Objective To analyze the efficacy and adverse reactions of donepezil in the treatment of patients with a continuous disease spectrum of Alzheimer's disease(AD)with pharmacogenomics.Methods Seventy-two patients who took donepezil therapy at the time of initial molecular pa-thology diagnosis of AD continuous disease spectrum in Chinese PLA General Hospital from Jan-uary 2022 to January 2023 were recruited.Cells from the oral buccal mucosa were collected,and MassARRAY nucleic acid mass spectrometry was applied to detect the genotypes of CYP2D6,the gene encoding cytochrome P450 2D6 enzyme,and CHAT,the gene encoding acetylcholine trans-ferase.After 9 months of follow-up,drug efficacy was indirectly determined by neurological func-tion scales,caregiver evaluations,and drug prescribing behaviors,and thus,the 50 patients on donepezil alone were divide into effective group(n=28)and ineffective group(n=22).Seventy-two patients were divided into adverse reaction group(n=12)and no adverse reaction group(n=60).Multivariate logistic regression analysis was used to analyze the correlation between donepezil efficacy and pharmacogenomics.Results The frequencies of CHAT rs3793790 locus carrying G allele and rs2177370 locus carrying A allele were significantly higher in the effective group than the ineffective group(35.71％vs 9.09％,P=0.029;42.86％vs 9.09％,P=0.008).Multivariate lo-gistic regression analysis showed that donepezil was more effective in those who carrying rs3793790 G allele and/or rs2177370 A allele in the CHAT gene than those who carrying neither of the alleles(95％CI:1.20-34.47,P=0.030).There were no statistical differences in the CYP2D6 gene-adjusted activity score and whether or not carrying*10 between the patients with and without adverse reactions(P＞0.0 5).Conclusion In patients with a continuous spectrum of AD,donepezil efficacy is associated with CHAT gene polymorphisms,but there is no correlation between donepezil adverse reactions and CYP2D6 genotype.

Objective:To study the clinicopathological features, immunophenotype, molecular genetic characteristics and prognosis of renal cell carcinoma associated with TFEB gene rearrangement (TFEBr-RCC).Methods:Eight cases of TFEBr-RCC diagnosed at the West China Hospital of Sichuan University from 2014 to 2022 were collected for clinicopathological, immunohistochemical, fluorescence in situ hybridization and RNA sequencing analyses, with review of literature.Results:Six patients were male and two were female. The patient ages ranged from 25 to 50 years (mean: 34 years, median: 32 years). The tumors were present in the right kidney (3 cases) or the left kidney (5 cases). The maximum diameters of the tumors ranged from 4.0 cm to 18.5 cm, with an average of 8.5 cm. Histologically, majority of the cases (5/8) showed typical biphasic "pseudorosette" structure, while the remaining three cases demonstrated atypical morphology that was similar to epithelioid angiomyolipoma or clear cell renal cell carcinoma. Immunohistochemical study showed positivity of TFEB (8/8), PAX8 (8/8), MART-1 (7/7), and HMB45 (5/6). Interestingly, PD-L1 was variably expressed in all five tested cases. Staining for TFE3 in all cases was negative. TFEB translocation was verified in all 8 cases using TFEB fluorescence in situ hybridization. RNA sequencing showed MALAT1-TFEB gene fusion in 4 of the 5 tested cases (two of which showing novel MALAT1-TFEB fusion sites), and one case with a novel ACTB-TFEB gene fusion. Patient follow-ups ranged from 5 to 96 months (average 47 months). All patients were alive without recurrence or metastasis.Conclusions:TFEBr-RCC tends to occur in young adults and has a good prognosis. Histologically, most of the cases show characteristic biphasic structure, and some cases show epithelioid angiomyolipoma-like or clear cell RCC-like morphology. Immunohistochemical reactivity to TFEB, melanocytic markers and PD-L1 is characteristic. MALAT1-TFEB gene fusion is the most common molecular change, with variable fusion sites.

Objective:To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) .Methods:In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ 2 test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results:At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant ( P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine ( r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion:AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.

