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 explore prescription and syndrome law of TCM in the treatment of non-alcoholic fatty liver disease(NAFLD);To provide reference for clinical medication.Methods The relevant literature on the treatment of NAFLD with TCM was retrieved from CNKI,VIP,Wanfang Data and CBM from the establishment of the databases to October 31,2023.Excel 2019,Lantern 5.0 and SPSS Modeler 18.0 software were used to analyze the latent structure model,association rules and frequency statistics of high-frequency drugs(≥3%)to explore the prescription and syndrome law of TCM in the treatment of NAFLD.Results A total of 453 prescriptions were included,involving 260 kinds of Chinese materia medica,with a cumulative frequency of 4 910 times.The high-frequency drugs were Crataegi Fructus,Salviea Miltiorrhizae Radix et Rhizoma,Alismatis Rhizoma,Bupleuri Radix,Poria and Atractylodis Macrocephalae Rhizoma,etc.The efficacy categories were mainly tonic medicine,diuretic dampness medicine,blood circulation-activating and stasis-resolving medicine,heat-clearing medicine and qi-regulating medicine.The latent structure model obtained 12 latent variables,24 latent classes,and 7 comprehensive clustering models.The commonly used prescriptions were Erchen Decoction,Yinchenhao Decoction,Danggui Shaoyao Powder,Sini Powder,Sijunzi Decoction,Weiling Decoction,Zhuyu Decoction and Dihuang Decoction categorized formula.Conclusion NAFLD is the syndrome of deficiency in root and excess in superficiality.Spleen deficiency is the root cause,phlegm,dampness,heat and blood stasis are the symptoms.In clinical practice,it is mainly based on tonifying qi and spleen,cooperating with the methods of resolving phlegm,eliminating dampness,clearing heat and activating blood circulation.

Objective:To explore the relationship between executive function and gait in cases of mild amnestic cognitive impairment (aMCI).Methods:Twenty aMCI hospital patients formed an observation group, while 20 healthy counterparts were the control group. Both groups underwent the Tinetti test, followed by the " normal walking" single-task test and the " normal walking + Go/No-go" dual-task test. The pace, step width, stride length, Go/No-go task response time and accuracy rate were recorded.Results:In the single-task test, there was no significant difference in pace or stride width between the two groups, but the average stride length of the observation group (1.11±0.04)cm was significantly shorter than that of the control group. However, in the dual-task test, the average pace time (0.96±0.08)sec and stride length (1.02±0.06)cm of the observation group were significantly smaller than the control group′s averages, while their step width (0.11±0.02)cm was significantly wider. There was no significant difference between the two groups in the response time in a single (Go/No-go) task, but in the dual-task test, the observation group′s average time was significantly longer than the control group′s and the accuracy was significantly poorer. Both the error rate and the non-response rate were significantly higher than among the control group.Conclusions:Mild amnestic cognitive impairment reduces stride length and pace when walking and impairs executive function.

Cellular and Molecular Basis of Medicine is a basic module course newly established by our school that is compulsory for medical students. This module course overthrows traditional disciplinary boundaries, and adopts the forms of combining classroom teaching with students' self-learning and teachers' instruction with topic discussion of students guided by teachers. In the teaching of the module course, discussion was adopted among students which involves teachers giving out the range of topics to students so that they can prepare for the topic of their intertest. After group discussion during class, the head of the teaching group gave comment on students' discussion and prize for whom had the best performance. Then, students were asked to summarize and analyze the questions raised during discussion after class. In conclusion, discussion class has stimulated students' interest in learning, improved their ability to think independently and encouraged them to demonstrate their abilities, which has achieved good teaching outcomes.

Objective:To investigate whether the squirrels in Yunnan Province carried Yersinia pestis phages and their epidemiological significance. Methods:From 2015 to 2018, plague host animals were investigated in five of Yunnan plague foci and non-plague foci. The spleen, liver and intestinal specimens of the squirrels captured in the investigation were taken and stored at low temperature for later use. Intestinal specimens with PBS solution, were filtered by 0.22 μm and added to LB liquid medium containing 100 μl suspension of plague vaccine strain (EV76) and then oscillated in a constant temperature gas bath at 28 ℃ and 220 r/min for 18 to 24 h. The double-layer plate method was used to isolate and observe the growth of plaque. The morphology and structure of Yersinia pestis phages were observed under electron microscope. Meanwhile, spleen, liver and intestinal specimens were taken for detection of Yersinia pestis specific marker gene caf1. Results:A total of 10 squirrels were captured (8 Callosciurus erythraeus and 2 Dremomys pernyi), and four Yersinia pestis phages were isolated (2 in Callosciurus erythraeus and 2 in Dremomys pernyi). Two were isolated from non-plague foci (Yongshan County), two from house rats plague foci (Mile County and Xinping County), and none was isolated from wild radents plague foci (Jianchuan County and Eryuan County). By naked eye observation, two bacteriophages from the plague foci produced transparent plaques and grew well, while two bacteriophages from non-plague foci produced translucent plaques and with poor growth. By electron microscopy, these Yersinia pestis phages were of typical Myoviridae family, their head diameter was about 40 nm, muscle tail was about 120 nm, and tail filament cluster was slightly visible at the end of muscle tail. And all the 10 samples of squirrels were negative of plague-specific caf1 gene. Conclusions:The proportion of plague phages carried by Yunnan squirrels is relatively high. Although the detection of caf1 is negative. Squirrels may be a carrier of plague transmission due to the existence of Yersinia pestis phages.

