RESUMEN
ObjectiveTo perform a predictive analysis of the quality marker（Q-Marker） for the anticoagulant activity of Kunning granules. MethodThe chemical components of Kunning granules were analyzed by ultra high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry（UHPLC-Q-TOF-MS/MS） on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with the mobile phase of acetonitrile（A）-25 mmol∙L-1 ammonium acetate aqueous solution（B） for gradient elution （0-5 min， 5%-22%A； 5-10 min， 22%-30%A； 10-15 min， 30%-95%A； 15-20 min， 95%-5%A； 20-30 min， 5%A）， flow rate of 0.2 mL∙min-1， column temperature at 30 ℃， injection volume of 1 μL， electrospray ionization（ESI）， positive and negative ion detection modes. Interaction analysis between the targets of chemical components and the targets of abnormal uterine bleeding（AUB） was performed by network pharmacology， and the key components were screened through network topology analysis. The fingerprints of 10 batches of Kunning granules were established by high performance liquid chromatography（HPLC）， the anticoagulant activity of the granules was determined by blood coagulation method and fibrinogen plate method， and the spectrum-effective relationship was established. The components co-occurring in the topological analysis and spectrum-effective relationship were selected as Q-Markers， and their anticoagulant activities were verified and confirmed. ResultA total of 475 chemical components were identified from Kunning Granule， of which 22 key components such as salvianolic acid B， paeoniflorin， naringin and neohesperidin， were the potential material basis for the treatment of AUB. The spectrum-effective analysis showed that peaks 7（paeoniflorin）， 9（naringin）， 10（neohesperidin） and 11（salvianolic acid B） were the optimal principal components， and in vitro activity test showed that these four components could better characterize their anticoagulant activity. ConclusionSalvianolic acid B， paeoniflorin， neohesperidin and naringin may be Q-Markers for the anticoagulant activity of Kunning granules.
RESUMEN
Neck radiotherapy is an important means to prevent and treat cervical lymph node metastasis of nasopharyngeal carcinoma. Studies have found that radiation can directly or indirectly damage blood vessels, accelerate the process of atherosclerosis, and then cause carotid artery stenosis, increasing the risk of transient cerebral ischemia and stroke after radiotherapy. At present, we often apply color doppler ultrasound to detect the changes of carotid artery and actively prevent and reduce risk factors to decrease the occurrence of carotid artery stenosis. Carotid artery stenosis can be treated with early drug intervention and surgery. This article reviews the current research status of carotid artery injury caused by radiotherapy.
RESUMEN
Objective:To investigate the cardiac presentations and the possible influencing factors of severe and critical coronavirus disease 2019 (COVID-19).Methods:A retrospective study was conducted. Patients with severe and critical COVID-19 admitted to the Eighth People's Hospital of Guangzhou from January 21st to February 24th 2020 were enrolled. According to the clinical classification, the patients were divided into severe group and critical group. The myocardial injury markers, such as lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK), cardiac troponin I (cTnI), myoglobin (MYO), MB isoenzyme of creatine kinase (CK-MB), B-type natriuretic peptide (BNP) and electrocardiogram (ECG) changes were compared between the two groups.Results:A total of 55 COVID-19 patients were selected, including 15 critical cases and 40 severe cases. The patients with severe and critical COVID-19 were male-dominated (61.8%), the average age was (61.2±13.0) years old, 83.6% (46 cases) of them had contact history of Hubei, 38.2% (21 cases) of them were complicated with hypertension. There was no significant difference in baseline data between the critical group and the severe group. Myocardial injury markers of critical and severe COVID-19 patients were increased in different proportion, LDH increased in most patients (20 severe cases and 7 critical cases), followed by AST (16 severe cases and 5 critical cases). There was significant difference in the number of patients with elevated CK between severe group and critical group (cases: 1 vs. 4, P = 0.027). Abnormal ECG was found in 39 of 42 patients with ECG examination. Nonspecific change of T wave was the most common. Before and after treatment, 9 of 15 patients with changes of ECG and myocardial injury markers had oxygenation index less than 100 mmHg (1 mmHg = 0.133 kPa), and the prominent changes of ECG were heart rate increasing and ST-T change. Conclusions:The increase of myocardial injury markers and abnormal ECG were not specific to the myocardial injury of severe and critical COVID-19 patients. At the same time, the dynamic changes of myocardial injury markers and ECG could reflect the situation of myocardial damage.
