The coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID‐19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID‐19, especially for severe and critical patients. Menstrual blood‐derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty‐four patients were enrolled from January to April 2020 in a multicenter, open‐label, nonrandomized, parallel‐controlled exploratory trial. Twenty‐six patients received allogeneic, menstrual blood‐derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 10
7
MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1‐month period following MSC infusion. Safety was measured using the frequency of treatment‐related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group;
P
= .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO
2
was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC‐based therapy may serve as a promising alternative method for treating severe and critical COVID‐19.
medRxiv preprint 17. WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf. 18. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39(5): 529-39. 19. Huang KJ, Su IJ, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients.J Med Virol 2005; 75(2): 185-94. 20. Jiang Y, Xu J, Zhou C, et al. Characterization of cytokine/chemokine profiles of severe acute respiratory syndrome. Am J Respir Crit Care Med 2005; 171(8): 850-7. 21. Ying T, Prabakaran P, Du L, et al. Junctional and allele-specific residues are critical for All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Generating two long-living low-energy excitations after absorption of a single high-energy photon has stoked interest in singlet fission (SF) to enhance solar energy conversion in photovoltaics. To this end, survival of the triplet states is critical. This process is investigated in diethynylbenzene-linked tetraaza-triisopropylsilylethynylpentacene dimers, for which SF is energetically feasible and facilitated by the close distances between the azapentacenes. The ortho and meta connectivities are explored and compared with the tetraazapentacene molecule and the (1,3,5) trimer. Efficient SF (potential Φ T ≥ 160%) is demonstrated in all oligomers by quantitative kinetic analysis of broadband transient absorption and fluorescence signals. Together with dynamics of the starting singlet, the triplet pair, and the final free triplet state, our results show an intermediate component with spectral properties compatible with a biexcitonic state. Long-living triplets represent only a fraction of the high number of transient triplet pair intermediates, which undergo triplet−triplet annihilation as well as fusion between neighboring pentacenes. Therefore, our work provides new insight into the SF in covalent dimers and paves the way for the application of these materials for carrier multiplication.
Increased colonic bile acid (BA) exposure, frequent in diarrhea‐predominant irritable bowel syndrome (IBS‐D), can affect gut function. Nerve growth factor (NGF) is implicated in the development of visceral hyper‐sensitivity (VH). In this study, we tested the hypothesis that BAs cause VH via mucosal mast cell (MMC)‐to‐nociceptor signaling, which involves the farnesoid X receptor (FXR)/NGF/transient receptor potential vanilloid (TRPV)1 axis. BAs were intracolonically administered to rats for 15 d. Visceral sensitivity to colorectal distention and colonic NGF expression were examined. BAs caused VH, an effect that involved MMC‐derived NGF and was accompanied by enhanced TRPV1 expression in the dorsal root ganglia. Anti‐NGF treatment and TRPV1 antagonism inhibited BA‐induced VH. BAs induced NGF mRNA and protein expression and release in cultured mast cells. Colonic supernatants from patients with IBS‐D with elevated colonic BA content transcriptionally induced NGF expression. In FXR−/− mice, visceral sensitivity and colonic NGF expression were unaltered after BA treatment. Pharmacological antagonism and FXR silencing suppressed BA‐induced NGF expression and release in mast cells. Mitogen‐activated protein kinase kinase (MKK) 3/6/p38 MAPK/NF‐κB signaling was mechanistically responsible for FXR‐mediated NGF expression and secretion. The findings show an MMC‐dependent and FXR‐mediated pronociceptive effect of BAs and identify the BA/FXR/NGF/TRPV1 axis as a key player in MMC‐to‐neuron communication during pain processing in IBS.—Li, W.‐T., Luo, Q.‐Q., Wang, B., Chen, X., Yan, X.‐J., Qiu, H.‐Y., Chen, S.‐L. Bile acids induce visceral hypersensitivity via mucosal mast cell–to–nociceptor signaling that involves the farnesoid X receptor/nerve growth factor/transient receptor potential vanilloid 1 axis. FASEB J. 33, 2435–2450 (2019). http://www.fasebj.org
Term pregnancies with idiopathic polyhydramnios, especially moderate-severe ones are at a significantly increased rate for adverse pregnancy outcome. Increased antepartum surveillance of fetal well-being and timed delivery are warranted.
COVID-19 has become a global concern. A large number of reports have explained the clinical characteristics and treatment strategies of COVID-19, but the characteristics and treatment of COVID-19 patient with systemic lupus erythematosus (SLE) are still unclear. Here, we report the clinical features and treatment of the first SLE patient with confirmed COVID-19 pneumonia. This was a 39-year-old woman, diagnosed with SLE 15 years ago, whose overall clinical characteristics (symptoms, laboratory tests, and chest CTs) were similar to those of the general COVID-19 patients. She continued to take the previous SLE drugs (doses of glucocorticoids, hydroxychloroquine, and immunosuppressive agents were not reduced) and was treated with strict antiviral and infection prevention treatment. After the first discharge, she got a recurrence of COVID-19 during her home isolation, and then returned to hospital and continued the previous therapy. Finally, this long-term immune suppressive patient’s COVID-19 was successfully cured. The successful recovery of this case has significant reference value for the future treatment of COVID-19 patients with SLE.
Key Points
• COVID-19 patients with SLE is advocated to continue the medical treatment for SLE.
• Hydroxychloroquine may have potential benefits for COVID-19 patients with SLE.
• COVID-19 patients with SLE is prone to relapse, and multiple follow-ups are necessary.
Metabolic syndrome has been previously identified as a risk factor for breast cancer and is increasingly a public health concern. This study aims to investigate the prevalence of metabolic syndrome and its components among primary breast cancer and control population. The clinical data of metabolic syndrome and its components in the breast cancer (605 cases) and control population (3212 cases), from Breast Cancer Center and Physical Examination Center of Chongqing, China, from July 2015 to February 2017, were collected for comparative analysis. This study was prospectively registered in Chinese Clinical Trial Registry (http://www.chictr.org.cn/, number: ChiCTR-OOB-15007543). The prevalence of metabolic syndrome in breast cancer (32.6%) was obviously higher than that in control population (18.2%) (p<0.001; OR: 2.173, 95%CI: 1.793 to 2.633). With age stratification, the prevalence of metabolic syndrome in breast cancer group aged below 60 years (24.9%, p<0.001; OR: 2.216, 95%CI: 1.744 to 2.816) and equal/above 60 years (58.3%, p<0.001; OR: 2.291, 95%CI: 1.580 to 3.322) were also statistically higher than those (13.0% & 37.9%) in control population, respectively. Breast cancer women were more likely to have preobese (BMI 25.0-29.9) or obesity (BMI ≥30.0), broader waist circumference, lower HDL-C level, higher systolic and/or diastolic blood pressure and higher fasting blood glucose level compared to the control population, corresponding prevalence were 31.7%vs.19.4%, 76.0%vs.29.6%, 37.4%vs.30.4%, 34.2%/27.3%vs.27.6%/14.2% and 25.0%vs.20.1%, respectively (p<0.01). In summary, there is high prevalence of metabolic syndrome and its components in Chinese breast cancer women, and metabolic syndrome is closely related with breast cancer. Therefore, screening and prevention strategy of metabolic syndrome should be carried out in the management of breast cancer.
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