Abstract: Objective　To explore the antiviral effect of baricitinib in the SARS-CoV-2 infection and influence on cytokine levels. Methods　Calu-3 cells were infected with SARS-CoV-2 at MOI of 0.1, and the levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-1β), interferon β (IFN-β) and interferon-stimulated gene, IFIT2 in the infected cells were analyzed by qRT-PCR methods. At the same time, Calu-3 cells were infected with SARS-CoV-2 (MOI=0.1) after being treated with baricitinib for 2 hours. Cells were collected at 0, 24, 36, and 48 hours, and analyzed for the mRNA of the above genes in the drug-treated and untreated groups. Results　The mRNA levels of IL-6, TNF-a, IL-1β, IFN-β and IFIT2 in Calu-3 infected by SARS-CoV-2 cells were increased significantly. These cytokines were increased by nearly 100-fold post-infection 48 h compared with the control (P<0.000 1), and continued to increase with the infection time (P<0.001 or P<0.000 1). The increase of IL-8 mRNA level was not as significant as IL-6, TNF-α, IL-8, IL-1β, but it also showed a 2-4 folds increase. Baricitinib does not affect the level of viral RNA in Calu-3 cells after SARS-CoV-2 infection (P>0.05). However, baricitinib can significantly inhibit the up-regulation of IL-6 and TNF-α levels induced by SARS-CoV-2 infection (5.25-fold and 3.90-fold down-regulation, respectively, P<0.01), and has little effect on the levels of IL-8 and IL-1β . In addition, the drug could also significantly down-regulate the increase in IFN-β and IFIT2 levels caused by viral infection (10.51-fold and 90.78-fold down-regulation, respectively, P<0.000 1). Conclusions　Baricitinib inhibits the release of inflammatory cytokines to some extent, but it drastically down-regulates the expression of interferons and interferon-stimulated genes (ISGs), and has limited antiviral effect on SARS-CoV-2. Considering that interferon signal pathways play important roles on viral infection, caution should be exercised when using baricitinib to treat COVID-19 patients.

BACKGROUND: Autologous bone graft was always applied to repair bony cavity defect produced by benign bone tumor.OBJECTIVE: Taking autogenous bone graft for repairing bony cavity defect caused by bone tumor or tumor-like pathological change as control standard, to observe transplantation of deproteined bovine cancellous bone combined with autogenous red marrow in occluding the residual cavity and the density of newly formed bone.DESIGN: A randomized grouping design, controlled observation SETTING: Department of Orthopaedics, the 175 Hospital of Chinese PLA PARTICIPANTS:We recruited 175 cases of bony cavity defect who received treatment in the Department of Orthopaedics, the 175 Hospital of Chinese PLA from July 1993 to July 1998. They were randomly assigned into two groups: experimental group and control group. There were 63 cases treated in the experimental group. The average disease-suffering time was (6.2±2.1) months and bone defect was (136±30) mm3. There were 62 cases treated in the control group. The average disease-suffering time was (6.1±2.3)months, and bone defect was (133±37) mm3.METHODS: Deproteined bovine cancellous bone combined with autogenous red marrow was transplanted in the experimental group and autologous bone graft was applied in the control group. We curetted tumor completely, cauterized the wound with alcohol of 0.95 volume fraction, then curetted the area of cauterization to make it bled. Bone graft was applied.The quantity of implanted bone should be abundant, and disposed compactly. The X-ray films of the first week after operation were used as a standard for density of new bone growth. X-ray films were taken at the 3rd,6th and 8th months postoperatively, and the X-ray films of the eighth months after operation were used as a standard.MAIN OUTCOME MEASURES: To compare the bone union in two groups with a standard of residual cavity occluding and density of bone growth.RESULTS: All patients were followed up for an average of 20 months.One case was lost six months after operation. And two cases were lost eighteen months after operation respectively in the experimental group and control group. After 8 months of operation, residual cavities of bone defect of 44 cases in experimental group and 46 cases in control group were disappeared. Palingenetic bone fused with left bone organization. Its density was the same as or higher than normal bone organization. Residual cavities of 12 cases in experimental group and 10 cases in control group were disappeared basically. The density of palingenetic bone was approximate to normal bone organization. To compare with autologous bone graft, deproteined bovine cancellous bone and an autogenous red marrow had an identical effect for repairing bony cavity defect.CONCLUSION: Bony cavity defect produced by benign bone tumor is often repaired by bone transplantation. To explore the substitutable grafting materials of autogenous bone in this study, a composite material composed of deproteined bovine cancellous bone and an autogenous red marrow (DBCAM) is applied to repair the bony cavity defect.

