Trifluridine/Tipiracil (FTD/TPI, TAS102) has been approved for the treatment of patients with colorectal cancer (CRC) for its promising anticancer activity enabled by its incorporation into double strands during DNA synthesis. However, the mechanisms underlying the anticancer targets of FTD/TPI remain not fully understood. Here we report our observation of the activation of ferroptosis in CRC by FTD/TPI. Mechanistically, FTD/TPI directly promotes the ubiquitination and degradation of MDM2, thereby stabilizing the p53. Nuclear accumulation of p53 subsequently downregulates SLC7A11 expression, leading to ferroptosis. Furthermore, we observed that FTD/TPI combined with sulfasalazine (SAS), a system Xc– inhibitor, works in a synergistic manner to induce ferroptosis and further inhibit the proliferation of CRC cells. Finally, we confirmed the synergistic effect of SAS and FTD/TPI on patient-derived organoids in vitro and patient-derived xenograft mouse models in vivo. Our findings are the first to reveal that FTD/TPI induces ferroptosis via the p53-SLC7A11 axis and that SAS enhances the sensitivity and therapeutic effect of FTD/TPI. These findings suggest that the synergistic effect of FTD/TPI and SAS may represent a new therapeutic strategy for patients with CRC.

BACKGROUND:The primary cilia (PC) is a microtubule-based and nonmotile organelle which protrudes from the surface of almost all mammalian cells. At present, PC has been found to be a deficiency or loss in multiple cancers. Restoring PC could be a novel targeting therapy strategy. Our research showed that PC was reduced in human bladder cancer (BLCA) cells, and PC deficiency promotes cell proliferation. However, the concrete mechanisms remain unknown. SCL/TAL1 interrupting locus (STIL), a PC-related protein, was screened in our previous study and could influence the cell cycle by regulating PC in tumor cells. In this study, we aimed to elucidate the function of STIL for PC to explore the underlying mechanism of PC in BLCA.METHODS:Public database analysis, western blot, and enzyme-linked immunosorbent assay (ELISA) were used to screen genes and explore gene expression alteration. Immunofluorescence and western blot were utilized to investigate PC. Wound healing assay, clone formation assay, and CCK-8 assay were used to explore cell migration, growth, and proliferation. The co-immunoprecipitation and western blot were employed to reveal the interaction of STIL and AURKA.RESULTS:We found that high STIL expression is correlated with poor outcomes of BLCA patients. Further analysis revealed that STIL overexpression could inhibit PC formation, activate SHH signaling pathways, and promote cell proliferation. In contrast, STIL-knockdown could promote PC formation, inactivate SHH signaling, and inhibit cell proliferation. Furthermore, we found that the regulatory functions of STIL for PC depend on AURKA. STIL could influence proteasome activity and maintain AURKA stabilization. AURKA-knockdown could reverse PC deficiency caused by STIL overexpression for PC in BLCA cells. We observed that co-knockdown in STIL and AURKA significantly enhanced PC assembly.CONCLUSION:In summary, our result provides a potential therapy target for BLCA based on the restoration of PC.

Supplementary Table S1 from Drozitumab, a Human Antibody to Death Receptor 5, Has Potent Antitumor Activity against Rhabdomyosarcoma with the Expression of Caspase-8 Predictive of Response

Glioma is life-threatening tumor of the central nervous system. Although lidocaine is usually used as local anesthetic, it also has antitumor effects. However, its clinical application in glioma is hampered by limited distribution to the brain. The aim of the present study was to enhance the ability of lidocaine to penetrate the blood-brain barrier (BBB) to target glioma and investigate its antitumor mechanism. A folic acid (FA)-modified lidocaine-carrying liposome (Lid-FA-Lip) was prepared, and its particle size, ζ potential, encapsulation efficiency, release profile stability and hemolytic effect were characterized in vitro. The targeting capacity and antitumor activities of Lid-FA-Lip were also investigated in vitro and in vivo. The results indicated that the modification of liposomes with FA significantly improved the ability of lidocaine to cross the BBB in an in vitro model and increased its uptake by U87 cells. Additionally, Lid-FA-Lip significantly suppressed the motility of U87 glioma cells and stimulated apoptosis. Furthermore, the results confirmed that Lid-FA-Lip targeted the PI3K/AKT pathway and suppressed the growth of glioma xenografts in mice. In summary, the study demonstrated that Lid-FA-Lip is a promising liposomal formulation of lidocaine that may provide improved therapeutic effects on glioma, mediated via the PI3K/AKT pathway.

