Objective To investigate the inhibitory effect and mechanism of epigallocatechin (EGC) on LPS-induced inflammatory response in BV2 cells. Methods Inflammatory response in BV2 cells was induced by LPS.The effect of LPS on cell viability was determined by MTT assay.The effect of EGC on NO expression level in cell supernatant was detected by Griess reagent.The secretions of TNF-α,IL-1β,and IL-6 were detected by ELISA assays.The expressions of Toll-like receptor 4 (TLR4),myeloid differentiation factor 88 (MyD88),and nuclear factor kappa-B (NF-κB) in BV2 cells were detected by Western blotting method.The nuclear translocation of NF-κB p65 and the expression levels of TLR4 and MyD88 in BV2 cells were detected by immunofluorescence method. Results LPS (1 μg·mL-1) and EGC (1-100 μmol·L-1) had no significant toxic effect on BV2 cells.After gived LPS stimulation,the release of NO in cell supernatant increased significantly.ECG (20 μmol·L-1) could significantly reduce the release of NO induced by LPS.The secretions of TNF-α,IL-1β,and IL-6 in other groups were significantly higher after LPS stimulation than those in the control group.Besides that,EGC at the concentrations of 10 and 20 μmol·L-1 significantly inhibited the secretion of inflammatory cytokines.Moreover,EGC could also significantly inhibit the activation of TLR4/MyD88/NF-κB signaling pathway induced by LPS,and suppress the nuclear translocation of NF-κB p65. Conclusion The inhibitory effect of EGC on LPS-induced inflammatory response in BV2 cell might be related to its inhibition on TLR4/MyD88/NF-κB signaling pathway and the expression of inflammatory cytokines.
Objective To investigate the inhibitory rate of curcumin analogues on 17β-HSD3 activity and the effect on inducing apoptosis of prostate cancer cells LNCaP. Methods Curcumin was used as the lead compound,and 9 compounds were designed and synthesized.The inhibition of 17β-HSD3 activity by the nine compounds was determined by a radioactive microplate assay.Six concentration gradients were designed for each compound,and IC50 were calculated.The compound with minimum IC50 value was used as the best inhibitor of 17β-HSD3,and it was used as the main drug for the subsequent study.Prostate cancer cells LNCaP were cultured and divided into 4 groups: blank control group,curcumin group (150 μmol·L-1),AR inhibitor group (5 μmol·L-1),and curcumin analogue H7 group (150 μmol·L-1).The LNCa cell viability was determined by MTT.The expressions of p53,Caspase-9,and Bax/bcl-2 mRNA were measured by Q-PCR.The content of testosterone in cells was determined by ELISA.The apoptosis related proteins p53,Bcl2,and Bax protein in LNCaP cells were detected by western blotting. Results The inhibitory IC50 of H1-H9 on 17β-HSD3 activity in rats were from (20.9±0.02) to (1120.4±124.6) μmol·L-1,and that in human were from (4.9±0.02) to (3140.7±165.7) μmol·L-1,among which the IC50 of H7 was the lowest.Therefore,H7 was selected as the experimental drug for the cell study.Compare to the control group,curcumin,AR inhibitor,and H7 inhibited LNCaP cell proliferation in various degrees (P<0.05 or P<0.01),and the effect of H7 was more significant than curcumin (P<0.05).Compared with the control group,curcumin,AR inhibitor,and H7 increased p53,caspase-9,Bax / Bcl-2 (P<0.05 or P<0.01) expressions in LNCaP cells in various degrees,and induced LNCaP cell apoptosis.It was found that H7 had more significant effect on LNCaP cell apoptosis.Compare to the control group,testosterone in curcumin,AR inhibitor,and H7 group were reduced in various degrees (P<0.01),and H7 group was more significant than Cur (P<0.01). Conclusion LNCaP cells and testosterone contents are inhibited by curcumin analogue H7.H7 can induce apoptosis of LNCaP cells and is a potential candidate for a new targeted drug in the treatment of prostate cancer.
