[Clinical features of 141 fatal cases of coronavirus disease in Jinyintan Hospital in Wuhan, China].

Objective: To describe the epidemiological characteristics and clinical features of patients with fatal coronavirus disease (COVID-19), in order to provide evidence for clinical diagnosis and treatment. Methods: In this retrospective study, we analyzed data on 141 fatal cases of confirmed COVID-19 that occurred among patients in Jinyintan Hospital in Wuhan, China, from January 20 to March 6, 2020. We analyzed their epidemiological characteristics, clinical and radiological features, laboratory results, and treatment. Results: Of the 141 patients (49 females, 92 males), the median age was 77 years (range: 24-92 years). The most likely source of exposure included the Huanan seafood market (n=3, 2%), family members (n=6, 4%), and hospital-acquired infection (n=8, 6%). The remaining 116 patients (72%) had no known source of exposure. Of the patients, 101 (72%) had chronic diseases. The most common comorbidities were hypertension, diabetes and coronary heart disease. The most common clinical manifestations were fever (n=121, 85%), dry cough (n=77, 54%), shortness of breath (n=23, 16%), and chest pain (n=15, 10%). Less common clinical manifestations included fatigue (n=7, 4%), headache (n=3, 2%), disorders of consciousness (n=2, 1%), diarrhea (n=2, 1%) and lumbago (n=1, 0.7%). In terms of laboratory tests, the absolute value of lymphocytes in most patients was reduced (n=132, 94%), but C-reactive protein (n=141, 100%), procalcitonin(n=121, 89%), serum amyloid (n=140, 99%) were significantly increased. The most common findings on imaging of the lungs were bilateral multiple mottling and ground-glass opacity (n=101, 72%), mainly in the lower lobes (n=15, 10%), with lesions being more common on the right. Other imaging findings included diffuse consolidation (n=4, 3%), ground-glass opacity and consolidation (n=20, 14%), and pneumothorax (n=1, 0.7%). All patients were treated with antibiotics and antiviral drugs. Other treatments included immunoglobulin (n=49, 35%), corticosteroids (n=45, 32%), continuous renal replacement therapy (n=24, 17%), and extracorporeal membrane oxygenation (n=12, 9%). All patients were treated with oxygen therapy. The mode of administration included invasive mechanical ventilation (n=61, 43%), noninvasive mechanical ventilation (n=65, 46%), and nasal catheter oxygen inhalation (n=15, 11%). The direct causes of death were acute respiratory distress syndrome (n=90, 64%), multiple organ failure (n=24, 17%), sudden cardiac arrest (n=11, 8%), viral myocarditis (n=8, 5%), acute myocardial infarction (n=4, 3%), cerebrovascular accident (n=3, 2%), and acute gastrointestinal bleeding (n=1, 0.7%). Conclusions: Risk factors for death due to COVID-19 included older age, male sex, and the presence of comorbidities. The most common direct causes of death were acute respiratory distress syndrome, multiple organ failure, sudden cardiac arrest, and viral myocarditis.

The role of miR-99b in mediating hepatocellular carcinoma invasion and migration.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The role of miR-99b in mediating hepatocellular carcinoma invasion and migration, by C.-J. Liu, J.-H. Yang, F.-Z. Huang, J.-H. Yang, C.-P. Liu, X.-H. Mao, W.-M. Yi, X.-B. Shen, C. Peng, M.-F. Chen, B. Jiang, J.-S. Wu, published in Eur Rev Med Pharmacol Sci 2018; 22 (8): 2273-2281-DOI: 10.26355/eurrev_201804_14815-PMID: 29762829" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/14815.

miRNA and mRNA expression profiles in gastric cancer patients and the relationship with circRNA.

