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.

Carbocisteine is a commonly used expectorant drug.Currently,the reported detection methods for carbocisteine mainly include the electrochemical method,potassium bromated titration,kineticmethod,spectrometry,chromatography,HPLC-FLD precolumn derivation determination,HPLC-MS,etc.The advantages and disadvantages of each method were compared and analyzed in this paper,and it is found that HPLC was more suitable for the quality analysis of carbocisteine,which could serve as a reference for upgrading standard of carbocisteine content determination.

Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective:To explore the prognosis and clinical risk factor of thymoma patients after resection.Methods:A retrospectively analysis of 154 cases of thymoma patients underwent thymoma resection in Beijing Tongren Hospital (Myasthenia Gravis & Thymoma Diagnosis and Treatment Center, Capital Medical University) from January 2005 to December 2015, and then the progress-free survival was calculated by Kaplan- Meier method, the differences between curves were analyzed by log- rank test. There were 74 males and 80 females; the median age was 52(22-77)years. 121 cases(78.6%)complicated with myashenia gravis. Thymoma cases were classfied into 5 cases A, 35 cases AB, 27 cases B1, 56 cases B2 and 31 cases B3 respectively. There were 80, 16, 45 and 13 patients with Masaoka-Koga type Ⅰ-Ⅳ, respectively. 122 cases were treated by thoracoscopic assisted operation, 32 cases were treated by median sternum. The risk factors about group of gender, age, thymoma-associated MG (Myasthenia Gravis), completeness of resection, histologic type and Masaoka-Koga stage were calculated by Cox regression analysis. Results:The overall 1-, 5- 10-year progress-free survival rate of 154 cases were 98.7%, 88.3%, and 78.7%, respectively. The adverse prognostic factors for progress-free survival were age, completeness of resection, WHO histologic classification and Masaoka-Koga stage at univariate analysis. The age, WHO histologic classification and Masaoka-Koga stage were the independent risk factors at multivariate analysis.Conclusion:For thymoma, we suggest early discovery and early treatment. For the thymoma patients who are available for surgical treatment, all the tumor, thymus and surrounding adipose tissue should be resected. For the thymoma patients whose tumors cannot excise completely, adjuvant radiotherapy can reduce the risk for tumor recurrence after resection. For patients with thymoma after surgery, MG treatment is particularly critical for prognosis.

Objective:To investigate effects of bone-resorptive lesion on stress distribution of femoral head and on progression in patients with osteonecrosis of the femoral head (ONFH).Methods:From April 2014 to September 2018, a total of 155 femoral heads from 94 patients diagnosed with ARCO stage II and III ONFH were retrospectively reviewed, including 77 males and 17 females with aged 39.90±10.45 years old (ranged from 18-64 years). The hips were divided into two groups according to whether there were bone-resorptive lesions. Further, we compared whether there was statistical difference between the two groups in staging. Then, a case of ARCO II hip joint without bone-resorptive lesion was selected from the included patients. Six femoral head with different diameters of spherical bone-resorptive lesion of 5 mm, 7 mm, 10 mm, 14 mm, 18 mm, and 23 mm were simulated. The influence of bone-resorptive lesion on the stress distribution of necrotic area and a spherical shell extending 1 mm radially around the bone-resorptive lesion was investigated by finite element method in slow walking conditions.Results:Of the 155 ONFH hips, 67 hips are complicated by bone-resorptive lesions, of which 17 were ARCO II, 50 were ARCO III. A total of 88 hips did not contain bone-resorptive lesions, of which 58 were ARCO II, ARCO III 30 cases. The proportion of ARCO stage II in the group with bone-resorptive lesions was significantly higher than that in the group without bone-resorptive lesions (χ 2=25.03, P=0.000). The finite element stress distribution cloud diagram showed that there was a stress concentration area around the bone-resorptive lesions. The maximum von Mises stress around bone-resorptive lesions in the models that contained a synthetic bone-resorptive lesions were significantly higher than those reported in the matched, non-synthetic bone-resorptive lesions finite element models ( t=3.139, P=0.026). The values for maximum von Mises stress around bone-resorptive lesions were 6.94±1.78 MPa and 5.01±0.35 MPa for the group with synthetic bone-resorptive lesions and the group non-synthetic bone-resorptive lesions, respectively. There was a positive correlation between the diameter of bone-resorptive lesions and the maximum and mean von Mises stress of necrotic areas as well as the maximum von Mises stress around bone-resorptive lesions. Conclusion:Bone-resorptive lesions can increase the maximum stress and average stress in the necrotic area. The larger the bone-resorptive lesion, the more the stress increases. There is a stress concentration area around the bone-resorptive lesions, which may accelerate the collapse of the femoral head.

