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Background Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature. Case presentation In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy. Conclusion This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.

Background Syphilis, a sexually transmitted disease, presents with a wide range of clinical manifestations. As the global rate of syphilis infection continues to rise, so does the incidence of syphilis-associated nephritis. Characterized by diverse clinical and pathological features, the disease shows a good response to penicillin treatment. This article presents the case of a 46-year-old Chinese male patient exhibiting edema, hematuria, proteinuria, and a tendency towards rapidly progressive glomerulonephritis (RPGN). The patient was diagnosed with membranoproliferative glomerulonephritis (MPGN), with syphilis being a likely etiology and co-infection with Hepatitis B virus (HBV). He was treated with benzathine penicillin for three weeks, followed by low-dose glucocorticoids and mycophenolate mofetil (MMF) for subsequent treatment, leading to a significant improvement in his condition. Conclusion Highlighting the significance of syphilis as a cause of nephritis and emphasizing the importance of timely diagnosis and treatment can greatly alleviate the patient’s condition. Additionally, the role of Hepatitis B virus as a contributing factor in the development of nephritis should not be overlooked. Clinical trial number Not applicable.

Background To assess the safety and efficacy of dabigatran-based triple antithrombotic (TAT) regimen in patients after percutaneous coronary intervention (PCI) with atrial fibrillation (AF). Methods A multicenter, open-label, randomized controlled trial across 50 Chinese hospitals enrolled nonvalvular AF patients after coronary stenting. Participants were randomly assigned to receive dabigatran (110 mg twice/daily) or warfarin-based TAT regimen (dabigatran or warfarin with aspirin and clopidogrel) for 1 month and then convert to dual antithrombotic therapy (dabigatran or warfarin with clopidogrel) for 6 months. The primary safety endpoint was the first occurrence of clinically relevant bleeding (BARC types 2–5). Secondary endpoints included net adverse clinical events (NACEs) and major or clinically relevant non-major bleeding (CRNB). And the efficacy endpoint was the major adverse cardiac and cerebral events (MACCEs). Results The study was terminated early due to COVID-19 impacting recruitment. A total of 540 patients were enrolled. BARC types 2–5 bleeding occurred in 8.0% and 4.3% of patients in warfarin and dabigatran groups, respectively (HR 0.54; 95% CI 0.26–1.09; P  = 0.0861). And total bleeding events (BARC 1–5) were 20.5% and 9.4% (HR 0.44; 95% CI 0.27–0.70; P  = 0.0005). Dabigatran showed a lower total bleeding risk than warfarin, with similar risks for BARC types 2–5 bleeding, NACEs, CRNB, major bleeding, and MACCEs. Conclusions Among AF patients underwent PCI, the dabigatran-based TAT regimen did not significantly reduce the rate of BARC types 2–5 bleeding at 6 months compared with warfarin-based regimen, although the power of the study to find a difference was low due to early termination (COACH-PCI, NCT03536611, https://clinicaltrials.gov/show/NCT03536611 ).

Past epidemiologic studies have indicated that the ideal cardiovascular health (CVH) metrics are associated with a lower risk of cardiovascular diseases (CVDs) and stroke. Carotid artery stenosis (CAS) causes approximately 10% of ischemic strokes. The association between ideal CVH and extracranial CAS has not yet been assessed. In the current study, extracranial CAS was assessed by carotid duplex ultrasonography. Logistic regression was used to analyze the association between ideal CVH metrics and extracranial CAS. A total of 3297 participants (52.2% women) aged 40 years and older were selected from the Jidong community in China. After adjusting for sex, age and other potential confounds, the odds ratios (95% confidence intervals) for extracranial CAS were 0.57 (0.39–0.84), 0.46 (0.26–0.80) and 0.29 (0.15–0.54) and for those quartiles, quartile 2 (9–10), quartile 3 (11) and quartile 4 (12–14), respectively, compared with quartile 1 (≤8). This negative correlation was particularly evident in women and the elderly (≥60 years). This cross-sectional study showed a negative correlation between the ideal CVH metrics and the prevalence of extracranial CAS in northern Chinese adults.

Background Circulating microRNAs (miRNAs) are recently a rapidly increasing of interest as non-invasive biomarkers for diagnosis and prognosis of acute myocardial infarction (AMI). Previous studies revealed that several miRNAs exhibited the capacity for diagnosis and prognosis of AMI, the reasons why these circulating miRNAs are concerned as targets for investigation are quite cryptogenic, presumably due to the lack of clues provided by global surveillance at the transcriptome level, and the current data for some miRNAs are controversial and inconsistent among independent studies. Methods To comprehensively profiling the potential miRNAs for diagnosis and prognosis of AMI, we reported transcriptomes of circulating miRNAs in the plasma of 27 healthy controls, 64 AMI patients (37 STEMI and 27 NSTEMI) and 20 AMI patients who were subjected to reperfusion therapy. Meanwhile, the cTnI of AMI patients was parallel determined. Differentially-circulated miRNAs were analyzed between each group. All detected circulating miRNAs were examined by ROC analysis and then LASSO dimension reduction to obtain an optimal panel for diagnosis of AMI. A five-year period follow-up towards the AMI and reperfusion patients was performed, and the prognostic value of circulating miRNAs in these patients was estimated by using the Cox regression model, ROC and Kaplan-Meier curves. Results Comprehensive global differences of miRNAs transcriptome among AMI, reperfusion patients and healthy controls were identified. A total of 40 miRNAs, called high diagnostic performance miRNAs, including several previous well-studied miRNAs with AUC greater than 0.85 were shown to discriminate AMI with healthy controls. In addition, 29 miRNAs were analyzed to be strongly correlated with the plasma cTnI level, of which 20 overlapped with high diagnostic performance miRNAs. These overlapped miRNAs are over-represented in the pathways which actually reflect the pathological cause of myocardial infarction, as well as the regulation of gene expression and energetic pathway of cellular response to hypoxia. Finally, two miRNAs were analyzed to be significantly correlated to all-cause mortality. Conclusion This is the first time to survey plasma miRNAs for the development of AMI diagnostic and prognostic biomarkers at the transcriptome level. A subset of miRNAs exhibited potential diagnostic and prognostic merits for AMI.

