Objective Bioinformatics tools were used to conduct a prediction analysis of common CYP2C9 variants(*3)and new variants(*76-*85)in our population,aiming to illustrate the impact of amino acid variants on the multidimensional aspects of CYP2C9 protein structure,properties,and functions.Methods The physicochemical properties,glycosylation and phosphorylation mod-ification,important structural domains,spatial structure and functional changes,and docking mode with the probe drug,tolbutamide,were predicted for each variant by applying various analytical tools.Results Compared with CYP2C9*1,the variants showed different degrees and multiple levels of alterations in amino acid sequence,local structural domains,phosphorylation sites,physicochemical proper-ties,tertiary structure,and docking patterns with substrates.*76 and*84 showed local structure,overall spatial structure,and function disruptions,and they were also correlated with disease outbreaks.*78-*79 and*81-*82 variants showed significant heterogeneity in the predicted results at different levels;*85 had an early termination codon and deletion of most critical structural domains due to a code-shift mutation,and the results suggested that it might affect the protein translation and the assembly of the whole enzyme.The pre-dicted results of the physicochemical properties,local structural domains,and stability of*3 were all non-significantly altered in com-parison with*1;however,docking results showed that*3 protein and tolbutamide were significantly changed in the shape,three-di-mensional size,and contact pattern of the docking pocket.Conclusion This study analyzed the effects of amino acid variants on pheno-types from multiple perspectives and levels,including protein primary,secondary,and tertiary structures,holoenzyme-drug docking,physicochemical properties,and functions,which provides essential references and new interpretative perspectives for future structural elu-cidation,ex vivo and in vivo drug metabolism experiments,and individualized dosing of CYP2C9 variants.

Spontaneous intracerebral hemorrhage (ICH) is a neurological disease with high mortality and morbidity rates, and early neurological deterioration (END) is one of the key factors in evaluating outcome of patients. Early identification and effective intervention of END in patients with ICH is of great significance for their treatment and prognosis. This article reviews the predictive factors for END in patients with ICH from the perspectives of blood markers, hematoma characteristics, blood pressure variability, and imaging signs.

Objective:To investigate the correlation between overweight or obesity defined by body mass index (BMI) and functional outcome in patients with hypertensive intracerebral hemorrhage (HICH).Methods:Patients with HICH admitted to the Department of Neurosurgery, the First People's Hospital of Lianyungang from October 2020 to February 2022 were included retrospectively. According to BMI, they were divided into underweight or normal group (<24 kg/m 2) and overweight or obese group (≥24 kg/m 2). At one year after onset, the functional outcome were evaluated using the modified Rankin Scale. 0-2 was defined as good outcome, while >2 were defined as poor outcome. Cox proportional hazards regression model was used to analyze the correlation between BMI and the outcome of patients. Results:A total of 394 patients with HICH were enrolled, including 263 males (66.8%), aged 60.2±12.0 years. At one year after onset, 145 patients (36.8%) had poor outcome and 54 (13.7%) died. Compared with the underweight or normal group, the overweight or obese group had a higher proportion of previous type 2 diabetes history, as well as higher baseline diastolic blood pressure, low-density lipoprotein cholesterol and liver enzyme levels, better early outcome after discharge, and lower mortality at 1 year (all P<0.05). Multivariate analysis showed that the overweight or obese group had significantly better functional outcome compared to the underweight or normal group (hazard ratio 0.598, 95% confidence interval 0.419-0.854; P=0.005), but there was no statistically significant difference in all-cause mortality risk (hazard ratio 1.201, 95% confidence interval, 0.462-3.126; P=0.707). Conclusion:The overweight or obese patients with HICH have significantly better functional outcome at one year after onset, indicating that the obesity paradox also exists in patients with HICH.

