Virologic and clinical characteristics for prognosis of severe COVID-19: a retrospective observational study in Wuhan, China

BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has progressed to a pandemic associated with substantial morbidity and mortality. The WHO and the United States Center for Disease Control and Prevention (CDC) have issued interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19), but there is limited data on the virologic and clinical characteristics for prognosis of severe COVID-19. MethodsA total of 50 patients with severe COVID-19 were divided into good and poor recovery groups. The dynamic viral shedding and serological characteristics of SARS-CoV-2 were explored. The risk factors associated with poor recovery and lung lesion resolutions were identified. In addition, the potential relationships among the viral shedding, the pro-inflammatory response, and lung lesion evolutions were characterized. ResultsA total of 58% of the patients had poor recovery and were more likely to have a prolonged interval of viral shedding. The longest viral shedding was 57 days after symptom onset. Older age, hyperlipemia, hypoproteinemia, corticosteroid therapy, consolidation on chest computed-tomography (CT), and prolonged SARS-CoV-2 IgM positive were all associated with poor recovery. Additionally, the odds of impaired lung lesion resolutions were higher in patients with hypoproteinemia, hyperlipemia, and elevated levels of IL-4 and ferritin. Finally, viral shedding and proinflammatory responses were closely correlated with lung lesion evolutions on chest CT. ConclusionsPatients with severe COVID-19 have prolonged SARS-CoV-2 infection and delayed intermittent viral shedding. Older age, hyperlipemia, hypoproteinemia, corticosteroid usage, and prolonged SARS-CoV-2 IgM positive might be utilized as predicative factors for the patients with poor recovery.

Correlation of visfatin and endothelin with subclinical hypothyroidism in patients with cerebral infarction / 医学研究生学报

Objective Few studies are reported on the relationship of subclinical hypothyroidism ( SCHT ) with visfatin and endothelin .This study aimed to investigate their relationship in patients with cerebral infarction . Methods A total of 200 cerebral in-farction patients treated in The Second Affiliated Hospital of Hainan Medical University from January 2011 to July 2017 were divided in-to a control ( with normal thyroid function , n=40 ) , a mild SCHT ( with thyroid-stimulating hormone TSH <10 mIU/L, normal free triiodothyronine FT3 and normal free thyroxine FT4, n=60), a se-vere SCHT (with TSH≥10 mIU/L, normal FT3 and normal FT4, n=60) , and a clinical hypothyroidism ( CHT ) group ( with TSH ≥4 mIU/L, decreased FT3 and decreased FT4, n=40).The mild SCHT patients were subdivided into medication group A and non-medication group A, and the severe SCHT patients into medication group B and non-medication group B, 30 in each group, those in the medica-tion groups A and B treated by routine therapy plus oral levothyrocine , and those in the non-medication groups A and B by routine ther-apy only.We recorded the age, gender, body mass index, blood pressure, blood glucose, blood lipid, and thyroid function of the pa-tients, and compared the levels of visfatin and endothelin among different groups . Results The level of visfatin was significantly ele-vated in the severe SCHT and CHT groups as compared with the controls ([46.3±10.1] and [49.5±13.6] vs [40.2±9.7] ng/mL, P<0.05), and so was it in medication group B as compared with non-medication group B at 6 months after treatment ([42.9±6.4] vs [39.3±5.5] ng/mL, P<0.05). Conclusion Visfatin is closely related with thyroid hormone in cerebral infarction patients with se -vere subclinical hypothyroidism .Examination of thyroid function is necessary for cerebral infarction patients for the sake of early detec -tion of severe subclinical hypothyroidism and timely intervention .

Correlation of visfatin and endothelin with subclinical hypothyroidism in patients with cerebral infarction / 医学研究生学报

