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.

BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.

ObjectiveTo provide reference for further strengthening the management of laboratory animals in Sichuan Province by reviewing and analyzing the results of parasitic and microbial quality inspections of laboratory animals from 2017 to 2023. Methods Sichuan Province has 31 licensed laboratory animal production units, with the main species including mice, rats, guinea pigs, rabbits, dogs, monkeys, and pigs. Sampling inspections and reports were conducted for units with laboratory animal production qualifications in accordance with current national and local standards for laboratory animal classification. The quality inspection results for various laboratory animals in Sichuan Province from 2017 to 2023 were analyzed. Results With the exception of 2018, annual quality inspections of laboratory animals were conducted every year between 2017 and 2023. Mice: In 2017, positive results for helminths, flagellates, Salmonella, murine hepatitis virus antibodies, and murine pneumonia virus antibodies were detected, with a pass rate of only 42.9%. In 2019, Staphylococcus aureus and Klebsiella pneumoniae were detected, with a pass rate of 86.7%. In 2021, Sendai virus antibodies were detected, yielding a pass rate of 85.7%.The pass rate in 2020, 2022, and 2023 was 100%. Rats: In 2017, positive results were found for helminths, mycoplasma antibodies, Staphylococcus aureus, Sendai virus antibodies, murine pneumonia virus antibodies, rat parvovirus RV strain antibodies, rat parvovirus (H-1) strain antibodies, and rat coronavirus antibodies, with a pass rate of 40.0%. In 2019, mycoplasma antibodies, Staphylococcus aureus and Klebsiella pneumoniae were detected, with a pass rate of 35.0%. No positive indicators were detected in 2020. In 2021, Sendai virus antibodies and rat parvovirus RV strain antibodies were detected, with a pass rate of 50.0%. In 2022, positive results for rat parvovirus RV strain antibodies were found, yielding a pass rate of 87.5%. In 2023, Pasteurella pneumotropica and Klebsiella pneumoniae were detected, with a pass rate of 85.7%. Dogs: In 2017 and 2019, the antibody titers for rabies virus and canine distemper virus were below the required standard, with pass rates of 33.3% and 20.0%, respectively. In 2020 and 2022, the pass rate was 100%. Guinea pigs (general grade): In 2019, positive results for Toxoplasma antibodies were detected, with a pass rate of 80.0%. In all other years, the pass rate was 100%. Monkeys: In 2019, positive results for Toxoplasma gondii and rhesus herpesvirus type I antibodies were found, with a pass rate of 87.5%.In 2020 and 2022, rhesus herpesvirus type I antibodies were positively detected, yielding pass rates of 93.3% and 97.5%, respectively. The pass rates in 2021 and 2023 were 100%. Clean guinea pigs, rabbits and pigs all passed the inspection each year. ConclusionIssues related to the parasitic and microbial quality of laboratory animals persist in Sichuan Province. Supervision and sampling inspections have proven to be effective in identifying these issues promptly, serving as a critical measure to ensure the quality of laboratory animals. The results of these inspections offer valuable data to support the healthy development of the laboratory animal industry in Sichuan Province.

Objective A HPLC-quantitative analysis of multi-components by single marker(QAMS)was established to determine 5 ingredients including uracil,uridine,hypoxanthine,inosine and guanosine in Periplaneta americana.Methods Separation took place on a Agilent ZORBAX SB-Aq column(250 mm×4.6 mm,5 μm)by gradient elution of methanol-0.01 mol·L-1 potassium dihydrogen phosphate at 20℃with a flow rate of 1.0 mL·min-1.The detection wavelength was 260 nm and the injection amount was 10 μL.The relative correction factors(fa/b)was calculated for the other four components with uridine as an internal standard.The content of 5 ingredients in 10 batches of Periplaneta americana was determined by QAMS.Results were compared with those of external standard method(ESM).Results Five nucleosides showed good linear relationships in their own ranges(r＞0.999 5),and the average recoveries ranged from 97.0%to 100.8%.The relative correction factors of uracil,hypoxanthine,inosine and guanosine were 0.908 0,1.005 3,1.969 5 and 1.303 4,respectively.Conclusion The established method is accurate and stable.It can provide theoretical reference for the quality control of Periplaneta americana.

