this study, we aimed to investigate the presence of Epstein–Barr virus (EBV) in the eyelid sebaceous gland carcinoma (SGC) and its association with the clinicopathologic features. Methods. One hundred and thirty paraffin-embedded SGC specimens were retrieved from the Clinical Pathology Department of Zhongshan Ophthalmic Center. Epstein–Barr virus-encoded RNA (EBER) was detected with in situ hybridization (ISH) using the Leica BOND system autostainer. The age and gender distributions of all patients were analyzed and compared with earlier reports. Pearson’s χ2 and Fisher’s exact tests were used to determine the association between clinicopathological features such as age, gender, laterality eye, tumor basal dimension, degree of tumor differentiation, and EBER positivity. Likewise, the relationship between the grade and tumor basal dimension in EBER-positive SGC of the eyelid was analyzed. Results. Thirty-four out of one hundred and thirty (26.2%) eyelid SGC specimens were positively stained for EBER. The age range of highest incidence was 46–75 years, and the female to male ratio was 1 : 0.9. No significant correlation was found between EBER-positivity and age (p=0.5370), gender (p=0.4758), and degree of tumor differentiation (p=0.7787). However, EBV positivity was strongly correlated with the right eye (p=0.0287), the tumor basal dimension (p=0.0001). EBV positivity grade presented statistically associated with tumor size (p=0.0329). Conclusion. We conclude that ISH is a sensitive method to identify EBV in SGC of the eyelid. A possible causal association of EBV in SGC patients is suggested by high frequency of EBER-ISH positivity and its association with the clinicopathologic features.

目的:探讨不同化疗药膀胱灌注预防浅表性膀胱癌术后复发的效果.方法:选取2012年2月11日至2015年6月20日大同市第五人民医院收治的浅表性膀胱癌患者96例,以随机数字表法分为观察组和对照组,每组48例.两组患者均实施经尿道膀胱肿瘤切除术,观察组患者给予羟基喜树碱灌注化疗,对照组患者给予丝裂霉素灌注化疗.比较两组患者治疗前后的成纤维细胞生长因子(FGF)、血管内皮生长因子(VEGF)及基质金属蛋白酶9(MMP-9)水平的差异;随访3年,观察两组患者的复发情况、生存情况及不良反应发生情况.结果:治疗后,观察组患者FGF、VEGF及MMP-9水平明显低于对照组,差异均有统计学意义(P<0.05);观察组患者的1、2和3年生存率明显高于对照组,复发率明显低于对照组,差异均有统计学意义(P<0.05);观察组、对照组患者的不良反应发生率分别为16.67％(8/48)、20.83％(10/48),差异无统计学意义(P>0.05).结论:与丝裂霉素灌注化疗相比,羟基喜树碱灌注化疗用于经尿道膀胱肿瘤切除术的浅表性膀胱癌患者的效果更好,更有助于提高患者生存率,减少复发率,且安全性较高.

舟状骨骨折作为最常见的腕骨骨折,不仅易漏诊和误诊,而且治疗不当很容易引起延迟愈合或不愈合.对于稳定性舟状骨骨折患者,一般可采取石膏固定;对于不稳定性舟状骨骨折及骨不愈合患者,可采取腕关节镜辅助经皮螺钉内固定,其中舟状骨远极及腰部骨折采用掌侧入路,近极骨折采用背侧入路.该文就舟状骨骨折诊断、分型及治疗的研究进展作一综述.

Antitumor T cell receptor (TCR)-modified T cell (TCR-T) therapy is a specific immunotherapy with great potential for application. However, T cell preparation for TCR-T therapy is an individualized process that is poorly managed by industry standards. The lack of suitable animal models for preclinical experiments also delays the development of TCR-T therapy. To solve these problems, we combined TCR and embryonic stem (ES) cell technologies to produce antigen-specific mouse T cells using TCR-modified mouse ES (mES) cells specific for a human HLA-A2-restricted MAGE-A1 peptide. To establish a human HLA-TCR antigen recognition system in mouse T cells, we used MAGE-A1-specific TCR and HLA-A2 as models to generate human and mouse hybrid (T1367 and HHD) MHC and TCR molecules and then modified the mES and OP9-DL1 cell lines with the T1367 and HHD genes, respectively. T1367 gene-modified mES cells (T1367-mES) maintained pluripotency and differentiated into the major tissue types of all three dermal layers in vivo. Eight weeks after subcutaneous co-injection of T1367-mES and OP9-DL1-HHD (OP9-DH) cells into NOD/SCID mice, we generated ES cell-derived teratomas. Mature T cells were detected in the peripheral blood and spleen and were specific for MAGE-A1. In the future, we hope to improve this method with 3D nanotechnologies for the increasing the bone marrow formation in teratoma and translate it to human TCR-iPS cells. Human T cells differentiated from TCR-iPS cells could be applied in adoptive immunotherapy for cancer.

