Objective To investigate the expression of ubiquitin binding enzyme E2T (UBE2T) in breast cancer (BRCA) and its role and mechanism in the prognosis of BRCA patients. Methods The Tumor Genome Atlas (TCGA) database was used to analyze UBE2T expression in BRCA tissues, and the effects of UBE2T expression on disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan-Meier (KM) survival curve. In vitro, real-time quantitative PCR and Western blot were used to confirm the knock-down and overexpression efficiency, to analyze its effect on tumor cell biological behavior. The effect of UBE2T on cell epithelial–mesenchymal transition (EMT) was studied by Western blot. A xenograft tumor model was established to verify the effect of UBE2T knockdown on the growth of BRCA cells in vivo. Results The UBE2T expression levels in BRCA and adjacent tissues were statistically different (P<0.001), and the expression was increased in tissues with distant metastasis or late stage (all P<0.05). The DFS and OS were decreased in the UBE2T high-level group (both P<0.05). UBE2T was highly expressed in MCF-7 and MDA-MB-231 cells and lowly expressed in MDA-MB-361 cells (all P<0.01). After UBE2T was silenced by shRNA, the proliferation ability of tumor cells significantly decreased, whereas it increased after UBE2T up-expression (all P<0.05). The apoptotic rates of MCF-7 and MDA-MB-231 cells in the silent groups were significantly higher than those in the shNC groups, while the apoptotic rates of MAD-MB-361 cells in the overexpression group decreased (all P<0.001). The mobility in the knockdown groups were lower than in the shNC groups, while the mobility in the overexpression group significantly increased (both P<0.01). The migration and invasion cells in the shUBE2T groups were lower than those in the shNC groups, and the migration and invasion cells in the UBE2T group were higher than those in the vector group (all P<0.01). Downregulation of UBE2T decreased the expression levels of N-cadherin, Snail, and Vimentin (all P<0.05) and increased that of E-cadherin; however, the result of UBE2T upregulation was opposite (all P<0.01). TIMER results showed that UBE2T was positively correlated with E-cadherin (P<0.001), N-cadherin (P=0.013), and Snail (P<0.001) and negatively correlated with Vimentin (P<0.001). In vivo experiments showed that downregulation of UBE2T slowed down the growth of transplanted tumors. Conclusion UBE2T is highly expressed in BRCA tissues and may affect the prognosis. UBE2T can promote the proliferation of BRCA cells, inhibit apoptosis, and increase the migration and invasion abilities by changing the expression levels of EMT-related proteins.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

The activation proteins released by fibroblasts in the tumor microenvironment regulate tumor growth, migration, and treatment response, thereby influencing tumor progression and therapeutic outcomes. Owing to the proliferation and metastasis of tumors, fibroblast activation protein (FAP) is typically highly expressed in the tumor stroma, whereas it is nearly absent in adult normal tissues and benign lesions, making it an attractive target for precision medicine. Radiolabeled agents targeting FAP have the potential for targeted cancer diagnosis and therapy. This comprehensive review aims to describe the evolution of FAPI-based radiopharmaceuticals and their structural optimization. Within its scope, this review summarizes the advances in the use of radiolabeled small molecule inhibitors for tumor imaging and therapy as well as the modification strategies for FAPIs, combined with insights from structure-activity relationships and clinical studies, providing a valuable perspective for radiopharmaceutical clinical development and application.

OBJECTIVE To evaluate the clinical efficacy of modified Zhujing Pills in the treatment of dry age-related macular degeneration(AMD)of liver and kidney insufficiency type.METHODS 64 patients with dry AMD of liver and kidney insufficiency type were randomly divided into an experimental group and a control group,32 patients each.The control group was given oral treat-ment with Laishiding capsules,and the experimental group was given oral treatment with modified Zhujing Pills granules.The treatment course for both groups was 3 months.Before and after treatment,the patients in the two groups were observed for TCM syndrome scores,visual acuity,fundus autofluorescence(AF),changes in drusen area within 5 mm of the fovea,and plasma superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)levels.RESULTS After treatment,the scores of TCM syndromes in the experimental group were significantly reduced(P＜0.05,P＜0.01),and the efficacy of TCM syn-dromes was better than that of the control group(P＜0.01);the visual acuity of the patients in the experimental group was significantly improved,AF was significantly weakened and the area of drusen was reduced(P＜0.05,P＜0.01),which were better than those in the control group(P＜0.05);the plasma SOD and GSH-Px activities of the experimental group were increased,and the MDA level was significantly lowered(P＜0.05,P＜0.01),which were better than the control group(P＜0.05).CONCLUSION Modified Zhujing Pills can reduce fundus AF intensity,decrease macular drusen area,improve visual acuity,and reduce TCM syndrome scores in pa-tients with dry AMD.The therapeutic mechanism may be related to its antioxidant effect.

