Camrelizumab(SHR-1210) leading to reactive capillary hemangioma in the gingiva: A case report

BACKGROUND Oncologic immunotherapy is attracting attention as an effective strategy for cancer treatment. Currently, there are two kinds of inhibitors: Anti-PD-1 antibodies and anti-PD-L1 antibodies. These inhibitors have shown significant implications in improving the outcomes of certain cancer types in recent years.However, along with its effectiveness, adverse events cannot be ignored. As an anti-PD-1 antibody, camrelizumab(SHR-1210) has some side effects in tumor immunotherapy. The most common adverse event is reactive capillary hemangioma. While it is widely reported to occur in the skin, gingival reactive capillary hemangioma is rarely reported.CASE SUMMARY A 54-year-old man complained of gingival overgrowth on the anterior aspect of the maxilla and mandible for more than 6 mo. He had been placed on SHR-1210 for lung cancer for 7 mo. A gingival mass extending from canine to canine was noted on the lingual surfaces of the mandible. Gingival enlargement was noted in the front teeth. A clinical diagnosis of gingival reactive capillary hemangioma and chronic periodontitis was made. The treatment involved a complex local treatment(repeated local applications of an antibiotic paste, scaling and root planning, and surgery). The excised tissue was sent for histopathological examination, which confirmed the diagnosis of capillary hemangioma. After the operation, most of the gingival enlargement was reduced. At the 2-mo follow-up,it was noted that the gingival overgrowth was immediately reduced after the replacement of the anti-PD-1 agent with an anti-PD-L1 agent.CONCLUSION As the prescription for SHR-1210 has increased considerably in recent years, the occurrence of its possible side effects, including gingival reactive capillary hemangioma, has increased. It is recommended that regular oral examinations be performed before and during the treatment of tumors with SHR-1210.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes.From January 2014 to September 2017,431 patients with FUO were prospectively enrolled in the study population.This study established a list of 26 variables from the following 4aspects:host factors,epidemiological factors,behavioral factors,and iatrogenic factors.Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model.The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified.These factors were incorporated into the predictive model.This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72,sensitivity of 0.71, and specificity of 0.63.The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19

Infection-associated hemophagocytic syndrome(IAHS),a severe complication of various infections,is potentially fatal.This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019(COVID-19).We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st,2020 and February 26th,2020.Demographics,clinical characteristics,laboratory results,information on concurrent treatments and outcomes were collected.A diagnosis of secondary hemophagocytic lymphohistiocytosis(sHLH)was made when the patients had an HScore greater than 169.Histopathological examinations were performed to confirm the presence of hemophagocytosis.Of 268 critically ill patients with confirmed SARS-CoV-2 infection,17(6.3%)patients had an HScore greater than 169.All the 17 patients with sHLH died.The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days.Ten(59%)patients were infected with only SARS-CoV-2.Hemophagocytosis in the spleen and the liver,as well as lymphocyte infiltration in the liver on histopathological examinations,was found in 3 sHLH autopsy patients.Mortality in sHLH patients with COVID-19 is high.And SARS-CoV-2 is a potential trigger for sHLH.Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Genome assembly of autotetraploid Actinidia arguta highlights adaptive evolution and enables dissection of important economic traits

Actinidia arguta,the most widely distributed Actinidia species and the second cultivated species in the genus,can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit,rapid softening,and excellent cold tolerance.Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear.Here,we generated a chromosome-scale genome assembly of an autotetraploid male A.arguta accession.The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes.Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups,Southern and Northern,which first diverged 12.9 million years ago.A.arguta underwent two prominent expansions and one demographic bottleneck from the midPleistocene climate transition to the late Pleistocene.Population genomics studies using paleoclimate data enabled us to discern the evolution of the species’adaptation to different historical environments.Three genes(AaCEL1,AaPME1,and AaDOF1)related to flesh softening were identified by multi-omics analysis,and their ability to accelerate flesh softening was verified through transient expression assays.A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome(Chr3)or autosomal chromosomes showed biased expression during stamen or carpel development.This chromosome-level assembly of the autotetraploid A.arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A.arguta.

Palynoflora and climatic dynamics of the Laizhou Bay of Bohai Sea,North China Plain,since the late middle Pleistocene

The coastal plain of Laizhou Bay in Bohai Sea is a transitional area of land-sea interaction.Sediments in this area can bear significant information of sea-level fluctuation,climate change,as well as regional geological setting.Here,in this study,new sporopollen data from three boreholes(GK138,GK111 and GK95)in the coastal plain of Laizhou Bay,Bohai Sea were investigated,and the pollen spectrum since the late middle Pleistocene was established as six sporopollen assemblage zones(Ⅰ-Ⅵ),i.e.,Pinus-Quercus-Artemisia,Gramineae-Artemisia-Chenopodiaceae,Picea-Pinus-QuercusArtemisia,Picea-Pinus-Betula-Gramineae-Artemisia,Picea-Pinus-Cupressaceae-Chenopodiaceae and Pinus-Quercus-Gramineae-Artemisia-Chenopodiaceae.Combining with existing sedimentary successions and detailed radiocarbon dating results of the sediments from the three boreholes,paleovegetation and climatic evolution since the late middle Pleistocene were reconstructed.The findings revealed that climatic changes in this area since the late middle Pleistocene were characterized by alternating cold-arid and warmhumid conditions,which were well correlated with marine isotopic stages(MIS).The present study offers specific insight into the climatic dynamics in the North China Plain since the late middle Pleistocene and provides evidence of a clear link among the palynoflora in the area,the glacial-interglacial period climatedriven sea-level changes,and the marineδ^(18)O records.

Tongxinluo promotes mesenchymal stem cell tube formation in vitro

Objective： To study whether Tongxinluo （TXL） can induce angiogenesis in bone marrow mesenchymal stem cells （MSCs）, and to investigate the underlying mechanism. Methods： Bone marrow MSCs were obtained from male Sprague-Dawley rats. We established an angiogenesis model in vitro via matrigel experiment. MSCs were seeded on matrigel coated 24-well plates, and treated by TXL 50 and 100 mg/L. After 24 h, we observed the tube formations of MSCs in the matrigel. Cell migration ability was examined by wound scratch test and transwell assay. Expressions of vascular endothelial growth factor （VEGF）, fetal liver kinase-1 （FIk-1）, matrix metalloproteinase-2 （MMP-2）, MMP-9, and tissue inhibitor of metalloproteinase-2 （TIMP-2） were analyzed at the protein level by Western blot. Gelatin zymography assay was applied to investigating the MSC paracrine abilities of pro-MMP-2 and activated MMP-2. Results： TXL promoted MSC tube formation in matrigel. The ratio of TXL 100 mg/L treated-MSC tubular length was increased 3.04-fold compared to the control group （P〈0.05）. Scratch test and transwell assay showed that TXL could improve the cell migration ability of MSCs. Western blot experiments showed that TXL promoted MSC synthesis of MMP-2, but it had no influence on the expressions of MMP-9 and TIMP-2. This effect was confirmed by gelatin zymography assay, which showed that TXL increased MSC secretion of pro-MMP-2 and activated MMP-2. VEGF expression of TXL treated-MSCs was increased compared to the control group. The expression of FIk-1 was not different among the groups. Conclusions： This study demonstrates that TXL can promote the tube formation of MSCs, and the underlying mechanisms are associated with increased migration ability of MSCs and the up-regulation of MMP-2 and VEGF expressions.