Gastric cancer (GC) is a malignant tumor that affects individuals worldwide, and miRNA and mRNA are closely connected to this disease. However, it is still unclear how these molecules affect GC and whether their effects are associated with circRNA in GC patients. Therefore, we obtained the miRNA, mRNA and circRNA expression profiles of GC patients from the GEO database. For comparison, shared miRNAs and mRNAs from the results of microarrays were annotated by gene ontology (GO) and pathway analysis. We also identified mRNAs that were targeted by miRNA through TargetScan 7.2 and circRNAs that were targeted by miRNA through CircInteractome. A comprehensive analysis of the microarray results revealed 72 shared miRNAs, and the expression profiles of 6 miRNAs were significantly different between the tumor and control groups (the absolute value of fold change>2, P<0.05). Hsa-miR-1, hsa-miR-142-3p, hsa-miR-95, hsa-miR-133a and hsa-miR-181d were upregulated in GC, whereas hsa-miR-375 was downregulated. The analysis results also revealed 1201 shared mRNAs and 27 mRNAs, respectively, by microarray and TargetScan. Pathway analysis demonstrated that the Glypican pathway, Proteoglycan syndecan-mediated signalling events, Glypican 1 network and PAR1-mediated thrombin signalling events play important roles. GO analysis revealed significant enrichment in the three terms cellular component, molecular function and biological process, suggesting that organelles, enzyme binding, RNA-binding and nitrogen metabolism may have a strong relationship in GC. The increase in PAX6 in GC may be related to hsa-miR-375. Three circRNAs, hsa_circ_0001658, hsa_circ_0004928 and hsa_circ_0000376, were then found to be significantly differentially expressed between GC and normal tissues (the absolute value of fold change>2, P<0.05). In conclusion, the circ0001658/circ0004928/circ0000376-miR-375-PAX6 axis may represent a new regulatory network that should be further investigated, and the results of this study provide a better understanding of GC.

MALAT1 promotes cisplatin resistance in cervical cancer by activating the PI3K/AKT pathway.

OBJECTIVE: To investigate the role of MALAT1 in the cisplatin treatment of cervical cancer and its underlying mechanism. MATERIALS AND METHODS: The effects of different doses of cisplatin on the proliferation and apoptosis of cervical cancer cells were detected by cell counting kit-8 (CCK-8) assay and apoptosis assay, respectively. We used bioinformatics methods to predict the downstream genes of MALAT1 and examined the expression relationship between the target gene BRWD1 and MALAT1 by quantitative Real-time polymerase chain reaction (qRT-PCR). Western blot was performed to detect the expression levels of apoptosis-related proteins and key genes in PI3K/AKT signaling pathway. RESULTS: After MALAT1 was knocked down, cisplatin showed an inhibited effect on the proliferation of HeLa and C-33A cells in a concentration-dependent manner. After treatment of cervical cancer cells with 5 µM cisplatin, MALAT1 knockdown enhanced the apoptosis of HeLa and C-33A cells, and up-regulated expression of cleaved caspase-3. Over-expression of MALAT1 in cells showed the opposite results. Starbase website was used to predict that MALAT1 might regulate BRWD1 expression. Over-expression of MALAT1 significantly up-regulated the mRNA expression of BRWD1 in HeLa and C-33A cells. After knockdown of BRWD1, cisplatin markedly decreased the proliferation of HeLa and C-33A cells, and promoted cell apoptosis and cleaved caspase-3 expression. Besides, HeLa and C-33A cells showed increased expressions of p-PI3K and p-AKT after MALAT1 was up-regulated. CONCLUSIONS: MALAT1 promoted the cisplatin resistance of cervical cancer, which might be related to regulation of cell apoptosis via BRWD1 and PI3K/AKT pathway.

The role of miR-99b in mediating hepatocellular carcinoma invasion and migration.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults with a high rate of malignancy. The potent invasion and migration of HCC mainly impact the prognosis and recurrence of the disease. Our previous study found that miR-99b was highly expressed in HCC, and its expression was associated with vascular invasion. It was speculated that miR-99b may play a role in HCC invasion and migration, while the specific mechanism remains unclear. MATERIALS AND METHODS: qRT-PCR was applied to detect expressions of miR-99b and KAI1 genes in L02, HepG2, and MHCC97H cells. HepG2 cells were transfected with miR-99b inhibitor, miR-99b mimic, and NC. Flow cytometry was used to test cell cycle and apoptosis. Dual-luciferase reporter gene assay was adopted to validate the target gene of miR-99b. Wound healing assay was used to detect cell migration. Transwell assay was performed to detect cell invasion. Western blot was performed to detect KAI1, E-cadherin, and N-cadherin expressions. Immunofluorescence assay was adopted to test Vimentin expression. RESULTS: The level of miR-99b was reduced in L02 while up-regulated in MHCC97H. By contrast, the expression of KAI1 was increased in L02 but declined in MHCC97H. The transfection of miR-99b mimic inhibited HepG2 apoptosis and accelerated cell cycle. MiR-99b suppressed KAI gene expression through targeting its 3'-UTR. MiR-99b mimic or si-KAI1 transfection promoted cell invasion and migration, while their simultaneous action significantly enhanced cell invasion and migration. The overexpression of miR-99b or knockdown of KAI1 significantly weakened HepG2 cell adhesion, reduced E-cadherin expression, upregulated N-cadherin and Vimentin, and promoted cell epithelial-mesenchymal transition (EMT). CONCLUSIONS: MiR-99b contributes to promoting function in HCC migration and invasion through inhibiting KAI1 expression.

