Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is challenging to treat and lacks targeted therapeutic drugs in the clinic. Natural active ingredients provide promising opportunities for discovering and developing targeted therapies for TNBC. This study investigated the effects of daurisoline on TNBC and elucidated its potential mechanisms. Using network pharmacology, a correlation was identified between daurisoline, derived from Menispermum dauricum, and breast cancer, particularly involving the Notch signaling pathway. The effects of daurisoline on the proliferation, migration, and apoptosis of MDA-MB-231 and MDA-MB-468 cells were evaluated in vitro. Additionally, the impact of daurisoline on the growth of MDA-MB-231 xenograft tumors in nude mice was assessed through in vivo experiments. Expression levels of Notch signaling pathway-related proteins, including Notch-1, NICD, PSEN-1, Bax, and Bcl-2, were examined using molecular docking and Western blotting to explore the underlying mechanisms of daurisoline’s anti-breast cancer effects. It was revealed that daurisoline could effectively inhibit the proliferation and migration of MDA-MB-231 and MDA-MB-468 cells and promote apoptosis. Furthermore, it significantly reduced the growth of subcutaneous tumors in nude mice. Notably, daurisoline could reduce the hydrolytic activity of γ-secretase by binding to the catalytic core PSEN-1, thereby inhibiting activation of the γ-secretase/Notch axis and contributing to its anti-TNBC effects.This study supported the development of naturally targeted drugs for TNBC and provided insights into the research on dibenzylisoquinoline alkaloids, such as daurisoline.

Objective To establish the methods of galvanic vestibular stimulation-vestibular evoked myogenic potentials(GVS-VEMPs)in healthy children and to obtain the normal value of GVS-cVEMP and GVS-oVEMP in these children in China.Methods Twenty(3～14 years)healthy children and 24 healthy adults(18～30 years)were enrolled for conventional examinations of GVS-cVEMP and GVS-oVEMP.Using the galvanic stimulation in-tensity under 3 mA/1 ms for children and 5 mA/1 ms for adults.The characteristics of elicitation and parameter re-sults of GVS-cVEMP and GVS-oVEMP in children and adults,as well as the pain scores and the elicitation of differ-ent stimulus intensities in the two age groups were recorded.Results The elicitation of GVS-cVEMP and GVS-oVEMP were both 100.0％in children and adult groups.The p1 latency,n1 latency and p1-n1 interval latency of GVS-cVEMP were 10.46±1.84 ms,16.98±2.12 ms and 6.52±1.42 ms respectively in children group,the n1 la-tency and p1-n1 interval latency were significantly shorter than the adult group(P＜0.05).The n1 latency,p1 la-tency and p1-n1 interval latency of GVS-oVEMP were 8.87±1.40 ms,12.25±1.80 ms and 3.39±1.07 ms re-spectively in children group with no significant difference between the two groups.The thresholds of GVS-cVEMP and GVS-oVEMP in children group were significantly lower than adult group(P＜0.01),but no differences were found in adult group regarding on the amplitude and interaural amplitude asymmetry ratio.In addition,with the in-crease of the intensity of galvanic stimulation,the correlation between pain scores and the elicitation rates of GVS-cVEMP and GVS-oVEMP also increased.Conclusion Using appropriate stimulus intensity and recording methods,GVS-cVEMP and GVS-oVEMP could be successfully assessed and detected in healthy children over 3 years old and adolescents.The latency of GVS-cVEMP in children is slightly shorter than that in adults,therefore we recommend selecting the matched age group for assessment in the children group.

Objective:To explore a type of teaching teeth that can highly simulate natural teeth, and to investigate its application in the practice teaching of crown preparations.Methods:A total of 44 senior students majoring in stomatology Fourth Military Medical University were selected, and each student received the training of crown preparations using interpenetrating polymer network (IPN) enamel-like teaching teeth, extracted natural teeth, and traditional composite resin teeth. Operation assessment was performed, and the operation time of each crown preparation was recorded. According to the requirements for crown preparations, scores were determined from the five aspects of axial converging, space for repair, line angle, shoulder quality, and posture, with 10 points for each aspect and 50 points in total, and the total score was calculated. A questionnaire survey on IPN enamel-like teeth was performed for each student after assessment, and SPSS 23.0 was used to perform the least significant difference t-test and the Tambane's T2 test. Results:There was no significant difference in total assessment score between the IPN enamel-like teeth group and the natural teeth group (37.15±1.17 vs. 37.20±1.20, P>0.05), and both groups had a significantly higher total score than the resin teeth group (31.53±1.41) ( P<0.05). The IPN enamel-like teeth group and the natural teeth group had significantly higher scores than the traditional composite resin teeth group in terms of axial converging, space for repair, and shoulder quality ( P<0.05). The questionnaire survey of the students showed a relatively high score of 3.7-4.9 for each item. Conclusion:Compared with traditional composite resin teeth, IPN enamel-like teeth can more comprehensively and effectively simulate the operation and experience of natural teeth for crown preparations and thus have potential advantages in the practice teaching of crown preparations.

