Laboratory Biomarkers for the Diagnosis and Management of Patients with COVID-19: an Updated Review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global crisis due to strong infectivity and fast transmission speed. Some patients with Coronavirus Disease 2019 (COVID-19) progress rapidly and may develop fatal complications, which brings serious challenges in disease assessment and treatment. Recent progress in the understanding of the molecular biology of SARS-CoV-2 has led to the identification of a variety of laboratory biomarkers that could be potentially applied to clinical practice for the diagnosis, treatment, and prognosis of patients with COVID-19. In this review we summarize the updated status on the identification of COVID-19 related laboratory markers, and propose further direction on the application of these markers to clinical diagnosis and management of patients with COVID-19.

TREML4: a Potential Target for Immunotherapy of Sepsis.

Sepsis is a serious syndrome with a series of abnormalities caused by dysfunctional host response to infection. Toll-like receptor 4 (TLR-4) has been considered as a key regulator of inflammatory response and immune cell apoptosis in lipopolysaccharides (LPS) challenged models. However, in clinical trials, monoclonal antibodies of TLR-4 have not shown therapeutic effects as expected. Moreover, clinical trials based on immunotherapy by regulating inflammatory cytokines during the acute phase of sepsis have also failed. Recent evidence indicates that the fast-acting innate immune system plays a bigger role in blocking the fast progression of sepsis upon infection than the adaptive immune system. Consequently, the strategies for clinical management of sepsis should be shifted from targeting adaptive immune system to targeting innate immune system. In this review, we summarize our understanding of the role of TREML4 in sepsis, and highlight potential value of TREML4 in clinical management of sepsis. Further mechanistic studies on TREML4 such as the identification of its ligand will provide more clues on the development of novel and effective approaches to the prevention and therapy of sepsis.

Two new CdII MOFs of 1,4-bis(1H-benzimidazol-1-yl)butane and flexible dicarboxylate ligands: luminescence sensing towards Fe3.

Two new CdII MOFs, namely, two-dimensional (2D) poly[[[µ2-1,4-bis(1H-benzimidazol-1-yl)butane](µ2-heptanedioato)cadmium(II)] tetrahydrate], {[Cd(C7H10O4)(C18H18N4)]·4H2O}n or {[Cd(Pim)(bbimb)]·4H2O}n (1), and 2D poly[diaqua[µ2-1,4-bis(1H-benzimidazol-1-yl)butane](µ4-decanedioato)(µ2-decanedioato)dicadmium(II)], [Cd2(C10H16O4)2(C18H18N4)(H2O)2]n or [Cd(Seb)(bbimb)0.5(H2O)]n (2), have been synthesized hydrothermally based on the 1,4-bis(1H-benzimidazol-1-yl)butane (bbimb) and pimelate (Pim2-, heptanedioate) or sebacate (Seb2-, decanedioate) ligands. Both MOFs were structurally characterized by single-crystal X-ray diffraction. In 1, the CdII centres are connected by bbimb and Pim2- ligands to generate a 2D sql layer structure with an octameric (H2O)8 water cluster. The 2D layers are further connected by O-H...O hydrogen bonds, resulting in a three-dimensional (3D) supramolecular structure. In 2, the CdII centres are coordinated by Seb2- ligands to form binuclear Cd2 units which are linked by bbimb and Seb2- ligands into a 2D hxl layer. The 2D layers are further connected by O-H...O hydrogen bonds, leading to an 8-connected 3D hex supramolecular network. IR and UV-Vis spectroscopy, thermogravimetric analysis and solid-state photoluminescence analysis were carried out on both MOFs. Luminescence sensing experiments reveal that both MOFs have good selective sensing towards Fe3+ in aqueous solution.

Oreocharis flavovirens, a new species of Gesneriaceae from Southern Gansu Province, China.

Oreocharis flavovirens is a new species of Gesneriaceae from Gansu, China and is described and illustrated here. It is morphologically similar to O. glandulosa, O. humilis and O. farreri, but those congeners of this new taxon can be distinguished by several salient characters. A description of O. flavovirens, together with illustrations and photos, are presented.

Liver damage at admission is an independent prognostic factor for COVID-19.

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.

Two new NiII and ZnII metal-organic frameworks of glutarate and 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene ligands: syntheses, structures and luminescence sensing properties.

