Diagnostic efficacy of [68Ga]Ga-NY104 PET/CT to identify clear cell renal cell carcinoma.

PURPOSE: Most clear cell renal cell carcinoma (ccRCC) overexpresses carbonic anhydrase IX (CAIX). [68Ga]Ga-NY104 is a small-molecule PET agent selectively targeting CAIX. This study aims to assess the efficacy of [68Ga]Ga-NY104 PET/CT to identify ccRCC. MATERIALS AND METHODS: Participants were prospectively recruited in the study (ClinicalTrials.gov: NCT05902377). They were further divided into two groups: group 1, patients with primary renal mass who were scheduled for surgery, group 2, patients with suspected/confirmed metastatic ccRCC. All patients underwent [68Ga]Ga-NY104 PET/CT. RESULTS: A total of 47 patients (mean age, 58.8 years ± 13.5, 34 men) were recruited, including 20 patients in group 1 and 27 patients in group 2. The patient-level sensitivity, specificity, and accuracy of [68Ga]Ga-NY104 PET scan was 62%, 33%, 58% for group 1 and 95%, 100%, 96% for group 2. [68Ga]Ga-NY104 PET identified additional 26 disease regions in 67% (14/21) of patients that were previously unknown. The tumor uptake was correlated with immunohistochemical staining results. CONCLUSIONS: [68Ga]Ga-NY104 PET/CT has a high diagnostic efficacy for patients with metastatic ccRCC, while it might be of limited value in the diagnosis of primary ccRCC.

The status of nuclear medicine in China: the first official national survey.

AIM/INTRODUCTION: The National Nuclear Medicine Quality Control Center of China conducted the first official survey to investigate the nationwide situation of nuclear medicine in 2020. The survey aimed to unveil the current nuclear medicine situation and its quality control in China. MATERIALS AND METHODS: The web-based survey was conducted and the data was collected via the National Clinical Improvement System (NCIS) of China from 1st April to 31st May 2021. RESULTS: A total of 808 institutes across 30 provinces responded to the national survey. For human resources, there are 4460 physicians, 3077 technologists, 339 physicists, and 309 radiochemists. There are 887 single-photon imaging instruments, including 823 SPECT or SPECT/CT, and 365 PET instruments including 314 PET/CT. Six hundred twenty-four institutes perform SPECT examinations and 319 institutes perform PET examinations. 60% of SPECT scans are bone scintigraphy. A total of 97% of PET scans use an [18F]F-FDG tracer. Furthermore, 587 institutes provide radionuclide therapy services but only 280 institutes have admission rooms. The top three radionuclide therapies are [131I] therapy of hyperthyroidism with 546 institutes, [89Sr] therapy of bone metastasis with 400 institutes, and [131I] therapy of differentiated thyroid cancer with 286 institutes. Finally, for the frequency of equipment quality control per year, there are about 67 times self-test within the department for SPECT instruments and 111 times for PET instruments on average in each province. There are about three failures of SPECT and five failures of PET on average per year in each province. There are 408 institutes (of 624 SPECT institutes) performing quality control of SPECT radiopharmaceuticals, 216 (of 319) for PET radiopharmaceuticals, and 373 (of 587) for radionuclide therapy. CONCLUSION: These results of the first official survey towards current status of nuclear medicine in China are the foundation for the establishment of the quality control management system.

Gallium-68 labeled somatostatin receptor antagonist PET/CT in over 500 patients with neuroendocrine neoplasms: experience from a single center in China.