Objective:To discuss the classification and treatment of ureteroileal anastomotic stricture (UAS) after radical cystectomy.Methods:The clinical data of 34 patients with UAS after radical cystectomy in the Department of Urology of Tongji Hospital from January 2017 to January 2022 were reviewed and analyzed. There were 25 males and 9 females. The average age was (66.3±7.7)years, including 2 cases of bilateral hydronephrosis and 32 cases of unilateral hydronephrosis. The average time of UAS was detected (14.7±6.5)months after radical cystectomy. There were 32 patients of unilateral hydronephrosis and 2 patients of bilateral hydronephrosis. Two patients had undergone nephrostomy in an external hospital. Three patients had elevated leukocytes in blood routine. Among them, two patients had fever. First, nephrostomy on the hydronephrosis side and anti-infection treatment were performed. After routine blood tests showed that the white blood cells were normal and antibiotics were stopped for 24 hours without fever, the operation was performed. 34 patients had preoperative hydronephrosis of (2.7±0.6) cm. Of the 34 cases in this group, 5 cases were injected with methylene blue through a preoperative nephrostomy tube, and 29 were injected with methylene blue through the renal pelvis using an 18G puncture needle under ultrasound guidance. Using a ureteroscope to observe in the ileal bladder, methylene blue was seen in 4 cases. Methylene blue was used to guide the search for the stenosis and a super smooth guide wire was inserted. Among them, 3 cases were dilated with a 5 mm ureteral dilation balloon catheter, 1 case was dilated with a F14 ureteral access sheath, and then a F6 single J stent was inserted. Methylene blue was not seen in the ileal conduit in 30 cases, of which 16 cases were treated with a flexible ureteroscope through the nephrostomy to locate the stenosis, incised with a 30 W holmium laser. 9 cases were treated with 5 mm ureteral dilation balloon catheter, and 7 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 14 cases were unable to find the stenosis by antegrade method. According to the operation time and patient's condition, it was decided to perform immediate or second stage dual endoscope surgery. Through the nephrostomy, a flexible ureteroscope was used to enter the stenosis along the super slide guide wire. A rigid ureteroscope was used to observe the stenosis through the ileal conduit, and the stenosis was found. The stenosis was found in 10 cases and incised with a 30 W holmium laser. 8 cases were treated with 5 mm ureteral dilation balloon catheter, and 2 cases were treated with a F14 ureteral access sheath, and then an F6 single J stent was inserted. 4 cases were still unable to accurately locate the stenosis using the dual endoscope surgery(one case was bilateral stenosis, and one side was relieved), and continued indwelling nephrostomy. The definition of successful removal of stricture in this study is that an F6 single J stent can be inserted into the ureter.Results:UAS were classified into four types based on the severity of the intraoperative findings: Type Ⅰ, the narrow ureteral lumen is more than 50% narrower than the normal ureteral lumen, but methylene blue can pass through in strands; Type Ⅱ, needle like stricture of the ureteral lumen, allowing only methylene blue filaments to pass through; Type Ⅲ, membranous atresia of the ureter, with a narrow segment of 1 to 3 mm in length, and methylene blue cannot pass through; Type Ⅳ, long segment stenosis. Of the 34 cases in this group, 4 cases were type Ⅰ, and the stenosis was dredged by retrograde method; 16 cases were type Ⅱ, and the stenotic segments were dredged by antegrade method; 10 cases were type Ⅲ, and the stenosis was dredged by the dual endoscope surgery; Four cases were of type Ⅳ (one case was of bilateral UAS, one side was of type Ⅲ, and the other side was of type Ⅳ, which was classified as type Ⅳ). The stenotic segment could not be solved through the above methods. Among the 34 patients, 30 patients were successfully relieved of anastomotic obstruction, and 1 patient with bilateral obstruction was unilaterally relieved of anastomotic obstruction. In the other 3 cases, because the stenosis segment was too long, 2 cases were changed to nephrostomy, and 1 case was changed to open surgery, with a success rate of 88.2%. UAS was classified into 4 types based on the severity of UAS seen during surgery. No serious complications occurred during and after the operation. During the follow-up of 6-24 months, the imaging evaluation of 4 patients showed that hydronephrosis was aggravated, with an average increase in creatinine of (32.5±10.9)μmol/L, requiring replacement of a single J tube. The imaging evaluation of the remaining 26 patients showed that the postoperative hydronephrosis was 0.9 ± 0.6 cm less than the preoperative hydronephrosis 2.6 ± 0.6 cm, with a statistically significant difference ( P<0.01). The quality of life score at 3 months after surgery was (1.9±0.6), which was significantly improved compared to the preoperative indwelling nephrostomy period (5.2±0.7), with a statistically significant difference ( P<0.01) Conclusions:The treatment of UAS after radical cystectomy with retrograde, antegrade, and dual endoscope surgery has a high success rate, which can help some patients avoid the inconvenience of indwelling external drainage tubes and the risk of open surgery. Choosing an appropriate surgical method can achieve the goal of treating UAS with minimal trauma.