Objective:To study the emergency cerebral hemorrhage grading scale (EDICH) score and the modified emergency intracerebral hemorrhage grading scale (mEDICH) score on the adverse prognosis of patients with cerebral hemorrhage 90 days after discharge.Methods:The clinical data of 248 patients with cerebral hemorrhage in the Department of Neurosurgery, Lianyungang Hospital Affiliated to Xuzhou Medical University from January 2022 to December 2022 were retrospectively analyzed. According to the modified Rankin scale (mRS) 90 days after discharge, patients were divided into a good prognosis group (212 cases) and a poor prognosis group (36 cases). Independent-samples t-test and rank-sum test were used to compare the basic information, vital signs, laboratory tests, imaging characteristics, EDICH score and mEDICH score of the two groups. Multivariate Logistic regression was used to analyze the risk factors affecting the poor prognosis of patients with cerebral hemorrhage. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of EDICH score and mEDICH score for the poor prognosis of patients with intracerebral hemorrhage 90 days after discharge.Results:The diameter of intracerebral hematoma (5.53±0.32) cm, the rate of intraventricular hemorrhage (61.11%,22/36) and the rate of subtentorial hemorrhage (27.78%, 10/36) in poor prognosis group were significantly higher than those in good prognosis group (3.50±0.07) cm, intraventricular hemorrhage (30.19%, 64/212) and infratentorial hemorrhage (14.15%, 30/212), the differences were statistically significant ( t=6.19, P<0.001; χ 2=12.99, P<0.001; χ 2=4.22, P=0.040). GCS scores in the poor prognosis group were lower than those in the good prognosis group ( H=72.01, P<0.001). EDICH scores and mEDICH scores in the poor prognosis group were higher than those in the good prognosis group (EDICH score: H=65.79, P<0.001; mEDICH score: H=76.56, P<0.001). Multivariate Logistic regression analysis showed EDICH score ( OR=5.869,95% CI 3.451-9.981, P<0.05) and mEDICH score ( OR=10.353,95% CI 4.842-22.137, P<0.05)could predict the prognosis of patients with cerebral hemorrhage 90 days after discharge. ROC curve analysis showed that the sensitivity and specificity of EDICH score and mEDICH score were 0. 861,0.889 and 0. 821,0.953, respectively, but the predictive effect of mEDICH score was significantly better than that of EDICH score ( Kappa values were 0. 787 and 0. 494, respectively). The predicted results are highly consistent with the actual results. Conclusion:MEDICH score can accurately predict the prognosis of patients with intracerebral hemorrhage 90 days after discharge, which has clinical application value.

Objectives:To explore the clinicopathological characteristics and prognostic risk factors in differentiated thyroid cancer (DTC) patients with lung metastasis.Methods:Patients of differentiated thyroid cancer with lung metastasis in Tianjin Medical University Cancer Institute & Hospital were enrolled from Jan 1, 2010 to Dec 31, 2016. The clinicopathological characteristics and risk factors affecting the prognosis were analyzed retrospectively.Results:A total of 65 DTC patients with lung metastasis were collected in this study, including 56 patients with papillary thyroid carcinoma and 9 patients with follicular thyroid carcinoma; 23 patients died and 42 patients survived. Median follow-up time was 99.4 months. There were 18 males, 47 females. Age 14-73 years, median age 51.0 years. High incidence of DTC lung metastasis was 50-59 years for males and 40-49 years for females. Based on AJCC 8th edition TNM staging, there were 37 patients in stage Ⅱ (age <55 years) and 28 patients in stage Ⅳb (age ≥55 years). The number of 131Ⅰ treatments performed ranged from 1 to 13 times, with a mean of 3.9 times. Firty-five patients were with lung metastasis alone, and 10 patients with lung metastasis and distant metastasis in other organs. Eleven patients suffered from hypoparathyroidism after 131Ⅰ treatment. COX multifactorial regression analysis found that age was independent risk factor affecting prognosis, multiple organs distant metastasis and pathologic subtype were relative risk factors affecting prognosis. There was no correlation between gender, number of 131Ⅰ treatments and poor prognosis. Conclusions:DTC has a high survival even with the occurrence of lung metastasis, but the prognosis is poor when combined with multi-organ metastasis. Age and multiple organ distant metastatic are independent risk factors affecting prognosis.