文中提出一种基于CT图像引导机器人辅助经皮肺穿刺活检术空间定位的新机制。首先,设计6个标记点,并将其同时固定于CT检查床,以在硬件上参考定位;其次,在软件上以改进的D-H逆向运动算法实现CT图像引导机器人进行经皮肺穿刺操作。仿真实验结果表明,使用文中提出的定位机制可有效地保证一次性穿刺成功率。

The original version of this Article omitted a declaration from the Competing Interests statement, which should have included the following: ‘J.D.B. is a founder and Director of the following: Neochromosome, Inc., the Center of Excellence for Engineering Biology, and CDI Labs, Inc. and serves on the Scientific Advisory Board of the following: Modern Meadow, Inc., Recombinetics, Inc., and Sample6, Inc.’. This has now been corrected in both the PDF and HTML versions of the Article.

Objective: To explore the clinical presentation and therapy of primary cutaneous anaplastic large cell lymphoma (PCALCL). Methods:We reviewed and analyzed six cases of PCALCL who were treated at our hospital from January 2009 to Decem-ber 2012. Results:The subjects were three males and three females with a median age of 54 years old (range:38 years to 60 years). Three patients had a single subcutaneous nodule and three had multiple nodules. The subcutaneous lesions appeared red, solid, and sta-ble nodules. Some patients developed pruritus around the lesions, or developed more nodules, which coalesced with other nodules. Some of the lesions exhibited partial spontaneous regression and new nodules appeared at the same site or at different sites. Finally, the lesions changed color from red to brown. The surfaces of some lesions developed ulcerations. Only 1 case had superficial lymph node metastasis. Three cases with single lesions received surgical excision plus radiotherapy, chemotherapy, or radiochemotherapy;all three cases survived and achieved complete remission. The three cases with multiple lesions mainly received systemic chemotherapy, with two of the cases recurring and one surviving with complete remission. The median follow-up was 24 months (range: 11 months to 35 months), with a progression free survival of 66.7%and an overall survival of 100%. Conclusion:Surgical excision or radiotherapy provides satisfactory control in patients with single lesions. Chemotherapy may be prescribed to patients with multiple lesions or with extracutaneous metastasis.

近年来,医患纠纷、医疗诉讼案件呈迅速增长态势,成为社会关注的热点问题之一.如何建立良好的医患关系?如何有效减少医疗纠纷的发生?这些都困扰着医务人员以及医院管理者们.通过分析医疗纠纷的成因,可以发现加强医患沟通在防范处理医疗纠纷中具有重要地位.

进入二十一世纪以来,人们面对着信息多元化,思想多元化,价值多元化的社会,各行各业对人才的竞争越来越强烈,如何培养多学科多领域创新型全方位人才,充分发挥学校在加强学子知识储备中的作用,切实增强教职人员全面育人意识已成为提高国际竞争力的迫切需要。本文旨在将全员全过程育人纳入学校文化领域,以推动全面育人教育思想的理论研究和实践,努力提高教学质量,全面落实教育目标,实现学校的科学管理。并对我校全面育人教育的实践工作做一总结,力求丰富教学方法建设,培养更多更优更高层次医学人才。

Objective:To evaluate the clinical and pathological characteristics and treatments of bladder carcinosarcoma.Methods:4 cases were reported of bladder carcinosarcoma from the secondary hospitals of Tianjin medical university from 1995 to 2010,combining the literature on the diagnosis,pathological characteristics,treatment.Results:4 patients,2 males and 2 females.Age of 63 to 80 years,complained intermittent painless gross hematuria full admission.Cystoscopy prompted cauliflower mass were invasive growth.2 cases partial cystectomy,2 patients had bilateral ureteral bladder full Shaver and skin fistulization.Seen in these patients was basically the same as bladder cancer.Pathology are composed of two components of carcinoma and sarcoma,immunohistochemistry had its specific performance.Different chemotherapy were given after operations.10 months later 2 patients died due to systemic metastasis,and 2 patients were followed up for 10 months and 6 months,whom were still alive and need further observation.Conclusions:Carcinosarcoma of the urinary bladder is a rare sarcomaof bladder.There is no characteristic clinical manifestations.And diagnosis mainly depends on the pathological and immunohistochemical examination,treatment by radical cystectomy better,but its high degree of malignancy and poor prognosis,diagnosis and treatment need further observation.