Objective To investigate the protective effect of Bufei decoction on bleomycin induced pulmonary fibrosis in mice and its possible mechanism. Methods Fifty C57BL/6 mice were randomly divided into the normal control group,model control group,pirfenidone group,low- and high-dose Bufei decoction groups,and 10 mice in each group.Except for the normal control group,bleomycin was infused into the trachea to establish the pulmonary fibrosis model in mice.On day 3 after the modeling,the mice were treated with Bufei decoction (3 and 12 g·kg-1 by gavage) in low- and high-dose Bufei decoction group.Pirfenidone group were treated with 300 mg·kg-1 of pirfenidone.The normal control group and the model control group were treated with equal volume of 0.9% sodium chloride solution.On day 28,all of mice were sacrificed.The serum hydroxyproline (HYP),hyaluronic acid (HA),laminin (LN) levels were measured by commercial kits.The lung tissues of each group were photographed,hematoxylin eosin (HE) staining and Masson staining were performed to observe the changes of lung morphology.The protein expression of transforming growth factor-β (TGF-β),p-Smad3,α-smooth muscle actin (α-SMA),and collagen I were analyzed by Western blotting. Results Compared with normal control group,HYP,HA,and LN levels in model control group were significantly increased (P<0.05).Several morphological and pathological changes,including alveolar space collapse,emphysema,infiltration of inflammatory cells,and collagen deposition were observed.The expression of TGF-β,p-Smad3,α-SMA and collagen I were increased significantly (P<0.05).Compared with model control group,the levels of HYP,HA,and LN in low- and high-dose Bufei decoction groups were decreased significantly (P<0.05).Morphological and pathological changes were markedly attenuated.In addition,the protein expressions of TGF-β,p-Smad3,α-SMA,and Collagen I were decreased obviously (P<0.05). Conclusion Bufei decoction can effectively improve the pathological process of pulmonary fibrosis,and the mechanism may be related to the regulation of TGF-β/Smad3 signaling pathway.
Objective To investigate the role and the mechanism of interleukin 1 receptor associated kinase M (IRAKM) in the protection of Buyang Huanwu Decoction (BHD) against neuronal injury in the model cerebral ischemia-reperfusion in mice. Methods Mice cerebral middle artery occlusion model (MCAO) was employed.IRAKM expression was observed in both Sham operative and model mice after administration of BHD.Transcranial doppler was used to monitor the blood flow of MCA territory.Fluorescent quantitative PCR was used to determine the expression of inflammatory factors in the brains from IRAKM knockout and wild-type mice.TTC staining was employed to observe the infarct volume in mice brain between vehicle and BHD treatment,or between IRAKM KO and WT littermates. Results BHD could significantly induce the expression of IRAKM gene in the brains from both Sham operative and MCAO mice.IRAKM gene deficiency induced further transcriptional activation of inflammatory factors,including tumor necrosis factor α (TNF-α),induction nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2).Knockout of IRAKM gene could obviously exacerbate neuronal injury and weaken the cerebra-protective effect of BHD in ischemia-reperfused mice. Conclusion BHD protects brain against ischemia-reperfusion through induction of IRAKM.
Objective To observe the effect of Hawthorn leaves flavonoids(HLF) on blood lipid in hyperlipidemic rats and to explore its mechanism. Methods Forty-eight male SD rats were randomly divided into normal control group,model control group,simvastatin group (4 mg·kg-1),low,medium and high dose HLF groups (100,200,400 mg·kg-1) with 8 rats in each group.In addition to the normal control group,the other groups were given high fat diet to establish hyperlipidemia model.After 8 weeks of administration,the rats were killed,the liver index was calculated,the biochemical indexes were observed by kit,the pathological changes of liver tissue were observed by HE staining,the lipid droplets of liver were measured by oil red O staining,and the protein expression of AMPK,p-AMPK,ACC,p-ACC in liver tissues was determined by Western blotting method. Results Compared with the normal control group,the levels of TG,TC,LDL-C in plasma and the index of liver in the model control group were higher than those in the normal control group (P<0.01),the lipid droplets in hepatocytes were increased,the lipid deposition was more obvious,the degree of hepatic steatosis was more serious,and the expression of p-AMPK decreased while the expression of ACC,p-ACC increased(P<0.01).Compared with the model control group,the plasma levels of TG,TC and LDL-C,the liver index were significantly lower,the lipid droplets inhepatocytes were significantly fewer (P<0.05 or P<0.01),the lipid deposition in hepatocytes and the degree of hepatic steatosis were less obvious in low,medium and high dose HLF groups and simvastatin group.There was no significant difference in the expression of AMPK,ACC protein and p-ACC protein expression among different groups (P<0.05 or P<0.01).The expression of p-AMPK in high dose HLF group and simvastatin group was significantly higher than that in model control group (P<0.05 or P<0.01). Conclusion Hawthorn leaves flavonoids can decrease the lipid level in hyperlipidemia rats.The mechanism may be related to upregulating the protein expression of p-AMPK and downregulating the protein expression of p-ACC in the liver of hyperlipidemic rats.
