目的:探讨基础转录因子 3(basic transcription factor 3,BTF3)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)组织中的表达及其与PINCH的相关性.方法:采用免疫组织化学法检测BTF3 在 73对OSCC组织及相邻癌旁正常组织(45 例伴淋巴结转移)中的表达,并通过肿瘤基因组图谱(the Cancer Ge-nome Atlas,TCGA)数据库分析BTF3、PINCH在OSCC组织及相邻癌旁正常组织中的表达以验证免疫组织化学检测结果.分析BTF3 表达与患者年龄、性别、肿瘤分化程度及淋巴结转移等临床病理参数的关系及其与PINCH在OSCC中表达的相关性.结果:免疫组织化学检测结果显示,BTF3 在OSCC组织中的表达明显高于相邻癌旁正常组织(60.27%vs 39.73%,P =0.013);TCGA数据库分析显示,OSCC组织中BTF3、PINCH的阳性表达率均显著高于二者在相邻癌旁正常组织中的阳性表达率.在OSCC中,BTF3 在淋巴结转移组中的阳性表达率明显高于其在无淋巴结转移组中的阳性表达率(71.11%vs 42.86%,P =0.016);BTF3 在低分化组OSCC中的阳性表达率明显高于其在高分化组 OSCC 中的阳性表达率(71.43%vs 45.16%,P =0.023);BTF3 的表达与患者性别、年龄、肿瘤大小和部位无相关性(P>0.05);BTF3 和PINCH在OSCC中的表达呈正相关(r =0.286,P =0.015).结论:BTF3 与OSCC的发生、发展及淋巴结转移有关,有望成为判断OSCC发生、发展及预测淋巴结转移的潜在分子标志物,其机制可能与PINCH正协同作用有关.

目的 研究Tafazzin在口腔鳞状细胞癌(OSCC)中的表达及其与MAC30的相关性.方法 采用免疫组化ABC法检测Tafazzin在24例正常口腔黏膜和59例OSCC组织中的表达,分析其与患者年龄、性别、肿瘤分化程度及淋巴结转移等临床病理特征的关系及其与MAC30在OSCC中的相关性.结果 Tafazzin在OSCC中的阳性表达率明显高于其在正常口腔黏膜中的表达率,差异有统计学意义(66.1％vs8.3％,P=0.000);在OSCC中,Tafazzin在低分化患者中的阳性表达率明显高于其在高分化患者中的阳性表达率(88.9％vs56.1％,P=0.014);其在伴淋巴结转移患者中的阳性表达率高于其在无淋巴结转移患者中的阳性表达率(86.4％vs 54.1％,P=0.011);Tafazzin的表达与患者性别、年龄、部位、肿瘤大小无相关性(P＞0.05).Tafazzin与MAC30在OSCC中的表达呈正相关(r=0.492).结论 Tafazzin可能在OSCC的发生、发展及淋巴结转移中起重要的作用,有望成为预测OSCC发生、发展及预测淋巴结转移的新的潜在生物标志物,其作用机制可能与MAC30在OSCC中的正协同作用有关.

通用转录因子 3(basic transcription factors,BTF3)是一种通用的近端启动区元件转录因子,与RNA聚合酶Ⅱ结合参与转录活动.BTF3在促进细胞增殖、抑制凋亡方面发挥重要作用,可能导致恶性肿瘤早期事件[1-3].BTF3在多种恶性肿瘤中过表达[4-5].乳腺癌是女性最常见的恶性肿瘤,本研究拟检测BTF3在非特殊型浸润性导管癌中的表达,分析其与肿瘤进展、预后的相关性.

目的:评价Ezrin-radixin-moesin结合磷酸化蛋白50(Ezrin-radixin-moesin binding phosphoprotein 50,EBP50)、p16和Ki-67在正常宫颈组织和宫颈鳞状上皮内病变(Squamous intraepithelial lesion,SIL)中的表达及临床意义.方法:选取2018年10月至2020年06月正常宫颈组织21例、SIL组织80例,采用免疫组化方法检查EBP50、p16和Ki-67表达水平,通过相关性检验分析EBP50与p16、Ki-67表达的相关性.结果:EBP50在正常宫颈组织中表达明显高于SIL(P=0.000);SIL中p16和Ki-67表达显著高于正常宫颈组织中的表达(P=0.000);高级别鳞状上皮内病变(High-grade squamous intraepithelial lesion,HSIL)EBP50表达强度比低级别鳞状上皮内病变(Low-grade squamous intraepithelial lesion,LSIL)降低(P=0.003);EBP50与p16或Ki-67的表达在SIL中呈负相关.结论:EBP50、p16和Ki-67的检测对SIL的病理诊断具有参考价值.EBP50表达的降低与宫颈病变的级别升高相关,EBP50可作为判断SIL分级的有效辅助手段.

