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.

Objective:To analyze the clinicopathological characteristics and prognostic factors of patients with Castleman disease (CD).Methods:A retrospective case-series study was conducted. A total of 85 patients newly diagnosed with CD in the First Affiliated Hospital of Air Force Medical University between July 2007 and August 2024 were collected. Their clinical characteristics and prognostic factors were analyzed.Results:Among the 85 patients, 45 had unicentric Castleman disease (UCD) and 40 had multicentric Castleman disease (MCD). In the UCD group, females were more commonly affected (64.4%, 29/45), with a median age of onset of 39 years. The primary lesions were mainly located in the retroperitoneum, neck, abdomen, and axilla; and the hyaline vascular subtype was the predominant pathological type (69.4%, 25/36). In the MCD group, males were more frequently affected (62.5%, 25/40), with a median age of onset of 50 years; and the plasmacytic subtype was the main pathological type (68.2%, 15/22). Compared with UCD patients, MCD patients presented more systemic symptoms and signs [85.0% (34/40) vs. 13.3% (6/45), χ2 = 43.66, P < 0.001], splenomegaly [42.5% (17/40) vs. 2.2% (1/45), χ2 = 20.58, P < 0.001], hepatomegaly [25.0% (10/40) vs. 0 (0/45), χ2 = 10.46, P = 0.001], edema or effusion in serous cavity [67.5% (27/40) vs. 8.9%(4/45), χ2 = 31.40, P < 0.001], hematological system involvement [32.5% (13/40) vs. 0 (0/44), χ2 = 16.92, P < 0.001], and renal involvement [22.5% (9/40) vs. 2.3%(1/44), χ2 = 6.36, P = 0.012]. Laboratory findings showed that the levels of hemoglobin and albumin in MCD patients were lower than those in UCD patients, while white blood cell count in MCD patients was higher than that in UCD patients. Additionally, MCD patients exhibited elevated levels of C-reactive protein, interleukin-6, vascular endothelial growth factor, erythrocyte sedimentation rate, and ferritin compared to UCD patients (all P < 0.05). Among UCD patients, 40 cases underwent simple surgical resection, with no deaths during follow-up and the 5-year overall survival (OS) rate of 100.0%; among MCD patients, 34 cases received chemotherapy, 4 received siltuximab, 3 died during follow-up with a 5-year OS rate of 87.5%; and there was no statistically significant difference in OS between the MCD and UCD groups ( χ2 = 3.67, P = 0.055). Among MCD patients, the OS of those with renal involvement (9 cases) was worse than that of those without renal involvement (31 cases) ( χ2 = 8.39, P = 0.004). Conclusions:CD is a highly heterogeneous disorder. Surgical resection is the primary treatment for UCD, with a favorable prognosis. Chemotherapy is the main treatment for MCD, with a relatively poor prognosis.

Objective Fasting hypometabolism regulation technology has broad application potential in long-term space flight and survival in extreme extraterrestrial environments.In-depth research on the substrate conversion of energy metabolism and the formation of new steady states under fasting hypometabolism will provide theoretical basis and experimental data support for formulating effective prolonged fasting application mode.Methods 30 SD rats were randomly divided into control group and fasting group(fasting for 1,2,3,and 5 days).Blood biochemical examination,qRT-PCR,and western blotting were performed to analyze the body weight,blood biochemistry,and expression changes of genes and proteins related to glucose and lipid metabolism during different fasting periods.Results Prolonged fasting significantly reduced the body weight,blood glucose,and triglyceride levels of rats;increased the blood ketone level,and replaced glucose as the main energy substance in the body.There are temporal and tissue-specific changes as a whole.Hepatic and renal gluconeogenesis play major roles respectively during different fasting periods.As the fasting time prolongs,the level of hepatic gluconeogenesis gradually decreases,the content of FFA in the blood increases,the expression level of genes related to fat synthesis decreases,fatty acid oxidation is enhanced,and the expression level of the key gene HMGCS2 for ketone body generation increases.Conclusion During prolonged fasting,there is a significant conversion of glucose-ketone energy supply substrates,and a new steady state of energy metabolism mainly supplied by ketone bodies is formed within 2-5 days of fasting.The body maintains a low metabolic state by regulating changes in key genes in pathways such as glucose and lipid metabolism.

