ObjectiveThis paper aims to analyze the clinical characteristics and medication rationality of liver injury related to Epimedii Folium preparation （EP） and explore the possible risk factors of liver injury， so as to provide a reference for the safe clinical application of Epimedii Folium （EF）. MethodA retrospective analysis was conducted on liver injury cases related to EP from 2012 to 2016. ResultThe number of reported liver injury cases and the proportion of severe cases related to the use of EP show an increasing trend， indicating the objective existence of liver injury caused by EP. There are more cases of liver injury related to EP in women than in men， with an onset age range of 15-91 years old and a median onset age of 60 years old （median onset ages for men and women are 59 and 60 years old， respectively）. The time span from taking EP alone to the occurrence of liver injury is 1-386 days， with a median of 38 days. The time span from taking both EP and Western medicine to the occurrence of liver injury is 1-794 days， with a median of 34 days. EF-related liver injury preparations are mostly composed of traditional Chinese medicines that promote immunity and tonify the liver and kidney， indicating that immune stress in the body may be the mechanism of liver injury caused by the use of EP alone or in combination. There is no increasing trend of toxicity with time or dose in the liver injury caused by EP. By further exploring its risk factors， it is found that patients have unreasonable medication methods such as excessive dosage， repeated use， and multi-drug combination， which may also be one of the important risk factors for EF-related liver injury. ConclusionEP has a certain risk of liver injury and should be emphasized in clinical diagnosis and treatment. Immune stress may be the mechanism of liver injury caused by EP， and in clinical use， it is necessary to be vigilant about the risk of liver injury caused by unreasonable use and combined use with Western medicine.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)and reoxygenation on insulin resistance(IR)and expressions of miR-27a-3p/PPARγ/IRS1/PI3K/AKT in rat skeletal muscle.Methods GEO database was used for screening the differentially expressed miRNAs in CIH,and their target genes were subjected to GO and KEGG enrichment analysis followed by construction of the miRNA-mRNA-pathway regulatory network using Cytoscape.In the animal experiment,48 male SD rats were randomly divided into normoxia group and CIH group(8 weeks of CIH followed by 4 weeks of normoxic recovery).Blood and skeletal muscle samples were collected at baseline,8 weeks,and 12 weeks to evaluate the changes in fasting blood glucose(FBG)and fasting insulin(FINS)levels and muscular pathology.RT-qPCR and Western blotting were used to detect the changes in the expressions of miR-27a-3p,PPARγ,GLUT4,IRS1,p-IRS1,PI3K,p-AKT and AKT in the muscular tissues.Results No muscular miRNA datasets for CIH were available in GEO database,from which only a kidney-related dataset(GSE202480)was obtained,based on which a total of 165 differentially expressed miRNAs were identified.GO/KEGG analysis suggested that these miRNAs were involved in muscular regulation and insulin signaling.The miRNA-mRNA-pathway network highlighted miR-27a-3p as a crucial regulator in the PPAR and PI3K/AKT pathway.In the animal experiment,the rats subjected to CIH for 8 weeks showed significantly increased FBG,FINS,HOMA-IR,and PPARγ levels,loose muscle fiber arrangement,decreased cross-sectional area of the muscle fibers,and lowered expressions of miR-27a-3p,p-IRS1/IRS1,PI3K,and p-AKT/AKT in the skeletal muscles.Conclusion CIH increases IR,causes skeletal muscle pathology,downregulates miR-27a-3p expression,upregulates PPARγ expression,and inhibits IRS1/PI3K/AKT insulin signaling in the skeletal muscles of rats,and these changes can be reversed by reoxygenation.MiR-27a-3p may participate in CIH-induced IR by modulating the PPAR γ/IRS1/PI3K/AKT signaling pathway.

Objective The risk evaluation indicators for the occurrence of diaphragm dysfunction in ICU patients was constructed to provide a reference for the establishment of the disease risk evaluation tools for diaphragm dysfunction.Methods The literature related to diaphragm dysfunction from CNKI,Wanfang Data,PubMed,Embase and Web of Science from the establishment of databases to November 11 th,2022 was systematically searched.After the first draft was determined through the literature review method,the first draft of the indicators was revised by brainstorming,with the opinions of 10 medical and nursing experts from May to June 2023.From June to July 2023,the content and weight of risk evaluation indicators of diaphragmatic dysfunction in ICU patients were determined through expert letter inquiry and hierarchical analysis.Results 35 experts completed the first round of letter inquiry,and 34 experts completed the second round of letter inquiry.The recovery rates of the valid questionnaires in the 2 rounds of expert correspondence were 92.1％and 97.1％,respectively,and the expert authority coefficients were 0.884 and 0.904,respectively,and the Kendall harmony coefficients of all indicators were 0.356～0.570 and 0.369～0.604,respectively(all P＜0.001).The final constructed risk evaluation indicators of diaphragm dysfunction in ICU patients includes 7 first-level indicators,34 secondary indicators and 34 tertiary indicators.Conclusion The risk evaluation index of diaphragm dysfunction in ICU patients constructed in this study is comprehensive,specific,scientific and applicable,which can guide medical staff to conduct early risk evaluation of diaphragm function in ICU patients,and provide references for the establishment of disease risk assessment tools for diaphragm function.

