Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

Objective To discuss the safety and efficacy of arterial embolization combined with local ablation in the treatment of recurrent and refractory chest wall tumors.Methods The clinical data of 11 patients with chest wall tumor that recurred after surgery and progressed after treatment were retrospectively analyzed.On the basis of the original treatment regimen,DSA-guided arterial embolization and CT-guided local ablation were employed.VAS score of pain relief and postoperative complications were recorded,and the therapeutic efficacy was evaluated Results All the patients were follow up for a median time of 18.5 months.Successful DSA-guided arterial embolization was accomplished in all patients.Seven patients(9 lesions in total)initially received CT-guided radiofrequency ablation(RFA),and tumor reoccurred in 2 patients,who had to receive RFA once more.Four patients(5 lesions in total)initially received CT-guided microwave ablation(MWA),and tumor reoccurred in one patient,who had to receive MWA again.According to mRECIST criteria,the 6-month,12-month and 18-month objective response rates(ORR)were 72.7%(8/11),45.5%(5/11)and 18.2%(2/11)respectively,the 6-month,12-month and 18-month overall survival rates were 81.8%(9/11),63.6%(7/11)and 27.3%(3/11)respectively,with a median survival time of 13.2 months.The postoperative one-month and 3-month VAS scores were(2.42±1.25)points and(1.91±1.24)points respectively,which were strikingly lower than preoperative(6.78±1.13)points,the differences were statistically significant(P＜0.05).After surgery,3 patients developed pleural effusion,which disappeared after puncture and drainage treatment,and 2 patients developed fever,which was improved after symptomatic treatment.One patient died of respiratory failure six months after treatment.Conclusion Arterial embolization combined with local ablation can improve the symptoms of pain and prolong the survival time of patients with chest wall tumors.This combination therapy is less traumatic and clinically safe,and it can be used as an effective treatment for patients with recurrent and refractory chest wall tumors.

Coronary microvascular dysfunction （CMD） is one of the important causes of myocardial ischemia and non-obstructive coronary artery ischemic symptoms. However， effective diagnostic methods and targeted treatment strategies for CMD are currently lacking. According to traditional Chinese medicine （TCM）， the comorbidity theory of "blood-vessel-cardiac collaterals" plays a central role throughout the entire development process of CMD. It suggests that in the clinical diagnosis and treatment of CMD， the treatment of blood， vessels， and cardiac collaterals should not be neglected. In light of this， insect medicines， known for their efficacy in promoting blood circulation， resolving stasis， and alleviating spasms， hold promise as a potential treatment for CMD. However， there is currently no research or summary on the use of insect medicines for the treatment of CMD. Therefore， this article took the comorbidity theory of "blood-vessel-cardiac collaterals" as the starting point and divided the pathogenesis of CMD into five evolution stages： Beginning in the blood （changes in blood components and hemorheology）， progressing in the vessels （atheromatous plaque formation and unstable plaques）， occurring in the cardiac collaterals （microvascular endothelial damage and microvascular constriction and spasms）， ending in the cardiac collaterals （microvascular remodeling）， and resulting in energy metabolism disorders throughout the process， so as to explore the pathogenesis and evolution of CMD. In addition， based on the modern pharmacological research on insect medicines， this article discussed the clinical application of insect medicines in the treatment of CMD from four aspects： Promoting blood circulation and removing blood stasis to relieve vessels' obstruction， relieving spasms to alleviate pain， combating poison with poison to disperse stagnation， and tonifying cardiac collaterals to nourish the heart， which aims to provide a theoretical basis for the use of TCM in treating CMD， broaden the scope of medication， and improve clinical efficacy.