Objective To evaluate the effects of simulation training based on the concept of experiential education on im-proving first aid skills of medical staff in nursing homes.Methods The assessment data of 120 medical staff participating in first aid simulation training in our nursing home from January 2020 to June 2023 were retrospectively analyzed.Using a self-controlled design,the changes in skills operation,reaction time,team cooperation,etc.were statistically analyzed.Results All indicators were significantly improved after training.The skill operation score increased by 12.4 points(P＜0.05),the average reaction time decreased by 5.2 seconds(P＜0.05),and the team cooperation score increased by 13.8 points(P＜0.05)compared with before training.Conclusion Simulation training based on the experiential education model can effectively improve the first aid skills and cooperation ability of medical staff,which is an important means to continuously improve the emergency response capac-ity in nursing homes.

Objective:To explore the treatment experience of holmium laser enucleation of prostate (HoLEP) with preservation of longitudinal urethral mucosa at 12 o’clock for benign prostatic hyperplasia (BPH) with small-medium gland.Method:From October 2018 to April 2021, 256 patients diagnosed BPH with small-medium gland(prostate volume 30-60 ml)were retrospectively analyzed, including general information, way of operation, intraoperative parameters and follow-up data. From October 2018 to June 2020, 186 BPH patients underwent conventional HoLEP, which did not retain longitudinal urethral mucosa at 12 o’clock as a conventional operation group. From July 2020 to April 2021, 70 BPH patients underwent modified HoLEP, which retained longitudinal urethral mucosa at 12 o’clock as a modified operation group. There was no significant difference between the two groups( P>0.05) in term of the age[(70.5±4.4)years old vs.(68.5±3.2)years old], Q max[(7.5±2.8)ml/s vs.(7.5±2.1)ml/s], IPSS[(20.3±4.6)vs.(21.4±3.7)], QOL[(4.5±1.0)vs.(4.2±1.4)], postvoid residual volume[(126.9±29.36)ml vs.(132.2±32.3)ml], PSA[(1.5±1.3)ng/ml vs.(1.8±1.1)ng/ml] and prostate volume[(48.1±11.1)ml vs.(48.0±12.7)ml]. Both groups were treated with "trefoil" enucleation of prostate. The modified group was improved compared with the conventional group by retaining a 12 o’clock longitudinal urethra mucosa from the bladder neck to the apex of the prostate. The technical improvements were as follows: ①the left lobe of prostate was removed from at 5 o’clock at the verumontanum to 1 o’clock at the prostate apex along the gap between the hyperplasia gland and the surgical envelope; ②the right lobe was removed from 7 o’clock at the verumontanum to 11 o’clock at the apex; ③the urethra mucous membrane was cut vertically from 1 and 11 o’clock at the bladder neck to 1 and 11 o’clock at the apex respectively, and retaining the longitudinal mucous membrane between 11 and 1 o’clock (including 12 o’clock). Efficacy and postoperative complications of the two groups were compared. Results:The difference between the conventional group and the modified group in operation time[(36.5±10.4)min vs.(40.7±9.7)min], enucleated glandular weight[(35.5±12.2)g vs.(31.6±10.4)g], hemoglobin decline[(6.1±2.2)g/L vs.(5.6±2.5) g/L], postoperative hospitalization time [(1.2±0.2)d vs.(1.5±0.4)d]and catheter indwelling duration[(2.3±1.3)d vs.(2.0±1.0)d] were not statistically significant ( P>0.05). There were 252 patients for follow-up, including 183 cases in the conventional group and 69 cases in the modified group, and 4 cases were lost to follow-up. Mean time of follow-up was 8.4 months. In both groups, postoperative IPSS were 5.4±2.3 and 5.9±1.2 respectively, QOL1.5±0.3 and 2.0±1.0 respectively, Q max(24.3±9.2)ml/s and (22.5±11.3)ml/s respectively and postvoid residual volume (8.3±4.5)ml and (7.7±2.9)ml respectively, which were significantly different from that before the operation ( P<0.05). However, there was not significant difference between the two groups ( P>0.05). The postoperative immediate urinary continence