Two new metal-organic frameworks (MOFs), namely, three-dimensional poly[diaquabis{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}bis(µ2-glutarato)dinickel(II)] monohydrate], {[Ni2(C5H6O4)2(C16H18N4)2(H2O)2]·H2O}n or {[Ni2(Glu)2(1,4-mbix)2(H2O)2]·H2O}n, (I), and two-dimensional poly[[{µ2-1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene}(µ2-glutarato)zinc(II)] tetrahydrate], {[Zn(C5H6O4)(C16H18N4)]·4H2O}n or {[Zn(Glu)(1,4-mbix)]·4H2O}n (II), have been synthesized hydrothermally using glutarate (Glu2-) mixed with 1,4-bis[(2-methyl-1H-imidazol-1-yl)methyl]benzene (1,4-mbix), and characterized by single-crystal X-ray diffraction, IR and UV-Vis spectroscopy, powder X-ray diffraction, and thermogravimetric and photoluminescence analyses. NiII MOF (I) shows a 4-connected 3D framework with point symbol 66, but is not a typical dia network. ZnII MOF (II) displays a two-dimensional 44-sql network with one-dimensional water chains penetrating the grids along the c direction. The solid-state photoluminescence analysis of (II) was performed at room temperature and the MOF exhibits highly selective sensing toward Fe3+ and Cr2O72- ions in aqueous solution.

A new variety of Didymocarpus (Gesneriaceae) from Guangdong, China.

A new variety of Didymocarpus, D.heucherifoliusvar.gamosepalus from Guangdong, China, is described and illustrated with photographs. It closely resembles the more widespread D.heucherifolius within a number of morphological characters. However, it can be easily distinguished from the latter according to the new taxon: calyx base connate, 5-lobed from middle to above middle, larger flowers (up to 5 cm long) and glabrous corolla.

Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma.

Recently, XRCC1 polymorphisms were reported to be associated with glioma in Chinese population. However, only a few studies reported on the XRCC1 expression, and cancer progression. In this study, we investigated whether XRCC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that XRCC1 expression is significantly decreased in glioma compared with tumor adjacent normal brain tissue (P < 0.01, χ2 test) and reduced XRCC1 staining was associated with WHO stages (P < 0.05, χ2 test). The mRNA and protein levels of XRCC1 were significantly downregulated in human primary glioma tissues (P < 0.001, χ2 test). We also found that XRCC1 was significantly decreased in glioma cell lines compared to normal human astrocytes (P < 0.01, χ2 test). Overexpression of XRCC1 dramatically reduced the proliferation and caused cessation of cell cycle. The reduced cell proliferation is due to G1 phase arrest as cyclin D1 is diminished whereas p16 is upregulated. We further demonstrated that XRCC1 overexpression suppressed the glioma cell migration and invasion abilities by targeting MMP-2. In addition, we also found that overexpression of XRCC1 sharply inhibited angiogenesis, which correlated with down-regulation of VEGF. The data indicate that XRCC1 may be a tumor suppressor involved in the progression of glioma.

Two new species of Primulina (Gesneriaceae) from limestone karsts of China.

The limestone karst area of South China is a major biodiversity hotspot of global terrestrial biomes. During extensive field work on the Guangxi limestone formations, two unknown species of Gesneriaceae were collected. After conducting a comprehensive study of the literature and herbarium specimens, Primulina davidioides and P. hiemalis are recognized as two species new to science, and described and illustrated here. P. davidioides is morphologically close to P. lunglinensis based on the shape of the leaf and flower, but it can be easily distinguished by the shape of the bracts, corolla and stigma, indumentum of peduncles, pedicels and pistil and number of staminodes. P. hiemalis is closely relate to P. luzhaiensis in vegetative appearance, but differs in the shape of the calyx and stigma, number of bracts and staminodes, indumentum of the leaf blade and peduncle, and position of stamens in the corolla tube. Considering that not enough is known about their populations, it is proposed that their conservation statuses should currently be classed as data deficient (DD) according to the IUCN Red List Category and Criteria.

CTHRC1 mediates multiple pathways regulating cell invasion, migration and adhesion in glioma.

Recently, collagen triple helix repeat containing-1 (CTHRC1) has been reported to be increased in several types of human solid cancers and to be associated with tumor invasion and metastasis. However, the expression and function of CTHRC1 in glioma have not yet been reported. In the present study, we investigated whether CTHRC1 plays a role in glioma pathogenesis. Using the tissue microarray technology, we found that CTHRC1 expression is significantly increased in glioma compared with tumor adjacent normal brain tissue (P<0.01, χ2 test) and increased CTHRC1 staining was associated with WHO stages (P<0.05, χ2 test). The mRNA and protein levels of CTHRC1 were significantly upregulated in human primary glioma tissues (P<0.001, χ2 test). We also found that CTHRC1 was significantly increased in glioma cell lines compared to normal human astrocytes (P<0.01, χ2 test). Furthermore, Knockdown of CTHRC1 suppressed glioma cell invasion and inhibited enzyme activity of MMP-2. Moreover, our data showed that knockdown of CTHRC1 inhibited glioma cell migration and adhesion capacity when compared with the control cells, and CTHRC1-siRNA reduced the levels of phosphorylated Src and FAK protein expression. Taken together, this study suggests that CTHRC1 plays a role in glioma development and progression by regulating invasion, migration and adhesion capabilities of cancer cells.