RESUMEN
BackgroundAntiviral therapies against the novel coronavirus SARS-CoV-2, which has caused a global pandemic of respiratory illness called COVID-19, are still lacking. MethodsOur study (NCT04252885, named ELACOI), was an exploratory randomized (2:2:1) controlled trial assessing the efficacy and safety of lopinavir/ritonavir (LPV/r) or arbidol monotherapy for treating patients with mild/moderate COVID-19. FindingsThis study successfully enrolled 86 patients with mild/moderate COVID-19 with 34 randomly assigned to receive LPV/r, 35 to arbidol and 17 with no antiviral medication as control. Baseline characteristics of the three groups were comparable. The primary endpoints, the average time of positive-to-negative conversion of SARS-CoV-2 nucleic acid and conversion rates at days 7 and 14, were similar between groups (all P>0.05). There were no differences between groups in the secondary endpoints, the rates of antipyresis, cough alleviation, or improvement of chest CT at days 7 or 14 (all P>0.05). At day 7, eight (23.5%) patients in the LPV/r group, 3 (8.6%) in the arbidol group and 2(11.8%) in the control group showed a deterioration in clinical status from moderate to severe/critical(P =0.206). Overall, 12 (35.3%) patients in the LPV/r group and 5 (14.3%) in the arbidol group experienced adverse events during the follow-up period. No apparent adverse event occurred in the control group. ConclusionsLPV/r or arbidol monotherapy present little benefit for improving the clinical outcome of patients hospitalized with mild/moderate COVID-19 over supportive care. FundingThis study was supported by project 2018ZX10302103-002, 2017ZX10202102-003-004 and Infectious Disease Specialty of Guangzhou High-level Clinical Key Specialty (2019-2021).
RESUMEN
Objective:To evaluate the efficacy and safety of lopinavir/ritonavir (LPV/r) and arbidol in treating patients with coronavirus disease 2019 (COVID-19) in the real world.Methods:The clinical data of 178 patients diagnosed with COVID-19 admitted to Guangzhou Eighth People′s Hospital from January 20 to February 10, 2020 were retrospectively analyzed. According to patient′s antiviral treatment regimens, 178 patients were divided into 4 groups including LPV/r group (59 patients), arbidol group (36 patients), LPV/r plus arbidol combination group (25 patients) and the supportive care group without any antiviral treatment (58 patients). The primary end point was the negative conversion time of nucleic acid of 2019 novel coronavirus (2019-nCoV) by pharyngeal swab.Results:The baseline parameters of 4 groups before treatment was comparable. The negative conversion time of viral nucleic acid was (10.20±3.49), (10.11±4.68), (10.86±4.74), (8.44±3.51) days in LPV/r group, arbidol group, combination group, and supportive care group respectively ( F=2.556, P=0.058). There was also no significant difference in negative conversion rate of 2019-nCoV nucleic acid, the improvement of clinical symptoms, and the improvement of pulmonary infections by CT scan ( P>0.05). However, a statistically significant difference was found in the changing rates from mild/moderate to severe/critical type at day 7 (χ 2=9.311, P=0.017), which were 24%(6/25) in combination group, 16.7%(6/36) in arbidol group, 5.4%(3/56) in LPV/r group and 5.2%(3/58) in supportive care group. Moreover, the incidence of adverse reactions in three antiviral groups was significantly higher than that in supportive care group (χ 2=14.875, P=0.002). Conclusions:Antiviral treatment including LPV/r or arbidol or combination does not shorten the negative conversion time of 2019-nCoV nucleic acid nor improve clinical symptoms. Moreover, these antiviral drugs cause more adverse reactions which should be paid careful attention during the treatment.
RESUMEN
ObjectiveTo investigate the efficacy and safety of elbasvir/grazoprevir in patients with genotype 1 hepatitis C in the real world. MethodsA total of 35 patients with hepatitis C who received elbasvir/grazoprevir treatment in Guangzhou Eighth People’s Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, and Guangdong General Hospital from August 2018 to March 2019 were enrolled, treated for 12 weeks, and then followed up for 12 weeks after drug withdrawal. The patients were observed in terms of sustained virologic response at week 12 after drug withdrawal (SVR12), biochemical response, and incidence rate of adverse events during treatment and follow-up. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to investigate the risk factors for virologic response in patients with hepatitis C. ResultsAmong the 35 patients with HCV infection, 97.1% (34/35) had genotype 1b HCV and 2.9% (1/35) had genotype 1a HCV; of all patients, 28 (80%) were non-cirrhotic patients with chronic hepatitis C and 7 (20%) had compensated liver cirrhosis. At the end of treatment, the virologic response rate of 100% (28/28) and SVR12 was 94.74% (18/19). In addition, age, sex, baseline HCV RNA load, previous treatment history, presence or absence of liver cirrhosis, renal function, and presence or absence of other diseases did not affect the treatment outcome (all P＞0.05). There were significant changes in the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and albumin from baseline to the end of 12-week treatment (Z=-7.131, -6.797, -3.060, and -2.875, all P＜0.05). No patient experienced drug withdrawal during treatment. ConclusionThis study confirms that elbasvir/grazoprevir has good efficacy and safety in the treatment of hepatitis C in domestic real-world studies.