PURPOSE: Somatostatin receptor antagonists have shown promising performance for imaging neuroendocrine neoplasms. However, there is a lack of studies exploring the diagnostic performance of SSTR antagonists or comparing them with agonists in a large cohort of patients with NENs. This study aimed to retrospectively review all SSTR antagonist PET/CT scans conducted at Peking Union Medical College Hospital since November 2018 in patients with confirmed or suspected NENs. METHODS: Four types of SSTR antagonists were utilized, including [68Ga]Ga-NODAGA-LM3, [68Ga]Ga-DOTA-LM3, [68Ga]Ga-NODAGA-JR11, and [68Ga]Ga-DOTA-JR11. The reference standard was based on a combination of histopathology, clinical evaluation, imaging results, and follow-up. Patient-based sensitivity, specificity, and accuracy were evaluated. The SUVmax and tumor-to-liver ratio (TLR) of the hottest lesions was recorded and compared between antagonists and [68Ga]Ga-DOTATATE. RESULTS: A total of 622 antagonist scans from 549 patients were included in the analysis. The patient-level sensitivity, specificity, and accuracy of antagonist imaging (all tracers combined) were 91.0% (443/487), 91.9% (57/62), and 91.1% (500/549), respectively. In 181 patients with a comparative [68Ga]Ga-DOTATATE PET/CT scan, the patient-level sensitivity, specificity, and accuracy were 87.5% (147/168), 76.9% (10/13), and 86.7% (157/181), respectively. For the hottest lesions, SSTR antagonists all tracers combined demonstrated an overall comparable SUVmax to [68Ga]Ga-DOTATATE (40.1 ± 32.5 vs. 39.4 ± 23.8, p = 0.772). While [68Ga]Ga-NODAGA-LM3 showed significantly higher uptake than [68Ga]Ga-DOTATATE (57.4 ± 38.5 vs. 40.0 ± 22.8, p<0.001), [68Ga]Ga-NODAGA-JR11 (39.7 ± 26.5 vs. 34.3 ± 23.9, p = 0.108) and [68Ga]Ga-DOTA-LM3 (38.9 ± 32.1 vs. 37.2 ± 22.1, p = 0.858) showed comparable uptake to [68Ga]Ga-DOTATATE, and [68Ga]Ga-DOTA-JR11 showed lower uptake (28.9 ± 26.1 vs. 44.0 ± 25.7, p = 0.001). All antagonists exhibited significantly higher TLR than [68Ga]Ga-DOTATATE (12.1 ± 10.8 vs. 5.2 ± 4.5, p<0.001). CONCLUSION: Gallium-68 labeled SSTR antagonists could serve as alternatives to SSTR agonists for imaging of NENs. Among various antagonists, [68Ga]Ga-NODAGA-LM3 seems to have the best imaging profile.

Evaluation of the safety, biodistribution, dosimetry of [18F]AlF-NOTA-LM3 and head-to-head comparison with [68Ga]Ga-DOTATATE in patients with well-differentiated neuroendocrine tumors: an interim analysis of a prospective trial.

PURPOSE: 18F-labelled somatostatin receptor (SSTR) analogs offer several advantages over 68Ga in terms of yield, cost, spatial resolution and detection rate. This study presents an interim analysis of a prospective trial designed to assess the safety, biodistribution and dosimetry of [18F]AlF-NOTA-LM3, and compare its diagnostic efficacy and clinical management outcomes with [68Ga]Ga-DOTATATE or [68Ga]Ga-NODAGA-LM3 in patients with well-differentiated NETs. METHODS: Twenty-one patients with histologically confirmed well-differentiated neuroendocrine tumors (G1 and G2) were prospectively recruited. The first eight patients underwent serial PET scans at 5, 15, 30, 45, 60, and 120 min after [18F]AlF-NOTA-LM3 injection to assess biodistribution and dosimetry. The remaining patients underwent whole-body PET/CT scans. [18F]AlF-NOTA-LM3 and [68Ga]Ga-DOTATATE PET/CT were done within a week, with a minimum 24-hour interval between the two scans. Focal uptake above the surrounding background activity and could not be explained by physiologic uptake was considered lesions of NETs. Lesion number, tumor uptake, and tumor-to-background ratio (TBR) were compared. In patients with discrepant findings, the size of the smallest lesions (measured on coregistered CT) detected on [68Ga]Ga-DOTATATE and [18F]AlF-NOTA-LM3 was compared. RESULTS: [18F]AlF-NOTA-LM3 was safe and well-tolerated. Physiological uptake of [18F]AlF-NOTA-LM3 was significantly lower than that of [68Ga]Ga-DOTATATE in abdominal organs and bone marrow, but higher in blood pool and lung. The mean effective dose was 0.024 ± 0.014 mSv/MBq. [18F]AlF-NOTA-LM3 detected significantly more liver lesions (457 vs. 291, P = 0.006) and lymph node lesions (30 vs. 22, P = 0.011) compared to [68Ga]Ga-DOTATATE. The tumor uptake was comparable, but TBR was significantly higher with [18F]AlF-NOTA-LM3 for lesions from all sites except for the duodenum. The size of the minimum liver lesions (0.54 ± 0.15 vs. 1.01 ± 0.49, P<0.001) and lymph node lesions (0.50 ± 0.19 vs. 1.26 ± 0.86, P = 0.024) detected on [18F]ALF-NOTA-LM3 were significantly smaller than those detected on [68Ga]Ga-DOTATATE. CONCLUSION: [18F]AlF-NOTA-LM3 shows favorable biodistribution, higher spatial resolution and superior performance than [68Ga]Ga-DOTATATE in detecting liver and lymph node metastases, with higher TBR. Notably, it is the first SSTR analog to show superiority in detecting lymph node lesions when compared to [68Ga]Ga-DOTATATE. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT06056362.

