Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

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.

Clinical Observation of Bufei Huoxue Capsules Combined with Azithr omycin Tablets in the Treatment of Patients with Stable COPD / 中国药房

OBJECTIVE： To observe the efficacy and safety of Bufei huoxue capsules combined with Azithromycin tablets in the treatment of patients with stable COPD. METHODS： Totally 140 patients with stable COPD were collected from Anhui Chest Hospital during Jun. 2014-Feb. 2018， and then divided into control group and observation group according to random number table， with 70 cases in each group. Both groups received smoking cessation intervention and symptomatic treatment. Control group was additionally given Tiotropium bromide powder for inhalation， once a day+Azithromycin tablets 0.25 g， twice a week. Observation group were additionally given Bufei huoxue capsules 4 pills， 3 times a day， on the basis of control group. Both groups were treated for 180 d continuously. The clinical efficacies of 2 groups were observed， and the levels of serum inflammatory factors （CRP， IL-6 and TNF-α）， lung function related indexes （PEF， FEV1 and FEV1/FVC） and COPD related symptoms （time of AECOPD attack and 6MWT） were observed before and after treatment. The occurrence of ADR was recorded. RESULTS： Totally 9 cases withdrew from the study in control group， and 3 cases in observation group. A total of 128 cases （61 cases in control group， 67 cases in observation group） completed the study. Total response rate was 92.54％ in observation group， which was significantly higher than 80.33％ in control group（P＜0.05）. Before treatment， there was no statistical significance in the levels of serum inflammatory factors， lung function related indexes or COPD related symptoms （P＞0.05）. After treatment， the levels of CRP， IL-6 and TNF-α in 2 groups were decreased significantly， and the times of AECOPD attack were decreased significantly； observation group was significantly lower or less than control group. PEF， FEV1 and FEV1/FVC were increased significantly in 2 groups and 6MWT was prolonged significantly； observation group was significantly higher or longer than control group （P＜0.05）. One case suffered from skin rash in control group， and two cases had mild nausea in observation group； no severe ADR was found in both groups. CONCLUSIONS： Bufei huoxue capsules combined with Azithromycin tablets can significantly reduce the level of serum inflammatory factors of stable COPD patients， improve their lung function， and relieve clinical symptoms with good safety.

Pravastatin sodium inhibits the release and activity of human peripheral blood neutrophil elastase induced by lipopolysaccharide / 安徽医科大学学报

Objective To study the effects of pravastatin sodium on the release and activity of neutrophil elastase ( NE) in human neutrophile granulocyte induced by lipopolysaccharide( LPS) . Methods Human neutrophile gran-ulocyte were isolated by Ficoll density gradient centrifugation, neutrophils and intracellular azurophilic granules were identified by myeloperoxidase( MPO) staining, LPS stimulated degranulation of neutrophils. The MPO activity in the supernatant was measured by colorimetric assay to determine the appropriate stimulus time and concentration, and neutrophil was treated with pravastatin sodium after LPS stimulation. ELISA mothed was used to detect the cell culture supernatant of NE content and NE activity was detected by colorimetric method. Results The content and activity of NE in the supernatant were significantly increased after LPS stimulation. The NE in the supernatant of the cells treated with pravastatin was significantly lower( P＜0.05) . Conclusion Pravastatin sodium can reduce neutrophil degranulation induced by LPS stimulation and decrease the release and activity of NE.

Effect of inhaled pravastatin on acute lung inflammation in cigarette smoking-exposed rat / 安徽医科大学学报

Objective To investigate the effect of inhaled pravastatin on the acute inflammation of lung in smoked rats.Methods 32 male SD rats were randomly divided into four groups(n=8 per group),as the controls,cigarette-smoking exposure group,saline or pravastatin treatment groups.The rats in the control group were treated routinely,the other groups were exposed to cigarette smoking for one week.Rats in saline or pravastatin group were treated with saline or pravastatin inhalation respectively.During smoking exposure period rats were weighted before and after the treatment,executed at day eight,blood,bronchoalveolar lavage fluid(BALF),and lung tissue were collected.The morphological alternations of lung tissue were observed.Total cell numbers in BALF were counted.Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of serum IL-10 and IL-17 content.Results The increase of body weight of smoke-exposed rats were less than that of the controls.In smoking-exposed rats,acute inflammatory changes were remarkable in the lung.The total cell numbers in BALF and levels of IL-10 were increased significantly(P<0.05).These changes were mitigated in pravastatin treated rats and an IL-10/IL-17 rebalance was observed.Conclusion Inhalation of pravastatin sodium has a certain inhibitory effect on cigarette smoke-induced acute lung inflammation in rats.

