Role of the extracellular matrix in COVID-19

An outbreak of coronavirus disease 2019(COVID-19)has spread globally,with over 500 million cases and 6 million deaths to date.COVID-19 is associated with a systemic inflammatory response and abnormalities of the extracellular matrix(ECM),which is also involved in inflammatory storms.Upon viral infection,ECM proteins are involved in the recruitment of inflammatory cells and interference with target organ metabolism,including in the lungs.Additionally,serum biomarkers of ECM turnover are associated with the severity of COVID-19 and may serve as potential targets.Consequently,understanding the expression and function of ECM,particularly of the lung,during severe acute respiratory syndrome of the coronavirus 2 infection would provide valuable insights into the mechanisms of COVID-19 progression.In this review,we summarize the current findings on ECM,such as hyaluronic acid,matrix metalloproteinases,and collagen,which are linked to the severity and inflammation of COVID-19.Some drugs targeting the extracellular surface have been effective.In the future,these ECM findings could provide novel perspectives on the pathogenesis and treatment of COVID-19.

Clinical characteristics of the patients with Hodgkin's lymphoma involving extranodal sites

Differences between Hodgkin's lymphoma (HL) patients in China and Western countries are known to exist, but data on Chinese patients with HL are limited. It is not clear whether there are clinical and histological differences in patients with HL involving different extranodal sites. This is the first study to analyze Chinese patients with HL involving different extranodal sites. We selected 22 HL patients with extranodal involvement from more than 250 previously untreated HL patients. Most patients were young males, and 20 of the 22 patients had stage IV disease. The major pathologic types were nodular sclerosis classical HL (NSCHL) and mixed cellularity classical HL(MCCHL). At diagnosis, the most commonly involved extranodal sites were the liver and lung, followed by the bones. There was no significant association between the international prognostic score(IPS) and survival in patients with different extranodal sites. Our data showed the overall survival (OS) and disease-free survival (DFS) rates of low-risk group (IPS = 0-2) were relatively higher than those of high-risk group (IPS ≥ 3), but the IPS did not show predictive power for survival. Although HL with extranodal involvement is rare, it should be considered as a unique form of HL.

EGFR inhibitors sensitize non-small cell lung cancer cells to TRAIL-induced apoptosis

Apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) can be regulated by the epidermal growth factor(EGF) signaling pathway.In this study,recombinant adenoviral vectors that encode TRAIL gene from the hTERT/RGD promoter(AdTRAIL) was combined with drugs including gefitinib,elotinib,and cetuximab that inhibit EGFR and the EGF signaling pathway in non-small cell lung cancer(NSCLC) cell lines to investigate their antitumor activity.In vitro,compared to single reagent,AdTRAIL combined with EGFR inhibitors reduced proliferation and enhanced apoptosis in H460,A549,and SW1573 cell lines.Western blot results suggested that these effects were relative to up-regulation of pro-apoptosis protein BAX and down-regulation of p-AKT.In vivo,AdTRAIL combined with cetuximab resulted in a significant growth reduction in H460 xenografts without damage to the main organs of nude mice.Histological examination and TUNEL analyses of xenografts showed that cetuximab enhanced cell apoptosis induced by AdTRAIL.These results indicate that EGFR inhibitors enhanced AdTRAIL anti-tumor activity in NSCLC cell lines and that inhibiting the AKT pathway played an important role in this enhancement.

Prognostic values of interim and post-therapy ^(18)F-FDG PET/CT scanning in adult patients with Burkitt's lymphoma

Background:The prognostic values of interim and post-therapy fluorine-18-fluorodeoxyglucose(^(18)F-FDG) positron emission tomography(PET) and PET/computed tomography(CT) scanning have been confirmed in several subtypes of lymphoma.However,its prognostic value in Burkitt's lymphoma has not been clearly defined.The aim of the present study was to assess the prognostic value of PET/CT scanning during different treatment processes of Burkitt's lymphoma.Methods:A total of 29 adult patients with newly diagnosed Burkitt's lymphoma were retrospectively involved in this study;of them,23 patients underwent baseline PET/CT,15 patients underwent mid-therapy PET/CT after 1-4 cycles of chemotherapy,and 17 patients underwent post-therapy PET/CT after all planned first-line chemotherapy cycles.Mid-therapy and post-therapy PET/CT results(positive vs.negative) were visually interpreted according to the criteria of the International Harmonization Project.The reduction in the maximum standardizes uptake values(ASUVmax)of 25%,50%,and 75%were regarded as cutoff points.Overall survival(OS) and progression-free survival(PFS) were regarded as the major endpoints.Results:The median OS and PFS were 27.6 months(range 6.5-78.3 months) and 27.2 months(range 3.0-78.3 months),respectively.The median SUVmax of the baseline PET/CT was 18.3(range 1.6-35.9),whereas the median SUVmax of the mid-therapy and post-therapy PET/CT decreased to 4.0(range 0-17.6) and 3.0(range 0-14.5),respectively.The patients' Eastern Cooperative Oncology Group(ECOG) scores(<2 vs.≥2) were significantly associated with the baseline PET/CT SUVmax.The mid-therapy and post-therapy PET/CT results(positive vs.negative) showed no significant association with OS or PFS.The optimal cutoff ASUVmax from the baseline to the post-therapy PET/CT that could predict a change in OS in patients with Burkitt's lymphoma was 50%(P = 0.019).Conclusions:^(18)F-FDG uptake was intense in Burkitt's lymphoma,and there was a significant reduction in SUVmax during the interim and post-therapy PET/CT procedures.A ASUVmax of greater than 50%was a favorable cutoff point to predict the OS of Burkitt's lymphoma patients.

Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis:a retrospective analysis from the MIMIC-IV database

Background:Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis,and whether heparin use improves sepsis survival remains largely unclear.This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis.Methods:A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care(MIMIC)-IV database was conducted.Cox proportional hazards model and propensity score matching(PSM)were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit(ICU)admission.The primary outcome was in-hospital mortality.Secondary outcomes included 60-day mortality,length of ICU stay,length of hospital stay and incidence of acute kidney injury(AKI)on day 7.EValue analysis were used for unmeasured confounding.Results:A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group(n=3211)and a nonheparin group(n=3435).In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group(prematched 14.7 vs 20.0%,hazard ratio(HR)0.77,95%confidence interval(CI)[0.68-0.87],p<0.001,and postmatched 14.9 vs 18.3%,HR 0.78,95%CI[0.68-0.89],p<0.001).Secondary endpoints,including 60-day mortality and length of ICU stay,differed between the heparin and nonheparin groups(p<0.01).Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates(HR 0.71-0.78,p<0.001),and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM(HR 0.70,95%CI 0.56-0.87,p<0.001).Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy,septic shock,sequential organ failure assessment score≥10,AKI,mechanical ventilation,gram-positive bacterial infection and gram-negative bacterial infection,with HRs of 0.74,0.70,0.58,0.74,0.73,0.64 and 0.72,respectively(p<0.001).E-Value analysis suggested robustness to unmeasured confounding.Conclusions:This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality.A prospective randomizedcontrolled study should be designed to further assess the relevant findings.

SbF_5-loaded microcapsules for ultrafast self-healing of polymer

To accelerate self-healing speed of epoxy materials,epoxy-SbF5 cure was introduced into the healing chemistry.Due to the high activity of SbF5,a milder SbF5-ethanol complex with improved processability was prepared,but it was still quite active and cannot be encapsulated by conventional encapsulation techniques like in situ polymerization.Accordingly,a novel route was proposed.Hollow silica microcapsules were firstly synthesized via sol-gel technique,which were then steeped in ethanol solution of SbF5-ethanol complex under vacuum,allowing infiltration of the latter into the capsules.The optimal formulation for creating the hollow silica capsules was studied in detail.Moreover,the results of optical pyrometry demonstrated that the encapsulated chemical retained its high reactivity toward the epoxy.

A Delayed Ovarian Hemorrhage with Severe Ovarian Hyperstimulation Syndrome after Transvaginal Ultrasound-guided Oocyte Retrieval for in vitro Fertilization-embryo Transfer

Objective To report a case of ovarian hemorrhage after transvaginal ultrasoundguided oocyte retrieval combined with severe ovarian hyperstimulation syndrome （OHSS）. Methods A 26-year-old woman who was on therapy for infertility presented with abdominal distension and a decrease of urine after transvaginal ultrasound-guided oocyte retrieval for in vitro fertilization-embryo transfer （IVF-ET）. Initial clinical presentation, ultrasound, and lab results were consistent with the diagnosis of severe OHSS. However with 4 d conservative treatments there seemed no recovery and the patient became more serious for her hemoglobin fell from 169.0 g/L to 60.2 g/L along with more abdominal fluid and a decrease of urine. Ultrasound guided paracentesis revealed an ovarian hemorrhage, and the patient underwent emergent surgery. Results The patient underwent emergent laparotomy for oophoroplasty and preservation of ovary. She got twin pregnancy in the second frozen-thawed embryo transfer （FET） cycle and delivered two female babies. Conclusion It is important to distinguish the OHSS from ovarian hemorrhage, because the ovarian hemorrhage with hemoperitoneum requires immediate operative management, whereas OHSS is nearly always managed conservatively. Clinicians must be aware that ovarian hemorrhage may be delayed in women presenting OHSS.