Effect of Laser Quenching-Shock Peening Strengthening on the Microstructure and Mechanical Properties of Cr12MoV Steel.

The automobile covering parts mold is a key piece of equipment in the automobile industry, and its drawbead is the core element that affects the life of the mold and the quality of the parts made. Due to the complex structure of the mold cavity for covering parts, there exist differences between material flow characteristics, load conditions, stress strain, failure forms and so on in the surface of different parts of its drawbead and the different directions of the same part of the drawbead, thus putting forward new requirements for material strengthening. For the differentiated lose efficacy forms of the dangerous end faces of the tension bars, this study carried out research into the effect of laser quenching-shock peening strengthening (LQ-LSP) on the organization, plastic deformation resistance and wear resistance of Cr12MoV steel. It was shown that the microhardness (722.30 HV) and residual stress (-383.84 MPa) of the specimens were further enhanced after laser quenching-shock peening composite strengthening. The residual austenite content of the specimen was reduced to 0.8%, and the eutectic carbide distribution morphology was improved. After three rounds of laser composite peening, the specimens had the smallest displacement of the nanoindentation load-depth curve, which exhibited the greatest nanohardness (20.0 Pa) and modulus of elasticity (565.25 Pa), while reducing the coefficient of friction (0.61) and surface roughness (0.152 Ra). The smooth and flat surface of the specimen with shallow and narrow plow grooves improved the resistance of Cr12MoV steel to plastic deformation and wear.

Efficacy of Thymosin Alpha 1 in the Treatment of COVID-19: A Multicenter Cohort Study.

Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.

Intravenous immunoglobulin treatment for patients with severe COVID-19: a retrospective multicentre study.

OBJECTIVES: Intravenous immunoglobulin (IVIG) is commonly used to treat severe COVID-19, although the clinical outcome of such treatment remains unclear. This study evaluated the effectiveness of IVIG treatment in severe COVID-19 patients. METHODS: This retrospective multicentre study evaluated 28-day mortality in severe COVID-19 patients with or without IVIG treatment. Each patient treated with IVIG was matched with one untreated patient. Logistic regression and inverse probability weighting (IPW) were used to control confounding factors. RESULTS: The study included 850 patients (421 IVIG-treated patients and 429 non-IVIG-treated patients). After matching, 406 patients per group remained. No significant difference in 28-day mortality was observed after IPW analysis (average treatment effect (ATE) = 0.008, 95% CI -0.081 to 0.097, p 0.863). There were no significant differences between the IVIG group and non-IVIG group for acute respiratory distress syndrome, diffuse intravascular coagulation, myocardial injury, acute hepatic injury, shock, acute kidney injury, non-invasive mechanical ventilation, invasive mechanical ventilation, continuous renal replacement therapy and extracorporeal membrane oxygenation except for prone position ventilation (ATE = -0.022, 95% CI -0.041 to -0.002, p 0.028). DISCUSSION: IVIG treatment was not associated with significant changes in 28-day mortality in severe COVID-19 patients. The effectiveness of IVIG in treating patients with severe COVID-19 needs to be further investigated through future studies.

Corticosteroid therapy in critically ill patients with COVID-19: a multicenter, retrospective study.