Objective:To explore the clinical and genetic features in a case of fatal familial insomnia (FFI).Methods:A case of 39 years old woman diagnosed as progressive supranuclear palsy based on the preliminary manifestation of imbalance and frequent falls was reported. The clinical features, imaging characteristics, electroencephalogram and polysomnography of the patient were analyzed, and the blood samples from the patient were collected for the sequencing of prion protein (PRNP) gene.Results:This patient is a middle-aged woman, whose clinical manifestations were posture instability and retropulsion, rapid progressive dementia and dysarthria, sleep-related dyspnea and laryngeal stridor, with autonomic symptoms of hypertension, sweating, tachycardia and irregular breathing. The results of PRNP gene sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions:Laryngeal stridor plays an important role in the diagnosis of FFI. Posture instability and retropulsion are relatively rare in the FFI clinical symptom spectrum. Here, a case of FFI presenting with posture instability and retropulsion during the early stage with Met/Met at the polymorphic codon 129 is reported in China.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells. In this study, we demonstrate that mouse EPS cells well maintain developmental potency and genetic stability after long-term passage. Based on gene targeting in mouse EPS cells, we established a new approach to directly and rapidly generate gene-targeted mouse models through tetraploid complementation, which could be accomplished in approximately 2 months. Importantly, using this approach, we successfully constructed mouse models in which the human interleukin 3 (IL3) or interleukin 6 (IL6) gene was knocked into its corresponding locus in the mouse genome. Our study demonstrates the feasibility of using mouse EPS cells to rapidly generate mouse models by gene targeting, which have great application potential in biomedical research.

Objective To investigate the risk factors of prolonged postoperative mechanical ventilation for adult patients with atrioventricular septal defect (AVSD). Methods We retrospectively analyzed the clinical data of 76 patients with AVSD aged more than 18 years in our hospital from January 1, 2011 to December 31, 2017. The patients ventilated longer than 24 hours were described as a prolonged ventilation group (n=27) and the others as a normal group (n=49). There were 9 males and 18 females aged 32.22±9.64 years in the prolonged ventilation group, and 16 males and 33 females aged 35.98±11.34 years in the normal group. Perioperative variables between the two groups were compared and selected, and then analyzed by logistic regression analysis. Results The result of univariate analysis showed that there was a statistical difference in weight, preoperative pulmonary artery systolic pressure, duration of cardiopulmonary bypass, the level of postoperative platelet, hemoglobin, blood glucose, lactic acid and serum creatinine, postoperative maximum heart rate and postoperative infection rate between the prolonged ventilated group and the normal group. Multivarable logistic regression showed that preoperative pulmonary artery hypertension (OR=1.056, 95%CI 1.005 to 1.110, P=0.030), prolonged duration of cardiopulmonary bypass (OR=1.036, 95%CI 1.007 to 1.066, P=0.016) and the low postoperative hemoglobin level (OR=0.874, 95%CI 0.786 to 0.973, P=0.014) were the risk factors of prolonged postoperative mechanical ventilation. Conclusion Preoperative pulmonary artery hypertension, long duration of cardiopulmonary bypass and postoperative anaemia are the risk factors associated with prolonged postoperative mechanical ventilation.

Objective To investigate the relationship between educational level and cognitive function in patients with non?dementia Parkinson′s disease (PD). Methods Forty non?dementia PD patients and forty healthy controls (HC) enrolled in Beijing Hospital from January to December 2018 were collected for the study. The two groups were divided into three subgroups (low, medium and high) according to their years of education. HC group and PD group were matched in age, gender, years of education, and Mini?Mental State Examination score. All subjects underwent three tests of executive function: the Trail Making Test (TMT?A and TMT?B), the Verbal Fluency Test (VFT) and the WAIS digital span test (forward and backward). Results There were statistically significant differences in the error number of TMT?A (0.00 (0.00, 1.00),0.00 (0.00, 0.00), 0.00 (0.00, 0.00); χ2=10.11, P=0.006), the time of TMT?B ((81.17±36.83) s, (52.10 ± 27.88) s, (47.72 ± 23.18) s; F=5.16, P=0.011), the error number of TMT?B (3.00 (0.00, 4.00), 1.00 (0.00, 3.50), 0.00 (0.00, 0.00); χ2=7.16, P=0.028) and the number of backward (3.17±0.72, 3.50±1.08, 4.00± 0.77; F=3.68, P=0.035) among the three subgroups of PD group. There were statistically significant differences between the PD group and the HC group in the time of TMT?A (PD: (64.03±15.96) s, HC: (53.00± 19.50) s; t=2.77, P=0.007), the time (PD: (58.85±31.91) s, HC: (37.35±19.42) s; t=3.64, P=0.001) and error number (PD: 0 (0, 4), HC: 0 (0, 0); Z=-3.15, P=0.002) of TMT?B, the number of backward (PD: 3.63±0.90, HC: 4.98±1.21; t=-5.67, P=0.000) and VFT (PD: 14.48±3.37, HC: 16.15±2.03; t=-2.69, P=0.009). In the low and medium education level subgroups, the PD group showed worse results in three tests of executive function than the HC group, some with statistically significant differences (P<0.05). There was no statistically significant difference in the results of three tests of executive function between two subgroups of high education in the PD group and the HC group (P>0.05). Conclusions Executive functions of non?dementia PD patients are impaired. Education level may have a certain impact on cognitive function of PD patients.

