Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most ...likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI −7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 ( P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI −99.17% to −17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
This investigation examined how the Bacillus vallismortis laccase (rBVL-MRL522) influenced the physicochemical characteristics, structural attributes, and functional capabilities of both dough and ...noodles. Incorporating rBVL-MRL522 (1 U/g) did not lead to a substantial change in the water absorption of wheat flour. However, the introduction of rBVL-MRL522 caused a significant elongation in the formation time of wheat flour dough, extending it by 88.9%, and also resulted in a 50% increase in the stabilization duration of wheat flour dough. Furthermore, adding rBVL-MRL522 led to a proportional rise in both the elastic and viscous moduli (G’’ of the dough, signifying that r-BVL (rBVL-MRL522) has a beneficial effect on the gluten strength of the dough. Integrating rBVL-MRL522 promoted the consolidation of the gluten-based cross-linked structure within the dough, decreasing the size of starch particles and, more evenly, the dispersion of these starch particles. In the noodle processing, adding rBVL-MRL522 at a rate of 1 U/g raised the L* value of the noodles by 2.34 units compared to the noodles prepared without the inclusion of rBVL-MRL522. Using a greater amount of rBVL-MRL522 (2 U/g) substantially increased the hardness of the noodles by 51.31%. Additionally, rBVL-MRL522 showed a noteworthy enhancement in the elasticity, cohesiveness, and chewiness of the noodles. In conclusion, rBVL-MRL522 promoted the cross-linking gluten, leading to a more extensive and condensed three-dimensional network structure in raw and cooked noodles. As a result, this study offers valuable insights into the environmentally friendly processing of dough and associated products.
The uncertainty and unpredictability of a transportation network roots in the dynamics of individual travel behavior, which can be revised consciously or repeated habitually depending upon the ...reality and personality. In this paper, we propose to study the day-to-day departure time choice behavior of the travelers, using real observation data collected from a smartphone app, "Metropia". Influenced by the information and incentives provided in the app and the comparison with the experience gained from the last trip, a transformation process of traveler's day-to-day experience on departure time from an existing habit to a new one is analyzed in this study. The analysis result in a binary choice model for the shift of departure time for each repeated morning commute trip comparing with the last one, which proves that users' experience in app engagement, previous travel time saving, habitual travel time, incentives, and commute flexibility are able to trigger day-to-day behavioral change for their morning home-to work commutes. The findings of this research provide insights on the users' adaption to a new traffic information service along with incentives, and corresponding behavior changes over a transition period. The outcomes suggest ways to improve ICT services and incentive scheme, as well as the transportation operation and demand management.
Long-term grazing leads to soil degradation in Inner Mongolia grassland. Based on the Hulunbeier meadow steppe, the variation characteristics of soil nitrogen content and storage in soil layers ...between 0-40 cm, under six different grazing intensities, and the response of vegetation and other physical and chemical properties of soil to grazing were studied. The main results were as follows: (1) Moderate grazing increased soil total nitrogen (TN), soluble total nitrogen (STN) and microbial biomass nitrogen (MBN) contents, while heavy grazing decreased MBN content. In the year with more rain, heavy grazing increased nitrate nitrogen (NOsub.3 sup.−-N) content and storage, while less rain increased ammonium nitrogen (NHsub.4 sup.+-N) content. (2) The proportion of 0-40 cm nitrogen components showed an upward trend in the year with more rain, and the opposite in the years with less rainfall with the increase of grazing intensity. Soil soluble organic nitrogen (SON) and NOsub.3 sup.−-N storages decreased and MBN storage increased in rainy years. (3) Soil nitrogen component contents and storages were correlated with plant growth status, soil moisture (SM) and soil bulk density (SBD), and were significantly negatively correlated with soil temperature (ST) and pH (p < 0.05). The content and storage of soil nitrogen were affected by grazing, soil, vegetation, meteorological and other environmental factors. Moderate grazing was more conducive to the improvement of soil nitrogen storage capacity and the healthy development of grassland.