Objective Few studies are reported on the relationship of subclinical hypothyroidism ( SCHT ) with visfatin and endothelin .This study aimed to investigate their relationship in patients with cerebral infarction . Methods A total of 200 cerebral in-farction patients treated in The Second Affiliated Hospital of Hainan Medical University from January 2011 to July 2017 were divided in-to a control ( with normal thyroid function , n=40 ) , a mild SCHT ( with thyroid-stimulating hormone TSH <10 mIU/L, normal free triiodothyronine FT3 and normal free thyroxine FT4, n=60), a se-vere SCHT (with TSH≥10 mIU/L, normal FT3 and normal FT4, n=60) , and a clinical hypothyroidism ( CHT ) group ( with TSH ≥4 mIU/L, decreased FT3 and decreased FT4, n=40).The mild SCHT patients were subdivided into medication group A and non-medication group A, and the severe SCHT patients into medication group B and non-medication group B, 30 in each group, those in the medica-tion groups A and B treated by routine therapy plus oral levothyrocine , and those in the non-medication groups A and B by routine ther-apy only.We recorded the age, gender, body mass index, blood pressure, blood glucose, blood lipid, and thyroid function of the pa-tients, and compared the levels of visfatin and endothelin among different groups . Results The level of visfatin was significantly ele-vated in the severe SCHT and CHT groups as compared with the controls ([46.3±10.1] and [49.5±13.6] vs [40.2±9.7] ng/mL, P<0.05), and so was it in medication group B as compared with non-medication group B at 6 months after treatment ([42.9±6.4] vs [39.3±5.5] ng/mL, P<0.05). Conclusion Visfatin is closely related with thyroid hormone in cerebral infarction patients with se -vere subclinical hypothyroidism .Examination of thyroid function is necessary for cerebral infarction patients for the sake of early detec -tion of severe subclinical hypothyroidism and timely intervention .

Paris Agreement climate proposals need a boost to keep warming well below 2 °C.

The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to "pursue efforts" to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess the effect of current INDCs on reducing aggregate greenhouse gas emissions, its implications for achieving the temperature objective of the Paris climate agreement, and potential options for overachievement. The INDCs collectively lower greenhouse gas emissions compared to where current policies stand, but still imply a median warming of 2.6-3.1 degrees Celsius by 2100. More can be achieved, because the agreement stipulates that targets for reducing greenhouse gas emissions are strengthened over time, both in ambition and scope. Substantial enhancement or over-delivery on current INDCs by additional national, sub-national and non-state actions is required to maintain a reasonable chance of meeting the target of keeping warming well below 2 degrees Celsius.

Ketamine promotes inflammation through increasing TLR4 expression in RAW264.7 cells / 华中科技大学学报（医学）（英德文版）

Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.

Ketamine promotes inflammation through increasing TLR4 expression in RAW264.7 cells / 华中科技大学学报（医学）（英德文版）

Ketamine (KTM), a N-methyl-D-aspartate (NMDA) receptor antagonist, was found to has an anti-inflammatory effect, but some patients suffered from exacerbated pro-inflammatory reactions after anesthesia with KTM. The present study was aimed to examine the underlying mechanism of pro-inflammatory effects of KTM. In this study, RAW264.7 cells were exposed to KTM and NMDA alone or combined for 30 min before lipopolysaccharide (LPS) stimulation. The expression levels of IL-6 and TNF-α were detected by RT-PCR and ELISA, and those of NMDA receptors by RT-PCR in RAW264.7 cells. Additionally, the TLR4 expression was determined by RT-PCR and flow cytometry, respectively. The results showed that in RAW264.7 cells, KTM alone promoted the TLR4 expression, but did not increase the expression of IL-6 or TNF-α. In the presence of LPS, KTM caused a significantly higher expression of IL-6 and TNF-α than LPS alone. NMDA could neither alter the IL-6 and TNF-α mRNA expression, nor reverse the enhanced expression of IL-6 and TNF-α mRNA by KTM in LPS-challenged cells. After TLR4-siRNA transfection, RAW264.7 cells pretreated with KTM no longer promoted the IL-6 and TNF-α expression in the presence of LPS. In conclusion, KTM accelerated LPS-induced inflammation in RAW264.7 cells by promoting TLR4 expression, independent of NMDA receptor.

Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement / 癌症

<p><b>INTRODUCTION</b>The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.</p><p><b>METHODS</b>A total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization (FISH) assay.</p><p><b>RESULTS</b>Among the 487 patients, 44 (9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non-smokers and of a young age (≤ 58 years old), the frequency of ALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non-adenocarcinoma tumor type (P = 0.006), poorly differentiated tumors (P = 0.001), advanced-stage tumors (P < 0.001), smoking history (P = 0.008), and wild-type epidermal growth factor receptor (EGFR) (P = 0.008). Moreover, patients with poorly differentiated and advanced-stage tumors had a shorter time to cancer progression compared with those with well differentiated (P = 0.023) and early-stage tumors (P = 0.001), respectively.</p><p><b>CONCLUSIONS</b>ALK-rearranged NSCLC tends to occur in younger individuals who are either non-smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might benefit from ALK inhibitor therapy.</p>

Clinical applicability of xTAG liquidchip technology as EGFR mutations detection method in lung cancer / 临床与实验病理学杂志