RATIONALE:Malignant melanoma (MM) is notorious for its remarkable morphological variation and aberrant histopathological patterns. In addition, Malignant Periopheral Nerve Sheath Tumor (MPNST) is an uncommon but aggressive soft tissue sarcoma. Because of the common embryological origin of melanocytes and Schwann cells in the neural crest, discriminating between a particular type of MM and MPNST can be difficult, particularly when they are amelanotic. Our goal is to increase awareness among clinicians of the rare variations of MM and the importance of medical history in improving the accuracy of the final clinical diagnosis.PATIENT CONCERNS:A 68-year-old man was admitted to the hospital due to pain in his right ankle, which had persisted for 8 months, along with swelling for 4 months. Medical history revealed delayed healing of right plantar for 5 years after a traumatic injury.DIAGNOSES:The ankle mass was initially diagnosed as MPNST through biopsy. After reviewing the patient's medical history and receiving the final pathological report following amputation, we have revised the diagnosis to metastatic amelanotic desmoplastic melanoma in the ankle part and lentigo maligna melanoma in the plantar part. This is due to both lesions displaying positive markers or mutated genes in immunohistology and Gene Mutation Detection, indicating homology between the 2 tumors.INTERVENTIONS:Due to the malignant characteristics of the tumor and the patient's wishes, amputation of the right lower leg was carried out.OUTCOMES:Subsequently, the patient was treated with interferon-γ and immunosuppressant PD-1 inhibitor, and survived for 1 year after amputation.LESSONS:Clinical data, immunohistochemisty biomarkers and genes detection results can serve as valuable evidence for pathologists and clinicians in identifying the disease process. Collaborative efforts between clinicians and scientists are crucial in order to identify specific markers that can effectively differentiate between the 2 tumors, thereby enhancing the conclusiveness of the diagnosis.

Objective The osteoclastic bone resorption inhibitors might have positive effect in preventing femoral head collapse in patients with osteonecrosis of the femoral head (ONFH). However, as a novel osteoclastic inhibitor, whether denosumab can prevent collapse in steroid‐induced ONFH remains unknown. This study aims to evaluate the treatment effect of denosumab and the potential protective mechanism. Methods This was a retrospective study. A total of 161 patients with steroid‐induced ONFH who underwent denosumab treatment were reviewed, and 209 untreated patients were selected as controls. Their clinical characteristics and radiological exam results were obtained. Patients were treated with 60 mg denosumab every 6 months for 2 years. The primary outcome was the incidence of femoral head collapse at 2 years after the initial diagnosis of ONFH. Secondary outcomes included the Harris hip score, progression of osteosclerosis, increase in necrotic area, bone marrow oedema relief, and bone mineral density increase in the femoral head. The Mann–Whitney U test and chi‐square tests were performed to identify the differences between the continuous and categorical variables, respectively. A multivariate logistic regression model was built to identify the factors associated with the treatment effect of denosumab. Results The incidence of femoral head collapse was 42.24% (68/161) in the denosumab group and 54.07% (113/209) in the control group (χ2 = 5.094, p = 0.024; relative risk = 0.787, 95% CI = 0.627–0.973). The excellent‐good rates of the Harris hip score were 63.98% (103/161) in the denosumab group and 44.98% (94/209) in the control group (χ2 = 13.186, p < 0.001). The incidence of osteosclerosis progression in the denosumab group was 55.28% (89/161), which was significantly higher than that in the control group (43.54%, 91/209, χ2 = 5.016, p = 0.025). Meanwhile, a significant increase in bone mineral density was identified in 29.19% (47/161) and 7.18% (15/209) of patients in the denosumab and control groups, respectively (χ2 = 31.600, p < 0.001). The osteoclastic cytoplasm expression of LC3‐II was more positive in the control group than in the denosumab group (immunohistochemistry scoring: 3.58 ± 2.27 vs 6.33 ± 2.64, Z = −2.684, p = 0.007). A total of three independent factors were considered to be associated with the positive treatment effect of denosumab, the time of first denosumab administration (OR = 2.010, 95% CI = 1.272–3.177), osteosclerosis (OR = 1.583, 95% CI = 1.024–2.445), and the necrotic area before denosumab administration (medium necrotic area: OR = 2.084, 95% CI = 1.245–3.487; large necrotic area: OR = 2.211, 95% CI = 1.255–3.893). Conclusions The current study demonstrated that denosumab had a positive effect on preventing femoral head collapse in patients with steroid ONFH. This effect might be closely associated with the inhibition of osteoclasts and their autophagy.

