Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
Antibodies, Monoclonal, Humanized ; COVID-19/drug therapy* ; Humans ; SARS-CoV-2 ; Treatment Outcome

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

OBJECTIVETo explore the role of eukaryotic translation elongation factor 1A1 (eEF1A1) in regulating the invasion and metastasis of hepatocellular carcinoma (HCC) cells and the possible mechanism.

METHODSqRT-PCR and Western blotting were used to detect the mRNA and protein expression of eEF1A1 and NOB1 in different HCC cell lines and normal liver cells. The invasion and migration abilities of HCC cells with eEF1A1 knockdown or overexpression were examined using Transwell chamber assay and RTCA assay, and the changes in NOB1 mRNA and protein expressions in the cells were detected. The effects of increasing NOB1 expression in HCCLM3-sheEF1A1 cells and decreasing NOB1 expression in eEF1A1-overexpressing MHCC97h cells on eEF1A1 expression and cell invasion and migration abilities were analyzed using Western blotting, Transwell chamber assay and RTCA assay.

RESULTSThe expressions of eEF1A1 and NOB1 were significantly increased in positive correlation in HCC cells as compared with normal hepatocytes. Knockdown of eEF1A1 significantly decreased the invasion and migration of HCC cells and reduced the mRNA and protein expression of NOB1 ( < 0.01). Overexpression of eEF1A1 significantly enhanced invasion and migration of HCC cells and increased NOB1 mRNA and protein expressions ( < 0.01). Increasing NOB1 expression in HCCLM3-sheEF1A1 cells led to the restoration of NOB1 expression and cell invasion and migration abilities ( < 0.01), whereas decreasing NOB1 in MHCC97h-eEF1A1 cells resulted in inhibition of NOB1 expression and cell invasion and migration ( < 0.01).

CONCLUSIONSeEF1A1 positively regulates the expression of NOB1 to promote the invasion and migration of HCC cells .

OBJECTIVETo assess the association of IFNG gene polymorphisms with preeclampsia among pregnant woman from Shaanxi Province.

METHODSGenomic DNA was extracted from peripheral blood samples collected from 280 patients with preeclampsia and 344 healthy pregnant women. Five tag single nucleotide polymorphisms (SNPs) of the IFNG gene (rs2069705, rs2430561, rs1861493, rs2069718, and rs2193050) were genotyped with a SNaPshot method. Genotypic and allelic frequencies were evaluated with a Chi square test. Genotype data was corrected by Logistic regression for body mass index and age. The level of IFN-gamma was determined with an ELISA assay.

RESULTSThe distribution of five tag SNPs all conformed to Hardy-Weinberg equilibrium (P> 0.05). Significant association with preeclampsia was found with the T allele of rs2430561 (OR=1.54, 95% CI:1.15-2.09, P=6.99× 10), under a dominant model (OR=3.77, 95% CI: 1.09-13.29, P=0.029) and a recessive model (OR=1.53, 95% CI:1.09-2.15, P=0.018). For the patient group, the IFN-gamma level of those with a TT genotype for rs2430561 was significantly higher than those with an AA or AT genotype [(13.69± 0.79) pg/mL vs. (13.11± 1.56) pg/mL, P< 0.05].

CONCLUSIONPolymorphism of the rs2430561 locus of the IFNG gene is associated with increased risk for preeclampsia as well as serum level of IFN-gamma among pregnant woman from Shaanxi. The role of the IFNG gene in the regulation of preeclampsia requires further investigation.

Adult ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Interferon-gamma ; blood ; genetics ; Logistic Models ; Polymorphism, Single Nucleotide ; Pre-Eclampsia ; etiology ; genetics ; Pregnancy

Objective To investigate the change of coagulation indexes in the patients with bee sting injury .Methods A total of 294 cases of bee sting injury were selected as the study subjects and divided into the mild bee sting injury group (A ,1 -2 sites) , moderate bee sting injury group(B ,3-10sites) ,severe bee sting injury group(C ,11-20sites) and extremely severe bee sting injury group(D ,≥21sites) according to the number of sting site .Meanwhile 40 healthy people were selected as the control group .The changes of prothrombin time(PT),internation alnormalized ratio(INR),activated partial thromboplastin time(APTT)and fibrinogen(FIB) were compared among groups .Results PT and APTT in the severe bee sting injury group and extremely severe bee sting injury group were significantly prolonged within 4-9 h after bee sting injury compared with the control group (P＜0 .05) .APTT , PT and INR had obviously dose effect positive correlation with bee sting sites (r=0 .583 ,0 .340 ,0 .327 ,P＜0 .01) .Conclusion APTT is closely correlated with bee sting sites and seeing doctor time ,which can serve as the effective monitoring indexes in the treatment process of bee sting injury .