Objective:To evaluate the clinical and pathological characteristics and treatment of ductal adenocarcinoma of the prostate.Method:Twenty cases report of prostate ductal adenocarcinoma from the major hospitals in Tianjin in 1995-2010,and to combine the literature on the diagnosis and treatment of the line to further explore.Result:Age 64-82 years,mean 74.5 years,of which 13 patients with different degrees of dysuria main reason for hospital admission,9 patients with PSA higher than normal,17 cases of B-ultrasound and MRI abnormalities tips,20 cases were diagnosed after a puncture or biopsy.It requires line of different surgical condition and medication.Immunohistochemistry of prostate ductal adenocarcinoma than specific performance.Follow-up 12-60 months,14 patients died.Conclusion:Ductal adenocarcinoma of the prostate is a clinically rare subtype of prostate cancer and difficult to be found in early stage.The diagnosis depends on histopathologic and immunohistochemical studies.Radical prostatectomy is recommended for this disease.

Objective To investigate the clinical features,diagnosis and treatment of prostate sarcoma. Methods 19 cases of prostate sarcoma had been treated in our hospital from Oct 1995 to Sep 2010,aged from 16 to 48 years (mean,36 years).They were hospitalized due to different degrees of difficulty in urination,6 cases with bladder irritation,3 cases with gross hematuria,3 cases with blood clots in urination,3 cases with difficult defecation,2 cases with urinary tract infection,and 1 case with low back pain.Digital rectal examination showed prostate volume increased significantly in 16 cases,of which 6 cases prominent into bladder,and 3 cases touched hard nodules and tenderness.B ultrasound examination showed prostate neoplasms with internal echo uneven.Pelvic MRI in 12 cases indicated irregular soft tissue density in prostate with unclear edge,a high-low mixed signal inside,and mass protruding outward,among which 7 cases with significantly enlarged prostates and unclear bladder boundaries,6 cases with unclear boundaries with rectum,and 1 case with solid and cystic change. Pelvic CT in 10 cases showed irregular prostate tumors,among which 5 cases with tumor violation of bilateral seminal vesicle,2 cases with tumor invasion of unilateral seminal vesicle,and 3 cases with lymph node enlargement.Chest X-ray in 2 cases showed widespread metastatic lung. Results Different treatments were used according to different conditions:6 cases with full cystoprostatectomy,8 cases with radical prostatectomy,1 case with skin routine ureter fistulization and rectal fistulization,1 case with bladder fistulization,1 case with chemotherapy after prostate biopsy,and 2 cases with prostate biopsy alone. Pathological diagnosis showed 6 cases of leiomyosarcoma,6 cases of rhabdomyosarcoma,2 cases of malignant mesenchymal tumor,1 case of phyllodes sarcoma,1 case of granulocytic sarcoma,1 case of phyllodes sarcoma,1 case of malignant fibrous tissue sarcoma,and 1 case of poorly differentiated muscle induced sarcoma. Immunohistochemical examination in 19 cases of paraffin specimens stained with SP showed vimentin was positive,smooth muscle actin and myoglobin in leiomyosarcoma and rhabdomyosarcoma were positive respectively,and desmin in two kinds of afore-mentioned sarcoma expressed in different level.CD117 and S-100 were weakly positive in 1 patient with undifferentiated component and 1 patient with liposarcoma of the malignant mesenchymoma.Peroxidase was positive in granulocytic sarcoma,p63 was positive in lobulated sarcoma,and CD34 was positive in malignant fibrous histiocytoma.14 patients were given chemotherapy,among which 6 cases were combined with radiotherapy.19 cases were followed up for 4 -30 months (mean 13 months).4 patients survived for 24 -30 months without recurrence,while 15 cases died within 18 months after diagnosis. Conclusions The prostate sarcoma is a clinically rare malignant tumor with high degree of malignancy and unspecific clinical manifestations.The diagnosis relies on biopsy and immunohistochemistry,and early diagnosis and radical surgical excision are helpful for increasing survival rate.

目的 探讨膀胱尿路上皮癌伴肉瘤样变的病理和诊疗特点.方法 回顾性分析我院1995年至2010年收治的5例膀胱尿路上皮癌伴肉瘤样变的临床资料,并结合文献复习,分析其病理和诊疗特点.结果 5例患者中男4例,女1例,年龄40-63岁,4例因间歇性无痛全程肉眼血尿入院,1例因间歇性无痛终末肉眼血尿入院,膀胱镜均提示菜花样肿物,呈浸润性生长.3例行经尿道膀胱电切术,1例行膀胱部分切除术,1例行膀胱全切加双侧输尿管皮肤造瘘术.术中所见与膀胱癌基本相同.术后病理肿瘤均由癌细胞和似肉瘤构象的肿瘤细胞2种结构组成,病理均诊为膀胱尿路上皮癌伴肉瘤样变,免疫组化有该病较特异性的表现.术后予以不同的化疗等.结论 膀胱尿路上皮癌伴肉瘤样变在膀胱恶性肿瘤中罕见,没有特征性的临床表现,确诊主要依靠病理和免疫组化检查,治疗方法采用根治性膀胱切除术效佳,但其恶性程度高,预后不良,诊断和治疗需要进一步的探索.