Objective To investigate the mechanisms of propranolol in the treatment of prostate cancer. Methods Real-Time qPCR was employed to detect the expression levels of miR-382 and SETD8 mRNA;Western blotting was used to evaluate SETD8,p53,p21,apoptosis-associated proteins(including Bcl-2,Bax and Caspase 9) and metastasis-associated proteins(including N-cad,E-cad and Vimentin) expression levels.CCK-8 assay was performed to investigate cell proliferative ability and the dual luciferase reporter system was employed to explore the mechanisms of miR-383 targeting SETD8.Transwell assay was used to detect cell migration.Animal models was established to verify the inhibiting effects of propranolol on prostate cancer in vivo. Results Compared to normal cells and tissues,miR-382 downregulated and SETD8 upregulated in prostate cancer cells and tissues.Propranolol inhibited prostate cancer cell proliferation and migration,promoted cell apoptosis and prolonged survival time of tumor bearing mice by regulating miR-382/SETD8/p53/p21 pathway. Conclusion Propranolol inhibited prostate cancer progression via modulating miR-382/SETD8/p53/p21 pathway.
Objective To explore the role of macrophage polarization mediated by FoxO1 and p21 in sevoflurane-induced cognitive impairment after surgery. Methods Total 120 rats were randomly divided into control group,operation group and anesthesia group.The control group was anesthetized only with pentobarbital sodium,and the operation group and anesthesia group were operated by laparotomy,and the anesthesia group was given sevoflurane.The cognitive function of rats after sevoflurane-induced surgery was determined by Morris test.The apoptotic rate of hippocampal neurons and the concentration of cytoplasmic Ca2+ were detected by flow cytometry,and the expression levels of TNF-α,IL-1β and IL-6 in serum of rats were determined by qRT-PCR.The expression of FoxO1 and p21 protein in macrophages was measured by Western blotting,and the expression of macrophage-related inflammatory factors M1 and M2 were determined by ELISA. Results The escape latency of operation group was prolonged at all time points after operation,and the platform quadrant residence time was shortened,and the number of times of crossing the original platform was reduced in the operation group.In anesthesia group,the latency period was prolonged on the first,third,fifth,and seventh days after operation,and the platform quadrant residence time was shortened and the number of times of crossing the original platform was reduced.Compared with the control group,the apoptotic rate of hippocampal neurons in the operation group changed significantly (P<0.05).The[Ca2+] concentration of hippocampal neuron cytoplasm increased on the first day after the operation,and decreased on the seventh day after the operation.Compared with the control group,the[Ca2+] concentration of hippocampal neuron cytoplasm changed significantly in the operation group (P<0.05).In the anesthesia group (P<0.05).The expression levels of TNF-α,IL-1β,and IL-6 were higher than those in the control group,but there were no significant difference (P>0.05).The expression levels of FoxO1 and p21 in anesthesia group were lower than those in control group (P>0.05).Compared with control group,the expression levels of macrophage markers iNOS in operation group were significantly lower (P<0.05),and the expression levels of macrophage markers IL-10 and Arg-1 in M2 group were significantly lower (P<0.05).The expression of iNOS and IL-10 and Arg-1 were significantly increased in anesthesia group (P<0.05),but decreased in M2 group (P<0.05). Conclusion FoxO1 and p21 mediated macrophage polarization can promote the alleviation of sevoflurane-induced cognitive impairment.
Objective To investigate the drug utilization of ribavirin in patients with severe coronavirus disease 2019 (COVID-19),and to provide references for its clinical rational use. Methods The medical records of patients who was treated with ribavirin in a designated hospital for COVID-19 from February 1,2020 to February 29,2020 were retrospectively collected.And the demographic characteristics,usage,dosage,timing,the course of ribavirin treatment,and the combined use of antiviral drugs were analyzed. Results A total of 131 patients treated with ribavirin were distributed in all age groups,and the proportion of male was slightly higher than female.Among them,126(96.18%)patients were treated by intravenous.There were 102(77.86%)patients whose dose and frequency of administration were in accordance with the national diagnosis and treatment plan for COVID-19.The shortest treatment interval from symptom onset was 3 days,and the longest one was 41 days.The course of treatment varied from 1 to 22 days.Moreover,110 patients were given a combination of ribavirin and other antiviral drugs,including arbidol,lopinavir/ ritonavir,interferon α2b,and oseltamivir,etc. Conclusion The usage and dosage of ribavirin in patients with severe COVID-19 were generally reasonable,but there were significant differences in the timing and duration of medication.In a few cases,patients were treated with ribavirin alone or combined with three or more antiviral drugs.The rationality and safety of ribavirin use should be paid more attention.
Objective To assess the clinical application of lopinavir/ritonavir(LPV/r)in patients with severe coronavirus disease 2019(COVID-19),and to provide references for future clinical practice. Methods The medical records of patients who treated with LPV/r in a designated hospital for severe COVID-19 in February 2020 were retrospectively collected. The patients’ demographic characteristics,dosage,timing,course of treatment,combined medication and adverse reactions were statistically analyzed. Results A total of 217 patients received LPV/r during the monitoring period,and most of them were older than 64 (90 cases,41.5%).The course of LPV/r was usually within 10 days (159 cases,73.3%).Antiviral treatment regiments were mainly LPV/r alone (125 cases,57.6%)or combined with arbidol(71 cases,32.7%). Conclusion The treatment course,dose and antiviral combination of LPV/r during the treatment of COVID-19 generally met the recommendations of guidelines and literature.However,there were still cases of three kinds of antiviral drugs used in combination,the safety and rationality of LPV/r use should be extensively concerned.