Objective To analyze changes in sleep,mood state,and brain function in healthy populations living in near-sea-level environments before and after exposure to high-altitude environment,and to explore the correlations between regional brain functional changes and variations in sleep and mood states.Methods A total of 45 healthy volunteers were enrolled.The participants came from regions of near-sea-level altitudes and were exposed to the high-altitude environment for a short period of time.The Pittsburgh Sleep Quality Index(PSQI),Zung Self-Rating Depression Scale(SDS),Patient Health Questionnaire-9(PHQ-9),Zung Self-Rating Anxiety Scale(SAS),and Generalized Anxiety Disorder-7(GAD-7)were administered to assess sleep quality as well as depressive and anxiety symptoms at 4 time points—prior to high-altitude exposure,immediately after exposure,one month after returning to low-altitude regions,and three months after returning to low-altitude regions.Resting-state functional magnetic resonance imaging(rs-fMRI)data were collected before and after high-altitude exposure,and regional brain functional parameters,including the amplitude of low-frequency fluctuations(ALFF)and functional connectivity strength,were analyzed.Statistical analyses were performed,including a linear mixed-effects model to evaluate longitudinal changes in scale scores,paired-sample t-tests to compare brain function differences before and after exposure,and Pearson correlation analyses to examine the relationship between brain functional changes and alterations in sleep and mood states.Results Compared with the pre-exposure findings,the participants exhibited significantly increased PSQI scores(8.89±4.41 vs.5.08±2.69,P<0.05)and PHQ-9 scores(3.60±4.19 vs.1.54±2.30,P<0.05)immediately after high-altitude exposure.One month after returning to the low-altitude environment,both sleep and depression scores decreased relative to the findings immediately after exposure(PSQI:3.88±2.13 vs.8.89±4.41,P<0.05;PHQ-9:1.50±2.25 vs.3.60±4.19,P<0.05)and showed no statistically significant difference compared with the pre-exposure findings(P>0.05).Three months after returning to near-sea-level environment,sleep,depression,and anxiety scores were all reduced compared with the findings immediately after exposure(PSQI:3.76±2.31 vs.8.89±4.41,P<0.05;PHQ-9:1.24±2.13 vs.3.60±4.19,P<0.05;SAS:23.84±5.93 vs.27.93±7.05,P<0.05),also showing no significant difference compared with the pre-exposure levels(P>0.05).Brain function analysis revealed that,relative to the pre-exposure levels,ALFF in the bilateral superior temporal gyrus,insula,and dorsolateral prefrontal cortex(DLPFC)increased after high-altitude exposure(P<0.05),and that functional connectivity strength in the DLPFC was also elevated(P<0.05).Furthermore,changes in DLPFC functional connectivity strength were positively correlated with changes in sleep and mood scores(P<0.05).Conclusion High-altitude exposure has a significant impact on the sleep,mood states,and brain function of populations from near-sea-level regions,and DLPFC,in particular,is closely associated with changes in sleep and mood states.The findings of this study provide a theoretical basis for health management and intervention strategies in high-altitude environments.

