BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

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 expression of monocyte subsets and their chemokine,i.e.,monocyte chemoattractant protein (MCP-1) and fractalkine (FKN),in patients with acute coronary svndrome (ACS),and to analyze their correlation.Methods Patients with the syndrome of pectoralgia and to be inspected with coronary angiography (CAG) in our hospital from Sep.to Dec.,2016 were included.Patients' venous blood was collected on the operation day before operation,the level and proportion of monocyte (Mon) subsets,which was namely CD14 + CD16-Mon (Mon1),CD14+CD16 + Mon (Mon2) and CD14-CD16 + Mon (Mon3) according to the expression of cluster differentiation-14 (CD14) and CD16,were detected by flow cytometry (FCM).Patients' venous blood was collected on the operation day before operation and one day after operation,the concentrations of MCP-1 and FKN in plasma were measured by ELISA.We compared the expression levels of MCP-1-Mon1 and FKN-Mon3,and analyzed their relationship between each other respectively in different groups.Results Diagnosed according to the clinical symptoms,myocardial markers,electrocardiogram and CAG results,70 individuals were analyzed,including 30 patients with acute myocardial infarction (AMI group),25 patients with unstable angina pectoris (UAP group) and 15 patients with the chest pain symptoms and normal CAG results (control group).The percentage of Mon1 in the AMI group was higher than that in the other groups (P＜0.05);no difference was observed for Mon3 among the groups (P＞0.05).The Mon3/Mon1 ratio in the AMI group was lower than that in the control group (P＜0.05).Moreover,the levels of FKN and MCP-1 in the ACS group were greater than those in the control group.The level of red blood cell distribution width (RDW) was significantly increased in the AMI and UAP group than that in the control group (P＜0.05).There was a significant correlation between FKN and Mon3 (P＜0.05,R=0.650 2).Conclusions The monocyte subset of Mon1 and Mon3 increased in the early stage of ACS,with their chemokine (FKN and MCP-1) increasing at the same time.There is a significant correlation between FKN and Mon3,which indicates MCP-1-Mon1 and FKN-Mon3 may participate in the pathophysiological process of early ACS in patients.

Objective To explore the feasibility of repairing the large area skin and soft tissue defect in thefront upper of tibia by free flap with anastomosis of saphenous vessels.Methods From June,2009 to April,2014,16 cases (10 males and 6 females) of large area skin and soft tissue defect in the front upper of tibia were treatedwith free flap.The ages ranged from 24 to 56 years old,averaged of 34.5 years old.The supportive therapy and repeated debridement combined with VSD,and designed to use free anterolateral thigh flap with anastomosis of saphenous vessels before repairing operation.Results Fourteen patients accorded with preoperative design,in which 2 cases were adopted cross leg flap anastomosis posterior tibia vessels of the healthy side (1 case of saphenous artery diameter too small,and 1 case of saphenous artery long injury degeneration,unsuitable for vascular anastomosis).All 14 flaps survived,expect 2 cases were part-necrosis in the end of the flap,and gradually healed by dressing exchange.Conclusion Reconstruction of large area skin and soft tissue defect in the front upper of tibia with free flap can use anastomosis of saphenous vessels.

Electric and electronic products are required to pass through the certification on electrical safety performance before entering into the market in order to reduce electrical shock and electrical fire so as to protect the safety of people and property. The leakage current is the most important factor in testing the electrical safety performance and the test theory is based on the perception current effect and threshold. The traditional method testing the current threshold for perception only depends on the sensing of the human body and is affected by psychological factors. Some authors filter the effect of subjective sensation by using physiological and psychological statistical algorithm in recent years and the reliability and consistency of the experiment data are improved. We established an experiment system of testing the human hody's current threshold for perception based on EEG feature analysis, and obtained 967 groups of data. We used wavelet packet analysis to detect a wave from EEG, and used FFT to do spectral analysis on alpha wave before and after the current flew through the human body. The study has shown that about 97.72% alpha wave energy changes significantly when electrical stimulation occurs. It is well proved that when the EEG feature identification is applied to test the human body current threshold for perception, and meanwhile alpha wave energy change and human body sensing are used together to confirm if the current flowing through the human body reaches the perception threshold, the measurement of the human body current threshold for perception could be carried out objectively and accurately.
Algorithms ; Electric Stimulation ; Electroencephalography ; Humans ; Reproducibility of Results ; Sensory Thresholds ; physiology ; Wavelet Analysis