Objective To provide references for the treatment of COVID-19 by systematic literature search and analysis of chloroquine phosphate in the treatment of virus infectious diseases. Methods Computer databases searches from Pubmed,Embase,Cochrane Central Register of Controlled Trials (CENTRAL),CNKI databases were carried out within the time limit from the establishment of the databases to February 27,2020.Descriptive analysis was made on the main results of the eligible articles that met the inclusion criteria. Results There were 2788 initially screened literatures,and 481 articles of chloroquine phosphate for viral infectious diseases were finally included.Chloroquine phosphate was used in 456 studies of malaria research,4 studies of acquired immunodeficiency syndrome(AIDS),2 studies of severe acute respiratory syndrome (SARS),4 studies of Zika virus (ZIKV),1 study of human infection with avian influenza,4 studies of flu,2 studies of Ebola virus (EBOV), 7 studies of dengue,and one study on the treatment of coronavirus disease 2019 (COVID-19).The results show that chloroquine phosphate was effective in treating malaria.In vitro studies have shown that chloroquine phosphate can inhibit HIV,SARS-CoV,ZIKV,DENV,and COVID-19.Animal studies have shown that chloroquine phosphate can inhibit the increase of pulmonary autophagy induced by avian influenzain mice,but cannot inhibit viral load and pro-inflammatory cytokines.Chloroquine phosphate was not effective against ebola.For the drug safety,chloroquine phosphate caused nausea,vomiting,and other common adverse reactions,and it also led to heart and eye toxicity. Conclusion Chloroquine phosphate has inhibitory effects on HIV,SARS-CoV,ZIKV,DENV,and SARS-CoV-2 in vitro.It is suggested that the adverse reactions of chloroquine phosphate should be paid attention to when the drug is given according to the diagnosis and treatment scheme,and the drug interaction should be considered when the drugs are combined.
Objective To investigate clinical characteristics and short-term risk factors for chest imaging lesions progression of COVID-19,and to early identify patients who may develop into severe COVID-19. Methods A total of 312 patients with COVID-19 from the fever clinic of Wuhan Pulmonary Hospital from January 10,2020 to February 8,2020 were included in the present study.A comparative study was carried out in 180 patients with advanced lesions and 132 patients with non-advanced lesions.The general situation,clinical symptoms,laboratory examination,imaging data,treatment and outcome of these patients were analyzed retrospectively. Results The median age of 312 patients was 52 years old with a male to female ratio of 0.9:1.The average age in both advanced group and non-advanced group was more than 50 years old,and there was no significant difference in age and sex composition ratio (P>0.05).In the advanced group,18 cases (10.0%) were complicated with diabetes,which was significantly higher than that in non-advanced group[3 cases (2.3%)](P<0.01).The treatment time (3.5 days,IQR 1-6),the time from symptoms onset to the first chest CT examination (5 days,IQR 2-7),the time from symptoms onset to the second chest CT examination (9 days,IQR 6-11),and the interval between the first chest CT examination and the second CT examination (4 days,IQR 3-5) in the advanced group were significantly lower than those in the non-advanced group (P<0.01).The symptoms of COVID-19 were fever (84.6%),chills (53.2%),cough (48.4%),fatigue (37.5%),sore throats (16.0%),diarrhea (8.0%),and polypnea (4.2%).The proportion of patients with fever in the advanced group (91.7%) was significantly higher than that in the non-advanced group (P<0.01).WBC count was normal or below in 300 cases (96.2%).Peripheral blood lymphocyte count was less than 1.1×109·L-1 in 163 cases (52.2%),and the peripheral blood lymphocyte count in the advanced group was significantly lower than that in the non-advanced group (P<0.01).C-reactive protein in the advanced group was 19.0 mg·L-1 (IQR 4.5-48.1),which was significantly higher than that in the non-advanced group (P<0.01).Two hundred and one patients with more than two lobes detected in chest CT.Among them,106 (58.9%) cases were in the advanced group and 95 (72.0%) cases were in the non-advanced group,respectively.There was no significant difference between the two groups in the involved location and imaging features of chest CT lesions (P<0.05). Conclusion The common symptoms of COVID-19 were fever,followed by chills,cough and fatigue.All patients with fever should be screened by chest CT in the early time.It is suggested that chest CT should be reexamined in a short period (3-5 days) to identify the patients who may develop into severe COVID-19.