Intermittent theta-burst stimulation improves motor function by inhibiting neuronal pyroptosis and regulating microglial polarization via TLR4/NFκB/NLRP3 signaling pathway in cerebral ischemic mice.

BACKGROUND: Neuronal pyroptosis and neuroinflammation with excess microglial activation are widely involved in the early pathological process of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuromodulatory technique, has recently been reported to be anti-inflammatory and regulate microglial function. However, few studies have elucidated the role and mechanism of rTMS underlying regulating neuronal pyroptosis and microglial polarization. METHODS: We evaluated the motor function in middle cerebral artery occlusion/reperfusion (MCAO/r) injury mice after 1-week intermittent theta-burst rTMS (iTBS) treatment in the early phase with or without depletion of microglia by colony-stimulating factor 1 receptor (CSF1R) inhibitor treatment, respectively. We further explored the morphological and molecular biological alterations associated with neuronal pyroptosis and microglial polarization via Nissl, EdU, TTC, TUNEL staining, electron microscopy, multiplex cytokine bioassays, western blot assays, immunofluorescence staining and RNA sequencing. RESULTS: ITBS significantly protected against cerebral ischemia/reperfusion (I/R) injury-induced locomotor deficits and neuronal damage, which probably relied on the regulation of innate immune and inflammatory responses, as evidenced by RNA sequencing analysis. The peak of pyroptosis was confirmed to be later than that of apoptosis during the early phase of stroke, and pyroptosis was mainly located and more severe in the peri-infarcted area compared with apoptosis. Multiplex cytokine bioassays showed that iTBS significantly ameliorated the high levels of IL-1ß, IL-17A, TNF-α, IFN-γ in MCAO/r group and elevated the level of IL-10. ITBS inhibited the expression of neuronal pyroptosis-associated proteins (i.e., Caspase1, IL-1ß, IL-18, ASC, GSDMD, NLRP1) in the peri-infarcted area rather than at the border of infarcted core. KEGG enrichment analysis and further studies demonstrated that iTBS significantly shifted the microglial M1/M2 phenotype balance by curbing proinflammatory M1 activation (Iba1+/CD86+) and enhancing the anti-inflammatory M2 activation (Iba1+/CD206+) in peri-infarcted area via inhibiting TLR4/NFκB/NLRP3 signaling pathway. Depletion of microglia using CSF1R inhibitor (PLX3397) eliminated the motor functional improvements after iTBS treatment. CONCLUSIONS: rTMS could alleviate cerebral I/R injury induced locomotor deficits and neuronal pyroptosis by modulating the microglial polarization. It is expected that these data will provide novel insights into the mechanisms of rTMS protecting against cerebral I/R injury and potential targets underlying neuronal pyroptosis in the early phase of stroke.