BACKGROUND: Corticoid therapy has been recommended in the treatment of critically ill patients with COVID-19, yet its efficacy is currently still under evaluation. We investigated the effect of corticosteroid treatment on 90-day mortality and SARS-CoV-2 RNA clearance in severe patients with COVID-19. METHODS: 294 critically ill patients with COVID-19 were recruited between December 30, 2019 and February 19, 2020. Logistic regression, Cox proportional-hazards model and marginal structural modeling (MSM) were applied to evaluate the associations between corticosteroid use and corresponding outcome variables. RESULTS: Out of the 294 critically ill patients affected by COVID-19, 183 (62.2%) received corticosteroids, with methylprednisolone as the most frequently administered corticosteroid (175 accounting for 96%). Of those treated with corticosteroids, 69.4% received corticosteroid prior to ICU admission. When adjustments and subgroup analysis were not performed, no significant associations between corticosteroids use and 90-day mortality or SARS-CoV-2 RNA clearance were found. However, when stratified analysis based on corticosteroid initiation time was performed, there was a significant correlation between corticosteroid use (≤ 3 day after ICU admission) and 90-day mortality (logistic regression adjusted for baseline: OR 4.49, 95% CI 1.17-17.25, p = 0.025; Cox adjusted for baseline and time varying variables: HR 3.89, 95% CI 1.94-7.82, p < 0.001; MSM adjusted for baseline and time-dependent variants: OR 2.32, 95% CI 1.16-4.65, p = 0.017). No association was found between corticosteroid use and SARS-CoV-2 RNA clearance even after stratification by initiation time of corticosteroids and adjustments for confounding factors (corticosteroids use ≤ 3 days initiation vs no corticosteroids use) using MSM were performed. CONCLUSIONS: Early initiation of corticosteroid use (≤ 3 days after ICU admission) was associated with an increased 90-day mortality. Early use of methylprednisolone in the ICU is therefore not recommended in patients with severe COVID-19.

Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome.

BACKGROUNDCorticosteroids are widely used in patients with COVID 19, although their benefit-to-risk ratio remains controversial.METHODSPatients with severe COVID-19-related acute respiratory distress syndrome (ARDS) were included from December 29, 2019 to March 16, 2020 in 5 tertiary Chinese hospitals. Cox proportional hazards and competing risks analyses were conducted to analyze the impact of corticosteroids on mortality and SARS-CoV-2 RNA clearance, respectively. We performed a propensity score (PS) matching analysis to control confounding factors.RESULTSOf 774 eligible patients, 409 patients received corticosteroids, with a median time from hospitalization to starting corticosteroids of 1.0 day (IQR 0.0-3.0 days) . As compared with usual care, treatment with corticosteroids was associated with increased rate of myocardial (15.6% vs. 10.4%, P = 0.041) and liver injury (18.3% vs. 9.9%, P = 0.001), of shock (22.0% vs. 12.6%, P < 0.001), of need for mechanical ventilation (38.1% vs. 19.5%, P < 0.001), and increased rate of 28-day all-cause mortality (44.3% vs. 31.0%, P < 0.001). After PS matching, corticosteroid therapy was associated with 28-day mortality (adjusted HR 1.46, 95% CI 1.01-2.13, P = 0.045). High dose (>200 mg) and early initiation (≤3 days from hospitalization) of corticosteroid therapy were associated with a higher 28-day mortality rate. Corticosteroid use was also associated with a delay in SARS-CoV-2 coronavirus RNA clearance in the competing risk analysis (subhazard ratio 1.59, 95% CI 1.17-2.15, P = 0.003).CONCLUSIONAdministration of corticosteroids in severe COVID-19-related ARDS is associated with increased 28-day mortality and delayed SARS-CoV-2 coronavirus RNA clearance after adjustment for time-varying confounders.FUNDINGNone.

Alleviation of sepsis-associated encephalopathy by ginsenoside via inhibition of oxidative stress and cell apoptosis: An experimental study.

Ginsenoside (Rg1) has biological effects including anti-oxidation, anti-inflammation, neuroprotection and neural function improvement, but with few studies in sepsis-associated encephalopathy (SAE). This study thus evaluated Ginsenoside in alleviating SAE, suppressing oxidative stress (OS) or neuronal apoptosis. SAE mouse model was generated and were assigned into SAE, SAE + LD-Rg1, and SAE + HD-Rg1 groups to measure neural apoptosis by flow cytometry. Contents of malondialdehyde (MDA), superoxide dismutase (SOD), GSH-Px and caspase-3 were quantified, and mouse neural reflex function was evaluated. Expression of Nrf2, HO-1 was measured. Mouse neuron MN-c and microglia BV2 were co-cultured in control, LPS, LPS+Rg1 (20µM) and LPS+Rg1 (40µM) groups. Iba-1 expression of BV2 cells was measured by flow cytometry. Contents of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 were quantified. Apoptosis of MN-c cells was measured by flow cytometry, and reactive oxygen species (ROS) content was measured by DCFH-DA staining. SAE mice had elevated caspase-3 activity, cell apoptosis, MDA content, and decreased SOD, GSH-Px activity or neural reflex score comparing to Sham group. Rg1 treatment suppressed caspase-3 activity, apoptotic rate or MDA content, recovered SOD activity, neural reflex score, and expression of Nrf2 and HO-1. LPS treatment elevated Iba-1 expression and release of inflammatory cytokines TNF-α, IL-1ß and IL-6, induced MN-c apoptosis or ROS production, and enhanced Nrf2 and HO-1 expression. Rg1 treatment remarkably inhibited LPS-induced response or cell apoptosis. Ginsenoside can alleviate SAE damage via up-regulating Nrf2 and HO-1 to enhance anti-OS potency and to reduce neural cell apoptosis.