Methods: Study participants were recruited from Shuguang East Hospital, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, and Shanghai Municipal Hospital of Traditional Chinese Medicine, affiliated with Shanghai University of Traditional Chinese Medicine, from April 15 to September 15, 2021. They were categorized into three groups: healthy controls (Group 1), CHD patients without a history of ischemic stroke (Group 2), and CHD patients with a history of ischemic stroke (Group 3). The wrist pulse signals of the study participants were non-invasively collected using a pulse diagnosis instrument. The linear time-domain features and nonlinear time-series multiscale entropy (MSE) features of the pulse signals were extracted using time-domain analysis and the MSE methods, which were subsequently compared between groups. Based on these extracted features, a recognition model was developed using a random forest (RF) algorithm. The classification performance of the models was evaluated using metrics, including accuracy, precision, recall, and F1-score derived from confusion matrix as well as the area under the receiver operating characteristics (ROC) curve (AUC). Results: A total of 189 participants were enrolled, with 63 in Group 1, 61 in Group 2, and 65 in Group 3. Compared with Group 1, Group 2 showed significant increases in pulse features H2/H1, H3/H1, W1, W2, and W2/T, and decreased in MSE1 – MSE7 (P < 0.05), while Group 3 showed significant increases in pulse features T5/T4, T, H1/T1, W1, W2, AS, and Ad, and decreased in MSE1 – MSE20 (P < 0.05). Compared with Group 2, Group 3 demonstrated notable increases in H1/T1 and As (P < 0.05). The RF model achieved precision of 80.00%, 61.54%, and 61.54%, recall of 74.29%, 60.00%, and 68.97%, F1-scores of 70.04%, 60.76%, and 65.04%, and AUC values of 0.92, 0.74, and 0.81 for Groups 1, 2, and 3, respectively. The overall accuracy was 67.69%, with micro-average AUC of 0.83 and macro-average AUC of 0.82. Conclusion Differences in pulse features reflect variations in arterial compliance, peripheral resistance, cardiac afterload, and pulse signal complexity among healthy individuals, CHD patients without a history of ischemic stroke, and those with such a history. The developed pulse-based recognition model holds the potential in distinguishing between these three groups, offering a novel diagnostic reference for clinical practice.

Objective To investigate the risk factors and prevention strategies of postoperative delirium in Stanford B aortic dissection. Methods Clinical data of the patients diagnosed with Stanford B aortic dissection and undergoing endovascular aortic repair from January 2020 to August 2021 in our department were retrospectively collected. Patients were divided into a non-delirium group and a delirium group according to the presence of postoperative delirium. The risk factors for postoperative delirium after Stanford type B aortic dissection and the protective effect of dexmedetomidine on delirium were analyzed. Results A total of 659 patients with Stanford type B aortic dissection were enrolled, including 540 males and 119 females with a median age of 58.00 (41.00, 75.00) years. There were 450 patients in the non-delirium group, and 209 patients in the delirium group. There was no statistical difference in gender, body mass index, hypertension, hyperlipidemia, smoking and drinking history, cholesterol triglyceride level, or creatinine glomerular filtration rate (P＞0.05). Age was an independent risk factor for postoperative delirium in Stanford type B aortic dissection (OR=1.392, 95%CI 1.008-1.923, P=0.044). Moreover, whether dexmedetomidine was used or not had no effect on the duration of postoperative delirium (χ2=4.662, P=0.588). Conclusion Age is an independent risk factor for postoperative delirium in patients with Stanford type B aortic dissection. The incidence of postoperative delirium in young patients is lower than that in the patients with middle and elderly age, and it may be of reference value to prevent postoperative delirium. Dexmedetomidine has no significant effect on controlling the duration of postoperative delirium.