Enriched Environment-Induced Neuroprotection against Cerebral Ischemia-Reperfusion Injury Might Be Mediated via Enhancing Autophagy Flux and Mitophagy Flux.

Background: Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia-reperfusion injury. Methods: We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results: Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion: These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study.

Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts-mediated osteogenic differentiation of BMSCs.

BACKGROUND: Bone homeostasis is a dynamic process maintained by osteoblasts and osteoclasts, which may be regulated by excessive mechanical stress (EMS). OBJECTIVES: Our study aimed to explore the relationship between osteogenic differentiation of BMSCs and EMS-activated osteoclast differentiation of RAW 264.7 cells in order to optimise orthodontic treatment. METHODS: We established the model of EMS in vivo and in vitro. In vivo, HE, Safranin-O staining, micro-CT, and immunofluorescence double-labelling were utilised to assess the changes in condylar, the distributions of osteoblasts, osteoclasts and MAPKs. In vitro, the effects of EMS-activated osteoclast differentiation exerting on osteogenic differentiation of BMSCs were observed by Western Blot, qRT-PCR and Alizarin Red staining. Furthermore, the role of MAPKs in this progress was explored by using inhibitors of MAPKs and co-culture supernatants. RESULTS: In vivo, EMS led to the degradation of condylar cartilage and destruction of subchondral bone, diagnosed as temporomandibular joint osteoarthritis (TMJ OA). Osteoclasts and osteoblasts were both enriched in subchondral bone, but osteoclast predominated. The expressions of p-JNK, p-ERK1/2, and p-p38 were all activated in vitro and in vivo, which were localised mainly in the Trap+ area in subchondral bone. Interestingly, only the inactivation of p-ERK1/2 in osteoclasts significantly inhibited the osteogenic differentiation of BMSCs in vitro. This revealed that p-ERK1/2 played a key role in the osteoclasts-induced osteogenic differentiation of BMSCs. CONCLUSION: Our results proved that EMS led to TMJ OA, in which upregulated p-ERK1/2 in osteoclasts was mechanosensitive and facilitated the osteogenic differentiation of BMSCs.

Unique TP53 neoantigen and the immune microenvironment in long-term survivors of Hepatocellular carcinoma.

Neoantigens are T-cell antigens derived from protein-coding mutations in tumor cells. Although neoantigens have recently been linked to anti-tumor immunity in long-term survivors of cancers such as melanoma, their prognostic and immune-modulatory role in many cancer types remain unexplored. We investigate neoantigens in hepatocellular carcinoma (HCC) through a combination of whole exome sequencing (WES), RNA sequencing (RNA-seq), computational bioinformation, and immunohistochemistry. Our analysis reveals that patients carried with TP53 neoantigen have a longer overall survival than others (p = 0.0371) and they showed higher Immune score (p = 0.0441), higher cytotoxic lymphocytes infiltration (p = 0.0428), and higher CYT score (p = 0.0388). In contrast, the prognosis is not associated with TMB and neoantigen load. Our study draws a preliminary conclusion that it is not TMB or neoantigen load but the TP53 specific neoantigen is related to overall survival of HCC patients. We suggest that the TP53 neoantigen may affect prognosis by regulating anti-tumor immunity and that the TP53 neoantigen may be harnessed as potential targets for immunotherapies of HCC.

High-Intensity Interval Training Improves Physical Function, Prevents Muscle Loss, and Modulates Macrophage-Mediated Inflammation in Skeletal Muscle of Cerebral Ischemic Mice.