Diabetic nephropathy (DN) is a common complication of diabetes. The Notch pathway plays an important role in podocyte injury and decreases the expression of podocyte-specific proteins in DN. However, the exact mechanisms are still elusive. The purpose of this study was to investigate the effect of the Notch pathway on podocyte injury by regulating Krüppel-like factor 4 (KLF4) in high glucose (HG)-induced podocytes. The expression of the Notch pathway and KLF4 was regulated in HG-induced podocytes. Western blotting was used to detect the protein expression of Notch1, Notch intracellular domain 1 (NICD1), KLF4, nephrin, and integrin β1. The mRNA levels of Notch1, KLF4, nephrin, and integrin β1 were determined by real-time polymerase chain reaction. HG increased the expression of Notch1 and NICD1 in podocytes and inhibited the expression of KLF4 (p < 0.05 or p < 0.01). Inhibition of the Notch pathway by DAPT increased the KLF4, nephrin, and integrin β1 levels in HG-induced podocytes (p < 0.01). Downregulation of KLF4 expression by KLF4-siRNA inhibited the expression of nephrin and integrin β1 in HG-induced podocytes (p < 0.01). The Notch pathway may regulate the expression of nephrin and integrin β1 through KLF4 in HG-induced podocytes.

目的:探讨Notch通路通过调控Krüppel样因子4(Krüppel-like factor 4,KLF4)在糖尿病肾病进展中的作用.方法:选取8周龄雄性db/db小鼠作为糖尿病模型,分成db/db组和db/db+γ-分泌酶抑制剂DAPT组(n=6),分别腹腔注射二甲基亚砜(dimethyl sulfoxide,DMSO)和DAPT 10 mg?kg-1,每日一次,从第9 w开始连续给药8 w.另选8周龄雄性db/m小鼠作为对照(n=6).于第16 w分别采用免疫组化检测Nephrin蛋白表达,Western blot检测Notch1、Notch胞内域1(Notch intracellular domain 1,NICD1)、KLF4和Nephrin蛋白表达,Real-time PCR检测Notch1、KLF4和Nephrin mRNA表达.结果:与db/m组相比,db/db组小鼠肾组织Notch1和NICD1表达增加,KLF4和Nephrin表达降低(P<0.01);DAPT抑制Notch通路活化后,增加KLF4和Nephrin表达(P<0.01或P<0.05).结论:Notch通路通过KLF4调控糖尿病肾病肾组织损伤.

OBJECTIVE:Lipomatosis of nerve (LN) is a rare tumor-like condition with epineural and perineural infiltration by adipose and fibrous tissue. The purpose was to analyze the ultrasonographic findings of LN involving upper limb peripheral nerves.METHODS:This was a retrospective analysis of a series of 8 patients with LN involving upper-limb peripheral nerves between 2013 and 2019. All patients underwent preoperative ultrasonography for the upper-extremity nerves and were diagnosed as LN by surgery. The clinical manifestations, ultrasonography characteristics, and accuracy were analyzed.RESULTS:In this series, LN was involved in 10 peripheral nerves from 8 patients. The median nerve was the most commonly affected nerve (60%). Four cases presented macrodactyly combined with masses from distal forearm and extending to wrist and palm areas. Among 8 patients, 5 cases were diagnosed with LN by preoperative ultrasonography, an accuracy of 62.5%. Axial ultrasonic imaging showed the punctate hypoechoic fascicles was embedded in hyperechoic adipose tissue in the "lotus root-like" appearance; longitudinal ultrasonic imaging showed the strip hypoechoic fascicles alternates with hyperechoic adipose tissue in the "cable-like" appearance. Meanwhile, ultrasonic imaging showed the thickened of adipose tissue around the affected nerve and the enlargement of flexor tendons in some patients.CONCLUSIONS:Ultrasonography has the potential to be a useful tool for the noninvasive examination of LN. The possibility of LN should be considered in patients with a mass in wrist and palm, macrodactyly, or syndactyly. Our finding may benefit the preoperative differential diagnosis with common nerve tumors.