In order to clarify material basis of effective parts of liangxue tongyu prescription, blood-heat and blood-stasis rat model induced by dry yeast was established. The changes of rectal temperature, blood viscosity and plasma viscosity were used to evaluate the cooling-blood and activating-blood effects of liangxue tongyu prescription and its parts. Compared with the model group, the extract from liangxue tongyu prescription, its volatile oil and n-butanol part could significantly reduce rectal temperature (P<0.01), and also reduce blood viscosity and plasma viscosity to various degrees (P<0.01 or P<0.05). So volatile oil and n-butanol part were primarily identified as effective parts of liangxue tongyu prescription. By using GC-MS with normalization method of area to analyze volatile oil of liangxue tongyu prescription, 70 compounds were identified, accounting for about 92.54%, mainly as β-asarone, paeonol, α-asarone and shyobunone. 42 compounds such as peony glycosides, tannins, and iridoid glycosides were identified by HPLC-MS techniques and standard comparison. The study determined the effective parts of liangxue tongyu prescription and clarified the chemical composition providing the foundation for further studies on material basis of liangxue tongyu prescription.
Acetophenones ; chemistry ; Animals ; Anisoles ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Gas Chromatography-Mass Spectrometry ; Oils, Volatile ; chemistry ; Rats ; Tannins ; chemistry

Objective To observed the expression of serum TNF-α and IL-10 in rats with severe acute pancreatitis (SAP) at different altitudes,and to explore the relationships between TNF-α and IL-10,the pathological changes of the pancreas,and the experimental basis for clinical diagnosis and treatment of SAP.Methods 72 specific pathogen free (SPF) Wistar male rats were divided randomly into three groups:1 500 meters altitude (group L),3 300 meters altitude (group M),and 4 300 meters altitude (group H).These three groups were then each divided randomly into four subgroups:control (group n),6 hours after pancreatitis (group p 6 h),12 hours after pancreatitis (group p 12 h),and 24 hours after pancreatitis (group p 24 h).Pancreatitis was induced by intraductal administration of 5％ sodium taurocholate hydrate (NaTc).The rats were killed at 6,12,and 24 hours after NaTc injection in groups p.The group n rats were killed after 6 hours of pancreas observation.Blood samples and pancreatic tissues were collected post mortem and enzyme-linked immunosorbent assay (ELISA) measured serum TNF-α and IL-10.Results Compared with the control (group n),histopathological scores,IL-10,and TNF-α in the same altitude had a significant difference (P ＜ 0.05) in group p at each time point.In the same altitude of group p,histopathological scores and IL-10 were increased with time elapsed (P ＜ 0.05),while TNF-α was decreased with time elapsed (P ＜ 0.05).There was a significant difference between group Mp and Lp in histopathological scores,IL-10,and TNF-α (P ＜ 0.05),and the same result between group Hp and Lp (P ＜ 0.05),but there was no significant difference between group Hp and Mp (P ＜ 0.05).Meanwhile,IL-10 had a positive relationship with histopathological score,but TNF-α had a negative relationship with histopathological score.Conclusions The level of TNF-α increased with increasing altitude but significantly reduced with elapsed time.The level of IL-10 increased with both increasing altitude elapsed time.These results suggested that TNF-o and IL-10 might play a important role at different times in severe acute pancreatitis.