Although skeletal muscle is the main effector organ largely accounting for disability after stroke, considerably less attention is paid to the secondary abnormalities of stroke-related skeletal muscle loss. It is necessary to explore the mechanism of muscle atrophy after stroke and further develop effective rehabilitation strategy. Here, we evaluated the effects of high-intensity interval (HIIT) versus moderate-intensity aerobic training (MOD) on physical function, muscle mass, and stroke-related gene expression profile of skeletal muscle. After the model of middle cerebral artery occlusion (MCAO) was successfully made, the blood lactate threshold corresponding speed (S LT) and maximum speed (S max) were measured. Different intensity training protocols (MOD < S LT; S LT < HIIT < S max) were carried out for 3 weeks beginning at 7 days after MCAO in the MOD and HIIT groups, respectively. We found that both HIIT and MOD prevented stroke-related gastrocnemius muscle mass loss in MCAO mice. HIIT was more beneficial than MOD for improvements in muscle strength, motor coordination, walking competency, and cardiorespiratory fitness. Furthermore, HIIT was superior to MOD in terms of reducing lipid accumulation, levels of IL-1ß and IL-6 in paretic gastrocnemius, and improving peripheral blood CD4+/CD8+ T cell ratio, level of IL-10. Additionally, RNA-seq analysis revealed that the differentially expressed genes among HIIT, MOD, and MCAO groups were highly associated with signaling pathways involved in inflammatory response, more specifically the I-kappaB kinase/NF-kappaB signaling. Following the outcome, we further investigated the infiltrating immune cells abundant in paretic muscles. The results showed that HIIT modulated macrophage activation by downregulating CD86+ (M1 type) macrophages and upregulating CD163+ (M2 type) macrophages via inhibiting the TLR4/MyD88/NFκB signaling pathway and exerting an anti-inflammatory effect in paretic skeletal muscle. It is expected that these data will provide novel insights into the mechanisms and potential targets underlying muscle wasting in stroke.

Characterization and genome sequencing of a novel T7-like lytic phage, kpssk3, infecting carbapenem-resistant Klebsiella pneumoniae.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has spread globally and emerged as an urgent public health threat. Bacteriophages are considered an effective weapon against multidrug-resistant pathogens. In this study, we report a novel lytic phage, kpssk3, which is able to lyse CRKP and degrade exopolysaccharide (EPS). The morphological characteristics of kpssk3 observed by transmission electron microscopy, including a polyhedral head and a short tail, indicate that it belongs to the family Podoviridae. A one-step growth curve revealed that kpssk3 has a latent period of 10 min and a burst size of 200 plaque-forming units (pfu) per cell. kpssk3 was able to lyse 25 out of 27 (92.59%) clinically isolated CRKP strains, and it also exhibited high stability to changes in temperature and pH. kpssk3 has a linear dsDNA genome of 40,539 bp with 52.80% G+C content and 42 putative open reading frames (ORFs). No antibiotic resistance genes, virulence factors, or integrases were identified in the genome. Based on bioinformatic analysis, the tail fiber protein of phage kpssk3 was speculated to possess depolymerase activity towards EPS. By comparative genomics and phylogenetic analysis, it was determined that kpssk3 is a new T7-like virus and belongs to the subfamily Autographivirinae. The characterization and genomic analysis of kpssk3 will promote our understanding of phage biology and diversity and provide a potential strategy for controlling CRKP infection.

Peripheral T cell lymphoma after chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report.

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

Differential Role of Rapamycin in Epidermis-Induced IL-15-IGF-1 Secretion via Activation of Akt/mTORC2.

