The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph + ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph + ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.

The evolving stratified treatment approach based on molecular genetic alterations and minimal residual disease (MRD) monitoring has established a strong foundation for clinically managing Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL). However, with the growing use of immune-targeted therapies and the increased sensitivity of detection technologies, discrepancies in MRD assessment have emerged in some patients with Ph + ALL, particularly where BCR:: ABL1-based MRD levels remain consistently elevated compared to those detected by alternative methods. Research suggests that this persistent BCR:: ABL1 positivity may not solely reflect residual lymphoblasts but may also indicate the involvement of multilineage hematopoietic cells. This distinct biological feature has been termed Ph + ALL with multilineage involvement. Currently, the absence of standardized diagnostic criteria and prognostic frameworks for this subtype poses significant challenges in clinical decision-making. Therefore, this article offers a comprehensive review of its molecular and pathological characteristics, potential prognostic biomarkers, patterns of disease evolution, and clinical implications, with the goal of informing more accurate diagnostic and therapeutic strategies.

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.

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 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 evaluate the risk factors of septic shock after mini-percutaneous nephrolithotripsy (mPCNL). Methods Clinical data of 1 590 cases who underwent mPCNL from January 2013 to December 2014 were retrospectively analyzed. The x2 test and logistic regression were used to identify the key risk factors for septic shock after mPCNL. Results Of the 1 590 patients, 18 patients suffered septic shock, including 6 male patients and 12 fe﹣male patients. Their mean age was (45.6 ± 13.5) years (28 ~ 69 years). White cell in urine was 100 percent, the stone diameter ranged from 1.5 to 5.0 cm, unichannel for 15 cases while multichannel for 3 cases, the operation du﹣ration ranged from 45 to 200 min, mean (87.0 ± 56.0) min. 2 in 18 cases died in multiple organ failure, the others recovered till discharged. In x2 test, female gender (P = 0.001), (+++ ~ ++++) white cells in urine (P= 0.042), un-preoperative nephrostomy drainage (P=0.041) had significant association with septic shock after mPCNL. While in multivariate analysis, female gender ( O? = 5.471, 95 % CI: 0.756~21.452, P< 0.05) and un-preoperative nephrostomy drainage (O? =3.106, 95%CI:1.283~7.907, P<0.05) were identified as independent risk factors for septic shock after mPCNL. Conclusions Female gender and un-preoperative nephrostomy drainage are the key risk factors for septic shock after mPCNL.

ObjectiveTo evaluate the methods in treatment of upper urinary calculi in a low-head lithotomy with right or left lateral tilt by an ureteroscopy approach. Methods From September 2009 to May 2015, 110 patients with upper ureteral calculi (after failed ESWL) were underwent holmium laser lithotripsy by a ureteroscopy approach in a low-head lithotomy with right or left lateral tilt. Their clinical data and complications were analyzed retrospectively. Results Surgical effect of patients was satisfied with the success of gravel 91 patients, with a total rate of 82.7 %gravel. Conclusion Low-head lithotomy with right or left lateral tilt is a good body position to perform ureteroscopic lithotripsy for upper ureteral calculi. It is safe and effective.

Objective:To discuss the effect of pharmacist intervention on the use of antimicrobial agents in the clinical pathway of community-acquired pneumonia ( CAP) in our hospital to standardize the rational medication and promote the rational use of antimicro-bial agents. Methods:Totally 100 bacterial CAP patients in 2013 ( before the intervention) and 2014 ( after the intervention) in the pneumology department were studied. The antibacterial drug cost, total hospitalization cost, use intensity of antimicrobial drugs, hospi-talization time, therapeutic effects and so on in the two groups were observed during the treatment. Results: There were significant differences between the two groups in antibacterial drug cost, total hospitalization cost, use intensity of antimicrobial drugs, hospitaliza-tion time and so on, whereas there was no significant difference in the curative effect. Conclusion:After the pharmacist intervention, the application of antibiotics is more rational, the antibiotics use density and per capita cost are reduced, the hospitalization day is shortened and the value of pharmacists is also improved.

Rosiglitazone and pioglitazone belong to thiazolidinediones( TZD)insulin sensitizers, mainly used for the treatment of type 2 diabetes. Rosiglitazone was restricted to use or withdrawn from the market due to possibly increased cardiovascular events in 2010,and then was released for insufficient evidence in 2013. The large prospective clinical trial and Meta-analysis indicated that pioglitazone has cardiovascular protective effect,since the drug reduced risk of myocardial infarction/stroke/death of patients with type 2 diabetes. The different cardiovascular risk of rosiglitazone and pioglitazone maybe related to the differences in effect on lipid metabolism or in gene regulation.

Rosiglitazone and pioglitazone belong to thiazolidinediones( TZD)insulin sensitizers, mainly used for the treatment of type 2 diabetes. Rosiglitazone was restricted to use or withdrawn from the market due to possibly increased cardiovascular events in 2010,and then was released for insufficient evidence in 2013. The large prospective clinical trial and Meta-analysis indicated that pioglitazone has cardiovascular protective effect,since the drug reduced risk of myocardial infarction/stroke/death of patients with type 2 diabetes. The different cardiovascular risk of rosiglitazone and pioglitazone maybe related to the differences in effect on lipid metabolism or in gene regulation.