Background:
Previous studies show that the use of unrelated cord blood transplantation (UCBT) for severe aplastic anemia (SAA) has poor outcome because of high incidence of primary graft failure. ...Effective measures to completely prevent rejection in SAA remain to be identified, but higher cell dose, less HLA disparities and better conditioning regimen are known to improve the outcome. In this study we compare two conditioning regimens to determine which is better to facilitate early engraftment after UCBT.
Patients and methods:
We retrospectively analyzed the outcomes of 35 Chinese patients with acquired SAA who received UCBT since September 2016. Eighteen patients (ATG group) used a conditioning regimen consisting of ATG (thymoglobulin) 2.5 mg/kg (D-9 to D-7) with fludarabine 30 mg/m2 (D-9 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (3 Gray) on D-1. Median age at time of UCBT was 9 (4-37) years. The median total nucleated cell number and CD34-positive cell number at infusion were 4.08 (1.74-9.36) × 107/kg and 2.13 (0.67-4.29) × 105/kg, respectively. Another group (No-ATG) of 17 patients used a conditioning regimen without ATG consisting of fludarabine 40 mg/m2 (D-8 to D-4), cyclophosphamide 60 mg/kg (D-3 to D-2) and total body irradiation (4 Gray) on D-1. Median age at time of UCBT was 14 (4-52) years. The median total nucleated cell number and CD34-positive cell number at infusion were 3.5 (1.07-7.87)× 107/kg and 1.7 (0.69-5.27) × 105/kg, respectively. Ciclosporin (CsA) and mycophenolate mofetil (MMF) was given to both groups as prophylaxis for graft versus host disease (GVHD).
Results:
Neutrophil recovery (>0.5×109/L) was observed in 11 patients of the ATG group and the median time to engraftment was 19 (13-35) days. The median time to platelet recovery (>20 × 109/L) was 40 (24-153) days. Primary graft failure was observed in seven patients. Only 1 out of 17 patients in the No-ATG group had primary graft failure. The median time to neutrophil engraftment was 17 (13-36) days. The median time to platelet engraftment was 31 (17-65) days. During follow-up, 7 patients died before 1 year due to non-engraftment (n=4), infection (n=2) and encephalorrhagia (n=1) in the ATG group. Four patients died in the No-ATG group due to infection (n=3) and IV grade acute GVHD in the skin and the intestinal tract (n=1, induced by discontinuing medicine). Furthermore, conditioning regimen without ATG shows even more superiority in patients refractory to immunosuppressive therapy with ATG and/or CsA (n=8), who had neutrophil engraftment completely within 20 days after cord blood infusion.
Conclusion:
UCBT after a FLU-CY-TBI conditioning regimen without ATG for SAA patients is better than that with ATG, especially for patients refractory to immunosuppressive therapy. Pediatric and adult SAA patients who are younger than 50 years old, lack of HLA-matched sibling donor and refractory to immunosuppressive therapy should consider UCBT.
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No relevant conflicts of interest to declare.
The percentage of human CD56−CD16+ NK cells increases during chronic infection with human HIV; however, the biologic role of CD56−CD16+ NK cells in HIV infection is unclear. Our results demonstrate ...that the percentage of CD56−CD16+ NK cells producing IL‐10 and TGF‐β was higher than CD56dimCD16+ NK cells. CD56−CD16+ NK cells could inhibit IFN‐γ production by autologous CD8+ T cells, and this inhibition could be partially reversed by anti‐IL‐10, anti‐TGF‐β, or anti‐PD‐L1 mAbs. CD56−CD16+ NK cells are potential targets for the development of novel immune therapies against HIV infection.
CD56−CD16+ NK cells inhibit IFN‐γ production by autologous CD8+ T cells; the inhibition can be partially reversed by anti‐IL‐10, anti‐TGF‐β, or anti‐PD‐L1 monoclonal antibodies.
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