Head and neck rhabdomyosarcoma: follow-up results of four cases and review of the literature.

Head and neck rhabdomyosarcoma (HNRMS) is exceedingly rare and poorly documented. The difficult diagnosis often causes a poor prognosis and high mortality. Hence, we report 4 cases of HNRMS and their follow-up outcomes, and review the clinicopathological features of this rare tumor. The 4 patients ranged in age from 5 to 29 years. Among them, 3 patients had a good prognosis after combination of radiotherapy and chemotherapy or surgery alone. Another patient survived for only 3 months after diagnosis without therapy. Deeply insight into HNRMS might improve the ability of diagnosis and treatment for this disease.

MiR-29c inhibits glioma cell proliferation, migration, invasion and angiogenesis.

Previous studies reported that miR-29c is significantly downregulated in several tumors. However, little is known about the effect and molecular mechanisms of action of miR-29c in human glioma. Using quantitative RT-PCR, we demonstrated that miR-29c was significantly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues (P < 0.05, χ(2) test). Overexpression of miR-29c dramatically reduced the proliferation and caused cessation of cell cycle. The reduced cell proliferation is due to G1 phase arrest as cyclin D1 and cyclin E are diminished whereas p27 and p21 are upregulated. We further demonstrated that miR-29c overexpression suppressed the glioma cell migration and invasion abilities by targeting MMP-2. In addition, we also found that overexpression of miR-29c sharply inhibited angiogenesis, which correlated with down-regulation of VEGF. The data indicate that miR-29c may be a tumor suppressor involved in the progression of glioma.

[Maxillary sinus floor augmentation using gene-enhanced tissue engineered bone].

OBJECTIVE: To evaluate the effect of maxillary sinus elevation with gene-enhanced tissue engineering bone in dogs. METHODS: bone marrow stromal cells (BMSC) derived from dog marrow were cultured, and transduced with the adenovirus carrying bone morphogenetic protein-2 (BMP-2) gene (AdBMP-2), the adenovirus carrying green fluorescent protein (GFP) gene (AdGFP) in vitro. The bone formation ability of gene modified BMSC with scaffold was examined in nude mice and in elevated maxillary sinus of dog. Student's t-test was used for statistical analysis with SPSS 11.0 software package. RESULTS: Gene transfection efficiency reached up to (83.95 ± 2.43)% as demonstrated by GFP expression. Ectopic bone formation was detected in nude mice. As for maxillary sinus floor elevation in a dog model, new bone formation area in the AdBMP-2 gene transduced BMSC with Bio-Oss group was significantly higher than in BMSC with Bio-Oss group at 120 d (P < 0.05). CONCLUSIONS: AdBMP-2 gene transduced BMSC can stimulate ectopic bone formation in nude mice, and promote bone formation and maturation in the dog maxillary sinus.

[Liquid-based cytology for esophageal carcinoma screening].

BACKGROUND AND OBJECTIVE: Cytologic screening of asymptomatic high risk individuals can detect curable esophageal carcinomas and has been used for several decades. However, the sensitivity of such screening is relatively low, which limits its wide use and development. This study was to investigate the utility of liquid-based cytology in esophageal carcinoma screening. METHODS: A mass screening of esophageal carcinoma was performed for asymptomatic residents in Yaocun County, Linzhou City, Henan Province, China. Esophageal biopsy samples were put into a liquid buffer for cytologic diagnosis and subsequent endoscopic biopsies were made on all subjects. Cytologic categories were adapted from criteria of the Bethesda system (TBS). RESULTS of liquid-based cytology were compared with those from endoscopic biopsy. The sensitivity and the specificity of liquid-based cytology were evaluated. RESULTS: Carcinomas in situ and carcinomas were identified in 17 (2.4%) of 710 subjects. Measured by ASC/AGC (atypical squamous cells or atypical glandular cells) as the detection threshold, the sensitivity and the specificity of liquid-based cytology were 76.5% and 76.0%, respectively. CONCLUSION: In a hospital with a high level of conventional cytology, liquid-based technique can be used widely since the work load of reading slides may greatly decrease, although this technique do not significantly improve the sensitivity of screening.

[Application of protein markers in combination with ThinPrep bronchial brush cytology in classification of lung cancer subtypes].