Backgroud/Aims: The effects of rapamycin (RPM) on wound healing have been previously studied. However, reciprocal contradictory data have been reported, and the underlying mechanism remains unclear. This study aims to uncover differential role of RPM in regulation of wound healing and explore the possible mechanism. METHODS: C57BL/6J mice and epidermal cells were treated with different doses of RPM. The wound re-epithelialization was observed by hematoxylin and eosin (HE) staining. The expression of IL-15 and IGF-1 were detected by immunohistochemistry and quantitative real-time PCR. Epidermal cell survival was determined by CCK-8 assays. Moreover, the mTORC1 and mTORC2 pathway were examined by western blot analysis. RESULTS: This study showed that differential doses of RPM could lead to separate consequences in epidermis. Histological analyses showed that low-dose RPM promoted wound healing, and enhanced the expression of IL-15 and IGF-1. Furthermore, western blot analysis showed that the effect of low-dose RPM in epidermis were not through mTORC1 pathway. Instead, activation of the Akt/mTORC2 pathway was involved in low-dose RPM-induced IL-15 and IGF-1 production in epidermis, while high-dose RPM inhibited the expression of IL-15 and IGF-1 and the activity of mTORC1 and mTORC2 pathway. CONCLUSION: This study for the first time demonstrated that RPM-mediated wound healing was dose-dependent.

Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: a systematic review and meta-analysis.

Ethnopharmacological relevance: Ophiocordyceps sinensis (O. sinensis), a genus of ascomycete fungi, has been widedly used in China as a dietary supplement or natural remedy and intensively studied in various disease models with its immunomodulatory potentials. It is a rich source of various bioactive compounds and used for treating end-stage renal disease. This systematic review with clinical evidence aimed to highlight the efficacy and safety of O. Sinensis as an adjuvant treatment for patients undergoing dialysis. Materials and methods: A systematic search through nine electronic databases up to 31 April 2024, was conducted for related studies. The Cochrane risk-of-bias tool was used to evaluate the quality of studies. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the certainty of evidence. Two researchers independently searched the literature and evaluated the risk of bias. Results: After the screening, 35 randomized controlled trials (RCTs) involving 2,914 patients were eventually included. The meta-analysis showed that using O. sinensis effectively reduced the following outcomes in patients undergoing dialysis: C-reactive protein (15RCTs, MD = -2.22, 95% CI -3.24 to -1.20; very low certainty evidence); creatinine (22RCTs, MD =1.33, 95% CI -1.79 to -0.87; very low certainty evidence); blood urea nitrogen (21RCTs, MD = -1.57, 95% CI -2.07 to -1.07; low certainty evidence);. It could also effectively improve the following outcomes in patients undergoing dialysis: albumin (20RCTs, MD = -0.81, 95% CI -1.21 to -0.41; low certainty evidence); hemoglobin (19RCTs, MD = -1.00, 95% CI -1.43 to -0.57; low certainty evidence). The rate of adverse drug reactions was higher in the control group than in the experimental group (4RCTs, MD = 1.81, 95% CI 0.88-3.74). Conclusion: The current evidence indicates that patients with dialysis receiving O. sinensis in the adjuvant treatment may improve nutritional and micro-inflammatory status and renal function for both hemodialysis and peritoneal dialysis patients. However, some limitation affected the generalizability of our findings. High-quality studies evaluating mortality outcomes of patients with different dialytic modalities in CKD are warranted in future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324508, registration number CRD42022324508.

Fluorogenic Aptamer-Based Hybridization Chain Reaction for Signal-Amplified Imaging of Apurinic/Apyrimidinic Endonuclease 1 in Living Cells.

A fluorogenic aptamer (FA)-based hybridization chain reaction (HCR) could provide a sensitive and label-free signal amplification method for imaging molecules in living cells. However, existing FA-HCR methods usually face some problems, such as a complicated design and significant background leakage, which greatly limit their application. Herein, we developed an FA-centered HCR (FAC-HCR) method based on a remote toehold-mediated strand displacement reaction. Compared to traditional HCRs mediated by four hairpin probes (HPs) and two HPs, the FAC-HCR displayed significantly decreased background leakage and improved sensitivity. Furthermore, the FAC-HCR was used to test a non-nucleic acid target, apurinic/apyrimidinic endonuclease 1 (APE1), an important BER-involved endonuclease. The fluorescence analysis results confirmed that FAC-HCR can reach a detection limit of 0.1174 U/mL. By using the two HPs for FAC-HCR with polyetherimide-based nanoparticles, the activity of APE1 in living cells can be imaged. In summary, this study could provide a new idea to design an FA-based HCR and improve the performance of HCRs in live cell imaging.

