With the advent of Twenty-First century, more and more genome-wide association studies (GWAS) showed that idiosyncratic adverse drug reactions (ADRs) were closely related with human leukocyte antigen (HLA) alleles, such as the associations of abacavir-HLA-B*5701, allopurinol-HLA-B*5801, and carbamazepine-HLA-B*1502, etc. To explore the mechanisms of these idiosyncratic drug reactions, hapten hypothesis, danger signal hypothesis, pharmacological interaction (P-I) concept and autoimmune mechanism are proposed. In this paper, recent GWAS studies on the HLA-mediated adverse drug reactions and underlying mechanism are reviewed in detail.

Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Amino Acid Sequence ; Humans ; Matrix Metalloproteinase 14 ; chemistry ; Molecular Dynamics Simulation ; Neoplasms ; Peptide Library ; Peptides ; chemistry

Objective:To explore the application effect of precautionary nursing in patients with acute cerebrovascular disease.Methods:From August 2019 to February 2021, a total of 125 patients with acute cerebrovascular disease who were admitted to Zhumadian Central Hospital were selected as the research objects by the convenient sampling method. According to the random number table method, the patients were divided into the study group ( n=63) and the control group ( n=62) . The control group received routine nursing intervention in neurology department, while the study group implemented precautionary nursing intervention on the basis of the control group. The scores of National Institute of Health Stroke Scale (NIHSS) , Stroke Specific Quality of Life Scale (SS-QOL) , adverse events during hospitalization and complications within 3 months after onset were compared between the two groups before intervention and 3 months after intervention. Results:After 3 months of intervention, the NIHSS score of the study group was lower than that of the control group, the SS-QOL score was higher than that of the control group, the incidence of adverse events and the incidence of complications within 3 months after onset were lower than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The application of precautionary nursing in patients with acute cerebrovascular disease can reduce the risk of related complications and adverse events, promote the recovery of neurological function and improve the quality of life of patients, which is worthy of clinical application.

Objective To explore the fall prevention bundle management strategy among tumour inpatients and to evaluate its application effects.Methods Data of 139 tumour patients with fall events in Cancer Center of Guangzhou Medical University between 2014 to 2016 was analyzed based on data analysis.The root cause analysis (RCA) and Plato management tool was used to find the primary cause.We built a fall prevention bundle management team,revised the fall scale,established prevention programs for grading nursing,information setting as well as quality monitoring for implementation process to form bundle management strategy.The fall incidence before and after the implement of the bundle strategy was compared.Results After implementing fall prevention bundle management strategy,the incidence of fall decreased from 0.185‰ (2016) to 0.107‰ (2017) with a significant difference (P=0.004).Conclusions Fall prevention bundle management strategy based on data analysis can effectively reduce the incidence of fall to guarantee patient safety.

We report a female infant born preterm to a woman at 35 gestational weeks and four days in a normal pregnancy prior to delivery, with normal liquor volume and good maternal and infant outcomes. The baby was transferred to the neonatal department 30 min after birth at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, on March 21, 2020. The infant weighed 2 800 g with 7 and 9 Apgar scores respectively at 1 and 5 min. The mother had been diagnosed with COVID-19 at 26 +6 weeks of pregnancy and the maternal serum level of IgM was negative and that of IgG was 20.77 AU/ml (normal reference <10 AU/ml) before delivery. The baby had hypoglycemia on admission, and the blood sugar stabilized after treatment. Though early mild feeding intolerance occurred, the baby was able to feed normal by eight days after birth. The baby was in good condition during hospitalization and discharged. Throat swab specimens obtained from the infant on the 2nd, 3rd and 8th day after birth for SARS-Cov-2 RNA detection were all negative. On the 2nd and 8th day after birth, SARS-Cov-2 IgM in the neonatal serum were negative, while elevated IgG levels of 30.2 AU/ml and 25.3 AU/ml (normal reference value <10 AU/ml) were observed, suggesting that the infant's IgG antibody of SARS-CoV-2 may have come from the mother. According to this case report, no intrauterine vertical transmission was found in the pregnancy with SARS-CoV-2 infection in the second trimester, while further follow-up is still needed.

Objective:To investigate the effects of neonatal respiratory distress syndrome(NRDS)on thymus of premature infants.Methods:We collected baseline data from premature infants with gestational age of 28~32 weeks in neonatal intensive care unit of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2019 to December 31, 2019.The largest transverse diameter and the sagittal of thymus were measured by ultrasonography within 24 h of birth, then, the thymic index(TI)and thymic weight index(TWI)were calculated to assess the size of thymus.The preterm neonates were divided into NRDS group and non-NRDS group according to the diagnosic criteria of NRDS, and the two groups were then divided into antenatal corticosteroid administration(ACS)group and non-ACS group according to ACS exposure.We then compared the TI and TWI between these groups.Results:One hundred and sixty-three preterm neonates were enrolled in our study, including 98 NRDS preterm neonates and 65 non NRDS preterm neonates.After matching gestational age and birth weight of the preterm neonates from two groups, 65 preterm neonates with NRDS comprised the NRDS group, and 65 preterm neonates without NRDS served as controls.Preterm neonates in NRDS group had significantly smaller TI[(1.788 ± 0.803)cm 3 vs.(2.420±1.068)cm 3, t=3.818, P<0.01] and TWI[(1.278 ± 0.380)cm 3/kg vs.(1.695 ± 0.491)cm 3/kg, t=5.401, P<0.01] than those in non-NRDS group.Besides, preterm neonates in NRDS group had smaller lymphocytes count[(3.729 ± 1.263)×10 9/L vs.(4.437 ± 1.608)×10 9/L, t=2.789, P<0.01] than that in non-NRDS group.For NRDS preterm neonates, TI[(1.487 ± 0.515)cm 3 vs(2.185 ± 0.942)cm 3, t=3.542, P<0.01] ]and TWI[(1.134± 0.311)cm 3/kg vs(1.469± 0.385)cm 3/kg, t=3.882, P<0.01] in ACS group were significantly smaller than those in non-ACS group.For non-NRDS preterm neonates, TI and TWI in ACS group also were significantly smaller than those in non-ACS group( t=2.676、3.659, P<0.05). Conclusion:NRDS is associated with thymic involution of preterm neonates, and ACS exposure affected the size of thymic in premature infants.