Objective:To construct a double-layer bone-on-a-chip containing bone matrix, with which the process of osteoblast and osteoclast differentiation in vitro is stimulated, aiming to provide a new platform for the development of osteoporosis medications. Methods:Software WorkSoild was used to design the double-layer and double-channel bone-on-a-chip and the template was fabricated by photolithography. With polydimethylsiloxane (PDMS) as the raw material, the main body of the chip was prepared by mold fabrication. The inlets and outlets of the four channels of the culture room were separated with bovine cortex bones and sealed with liquid storage columns. In the chip verification experiment, chips were divided into osteogenic and osteoclastic induction groups and osteogenic and osteoclastic control groups. In the osteogenic and osteoclastic induction groups, precursor cells of mouse embryonic osteoblast, MC3T3-E1 and mouse macrophage RAW264.7 were inoculated on the chip separately. Osteogenic induction lasted 14 days and osteoclastic induction 7 days. MC3T3-E1 cells and RAW264.7 cells were not induced in the osteogenic and osteoclastic control groups. The following indicators were observed: (1) Appearance and sealing performance of the chip: After the chip was prepared, photos were taken to observe its appearance and sealing tests were conducted to observe its sealing performance. (2) Biocompatibility: At 3 days after MC3T3-E1 cells were inoculated onto the chip and cultured and at 1, 3 and 5 days after RAW264.7 cells were inoculated onto the chip and cultured, the cell survival was observed with calcein acetoxymethyl ester/propidium iodide (AM/PI) staining and Cell Counting Kit 8 (CCK-8). (3) Osteogenic differentiation: Alkaline phosphatase (ALP) staining and alizarin red staining were performed on the cells in the osteogenic induction group to observe the osteogenic induction. RNA was collected from the osteogenic induction group and the osteogenic control group, the expression of osteoblast marker Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and type I collagen (COL1A1) was detected by real-time florescent quantitative PCR (qPCR), and the differentiation degree and osteogenic ability of osteoblasts were observed. (4) Osteoclast differentiation: tartrate-resistant acid phosphatase (TRAP) staining was performed on cells in the osteoclastic induction group to observe osteoclast differentiation. RNA was extracted from the osteoclastic induction group and the osteoclastic control group for qPCR of osteoclast differentiation-related genes, and the expression levels of the osteoclast marker gene TRAP, cathepsin K (CTSK) and dendritic cell specific transmembrane protein (DC-STAMP) were detected.Results:The double-layer bone-on-a-chip containing bone matrix was 3 cm×3 cm in size and transparent as a whole. The structure of the system on the chip system was compact and had no seepage. It was shown by calcein AM/PI staining that at 3 days after MC3T3-E1 cells and RAW264.7 cells were cultured, very few red fluorescent dead cells were found. CCK-8 test showed that within 5 days after being cultured, the cell viability was all above 90%, indicating that the biocompatibility of the chip was good and the cells could survive and proliferate normally. The results of ALP and alizarin red staining showed that MC3T3-E1 cells successfully differentiated into osteoblasts and produced calcified nodules in the osteogenic induction group at 14 days after the induction. The qPCR results showed that the relative expression level of RUNX2 in MC3T3-E1 cells in the osteogenic induction group was 4.98±0.74, which was significantly higher than that of the control group (0.99±0.03) ( P<0.01). The relative expression level of OCN in MC3T3-E1 cells was 7.98±0.76, which was significantly higher than that of the control group (1.00±0.06) ( P<0.01). The relative expression level of COL1A1 in MC3T3-E1 cells was 7.07±0.56, which was significantly higher than that of the control group (0.97±0.03) ( P<0.01). The TRAP staining results showed that the RAW264.7 cells in the osteoclastic induction group differentiated to giant multinucleated osteoclasts, and TRAP protein was expressed in large quantity in the osteoclasts. The results of qPCR showed that the relative expression level of TRAP in RAW264.7 cells in the osteoclastic induction group was 3.35±0.37, which was significantly higher than that of the control group (1.01±0.06) ( P<0.01). The relative expression level of CTSK in RAW264.7 cells was 3.46±0.79, which was significantly higher than that of the control group (1.01±0.05) ( P<0.01). The relative expression level of DC-STAMP in RAW264.7 cells was 1.92±0.12, which was significantly higher than that of the control group (0.98±0.08) ( P<0.01). Conclusions:The double-layer bone-on-a-chip containing bone matrix is compact in structure, can be cultured in vitro for a long time, has good biocompatibility and can be used for inducing osteogenic and osteoclast differentiation. Therefore, it is expected to provide a new research platform for exploring the mechanism of osteoporosis and medication screening.

Objective:Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube.Methods:3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length.Results:In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice.Conclusion:MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

Objective·To establish various in vitro screening systems for the discovery of peptide inhibitors targeting the interaction between small ubiquitin-like modifier(SUMO)-activating enzyme subunit 1(SAE1)and subunit 2(SAE2),as well as to evaluate their advantages,disadvantages,and applicability to this research.Methods·The DNA fragments encoding human SAE1 and SAE2 were cloned into vector pET-28a,respectively,to generate protein SAE1 and SAE2.Purified proteins were used to establish screening assays,including isothermal calorimetry(ITC),fluorescence polarization(FP),surface plasmon resonance(SPR)and a fluorescence assay based on the SAE enzyme activity.The inhibitory activity of peptide candidates in different screening systems was examined,and their performance in terms of sensitivity,robustness,throughput and cost was evaluated.Results·The dissociation constant(Kd)of in vitro SAE1 and SAE2 interaction was determined to be 0.96 μmol/L by ITC,and PEPT7 was identified as the most potent peptide.However,the tracer of FP,which was derived from PEPT7,was not up to snuff due to its low affinity with SAE2.In the SPR assay,the Kd value(=1.13 μmol/L)of SAE1 and SAE2 interaction was in line with the results from ITC.The SAE enzyme activity-based screening assay revealed that HP1B,the most effective peptide,inhibited SAE with an half-maximal inhibitory concentration(IC50)of 15.72 μmol/L.The affinity of HP1B for SAE1 was determined to be 34.4 μmol/L by SPR.Conclusion·Several common screening systems for protein-protein interation(PPI)inhibitors are established and compared.Among them,ITC does not allow for high-throughput screening and it is difficult to accurately evaluate the low-affinity polypeptides with insignificant binding heat.The feasibility of FP relies heavily on the strong affinity between a tracer peptide and the protein target,making it unsuitable for the screening and optimization of low-affinity peptides.SPR is highly sensitive but the cost is high.The SAE enzyme activity-based assay stands out because it is a combination of high sensitivity,robustness,throughput and acceptable cost.