AIM: To reveal the expression of multidrug-resistance associated proteins: glutathione-S-transferase π (GSTπ), P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP) in retinoblastoma (RB) without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. METHODS: A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP. RESULTS: GSTπ was expressed in 39/42 (92.86%) RBs and in 9/9 (100%) well-differentiated RBs. P-gp/GSTπ was found in 30 (71.42%) of 42 RBs. Totally 9 (21.43%) tumors were well differentiated and 33 (78.57%) were poorly differentiated. Totally 15 (35.71%) eyes had optic nerve (ON) tumor invasion, 36 (85.71%) had choroidal tumor invasion, and 14 (33.33%) had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion (P>0.05). CONCLUSION: RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% well- differentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.

目的:比较过碘酸-Schiff法(Periodic Acid-Schiff,PAS),六亚甲基四胺银法(Grocott Methenamine silver,GMS),Gomori氏氢氧化银氨法(Gomori)三种特殊染色方法显示角结膜原位癌基底膜完整性的优缺点,寻找较合适的染色方法.方法:选取中山大学中山眼科中心2012年1月至2017年9月期间收治的20例角结膜原位癌标本,分别采用PAS、GMS、Gomori三种染色,显微镜下观察角结膜原位癌基底膜显示状态.结果:三种染色方法都能显示角结膜原位癌基底膜,但其鲜艳程度不同,与背景反差程度不同.GMS染色基底膜呈深棕色而与黄棕色背景反差较小;Gomori染色基底膜显黑色与背景区分较明显,但有较多银颗粒沉积而影响观察;PAS染色基底膜呈紫红色,基底膜形态清晰可见,背景浅,反差明显.结论:三种染色均可良好地显示角结膜原位癌基底膜,其中PAS染色显色更为鲜明、与背景反差更明显、操作更为方便,是一种理想的基底膜染色方法.

目的:分析经皮肾镜气压弹道超声碎石术在肾结石治疗中的临床效果与安全性.方法:回顾性分析80例肾结石患者,分为对照组与联合超声组,各40例.对照组采用经皮肾镜气压弹道碎石术,联合超声组采用经皮肾镜气压弹道超声碎石术治疗,比较2组肾结石治疗效果、平均住院日数、手术实施时间、下床活动时间、治疗前后患者肾功能指标及并发症情况.结果:联合超声组肾结石治疗效果优于对照组(P＜0.05);联合超声组下床活动时间与对照组之间无明显差异,平均住院日数、手术实施时间短于对照组(P＜0.05);治疗后2组肾功能指标优于治疗前(P＜0.05),治疗后联合超声组肾功能指标和对照组之间无显著差异(P＞0.05).联合超声组并发症发生率低于对照组(P＜0.05).结论:经皮肾镜气压弹道超声碎石术在肾结石治疗中的临床效果与安全性高于单纯经皮肾镜气压弹道碎石术,可缩短手术时间和住院时间,减少并发症,对肾功能无明显影响.

To report a case of amelanotic melanoma located in the left upper eyelid misdiagnosed as chalazion in a 41-year-old woman. Examination showed a red 2 cm × 2 cm mass in the left upper palpebral conjunctiva. The tumor was excised and regular fixed in 10% formalin, embedded, sectioned, HE stained and immunohistochemistry stained. Histopathological examination revealed nests of round atypical tumor cells with vacuolated cytoplasm and sheets of spindle atypical tumor cells. Some tumor cells had conspicuous nucleoli. Immunohistochemistry some tumor cells were positive for melanocytic markers S-100, HMB-45 and negative for CK, EMA. So the pathological diagnosis was palpebral conjunctiva amelanotic melanoma in the left upper eyelid. For the mass in palpebral conjunctiva of senile patients without typical characteristics of chalazion, the surgical specimen should be performed for pathologic examination to rule out other tumors.