Objective To analyze the patterns of the clinical and epidemiologic features of 305 patients with COVID-19 at different stage of the epidemic to provide reference for the control of COVID-19 and the treatment of patients. Methods A total of 305 patients with COVID-19 admitted to Jinyintan hospital of Wuhan City from December 2019 to February 2020 were enrolled.According to the onset time of disease,the subjects were divided into four groups: A,B,C and D.In group A,there were 72 patients who were onset before December 31,2019;In group B,there were 72 patients who were onset from January 1,2020 to January 14,2020.In group C,there were 84 patients who were onset from January 15 to January 28,2020. In group D,there were 77 patients who were onset from January 29 to February 11,2020.The gender,age,the time length of onset of disease,hospitalization days,clinical symptoms,imaging characteristics,previous disease history,exposure history,treatment status and disease prognosis after admission among four groups of patients were compared and analyzed. Results The average age of patients showed an increasing trend,and the difference was significant (F=12.62,P<0.000 1).The difference of family exposure history among the four groups was statistically significant (χ2=12.051,P=0.007).The median number of fever days in each group was statistically significant (H=43.88, P<0.01).The proportion of the four groups of patients receiving corticosteroids,gamma globulin,antifungal and antiviral therapy was different,and the difference among the four groups was statistically significant (χ2=23.78,P<0.000 18;χ2=33.07,P<0.000 1;χ2=21.52,P<0.000 1;χ2=60.634,P<0.000 1).The overall comparison of the imaging presentation among the four groups showed statistical differences (χ2=38.43,P<0.000 1). Conclusion The characteristics of patients with COVID-19 showed a first increased and then decreased trend,which may because of the policy intervention,strengthening of protective measures and health care force,and improvements of treatment plan.
Objective To analysis the clinical characteristics of chronic virus excretion patients with Coronavirus disease 2019 (COVID-19) and to explore the management strategies. Methods A total of 179 cases of COVID-19 patients who were discharged from Jinyintan Hospital of Wuhan from January 20 to March 10,2020 were collected,including 77 patients with chronic virus excretion and 102 patients with acute excretion.The clinical manifestations and imaging features before medication,time of nucleic acid turning negative and outcomes of the two groups were analyzed to explore management strategies. Results The clinical manifestations of the two groups were mainly fever (84.31% vs.74.03%),cough (64.71% vs.58.44%),chest tightness and shortness of breath (28.43% vs.20.73%),and digestive tract disorder (6.86% vs.9.09%,all P>0.05).Imaging features in parts of pulmonary involved of the two groups showed no significant difference in statistics (P>0.05).At the time of discharge,the proportion of patients who recovered to normal function (scoring 1) in two groups,showed a significant difference in statistics (87.25% vs.68.83%,P<0.0001).At the time of discharge,the proportion of patients who discharged but did not return to normal functional state (scoring 2) showed a significant difference in statistics (9.80% vs.29.87%,P<0.000 1).The mortality (scoring 7) of two groups were 2.94% and 1.30%,respectively (P>0.05). Conclusion The time of positive detection of nucleic acid in patients with chronic excretion virus is too long,which led to delay in treatment,increased hospitalization time,significantly longer virus duration,and more serious outcomes.For chronic virus excretion patients who are discharged with affected pulmonary function,the management mode should be rest at home plus on-site service by regional community health service center.Traditional Chinese medicine treatment and food adjustment could be given according to dialectics.Throat swab tests should be done regularly to confirm the rehabilitation and contagiousness situation of patients.
Objective To analyze the clinical characteristics of COVID-19 patients with underlying diseases and to explore risk factors in order to provide reference for the control of COVID-19 and the treatment of patients. Methods A total of 306 cases of COVID-19 patients,who were admitted to Jinyintan hospital of Wuhan from December 30,2019 to March 8,2020 were collected,and the treatment and outcome of 112 cases of patients with clinical symptoms,laboratory examination and imaging data of patients with underlying diseases were analyzed by taking patients without underlying diseases as control. Results There was no statistically significant difference between the two groups in terms of age,gender and hospitalization time.The incidence of fever in the group with underlying disease was 78.57%,which is lower than the group without underlying disease (P=0.012).Compared with the group without underlying disease,the incidence of cough in the group with underlying disease was higher (P=0.025),the incidence of symptoms of chest distress was higher (P=0.007),the cases of pneumonia involving more than 75% of the pulmonary imaging range was higher(P=0.015).Compared with the group without underlying disease ,the proportion of ordinary patients(P<0.001),and the proportion of critical severe patients(P=0.013) in the underlying disease group were lower.There was no statistically significant difference between the groups treated with corticosteroids,gamma globulin and antifungal therapy.Compared with the group without underlying disease,The proportion of patients discharged from hospital and returned to normal activity was lower in the group without underlying disease(P<0.000 1),The proportion of patients in the underlying disease group who were discharged but did not return to normal activity was higher(P<0.000 1). Conclusion The proportion of fever in COVID-19 patients with underlying diseases was lower than that of COVID-19 patients without underlying diseases,but the proportion of cough,chest tightness,shortness of breath symptoms was increased,the disease progressed rapidly,the rate of critical illness involving large areas of the lungs was high,and the prognosis was poor.Through reasonable treatment,the death rate could be reduced and the cure rate could be improved.
