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 explore the diagnostic performance of ultrasound attenuation imaging (ATI) in grading the degree of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD).Methods:The liver gray-scale ultrasound and ATI examinations were performed on 212 subjects who were treated in Zhongshan Hospital Affiliated to Fudan University from August 2020 to March 2021. The attenuation coefficient(AC) values among different degrees of hepatic steatosis were analyzed and the diagnostic performance of ATI was evaluated. Relationships between AC values and clinical characteristics were assessed by Pearson′s correlation analysis.Results:The AC values for normal liver, mild, moderate and severe fatty liver were (0.56±0.05)dB·cm -1·MHz -1, (0.68±0.09)dB·cm -1·MHz -1, (0.82±0.09)dB·cm -1·MHz -1, (0.94±0.09)dB·cm -1·MHz -1, respectively. There were significant differences in AC values among different hepatic steatosis divisions( P<0.008). There was highly significant correlation between AC values and the degree of hepatic steatosis( r=0.860, P<0.01), moderate correlation between AC values and BMI( r=0.425, P<0.01), weak correlation between AC values and HDL-C( r=-0.237, P=0.029), no correlations between AC values and age, TC, TG, LDL-C ( r=0.083, 0.055, 0.133, -0.039, all P>0.05) .The areas under the receiver operating characteristics curve of ATI for mild fatty liver and above, moderate fatty liver and above, severe fatty liver and above were 0.958, 0.962, 0.918; the sensitivity were 90.1%, 95.8%, 94.9%, the specificity were 96.1%, 87.1%, 73.9%, and the cut-off values were 0.666 dB·cm -1·MHz -1, 0.719 dB·cm -1·MHz -1, 0.803 dB·cm -1·MHz -1, respectively. Conclusions:ATI is a reliable and convenient method for evaluating the degree of hepatic steatosis in MAFLD.

Objective To evaluate the role of astrocyte chemokine (C-C motif) ligand 2 (CCL2) in microglial activation in an in vitro experiment.Methods Primary astrocytes and microglias were isolated from the brain tissues of C57BL/6J mice at postnatal day 1-2.The experiment was performed in two parts.Experiment Ⅰ Astrocytes were inoculated in 6-well culture plates at a density of 3 × 104 cells/well (2 ml/well) and divided into 5 groups (n=3 each) using a random number table:control group (group C),tumor necrosis factor-alpha (TNF-cα) group,1 μg/ml CCL2 small interference RNA (siRNA) group (group CCL2-siRNA1),2 μg/ml CCL2-siRNA (group CCL2-siRNA2) and negative control siRNA group (group NC-siRNA).Astrocytes were cultured routiuely in group C,and 10 ng/ml TNF-α was added and astrocytes were incubated for 15 min followed by washout with phosphate buffer solution (PBS),and then astrocytes were incubated for 3 h in the other 4 groups.At 24 h before TNF-α was added,CCL2-siR-NA 1 and 2 μg/ml were added in CCL2-siRNA1 and CCL2-siRNA2 groups,respectively,and NC-siRNA 2 μg/ml was added in group NC-siRNA.The concentrations of CCL2 were determined by enzyme-linked immunosorbent assay.Experiment Ⅱ Microglias were inoculated in 6-well culture plates at a density of 3×104 cells/well (2 ml/well) and divided into 3 groups (n=3 each) using a random number table:control group (group C),TNF-α group and CCL2-siRNA group.Microglias were cultured routinely in group C.In group TNF-α,10 ng/ml TNF-α was added to astrocytes which were incubated for 15 min followed by washout with PBS,astrocytes were then incubated for 3 h,and the supernatant was collected and added to microglias which were incubated for 24 h.In group CCL2-siRNA,2 μg/ml CCL2-siRNA was added to astrocytes which were incubated for 24 h,10 ng/ml TNF-α was also added to astrocytes which were incubated for 15 min followed by washout with PBS,astrocytes were then incubated for 3 h,and the supernatant was collected and added to microglias which were incubated for 24 h.The activity of microglias was measured by immunofluorescence,and the migration of microglias was evaluated by Transwell migration assay.Results Experiment Ⅰ The concentrations of CCL2 were significantly higher in TNF-α,CCL2-siRNA1,CCL2-siRNA2 and NC-siRNA groups than in group C (P＜0.05).The concentrations of CCL2 were significantly lower in CCL2-siRNA1 and CCL2-siRNA2 groups than in TNF-α and NC-siRNA groups (P＜0.05).There was no significant difference in CCL2 concentrations between group TNF-α and group NC-siRNA (P＞0.05).Experiment 1Ⅱ Compared with group C,the activity of microglias was significantly increased,and the migration of microglias was enhanced in TNF-α and CCL2-siRNA groups (P＜0.05).Compared with group TNF-α,the activity of microglias was significantly decreased,and the migration of microglias was weakened in group CCL2-siRNA (P＜0.05).Conclusion Astrocyte CCL2 is involved in mieroglial activation in an in vitro experiment.