[Acute effect of ambient air pollution on small airway lung functions among school children in Shanghai].

Objective: To study the acute effects of compound ambient air pollution on small airway lung functions among school children in Shanghai. Method: A longitudinal survey on lung functions was conducted among 233 school-children from three schools (A, B and C, located in innerring, mid-ring and outer-ring areas). Lung function test was performed once a week for 3 times respectively, among children in school A and B in Dec. 2013 and in school C in Dec. 2014. The fourth lung function test was tested in Jun. 2014 and May 2015 in the respective schools. Results: from the lung function would include items as: forced mid-expiratory flow at 25% of forced vital capacity (MEF(25%)), mid-expiratory flow at 50% of forced vital capacity (MEF(50%)), mid-expiratory flow at 75% of forced vital capacity (MEF(75%)) and mid-expiratory flow between 25% and 75% of the forced vital capacity (FEF(25%-75%)). Data regarding the daily air quality real-time of PM(2.5), PM(10), SO(2) and NO(2) in Dec. 2013, Dec. 2014, Jun. 2014 and May. 2015 from the three environmental monitoring spots and meteorological data from the Shanghai Meteorological Service system which were physically close to the three schools, were collected simultaneously. Linear mixed effect model was used to examine the levels of correlation between lung function indicators and ambient air pollutants. Results When confounding factors on meteorology and individuals were controlled, the lag effects and accumulated lag effects were found to have existed between the internal quarter rang (IQR) concentration of PM(2.5) and PM(10) in lag2 day and lag02 days, IQR concentration of SO(2) in lag02 day and IQR concentration of NO(2) lag0 day, when small airway lung functions like MEF(25%), MEF(50%), MEF(75%) and FEF(25%-75%)(P<0.05) were inspected. Results from the two air pollutants model analysis showed that SO(2) and NO(2) presenting interactive effects with PM(2.5), PM(10) and lag effects more significant than the individual SO(2) and NO(2), respectively (P<0.05). Conclusion: Contents on the ambient air pollutants as PM(2.5), PM(10), SO(2) and NO(2) were negatively associated with the lung functions in the small airways of children, in Shanghai.

[Analysis of Koch phenomenon of Mycobacterium tuberculosis-infected guinea pigs vaccinated with recombinant tuberculosis vaccine AEC/BC02].

OBJECTIVE: To observe the Koch phenomenon of Mycobacterium tuberculosis(MTB)-infected guinea pigs after vaccinated with killed H37Ra bacteria or tuberculosis vaccine candidate AEC/BC02. METHODS: Eighteen guinea pigs were challenged subcutaneously with 5.0×10(3) CFU MTB and after 40 days were divided into 3 groups (6 per group): NS group, AEC/BC02 group and H37Ra group, which were injected intramuscularly 3 times at 1 day interval with normal saline, AEC/BC02 vaccine and killed H37Ra bacteria respectively. Three weeks after the first vaccination, all guinea pigs were sacrificed to evaluate gross pathological scores for liver, spleen and lung, bacterial loads in lung and spleen, and lung inflammation. RESULTS: The gross pathological score in H37Ra group (48±26) was lower than that in NS group(62±15), but the difference was not significant (t=1.093, P=0.300). The AEC/BC02 group had a significantly lower gross pathological score (36±15) than NS group (t=2.980, P=0.014). No significant difference between H37Ra group and AEC/BC02 group was observed (t=1.009, P=0.337). The spleen bacterial load [(5.31±0.80) log10 CFU]in H37Ra group was slightly lower than that in NS group[(5.57±0.75) log10 CFU] but the difference was not significant (t=1.581, P=0.574). In AEC/BC02 group bacterial load in the spleen was (4.64±0.64) log10 CFU and significantly lower than NS group (t=2.306, P=0.044) and no significant difference between H37Ra group and AEC/BC02 group was observed (t=1.602, P=0.140). Meanwhile, the lung bacterial load in AEC/BC02 group was (3.71±1.01) log10 CFU and in H37Ra group was (3.82±1.25) log10 CFU. Compared to (4.15±0.69) log10 CFU in the NS group, no significant differences were found (t=0.881, P=0.399; t=0.566, P=0.584, respectively). For the lung inflammation, the inflamed areas in H37Ra group were significantly larger [(33.0±4.4%)] than those in both NS group [(14.8±8.4) %, t=4.719, P=0.001] and AEC/BC02 group [(14.8±8.4) %, t=3.616, P=0.005], and no significant differences were seen between AEC/BC02 group and NS group (t=1.041, P=0.322). CONCLUSION: The lung inflammation indicated that killed H37Ra bacteria evoked an obvious Koch reaction in the MTB-infected guinea pigs, whereas AEC/BC02 vaccine showed a low risk of causing Koch phenomenon.