Purpose To analyze EGFR exon 18 ~21 gene mutations in lung cancer, and compare xTAG liquidchip technology and Sanger sequencing technology in clinical practice. Methods 1 139 tumor tissue samples from phaseⅠtoⅣlung cancer patients were randomly collected. DNA was extracted from the samples. EGFR gene mutation status in exon 18~21 was detected by xTAG liquidchip technology and Sanger sequencing technology respectively. Results The mutation status of EGFR was obtained by xTAG liquidchip technology in 1 134 patients, and 1 105 by Sanger sequencing technology, detection success rate was 99. 56% and 97. 01% respective-ly. The sensitivity and specificity of xTAG liquidchip technology Comparing with Sanger sequencing was 99. 59% and 94. 54%. Sever-al cases of multiple mutations were detected by both methods. All mutation types detected by two methods are fully consistent. Conclu-sions Comparing with Sanger sequencing technology, xTAG liquidchip technology, which is able to detect mutations of exon 18~21 simultaneously, is more convenient and efficient for EGFR gene mutation detection in lung cancer.

Epstein-Barr virus-encoded RNAs as a survival predictor in nasopharyngeal carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Epstein-Barr virus (EBV) infection is one of the most important factors of nasopharyngeal carcinoma (NPC) endemic areas. Transcription of EBV-encoded non-polyadenylated RNAs (EBERs) are presented in most of NPC tumors. Exploring EBERs as a prognostic marker for NPC might further be informative about the biology and the progression of the disease. The aim of this study was to analyze the role of EBV latency in the clinical management of nasopharyngeal carcinoma (NPC), by detecting EBERs.</p><p><b>METHODS</b>RNA in situ hybridization (ISH) for detecting EBERs was carried out on 908 NPC tumor tissues. Overall survival (OS) curves were analyzed with the Kaplan-Meier method and the Cox proportional-hazards regression models.</p><p><b>RESULTS</b>The median follow-up time was 70 months (1-120 months). Eight hundred and sixteen (89.9%) from a total of 908 consecutive NPC cases were found to be EBV-EBER positive. EBER-ISH staining revealed nuclear localization in NPC cells. In the Kaplan-Meier analysis for OS, high EBER expression levels in NPC patients were statistically significant positive prognostic factors for survival (log-rank, P = 0.022), especially in adults aged 17-40 years (P = 0.023) and in those with advanced stage disease (log-rank, P = 0.002). Cox proportional-hazards regression model analysis showed that the EBER expression level was an independent risk factor for OS (hazard ratio 0.724, P = 0.005).</p><p><b>CONCLUSIONS</b>EBERs were frequently detected in NPC tumor tissues, and high-level EBER expression correlated with good prognosis in NPC patients, especially in adult patients and in those with advanced stage disease. EBER may serve as a potential prognostic predictor in NPC.</p>

Relationship between mutations of epidermal growth factor receptor gene and clinicopathologic features of non-small cell lung cancers / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the mutations of epidermal growth factor receptor (EGFR) gene and clinicopathological characteristics in patients with non-small cell lung cancers (NSCLC).</p><p><b>METHODS</b>Paraffin-embedded tissue specimens were obtained from 1444 patients with NSCLC. The genomic DNA was extracted. Mutations of EGFR gene (exons 19 and 21) were detected by real-time PCR.</p><p><b>RESULTS</b>DNA was available in 1410 cases. Somatic mutations of the EGFR gene were identified in 401 cases (27.8%). Among patients with EGFR mutations, 41.4% (n=166) had del E746-A750 of exon19, 6.7% (n=27) had del L747-P753insS of exon 19, 50.3% (n=201) had L858R of exon 21, and 1.5% (n=6) had L861Q of exon 21. Woman, non-smoker and adenocarcinoma showed a higher percentage of EGFR mutation (43.2%, 37.6%, and 33.5%, respectively). However, there was no association among age, grades, lymph node metastasis, and TNM stages (P>0.05). The mutation rate of BAC subtype (61.3%, 19/31) and adenocarcinoma with BAC features (48.0%, 12/25) was significantly higher than that of conventional adenocarcinoma (32.4%, 336/1038). A further assess of the smoking status found a trend that the more increased smoking exposure, the lower the incidence of EGFR mutations. A multivariable analysis revealed that adenocarcinoma, never smoking, and female were independently associated with EGFR mutations (odds rations=3.381, 2.393, and 1.727, respectively).</p><p><b>CONCLUSIONS</b>The detection rate of EGFR mutation is higher in Chinese patients, especially in non-smoking female patients with adenocarcinoma. Real-time PCR is a sensitive and accurate method to detect the mutations of EGFR gene and can therefore provide useful information for clinical treatment.</p>