Objective To study the correlation between radial artery graft patency and the degree of native coronary stenosis in coronary artery bypass grafting. Methods The clinical data of 290 patients who had underwent off-pump coronary artery bypass grafting were retrospectively analyzed. The left internal mammary artery, radial artery and saphenous veins were as grafts. The patients were divided into 3 groups according to the stenosis of right coronary artery before operation:group Ⅰ(right coronary artery stenosis 50%-75%, 85 cases), groupⅡ(right coronary artery stenosis 76%-89%, 95 cases) and group Ⅲ (right coronary artery stenosis 90%-100%, 110 cases). The patients were followed up for 2 to 5 years, and the graft patency was assessed using CT coronary angiography. Results There was no death and serious complications in 3 groups. Among the 3 groups, the total graft patency rate of left internal mammary artery grafts was 93.3% (270/290), the total graft patency rate of saphenous veins grafts was 70.2%(433/617), and the total graft patency rate of radial artery grafts was 69.7%(202/290). There was no statistical difference in the graft patency rate of radial artery grafts between group Ⅱ and group Ⅰ(P>0.05). The graft patency rate of radial artery grafts in group Ⅲwas significantly higher than that in groupⅡand group Ⅰ:85.5%(94/110) vs. 68.4%(65/95) and 50.6%(43/85), and there was statistical difference (P<0.05). The graft patency rate of radial artery grafts was significantly higher than the graft patency rate of saphenous veins grafts in group Ⅲ :85.5%(94/110) vs. 71.5%(168/235), and there was statistical difference (P<0.05). There were no statistical differences in the graft patency rates of left internal mammary artery grafts and saphenous veins grafts among 3 group (P>0.05). Conclusions The correlation between radial artery graft patency and the degree of native coronary stenosis is significant in coronary artery bypass grafting. Patients with severe proximal right coronary artery stenosis (≥90%) may have better patency rates at mid-term follow up after using radial artery grafts.

Objective To analyze the reasons and treatment methods of high transprothetic pressure gradient after aortic valve replacement. Methods The clinical data of 45 patients with high transprothetic pressure gradient after aortic valve replacement were retrospectively analyzed. The patients were followed up for average 24.6 (12 - 40) months. The postoperative effective orifice area (EOA) of artificial valve was measured by transthoracic color Doppler ultrasound. Compared with published referred EOA of different artificial valve, there were 2 kinds results:measured EOA=referred EOA and measured EOA0.85 cm2/m2 and EOAI<0.85 cm2/m2. The reasons of high transprothetic pressure gradient were analyzed according to the above different standard. Results In the 45 patients with high transprothetic pressure gradient after aortic valve replacement, prosthesis-patient mismatch (PPM) was in 33 cases, and prosthetic dysfunction was in 10 cases, among whom 5 cases were because of thrombus (3 cases improved after increasing the dosage of warfarin, 2 cases underwent re-aortic valve replacement), 3 cases were because of severe bioprosthetic calcification (underwent re-aortic valve replacement), and 2 cases were because of prosthetic ring pannus and influenced movement of the leaflets (underwent re-aortic valve replacement). High flow in the left ventricular outflow tract occurred in 2 cases. The patients had no obvious discomfort, and did not receive special treatment. Four cases died, among whom 2 cases were because of severe PPM, and the other 2 cases were because of noncardiac. Conclusions Many reasons can result to the high transprothetic pressure gradient, and the PMM is the most common reason. Choosing the right treatment plan can improve the survival rate of patients.