On February 11, 2019, a 37-year-old female patient with neuromyelitis optica spectrum disorders was admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine, and her acute osteomyelitis was caused by infection of multiple pressure ulcer wounds with Staphylococcus aureus. The patient was diagnosed and treated with multidisciplinary cooperation. The nurses focused on the strict observation of the syndrome of neuromyelitis optica spectrum disorders during hormone reduction therapy, guarded against the rebound of condition, implemented wound care in stages according to the diagnosis and treatment plan, maintained effective drainage, ensured appropriate negative pressure, and strengthened nutrition to promote wound healing. After active treatment and careful nursing care, the patient recovered and was discharged on the 39th day after admission.

Objective To compare the coding sequences (CDS) of Yersinia pestis D106004 strain from Yulong County in Yunnan Province and Z176003 strain from Qing-Tibet Plateau in order to find the differences between their genomes and the genetic characteristics. Methods The CDS of Yersinia pestis D106004 strain and Z176003 strain were searched and compared by BLAST. Twenty-two differential CDS were selected to design 22 pairs of primers. PCR amplification was carried out in 119 representative plague strains from different isolation sources (natural foci of Himalayan marmot plague in the Qinghai-Tibet Plateau, natural foci of Apodemus chevrieri and Eothenomys miletus plague in Yunnan), time span of about 50 years, and distribution in six ecological types including Tibet, Qinghai, Sichuan, Gansu and Yunnan, and PCR products were sequenced and verified. The strains were all from the State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Infectious Disease Control and Prevention, Chinese Center for Disease Control and Prevention. Results In 119 representative plague strains of 6 ecological types, the cumulative sequence length of 22 differential CDS PCR amplification products was 2.13 × 106 bp. Among the 119 representative plague strains in the foci of Yulong D106004 strain and Qinghai-Tibet Plateau Z176003 strain, 22 differential CDS had high homology, there was no difference in 78.2％ (2047/2618) sequences of differential CDS, and 21.8％ (571/2618) sequences had three types of gene mutations ( deletion , missense and frameshift mutations). The characteristics of the differences were stable in the 6 ecological plague strains of the foci, and they were divided into 6 geographical distributions. Conclusion Yulong D106004 strain and Qinghai-Tibet Plateau Z176003 strain have high homology, close genetic relationship, and little difference in genome, but the genetic characteristics of different ecotype strains are stable.

Objective To study the changes of Young's modulus value of the renal cortex,vertebral body and sinus when there was a different degree of acute renal artery stenosis.Methods 10 Japanese white rabbits were used for this study.The left renal artery was dissected.An ultrasound probe was placed on the left kidney,Young's modulus of the renal cortex,vertebral body and sinus were recorded using shear wave ultrasound elastic imaging technique during three stages:when the renal artery was intact (0％ stenosis),tied with a suture (＞ 50％ stenosis),and ligated (100％ stenosis).Renal tissue elasticity with different degrees of renal artery stenosis were compared.Pathological study was carried out in the kidneys,each with either 0％,＞ 50％ or 100％ renal artery stenosis.Results The mean values of Young's modulus from the renal cortex,vertebral body and sinus with different degrees of renal artery stenosis were as follows:0％ stenosis,(16.31 ±1.70) kPa,(13.38± 1.63) kPa,and (12.75±2.26) kPa;＞ 50％ stenosis,(14.16±2.34) kPa,(11.49±2.70) kPa,and (10.72±2.56) kPa;100％ stenosis,(11.35 ± 1.48) kPa,(8.39± 1.29) kPa,and (7.08 ± 1.52) kPa.The mean value of Young's modulus from the renal cortex was significantly higher than those from the renal vertebral body and sinus (P ＜ 0.05).The mean values of Young's modulus from different parts of the kidney decreased progressively with an increase in renal artery stenosis (P ＜ 0.05).The pathological study demonstrated that with the increase in the severity of renal artery stenosis,glomerular volume,renal interstitial capillary diameter and red blood cells decreased.When renal artery stenosis reached 100％,there was patch degeneration and inflammatory cell infiltration within the renal interstitium,and mild degeneration of tubular epithelial cells with obscure cell borders.Conclusions The value of Young's modulus from the renal cortex was higher than those from the renal pyramid and sinus in rabbits.The values of Young's modulus from the renal cortex,pyramid and sinus decreased with an increase in the severity of renal artery stenosis,which suggest that,in the study of the elasticity of the kidney,the renal artery blood flow dynamic state can obviously affect the value of the elasticity of the kidney.

Objective To determine the principle of applying lysogenicity in Phage-Biotyping Scheme developed for the subtyping of O1 E1 Tor Vibrio cholerae strains.Methods 118 V.cholerae strains including 76 E1 Tor strains,8 classical strains and 34 serogroup O139 were selected to analyze the lysogenicity and sensitivity to lysogenic phage 919TP as described in the Manuals of cholera prevention and control,the genes of this phage were also determined among the genome sequences of these strains and the phages produced by them.Results All O1 E1Tor Vibrio cholerae 19 strains that produced positive results in lysogenicity,had the lysogenic K139 phage in genome and could both resist to lysogenic phage 919TP and release the K139 family phage.All the O1 E1Tor Vibrio cholerae 22 strains that produced positive results in sensitivity to the lysogenic phage,had no K139 family phage genes and got negative results in lysogenicity.However,the phages of this family were not released from 6 classical strains with positive lysogenicity result.Five serogroup O139 strains were detected releasing temperate phages K139 without the sensitivity to phage 919TP.Conclusions Applying the lysogenicity in Phage-Biotyping Scheme for subtyping O1 E1 Tor Vibrio cholerae strains is based on the ability to produce lysogenic bacteriophage K139.The index of "sensitivity to the lysogenic phage" was also associated with this ability.