Objective: To investigate the relationship between educational level and cognitive function in patients with non-dementia Parkinson′s disease (PD). Methods: Forty non-dementia PD patients and forty healthy controls (HC) enrolled in Beijing Hospital from January to December 2018 were collected for the study. The two groups were divided into three subgroups (low, medium and high) according to their years of education. HC group and PD group were matched in age, gender, years of education, and Mini-Mental State Examination score. All subjects underwent three tests of executive function: the Trail Making Test (TMT-A and TMT-B), the Verbal Fluency Test (VFT) and the WAIS digital span test (forward and backward). Results: There were statistically significant differences in the error number of TMT-A (0.00 (0.00, 1.00), 0.00 (0.00, 0.00), 0.00 (0.00, 0.00); χ²=10.11, P=0.006), the time of TMT-B ((81.17±36.83) s, (52.10±27.88) s, (47.72±23.18) s; F=5.16, P=0.011), the error number of TMT-B (3.00 (0.00, 4.00), 1.00 (0.00, 3.50), 0.00 (0.00, 0.00); χ²=7.16, P=0.028) and the number of backward (3.17±0.72, 3.50±1.08, 4.00±0.77; F=3.68, P=0.035) among the three subgroups of PD group. There were statistically significant differences between the PD group and the HC group in the time of TMT-A (PD: (64.03±15.96) s, HC: (53.00±19.50) s; t=2.77, P=0.007), the time (PD: (58.85±31.91) s, HC: (37.35±19.42) s; t=3.64, P=0.001) and error number (PD: 0 (0, 4), HC: 0 (0, 0); Z=-3.15, P=0.002) of TMT-B, the number of backward (PD: 3.63±0.90, HC: 4.98±1.21; t=-5.67, P=0.000) and VFT (PD: 14.48±3.37, HC: 16.15±2.03; t=-2.69, P=0.009). In the low and medium education level subgroups, the PD group showed worse results in three tests of executive function than the HC group, some with statistically significant differences (P<0.05). There was no statistically significant difference in the results of three tests of executive function between two subgroups of high education in the PD group and the HC group (P>0.05). Conclusions Executive functions of non-dementia PD patients are impaired. Education level may have a certain impact on cognitive function of PD patients.

Objective: To assess the trend of early beta receptor blocker (β-blocker) application (with 24h of admission) for acute myocardial infarction (AMI) patients in western rural China from 2001 to 2011. Methods: A 2-stage random sampling design was performed. The 1st stage: a simple random sampling was used to identify participating hospitals and the 2nd stage: a systematic random sampling approach was conducted in 3 specific years of 2001, 2006 and 2011 to take case study for central medical information abstraction. The changing trends and impact factors of early β-blocker application for AMI patients in western rural area were assessed by multivariate model analysis. Results: 35 hospitals were sampled and 33 of them were finally participated. With necessary exclusion, a total of 486 AMI patients without β-blocker contraindication were enrolled for 2 groups: Suitable group, the patients were suitable for early β-blocker application, n=247 and High risk group, the patients with the high risk for shock occurrence, n=239. The application rates for β-blocker within 24h of admission at 2001, 2006 and 2011 in Suitable group were 19.06%, 54.30% and 56.20%, Ptrend=0.0020; in High risk group were 31.53%, 59.49% and 69.62%, Ptrend=0.0001. In Suitable group, the patients with history of hypertension (OR=1.87, 95% CI 1.06-3.29), smoking (OR=1.97, 95% CI 1.11-3.48) or admitted in 2006 (OR=2.93, 95% CI 1.22-7.03) and 2011(OR=4.67, 95% CI 2.06-10.59) had the higher chance to use β-blocker within 24h of admission. Conclusion: Application of β-blocker within 24h of admission in AMI patients presented the increasing trend in western rural China from 2001 to 2011, while there was still difference from the guideline recommendation. Improved normative application of β-blocker is helpful to enhance the quality of care and prognosis in AMI patients.