The role of angiotensin II activation of yes-associated protein/PDZ-binding motif signaling in hypertensive cardiac and vascular remodeling.

Vascular remodeling is the pathogenic basis of hypertension and end organ injury, and the proliferation of vascular smooth muscle cells (VSMCs) is central to vascular remodeling. Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are key effectors of the Hippo pathway and crucial for controlling cell proliferation, apoptosis and differentiation. The present study investigated the role of YAP/TAZ in cardiac and vascular remodeling of angiotensin II-induced hypertension. Ang II induced YAP/TAZ activation in the heart and aorta, which was prevented by YAP/TAZ inhibitor verteporfin. Treatment with verteporfin significantly reduced Ang II-induced cardiac and vascular hypertrophy with a mild reduction in systolic blood pressure (SBP), verteporfin attenuated Ang II-induced cardiac and aortic fibrosis with the inhibition of transform growth factor (TGF)ß/Smad2/3 fibrotic signaling and extracellular matrix collagen I deposition. Ang II induced Rho A, extracellular signal-regulated kinase 1/2 (ERK1/2) and YAP/TAZ activation in VSMCs, either Rho kinase inhibitor fasudil or ERK inhibitor PD98059 suppressed Ang II-induced YAP/TAZ activation, cell proliferation and fibrosis of VSMCs. Verteporfin also inhibited Ang II-induced VSMC proliferation and fibrotic TGFß1/Smad2/3 pathway. These results demonstrate that Ang II activates YAP/TAZ via Rho kinase/ERK1/2 pathway in VSMCs, which may contribute to cardiac and vascular remodeling in hypertension. Our results suggest that YAP/TAZ plays a critical role in the pathogenesis of hypertension and end organ damage, and targeting the YAP/TAZ pathway may be a new strategy for the prevention and treatment of hypertension and cardiovascular diseases.

Hypermetabolic Broad Ligament Leiomyoma in Postmenopausal Women Mimicking Ovarian Tumors on 18 F-FDG PET/CT.

ABSTRACT: Extrauterine leiomyomas are rare and often occur in broad ligament or fallopian tube. Diagnosis of broad ligament leiomyoma is challenging for its solid nature and special location. Leiomyomas typically exhibit mild FDG uptake, especially in postmenopausal woman. We here reported a 57-year-old postmenopausal woman with intense FDG-avid broad ligament leiomyoma on 18 F-FDG PET/CT, which might be misdiagnosed as ovarian tumor.

Efficacy of L-arginine and Pycnogenol ® in the treatment of male erectile dysfunction: a systematic review and meta-analysis.

Background: The objective of this meta-analysis was to review clinical trials of the combination of Pycnogenol ® and L-arginine (PAL) in the treatment of erectile dysfunction in men and to observe the effect of PAL combined therapy on sexual function in patients with erectile dysfunction (ED), and we hope to provide more choices of drugs for treating patients with ED. Methods and analysis: The study was constructed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched seven databases from inception to 15 February 2023, for a comprehensive search of clinical trials using relevant keywords. Continuous variables in this meta-analysis were calculated using the mean difference and 95% confidence interval. All relevant statistical analyses were performed using RevMan v. 5.4 software. Results: Three studies with 184 patients were included in the present meta-analysis. There were no significant differences in the basic characteristics of the included studies. The results of the current meta-analysis showed that there were significant differences in the international index of erectile function scores (erectile domain), intercourse satisfaction scores, orgasmic function scores, overall satisfaction scores, and sexual desire scores between the combination treatment group and the control group. There was no significant difference in improving the testosterone levels between the two groups. Conclusion: These results indicate that the combination of PAL may have a significant effect on improving sexual function in patients with mild to moderate ED. This study will provide clinicians with more options for treating patients with ED. More randomized controlled trials are needed in the future to further demonstrate the effect of combination therapy on sexual function in patients with ED. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprosperoUnique, Identifier: CRD42023411781.