Objective To analyze the status quo of cognitive frailty (CF) in community elderly patients with chronic obstructive pulmonary disease (COPD) and its correlation with sleep quality, anxiety and depression. Methods Elderly patients with COPD receiving health management in the center were selected from July 2023 to June 2024. The general data of patients were collected and Mini-Mental State Examination (MMSE), Fried Frailty Phenotype (FP), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) were used for investigation, and the above scores were analyzed. All patients were divided into CF group (n=129) and non-CF group (n=319) according to MMSE score and FP score. Univariate and multivariate logistic analyses were used to analyze the influencing factors of CF in elderly COPD patients. Results Pearson correlation analysis showed that MMSE score was significantly negatively correlated with PSQI score and HADS score in elderly COPD patients (P<0.05), and FP score was significantly positively correlated with PSQI score and HADS score (P<0.05). After logistic regression analysis, it was found that education level, marital status and sleep time were protective factors of CF in elderly COPD patients (P<0.05), and PSQI score and HADS score were risk factors of CF in elderly patients with COPD (P<0.05). Conclusion CF in community elderly COPD patients is related to sleep quality, sleep duration and anxiety and depression. It is necessary to take clinical measures to improve the sleep quality and psychological status, so as to avoid or slow down the occurrence of CF.

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

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.

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

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.

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To investigate the sedative effect of remimazolam on ICU elderly patients undergoing mechanical ventilation and its influence on circulatory system.Methods:Using a prospective research approach, 189 ICU elderly patients undergoing mechanical ventilation in Hebei Petro China Central Hospital from October 2021 to June 2023 were selected. The patients were divided into remimazolam group, dexmedetomidine group and propofol group by random number table method with 63 cases in each group. The patients in remimazolam group, dexmedetomidine group and propofol group were sedated with remimazolam, dexmedetomidine and propofol, respectively. The sedation standard time, sedation standard rate, sedation maintenance time and recovery time after drug withdrawal were compared among the three groups. The heart rate, mean arterial pressure (MAP), respiratory rate and pulse oxygen saturation (SpO 2) before medication (T 0) and medication for 15 min (T 1), 30 min (T 2), 1 h (T 3), 6 h (T 4), 12 h (T 5) were recorded. The incidences of bradycardia, hypotension, respiratory depression, body movement and delirium during sedation were recorded. Results:The sedation standard time and recovery time after drug withdrawal in remimazolam group were significantly shorter than those in dexmedetomidine group and propofol group: (22.27 ± 5.31) min vs. (29.45 ± 6.24) and (30.12 ± 5.87) min, (28.66 ± 7.06) min vs. (32.22 ± 6.85) and (34.34 ± 7.24) min, and there were statistical differences ( P<0.05); there were no statistical difference between dexmedetomidine group and propofol group ( P>0.05). The sedation standard rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group: 87.43% (661/756) and 83.60% (632/756) vs. 72.49% (548/756), and there was statistical difference ( P<0.016 7); there was no statistical difference between remimazolam group and dexmedetomidine group ( P>0.016 7). There was no statistical difference in sedation maintenance time among the three groups ( P>0.05). There were no statistical difference in T 0 heart rate, MAP, respiratory rate and SpO 2 among the three groups ( P>0.05). The T 1 to T 5 heart rate and MAP in remimazolam group were significantly higher than those in dexmedetomidine group and propofol group, the T 2 to T 5 heart rate and MAP in dexmedetomidine group were significantly lower than those in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 respiratory rate in remimazolam group was significantly lower than that in dexmedetomidine group, the T 1 to T 5 respiratory rate in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there were statistical differences ( P<0.05). The T 2 to T 5 SpO 2 in remimazolam group and dexmedetomidine group was significantly higher than that in propofol group, and there was statistical difference ( P<0.05). The incidence of bradycardia in remimazolam group was significantly lower than that in dexmedetomidine group: 7.94% (5/63) vs. 25.40% (16/63), the incidence of hypotension was significantly lower than that in propofol group: 6.35% (4/63) vs. 23.81% (15/63), and there were statistical differences ( P<0.016 7). The incidence of respiratory depression in remimazolam group and dexmedetomidine group was significantly lower than that in propofol group: 4.76% (3/63) and 1.59% (1/63) vs. 22.22% (14/63), and there was statistical difference ( P<0.016 7). There was statistical difference in incidence of delirium among the three groups ( P<0.05), but there was no statistically significant difference in pairwise comparison ( P>0.016 7). There was no statistical difference in the incidence of body movement among the three groups ( P>0.05). Conclusions:The effect of remimazolam sedation in ICU elderly patients undergoing mechanical ventilation is satisfactory, with little influence on circulation and respiratory system and few adverse reactions.

Objective Space radiation is an important environmental factor affecting the health and efficiency of astronauts.To explore the effects of radiation on electroencephalogram(EEG)signal,and to provide references for further study of the effects of radiation on Central Nervous System(brain)injury.Methods The resting state EEG of radiotherapy volunteers were collected before and after X-ray exposure.The effects of radiation on EEG was studied by means of spectral analysis,nonlinear dynamic characteristic analysis,correlation coefficient analysis and microstate analysis.Results The results show that radiation induced a"slow wave"phenomenon in the EEG spectrum,with a decrease in Gravity Frequency,Sample Entropy,and Lempel-Ziv Complexity,and an increase in Fatigue Index.The average duration and frequency of EEG microstate C both significantly decreased,and the proportion of time for microstate D decreased,while the average correlation coefficient between microstates A and C increased.Conclusion A decrease was induced by radiation in neuronal excitability,which may affect cognitive brain networks and brain attention.This study can provide reference for the study of radiation damage to the Central Nervous System(brain).