Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was −13.31%, 95% CI −29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: −15.45%; 95% CI −30.82%, −0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

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Background/Aims: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm²), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. Methods: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated β-galactosidase (SA-β-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. Results: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-β-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. Conclusions: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study.

Total scalp avulsion is an intractable problem in clinical practice. It often occurs in female adults, but rarely in children. In this article, we described the replantation of 2 scalp segments in a 4-year-old girl. The right segment involved the hairy scalp merely, whereas the left one involved the hairy scalp, forehead, eyelid, ear, and part of the face. Warm ischemia time was about 28 hours, and operation time was 13 hours. Although an explorative operation was performed, the left segment survived partly. A relatively satisfactory aesthetic result was obtained by transplanting split skin from the abdomen and part of the survived right avulsed scalp. According to our experience, every effort should be undertaken to save the avulsed scalp, even in severely damaged and juvenile cases.

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Genetic parameters for height (H), diameter at breast height (DBH), stem straightness (STR), and under crown clear bole height (CH) of loblolly pine (Pinus taeda L.) were estimated for 255 families (209 open pollinated (OP) and 46 controlled pollinated (CP) families) using a family model and an individual tree model at age 1, 2, 3, 5, 11, and 15 years. Heritability estimates for growth traits of individual trees at age 11 years were the highest (0.17-0.78), and those at age 15 years were the lowest (0.05-0.74). Heritability estimates for DBH, STR, and CH were lower than those for H. Genetic correlations between H and DBH were generally strongly positive, attained a maximum values at age 2 to 3, and declined slightly thereafter. The genetic correlations between CH at age 11 and both H and DBH at different ages were moderate. Age-age genetic correlations for growth traits were moderate to high (0.56-0.91) at age 5 for half-rotation age (15 years), indicating the opportunity exists for early selection. Indirect selection from the age 5 to 11 years for H and DBH could be expected to produce gains of over 50 % and 35 % respectively, for these two ages, relative to direct selection at age 15. Efficiencies of early selection for H and DBH indicated that growth at maturity could be improved by early selection.