Objective:To explore the risk factors of acute renal injury (AKI) in exertional heat radiation disease (EHS) .Methods:In november 2019, the clinical data of 69 EHS patients admitted from July 2015 to September 2019 were reviewed. The general data, laboratory indexes, Glasgow score (GCS) at admission, 24-hour acute physiology and chronic health score Ⅱ (APACHE Ⅱ) , exposure time rate and physical labor intensity were collected. According to the occurrence of AKI, the patients were divided into AKI group and non-AKI group, 31 and 38 in each group. The differences of general data and laboratory indexes between the two groups were compared, and the t and Mann-Whitney U test were used to compare the two groups. The enumeration data are expressed by examples and constituent ratio (%) . Independent sample χ 2 test is used for inter-group comparison, and multiple test is used for multi-sample comparison. The correlation was analyzed by linear regression. Risk factors were analyzed by Logistic regression analysis. Results:At discharge, 31 of 69 EHS patients developed AKI. Compared with the non-AKI group, the heart rate, white blood cell count, lactic acid, D-dimer and myoglobin were higher; MAP, platelet count and PH were lower in the AKI group. The difference was statistically significant ( P<0.05) . APACHE Ⅱ score, core temperature, time to drop to 38.5 ℃, contact time rate, platelet count, pH, lactic acid, D-dimer and myoglobin were all correlated with creatinine ( r=0.57, 0.42, 0.80, 0.78, 0.57, 0.43, 0.51, 0.55, 0.79) . APACHE Ⅱ score, time to drop to 38.5C, Lac and MYO are the risk factors of AKI in EHS patients. Multivariate Logistic regression analysis showed that the time required to drop to 38.5C was an independent risk factor for the occurrence of AKI. Conclusion:AKI is a serious complication of EHS. EHS complicated with AKI, should be identified early and effective intervention measures should be taken.

Objective:To evaluate the prognostic value of different critical care scoring systems in 28-day survival rate of patients with heat stroke.Methods:A retrospective analysis was conducted on the clinical data of 71 patients with heat stroke admitted to the department of emergency medicine of Beijing Luhe Hospital. Capital Medical University from July 2015 to September 2018. The general information and the worst values of vital signs and related pathophysiological indicators within 24 hours were collected and the sequential organ failure assessment (SOFA) , multiple organ dysfunction (MODS) , simplified acute physiological scoreⅡ (SAPS Ⅱ) and acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) were calculated. The patients were divided into the survival group ( n=45) and the non-survival group ( n=26) according to 28-day prognosis, and the clinical data and scores of the two groups were compared.The ROC curve was drawn to analyze the evaluation value of each scoring system on the survival rate of patients at 28-day. Kaplan-Meier method was used to plot the survival curve of patients. Results:There were no significant differences in age, sex, vital signs and laboratory parameters between two groups ( P>0.05) . In non-survival patients, SOFA, SAPS Ⅱ, APACHE Ⅱ scores were significantly elevated in the survival group ( P<0.05) . ROC curve analysis showed that the area under ROC curve (AUC) of SOFA score for predicting 28-day survival rate was the highest, which was significantly higher than the APACHE Ⅱ, SAPS Ⅱ, MODS score. When the best cut-off value of SOFA score was 9.0, the sensitivity was 84.6%, and the specificity was 71.1%. Kaplan-Meier survival analysis showed that 28-day survival rate after hospital discharge in patients with SOFA score<9 ( n=27) was significantly higher than that in patients with SOFA score ≥9.0 (χ 2=1.0, P<0.01) . Conclusion:SOFA, APACHE Ⅱ, SAPS Ⅱ on admission have been proved to have good prognostic ability to predict 28-day prognosis in heat stroke patients. Among them, SOFA score system has more accurate prediction value.

Objective:To evaluate the prognostic value of different critical care scoring systems in 28-day survival rate of patients with heat stroke.Methods:A retrospective analysis was conducted on the clinical data of 71 patients with heat stroke admitted to the department of emergency medicine of Beijing Luhe Hospital. Capital Medical University from July 2015 to September 2018. The general information and the worst values of vital signs and related pathophysiological indicators within 24 hours were collected and the sequential organ failure assessment (SOFA) , multiple organ dysfunction (MODS) , simplified acute physiological scoreⅡ (SAPS Ⅱ) and acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) were calculated. The patients were divided into the survival group ( n=45) and the non-survival group ( n=26) according to 28-day prognosis, and the clinical data and scores of the two groups were compared.The ROC curve was drawn to analyze the evaluation value of each scoring system on the survival rate of patients at 28-day. Kaplan-Meier method was used to plot the survival curve of patients. Results:There were no significant differences in age, sex, vital signs and laboratory parameters between two groups ( P>0.05) . In non-survival patients, SOFA, SAPS Ⅱ, APACHE Ⅱ scores were significantly elevated in the survival group ( P<0.05) . ROC curve analysis showed that the area under ROC curve (AUC) of SOFA score for predicting 28-day survival rate was the highest, which was significantly higher than the APACHE Ⅱ, SAPS Ⅱ, MODS score. When the best cut-off value of SOFA score was 9.0, the sensitivity was 84.6%, and the specificity was 71.1%. Kaplan-Meier survival analysis showed that 28-day survival rate after hospital discharge in patients with SOFA score<9 ( n=27) was significantly higher than that in patients with SOFA score ≥9.0 (χ 2=1.0, P<0.01) . Conclusion:SOFA, APACHE Ⅱ, SAPS Ⅱ on admission have been proved to have good prognostic ability to predict 28-day prognosis in heat stroke patients. Among them, SOFA score system has more accurate prediction value.