Carotid artery stenosis is an important cause of ischemic stroke. Carotid endarterectomy and carotid artery stenting are the effective methods for treating carotid artery stenosis, but postoperative restenosis remains a challenge. The pathogenesis of postoperative restenosis is currently not fully understood. However, multiple factors, including biomarkers, imaging features, and surgical related factors, have been proven to be associated with postoperative restenosis and can predict the occurrence of postoperative restenosis. This article reviews the predictors of restenosis after carotid endarterectomy and carotid artery stenting.

Objective:To understand the infection rate of Coronavirus Disease 2019 (COVID-19) in close contacts in Shandong province and explore the risk factors of infection.Methods:All data from close contacts of 2019 novel coronavirus (2019-nCoV) infected persons in Shandong province were collected for descriptive epidemiological analysis, and risk factors were analyzed by logistic regression.Results:Up to March 6, 2020, a total of 15 702 close contacts had been reported in Shandong province, of whom 321 cases were infected with 2019-nCoV, with an infection rate of 2.04%. Among all the factors, the top five with the highest infection rate were close relatives (13.39%), frequent contact (9.58%), working/living/studying in the same room (7.54%), two or more contact cases (4.58%), and over 60 years old (3.10%). Single-factor analysis showed that exposure to two or more cases, over 60 years old, close relatives with cases, frequent contact and working/living/studying in the same room were the risk factors for infection in close contacts. Multivariate analysis showed that exposure to two or more cases ( OR=2.510, 95% CI: 1.843-3.417), 30~60 year old group ( OR=1.513, 95% CI: 1.141-2.007), frequent exposure group ( OR=20.025, 95% CI: 14.625-27.419), working/living/learning in the same room ( OR=2.406, 95% CI: 1.385-4.182) and medical institution exposure ( OR=2.366, 95% CI: 1.149-4.871) were risk factors of infection in close contacts. Conclusions:Tracking and managing close contacts was an important measure to control the COVID-19 epidemic situation, and reducing crowd concentration, keeping a proper social distance and taking effective protection were effective measures to control 2019-nCoV infection.

Objective:To explore the application effect of health management in extended nursing for patients with hemorrhagic stroke.Methods:Using the convenient sampling method, a total of 120 patients with hemorrhagic stroke who were admitted to the First People's Hospital of Lianyungang in Jiangsu Province from August 2018 to August 2019 were selected as the research objects. According to the random number table method, they were divided into the control groups and the observation group, with 60 cases in each group. The control group and the observation group were respectively given traditional family follow-up nursing and extended nursing based on health management. The mastery degree of knowledge about hemorrhagic stroke disease, self-health management ability, medication compliance and psychological status of patients with hemorrhagic stroke were observed in the two groups.Results:After the implementation of extended nursing based on health management, the total scores of mastery degree of knowledge about nursing for hemorrhagic stroke and self-health management ability in the observation group were respectively (90.38±2.13) and (149.65±4.65) , which were higher than (59.07±2.45) and (115.79±5.34) of the control group, and the differences were statistically significant ( P<0.01) . The total compliance rate of patients in the observation group was 86.67% (52/60) , which was higher than 43.33% (26/60) in the control group, and the difference was statistically significant ( P<0.01) . After the intervention, scores of SDS and SAS of the observation group were (41.87±8.23) and (40.68±7.34) , which were lower than (54.23±7.45) and (52.02±9.86) of the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The extended nursing based on health management is well applied in the family follow-up work of patients with hemorrhagic stroke. Mastery degree of knowledge of patients, self-health management ability, and treatment compliance are improved and levels of depression and anxiety are reduced.

