Obsessive-compulsive disorder （OCD） is a highly disabling mental disorder that impairs patients' social function and quality of life， and impose a substantial economic burden. Intolerance of uncertainty （IU） refers to a cognitive bias in perceiving， interpreting and responding to uncertain situations or events. IU is closely associated with the cognitive patterns of OCD patients. Based on magnetic resonance imaging （MRI）， this paper discusses the research progress of the relationship between IU and psychopathological characteristics of OCD， and put forward the research direction， aims to provide evidence-based references for the development of optimized therapeutic interventions for OCD.

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 investigate the genetic and evolutionary characteristics of hemagglutinin (HA) and neuraminidase (NA) genes of influenza B/Victoria (BV) virus in Xi′an city from 2019 to 2023.Methods:Twenty-five BV strains isolated from the Xi′an influenza surveillance network laboratory between 2019 and 2023 were collected. The HA and NA genes were sequenced using MiniSeq high-throughput sequencing platform. An evolutionary tree was constructed using bioinformatics software to analyze homology and mutation sites, and to predict N-glycosylation sites online. The antigenicity of the strains was analyzed through hemagglutination inhibition tests.Results:The BV influenza in Xi′an exhibited a distinct seasonal transmission pattern from 2019 to 2023, with peak prevalence occurring during the winter and spring seasons. The evolutionary analysis of the HA genes shows that the strains from Xi′an in 2019 belong to the V1A.3 branch, and the strains from 2021 to 2023 belong to the V1A.3a.2 branch. Analysis of antigenic sites showed that there were variations in 6 sites of 3 antigenic determinants in the HA proteins of the BV strains from 2021-2022 compared to 2019, and 2 sites of 1 antigenic determinant changed in the HA proteins in 2023 compared to 2021-2022. The evolutionary analysis of the NA genes indicates that the BV strains from Xi′an in 2019 belong to the A. 1.1 branch. By 2021 and 2022, it had evolved into the A. 1.2 clade, and by 2023, it had further evolved into the B clade and its derivatives, with no strains showing mutations associated with resistance to NA inhibitors. Antigenic analysis indicated that the majority of BV strains in Xi′an were similar to the strains included in the vaccine composition. Furthermore, glycosylation analysis showed that the potential N-glycosylation sites in the HA proteins of BV strains from 2021-2023 were reduced by one compared to those from 2019, and only a few strains from 2023 displayed alterations in the potential N-glycosylation sites of the NA proteins.Conclusions:The HA and NA genes of the BV strains from 2019 to 2023 are continuously mutating and evolving into new branches. Since 2021, V1A.3a.2 has become the dominant evolutionary branch of the HA genes, while the evolutionary branches of the NA genes from 2019 to 2023 have been continuously changing.

Evoked Potentials ; Social Isolation ; Attention ; Humans

β-Thalassemia is a single-gene disease caused by mutations in β-globin and has a distinct geographical characteristics. Current treatment for patients with moderate to severe thalassemia has mainly relied on long-term blood transfusion and/or hematopoietic stem cell transplantation. B cell lymphoma/leukemia 11A (BCL11A) as a transcriptional repressor plays a vital role in monitoring γ/β hemoglobin switching, maintaining the normal function of hematopoietic stem cells, and regulating erythrocyte differentiation and lymphocyte development. With the rapid progress in gene editing technology, the BCL11A as a therapeutic target for β-thalassemia has shown promising results. This article has systematically summarized the regulatory mechanism and therapeutic potential of the BCL11A, with an aim to provide new ideas for the treatment of β-thalassemia.

Objective     To summarize the surgical treatment experience in neonates with coarctation of the aorta (CoA) and aortic arch hypoplasia (AAH). Methods     The neonates with CoA and AAH who underwent surgical treatment in the Department of Pediatric Cardiac Surgery of Guangdong Provincial People's Hospital from 2013 to 2020 were retrospectively enrolled. The postoperative complications, long-term survival rate, and freedom from aortic reobstruction were analyzed. Patients undergoing extended end-to-end anastomosis were allocated into an extended end-to-end group, those undergoing extended end-to-side anastomosis into an extended end-to-side group, and those undergoing pulmonary autograft patch aortoplasty into a patch aortoplasty group. Results     Finally 44 patients were  enrolled, including 37 males and 7 females, aged 5.00-30.00 (19.34±7.61) days and weighted 2.00-4.50 (3.30±0.60) kg. There were 19 patients of extended end-to-end anastomosis, 19 patients of extended end-to-side anastomosis, and 6 patients of pulmonary autograft patch aortoplasty. The mean values of the Z scores of the proximal, distal, and isthmus of the aortic arch were –2.91±1.52, –3.40±1.30, and –4.04±1.98, respectively. The mean follow-up time was 45.6±3.7 months. There were 2 early deaths and no late deaths. Aortic reobstruction occurred in 8 patients, and 3 patients underwent reoperation intervention. The 5-year rate of freedom from reobstruction was 78.8%. The Cox multivariable regression analysis showed that the related factors for postoperative reobstruction were the Z score of the preoperative proximal aortic arch (HR=0.152, 95%CI 0.038-0.601, P=0.007) and the postoperative left main bronchus compression (HR=15.261, 95%CI 1.104-210.978, P=0.042). Conclusion     Three surgical procedures for neonates with CoA and AAH are safe and effective, but the aortic reobstruction rate in long term is not low. The smaller Z score of the preoperative proximal aortic arch and the postoperative left main bronchus compression are risk factors for long-term aortic reobstruction.