Objective: To investigate the prognostic value of arterial blood lactate for patients with cardiogenic shock receiving extracorporeal membrane oxygenation(ECMO). Methods: A retrospective analysis was conducted. Twenty-three patients diagnosed with cardiogenic shock receiving veno-arterial(V-A) ECMO admitted to department of Emergency Intensive Care Unit(EICU) of Beijing Luhe Hospital Affiliated to Capital Medical University from January 2017 to December 2018 were enrolled. Results: There were 10 cases in the survival group and 13 cases in the death group. Compared with survival group, APACHE-Ⅱ score was higher, CRRT applied higher percentage, PH and oxygenation index was worse in the death group(P<0.05). The lactate of the death group was significantly higher than that of the survival group at initial time at EICU, 1 h before ECMO and 0h before ECMO(P<0.05). During the ECMO operation, lactate levels in the death group at 8 h and 12 h were significantly higher than those in the survival group(P<0.05). There was no statistically significant difference in lactate clearance rate between the two groups before and after ECMO operation in each observation period(P>0.05). On the 2nd day of ECMO operation, CRRT usage time was shorter and daily liquid balance was more negative in the survival group(P<0.05). APACHE-Ⅱscore, initial lactate at EICU, lactate at ECMO 8 h and lactate at ECMO 12 h had predictive value for 30-day death of patients. The area under ROC curve(AUC) of initial lactate at EICU was 0.845, and 95% confidence interval(95%CI)=0.653-1.000. The AUC of ECMO 8 h lactate was 0.836, 95%CI: 0.634-1.000. The AUC of ECMO 12 h lactate was 0.873, 95%CI: 0.697-1.000. The AUC of APACHE-Ⅱscore was 0.891, 95%CI: 0.717-1.000. The sensitivity and specificity of prognosis prediction were 72.7% and 100% when lactate was more than 7.3 mmol/L at the time of admission into EICU as the optimal critical value. Conclusion Arterial blood lactate could be used as an important marker for evaluating the prognosis of cardiogenic shock patients on ECMO. The value of lactate clearance rate may be affected by combined CRRT.

Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.

The recovery of disorders of consciousness after brain injury is very difficult, music therapy is one of the important ways to promote the awakening. The effects of music therapy are various among individuals, the vegetative state and the minimally conscious state, and the pieces of music. The default mode network is one of the most important networks to maintain awareness, which many other networks participate in. The brain regions affected by music involve in many networks, including hearing, cognition, emotion, and so on.

To discuss clinicopathological features and molecular genetic change of congenital mesoblastic nephroma (CMN).Methods Nine cases diagnosed as CMN were analyzed retrospectively in this study.Histological features,immunohistochemical profiles and ETV6 gene rearrangement status were assessed.Results All patients were within two years of age and eight of them were within one year.The average diameter of tumors was 9.5 cm (3.2-15.0 cm).These series cases included 3 classic CMN,5 cellular CMN and 1 mixed CMN.Cystic degeneration was found in 5 cases,and cartilage islands were observed in 2 cases.Compared with classic CMN,tumor size was bigger,and hemorrhage,necrosis and mitotic figures were easily to see in cellular CMN.All the tumor cells were positive for vimentin and negative for WT-1 by immunohistochemistry.ETV6 gene rearrangement was detected in 5 cases (including 4 cellular CMN and 1 classic CMN).Three cellular CMN harbored ETV6 gene translocation,1 mixed CMN and 1 cellular CMN were negative for ETV6 gene translocation by FISH analysis.The follow up data were obtained in 7 cases and 2 cases were lost.All the 7 patients were alive without evidence of recurrence and metastasis from 5 to 46 months.Conclusion CMN is a rare infant renal tumor with unique clinicopathological characteristics.Most of cellular CMNs harbor ETV6 gene translocation.The prognosis of CMN is relative good and needs to be differentiated from other malignant renal tumors.