As a thymoid-related autoimmune disease, thymectomy has become one of the effective treatments for MG. We review the surgical indications of MG in this artical.

Objective:To investigate the role and possible molecular mechanisms of m6A methyltransferase METTL3 and demethylase FTO in H7N9 virus infection.Methods:Western blot(WB) was used to detect the expression of METTL3 and FTO after H7N9 virus infected A549 cells. After knocking down and over-expressing METTL3 and FTO, H7N9 virus infection was tested by WB and TCID 50 for its effect on virus replication. Transcriptome sequencing method were used to analyze differentially expressed genes at the transcriptome level in METTL3 or FTO knockdown and wild-type control cells, and preliminary analysis of potential targets was performed. Results:After 24 h of H7N9 virus infection in A549 cells, METTL3 expression was up-regulated, and FTO did not significantly change. After knocking down METTL3 and FTO, the virus nucleoprotein (NP) expression level and virus titer decreased significantly. Consistent with the result of the knockdown experiments, we found that the viral titer was increased by METTL3 and FTO overexpression. Transcriptome sequencing result showed that 314 and 555 differentially expressed genes were found between the METTL3 or FTO knockdown group and the control group, respectively. GO functional enrichment analysis and KEGG pathway enrichment analysis showed that these genes were related to the host immune response.Conclusions:METTL3 and FTO may play a key role in H7N9 virus infection by regulating host-virus interactions.

Objective To determine the value of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natri-uretic peptide and homocysteine in the risk stratification of patients with unstable angina pectoris;thus to provide an assessment for the condition of patients in clinic.Methods 135 patients with unstable angina were included in the disease group and subjected to risk stratification according to GRACE risk score software,70 cases of low-risk group,60 cases in the middle-risk group and 5 cases in the high-risk group.Another 145 healthy people were in the control group.The levels of ischemia modified albumin,heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine were detected and compared.Results Between the control group and the disease group,significant difference of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocys-teine was found (P <0.05),but the difference of ischemia modified albumin was not statistically significant(P >0.05).In the dis-ease group,the levels of ischemia modified albumin,heart-type fatty acid-binding protein and homocysteine in each risk stratification showed no significant difference(P >0.05).The level of B-type natriuretic peptide in high-risk group was higher than that in the low-risk group and in the middle-risk group and the difference was statistically significant (P <0.05),while there was no statisti-cally significant difference between the low-risk group and the middle-risk group(P >0.05 ).Conclusion The detection of heart-type fatty acid-binding protein,B-type natriuretic peptide and homocysteine possesses certain meaning in diagnosing unstable angi-na,and the level of B-type natriuretic peptide indicates the risk degree of the disease.

Objective To review the experience with partial cystectomy combined with chemo-and radiation therapies in the treatment of muscle-invasive bladder cancer (MIBC) to assess the local control and survival rates,and to identify predictive factors for recurrence and survival.Methods From 2002 through 2007,a total of 100 patients with MIBC underwent partial cystectomy combined with adjuvant chemotherapy and radiation therapy (PC group).Meanwhile,36 patients with MIBC underwent radical cystectomy (RC group).The clinical and pathological data of these patients were retrospectively reviewed.Primary endpoints were cancer-specific survival (CSS),bladder-intact cancer-specific survival and bladder cancer recurrence.Results The 5-year CSS rate of the entire cohort was 65％,which was higher in PC group than in RC group (68％ vs 55％,P =0.033).In PC group,only 2 patients (2％) were confirmed to have residual tumor at the time of re-evaluation TUR 3 months after partial cystectomy.After a mean of 33.1 months,46 patients (46％) experienced superficial recurrence and 14 patients (14％) developed muscle-invasive recurrence.75％ of recurrence occurred within 16 months.8 patients underwent salvage cystectomy.The 5-year bladder-intact survival rate was 63％ in PC group.In multivariate analysis,the presence of tumor numbers more than 3 and tumors with infiltrating growth pattern were 2 predictive factors for cancer recurrence in PC group.In terms of survival,the presence of tumor numbers more than 3,lymphovascular invasion and partial cystectomy plus ureteral reimplantation (PC plus UR) were significantly associated with 5-y CSS in PC group and PC plus UR was indeed a protective factor for survival.By looking at the entire MIBC cohort,lymphovascular invasion,tumor numbers more than 3,history of superficial bladder cancer and age greater than 70 years old were identified as independent predictive factors for 5-y CSS.Conclusions Combined with adjuvant chemo-and radiation therapies,partial cystectomy might be a alternative to radical cystectomy for the treatment of MIBC,which provides adequate local control in selected patients,as well as acceptable survival rate.