Objective To investigate the etiological factors, clinical features and prognosis of non- traumatic rhabdomyolysis(RML). Methods The medical records of 13 non-traumatic RML patients hospital- ized between 1995-2006 were reviewed. The etiological, clinical, laboratory and therapeutic data were anal- ysed. Results Among 13 patients with non-traumatic RML, multiple factors were responsible for rhabdomyol- ysis in eight patients and single etiologic factor in 5 patients. Different etiological factors were identified, in- cluding 6 with excessive exercise, 3 with hyperpyrexia, 3 with drugs(including illicit drugs, fenofibrate, cy- closporine), 3 complicated with inflammatory myopathy and 2 with limbs compression. Nine patients had myal- gia and muscle weakness, 6 patients had abnormality in nervous system, 4 patients had hyperpyrexia, 3 pa- tients had digestive symptoms. Nine patients were complicated by coagulation disorders and 6 with acute renal failure(ARF). The serum levels of creatine kinase(CK)were decreased to normal within one month in 6 patients, the patient whose rhabdomyolysis was induced by fenofibrate with diabetes and chronic renal failure showed to inadequate decrease within 60 days. Three patients whose problem was induced by inflammatory myopathy, CK levels decreased within 4 months and 6 months in 2 patients, respectively, but CK level was not returned to normal level in one patient during the 80 follow-up days. Three patients died from multiple causes, such as ARF, coagulation disorders,electrolyte and metabolic disturbances. Conclusion Excessive exercise is the most common cause of non-traumatic RML, followed by drugs and inflammatory myopathy. The prognosis is poor in patients with multiple etiological factors and ARF.

Objective: To explore the inhibitory effect of artesunate(Art)on human esophageal carcinoma cells and to study the related mechanism.Methods: Nude mice were inoculated with Eca109 cells subcutaneously on the left upper limbs to establish esophageal carcinoma model.The model mice were divided into 5 groups: first group received 100 mg/kg Art,second group 200 mg/kg Art,third group 300 mg/kg Art,forth group 3 mg/kg cisplatin(DDP),and the fifth group received normal saline.Mass and volume changes of transplant tumors in different groups were observed.Flow cytometry was used to detect the cell cycle,apoptosis,and the expression of CDC25A protein,Smad3 protein and TGF-?protein in the transplanted tumors in mouse model.RT-PCR was used to detect the expression of CDC25A,Smad3 and TGF-?mRNA in the transplanted tumors.Results: Nude mouse model bearing human esophageal carcinoma was success- fully created.Compared with the control group,the volume and mass of transplant tumors in Art groups were significantly smaller(P

Aged ; Bronchoscopy ; Esophageal Neoplasms ; complications ; Female ; Humans ; Male ; Middle Aged ; Stents ; Thyroid Neoplasms ; complications ; Tracheal Stenosis ; etiology ; therapy

Objective To study and analyze the CT and MRI findings of hepatic eosinophilic infiltration. Methods Twenty nine patients of hepatic eosinophilic infiltration who were confirmed by biopsy or clinical diagnosis were retrospectively analyzed. All the patients underwent CT and/or MRI scan. Twenty seven cases underwent upper abdominal CT plain scan and three phase enhanced scan, and 5 cases underwent upper abdominal MR plain scan and three phase enhanced scan, of which 3 cases underwent CT and MRI scan. Evaluations were made regarding to the numbers of lesion, distribution, size, shape, margin, density or signal characteristic, enhancement parttern and other special features. Pearson correlation analysis was used to analyze the correlation between the number of hepatic lesions and the number of eosinophils in peripheral blood. Results A total of 108 lesions of eosinophilic hepatic infiltration were observed in 29 cases, including 2 cases with single lesion and 27 cases with multiple lesions. Ninety five of the lesions were located in subcapsular parenchyma or surrounding the portal vein. Most subcapsular lesions were wedge-shaped(n=28). Lesions surrounding portal vein were round-shaped(n=32), while the hepatic parenchymal lesions were irregular or round-shaped(n=13). The mean size of lesion was 34 mm, ranging from 3 to 61 mm. The margin of all the lesions were obscure. The lesions showed slightly low density or isodensity on CT pre-contrast images. On MR pre-contrast images, lesions showed slightly low signal or isointense on T1WI, and hyperintense on T2WI. Branches of portal vein were found infilrated by all lesions. Tueleve cases showed“stripe sign”along the portal vein branches, 16 cases showed“halo ring sign”around the portal vein. Pearson analysis indicated a significant correlation between the number of eosinophilic hepatic infiltrated lesions and the increase of eosinophils in peripheral blood (r=0.783, P<0.05). Conclusion The imaging features of EHI had certain characteristics, especially in the three phase dynamic enhanced scanning, from which we can mainly find“progressive enhancement”,“portal vein sign”,“stripe sign”and“halo ring sign”.

