RESUMEN
Skin ulcers are the most prevalent consequence of diabetes mellitus, and people with diabetic ulcers have a substantially greater death risk than those who do not have ulcers. Herbal medications have gained wide concern in recent years due to their multi-component, multi-target, and multi-pathway synergistic therapeutic effects. Clinical trials have demonstrated the safety and efficacy of herbal treatments in diabetic refractory ulcers. To systematically evaluate the healing effect of herbs on diabetic wounds, a literature search was conducted, the mechanism of action of 15 herbal extracts in promoting diabetic wound healing were reviewed, and the classification based on traditional Chinese medicine theory was discussed, which could provide a reference for the precise treatment and exploitation of herbal medicines for diabetic ulcers.
RESUMEN
OBJECTIVE To provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole. METHODS The clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration， daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software； multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus. RESULTS A total of 153 lung transplantation patients were included. After the combination of voriconazole， the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg， and valley concentration and standardized blood concentration were increased significantly （P＜0.000 1）. The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus （P＝0.000 1，r＝－0.224）. The valley concentration of voriconazole was positively correlated with valley concentration （P＜0.000 1，r＝0.316） and standardized blood concentration （P＜0.000 1，r＝ 0.249） of tacrolimus. After combination with voriconazole， the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation， and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole （P＜0.05）. Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus （P＜0.001）. CONCLUSIONS The valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus， which is an independent influencing factor. In clinical practice， the dose of tacrolimus should be reduced in combination with voriconazole， and therapeutic drug monitoring should be conducted for both drugs.
RESUMEN
Since December 2019, the COVID-19 caused by SARS-CoV-2 has been widely spread all over the world. It is reported that SARS-CoV-2 infection affects a series of human tissues, including lung, gastrointestinal tract, kidney, etc. ACE2 has been identified as the primary receptor of the SARS-CoV-2 Spike (S) protein. The relatively low expression level of this known receptor in the lungs, which is the predominantly infected organ in COVID-19, indicates that there may be some other co-receptors or alternative receptors of SARS-CoV-2 to work in coordination with ACE2. Here, we identified twenty-one candidate receptors of SARS-CoV-2, including ACE2-interactor proteins and SARS-CoV receptors. Then we investigated the protein expression levels of these twenty-one candidate receptors in different human tissues and found that five of which CAT, MME, L-SIGN, DC-SIGN, and AGTR2 were specifically expressed in SARS-CoV-2 affected tissues. Next, we performed molecular simulations of the above five candidate receptors with SARS-CoV-2 S protein, and found that the binding affinities of CAT, AGTR2, L-SIGN and DC-SIGN to S protein were even higher than ACE2. Interestingly, we also observed that CAT and AGTR2 bound to S protein in different regions with ACE2 conformationally, suggesting that these two proteins are likely capable of the co-receptors of ACE2. Conclusively, we considered that CAT, AGTR2, L-SIGN and DC-SIGN were the potential receptors of SARS-CoV-2. Moreover, AGTR2 and DC-SIGN tend to be highly expressed in the lungs of smokers, which is consistent with clinical phenomena of COVID-19, and further confirmed our conclusion. Besides, we also predicted the binding hot spots for these putative protein-protein interactions, which would help develop drugs against SARS-CoV-2.
RESUMEN
Since 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has infected ten millions of people across the globe, and massive mutations in virus genome have occurred during the rapid spread of this novel coronavirus. Variance in protein sequence might lead to change in protein structure and interaction, then further affect the viral physiological characteristics, which could bring tremendous influence on the pandemic. In this study, we investigated 18 non-synonymous mutations in SARS-CoV-2 genome which incidence rates were all [≥]1% as of July 15th, 2020, then modeled the mutated protein structures and compared them with the reference ones. The results showed that four types of mutations could cause dramatic changes in protein structures (RMSD [≥]5.0 [A]), which were Q57H and G251V in open reading frames 3a (ORF3a), S194L and R203K/G204R in nucleocapsid (N). Next, we found that these mutations could affect the binding affinity of intraviral protein interactions. In addition, the hot spots within these docking complexes were altered, among which the mutation Q57H was involved in both Orf3a-Orf8 and Orf3a-S protein interactions. Besides, these mutations were widely distributed all over the world, and their occurrences fluctuated as time went on. Notably, the incidences of R203K/G204R in N and Q57H in Orf3a were both over 50% in some countries. Overall, our findings suggest that SARS-CoV-2 mutations can change viral protein structure, binding affinity and hot spots of the interface, thereby may have impacts on SARS-CoV-2 transmission, diagnosis and treatment of COVID-19.
RESUMEN
OBJECTIVE:To explore the necessity of developing therapeutic drug monitoring of vancomycin in our hospital and its existing problems,and provide a reasonable basis for the clinical rational use of vancomycin. METHODS:The cross-sectional survey was designed to collect the clinical data of 92 patients with therapeutic drug monitoring of vancomycin and statistically ana-lyze 192 cases of plasma concentration monitoring data. RESULTS:The average plasma trough concentration was (15.96 ± 8.06) mg/L;with the increase of age,the plasma trough concentration was increasing,there was no significant difference in the plasma trough concentration among different age groups (P=0.000);there were only 13 cases (6.77%) that obtained the plasma trough concentration within 30 min before the fourth dose;after using wancomycin,clearance rates of Cr and the endogenous creatinine were slightly higher than before,but there was no significant difference(P=0.722);36 cases(39.13%)showed vancomycin sus-ceptible gram positive cocci;after using wancomycin,the body temperature,white blood cell count and neutrophil percentage were lower than before,the differences were statistically significant (P=0.006,P=0.000,P=0.000);48 cases (52.17%) in treatment received initial loading dose,and only 15 cases (16.30%) did not use in combination with other anti infective drugs. CONCLU-SIONS:The results showed there are still a lot of problems in the treatment of vancomycin in our hospital,for example,the stan-dard rate of the plasma trough concentration is about 50%;most of the time of blood sampling is not reasonable;the detection rate of the pathogen is low;only about half of the cases are given the loading dose,etc. Therefore clinical pharmacists’intervention for blood sampling is an important part to promote rational drug therapy monitoring. Meanwhile,data interpretation of the monitoring results of serum drug concentration of vancomycin is a basic method for clinical pharmacists in clinical monitoring to correct the un-reasonable operations,and also the necessary measures for preventing the drug renal toxicity,it is a very important significance for the medication safety and effectiveness especially in severe infection patients,the elderly,the children and the people with renal function insufficiency.
RESUMEN
Serum Cardiac troponin Ⅰ (cTn Ⅰ) and lactic acid were measured in 128 neonatal patients with hypoxic-ischemic encephalopathy and 38 healthy neonates (control group). Serum cTn Ⅰ and lactic acid levels were higher in neonates with hypoxic-ischemic encephalopathy than those in healthy neonates (P < 0. 05 ); and the differences of these values were also statistically significant between the serious patients and the mild patients (P<0.05). Serum cTn Ⅰ and lactic acid are two sensitive markers for degree of myocardial injury and hypoxia in neonatal patients with hypoxic-ischemic encephalopathy.