Primary prostate signet ring cell carcinoma (PPSRCC) is one of the extremely rare malignant tumors in the male urogenital system, and its diagnosis mainly relies on pathological and immunohistochemical examination. Compared with typical prostate cancer, PPSRCC is characterized by more aggressive with less treatment response and poor prognosis. Current researches on the pathogenesis, clinical manifestations, pathological characteristics, diagnosis, treatment and prognosis of PPSRCC were reviewed.

Background and Objectives: Myocardial ischemia-reperfusion injury (MIRI) refers to the damage of cardiac function caused by restoration of blood flow perfusion in ischemic myocardium. However, long non-coding RNA prostate androgen regulated transcript 1 (PART1)’s role in MIRI remain unclear. Methods: Immunofluorescence detected LC3 expression. Intermolecular relationships were verified by dual luciferase reporter assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry and transferase-mediated dUTP nick-end labeling (TUNEL) assays analyzed cell viability and apoptosis. The release of lactate dehydrogenase was tested via enzyme-linked immunosorbent assay (ELISA). Left anterior descending coronary artery surgery induced a MIRI mouse model. Infarct area was detected by 2,3,5-triphenyltetrazolium chloride staining. Hematoxylin and eosin staining examined myocardial injury. ELISA evaluated myocardial marker (creatine kinase MB) level. Results: PART1 was decreased in hypoxia/reoxygenation (H/R) induced AC16 cells and MIRI mice. PART1 upregulation attenuated the increased levels of Bax, beclin-1 and the ratio of LC3II/I, and enhanced the decrease of Bcl-2 and p62 expression in H/R-treated cells.PART1 upregulation alleviated H/R-triggered autophagy and apoptosis via miR-302a-3p. Mechanically, PART1 targeted miR-302a-3p to upregulate transcription factor activating enhancer-binding protein 2C (TFAP2C). TFAP2C silencing reversed the protected effects of miR-302a-3p inhibitor on H/R treated AC16 cells. We further established TFAP2C combined to dual-specificity phosphatase 5 (DUSP5) promoter and activated DUSP5. TFAP2C upregulation suppressed H/R-stimulated autophagy and apoptosis through upregulating DUSP5.Overexpressed PART1 reduced myocardial infarction area and attenuated MIRI in mice. Conclusion PART1 improved the autophagy and apoptosis in H/R-exposed AC16 cells through miR-302a-3p/TFAP2C/DUSP5 axis, which might provide novel targets for MIRI treatment.

Objective:To explore the effect of hip arthroscopy on improving the cross-sectional kinematics of the lower limbs in patients with femoral acetabular impingement (FAI).Methods:Eight FAI patients who underwent hip arthroscopy in the Department of Sports Medicine of Peking University Third Hospital from October 2021 to February 2022 were prospectively included, including 3 males and 5 females, with an age of 35.3±13.0 years (range 17-53 years), height of 168.0±12.8 cm (range 154-192 cm), weight of 61.1±8.5 kg (range 52-74 kg) and body mass index of 21.7±2.6 kg/m 2 (range 17.6-24.5 kg/m 2). There were 3 left hips and 5 right hips. FADIR (flexion, adduction and internal rotation test) was positive in all patients and FABER (flexion, abduction and external rotation test) was positive in 4 patients. Modified Harris hip score (mHHS) and visual analogue scale (VAS) of the affected hip joint were compared before the surgery and at the follow-up of 10 months. By using a markerless motion capture system, foot progression angles during normal gait, double-leg squat, forward lunge, single-leg standing and stepping in place were measured and compared before the surgery and at the follow-up of 10 months postoperative results. Results:All the 8 patients underwent the surgery successfully and were followed up for 11.0±1.2 months. The mHHS scores before the surgery and at the follow-up of 10 months were 60.9±20.5 vs. 82.9±7.3 with significant difference ( t=-3.07, P=0.018). The iHOT-12 scores before the surgery and at the follow-up of 10 months for the affected hips were 51.4±23.7 vs. 79.2±14.6 with significant difference ( t=-3.76, P=0.007). The VAS scores before the surgery and at the follow-up of 10 months were 4.6±2.3 vs. 1.5±0.9 with significant difference ( t=3.16, P=0.016). There was no significant difference in foot progression angle between the healthy side and the affected side for all movement trials before the surgery and at the follow-up of 10 months ( P>0.05). During normal gait, the postoperative and preoperative foot progression angles for the healthy side and the affected side were 26.52°±5.97 vs. 34.4°±7.20° and 24.41°±3.70° vs. 30.80°±6.43°with significant reduction ( t=2.83, P=0.013; t=3.05, P=0.041). While there was no significant difference in foot progression angles for double-leg squat, forward lunge, single-leg standing and stepping in place before the surgery and at the follow-up of 10 months ( P>0.05). Conclusion:Hip arthroscopy can change the cross-sectional kinematic characteristics of the lower limbs, potentially improving the progression angle in FAI patients.