Objective To investigate the imaging features of papillary tumor of the pineal region(PTPR).Methods The ima-ging data of 10 patients with PTPR confirmed by operation and pathology were analyzed retrospectively.Results All lesions were located in the posterior commissure area of the posterior inferior wall of the third ventricle.All lesions were heterogeneously hyper-intensity on T1WI and hyperintensity on T2WI.Multiple small cysts or microcapsules signal intensity were observed within the tumor.Of all 10 lesions,there were 9 lesions with high signal intensity within or at the edge of the lesion on T1WI.All lesions showed restricted diffusion.All 10 cases showed uneven and obvious enhancement patterns.Midbrain tectum was compressed and moved backward in 5 cases,moved downward in 2 cases,moved forward and downward in 1 case,and was not clearly displayed in other 2 cases.One case was disseminated and 1 case was hyperperfusion.There were all 10 cases with obstructive hydrocephalus and equal or slightly high density on CT imaging,and 4 cases with calcification.Conclusion Imaging characteristics of PTPR included the lesions centered on the posterior commissure,compressed tectum with backward and downward,multiple small cysts or micro-capsules components within the tumor,hyperintensity on T1WI,and uneven and obvious enhancement patterns.

Objective:To explore the clinical effect of composite skin transplantation combined with systemic rehabilitation in the treatment of extensive scar contracture deformity around the popliteal fossa in children after burns.Methods:A retrospective observational research method was adopted. Seventeen children with extensive scar contracture deformities around the popliteal fossa after burns who met the inclusion criteria and were admitted to the First Affiliated Hospital of Air Force Military Medical University from March 2018 to April 2022 were selected. Among them, there were 10 males and 7 females, aged 2-11 years, with scar contracture deformities lasting from 10 months to 9 years, all located around the popliteal fossa, 10 cases of right popliteal fossa, 5 cases of left popliteal fossa, 2 cases of bilateral popliteal fossa, scars around the popliteal fossa result in a knee joint extension angle of only 95° to 115°. The scar contracture during surgery was thoroughly released, joint mobility was restored, so as to form a secondary wound range of 10 cm×8 cm-20 cm×13 cm. In stage Ⅰ, after completely releasing the scar contracture, the wound was covered with negative pressure closure drainage (VSD) for 2-3 days. In stage Ⅱ, a large autologous blade thick scalp and allogeneic decellularized dermal matrix composite graft was performed to repair the wound around the popliteal fossa. After 8-10 days of surgery, the dressing was changed to check the survival of the skin graft. One week after the skin graft survived, a 12 month orderly knee joint function training was conducted under the guidance of a rehabilitation therapist. Postoperative sequential treatment with a combination of strong pulsed light and ultra pulsed carbon dioxide lattice laser for 5-7 courses of significant scar hyperplasia in the skin graft area and edges.Results:15 cases of pediatric patients had good skin graft survival; One patient developed a wound due to partial displacement of the transplanted autologous scalp, and one patient developed a plasma swelling under the limb graft, which was drained through an opening. Two patients underwent dressing changes for 3 weeks before the wound healed. After follow-up for 6 to 36 months, the elasticity and appearance of the skin graft were similar to those of a medium thickness skin graft. Children with knee joint contracture were able to fully extend to 180°, and knee joint function was significantly improved. There was no scar formation or hair loss in the donor skin area.Conclusions:The combination of composite skin transplantation and systematic rehabilitation has a good effect on the treatment of extensive scar contracture around the popliteal fossa in children after burns, avoiding the problem of scars left in the donor area due to autologous skin grafting.

Objective:To explore the real experience and needs of lymphoma patients during chimeric antigen receptor T cell (CAR-T) therapy, so as to provide guidance for developing nursing intervention strategies.Methods:The phenomenological research method was used to conduct semi-structured interviews with 13 lymphoma patients receiving CAR-T therapy, and the interview data was analyzed using the Colaizzi 7-step analysis method.Results:Three themes were extracted, including diverse symptom perception (systemic symptoms such as fever and fatigue, as well as multiple system symptoms such as breathing, digestion, and nerves), complex emotional experience interweaving (coexistence of hope and doubt, changes and loss of environmental adaptability, and a variety of negative emotions), and urgent social needs (treatment related information needs, desire for medical and nursing staff's attention and help, family emotional support, and home rehabilitation continuing care) .Conclusions:Lymphoma patients experience significant physical and mental pain during CAR-T therapy. Medical and nursing staff should provide patients with comprehensive support to help them identify and improve physical discomfort symptoms, reduce psychological burden, meet physical and mental needs, and promote disease recovery.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.