Evoked Potentials ; Social Isolation ; Attention ; Humans

Objective To explore the application value of modified prophylactic ileostomy in natural orifice specimen extraction surgery(NOSES)for patients with mid-low rectal cancer.Methods We retrospectively analyzed 63 patients who received prophylactic ileostomy in NOSES for mid-low rectal cancer in our hospital from September 2017 to May 2023.The patients were divided into the observation group(those who received modified ileostomy,n=31)and the control group(those who received conventional loop ileostomy,n=32)according to different ostomy methods.The operation time of ostomy,operation time of ostomy reversal surgery,early-stage complications(stoma leakage,peristomal dermatitis,stoma pain,peristomal trocar hole infection,stoma bleeding,stoma ischaemic necrosis,stoma oedema,peristoma skin-mucosal separation and stoma proximal bowel obstruction)and long-stage complications(stoma stenosis,stoma retraction,stoma prolapse,parastomal hernia),tumor recurrence and death of the two groups were compared and analyzed.Results Both prophylactic ileostomy and ostomy reversal surgery were successfully completed in all the 63 cases.The operation time of ostomy in the observation group was 7(6-8)min,which was significantly shorter than that of 23(21-24)min in the control group(Z=-6.853,P=0.000),and the operation time of ostomy reversal surgery in the observation group was(63.2±5.7)min,which was significantly shorter than(93.5±4.7)min in the control group(t=-23.109,P=0.000).Neither stoma bleeding nor stoma ischaemic necrosis were observed in both groups.The incidence of stoma pain in the observation group was lower than that in the control group[6.4％(2/31)vs.65.6％(21/32),x2=21.766,P=0.000].The incidence of peristomal incision infection in the observation group was lower than that in the control group[0％(0/31)vs.53.1％(17/32),P=0.000].There was no stoma stenosis in both groups.There were 3 cases of parastomal hernia,1 case in the observation group and 2 cases in the control group,the difference of the incidence being not statistically significant(P=1.000).There was 1 case of stoma retraction and 1 case of stoma prolapse in the control group.All the 5 cases with complications received prompt treatment in the second ostomy reversal surgery.Follow-up visits for 6-60 months in the 63 cases showed no tumor recurrence or death.Conclusion Modified prophylactic ileostomy in NOSES for patients with mid-low rectal cancer is safe,feasible,and easy to operate,having certain practicality and promotion value.

Studies have shown that ABO blood group is related to the susceptibility and disease progression of SARS-CoV-2 infection, and most studies indicated that group O individuals were less likely to get infected while group A conferred a higher susceptibility to infection and propensity to severe disease. ABO blood group antigens are oligosaccharides expressed on red cells and other tissues. People with different ABO blood type have different susceptibility to a variety of pathogens, including SARS-CoV-2. There are several hypotheses to explain the differences in SARS-CoV-2 infection between ABO blood group individuals. Firstly, anti-A and/or anti-B antibodies could bind to corresponding antigens on the viral envelope and contribute to viral neutralization, thereby preventing target cell from being infected. The SARS-CoV-2 virus and SARS-CoV spike (S) proteins may be bound by anti-A isoagglutinin, which may block interactions between virus and angiotensin-converting-enzyme-2-receptor, thereby preventing entering into lung epithelial cells. Secondly, the receptor binding domain (RBD) of S protein domain can bind to antigen A expressed in respiratory epithelium and promote its infection to respiratory epithelial cells. In conclusion, most studies indicated that group O may be associated with a lower risk of SARS-CoV-2 infection while group A with a higher risk along with severe disease, and the related mechanism needs to be further studied.