Objective To analyze affecting factors of conversion time of virus nucleic acid turn negative in coronavirus disease 2019 (COVID-19) and the relationship between the conversion time and prognosis. Methods Clinical data of 179 cases of COVID-19 patients were selected in Jinyintan hospital of Wuhan city from Jan.15, 2020 to Mar.8, 2020, and were analyzed retrospectively.Time of nucleic acid turning negative was analyzed.And patients were divided into A group (time of nucleic acid turning negative ≤19 d,n=105) and B group (time of nucleic acid turning negative >19 d,n=74) according to time of nucleic acid turning negative,correlation factor of time of nucleic acid turning negative in general conditions,clinical manifestations,imaging characteristic was analyzed with single factor analysis,influencing factors of the time of nucleic acid turning negative were analyzed with multi-factor Logistic regression analysis.The prognosis of the patients was evaluated with the prognosis turning “7-point scale”,and Pearson correlation test was used to analyze the relationship between the time of nucleic acid turning negative and the prognosis score. Results Time of nucleic acid negative time was from 1 d to 44 d,average time was (19.3±4.2) d,There was (8.6±2.7) d in group A, and (31.8±6.9) d in group B.Single factor analysis showed that diabetes mellitus,chronic lung disease,CT grade of lung,fever symptoms,duration of fever and digestive tract symptoms were related factors of nucleic acid negative time.Age,glucocorticoid,gamma globulin,respiratory symptoms and other symptoms were not related to nucleic acid negative time.Multivariate logistic regression analysis showed that diabetes mellitus,CT grade and fever duration were the independent influencing factors.In patients with COVID-19,the proportion of 1-score was 80.45%;the proportion of 2-score was 17.32%;and the proportion of 7-score was 2.23%.Correlation analysis showed that there was a positive correlation between the negative time of nucleic acid and the prognosis score (γ=0.416,P<0.05). Conclusion Time of nucleic acid turning negative in patients with COVID-19 is significantly different,and there are many related factors.Fever duration,diabetes mellitus and high CT grade are independent factors affecting the negative time of nucleic acid.The conversion time of nucleic acid is related to the prognosis of patients.Shortening the negative time of nucleic acid is the key to clinical treatment and improve the prognosis.
Objective To investigate the effects of hyporoteinemia on the severity and prognosis of coronavirus disease 2019(COVID-19). Methods The clinical data of 139 severely or critically ill patients with COVID-19,who were discharged from Jinyintan Hospital of Wuhan city from January 14 to March 18,2020,were divided into normal,low,moderate and severe groups according to serum albumin levels.Statistical analysis of respiratory failure,bacterial infection,improvement of chest imaging and mortality in different groups were conducted. Results Statistical analysis of the clinical data showed that there were significant difference in the rates of respiratory failure,bacterial infection,and pulmonary imaging degradation (P<0.05).There was significant difference in mortality among groups (P<0.05). Conclusion Serum albumin levels are related to the severity and mortality of COVID-19.In patients with lower serum albumin level,they are more seriously ill,more likely to get respiratory failure and bacterial infection,and recover slower in chest imaging performance;The lower albumin level contributed to the higher mortality rate.
Objective To explore the clinical characteristics of the elderly(≥60 years old) patients with COVID-19. Methods The clinical data of 171 patients with COVID-19 who had been discharged from the north second ward of Jinyintan hospital of Wuhan city from January 15,2020 to March 8,2020 were collected and analyzed.Patients were divided into two groups,A total of 75 elderly patients in group A,and 96 non-elderly patients (<60 years old) in group B.Clinical characteristics,time of onset,clinical classification,imaging presentation of lung,time of nucleic acid transferred into negative,hospitalization days,fever days and death cases in two groups were analyzed. Results Respiratory symptoms of group A were relatively mild,and non-respiratory symptoms were more common(P<0.05).The percent of lung lesions more than 75% in group A was bigger than that of group B,and the incidence of severe diseases in group A was significantly higher(P<0.05);In group A,the time of patients stay at hospital was significantly longer than group B,and the death rate was higher(P<0.05). Conclusion The elderly patients with COVID-19 had a higher incidence of severe disease and mortality.Attention should be paid to early detection and intervention to reduce the incidence of severe disease to improve survival rate in elderly patients with COVID-19.