rate of the conventional group and modified group were 85.2% (156/183), 98.6% (68/69), respectively, and two groups had statistical differences ( P<0.05). Incidence of postoperative bladder neck contraction were 4.4% (8/183) and 0 respectively in the conventional and modified group, whose difference was significant( P<0.05). Conclusions:HoLEP with preservation of longitudinal urethral mucosa at 12 o'clock is the same effective as conventional operation in the treatment of BPH with small-medium gland, likewise it could significantly improve immediate urinary continence rate and reduce the incidence of bladder neck contraction.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling, in which hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) plays an important role. The cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) is the critical redox regulatory cysteine to regulate SERCA2 activity. Heterozygous SERCA2 C674S knock-in mice (SKI), where one copy of C674 was substituted by serine to represent partial C674 oxidative inactivation, developed significant pulmonary vascular remodeling resembling human PH, and their right ventricular systolic pressure modestly increased with age. In PASMCs, substitution of C674 activated inositol requiring enzyme 1 alpha (IRE1α) and spliced X-box binding protein 1 (XBP1s) pathway, accelerated cell cycle and cell proliferation, which reversed by IRE1α/XBP1s pathway inhibitor 4μ8C. In addition, suppressing the IRE1α/XBP1s pathway prevented pulmonary vascular remodeling caused by substitution of C674. Similar to SERCA2a, SERCA2b is also important to restrict the proliferation of PASMCs. Our study articulates the causal effect of C674 oxidative inactivation on the development of pulmonary vascular remodeling and PH, emphasizing the importance of C674 in restricting PASMC proliferation to maintain pulmonary vascular homeostasis. Moreover, the IRE1α/XBP1s pathway and SERCA2 might be potential targets for PH therapy.

Objective:To examine the efficacy and safety of third-party bone marrow-derived mesenchymal stem cells (MSCs) in the treatment of refractory delayed hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Twenty patients with refractory LOHC received conventional therapy combined with MSCs obtained from third-party donors’ bone marrow (BM) . MSCs were given intravenously at a dose of 1 × 10 6 cells/kg once weekly until either the symptoms improved or no changes in LOHC were seen after continuous infusion four times. BK viruria (BKV) -DNA, JC viruria (JCV) -DNA, and CMV-DNA were detected by real-time quantitative PCR before and 8 weeks after the MSCs infusion. Results:① Of the 20 patients with refractory LOHC, 15 were males, and 5 were females, and the median age was 35 (15-56) years. There were 5 cases of acute lymphoblastic leukemia (ALL) , 9 cases of acute myeloid leukemia (AML) , 5 cases of myelodysplastic syndrome (MDS) , and 1 case of maternal plasma cell like dendritic cell tumor (BPDCN) . There were 4 cases of HLA identical transplantation and 16 cases of HLA incomplete transplantation. ②The median number of MSC infusions for each patient was 3 (range: 2-8) . Seventeen patients achieved complete response, and one had a partial response after treatment. The overall response rate was 90%. Over a median follow-up period of 397.5 days (range 39-937 days) post-transplantations, 13 patients survived, and 7 died. The causes of death included aGVHD (1 case) , infections (5 cases) , and TMA (1 case) . ③The copy numbers of BKV-DNA and CMV-DNA in urine in the 8th week after MSCs infusion were significantly lower than those observed before treatment (11342.1×10 8 copies/L vs 5.2×10 8 copies/L, P=0.016; 3170.0×10 4 copies/L vs 0.2×10 4 copies/L, P=0.006, respectively) , while JCV-DNA did not significantly differ when compared to before treatment ( P=0.106) . ④ No adverse reactions related to MSC infusion occurred in any of the 20 patients. Conclusion:Third-party bone marrow-derived MSC has significant efficacy and good safety in the treatment of refractory LOHC after allogeneic HSCT.