OBJECTIVETo investigate the systemic changes of iron metabolism following manganese exposure.

METHODSNinety-seven welders and 91 workers with no history of exposure to manganese were recruited from the same factory in Beijing serving as the exposure group and the control group respectively. The welding rods used were type J422. The concentration of the manganese in the air of the work place was determined respectively with the national standard method. The serum iron and manganese, ferritin, transferrin and transferrin receptors were measured with the graphite furnace atomic absorption spectrophotometry and ELISA in both groups.

RESULTSThe permissible concentration-STEL of ambient Mn in welders' breathing zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the breathing zone of the workplace. Serum Mn and Fe concentrations in welders were about 1.40 times (P < 0.0l) and 1.2 times (P < 0.01), respectively, higher than those of control subjects. At the same time, the transferrin concentrations in serum were significantly higher (about 1.2 times, P < 0.05) in welders than in controls. In contrast, transferrin receptors were significantly lower (about 1.2 times) in exposed subjects than controls (P = 0.001). There was no difference in serum ferritin between the two groups (P = 0.112). Although there was no significant trend, the serum ferritin level was increased by 18% in comparison with that of the control. The abnormal percentage of serum Fe and Serum Mn in welders were 55.67% and 67.01% respectively, higher than those of control subjects. In addition, the correlations between all indicators and the duration of employment were not observed.

CONCLUSIONThe long term exposure to the manganese can induce the disorder of the iron metabolism, which is found in the expression of increase of the serum iron and transferrin as well as the decrease of transferrin receptors.

Female ; Ferritins ; blood ; Humans ; Iron ; metabolism ; Iron Metabolism Disorders ; chemically induced ; Male ; Manganese ; adverse effects ; Occupational Exposure ; adverse effects ; Receptors, Transferrin ; blood ; Transferrin ; analysis ; Welding

Objective To investigate the effects of regular and irregular mandatory treadmill running (TR) on learning and memory abilities,stress response,survival and maturation of newborn neurons in dentate area of C57 mice. Methods Forty-eight male C57BL/6 mice were randomly divided into regular running group (n=16,definite time and quantity), irregular running group (n=16,definite time and different quantities) and sedentary group (n=16).Injection of bromodeoxyuridine (BrdU,50 mg/kg) was given intraperitoneally to mice from the 1st d to the 7th d of exercise,and then,these mice were subjected to a 4-wk TR training course or sedentary exercise.Double irnmunofluorescence labeling was employed to observe the effect of TR on survival and maturation of newborn neurons. Mice were trained on the Morris water maze to test the abilities of learning and memory. Corticosterone (CORT).level in the venous blood was measured with a radioimmunoassay kit. Results As compared with that in mice of the irregular running group and sedentary group,significant decrease of latency was noted in mice of the regular running group on the 1st, 3rd, 4th and 5th d of place navigation test (P＜0.05). As compared with that in mice of the sedentary group, significant decrease of latency was noted in mice of the irregular running group and regular running group on the 2nd d of place navigation test (P＜0.05),while no significant difference of that was noted between mice of the irregular running group and regular running group (P＞0.05).The platform was removed for a 60-s probe test 4 h after the last trial to test the recall ability, and the times of staying in the target zone in each group were regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The numbers of double immunofluorescence labeled cells in the dentate gyrus were counted as regular running group＞irregular running group＞control group, and significant difference was noted between each 2 groups (P＜0.05). The serum CORT level was measured as regular running group＜irregular running group＜control group, and significant difference was noted between each 2 groups (P＜0.05). Conclusion Mandatory treadmill running could improve the learning and memory abilities,which may be related to the increment of survival and maturation of neural precursor cells,and decreased level of serum CORT; and the effect of regular mandatory treadmill running is better than that of irregular mandatory treadmill running.