Objective To investigate the changes of WBC count and neutrophil ratio (NEU% ) in the patients with bee sting inju‐ry .Methods According to the number of bee sting and different time going to hospital ,the WBC count and NEU% in 315 cases of bee sting injury were analyzed and compared with those in healthy population .Results The changes of WBC count and NEU% had statistically significant difference between the patients with bee sting injury and the healthy people (P< 0 .05) .The changes of WBC count and NEU% had statistically significant difference between the patients with more than 20 bee sting injuries and the pa‐tients with less than 3 bee sting injuries(P<0 .05) .The WBC count had obvious difference between the patients with treatment within 3 h after bee sting and the patients with treatment at other time (P<0 .05) .Conclusion The WBC count and NEU% are obviously increased after bee sting ,which is closely correlated with the bee sting injury number and the time going to hospital .

Objective Previous studies have shown that genetic variants in the interferons regulatory factor 5 (IRF5) gene are associated with rheumatoid arthritis (RA) in European and Japanese, but not found in Han Chinese. We conducted this study to investigate whether genetic variants in the IRF5 gene are associated with RA in ShaanXi Han Chinese population. Methods This study was collected 576 RA patients and 768 normal controls. Six IRF5 gene polymorphisms (rs729302, rs2004640, rs752637, rs3807306, rs10954213 and rs2280714) were genotyped by the SNaPshot method. T-test and χ2 test were used for statistic analysis. The genotype and allele frequencies were evaluated using the chi square tests. Genotyping data were adjusted by Logistic regression method by age and gender. The linkage disequilibrium (LD) block structure was examined using Hapview 4.2 software. Results Six SNPs inspected complied with Hardy-weinberg equilibrium (P>0.05). Two SNPs were significantly associated with RA: rs729302 A risk allele [OR=1.29, 95%CI (1.10, 1.50), P=5.57×10-3];dominant model [OR=1.58, 95%CI (1.10, 2.27), P=0.024], recessive model [OR=1.31, 95%CI (1.17, 1.64), P=0.028]. rs2004640 T risk allele [OR=1.28, 95%CI (1.08, 1.54), P=0.039]; dominant model [OR=1.27, 95%CI (1.03, 1.58), P=0.036]. In addition, there was no significant difference in rs752637, rs3807306, rs10954213 and rs2280714 SNPs between RA group and control and genotyped polymorphisms were significantly associated with RA susceptibility. Conclusion The present study confirm that rs729302 and rs2004640 in the IRF5 gene is significantly associated with increased risk of RA in ShaanXi Han Chinese population.

Objective:To compare different non‐invasive hepatic fibrosis evaluation criteria for the evaluation of hepatic fibrosis in patients with type 2 diabetes mellitus(T2DM ) combined with non‐alcoholic fatty liver disease(NAFLD) .Methods:A total of 996 patients(male 578 ,female 418) definitely diagnosed with T2DM ,who were simultaneously identified as NAFLD by ultrasonography ,were involved in the analysis .The venous fasting blood was collected from patients ,and blood routine and hepatic enzymes were evaluated .Aspartate aminotransferase(AST)/alanine aminotransferase(ALT) ratio ,FIB‐4 index ,BARD score ,AST to platelet ratio index (APRI) and NAFLD fibrosis scores(NFS) were calculated .NFS was set as the evaluation criterium for hepatic fibrosis .The correlations between the other indexes and the NFS were compared with correlation analysis . As the next step ,consistency of these indexes was evaluated by Bland‐Altman method .Results:AST/ALT ratio ,FIB‐4 index , BARD score and APRI ratio had linear positive correlation with NFS among male and female patients with T2DM combined with NAFLD .Furthermore ,the most significant correlation was observed between FIB‐4 index and NFS(r=0 .619 ,P<0 .01) . Bland‐Altman analysis indicated that AST/ALT ratio and FIB‐4 index were highly consistent with NFS ,and the FIB‐4 index was the best among the indexes .Conclusions:AST/ALT ratio and FIB‐4 index can be used to identify whether there is hepatic fibrosis in patients with T2DM combined with NAFLD .