Objective To establish a method for the determination of seven phenolic acids in Echinacea purpurea extracts from different producing areas by high performance liquid chromatography (HPLC),and to classify them by hierarchical clustering analysis (HCA),for the aim of providing basis for quality consistency and rational application. Methods The analysis was performed on an Inertsil C18 column (250 mm×4.6 mm,5 μm),mobile phase of 0.1% phosphoric acid water (A) - methanol (B) in a linear gradient mode.The flow rate was 0.8 mL·min-1.The detector wavelength was 280 nm and the column temperature was 30 ℃.The injection volume was 10 μL.The content of phenolic acids in Echinacea purpurea from different areas was analyzed by cluster analysis. Results The content of phenolic acids in Echinacea purpurea could be accurately determined by HPLC.Seven phenolic acids had good separation resolution under this chromatographic condition,and showed good linear relationship in the corresponding linear range.The average recovery was in the range of from 98.41% to 101.9%,RSD<3.0%. Conclusion The established method is simple and accurate,which can be used for the quality control of Echinacea purpurea and its extracts by combining with hierarchical cluster analysis.
Objective To prepare chrysin nanostructured lipid carrier,and to compare its oral bioavailability and pharmacokinetics with chrysin suspension after intragastric administration in SD rats. Methods The microjet homogeneity method was employed to optimize the preparation of chrysin nanostructured lipid carrier using orthogonal test.The particle size,Zeta potential,and in vitro drug release profile were also investigated.Twelve SD rats were randomly divided into chrysin suspension group and chrysin nanostructured lipid carrier group,and the dosage of intragastric administration was 50 mg·kg-1.HPLC was used to determine the plasma concentration of chrysin and the main pharmacokinetic parameters were also been calculated. Results The encapsulation efficiency,drug loading,particle size,and Zeta potential of the optimized chrysin nanostructured lipid carrier were (84.92±1.38)%,(7.22±0.31)%,(217.42±11.06) nm,and (-30.4±3.6) mV,respectively.Chrysin nanostructured lipid carrier had obvious sustained release characteristics compared to chrysin suspension.The results of oral pharmacokinetics showed that the relative bioavailability of chrysin nanostructured lipid carrier was increased 3.10 times. Conclusion Chrysin nanostructured lipid carries could promote the absorption and improve the bioavailability of chrysin significantly.
Objective To investigate the bioequivalence of tenofovir alafenamide (TAF) fumarate under fasting and fed conditions and the food effect on the pharmacokinetics of TAF in healthy Chinese volunteers. Methods A randomized,open-label,single-dose,two-preparation,three-sequence,three-period,partial repeat cross-bioequivalence trial was performed in healthy Chinese volunteers.Both fasting and fed trials enrolled 42 healthy subjects.A single dose of test or reference tenofovir alafenamide fumarate tablet (25 mg) was administered under fasting or fed conditions per period with 10-day washout period.The concentrations of TAF and its metabolite tenofovir (TFV) in plasma were determined by HPLC-MS/MS. Results The pharmacokinetic parameters under fasting conditions for the test and reference tablets were as follows: for TAF,Cmax were (268±103) vs.(272±134) ng·mL-1,AUC0-120 were (146±51) vs.(135±52) ng·h·mL-1,t1/2 were (0.307±0.086) vs.(0.305±0.098) h; for TFV,Cmax were (9.94±3.16) vs.(9.50±2.92) ng·mL-1,AUC0-120 were (254±86) vs.(239±72) ng·h·mL-1,t1/2 were (39.9±6.7) vs.(40.0±6.7) h.For TAF,AUC0-120 was 77% higher under fed versus fasting conditions,while Cmax was 11% lower.tmax increased under fed compared with fasting conditions for both TAF and TFV. Conclusion The test and reference tablets are bioequivalent.Diet has a significant effect on the pharmacokinetics of TAF.
Objective To provide the drug safety of antitumor drugs in clinical use. Methods Literatures were searched to summarize the stability problems and current situation of antitumor drugs in infusion selection and combination order. Results A total of 36 literatures ware searched. For different antitumor drugs,the infusion matrix of intravenous injection and the order of combined drugs would affect drug stability and safety. Conclusion In the process of using antitumor drugs,the selection of infusion matrix and the order of drug use should be paid attention to in the combination therapy.
Objective To analyze the prognostic factors of acute paraquat poisoning (APP),and to explore the methods to improve the survival rate of these APP patients. Methods The clinical data of 235 APP patients from June 2013 to July 2018 were collected and analyzed retrospectively.The patients were divided into survival group and death group,and the differences of clinical characteristics and laboratory test indexes between the two groups were compared,and single-factor and multi-factor analysis and survival curve analysis were conducted. Results The mortality rate of 235 patients was 40.5%,and the average survival time was 22.35 days.Univariate analysis showed that the differences in poison dosage,blood glucose,AST,and WBC were statistically significant,and HR was greater than one.The combined use of cyclophosphamide and blood perfusion also showed a statistical difference,and HR was less than 1.Survival analysis suggested the difference between the use group and the non-use group was statistically significant.Multivariate analysis suggested that dosing was a decisive factor for the prognosis of the patients. Conclusion The dosage,AST,and WBC are related to patient prognosis,and the dosage is the main factor affecting the prognosis.Early hemoperfusion and cyclophosphamide combined with hemoperfusion can improve the prognosis of some patients.
