Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.

Despite the advancement of treatments, adults with relapsed/refractory (R/R) B-lineage acute lymphoblastic leukemia (B-ALL) have poor prognosis, with an expected five-year overall survival (OS) rate of 10%‒20% (Nguyen et al., 2008; Oriol et al., 2010). Extramedullary relapse of B-ALL is regarded as a high-risk factor generally associated with poor survival, occurring in about 15% to 20% of all relapsed patients (Ding et al., 2017; Sun et al., 2018). The central nervous system (CNS) and the testes are the most common sites of extramedullary relapse of B-ALL. In addition, extramedullary leukemia can appear in the skin, eyes, breasts, bones, muscles, and abdominal organs. The prognosis of relapsed extramedullary B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is extremely poor (Spyridonidis et al., 2012; Dahlberg et al., 2019). Conventional chemotherapy or radiation is often ineffective in such patients. At present, there are no optimal treatment strategies for treating extramedullary leukemia after allo-HSCT.
Adult ; Antigens, CD19 ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunotherapy, Adoptive/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Receptors, Chimeric Antigen ; Recurrence

OBJECTIVE: To establish a method of determination of difluorochloromethane in workplace air by direct sampling gas chromatography. METHODS: Difluorochloromethane in workplace air was collected with aluminum plastic composite film airbag and then directly injected. Difluorochloromethane was separated by DB-1 capillary column and detected with hydrogen flame ionization detector. RESULTS: Good linearity was obtained in the range of 1.50-15 042.90 mg/m~3 with the correlation coefficient of 0.999 96. The limit of detection was 1.26 mg/m~3 and the limit of quantitation was 3.78 mg/m~3. The minimum detection concentration was 1.26 mg/m~3 and the minimum quantification concentration was 3.78 mg/m~3. The standard recovery was 98.34%-99.19%. The within-run relative standard deviation(RSD) and the between-run RSD were 1.82%-3.72% and 2.17%-4.17%, respectively. The samples can be stored at room temperature for at least 7 days. CONCLUSION: This method is suitable for difluorochloromethane detection in workplace air.

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Objective To analyze the main causes for unplanned re-operation of pheochromocytoma (PCC) and explore the countermeasures on reducing the re-operation rate.Methods The clinical data of 6 patients with pheochromocytoma who underwent an unplanned re-operation were analyzed retrospectively between September 2011 and December 2016 in our hospital.There were 4 males and 2 females with a mean age of 46 years,ranged from 24 to 60 years.Only 1 patient had paroxysmal hypertension and headache,and the other 5 patients had no symptoms or atypical symptoms.Tumors of 3 cases were located in adrenal,and 3 were extra-adrenal PCCs.The average size of tumors was 5.25cm,ranged from 3 to 10 cm.Among the 6 cases,2 cases were diagnosed as PCC preoperatively and underwent adequate preparationwith stable hemodynamics during the first operation,who encountered post-operative bleeding soon after the surgery.Four cases were misdiagnosed,with poor preoperative preparation and operation was aborted.One case was misdiagnosed as bladder carcinoma and underwent transurethral resection.Results All 6 re-operations were performed by urologists.The main causes for unplanned re-operation were as follows:perioperative hemodynamic unstability (50％,3/6),post-operative bleeding (33.3％,2/6),uncertainty of surgical outcome (16.7％,1/6).Conclusions A precise diagnosis and an adequate preoperative preparation are the key to prevent a second-look surgery.An appropriate surgical approach and a complete surgical hemostasis could help lowering the re-operation rate.