Objective:To verify the accuracy of the International Warfarin Pharmacogenetics Consortium(IWPC)model, identify the effects of genetic and clinical factors on steady-state doses of Warfarin, and establish a Warfarin dose prediction model for the Han-Chinese population aged 75 years and over under the guidance of pharmacogenetics.Methods:A total of 544 Han-Chinese patients receiving Warfarin therapy for atrial fibrillation were divided into two groups: those aged 75 years and over(n=164)and those aged below 75 years(n=380). Data for the whole population and the two age groups were each substituted into the IWPC prediction model for accuracy verification.Demographic and clinical characteristics of 164 patients aged 75 years and over were recorded, and the genotypes of CYP2 C9 and VKORC1- G1639 A were detected by polymerase chain reaction.A new pharmacogenetic-guided dosing algorithm for the elderly was obtained by stepwise multiple linear regression.The accuracy of the new model was compared with that of the IWPC model. Results:The predictive accuracy of IWPC for steady-state dosing of warfarin was 35.47% in all subjects, 33.75% in 164 subjects aged below 75 years, and only 28.70% in subjects aged 75 years and over, respectively.In 164 subjects aged 75 years and over, three genotypes of *1/*1, *1/*3 and *1/*2 were detected in CYP2 C9 polymorphism, and the CYP2 C9*1/*1 genotype was the most common one, with a frequency of 87.80%(144/164), followed by the CYP2 C9*1/*3 genotype, at 11.59%(19/164). GG, GA and AA genotypes were detected in VKORC1 polymorphism, among which the AA genotype accounted for 82.32%(135/164)and the GG genotype accounted for only 1.83%(3/164). The steady state dose for Warfarin in patients with the wild-type CYP2 C9*1/*1 was higher than in those with the heterozygote CYP2 C9*1/*3 and *1/*2(3.18±0.86 mg/d vs.2.27±0.51 mg/d, t=5.637, P<0.05). Patients with a mutant homozygotic AA genotype of VKORC1 required lower maintenance doses than those with the heterozygotic GA and GG genotypes(2.96±0.66 mg/d vs. 3.59±1.43 mg/d, t=-2.092, P<0.05). The steady-state dose for Warfarin in subjects carrying CYP2 C9 (*1/*2 or *3)and VKORC1 (GA and GG)was(2.00±0.63)mg/d, lower than in those carrying other genotype combinations( P<0.05). We established a new Warfarin dosing algorithm for elderly subjects aged 75 years and over containing height, creatinine, amiodarone usage, CYP2 C9 and VKORC1 mutants, and the accuracy of the new model was 56.0%, which could explain 56.0% of individual variability, and the accuracy was higher than that of the IWPC algorithm(56.0% vs. 45.8%, P<0.05). Conclusions:Polymorphisms of CYP2 C9 and VKORC1 clearly affect the steady-state dose for Warfarin in the elderly Han-Chinese population aged 75 years and over.A combination of pharmacogenomics with clinical factors can better guide warfarin medication in Han-Chinese people aged 75 years and over.

Objective:To investigate the differential expression of miRNAs during white adipose tissue(WAT)browning in mice under different stimulation conditions, and to analyze the potential regulatory mechanisms.Methods:Mouse models of subcutaneous WAT(sWAT)browning were established by different methods: cold-induced browning and intraperitoneal injection of CL316-243.HE staining and analysis of thermogenesis-related gene expression were used to validate the browning models.miRNAs expression profiles in different conditions were described by RNA-sequencing(RNA-seq)and miRNAs with similar expression patterns in the two groups were detected via screening.Target genes of miRNAs were predicted by bioinformatics, and their expression levels were verified by quantitative real-time PCR(qRT-PCR).Results:Both cold-induced browning and intraperitoneal injection of CL316-243 were able to activate the browning of sWAT, and the miRNA expression profile of sWAT showed significant differences before and after induction.After screening differentially expressed miRNAs, the expression of Mir-30E-3p was increased and the expression of Mir-181A-5p was decreased under different browning-inducing conditions in WAT.The prediction and validation of target genes revealed that cyclin-dependent kinase 6(Cdk6)and sirtuin 1(Sirt1)were potential targets regulated by miR-30e-3p and miR-181a-5p in the browning of sWAT, respectively.Conclusions:There are significant differences in miRNA expression during the browning of sWAT in mice induced by cold stimulation and CL316-243 injection.MiR-30e-3p and miR-181a-5p may be involved in the regulation of the sWAT browning process through target genes Cdk6 and Sirt1, respectively.