Objective:To investigate the value of surgical classification and pelvic floor reconstruction in pelvic exenteration for locally recurrent or locally advanced rectal cancer. Methods:A retrospective descriptive study method was used.Perioperative data were collected from 67 consecutive patients with locally advanced or locally recurrent rectal cancer who underwent pelvic exenteration at the Department of Anorectal Surgery,the Second Affiliated Hospital of Navy Military Medical University between November 2021 and November 2022 through the Chinese Combined Pelvic Exenteration Case Database for rectal cancer.The surgical range was divided into two categories:mainly localized in the pelvic cavity(48 cases)and combined with resection of the main tissue of the pelvic wall(1 9 cases).Outcome indexes included:(1)preoperative general data of patients;(2)intraoperative conditions;(3)postoperative recovery and complications(postoperative complications were evaluated by international Clavien-Dindo classification);(4)follow-up(outpatient and telephone follow-up were used to understand the postoperative survival,tumor recurrence and metastasis of patients,and the follow-up time was up to February 28,2023 or the case died).Measurement data are expressed by median(range),and enumeration data are expressed by example(％). Results:In the pelvic resection group,the median age of 48 patients was 57.5 years(range:31-82 years);29 were males and 19 were females;26 of them had locally advanced rectal cancer and 22 had locally recurrent rectal cancer;39 had a history of chemotherapy,immunotherapy or targeted therapy,and 26 had a history of radiotherapy;the median operation time was 425 min(range:240-1 020 min);the median intraoperative blood loss was 500 mL(range:200-4 000 mL);the median time to recovery of intestinal function was 3 d(range:1-9 d);the median recovery time of empty pelvis syndrome was 25.3 d(range:5-105 d);43 patients had postoperative complications＜grade Ⅲ,and of the 5 patients with ≥ grade Ⅲcomplications,2 died of multiple organ failure 7 d after operation,2 patients had surgical hemostasis for massive hemorrhage of pelvic floor wounds after operation,and 1 patient recovered from postoperative respiratory failure after rescue.In the combined pelvic wall resection group,the median age of 1 9 patients was 54.5 years(range:43-76 years);9 were males and 10 were females;4 patients had locally advanced rectal cancer and 15 patients had locally recurrent rectal cancer,all of whom had a history of chemotherapy,immunotherapy or targeted therapy,and 1 5 patients had a history of radiotherapy;the median operation time was 580 min(range:360-960 min);the median intraoperative blood loss was 1 600 mL(range:400-4 000 mL);the median intestinal function recovery time was 3 d(range:2-7 d);the median empty pelvis syndrome recovery time was 62.3 d(range:7-120 d);15 patients had postoperative complications＜grade Ⅲ,and of the 4 patients with grade ≥ Ⅲ,3 patients had surgical hemostatis for postoperative pelvic floor wound bleeding and 1 patient recovered after the second operation for intestinal obstruction.As of February 28,2023 or death,67 patients were followed up for a median of 7.5 months(range:3-1 5 months),and 3 patients died 3-8 months after operation due to rapid tumor progression,severe urinary tract infection,and sudden heart disease during the follow-up period.The remaining 62 cases survived. Conclusion:The surgical classification has guiding significance for preoperative surgical planning in patients with locally advanced or locally recurrent rectal cancer who undergo combined pelvic exenteration,and the method of pelvic floor reconstruction based on biological mesh is safe and feasible in combined pelvic exenteration for locally advanced or locally recurrent rectal cancer.