Objective: To assess value of immediate postoperative intravesical instillation of pirarubicin after transurethral resection (TURBT)of non-muscle invasive bladder cancer. Methods: 484 patients diagnosed with non-muscle-invasive bladder cancer admitted to the Second Affiliated Hospital of Kunming Medical University were divided into two groups after transurethral resection of bladder tumor. 285 patients received postoperative intravesical instillation of pirarubicin within 6 hours after the surgery, 199 patients received first instillation of pirarubicin at 10 days after the surgery, after that, all the patients received routine bladder perfusion chemotherapy. Patients who received intravesical instillation of pirarubicin within 6 hours were defined as immediate intravesical instillation group and the other patients as the control group. Based on the European Organisation for Research and Treatment of Cancer risk tables, scores of recurrence and progression of patients were calculated and then stratified into risk groups accordingly. Recurrence and progression rates of the immediate intravesical instillation group were analyzed and then compared with the corresponding reference of the risk tables. Results: The 1-year and 5-year recurrence rate of patients with EORTC table scoring 0 in the immediate intravesical instillation group were significantly lower than that of the EORTC reference group (5.3% and 14.0% vs 15.0% and 31.0%, P<0.05). 1-year recurrence free rate between the immediate intravesical instillation group and the control group in patients scoring 1-4 was significantly different (81.3% vs 76.7%, P=0.014). However, 1-year recurrence free rate of the immediate intravesical instillation group was comparable with that of the control group in patients scoring 5-9, 10-17(P>0.05), which is quite close to the EORTC reference. The probability rates of 1-year and 5-year progression of the 285 patients who received immediate intravesical instillation group did not show significant difference with the EORTC reference. On multivariate analysis, previous recurrence, tumor grade G2-3, tumor multiplicity, delay of immediate intravesical instillation were independent risk factors of recurrence(P<0.05). Conclusions With the help of EORTC recurrence risk table stratifying the patients into different risk groups, our study showed that delay of immediate postoperative intravesical instillation of chemotherapy after TURBT was an independent risk factor of post-surgery recurrence of tumor. Moreover, patients with EORTC scoring 1-4 might obtain greatest benefits.

Objective To analyze the typical clinical manifestations and imaging characteristics of renal pelvic carcinoma.Methods The clinical data in 69 cases of renal pelvic carcinoma verified by postoperative pathology in this department of the hospital from July 2013 to November 2016 were retrospectively summarized to analyze its typical clinical manifestations,imaging features and treatment regimens.Results All the cases were hospitalized due to hematuria and presented gross hematuria.The detectable rate of B-ultrasonic examination was 71.43 ％,which of computed tomography urography(CTU) was 84.21％ and which of intravenous urography(IVU) + kidney ureter bladder(KUB) was 70.27 ％,which of retrograde pyelography(RP) was 90.32 ％,which of flexible ureteroscope(FU) was 91.67 ％,the pathological detection rate of biopsy tissue by this method was 58.33 ％ and detection rate of fluorescence in situ hybridization was 79.07 ％.Sixty-nine cases all were performed the retroperitoneal laparoscopy combined with hypogastric incision renal pelvic carcinoma radical operation,postoperative pathological examination verified renal pelvis carcinoma.Conclusion Flexible ureteroscope examination has the highest definite diagnosis rate of renal pelvic carcinoma,but the pathological positive rate of biopsy tissue by this method is not ideal;the definite diagnosis rate of RP and CTU were secondary,urinary system B-ultrasonic examination,FISH and KUB+IVP can serve as the preliminary screening and postoperative re-examination means of renal pelvic carcinoma.

Objective To analyze and summarize the short-term clinical efficacy and surgical points of transurethral columnar balloon dilation of prostate for middle-aged and high-risk prostatic hyperplasia patients.Methods A total of 30 patients with benign prostatic hyperplasia(BPH) admitted to our department from March 2016 to December 2016 was retrospectively analyzed,including 9 middle-aged patients(less than 60 years old) and 21 high-risk patients with various underlying diseases(more than 80 years old).Transurethral columnar balloon dilation of prostate was adopted and performed in accordance with standard operation process.Results All 30 patients were operated successfully by extending their prostate at the direction of 12 o'clock to the fat layer with short operation time and less amount of bleeding.The complication rate was 6.7％ (2/30),and the catheter was removed smoothly after the operation.After 1 month and 6 months follow-up,the international prostate symptom score(IPSS),quality of life score(QOL),maximum urinary flow rate(Qmax),residual urine(RUV) and other indicators were analyzed and were statistically significant(P＜0.05).Conclusion Transurethral columnar balloon dilation of prostate is an effective and supplemental method for the treatment of BPH in middle-aged and high-risk patients.

