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.

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.

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.

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.

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

OBJECTIVE: To systematically evaluate therapeutic efficacy and safety of Compound muni ziqi granules in the adjuvant treatment of chloasma, and to provide evidence-based reference for clinical treatment. METHODS; Retrieved from Chinese Journal Full-text Database (CJFD), China Scientific Journal Database (CSJD), Wanfang database, Medline and Embase, randomized controlled trials (RCTs) about therapeutic efficacy (total response rate, cure rate, the decrease level of E2, FSH and LH in serum) and safety of Compound muni ziqi granules alone or combined with routine drug (trial group) vs. routine drug (control group) in the treatment of chloasma were collected. Meta-analysis was conducted by using Rev Man 5. 3 statistical software after data extraction of clinical studies meeting inclusion criteria and quality evaluation with Cochrane systematic evaluator manual 5. 1. 0. RESULTS: Totally 12 RCTs were enrolled, involving 1 100 patients. Results of Meta-analysis showed that total response rate [OR=2. 84, 95％CI(2. 20, 3. 67), P<0. 001], cure rate [OR=2. 11, 95％CI(1. 59, 2. 79),P<0. 001],decrease level of Ez [OR=-98. 64, 95％ CI (-110. 84, -86. 44), P <0. 001], decrease level of FSH [OR=-1. 85, 95％CI(-2. 58,-1. 11),P<0. 001] and decrease level of LH [OR= - 5. 85, 95％ CI (-6. 83, -4. 87), P<0. 001] in trial group were significantly better than control group, with statistical significance. In trial group, a few patients suffered from the increase of menstruation, the decrease of menstruation, temporary pigmentation and transient burnout; but all symptoms did not affect the treatment. CONCLUSIONS: Compound muni ziqi granules show definite clinical efficacy and good response rate in the adjuvant treatment of chloasma with mild ADR.

Objective To investigate the expression of bone marrow γ-H2AX in the patients with multiple myeloma(MM) and its correlation with the prognosis.Methods The patients with newly diagnosed MM in this hospital were selected as the case group,and the patients with non-hemopoietic system tumor without obvious morphological abnormalities by bone marrow smear and biopsy served as the control group.The immunohistochemistry was adopted to detect the expression level of bone marrow γ-H2AX in the cases group and control group,the image-Pro Plus(IPP) semiquantitative analysis was performed.The expression differences were compared between the two groups,moreover the case group was re-divided into the strong expression group and weak expression group according to γ-H2AX expression level.Then the relation ship between γ-H2AX expression level and the prognosis in the patients with MM.Results The bone marrow γ-H2AX expression level in the case group was significantly higher than that in the control group (P＜0.05);the level of γ-H2AX expression in the strong expression group was significantly stronger than that in the weak expression group (P＜0.05).Conclusion The level of γ-H2AX expression was higher among MM patients,and the over expression of γ-H2AX predicts the shorter survival time.

Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports. Next, we demonstrated that the cell proliferation activity, determined by Ki67, PCNA and PH3, was significantly decreased at the different TS time points (TS for 14, 28 and 42 days) compared with that in the control group. Consistently, the positive cell cycle regulators Ccna2, Ccnd1, Cdk1, Cdk2 and cyclin D3 were also significantly decreased in the TS groups as shown by quantitative real-time PCR and western blotting analysis. Subsequent analysis revealed that the aberrant hepatocyte proliferation inhibition under simulated microgravity was associated with the upregulation of miR-223 in the liver. We further found that miR-223 inhibited the proliferation of Hepa1-6 cells and identified CDK2 and CUL1 as its direct targets. In addition, the decreased expression of CDK2 and CUL1 was negatively correlated with the level of p27 in vitro and in vivo, which may have been responsible for retarding hepatocyte proliferation. Collectively, these data indicate that upregulation of miR-223 was associated with the inhibition of liver cell growth and reveal the role of miR-223 in rat hepatocyte proliferation disorders and the pathophysiological process under simulated microgravity.
Alanine Transaminase ; Alkaline Phosphatase ; Animals ; Aspartate Aminotransferases ; Biomarkers ; Blotting, Western ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Cyclin D3 ; Hepatocytes* ; Hindlimb Suspension ; In Vitro Techniques ; Liver* ; Proliferating Cell Nuclear Antigen ; Rats* ; Real-Time Polymerase Chain Reaction ; Space Flight ; Up-Regulation* ; Weightlessness*