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.

OBJECTIVES: Spinal cord ischemia-reperfusion injury (SCIRI) remains a major challenge in the field of organ protection due to the lack of effective prevention and therapeutic strategies. Hyperglycemia, a common perioperative condition, contributes to neurological injury via multiple mechanisms. However, its role and underlying mechanism in SCIRI are still unclear. This study aims to investigate the involvement of the precursor of brain-derived neurotrophic factor (proBDNF) in hyperglycemia-induced SCIRI in mice. METHODS: Eight-week-old male C57BL/6 mice were randomly assigned to a control group (Vehicle) or a diabetes mellitus (DM) group. The DM group was established using intraperitoneal injection of streptozotocin (STZ) combined with 10% sucrose water. The Vehicle group received an equal volume of 50 mmol/L sodium citrate buffer (pH 4.5). Fasting blood-glucose levels ≥11.1 mmol/L were considered successful DM modeling. Both Vehicle and DM groups underwent SCIRI modeling via descending aortic clamping, while the Sham group underwent a sham procedure without aortic occlusion. Lower limb motor function was assessed using the Basso Mouse Scale (BMS) and its subscale (sub-BMS). Locomotor activity was evaluated using an open field test. Immunohistochemistry was performed to detect changes in neuronal nuclear protein (NeuN) and proBDNF expression in spinal cord tissues. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). To explore the effect of proBDNF inhibition, diabetic mice were divided into groups: A DM+SCIRI+monoclonal anti-proBDNF antibody (McAb-proB) group received an intraperitoneal injection of 100 μg of McAb-proB 30 minutes before SCIRI modeling, and a DM+SCIRI+Vehicle group received an equal amount of isotype immunoglobulin G. BMS and sub-BMS scores were recorded, and the gene expression of inflammatory cytokines mentioned above were evaluated. RESULTS: Compared with the Vehicle+SCIRI group, the DM+SCIRI group showed significantly reduced BMS and sub-BMS scores, decreased NeuN expression, shorter total movement distance, slower locomotion, increased proBDNF expression, and elevated IL-1β, IL-6, and TNF-α mRNA levels (all P<0.05 or P<0.01). Compared with the DM+SCIRI+Vehicle group, the DM+SCIRI+McAb-proB group exhibited significantly improved BMS and sub-BMS scores and decreased mRNA expression of IL-1β, IL-6, and TNF-α (all P<0.05 or P<0.01). CONCLUSIONS Hyperglycemia exacerbates neural injury and inflammatory response in SCIRI through upregulation of proBDNF expression, delaying motor functional recovery. Antagonizing proBDNF expression can alleviate neurological damage and promote functional recovery in diabetic mice after SCIRI.
Animals ; Male ; Hyperglycemia/metabolism* ; Brain-Derived Neurotrophic Factor/genetics* ; Mice, Inbred C57BL ; Reperfusion Injury/metabolism* ; Mice ; Diabetes Mellitus, Experimental/metabolism* ; Inflammation/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Protein Precursors/genetics* ; Spinal Cord Ischemia/metabolism* ; Interleukin-6/metabolism* ; Interleukin-1beta/metabolism*

Objective:To evaluate the kinetic metrics changes of FDG in key organs after chemo-immunotherapy in patients with locally advanced non-small cell lung cancer (NSCLC) identified by total-body PET/CT dynamic imaging, and explore its potential biological significance.Methods:From August 2020 to March 2021, 16 patients (13 males, 3 females; age: 43-67 years) with locally advanced NSCLC who underwent total-body 18F-FDG PET/CT dynamic imaging in Sun Yat-sen University Cancer Center were retrospectively analyzed. ROIs of key organs were drawn at baseline and after chemo-immunotherapy to obtain the time-activity curves (TACs). The kinetic metrics, including K1, k2, k3 and metabolic rate of FDG (MR FDG), were fitted by the two-tissue compartment model. Paired t test or Wilcoxon signed rank test was used to compare the differences of FDG kinetic parameters in each organ before and after treatment. Results:Compared with baseline, SUV max of colon (3.23±1.29 vs 4.81±2.73), MR FDG ((2.77±1.96) vs 3.56(1.07, 9.89) μmol·100 g -1·min -1) of lungs, SUV max (2.16±0.27 vs 2.33±0.41), k3 ((0.008±0.002) vs (0.012±0.004) min -1) and MR FDG ((2.65±0.81) vs (3.76±1.59) μmol·100 g -1·min -1) of spleen, and SUV max (2.59±0.45 vs 4.49±2.73), k2 ((0.76±0.37) vs (1.27±0.66) min -1), k3 ((0.032±0.007) vs (0.066±0.029) min -1) and MR FDG ((5.14±1.44) vs (8.39±2.67) μmol·100 g -1·min -1) of bone marrow were increased after chemo-immunotherapy with significant differences ( t values: from -5.40 to 3.47, z=-2.02, all P<0.05). There were no significant differences of SUV max, k values and MR FDG in other organs ( t values: from -2.00 to 2.35, z values: from -1.45 to -0.05, all P>0.05). Conclusions:After chemo-immunotherapy, the activation of immune system may be manifested as the increase of FDG kinetic rate constants in spleen and bone marrow. The lung and colon may be target organs for immune-related adverse effects.