Objective To investigate the influence of perioperative administration of Ambroxol on pulmonary function, postoperative complications, postoperative hospital-stay and cost in elderly lung cancer patients after thoracic lobectomy surgery.Methods One hundred and forty consecutive elderly patients who underwent thoracic lobectomy surgery for lung cancer were randomly assigned into 2 groups: control group (n=70) and Ambroxol group (n=70).In control group, subjects were given the standardized treatment.In the Ambroxol group, patients were given the standardized treatment plus Ambroxol (90 mg/q, 8 h/d) from the day of operation to postoperative 5 days.The preoperative general information, intraoperative conditions, pulmonary function tests, arterial blood gases, incidence of perioperative morbidity, duration of ICU stay, length and costs of postoperative hospital-stay were collected and compared between the 2 groups.Results The 2 groups were well matched for demographics and operative variables.The forced expiratory volume in 1 second (FEV1),the forced vital capacity (FVC), peak expiratory flow rate (PEF) and arterial oxygen pressure were reduced in the 2 groups after operation as compared with before treatment, while the decreases of the above indexes were more significant in the control group than in the Ambroxol group (P＜0.05).Compared with the control group, the postoperative pulmonary complications declined, oxygenation index improved, the postoperative ICU occupancy rate and the length and costs of postoperative hospital-stay were decreased in the ambroxol group (all P＜ 0.05).Conclusions Perioperative administration of Ambroxol could reduce the incidence of pulmonary complications, improve the lung function, decrease the total hospitalization cost, shorten the length of hospital-stay, promote a rapid recovery after surgery, which is worthy of clinical application.

Objective To explore the feasibility of ultra-long distance transport of lung from donation after cardiac death (DCD)or donation after brain death (DBD)by civil aviation for lung transplantation.Methods Clinical data of 6 cases with lung transplantation through ultra-long distance transport of lung from donors by civil aviation in Wuxi People's Hospital Affiliated to Nanjing Medical University from February to March in 201 5 were analyzed retrospectively.Results There were 6 donors who were DBD or DCD.It spent 5.0 ~8.5 h from lung removal,transport to lung transplantation in the operation room,including 2.0 ~3.0 h (mileage > 1 500 km)for flight.Five cases received sequential double lung transplantation.One case received right single lung transplantation.The operation was conducted successfully,with the lung's cold ischemia time of 7-1 2 h.After operation,all patients received ventilator assisted breathing,and suspended after 2-4 d.As of the date of submission,6 cases recovered well.Conclusions Long distance transport is feasible in the case of conducting sequential double lung transplantation with donor lung from DCD or DBD,if there are direct flights between the two cities of the donor and recipient,and the flight time is within 3 h.

ObjectiveTo approach the value of diagnosis with the 256-slice spiral CT in severe tetralogy of Fallot of infant.MethodsFrom January 2008 to December 2010,48 cases (severe tetralogy of Fallot of infant) were examined with 256-slice spiral CT preoperatively.All cases were then analyzed in workspace with maximum intensity projection(MIP),multiplanar reconstruction(MPR) and volume rendering (VR),while compared with transthoracic echocardiography (TTE) and surgical results.Results CT examination found that TTE misdiagnosis 4 cases of patent ductus arteriosus and 6 cases of aortic coarctation.Meanwhile,CT showed 6 aorta pulmonary collateral arteries in 5 cases.In 48 cases,surgical results confirmed 47 cases by 256-shce spiral CT,while 33 cases by TTE.The diagnosis accuracy rate of 256-slice spiral CT and TTE was 97.9％ (47/48) and 68.8％ (33/48) respectively.There was statistically significant difference of the two inspections in diagnostic accuracy (P ＜ 0.05).ConclusionThe inspection of 256-slice spiral CT can benefit the preoperative diagnosis and operation program in severe tetralogy of Fallot of infant.