Objective To evaluate the severity of non-alcoholic fatty liver disease(NAFLD) and progressive liver fibrosis(stage＞2)in hospitalized patients with type 2 diabetes mellitus(T2DM) by using NAFLD fibrosis score (NFS).The risk factors associated with progressive fibrosis were also analyzed.Methods A total of 721 hospitalized patients with T2DM and uhrasound verified NAFLD were involved.The history information and laboratory examinations were collected,NFS was calculated.The low cutoff score (-1.455) of NFS was used to exclude,and high cutoff score (0.676) to further accurately diagnose progressive fibrosis.Results (1) A total of 721 subjects (male/female 371/350) were diagnosed as NAFLD by ultrasound.In those subjects,173 patients were with progressive fibrosis (24.0％),111 patients without progressive fibrosis (15.4％),and 437 patients (60.6％) with NFS ranged from-1.455 to 0.676.(2) Aging,raised body mass index,aspartate amino transferase/alanine aminotransferase (AST/ALT) ratio,lowered albumin,and platelet were risk factors for progressive fibrosis of NAFLD.In addition,NFS was positively correlated with duration of diabetes,waist circumference,SBP,glycated albumin (GA),and GA/HbA1c(all P＜0.01),and negatively with red blood cell count,hemoglobin,white blood cell count (WBC),total cholesterol (TC),triglyceride,apolipoprotein-B,ALT,γ-glutamyltranspeptidase (all P＜0.01),AST,low-density lipoprotein cholesterol (all P＜0.05).(3) Logistic stepwise regression analysis showed diabetes duration,waist circunference,and GA were positively correlated with progressive liver fibrosis(OR =1.182,1.076,1.074,all P＜0.01),and negatively with WBC and TC (OR =0.613,0.703,all P＜0.01).Conclusions The detection rate of progressive fibrosis in patients with NAFLD and T2DM was approximately 24.0％ by applying NFS.Only 15.4％ of those subjects could be excluded from progressive fibrosis.It suggests that we should be alert to the risk of liver fibrosis in patients with type 2 diabetes.

Objective To investigate the effects of diabetic duration on liver fat content (LFC) in patients with type 2 diabetes,and to explore its relationship with the outcome of liver disease.Methods A total of 435hospitalized patients with type 2 diabetes were recruited.The history data,results of laboratory tests,and hepatic 1 H-MRS were collected,and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) was calculated.Results The prevalence of NAFLD in newly-diagnosed type 2 diabetes mellitus (NT2DM) group was higher than that in predousb-diagnosed type 2 diabetes mellitus (PT2DM) group (92.7％ vs 82.2％,P＜0.05),with higher LFC [(27.97 ± 16.88 vs 19.44± 15.54) ％,P＜0.01].The LFC was reduced with prolonged duration of diabetes.Partial correlation analysis showed that LFC was negatively correlated with duration of diabetes (rs =-0.233,P＜0.01) after adjustment for gender,age,body mass index (BMI),oral anti-diabetic drugs,lipid-lowering drugs,and insulin treatment.Multiple linear regression analysis showed that LFC was positively correlated with BMI,albumin,and alanine aminotransferase while negatively correlated with duration of diabetes.The proportion of patients without advanced fibrosis (NFS＜-1.455) was significantly higher in NT2DM group than that in PT2DM group (26.3％ vs 15.5％,P＜0.05),and the proportion of PT2DM in patients with advanced fibrosis (NFS＞0.676) was significantly higher than that of NT2DM (79.2％ vs 20.8％,P＜0.05).NFS was positively correlated with the duration of diabetes (rs =0.236,P＜0.01).The liver fat content in patients with advanced liver fibrosis decreased significantly,and the LFC was negatively correlated with NFS (rs =-0.164,P＜0.01).Conclusions The duration of diabetes is an independent influencing factor of LFC.With the extension of the duration of diabetes,the decreased LFC in type 2diabetic patients with NAFLD is related to the development of advanced fibrosis.The decrease in LFC in type 2diabetic patient is associated with poor outcome of NAFLD.