Objective:To investigate the diagnostic efficacy of 99Tc m-MIBI SPECT dual-phase imaging combined with rapid parathyroid hormone detection in thyroid cancer with suspected parathyroid mass. Methods:Data of 76 cases of thyroid cancer with suspected cervical parathyroid gland tumors receiving colorectal ultrasonography or CT examination in Thyroid Surgery Department of the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Blood samples were taken before surgery to detect parathyroid hormone. Parathyroid hormone was quickly detected after clamping the tumor blood vessels during surgery. Based on the postoperative pathological results, the sensitivity, specificity, accuracy and consistency of various diagnostic methods were evaluated. The ROC curve was drawn by measuring the value of the parathyroid gland concentration after reduction of the tumor blood vessels by clamping the tumor.Results:The sensitivity and accuracy of the 99Tc m-MIBI SPECT dual-phase imaging combined with the rapid detection of parathyroid hormone in diagnosis of suspected parathyroid tumors were (96.5%, 93.4%) better than the 99Tc m-MIBI SPECT dual-phase imaging methods (77.6%, 78.9%) and intraoperative rapid detection methods (86.2%, 82.8%) , and had a high consistency with the results of pathological examination, Kappa value of 0.81. The combined detection rate of suspected parathyroid tumors was significantly higher than that of 99Tc m-MIBI SPECT dual-phase imaging and rapid intraoperative detection, but there was no significant difference between 99Tc m-MIBI SPECT dual-phase imaging and intraoperative rapid detection. The area under the ROC curve of the reduction ratio a value after clamping the blood vessels of the tumor was 0.774, and the standard error was 0.073. The difference was statistically significant ( P<0.001,95% CI:0.631-0.918) . According to the results obtained by the ROC, the index (sensitivity + specificity-1) was plotted on the ordinate and a was the abscissa. The maximum value of the Jordan index was 0.584. The a value corresponding to this point was 0.52. 0.52 is the DCP value. The corresponding sensitivity, specificity, accuracy was 86.2%,72.2%,and 82.9%. Conclusion:99Tc m-MIBI SPECT dual-phase imaging combined with rapid parathyroid hormone detection during surgery has good diagnostic value for thyroid cancer with suspected parathyroid mass, and is completely consistent with pathological diagnosis.

Objective:To evaluate the effect of long-chain non-coding RNA MEG3(LncRNA MEG3) on the radiosensitivity of cervical cancer cells, and to explore its underlying mechanism.Methods:The expression of LncRNA MEG3 in cervical cancer cells was detected by qRT-PCR. In the overexpression control group (transfected with pcDNA 3.1), LncRNA MEG3 overexpression group (transfected with pcDNA 3.1-LncRNA MEG3), miR-NC inhibition group (transfected with anti-miR-NC), miR-181a-5p inhibition group (transfected with anti-miR-181a-5p), LncRNA MEG3+ miR-NC overexpression group (co-transfected with pcDNA3.1-LncRNA MEG3 and anti-miR-NC), LncRNA MEG3+ miR-181a-5p overexpression group (co-transfected with pcDNA 3.1-LncRNA MEG3 and anti-miR-181a-5p), all plasmids were transfected into SiHa cells by liposome method. The cell survival fraction was assessed by colony formation assay. The cell apoptosis rate was evaluated by flow cytometry. The cell fluorescence activity was assessed by dual luciferase reporter assay. The expression levels of PTEN, p-Akt and Akt proteins were detected by Western blot.Results:Compared with the radiosensitive group, the expression of LncRNA MEG3 was significantly down-regulated in radiation-resistant cervical cancer tissues ( P<0.05), and its expression level was positively correlated with the sensitivity of cervical cancer cells. Overexpression of LncRNA MEG3 or inhibition of miR-181a-5p could significantly enhance the irradiation sensitivity and promote the apoptosis of cervical cancer cell line SiHa (both P<0.05). The fluorescence activity of wild-type LncRNA MEG3 cells was inhibited by miR-181a-5p. Overexpression of miR-181a-5p reversed the irradiation sensitization and pro-apoptosis effect of LncRNA MEG3 and the regulation of the PTEN/Akt signaling pathway on cervical cancer cell. Conclusion:LncRNA MEG3 can enhance the sensitivity of cervical cancer cells to radiation exposure, probably by targeting the miR-181a-5p and regulating the PTEN/Akt signaling pathway, which will provide a new direction for improving clinical prognosis of cervical cancer patients.