RESUMEN
OBJECTIVE: To observe the pathological changes of rat silicosis model at different time points. METHODS: The specific pathogen free SD rats were randomly divided into control group and 7, 15, 21, 30, 45, 60, 75 and 90 day model groups based on their body weight, with 5 rats in each group. Non-exposed endotracheal intubation was performed. Silicosis rat model was established by intratracheal instillation of 250 g/L silica suspension in each rat, and 0.9% sodium chloride solution was perfused into the trachea of rats in the control group. The rats in the control group were sacrificed on the 90 th day after exposure, and the model rats in the other 8 groups were sacrificed on the 7 th, 15 th, 21 st, 30 th, 45 th, 60 th, 75 th and 90 th days after the end of exposure. The gross appearance of the lung tissue of rats was observed. The rat lung tissues were stained with hematoxylin-eosin and Masson staining to observe the pathological changes, and Ashcroft score was evaluated. RESULTS: The gross observation showed that the lungs of rats in the model groups had varying degree of gray changes, hardened texture, and spots and nodules on the surface of the lobes. These changes were aggravated with the increase of time after dust exposure. The results of histopathological examination of the lungs showed that the rats developed acute alveolar inflammation, and a large number of macrophages and neutrophils were seen in the lung tissues in the 7 th and 15 th day model groups. Cellular nodules appeared in the lung tissue, and fibrosis appeared in the center of the nodule in the rats of 21 st, 30 th, and the 45 th day model groups; the silicosis nodules appeared in the lung tissues of rats in the 60 th, 75 th, and 90 th day model groups, and the small nodules gradually merged into larger ones. Simultaneously, with the increase of time after dust exposure, the lung tissue of rats gradually showed severe pulmonary fibrosis. The lung organ coefficient and Aschcroft score of rats increased with the increase of time after dust exposure(P<0.01). CONCLUSION: The rat lung changes after dust exposure. Acute alveolar inflammation occurs on the 7 th to 15 th day after dust exposure; cellular nodules develop on the 21 st to 45 th day after dust exposure; silicosis nodules develop on the 60 th to 90 th day after dust exposure. The severity of lung fibrosis after dust exposure showed a time-effect relationship in rats.
RESUMEN
OBJECTIVE: To obtain information on the toxicity of lufenuron on the reproduction ability and the growth and development of offspring in female and male rats through two-generation reproduction toxicity study. METHODS: The specific pathogen free healthy SD rats were randomly divided into control group and low-, medium-and high-dose lufenuron groups, with 60 rats in each group, half females and half males. Rats in the low-, medium-and high-dose lufenuron groups were respectively fed with lufenuron at the dose of 5.0, 20.0 and 80.0 mg/(kg body weight·day) for 8 weeks before mating. The control group was fed with standard foot. The reproductive index, brain and reproductive organ coefficients and pathological changes were observed in P and F1 parents. The birth and growth indexes of the offspring were measured. RESULTS: i) P generation: from the 14 th day, the female rats in the medium-dose group had lower body weight than that of the female control group(P<0.05); from the 35 th day, the body weight was lower than that of the female low-dose group(P<0.05). From the 14 th day, the female rats in the high-dose group had lower body weight than that of the other three female groups(P<0.05). From the 14 th day, the male rats in the medium-and high-dose groups had lower body weight than that of the male control group and low-dose group(P<0.05). The body weight of pregnant rats in the parental high-dose group was lower than that of the control group, low-dose group, and medium-dose group at day 0, 7, 14, 19 of the pregnancy duration(P<0.05). The body weight of pregnant rats in the parental medium-dose group was lower than that of the low-dose group on day 0 of the pregnancy duration, and lower than that of the control and low-dose groups on day 7 and 14(P<0.05). The conception rate, the new-borne survival rates and the feeding survival rate of female rats in the high-dose group was lower than that of the other three female groups(P<0.008). The new-borne feeding survival rate of female rats in the medium-dose group was lower than that of the control group and low-dose group(P<0.008). The organ coefficients of brain in female rats in the medium-and high-dose groups were higher than that of the female control group and low-dose group(P<0.05). The organ coefficients of brain and testis in male rats in the medium-and high-dose groups were higher than that of the control group and low-dose group(P<0.05). The organ coefficient of epididymis in male rats in the high dose group was lower than that of the other three male groups(P<0.05). ii) F1 generation: the body weight of female rats in the low-and medium-dose group was higher than that of the female control group on the 42 th day(P<0.05). The body weight of male rats in the low-dose group was higher than that of the male control group on the 42 th, 49 th, and 56 th days(P<0.05). The body weight of male rats in the medium-dose group was higher than that of the male control group on the 14 th, 21 th, 42 th, 49 th, and 56 th days(P<0.05). The new-borne survival rate in the low-dose group was lower than that of the control group(P<0.017). The body weight of new-borne rats in the high-dose group on day 4 of birth was lower than that in the other three female groups(P<0.05). iii) F2 generation: the body weight of male rats in the male medium-dose group was lower than that in the control group on day 21 of birth(P<0.05). CONCLUSION: The reproductive and developmental toxicity of lufenuron is found in rats in the medium-and high-dose groups. Toxicities including low body weight, conception rate, new-borne survival rate and feeding survival rate are found in P generation; low body weight and feeding survival rate are found in F1 generation; low body weight is found in male F2 generation. The no-observed-adverse-effects levels of lufenuron in two-generation reproductive study are 5.87 mg/(kg·d) for females and 5.09 mg/(kg·d) for males in SD rats.