Objective To summary the experience of laparoscopic cystectomy ileal conduit (Bricker) and orthotopic ileal neo‐bladder (Hautmann) and compare the short‐term efficacy of the two types of urinary diversion for invasive bladder cancer . Methods Retorspective analysis of the patients in our hospital who accepted laparoscopic radical cystectomy from 2010 to 2014 was performed ,74 of them accepted ileal conduit ,and 30 of them accepted orthotopic ileal neobladder .The general clinical data ,postop‐erative recovery ,postoperative complications and Oncology feature were analyzed and compared between the two groups .Results There was no demonstrable difference was found in operation time ,blood loss ,intraoperative blood transfusion rate ,the number of removed lymph node ,average hospital stay ,specimens positive margin rate and postoperative pathology results between the two groups (P>0 .05) .But there were significant difference in postoperative intestinal function recovery time[(4 .2 ± 1 .4)d ,(5 .3 ± 2 .2)d] ,(P=0 .002) ,and the complication rates 31 .9% (23 cases)vs .53 .3% (16 case) ,P=0 .043 .After 6 months ,the daytime and nighttime urinary control were 76 .9% ,57 .7% ,after 12 months ,the daytime and nighttime urinary control increased to 90 .9% , 81 .8% .2 cases(7 .7% ) were diagnosed with recurrence or metastasis during follow‐up in Hautmann group ,while 9 cases(14 .1% ) were diagnosed with recurrence or metastasis in Bricker group .Conclusion Two kinds of surgical procedures both have the similar therapeutic effect ,but the postoperative quality of life is better for Hautmann orthotopic neobladder patients .

Objectives To screen the high-risk population of stroke in China using color Doppler flow imaging (CDFI)and to establish a stroke risk prediction model in Chinese population in order to prevent and treat stroke early. Methods Forty-one base hospitals and 715 286 people in the project areas of the first 6 provinces of China conducted routine physical examinations and investigated the related risk factors for cardiocerebrovascular diseases from July 2011 to April 2012 using a cross-sectional study,among them 61 860 patients underwent carotid CDFI screening,and 49 386 of them were high-risk population (exposed to≥3 risk factors). The bilateral common carotid interma-media thickness (IMT),the number of plaques and the degree of carotid stenosis were screened and documented. And whether carotid IMT thickening or not,with or without carotid plaques,and degree of carotid artery stenotic rate 0-49% and≥50% were performed by multivariate logistic regression analysis with the risk factors for stroke,respectively. Results (1)Logistic regression analysis showed that hypertension,atrial fibrillation,smoking,and lack of physical exercise were the independent risk factors for carotid IMT thickening (hypertension:OR,1. 17;95%CI 1. 12-1. 22;atrial fibrillation:OR,1. 15;95%CI 1. 09-1. 21;smoking:OR,1. 13;95%CI 1. 08-1. 17;and lack of physical exercise:OR,1. 12;95%CI 1.08-1. 16). (2)Hypertension,atrial fibrillation, smoking,and diabetes were the independent risk factors for carotid plaque and carotid artery stenosis rate≥50%(carotid plaque,hypertension:OR,1. 55;95%CI 1. 47-1. 62;atrial fibrillation:OR,1. 13;95%CI 1.06-1. 21;smoking:OR,1. 16;95%CI 1. 11-1. 22;and diabetes:OR,1. 30;95%CI 1. 24-1. 37). Carotid stenosis rate≥50%,hypertension:OR,1. 78;95%CI 1.55-2. 03;atrial fibrillation:OR,1. 59;95%CI 1. 39-1. 81;smoking:OR,1. 33;95%CI 1. 20-1. 48;and diabetes:OR,1. 30;95%CI 1. 17-1. 45. Simple obesity did not increase the incidences of carotid atherosclerotic plaque and carotid artery stenosis ≥50%(OR,0. 78, 0.83;95%CI 0. 75-0. 82 ,0. 75-0. 92,respectively). Conclusions Neck vascular ultrasound can be used as a valuable means for screening high-risk population and detecting risk factors of stroke. It has an important clinical significance for the early diagnosis and treatment of carotid atherosclerosis disease.