Nanogenerator (triboelectric nanogenerator and piezoelectric nanogenerator) has experienced a rapid development since it was proposed. This technique can covert various mechanical energies into electric energy, including human motion energy, wind energy, acoustic energy and ocean energy. The converted electricity can be used for health monitoring and physiological function regulation, such as pulse detection, bioelectrical stimulation and cardiac pacing. This review summarizes the structure, working mechanism, output performance of nanogenerator and its latest progress in circulatory system, nervous system, biological tissue, sleep and rescue system. Additionally, a further analysis was also made on the application challenge of nanogenerator in clinical treatment. In the future, nanogenerator is expected to be an auxiliary power source, or even to replace battery to power medical electronic device and realize the self-powered health monitoring and physiological function regulation of human body.
Electric Power Supplies ; Electricity ; Humans

Objective To evaluate the clinical effect of alveolar bone augmentation by applying autogenous tooth bone graft material to patients with alveolar bone deficiency in orthodontic treatment. Methods Four patients with a stable periodontal condition managed with fixed orthodontic treatment were included, and the number of graft sites was 17. Cone beam computed tomography (CBCT) showed labial alveolar bone deficiency. The treatment plan included extraction, and the extracted teeth were used to prepare autogenous tooth bone material. The alveolar bone width was measured at the same site at multiple heights prior to operation and at 3 and 6 months post-operation.Results The alveolar bone width was higher at both 3 and 6 months post-operatively (P ＜ 0.05) than that pre-operatively. The alveolar bone width at 6 months post-operation was lower than that at 3 months post-operation (P ＜ 0.05). Conclusion Applying autogenous tooth bone graft material to patients with alveolar bone deficiency in orthodontic treatment can expand the range of tooth movement and result in good clinical outcomes.