RESUMEN
OBJECTIVE: To study the effect of aquaporin 4(AQP4) in regulating the permeability of blood-brain barrier(BBB) induced by subacute 1,2-dichloroethane(1,2-DCE) inhalation. METHODS: Specific pathogen free healthy CD-1 male Aqp4 genetically engineered mice(Aqp4~(+/+)and Aqp4~(-/-)) were randomly divided into control and low-, medium-and high-dose groups. The mice were exposed to 1,2-DCE at the dosages of 0.00, 100.00, 350.00 and 700.00 mg/m~3 for 6 hours per day for consecutive 28 days by systemic dynamic inhalation. After the end of 1,2-DCE exposure, the BBB permeability was evaluated by Evans blue staining. Real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of genes related to BBB tight junction protein(Tjp)1, Tjp2, Tjp3, claudin(Cldn)3, Cldn5, Cldn11, occludin(Ocln), matrix metalloproteinase(Mmp)2, Mmp9 and Na-K-Cl cotransporter-1(Nkcc1). RESULTS: The BBB permeability in mice showed significant change with 1,2-DCE dose and Aqp4 genotype(P<0.01). The BBB permeability of Aqp4~(+/+) genotype mice was higher in low-, medium-and high-dose groups than that of control group(all P values were <0.05). The permeability of BBB was lower in Aqp4~(+/+) genotype mice in the control group than that of Aqp4~(-/-) genotype mice in the same group(P<0.05), but BBB permeability was higher in Aqp4~(+/+) genotype mice in the three dose groups than that of Aqp4~(-/-) genotype mice in the same group(all P values were <0.05). The Cldn3 and Olcn mRNA relative expression in the brain cortex had statistical difference in mice with different genotype(all P values were <0.01). The mRNA relative expressions of Cldn3 and Olcn in the brain cortex were higher in Aqp4~(-/-) genotype mice than that of Aqp4~(+/+) genotype mice(all P values were <0.01). The relative mRNA expression levels of Tjp1, Tjp2, Tjp3, Cldn5, Cldn11, Mmp2, Mmp9 and Nkcc1 in the cerebral cortex of mice were not statistically significant in aspect of 1,2-DCE exposure dose and genotype(all P values were >0.05). CONCLUSION: Exposure to 1,2-DCE can increase BBB permeability in mice, and the mechanism may be associated with 1,2-DCE-induced down-regulation of Aqp4 and up-regulation of mRNA expression of the cerebral cortex TJP-related molecules Cldn3 and Ocln.
RESUMEN
OBJECTIVE: To investigate the effects of 1,2-dichloroethane(1,2-DCE) subacute exposure on depression in rats as well as the relevant mechanism of monoamine neurotransmitters. METHODS: The specific pathogen free male SD rats were randomly divided into control group, low-, medium-, and high-dose groups, with 10 rats in each group. The rats in these 4 groups were intra-gastrically administered with 1,2-DCE(diluted in corn oil) at the dose of 0, 20, 40, 80 mg/kg body weight, every other day for 14 times. After exposure, the behavior change of rats was observed by open-field test, sucrose preference test and forced swim test. The levels of the monoamine neurotransmitters including 5-hydroxytryptamine(5-HT), noradrenaline(NA) and dopamine(DA) in prefrontal cortex, hippocampus, and striatum of rats were analyzed by high performance liquid chromatography-electrochemical detection method. RESULTS: The number of rearing, time and distance of central area, sucrose preference index of mice in medium and high dose groups were decreased(P<0.05), while immobility time of forced swim test was increased(P<0.05) when compared with the mice in control group. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum decreased with the increase of 1,2-DCE exposure(P<0.05), showing a dose-effect relationship. The levels of 5-HT, NA and DA in prefrontal cortex, hippocampus, and striatum in the high-dose group were lower than that of control group(P<0.05). CONCLUSION: The subacute exposure of 1,2-DCE can induce depression-like behavior in rats. The mechanism might be related to the reduction of monoamine neurotransmitters in striatum, hippocampus and prefrontal cortex.