<正>患者,男,29岁。主因"肛内肿物2年余,排尿困难、大便变细半年余"入院。曾因间断便血于外院诊断为直肠肿物行相应治疗,疗效欠佳。入院后直肠指检:直肠前壁可触及黏膜下一质韧肿物,下缘距肛缘约3 cm,未及上缘;肿物表面光滑,活动度差,无触痛,指套无血染。尿动力学检查提示膀胱出口梗阻,前列腺部尿道延长。B超报告前列腺后方低回声结构,大小8.3 cm×5.7 cm×4.9 cm,内

Objective:The aim of this article was to discuss the variety of semen criterion,seminal plasma fructose and PSA levels in the chronic prostatitis(CP) patients with infertility.Methods:A total of 12 CP patients were enrolled and classified into group A and B.22 patients of group A with normal semen liquefaction and 20 patients of group B with semen delayed liquefaction were examined.We also added another 15 cases as the control group.We analysed biochemical criterion of semen,fructose and PSA levels in each group.Results:Sperm density. Sperm motility,a grade motile sperm concentration in group A and group B were significantly lower than group C(.P<0.01).The PSA significantly lower than group C(P<0.01).Seminal plasma fructose in group B was lower than group C(P<0.01).Conclusions:Chronic prostatitis can cause decreased sperm quality and biochemical composition changes,which may affect the process of semen liquefaction and lead male infertility.

OBJECTIVE:To investigate the clinical presentations and pathologic features of undifferentiated sarcoma of the prostate with cartilage metaplasia, and to clarify its category.METHODS:We analyzed the clinical data of a case of undifferentiated sarcoma of the prostate with cartilage metaplasia treated by surgical resection. The tumor tissue was subjected to routine HE and immunohistochemical staining, its histological structure and immunohistochemical expression were observed under the light microscope, and relevant literature on its manifestations was reviewed.RESULTS:The case was pathologically diagnosed as gray prostate tumor, with chondrosarcomatous and undifferentiated malignant mesenchymal components under the light microscope. Immunohistochemical staining revealed vimentin (+), local CD117 (+/-), SMA (-), Des (-), myoglobin (-), CD34 (-), CK7 (-), and CK8 (-). Tumor metastasis was found 2 months after the operation, and the patient died 4 months later.CONCLUSION:Undifferentiated sarcoma of the prostate with cartilage metaplasia is a very rare and highly malignant aggressive tumor, which can be diagnosed by biopsy and immunohistochemistry.

<正>目前,国内外的医疗纠纷都呈现出上升的趋势,我国更是处于包括医疗体制在内的社会体制转型时期。由于医疗纠纷处理中反映出来的社会问题复杂程度更高,医患关系紧张表现得更为突出。医疗纠纷的解决是世界上大多数国家所面临的难题。从总体上讲,医疗纠纷解决机制包括了诉讼与替代诉讼纠纷解决方式

As a new-born thing since the reform and opening-up,volunteer service has accommodated itself to the deep-going changes undergone by different social structures,social organizations and different patterns of social benefits,and has fulfilled hopes of people of all walks of life to assist others,to serve society and to realize the value of their life with its multiple forms and its flexibility in operation.Again,as an effective form and an important vehicle for the broad social members to receive moral education and practice under the conditions of socialist market economy,it has become the synonym of "nobleness",abreast with the era in its own development.Volunteer service among College Students helps them to cultivate noble character,to create the fresh new atmosphere of the present era of devotion,love,and mutual aid.

Objective To investigate the efficacy and safety of tamsulosin for benign prostatic hyperplasia(BPH).Methods 30 cases of patients with BPH were selected,who were given tamsulosin 0.2 mg/d,for 4 weeks.Results The clinical onset times are after medication within 48 hours,the patient′s international prostate symptom score,quality of life score,maximum flow rate,residual urine,were significantly different(P0.05)between before and after treatment.Comparison of blood pressure,alanine aminotransferase,creatinine clearance did not change significantly(P0.05).Conclusion Tamsulosin treatment of lower urinary tract symptoms caused by BPH,is safe and effective with few complications,and especially it also has a high cardiovascular safety.

患者男性,14岁,因"双侧腰部间断疼痛5年"于2009年10月30日入院.疼痛多在受凉或劳累后出现,每年出现2～3次,每次疼痛时间持续2 d,休息后可自行缓解.不伴恶心、呕吐,无肉眼血尿,无发热等不适.既往无肾脏疾病病史,家族中无肿瘤或特殊遗传病史.