S-Allyl cysteine (SAC), an organic compound and a natural constituent of Allium sativum, commonly known as garlic have been consumed in routine foods are known to possess various biological activities. Nevertheless, scientific evidence on the protective effect of SAC against neonatal asthmatic rats is not available. Hence, the present study aimed at investigating the anti-asthmatic activity of SAC in neonatal asthmatic rats using Wistar rats. The study conducted in 4 groups consists of normal control rats, asthma-induced, asthma animals administered with SAC (25 mg/kg), and SAC control. At the end of the experimental period, inflammatory cells in bronchoalveolar lavage fluid (BALF), inflammatory markers, fibrinogen level, activated partial thromboplastin time, coagulation factor activity, and histopathology were elucidated. The current investigation exhibits that SAC significantly reduced the total leukocytes, with restored fibrinogen level, and activated partial thromboplastin time. In addition, the levels of inflammatory cytokines such as TNF-α (tumor necrosis factor- α), IL-6 (Interleukin 6), and IL-1β have also attenuated in SAC treated animals. Furthermore, the mRNA expression levels of COX2 (cyclooxygenase-2), MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cell expressed and secreted), and eotaxin were reduced in SAC treated animals. Treatment of rats with SAC significantly reduced inflammation and eosinophil infiltration in the lungs. These results suggest that SAC exert protection in neonatal asthmatic rats suffering from acute or chronic inflammation by inducing anti-inflammatory and cell-protective responses.

Background Measuring family members’ satisfaction with inpatient psychiatric care may help improve the quality of healthcare in psychiatric hospitals. This survey aimed to investigate the satisfaction of family members with inpatient psychiatric care and to explore its associated factors, using a newly-developed 5-item questionnaire. Methods This study included 1598 family members of psychiatric inpatients in 32 tertiary public psychiatric hospitals in 29 provinces of China. Satisfaction and demographic data were collected by research staff while patient and hospital data were retrieved separately. Results We found that the overall satisfaction level was 93.84% (23.46/25). The total satisfaction score in Northeast China was the highest, followed by the East, Middle and West regions ( p  < 0.001). There was no significant sex difference in total family satisfaction scores. Family members with a lower educational background (elementary school or less) had significantly lower satisfaction. Family members of patients who were diagnosed with schizophrenia were significantly less satisfied with doctor-family communication. In different treatment response subgroups, the marked improvement subgroup had significantly higher total satisfaction scores and subscores. Meanwhile, lower self-payment expenses and a higher number of psychologic treatments offered per day were significantly associated with higher total satisfaction scores and all subscores. Logistic regression showed a higher educational background, more psychologic treatments offered per day, adequacy of professional staffing (higher doctor/bed, nurse/bed and psychologist/bed ratio) were all significantly associated with higher family satisfaction. Conclusions We suggest government and hospital managers recruit more mental health professions to improve family satisfaction. If feasible, providing more psychologic treatments to inpatients may also improve families’ satisfaction and involvement.

Background/Aims: The transplantation of cardiac progenitor cells (CPCs) improves neovascularization and left ventricular function after myocardial infarction (MI). The bone morphogenetic protein antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. The present study examined the role of Grem2 in CPC differentiation and cardiac repair. Methods: To determine the role of Grem 2 during CPC differentiation, c-Kit+ CPCs were cultured in differentiation medium for different times, and Grem2, Notch1 and Jagged1 expression was determined by RT-PCR and western blotting. Short hairpin RNA was used to silence Grem2 expression, and the expression of cardiomyocyte surface markers was assessed by RT-PCR and immunofluorescence staining. In vivo experiments were performed in a mouse model of left anterior descending coronary artery ligation-induced MI. Results: CPC differentiation upregulated Grem2 expression and activated the Notch1 pathway. Grem2 knockdown inhibited cardiomyocyte differentiation, and this effect was similar to that of Notch1 pathway inhibition in vitro. Jagged1 overexpression rescued the effects of Grem2 silencing. In vivo, Grem2 silencing abolished the protective effects of CPC injection on cardiac fibrosis and function. Conclusions: Grem2 regulates CPC cardiac differentiation by modulating Notch1 signaling. Grem2 enhances the protective effect of CPCs on heart function in a mouse model of MI, suggesting its potential as the rapeutic protein for cardiac repair.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations 1 , 2 . RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants 3 . More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS 4 . Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance. RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.