Objective To approach the design and clinical application of large anterolateral thigh flap and its effect in wound repair.Methods The flaps were designed according to the anatomical features of perforating branches in the anterolateral thigh flaps.When a flap was chipped,a thick branch or a terminal branch of original vessel was reserved,another suitable perforating branch was selected in the proximal or distal end of the flap,and then the two vessels were anastomosed to enlarge the range of blood supply.If the vessel pedicle of a flap was a musculocutaneous perforating branch,the perforating branch of anastomosis was cut at out-point of muscle.If the vessel pedicle of a flap was a intermusclar branch or a direct skin artery,the perforating branch of anastomosis was cut widely.From May 2006 to May 2012,the technique was applied in 28 patients with large skin defect of limbs.The diameters of perforating branches obtained at out-point of muscles were measured during surgery.The survival of flaps was observed after surgery and complications in donor sites were checked during follow-ups.Results There were 18 flaps whose vessel pedicle were musculocutaneous perforating branches.The branches were cut at outpoint of muscles.The diameters of these vessels were measured during surgery.They ranged from 1.3 mm to 1.8 mm with an average of 1.45 mm.All of the vessels could be anastomosed.All 28 flaps survived.All flaps survived.The areas of the flaps ranged from 22 cm × 15 cm to 42 cm × 14 cm.Artery crisis happened in 2 flaps whose vessel pedicle were musculocutaneous perforating branches.The second look operation found that the areas of artery anastomosis of perforating branches and vessel pedicles were compressed by hematoma and thrombus formed.The 2 flaps survived after the hematoma was cleared away and the vessels were reanastomosed.There were no infections.Both the donor and recipient site healed by first intention with no necrosis of flap margin.All 28 patients were followed up by 4-13 months with an average of 8 months.There were no apparent collapse deformities,muscle necrosis,declines of muscle strength and muscle hernia in the donor sites.The appearance of flaps was flat,the color was close to normal and the quality was fine.Conclusion It is a safe and effective method to repair wound surface by large anaterolateral thigh flap obtained by the modus operandi of perforating branch anastomosis.

Objective To explore the influence of salinomycin in the growth, apoptosis and invasion of human bladder cancer 5637 cells,and to clarify its possible mechanism.Methods The human bladder cancer 5637 cells cultured invitro at logarithmic growth phase were divided into control group and different doses of salinomycin(15, 30 and 60μmol·L-1 )groups.The inhibitory rate of the growth of 5637 cells in various groups was measured by MTT assay. Flow cytometry was used to detect the apoptotic rates of 5637 cells in various groups. The invasiveness of 5637 cells was tested by Matrigel Invasion Assay.The expression levels ofβ-catenin protein in 5637 cells in various groups were determined by Western blotting method. Results Compared with control group,the inhibitory rates of growth of human bladder cancer 5637 cells in different doses of salinomycin groups were increased significantly(P<0.05);the apoptotic rates were increased(P<0.05).the number of cells passed the Matrigel was decreased(P<0.05),and the expression level ofβ-catenin protein was decreased (P<0.05).Compared with low dose of salinomycin group,the inhibitory rate of growth of 5637 cells in high dose of salinomycin group was increased(P<0.05);the apoptotic rate was increased(P<0.05),the number of cells passed the Matrigel was decreased (P < 0.05 ), and the expression levels of β-catenin protein was decreased (P<0.05). Conclusion Salinomycin can inhibit the growth of 5637 cells significantly,increase the apoptosis,and decrease the cell invasion;the inhibitory effect may act by inhibiting the Wnt/β-catenin pathway.