Objective To evaluate the clinical effect of lung transplantation for pediatric pulmonary artery hypertension (PAH).Methods The recepter 1 and 2 with idiopathic pulmonary artery hypertension (IPAH) were diagnosed by right catheterization.The heart fuction was NYHA IV.The pulmonary artery pressure and mean pulmonary artery pressure were 110/70mmHg and 148/72 mmHg respectively.They underwent bilateral sequential lung transplantation with extracorporeal membrane oxygenation (ECMO) support.During operation,the ECMO support time was 550 min and 450 min and the blood loss was 3000 ml and 1200 ml respectively.The recepter 3 with end-stage congenital ventricular septal defect with Eisenmenger syndrome (ES) who had received open heart exploration underwent right single lung transplantation and ventricular septal defect repair under cardiopulmoanry bypass(CPB).There were ventricular septal defect and bidirectional shunt through UCG assessment The pulmonary artery pressure and mean pulmonary artery pressure were 110/60 mmHg.CPB time was 244 min.The three recepters had the same ABO blood group and the similar body type with the three donors.Results The recepter 1 and 2 was sustained by ECMO after operation for 16 h and 13h respectively.But unstable hemadynamics and acute left heart failure occured on 3rd and 4th day after the operation respectively.We treated them with ventilate support and tracheotomy on 3rd and 6th day respectively.They were also treated with cardiotonic; dieresis and the patients were weaned away from the ventilation on 33rd and 12ed day after the operation respectively.The transplanted lung of the receptor 3 had pneumochysis in the first 3 days.The patient was treated with ventilate support and tracheotomy on 7th day and was weaned from the ventilation on 12ed day after the operation.An acute rejection episode occurred on 14th day.The cordioform and heart function of the three cases improved and especially the receptor 3 had intact repaired of ventricular septal defect.They were discharged from the hospital on 93rd,32ed and 62ed day afer the operation.The heart function all reached NYHA I and the pulmonary artery pressure and mean pulmonary artery pressure was reduced to 54/32 mmHg,60/36 mmHg and 53/39 mmHg respectively.The three cases have been followed up for 41 months,21 months,and 82 months.They are having an excellent quality life.Conclusion Lung transplantation is effective to improve the quality of life for end-stage pediatric pulmonary artery hypertension even with slight right ventricular dysfunction with satisfying short-term results.

Objective To explore the perioperative application of extracorporeal membrane oxygenation (ECMO) in lung transplantation. Methods Thirty patients with primary and end-stage pulmonary disease accompanied by pulmonary hypertension were subjected to operation under the accessory of ECMO. Eighteen patients received single-lung transplantation and 12 patients bilateral sequential lung transplantation without sternal division in our hospital from November 2005 to July 2009. In 2 patients ECMO was given before operation and maintained for 19 days and 6 days respectively. In the remaining patients, ECMO pipeline was placed after anesthesia. After lung trarnsplantation,ECMO was removed after the recipients' oxygen saturation and hemodynamics were stable. Results In all recipients lung transplantation was successfully done. ECOM was removed in 27recipients after operation, and the rest 3 recipients were supported by ECMO after operation: the ECMO was removed at 36th h and 7th day after lung transplantation in two patients respectively,and another one was supported by ECMO for 5 days after operation and suffered acute kidney failure, and died of multiple organ failure 2 weeks post-transplantation. Two recipients were infected in thigh arteriovenous cut and one suffered femoral artery thrombosis, but all of them got better and discharged from hospital after treatment. Conclusion ECMO can be used for lung transplantation on patients with primary and secondary pulmonary hypertension. The complications may be associated with patients'serious condition and unstable hemodynamics. Early detection and active and effective treatment can improve patient's prognosis.