OBJECTIVE: To evaluate the value of application of cellular protein markers stained by immunocytochemistry in combination with ThinPrep bronchial brush cytology in classification of lung cancer subtypes. METHODS: Remaining bronchial brush cytology samples from 206 lung cancer patients with positive cytological diagnosis and 45 fine needle aspiration samples of resected lung carcinomas were collected. The expressions of CK10/13, CK7, CK18, CD56 and SYN in those samples were detected by immunocytochemistry (ICC) using corresponding antibodies. RESULTS: The sensitivity and specificity of CK10/13 were 94.7% and 72.0%, respectively, in diagnosis of squamous cell carcinoma. The sensitivity and specificity of CK7 were 98.6% and 61.5%, and those of CK18 were 98.6% and 37.5%, respectively, in diagnosis of adenocarcinoma. The sensitivity and specificity of CD56 were 86.3% and 82.9%, and those of SYN were 81.6% and 93.5%, respectively, in diagnosis of small cell lung cancer. No significant difference was found in the expressions of CK10/13, CK7 and CK18 protein markers among differently differentiated lung squamous cell carcinomas and adenocarcinomas (P > 0.05). The classification rate of cytology in combination with ICC in differential diagnosis for 44 cases of unclassified lung cancer reached 90.0% for squamous cell carcinoma, 96.3% for adenocarcinoma, and 100.0% for small cell lung carcinoma. CONCLUSION: Application of cellular protein markers in combination with ThinPrep bronchial brush cytology is helpful to improve the differential diagnosis of lung cancer subtypes, and may become a supplementary diagnostic method in subclassification of lung cancer.

[Effects of osteogenic growth peptide on bone density adjacent to implant in irradiated tibia of the rabbits].

PURPOSE: To evaluate the effect of radiation and osteogenic growth peptide(OGP) on the bone density adjacent to the implants. METHODS: 24 rabbits underwent 48 implants placed in the tibia, then the rabbits were divided into one control group and two experimental groups randomly. Rabbits in one of the experimental groups were injected with OGP Sol, rabbits in the other groups were injected with normal saline; Then rabbits in the two experimental groups received radiation after the implant wound healed. 12 rabbits were sacrificed at 4 weeks and 16 weeks respectively. The samples were observed with gross, X-ray, histological examination. The data was analysed for Dunnett t test using SPSS13.0 software package. RESULTS: At 4 weeks, the bone density adjacent to the implant of the simple irradiation group was significantly less than that of the control group (P<0.05), while the difference was not significant between the irradiation and OGP group and the control group. At 16 weeks, the difference among the three groups wasn't significant. CONCLUSIONS: Radiation has considerable adverse effect on osteogenesis adjacent to the implants, while systemically administering OGP plays significant roles in the osteogensis of the irradiated rabbit tibia.

[Experimental study of maxillary sinus lifting with tissue engineered bone].

OBJECTIVE: To evaluate the effect of tissue engineering bone in maxillary sinus lifting. METHODS: The marrow stromal stem cells of dog were cultured in DMEM containing 100 m1/L fetal bovine serum and induced to differentiate to osteoblasts, which were then inoculated together with Bio-Oss for 5 days. Sixteen dog's bilateral maxillary sinus were elevated. One side was grafted with a compound of BMSC and Bio-Oss and the other side grafted with Bio-Oss alone. The samples were studied by gross, CT, histomorphology and histomorphometrical analysis at the 30th, 90th day after the operation. t-test was used for statistical analysis. RESULTS: In gross view and CT, new bone formation was observed in all maxillary sinus after 30 and 90 days respectively. Histomorphometrical analysis showed much more new callus in BMSC-Bio-Oss group than in Bio-Oss group (P < 0.05). CONCLUSIONS: A better effect of new bone formation could be obtained with tissue engineered bone in maxillary sinus lifting.

[Value of ThinPrep bronchial brushing cytology in the diagnosis of lung cancers].

OBJECTIVE: To evaluate the ThinPrep bronchial brushing cytology in the diagnosis of lung cancers. METHODS: The smear slides of ThinPrep bronchial brushing cytology in 1000 patients collected from April 2001 to April 2002 were reviewed. RESULTS: Of 389 patients diagnosed as having lung cancer clinically or histopathologically, 273 (70.2%) were revealed by ThinPrep bronchial brushing cytology. Among the 74 patients with benign lung diseases comfirmed by pathology, 3 had been suspected as having lung cancer by ThinPrep bronchial brushing cytology. Actually, they were two patients suffering from tuberculosis and one hamartoma proven by histopathology later. The sensitivity and specificity of ThinPrep bronchial brushing cytology were 70.2% and 95.9%, respectively. Of the 179 patients who had both cytological and histopathological results, the cytology and pathology concordance rate was 95.4% in squamous carcinoma, 87.0% in adenocarcinoma and 95.7% in small cell carcinoma. CONCLUSION: Although ThinPrep bronchial brushing cytology has a high specificity, it is not good in diagnosing lung cancer. Poor smearing technique may be responsible for most of the false negative. Type diagnosis of poorly differentiated carcinomas can be difficult when based on the ThinPrep bronchial brushing cytology alone.