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 investigate the efficacy and safety of CD19 chimeric antigen receptor T (CAR-T) lymphocytes for the treatment of B cell lymphoma. Methods: A total of 22 patients with B-cell lymphoma from February 1, 2017 to July 1, 2018 were reviewed to evaluate the efficacy and adverse reactions of CD19 CAR-T. Results: Of 22 patients with B-cell lymphoma received CD19 CAR-T cells, the median dose of CAR-T cells was 7.2 (2.0-12.0) ×10⁶/kg. Nine of 12 cases of relapse refractory patients were overall response. Complete remission (CR) occurred in 2 of 12 patients, partial remission (PR) in 7 of 12 patients. The overall response in minor residual disease positive (MRD) group was 8 of 10 patients. CD19 CAR-T cells proliferated in vivo and were detectable in the blood of patients. The peak timepoints of CAR-T cells proliferated in the relapsed refractory and MRD positive groups were 12 (5-19) and 4.5 (1-12) days after treatment respectively, and among peripheral blood cells, CAR-T cells accounted for 10.10% (3.55%-24.74%) and 4.02% (2.23%-28.60%) of T lymphocytes respectively. The MRD positive patients achieved sustained remissions during a median follow-up of 8 months (rang 3-18 months) . None of all the patients relapsed during a median follow-up time of 10 months (3-18 months) . However, 7 PR responders of the relapsed refractory patients maintained a good condition for 1.5-6.0 months. One patient bridged to hematopoietic stem cell transplantation, another one sustained remission for 12 months. Cytokine-release syndrome (CRS) occurred in 14 patients with grade 1-2 CRS in MRD positive group and grade 3 CRS in relapsed refractory group. Conclusions CAR-T cell therapy not only played a role in the rescue treatment of relapsed and refractory patients, but also produced a surprising effect in the consolidation and maintenance of B-cell lymphoma. CD19 CAR-T cells might be more effective in the treatment of MRD positive B-cell lymphoma patients than in the refractory or relapsed cases. High response rate was observed with fewer adverse reactions.

Objective To explore the optimal perioperative nursing program for patients receiving cardiac pacemaker by His bundle pacing or by para-His bundle pacing.Methods A total of 26 patients,who were receiving cardiac pacemaker by His bundle pacing or by para-His bundle pacing,were enrolled in this study.The bundle of cares,used as the nursing intervention measures,was executed in all patients,which included strengthening the professional training for specialist team members,improvement of preoperative intervention,careful intraoperative cooperation,postoperative observation of patient's condition and complications,prevention and health guidance,etc.Results Through the strict implementation of the special bundle of nursing cares,all the 26 patients could well cooperated with surgical procedure,and after the treatment the patients recovered smoothly and achieved the desired results with no occurrence of complications.Conclusion The intervention measures of the bundle of cares are scientific and reasonable.The implementation of the special bundle of nursing cares can promote the professional nursing ability of nurses and ensure the quality of nursing service.

Objective: To investigate the specific cytotoxicities of the second and third generations of chimeric antigen receptor (CAR) -engineered T cells (CAR-T) on different lymphomas. Methods: CAR-Ts were prepared by lentivirus packaging and infection of T cells. CCK-8, ELISA and Lactate dehydrogenase cytotoxicity assay were applied to detect the proliferation capacity, the secretion level of inflammatory factor and the specific cytotoxicity. Flow cytometry assay showed the specific cytotoxicity and residual level of CAR-T in lymphomas of treated mice. Results: The results showed that the third generation CAR-T had greater capacity of the specific cytotoxicity and proliferation capacity than of the second generation CAR-T. But there was no prominent change of the secretion level of inflammatory factor. The specific cytotoxicity of the second generation CAR-T on highly aggressive lymphomas Raji was more prominent than in inert EHEB, but also could achieve satisfactory effect. The tumor burden in the mice injected with Raji was lower than in the mice injected with EHEB from nude mice experiment. But the residual level of CAR-T in the EHEB-injected mice was higher than in the Raji-injected ones. So the second generation CAR-T was more suitable for the treatment of indolent lymphoma. Conclusion The second generation CD19 CAR-T could treat aggressive lymphoma in a relatively short period, while the second generation CD19 CAR-T need a longer time in vivo to achieve satisfactory curative effect on the noble lymphoma.

In order to train the clinical ophthalmic seven-year students to further comprehend their professional knowledge and further stimulate their imagination and creation ability, we developed several steps to promote these students' patent designing ability. These steps include: trained targets selection, theoretical knowledge training, clinical practice training, comprehensive quality control, et al. In the implementation of the concrete steps, we put emphasis on the elements such as step by step training, the high quality computer assisted mapping and the internationally compatible contents, et al., and encouraged the students to propose the assumption of solving the problems in the clinical and sci-entific research. And the stimulation mechanism and medical humanity were infiltrated all the while.

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.