Expression and significance of high mobility group box 1 protein in BALF of patient with COPD / 重庆医学

Objective To preliminarily investigate the effect of high mobility group box 1 (HMGB1) in the pathogenesis of chronic obstructive pulmonary disease (COPD) by detecting the HMGB1 level in bronchoalveolar lavage fluid(BALF) of the COPD patients and analyzing the relation between HMGB1 and airway limitation .Methods The research subjects were divided into the COPD group (stable COPD ,20 cases) and control group[20 cases of upper airway cough syndrome(UACS)] .All subjects were performed the bronchoscopic examination as well as bronchoalveolar lavage .The total cell counting and percentage of neutrophilic granulocytes in BLAF were detected and compared between the two groups .The HMGB1 ,IL‐1βand TNF‐αlevels in BLAF were detected by using ELISA and compared between the two groups .The relation between HMGB1 with IL‐1βand TNF‐αand the rela‐tion between HMGB1 with pulmonary function(FEV1% predicted value) in the COPD group was analyzed .Results The total cell counting and percentage of neutrophilic granulocytes of BLAF in the COPD group were higher than those in the control group (P<0 .01) .The levels of HMGB1 ,IL‐1β,TNF‐αof BALF in the COPD group were higher than those in the control group(P<0 .01 , P<0 .05 ,P<0 .01) .In the COPD group ,the HMGB1 level in BALF was positively correlated with the IL‐1βand TNF‐αlevels(r=0 .79 ,P< 0 .01 ;r= 0 .48 ,P< 0 .05) ,while negatively related with the pulmonary function value(FEV1% predicted value ,r=-0 .70 ,P<0 .01) .Conclusion HMGB1 participates in and promotes the occurrence and development of COPD airway inflamma‐tion and the HMGB1 level in BALF is correlated with the severity of COPD .

Oxidative stress and inflammatory changes in the lung caused by cigarette smoking exposure in mice and the effect of smoking cessation / 安徽医科大学学报

Objective To observe the changes of pulmonary oxidative stress after cigarette smoking exposure,its re-lationship with inflammatory cytokines,and the effects of smoking cessation. Methods Fifty male BALB / c mice were randomly divided into the smoke exposure group,smoke cessation group,and the controls. Mice in smoke cessation group were exposed to cigarette smoking for 16 weeks. On 4,8,and 12 week after smoking cessation mice were executed and the bronchoalveolar lavage fluid(BALF)and lung tissue were collected. The morphologi-cal alternations of lung tissue were observed. Mean length of interval and mean alveolar number were measured. Total cell numbers in BALF were counted. Superoxide dismutase(SOD)activity was measured with hydroxylamine method,malondialdehyde(MDA)level was measured with TBA method. The levels of pulmonary interleukin-8 (IL-8)and tumor necrosis factor-α(TNF-α)in BALF and lung tissue homogenate were measured with ELISA. Re-sults Compared with the mice in the controls,emphysematous changes were remarkable in the lung of cigarette ex-posed mice,the total cell numbers in BALF were increased significantly(P < 0. 05)and reduced gradually after smoking cessation(P < 0. 05). SOD and MDA levels increased remarkably in the cigarette exposure group(P <0. 05),and declined gradually after smoking cessation. The levels of IL-8 and TNF-α in BALF and lung tissue ho-mogenate in the smoke exposure group increased significantly( P < 0. 05),and lowered time-dependently after smoking cessation,but not reached to normal level even 12 weeks after smoking cessation. SOD and MDA levels were positively correlated with the cytokine changes. Conclusion Abnormal oxidative stress in the airways caused by cigarette smoking exposure was merely partially reversed after smoking cessation. And the inflammation remains persistent concomitantly.