Molecular cloning and immune responsive expression of a ribonuclease III orthologue involved in RNA interference, dicer, in grass carp Ctenopharyngodon idella.

In this study, the dicer gene (designated as cidicer) was identified and characterized from grass carp Ctenopharyngodon idella. The complementary DNA (cDNA) of cidicer contained an open reading frame (ORF) of 5646 nucleotides (nts) encoding a putative protein of 1881 amino acids (aa). The deduced Dicer protein contained all known functional domains identified in other organisms. Tissue tropism analysis indicated that cidicer is abundantly expressed in brain, gill, head kidney, liver, spleen, heart, muscle and intestine. In the C. idella kidney (CIK) cells, messenger RNA (mRNA) expression of cidicer was significantly up-regulated at 24 h (6·36-fold, P < 0·01) after grass carp reovirus (GCRV) infection, and its transcriptional expression level was also transiently induced to a high level (6·54-fold, P < 0·01) at 2 h post-stimulation of synthetic double-stranded polyinosinic-polycytidylic potassium salt [poly(I:C)]. In vivo analysis further showed that the expression of cidicer mRNA in the liver was induced to a significantly high level at 12 h (8·46-fold, P < 0·01), and then dropped to normal level at 72 h post-challenge with GCRV. The transcriptional expression pattern of cidicer in the spleen tissue was similar to that of liver tissue upon GCRV challenge. These results collectively implied that the identified cidicer was an inducible gene responding to viral infection both in vitro and in vivo, and the data would shed light on the interaction between RNA interference (RNAi) antiviral pathway and aquareovirus infection.

Relation of exposure to environmental tobacco smoke and pulmonary adenocarcinoma in non-smoking women: a case control study in Nanjing.

To examine the relationship between exposure to passive smoke (herein referred to as environmental tobacco smoke, ETS), cooking fumes, other risk factors and primary adenocarcinoma of the lung, 70 adenocarcinoma lung cancer cases of non-smoking women in Nanjing were studied in a 1:1 case-control study. Results show no statistical association between exposure to ETS and pulmonary adenocarcinoma. The respective odds ratios for chronic lung disease, cooking fume pollution and family tumor history were 3.90, 2.45 and 4.36.

Analysis and estimates of attributable risk factors for lung cancer in Nanjing, China.

A case-control study was performed on 83 cases of primary pulmonary squamous cell carcinoma and 180 cases of primary pulmonary adenocarcinoma in Nanjing. Multivariate conditional logistic regression analysis showed five risk factors for pulmonary squamous carcinoma. These were: smoking, indoor air pollution due to cooking fumes, family tumor history, type of fuel used in the home, and use of coal stoves for heating in winter. The relative risks (RR) for these five risk factors were: 1.03 (95% CI, 1.00-1.06), 3.81 (95% CI, 1.06-13.73), 5.61 (95% CI, 1.23-15.79), 4.97 (95% CI, 0.8-30.88) and 3.72 (95% CI, 0.88-15.71), respectively. The respective population attributable risks (PAR) were: 68%, 52%, 28%, 55% and 36%. The four risk factors for pulmonary adenocarcinoma were smoking, cooking fumes, chronic bronchitis and family tumor history. The respective RRs were: 1.01 (95% CI, 1.00-1.03), 2.99 (95% CI, 1.68-5.34), 2.49 (95% CI, 1.68-5.34) and 4.77 (95% CI, 1.93-11.83). The respective PARs were: 20%, 47%, 18% and 18%. The combined PAR for the five risk factors for pulmonary squamous cell carcinoma was 94% and the combined PAR for the risk factors for pulmonary adenocarcinoma was 79%.