Tracheostomy in 80 COVID-19 Patients: A Multicenter, Retrospective, Observational Study.

Background: The outbreak of coronavirus disease 2019 (COVID-19) has led to a large and increasing number of patients requiring prolonged mechanical ventilation and tracheostomy. The indication and optimal timing of tracheostomy in COVID-19 patients are still unclear, and the outcomes about tracheostomy have not been extensively reported. We aimed to describe the clinical characteristics and outcomes of patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who underwent elective tracheostomies. Methods: The multi-center, retrospective, observational study investigated all the COVID-19 patients who underwent elective tracheostomies in intensive care units (ICUs) of 23 hospitals in Hubei province, China, from January 8, 2020 to March 25, 2020. Demographic information, clinical characteristics, treatment, details of the tracheostomy procedure, successful weaning after tracheostomy, and living status were collected and analyzed. Data were compared between early tracheostomy patients (tracheostomy performed within 14 days of intubation) and late tracheostomy patients (tracheostomy performed after 14 days). Results: A total of 80 patients were included. The median duration from endotracheal intubation to tracheostomy was 17.5 [IQR 11.3-27.0] days. Most tracheotomies were performed by ICU physician [62 (77.5%)], and using percutaneous techniques [63 (78.8%)] at the ICU bedside [76 (95.0%)]. The most common complication was tracheostoma bleeding [14 (17.5%)], and major bleeding occurred in 4 (5.0%) patients. At 60 days after intubation, 31 (38.8%) patients experienced successful weaning from ventilator, 17 (21.2%) patients discharged from ICU, and 43 (53.8%) patients had died. Higher 60 day mortality [22 (73.3%) vs. 21 (42.0%)] were identified in patients who underwent early tracheostomy. Conclusions: In patients with SARS-CoV-2 pneumonia, tracheostomies were feasible to conduct by ICU physician at bedside with few major complications. Compared with tracheostomies conducted after 14 days of intubation, tracheostomies within 14 days were associated with an increased mortality rate.

Development of immunoaffinity chromatography to specifically knockout baicalin from Gegenqinlian Decoction.

Specific knockout technology provides a powerful tool to confirm the role of target compounds in a plant or its derived prescriptions, and this principle is the same as that with knockout genes. In this study, we generated an immunoaffinity column conjugated with an anti-baicalin monoclonal antibody and then loaded Gegenqinlian Decoction extracts, followed by washing with deionized water and an elution solvent. The results of the high-performance liquid chromatography fingerprints and high-performance liquid chromatography with mass spectrometry showed that the immunoaffinity column was able to specifically knockout baicalin, oroxylin A-7-O-glucuronide, wogonoside, wogonin, and baicalein from Gegenqinlian Decoction. A reliable one-step method to specifically knockout baicalin was established with an immunoaffinity column. Gegenqinlian Decoction and its knocked-out fraction induced the expression of superoxide dismutase and were compared in human umbilical vein endothelial cells cultured with a high glucose concentration; the results showed that the Gegenqinlian Decoction and its knocked-out fraction showed no significant difference, which indicated that the baicalin, oroxylin A-7-O-glucuronide, wogonoside, wogonin, and baicalein that were knocked out by the immunoaffinity column might not be key compounds for the induction of Gegenqinlian Decoction superoxide dismutase secretion.

Development of ELISA for detection of Rh1 and Rg2 and potential method of immunoaffinity chromatography for separation of epimers.