Objective: To evaluate the efficacy and safety of Saccharomyces boulardii in the prevention of antibiotic-associated diarrhea (AAD) in infants and young children. Method: From November 2012 to September 2013, ten research units of large teaching hospitals or children′s hospitals participated in this multicenter randomized controlled clinical trial. Hospitalized young children aged between 1 month and 3 years (nongastrointestinal infection and antibiotic therapy required)were involved in our study. The children were randomly divided into control group and prevention group by means of block random allocation method. The control group received antibiotic therapy and other conventional treatment. The prevention group was given additional Saccharomyces boulardii (250 mg/d) orally. Diarrhea rates of two groups were compared both during the usage of antibiotics and within 14 days after the antibiotics withdrawal. The adverse reactions of Saccharomyces boulardii were observed all through this study. The results were analyzed by χ² test or Kruskal-Wallis test or t test. Result: Totally 408 cases (213 cases in prevention group and 195 cases in control group) were enrolled. The age ranged from 1 month to 3 years, with an average age of 1.14 years. The basic diseases were parenteral infections: 368 cases with different kinds of respiratory tract infections or pneumonia, 10 cases of bacterial meningitis, 9 cases with septicemia or sepsis, 6 cases with pertussis or pertussis like syndrome, 5 cases with urinary infection, 5 cases with skin or subcutaneous tissue infections, 3 cases of Kawasaki disease, one with scarlet fever and one with congenital syphilis. During the administration of antibiotics, the incidence of AAD in prevention group was 10.3% (22 cases), which was significantly lower than that of control group (57 cases, 29.2%, χ²=23.296, P<0.05). Within 14 days after the discontinuation of antibiotics, the percent of new diarrhea cases in prevention group (2.4%, 5/213) was also significantly lower than that in control group (16.4%, 32/195, χ²=23.4, P<0.05). Further analysis revealed that the rate of AAD in children less than or equal to 1 year old (25.1%, 52/207) was significantly higher than that of over 1 year old (13.4%, 27/201, χ²=8.922, P<0.05). The incidence of AAD in children treated with antibiotics for more than 5 days was 22.2%(60/270), which was significantly higher than that of less than or equal to 5 days (13.8%, 19/138, χ²=4.180, P<0.05). Although no significant difference was observed, the AAD rate of patients with combined use of two antibiotics was higher than that of using one. During the antibiotic therapy, compared with the control group, the risk of AAD in children under 1 year old was reduced by 52% (χ²=9.217, P<0.05), and 91% (χ²=20.35, P<0.05) in the children over 1 year old in prevention group. The risk of AAD of prevention group decreased by 66% (χ²=13.67, P<0.05) in patients treated with one antibiotics, and 65% in children with combined use of antibiotics (χ²=10.57, P<0.05). In patients treated with antibiotics for less than or equal to 5 days, the risk of AAD decreased by 74% in prevention group (χ²=7.38, P<0.05); and 63% if the course lasted for over 5 days (χ²=16.87, P<0.05). Within 14 days after the withdrawal of antibiotics, compared with the control group, the risk of diarrhea in the prevention group decreased by 82% (χ²=13.35, P<0.05) in infants (≤1 year old) and 93% (χ²=12.00, P<0.05) in children (>1 year old); the risk of diarrhea was reduced by 86% (χ²=9.57, P<0.05) and 87% (χ²=17.71, P<0.05) respectively in prevention group with single and combined use of antibiotics. In patients treated with antibiotics for more than 5 days, the risk of diarrhea in prevention group was reduced by 63% (χ²=22.79, P<0.05), while there was no significant difference if the antibiotics course was less than or equal to 5 days (χ²=2.97, P>0.05). No adverse effects related with Saccharomyces boulardii were observed in our study. Conclusion Saccharomyces boulardii is effective and safe to prevent AAD of infants and young children both during the usage of antibiotics and up to 14 days after drug discontinuance. It can be one of the drugs of for choice prevention of AAD in infants and young children. Trial registration Chinese Clinical Trial Tegister, ChiECRCT-2012-25.

Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene.
Actin-Related Protein 2 ; genetics ; metabolism ; Activin Receptors, Type II ; genetics ; metabolism ; Bone Morphogenetic Protein 7 ; genetics ; metabolism ; Bone Morphogenetic Protein Receptors, Type II ; genetics ; metabolism ; Breast Neoplasms ; genetics ; metabolism ; Cellular Senescence ; Female ; HeLa Cells ; Humans ; MCF-7 Cells ; Neoplasm Proteins ; genetics ; metabolism ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta ; genetics ; metabolism ; Smad3 Protein ; genetics ; metabolism ; Telomerase ; genetics ; metabolism ; Telomere Homeostasis

Telomere assumes intra-molecular G-quadruplex that is a significant drug target for inhibiting telomerase maintenance of telomeres in cancer. Metal cations have been recognized as playing important roles in stabilizing G-quadruplex, but their binding processes to human telomeric G-quadruplex remain uncharacterized. To investigate the detailed binding procedures, molecular dynamics simulations were conducted on the hybrid [3 + 1] form-one human telomeric intra-molecular G-quadruplex. We show here that the binding of a potassium ion to a G-tetrad core is mediated by two alternative pathways. Principal component analysis illustrated the dominant concerted motions of G-quadruplex occurred at the loop domains. MM-PBSA calculations revealed that binding was energetically favorable and driven by the electrostatic interactions. The lower binding site was found more constructive favorable for binding. Our data provide useful information on a potassium-mediated stable structure of human telomeric intra-molecular G-quadruplex, implicating in ion disorder associated conformational changes and targeted drug design.
Binding Sites ; G-Quadruplexes ; Humans ; Molecular Dynamics Simulation ; Movement ; Potassium ; metabolism ; Principal Component Analysis ; Substrate Specificity ; Telomere ; chemistry ; metabolism ; Thermodynamics