Objective: To explore the application value of 3.0 T MultiVane XD (MVXD) technique in female patients with uterine adenomyosis and fibroids. Methods: Patients diagnosed with uterine fibroids with ultrasound and suspected of adenomyosis were involved prospectively from March to May 2018, 3.0 T pelvic MRI examinations were performed during peri-ovulatory period. Axialconventional turbo spin echo (TSE) T₂WI, axial MVXD T₂WI, sagittal conventional TSE T₂WI and MVXD sagittal T₂WI were acquired. Two observers rated those 4 series in the aspects of sharpness of uterine border, motion artifacts, identification capability of lesions, confidence of diagnosis and overall image quality. Cohen Kappa analysis was used to evaluate the consistency of scores between 2 observers. Scores of TSE T₂WI and MVXD T₂WI qualities were compared using Wilcoxon matched-pairs signed-ranks test. Results: Twenty patients were enrolled. Axial conventional TSE T₂WI, axial MVXD T₂WI were aquired on all of them. Sagittal conventional TSE T₂WI, sagittal MVXD T₂WI were aquired on 19 among them. Nine patients had only obvious adenomyosis, 6 had only uterinefibroids, and 5 had adenomyosis and uterine fibroids. Compared to conventional TSE technique, scores of two observers in the sharpness of uterine border, motion artifacts, and overall image quality is higher by MVXD with significant difference (P<0.05). The Kappa values for image quality scores of two observers ranged from 0.615 to 0.971, the agreement was good or very good. Conclusion Applying MVXD T₂WI technique to patients with uterine fibroids and adenomyosiscould improve image quality, without sacrificing the ability to recognize and diagnose lesions, compared to conventional TSE T₂WI technique.

The real-time reported data of treated patients from July 2017 to June 2019 Nanxiang Hospital of Jiading District were collected from chest pain center platform. The results showed that the average time of completing ECG examination from the first medical contact was 1.3 to 6.9 min with a median of 1.9 min (1.7, 2.2), meeting the quality control requirements (10 min); the time required to obtain troponin test results was 13.0 to 48.4 min with a median of 14.1 min (13.4, 18.1), meeting the requirements for quality control of 20 min; time from entry to transfer out of PCI patients was 19.0-100.0 min, with median 37.2 (29.3, 66.6) min, basically reaching quality control (30 min); the entering catheter chamber rate of STEMI patients was 50.0% to 100.0% with a median of 100.0% (73.3%, 100.0%), meeting the requirements of quality control (≥50%). Through the active construction, the main quality control indicators were well reached, the reported cases were basically stable, and the disease distribution was basically reasonable in the primary-level chest pain centers. Informed notification of transshipment and subsequent management of low-risk chest pain patients need to be further strengthened. It is suggested that the construction of chest pain centers should establish long-term normal working mechanism, strengthening the control of key quality control indicators, to play the important role of the regional treatment system.

We have previously reported that Cystatin C (CysC) is a pivotal mediator in the neuroprotection induced by hyperbaric oxygen (HBO) preconditioning; however, the underlying mechanism and how CysC changes after stroke are not clear. In the present study, we demonstrated that CysC expression was elevated as early as 3 h after reperfusion, and this was further enhanced by HBO preconditioning. Concurrently, LC3-II and Beclin-1, two positive-markers for autophagy induction, exhibited increases similar to CysC, while knockdown of CysC blocked these elevations. As a marker of autophagy inhibition, p62 was downregulated by HBO preconditioning and this was blocked by CysC knockdown. Besides, the beneficial effects of preserving lysosomal membrane integrity and enhancing autolysosome formation induced by HBO preconditioning were abolished in CysC rats. Furthermore, we demonstrated that exogenous CysC reduced the neurological deficits and infarct volume after brain ischemic injury, while 3-methyladenine partially reversed this neuroprotection. In the present study, we showed that CysC is biochemically and morphologically essential for promoting autophagic flux, and highlighted the translational potential of HBO preconditioning and CysC for stroke treatment.
Animals ; Autophagy ; physiology ; Beclin-1 ; metabolism ; Brain ; metabolism ; pathology ; Brain Ischemia ; metabolism ; pathology ; therapy ; Cystatin C ; genetics ; metabolism ; Disease Models, Animal ; Gene Expression ; Gene Knockdown Techniques ; Hyperbaric Oxygenation ; Lysosomes ; metabolism ; pathology ; Male ; Microtubule-Associated Proteins ; metabolism ; Neurons ; metabolism ; pathology ; Neuroprotection ; physiology ; Oxygen ; therapeutic use ; Random Allocation ; Rats, Sprague-Dawley ; Rats, Transgenic ; Reperfusion Injury ; metabolism ; pathology ; therapy