In this work, hybridomas producing anti-ginsenoside-Rh1 monoclonal antibodies (MAbs) were generated. These MAbs were subsequently used to create indirect competitive enzyme-linked immunosorbent assays (icELISAs). A linear correlation was obtained for G-Rh1 concentrations in the range from 26 to 512ng/mL. The regression equation was y=1.979-0.201Log2(X) with a regression coefficient of 0.9898. Precision and accuracy of the icELISA method were evaluated by the variations between replicates from well to well (intra-assay) and plate to plate (inter-assay). The recovery rates ranged from 93.16% to 108.43%. Testing with the icELISA demonstrated that the MAbs were specific for 20(S)-Rh1 and 20(S)-Rg2 with no cross-reactivity against 20(R)-Rh1 and 20(R)-Rg2. The immunoaffinity chromatography column (IAC) was constructed by covalently coupling monoclonal antibody (MAb) against G-Rh1 to CNBr-activated Sepharose 4B. When 20(R)-type-Rg2 passed through the IAC column, it was adsorbed, but the amount adsorbed was lower than that when 20(S)-type-Rg2 ran through the column. The differences in adsorption between the 20(S) and 20(R) type ginsenosides bring a new approach or method to separate 20(S)-Rg2 and 20(R)-Rg2 by IAC. Our results indicate that the icELISA is a sensitive and efficient approach for the identification of epimers, and the application of IAC using MAbs against small molecules provides a totally new thought and potential method for resolving epimers.

Pharmacokinetics of geniposide by monoclonal antibody-based icELISA in mice after oral administration of Huanglian-Jiedu-Tang.

Geniposide, Geniposide, the main active component in extracts of Gardenia jasminoides ELLIS., is one of the main components of Huanglian-Jiedu-Tang (HJT). This study aimed to validate an indirect competitive enzyme-linked immunosorbent assay (icELISA) based on monoclonal antibodies (mAb) against geniposide (anti-geniposide mAb), which was developed by our lab, and apply the assay to study the pharmacokinetics of geniposide in HJT in mice. Blood samples were drawn from mice at predetermined time points after oral administration of HJT in three dosages. A linear correlation was obtained for geniposide concentrations in the range from 1.17 to 37.50 µg/mL. The intra-day and inter-day precision values of the icELISA method were well within the recommended range (≤10%). The recovery rates ranged from 99.74 to 102.40%. Stability studies showed that geniposide sample solutions were intact for 12 h. The Tmax and mean residence time (MRT) of geniposide of the three groups were consistent with previous data. The results suggest that a reliable and effective method was established and could be applied to the study of the pharmacokinetics of geniposide in HJT.

Assessment of baicalin in mouse blood by monoclonal antibody-based icELISA.

An indirect competitive enzyme-linked immunosorbent assay (icELISA) based on monoclonal antibaodies (MAb) was recently developed. This new method displays high sensitivity and accuracy, and is especially suitable for pharmacokinetic studies in small laboratory animals. This study aimed to develop an icELISA procedure for baicalin (BAL) quantitation in blood. We successfully developed the icELISA and applied in pharmacokinetic assays of Gegen Qinlian Decoction in mice. A linear correlation was obtained for BAL concentrations in the range from 34.69 to 2220.00 µg/L. The regression equation was y = 1.5557 - 0.4028log(C) with a correlation coefficient of 0.9936. Precision and accuracy of the icELISA method were evaluated by the variations between replicates from well to well (intra-assay) and plate to plate (inter-assay). The values obtained for these parameters were within the normal range (<15%). The recovery rates ranged from 98.93 to 126.78%, meeting the requirements for biological samples. Stability studies showed that BAL sample solutions were intact for 1 h, enough time for UV detection. However, long-term storage and especially freeze-thaw procedures were detrimental to BAL. The pharmacokinetic parameters derived from mouse experiments were as follows: area under the curves from time 0 to 48 h, 1876.15 ± 1108.14 mg h/L; mean maximum blood concentrations, 101.09 ± 31.53 mg/L; time of maximum concentration, 3.58 ± 2.88 h; mean residence time, 79.30 ± 61.21 h.