Objective To evaluate the effect of clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot by antibiotics management index and health economics index. Methods 40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department of Air Force Medical Center from April to September 2017 were selected as control group, and 40 hospitalized patients with diabetic foot of Wagner Grade 4 in the Endocrine Department from April to September 2019 were selected as interventional group. No clinical pharmacists were involved in drug treatment of patients in the control group, while the clinical pharmacists in the interventional group participated in drug treatment, and implemented antimicrobial stewardship, medication reconciliation, pharmaceutical care and medication education. Antibiotics management indexes (use intensity of antibiotics, use rate of special class antibiotics) and health economics indexes (medicine expenses, hospitalization expenses) of the two groups were compared. Results The efficacy of the two groups was similar. The use intensity of antibiotics and use rate of special class antibiotics of the interventional group in which clinical pharmacists participated were significantly lower than the control group (P<0.01), so were the medicine expenses and hospitalization expenses (P<0.01). Conclusion Clinical pharmacists participating in the treatment of hospitalized patients with diabetic foot could reduce antibiotics administration index and health economics index, promote rational medicine use and save medical expenses.

Background/Aims: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological function of TCN1 by performing gain-of-function and loss-offunction analyses in HCT116 cell lines; examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells; and determined potential molecular mechanisms using HCT116 and SW480 CRC lines and mouse xenotransplantation models. Tumor xenograft and colonization assays were performed to detect the tumorigenicity and metastatic foci of cells in vivo. Results: TCN1 knockdown attenuated CRC cell proliferation and invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism analyses showed that TCN1 interacted with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1 knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A. Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/plectin complex, leading to cytoskeletal damage. Conclusions TCN1 might play an oncogenic role in CRC by regulating the ITGB4 signaling pathway.

Objective:To investigate the diagnostic value of a single hydrogen-methane breath test (SHMBT) for small intestinal bacterial overgrowth (SIBO).Method:The current investigation was a cross-sectional study. Questionnaires and SHMBTs were administered to 162 patients with gastrointestinal symptoms (case group) and 69 healthy volunteers (control group). Differences in SHMBT results between the two groups were assessed,and cut-off values of CH 4 (methane) and H 2 (hydrogen) were analyzed via receiver operating characteristic (ROC) curves. Lastly,archived SHMBT data from 2 655 patients with gastrointestinal symptoms (validation set) were used to evaluate the diagnostic value of the SHMBT with respect to SIBO. The Chi-square test,the Mann-Whitney U test,Spearman′s Rank correlation analysis,and the Z test were used for statistical analysis. Results:Based on the international recommended diagnostic criteria for SIBO,which are fasting CH 4 ≥10 ppm (parts per million) or H 2 ≥20 ppm,the SHMBT-positive rate in the case group was significantly higher than that of control group (35.2% vs. 21.7%, χ2=4.08, P=0.043). Levels of CH 4 and H 2 were higher in the case group than in the control group [CH 4: 3(2,7) vs. 3(1,3) ppm, H 2: 11(4,22) vs. 10(5,15) ppm],and the difference in CH 4 levels was statistically significant ( Z=6.22, P=0.001). ROC curves were generated based on whether the subjects had gastrointestinal symptoms. The areas under the ROC curves were 0.633 for CH 4 alone,0.531 for H 2 alone, and 0.620 for CH 4 combined with H 2. The cut-off values were fasting CH 4≥4 ppm,fasting H 2≥13 ppm,and fasting CH 4 ≥5 ppm (or CH 4≥4 ppm and H 2≥24 ppm),respectively. Measuring CH 4 alone and CH 4 combined with H 2 was effective for determining the presence of gastrointestinal symptoms ( P<0.05). When CH 4 alone or CH 4 combined with H 2 were used as diagnostic indicators of SIBO, the respective SHMBT-positive rates in the validation set were 34.2% and 30.4%. These rates did not significantly differ from the SIBO-positive rate of 32.0% obtained via the international recommended diagnostic criteria ( P>0.05). The specificity of CH 4 alone was 79.9%,and the accuracy of CH 4 alone was 68.8%. The specificity of CH 4 combined with H 2 was 85.0%,and the accuracy of CH 4 combined with H 2 was 71.7%. Conclusion:Rapid one-time determination of CH 4 and H 2 in exhaled breath may a viable diagnostic method for SIBO, and using CH 4 combined with H 2 ( i.e.,fasting CH 4≥5 ppm, or CH 4 ≥4 ppm and H 2 ≥24 ppm) as cutoff values may be feasible.