Changes of interleukin-17A and interleukin-22 in the lung of cigarette smoke exposed mice and the effect of N-acetylcysteine / 安徽医科大学学报

Objective To investigate the changes of interleukin-17A(IL-17A)and interleukin-22(IL-22)in the lung of cigarette smoke exposed mice and the effect of smoking cessation and N -acetylcysteine (NAC )treatment . Methods BALB /c mice in experimental groups were exposed to cigarette smoke.Then the smoke-exposure was stopped and mice were treated with NAC gavage.The mice were executed 1,2,and 3 months after smoking cessa-tion.Lung tissue sample and bronchoalveolar lavage fluid(BALF)were collected.HE staining was used to observe the pathologic changes of the lung and ELISA was used to measure the level of IL-17A and IL-22.Results Con-siderable emphysematous changes was found in the lung of mice exposed to cigarette smoke.Compared with the controls,the level of IL-17A and IL-22 elevated remarkably in pulmonary tissue and BALF after smoking exposure and declined gradually after smoking cessation.Additional NAC gavage treatment enhanced the decline tendency. Conclusion IL-17A and IL-22 might play a complex role in the chronic inflammatory changes of lung in mice ex-posed to cigarette smoke.

Reversal effect of delavirdine on multidrug resistance-associated protein 2-mediated multidrug resistance / 中国综合临床

Objective To study the effect and the possible mechanism of delavirdine on muhidrng resist-ance-aasociated protein 2(MRAP2)-mediated multidrug resistance in LLC/cMOAT cells. Methods MTT assay was used to determine the effects of delavirdine on proliferation of LLC/CMV and LLC/cMOAT cells. The inhibitory effects of vincristine (VCR),cisplatin (DDP),adriamycin (ADM) and etoposide (VP-16) used alone or in combi-nation with delavirdine on the proliferation of LLC/CMV and LLC/cMOAT cells were evaluated by MTT assay. The cell cycle distribution, the apoptosis rate of the cells treated with different concentration of delavirdine and the intra-cellular concentration of ADM were determined by flow cytometry (FCM). Results Delavirdine at the concentration of 4 μmol/L and below showed no significant cytotoxicity to LLC/CMV and LLC/cMOAT cells. The resistance of LLC/cMOAT cells to VCB, VP-16, ADM and DDP were 9.58,1.11,2.98 and 3.96 folds of that of LLC/CMV cells. When 2 μmol/L delavirdine was added, the resistance was 5.21 and 2.55 folds respectively;when 4 μmol/L dela-virdine was edded,the resistance was 7.56 and 3.03 ,while 2,4 μmol/L delavirdine made no significant changes to the chemosensitivity of LLC/CMV cells to VCR and DDP(P>0.05). Cellular cycle analysis demonstrated that 0,6, 12,24 hours after co-cultured with delavirdine the amount of cells at G1 phase increased from(38.92±0.15)% to (56.87±2.23)%,(65.36±2.76)% and (74.77±5.06)%. The cell apoptosis rate increased from 1.77% to 17.45% and 28.52% when treated with delavirdine at 2,4 μmol/L and VCR for 24 h. When treated with 2,4 μmol/L delavirdine, ADM accumulation in LLC/cMOAT cells was enhanced significantly(P<0.05). Conclusion DLV can partially reverse the multidrng resistance of LLC/cMOAT cells, and the reverse effect correlates to the concentration. The possible mechanism may involve the growth arrest at G1, increasing of intracellular drug concen-tration and promoting apoptosis.