Objective:To evaluate the efficacy and safety of Qingxuan Zhike granules in improving cough symptoms and shortening the course of influenza (wind-heat invading lung) in children.Methods:In this multicenter, randomized, controlled clinical trial, a total of 240 outpatient influenza patients from 7 hospitals, including the First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine, from April 2023 to December 2023 were collected.The subjects were randomly divided into the control group and the experimental group via SAS software using the block randomization method.The differences between two groups were compared with t test, corrected t test and χ2 test.Subjects in the control group were given Oseltamivir phosphate granules, orally, twice a day (weight ≤15 kg, 30 mg/time; weight >15-23 kg, 45 mg/time; weight >23-40 kg, 60 mg/time; weight >40 kg, 75 mg/time; age≥13 years, 75 mg/time).In addition to Oseltamivir phosphate granules, subjects in the experimental group were also given Qingxuan Zhike granules, orally, 3 times a day (1-3 years old, 1/2 bag each time; >3-6 years old, 3/4 bag each time; >6-14 years old, 1 bag each time).After 5 days of treatment, the medication was suspended for 2 days.The effect of cough, antipyretic effect, clinical recovery rate, clinical recovery time, Canadian Acute Respiratory Illness and Flu Scale (CARIFS) score, traditional Chinese medicine (TCM) syndrome effect, complication rate, and adverse reactions were evaluated between the two groups. Results:Finally, 232 cases were included in the study, including 115 cases in the experimental group and 117 cases in the control group.Before and after treatment, there were no significant difference in CARIFS cough score between the experimental group and the control group (all P>0.05).After treatment, the change in CARIFS cough score in the experimental group [(-1.00±0.91) scores]was significantly higher than that in the control group [(-0.75±0.98) scores] ( t=-1.995, P=0.047).After treatment, the change in TCM syndrome cough score in the experimental group [(-1.69±1.51) scores] was significantly higher than that in the control group [(-0.97±1.63) scores] ( t′=-0.035, P=0.001).The time of complete regression of fever in the experimental group [(44.82±22.72) h] was shorter than that in the control group [(51.35±27.07) h], and the difference between the two groups was statistically significant ( t=-1.966, P=0.050).The fever score showed that the area under the curve between the CARIFS symptom fever score and time in the experimental group was 4.40±2.42, while that in the control group was 5.12±2.44, and the difference between the two groups was statistically significant ( t=-2.252, P=0.025).The clinical recovery rate was 93.91%(108/115) in the experimental group and 92.31%(108/117) in the control group, and there was no significant difference between the two groups ( χ2=0.233, P>0.05).The clinical recovery time in the experimental group [(2.93±1.21) d] was shorter than that in the control group [(3.29±1.15) d], and the difference between the two groups was statistically significant ( t=-2.279, P=0.024).After treatment, there was a significant difference in TCM syndrome score variation between the experimental group [(-12.00±4.13) scores] and the control group [(-10.85±4.31) scores] ( t′=-2.067, P=0.040).No complication occurred in both groups, and there was no significant difference in the incidence of adverse events between the two groups ( χ2=1.299, P>0.05). Conclusions:Qingxuan Zhike granules combined with Oseltamivir phosphate can effectively improve the cough symptoms associated with influenza in children, shorten the time and course of fever, and improve the TCM syndrome score; thus, they are safe in clinical application.

In recent years,challenges persist in the grassroots Party building in the university-affiliated hospitals though increased efforts have been intensified.These challenges include a lack of alignment between Party building and the hospital's central tasks,an absence of distinctive Party building brands,an insufficiently prominent role of Party organizations in hospital development,and inadequate leveraging of the Party construction for promoting medical services and cultivating medical talents.Starting from an exploration of the connotation and significance of constructing framework of"One Integration and Two Highs"in university-affiliated hospitals,this paper conducts an in-depth analysis of the existing problems and their causes within this frame-work.From a holistic perspective,the paper proposes a new path for establishing the"One Integration and Two Highs"frame-work in university-affiliated hospitals,centered around"Seven Integrations":concept integration,organization integration,strength integration,vehicle integration,culture integration,innovation integration,and assessment integration.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

Objective To explore the application value of static progressive stretch(SPS)combined with step-wise progressive rehabilitation nursing in perioperative rehabilitation nursing of patients with unicompartmental knee arthroplasty(UKA).Methods From January 2022 to June 2023,a total of 74 patients who were scheduled to undergo UKA in the Department of Orthopedics of a tertiary A hospital in Beijing were selected by the convenient sampling method and divided into 2 groups by the random number table method,with 37 cases in each group.The experimental group was given step-by-step rehabilitation nursing combined with SPS technology,while the control group was only given step-by-step rehabilitation nursing,and the intervention lasted for 4 weeks.The knee joint activity,knee joint function score,comfort,and rehabilitation self-efficacy of the 2 groups were observed and measured before and after the intervention.Results Finally,35 patients were included in the experimental group and 36 patients in the control group.After the intervention,the knee joint range of motion,knee joint function score,comfort,rehabilitation self-efficacy and all dimensions and their total scores in the experimental group were higher than those before the intervention and those in the control group(P＜0.05).Conclusion SPS combined with progressive rehabilitation nursing can effectively improve the knee joint function and range of motion of patients after UKA,improve the comfort of patients,improve their quality of life,and enhance their rehabilitation self-efficacy,which is helpful to achieve early recovery.

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.