Objective To evaluate the efficacy of low-dose and long-term clarithromycin in treatment of chronic rhinosinusitis with positive bacterial biofilms.Methods Seventy-seven patients with chronic rhinosinusitis and positive bacterial biofilms underwent functional endoscopic sinusitis surgery between January 2008 and December 2009 in department of otolaryngology of Jinhua Central Hospital.Fortytwo patients were treated with clarithromycin 250 mg/d orally for at least 3 months (trial group).At the end of 3 months patients received endoscopic examination,for patients with mucosal epithelialization the clarithromycin therapy was stopped; for those with mucosal edema,granulation or polyoid formations the clarithromycin treatment was continued,but no longer than 5 months.Thirty-five patients in control group were not given clarithromycin.All patients were assessed by visual analogue scale (VAS) and nasal endoscopic examination (Lund-kennedy score) 6 months after surgery,the results were compared between two groups.Results Two patients in the trial group did not complete the protocol.VAS score and Lundkennedy score in trial group were 8.0 ± 0.8 and 3.6 ± 1.3 at 6 month after surgery respectively,while those in the control group were 7.3 ± 0.7 and 4.5 ± 1.7,and the differences were of statistical significance (t =5.311 and-3.187,P ＜ 0.01).Conclusion Low-dose and long-term oral administration of clarithromycin has positive impact on the prognosis of bacterial biofilms positive patients with chronic rhinosinusitis.

We tried to construct and identify the recombinant replication-deficient adenovirus vector coding for human tissue factor pathway inhibitor 2 (hTFPI-2) gene by AdMax system in HEK293 cells. Firstly, we obtained hTFPI-2 gene from the recombinant plasmid pIRES2-EGFP-TFPI-2 by PCR using primers with restriction endonuclease site of EcoRI or SacI. After digesting the hTFPI-2 gene and plasmid PDC316-IRES-EGFP shuttle vector, we ligated them with T4 ligase and formed the recombinant shuttle vector PDC316-IRES-EGFP-hTFPI-2. It was confirmed that the ligation product was inserted the gene of hTFPI-2 correctly by sequencing. Then we took cotransfection of HEK293 cells with the recombinant shuttle vector and genomic plasmid pBHGloxdeltaE1,3Cre by liposome lipofectamine2000, and finished the package of recombinant adenovirus Ad-hTFPI-2. The results of the PCR test and restriction endonuclease digestion confirmed the successful construction of the recombinants Ad-hTFPI-2. Furthermore, we measured the titre of Ad-hTFPI-2 with the aid of green fluorescence protein expression after multiplication and purification. The titre was 0.931 x 10(12) pfu/ml. Finally, we infected U937 monocytes by purified Ad-hTFPI-2, and determined the infection efficiency and the TFPI-2's level and activity. The efficiency of Ad-hTFPI-2 infection in U937 cells was 89.33%. After infected by Ad-hTFPI-2, the TFPI-2's level in supernatant increased about 7 fold. Also the TFPI-2 in supernatant had activities of inhibiting trypsin and plasmin. The recombinant adenovirus with the hTFPI-2 gene was constructed successfully. It will be helpful for the further investigation of its potentiality to be applied in antiatherosclerosis.
Adenoviridae ; genetics ; metabolism ; Defective Viruses ; genetics ; metabolism ; Genetic Vectors ; genetics ; Glycoproteins ; biosynthesis ; genetics ; Humans ; Monocytes ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; Transfection ; U937 Cells

As a famous traditional Chinese medicine, ginseng's metabolism has been a hot spot in recent years. In this review, relevant literatures on the research progress of the metabolism of ginsenosides in vitro have been introduced. This review focuses on artifical juice metabolism, intestinal bacteria metabolism, microbial and enzymatic biotransformation of ginsenosides. Main metabolic pathways of ginsenosides in vitro are also analyzed, which will provide a reference for the systematic study on metabolism of ginsenosides.
Biotransformation ; Ginsenosides ; chemistry ; metabolism ; Humans ; Medicine, Chinese Traditional ; Panax ; chemistry ; metabolism