A Retrospective Analysis of Distribution and Antibiotic Resistance Changes of Nonfermenters in Lower Respiratory Tract Infection / 中华医院感染学杂志

OBJECTIVE To investigate the distribution and antibiotic resistance of nonfermenting gram-negative bacilli isolated from lower respiratory tract infection patients from 2003 to 2007 for rational antimicrobial therapy in practice.METHODS The data of distribution and antibiotic resistance of nonfermenting gram-negative bacilli isolated from sputum samples of lower respiratory tract infection in our hospital from 2003 to 2007 were retrospectively analysed.RESULTS The most predominant nonfermenting gram-negative bacilli isolates were Pseudomonas aeruginosa,Acinetobacter baumannii,Acinetobacter lwoffii and Stenotrophomonas maltophilia.From 2003 to 2007,the resistance rates of these isolates to 15 antibiotics increased,especially P.aeruginosa to ceftazidime.The resistance changed from 30.2% in 2003 to 55.4% in 2005,54.8% in 2006,and reduced to 41.5% in 2007.The resistance to gentamicin,imipenem,netilmicin,ticarcillin and tobramycin varied in the similar way.The resistance of A.baumannii to imipenem increased from 21.1% to 59.7% within the five years.The resistance rate of A.lwoffi was still relatively low.S.maltophilis isolates were highly multi-resistant to antimicrobial agents tested with a rate ranging from 61.9%-100.0% except ceftazidime,ticarcillin and trimethoprim-sulfamethoxazole.CONCLUSIONS P.aeruginosa,A.baumanii and S.maltophilia are the main nonfermentive pathogens of lower respiratory tract infections and not susceptive to many antibiotics.The tendency of susceptibility and distribution changes of those bacteria should be considered in practice for proper antimicrobial therapy.

Pathogens Caused Acute Respiratory Tract Infection in Hefei Area:Epidemiological Studies / 中华医院感染学杂志

OBJECTIVE To investigate the etiology of acute respiratory tract infection(ARI)in Hefei area and risk factors that may influence the distribution of common pathogens.METHODS Direct immunofluorescence assay was applied to detect the respiratory syncytial virus(RSV),adenovirus(ADV),influenza virus A(FluA),influenza virus B(FluB),parainfluenza virus PIV(1,2,3)and real time fluorescent quantitation polymerase chain reaction (FQ-PCR)was applied to measuring Mycoplasma pneumoniae(MP)and Chlamydia pneumoniae(CP)in nasopharyngeal secretions and sputum specimens.RESULTS Among 530 cases included in this study,421 cases (79.43%)showed positive viral etiology.ADV accounted for 73(13.77%),FluA-68(12.83%),FluB-56 (10.56%),RSV-48(9.05%),PIVl-47(8.86%),PIV3-42(7.92%),PIV2-33(6.22%),MP-32(6.03%)and CP-22(4.15%).The detected positive rate of pathogens isolated in winter was the highest(85.07%).CONCLUSIONS Acute upper respiratory tract infection(AURTI)is common and more than 75%pathogens in Hefei area are virus in which the most commonly virus is ADV.Meanwhile atypical pathogens of infection should not be ignored.

The diagnostic value of flow cytometric DNA analysis of sputum in lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To evaluate the diagnostic value of flow cytometric DNA analysis of sputum cells in lung cancer patients.</p><p><b>METHODS</b>The DNA content of sputum cells was determined by flow cytometry in 44 patients (29 patients with lung cancer, and 15 patients with benign pulmonary disease). The results of DNA content of sputum cells were compared with those of cytologic morphology of sputum cells.</p><p><b>RESULTS</b>The last pathologic diagnosis was used as a diagnostic criterion, the sensitivity of DNA heteroploidy analysis was 82.8% , which was significantly higher than that of sputum cytology (82.8% vs 27.6%, P < 0.005); and the positive rate of heteroploidy in sputum samples in stage III and IV disease was significantly higher than that in stage I and II disease (87.5% to 76.9%, P < 0.002 5). In one case, the heteroploidy was found 10 months in advance of cytometry. In the control, heteroploidy was detected in 33.3% (2/6) patients with inflammatory pseudotumor and 50.0% (2/4) patients with tuberculous nodule, who were found with positive staining of Ki67 and PCNA.</p><p><b>CONCLUSIONS</b>Flow cytometry seems to be a valuable adjunctive method for the diagnosis of lung cancer, and probably for the early diagnosis.There are clonal changes in some inflammatory pseudotumor and tuberculous nodule.</p>