Objective To systematically evaluate the efficacy and safety of tulobuterol in the treatment of chronic airway obstructive disease. Methods The Cochrane library database,EMbase,Pubmed,CNKI,CBM,WANFANG DATA,and other databases were searched for randomized controlled trials of tulobuterol in the treatment of chronic airway obstructive diseases.Meta-analysis was performed using Rev Man version 5.0 software. Results A total of 19 randomized controlled trials were included in the analysis.The results of the meta-analysis showed that there was a statistically significant difference in the effective rate between the two groups [OR=2.50,95%CI(1.61,3.90),P<0.000 1];In terms of improving lung function,there was a slight difference in peak expiratory flow (PEF) between the two groups [MD=10.23,95%CI(0.65,19.82),P=0.04],but there was no statistical difference in the first second expiratory volume (FEV1);The frequency of using short-acting β2 receptor agonists was significantly reduced before and after treatment in TP group,and the difference was significant between the two groups [MD=-0.67,95%CI(-0.88,-0.46),P<0.000 01];In terms of medication compliance,the compliance of patients in TP group was better than that of the LABA group,and the difference was statistically significant [OR=3.75,95%CI(1.34,10.47),P=0.01];the difference of the incidence of adverse reactions between the two groups was not statistically significant. Conclusion Tulobuterol is effective and safe for chronic airway obstructive diseases.
Objective To investigate adverse drug reactions (ADRs) induced by montelukast sodium and provide references for clinical rational drug use. Methods Montelukast sodium induced ADRs reported in domestic and foreign literatures were collected and analyzed. Results A total of 68 literatures were included in this study involving 88 cases.The incidence rate of adverse events between males and females was 1.2:1.The ADRs involved multiple systems / organs,and ADRs from central and peripheral nervous systems accounted for the highest proportion up to 37.5%,followed by vascular (extracardiac) disorders accounting for 22.8%. Conclusion Montelukast sodium is widely used in clinical practice,and more attention should be paid to montelukast induced ADRs to ensure drug safety.
Objective To provide directions and ideas for the construction and improvement of Drug Safety Trust in local government. Methods The questionnaire empirical analysis method was used to analyze the influencing factors for Drug Safety Trust from the five aspects consumer individual characteristics,government supervision,drug enterprises,medical institutions,and social supervision,as well as attention,openness,integrity,daily performance,and problem-solving,etc of related subjects. Results The self-discipline literacy of each subject promoted the optimization of information communication channels,and enhanced the treatment effect of the drug safety issues.The handling effectiveness of drug safety issues of each subject was closely related to the social supervision force.The daily performance,problem handling,and social supervision of each subject accounted for a large proportion in the evaluation system of Drug Safety Trust. Conclusion Improving the information openness of drug safety,strengthening the education and training of the subjects with moral deficiency,unblocking the social supervision channels of multi-participation,and strengthening the risk controlling prevention of each subject and the constructing of emergency response system would effectively improve the local Drug Safety Trust.
Objective To analyze the characteristics of adjuvant drugs in China,and to provide a reference for promoting the rational use of adjuvant drugs. Methods The characteristics of adjuvant drugs were collected from the National Medical Products Administration,National Health Commission,China National Knowledge Infrastructure,Wanfang Medical Online,Pubmed,Medscape,and the other official websites and databases.Then analyzed the characteristics of adjuvant drugs,collected catalogue, classification, manufacturers, approval dates,adverse reactions,and recommended treatment of indications,etc. Results A total of 77 types of adjunctive drugs in 7 categories were identified,including 28 types of metabolic nutrition,17 types of immune enhancement,15 types of basic nutrients,7 types of improved microcirculation,5 types of proton pump inhibitors,4 types of hepatoprotective drugs,and 1 type of free radical scavenger.There are 2073 manufacturers of 77 modern adjunctive drugs.Sixty (77.9%)drugs were approved before 2003.The total number of adverse drug reactions (ADR)mentioned in adjunctive drug instructions was 513.There were 205 ADR in the drug instructions of proton pump inhibitors,with an average of 41 per types.The proton pump inhibitors were recommended for the treatment of all indications in their drug instructions. Conclusion There are too many manufacturers of the same adjuvant drug in China.The information of ADR in most adjunctive drug instructions may be incomplete.Pharmacoepidemiological investigation of rational use of adjuvant drugs should be carried out.