ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

ObjectiveTo investigate the effects of different fermentation methods and times on the fungal flora and chemical composition of Aurantii Fructus， in order to obtain the optimal fermentation conditions and flora structure， and to ensure the stability and controllability of the fermented varieties. MethodsScanning electron microscopy was used to observe and analyze the colony characteristics on the surface of Aurantii Fructus under different fermentation conditions. Internal transcribed spacer 2（ITS2） high-throughput sequencing， combined with fungal community diversity analysis and fungal community structure analysis， were used to obtain the fungal flora microbial categories of Aurantii Fructus under the conditions of traditional pressure-shelf fermentation and non-pressure-shelf natural fermentation for 7， 14， 21 d（numbered Y1-Y3 for the former， and numbered F1-F3 for the latter）， respectively. At the same time， the chemical components in the fermentation process were detected by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， combined with principal component analysis（PCA）， partial least squares-discriminant analysis（PLS-DA） and compound retention time， parent ions， characteristic fragment ions and other information， the differential compounds between the different fermentation samples were screened and identified. ResultsThe analysis of fungal community diversity showed that the dominant flora did not change at different fermentation time points in the traditional pressure-shelf fermentation method， while in the non-pressure-shelf natural fermentation method， there was a significant difference with the fermentation process， and at the genus level， the dominant genus of samples Y1， Y2， Y3 and F2 was Aspergillus， while the dominant genera of samples F1 and F3 were both Rhizopus. This indicated that the microbial growth environment provided by the traditional fermentation method was more stable， and the microbial community structure was more stable， which was more conducive to the stable and controllable fermentation process and fermented products. A total of 155 compounds were identified by compositional analysis， including 70 flavonoids， 38 coumarins， 10 alkaloids， 34 organic acids and 3 other compounds. After fermentation， two new components of ribalinine and pranferin were produced. Different fermentation conditions also brought about differences in chemical composition， multivariate statistical analysis obtained 26 differential compounds under two different fermentation methods， mainly including flavonoids， organic acids and coumarins. Comprehensively， the microbial community structure of samples fermented by the traditional pressure-shelf method of Aurantii Fructus for 14 d was stable， the species richness was high and the overall content of differential compounds was high， which was the optimal processing condition. ConclusionCompared with non-pressure-shelf natural fermentation， the traditional method has obvious advantages in terms of the stability of the microbial community structure and the content of chemical compounds， and the optimal condition is 14 days of fermentation. This study is helpful to promote the quality stability and fermentation bioavailability of fermented products of Aurantii Fructus， as well as to provide an experimental basis for the further improvement of the quality control methods of this variety.

The incidence of intracranial aneurysms is high, which is the first cause of spontaneous subarachnoid hemorrhage. The preparation of animal models for intracranial aneurysms is becoming increasingly mature, and has played an important role in research fields of etiology and intervention materials for intracranial aneurysms. This article reviews preparation methods and animal selection of animal model for intracranial aneurysms.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

Objective:To explore whether lung microorganisms influence the occurrence and development of early lung adenocarcinoma by analyzing the presence and changes of local microorganisms in early lung adenocarcinoma.Methods:Tumor tissues and alveolar lavage fluid were collected from 32 patients diagnosed with lung adenocarcinoma at the China-Japan Friendship Hospital. Nextseq550DX was used for DNA sequencing. R language was used to calculate the number of microorganisms in the tumor tissue and alveolar lavage fluid samples of different stages and grades. species and diversity, and use statistical methods such as TSEA and LEfSe analysis to compare the diversity and differences of microorganisms in different groups. Results:Both Actinobacteria and Proteobacteria accounted for a higher proportion in both the tumor tissue and alveolar lavage fluid samples of patients with lung adenocarcinoma. The number of microorganisms detected in the tumor tissue was greater than that in the lavage fluid, and the alpha diversity was higher, but the difference Not significant( P<0. 05). According to the analysis of differences in lung microorganisms in patients with different pathological grades: In the two samples, invasive adenocarcinoma has more microorganisms than carcinoma in situ + microinvasive carcinoma, and the alpha diversity of the lavage fluid is significantly higher, and the comparison between the groups is statistically significant( P=0. 011); the difference in β diversity was not statistically significant( P>0. 05). Group analysis based on different pathological types: the invasive adenocarcinoma group samples showed a decrease in Proteobacteria, the carcinoma in situ + minimally invasive cancer group was mainly composed of Proteobacteria, and most of the microorganisms related to lung cancer differences analyzed in each group belonged to Proteobacteria and Actinobacteria. Phylum. Conclusion:Most of the microbes in tumor tissues and lavage fluid of lung adenocarcinoma belong to the Actinobacteria and Proteobacteria. Most of the differentially associated microbes of lung cancer under different classifications also belong to Proteobacteria and Actinobacteria, which are the main characteristics of lung microbial composition in patients with early-stage lung adenocarcinoma.

Objective To systematically evaluate the efficacy and safety of the ceftazidime-avibactam(CAZ-AVI)regimen versus other regimens for treatment of carbapenem-resistant Enterobacteriaceae(CRE)bloodstream infections,and to provide an evidence-based foundation for drug selection in clinical CRE bloodstream infections.Methods A computerized search was conducted in Pubmed,Embase,Cochrane Library,Web of Science,Wanfang Medical Network,CNKI and China Science and Technology Journal Database for literature on CAZ-AVI for CRE bloodstream infections from the inception of each database up to November 2023.The literature quality evaluation and data extraction were independently performed by two researchers.A meta-analysis was performed using Review Manager 5.3 software.Results A total of 15 English articles and 1 580 patients were included.The results showed that the clinical cure rate[OR=3.32,95% CI=(2.25,4.90),P<0.000 01]and microbial clearance rate[OR=3.00,95% CI=(1.15,7.81),P=0.02]were significantly higher in the CAZ-AVI group than in the control group,and the 28 d/30 d all-cause mortality rate of patients in the CAZ-AVI group was lower than that of the control group[OR=0.38,95% CI=(0.29,0.51),P<0.000 01].The recurrence rates of infection in the two groups were equivalent and statistically non-significant[OR=0.75,95% CI=(0.39,1.42),P=0.37].Subgroup analysis indicated that the CAZ-AVI group had a lower all-cause mortality rate than the tigecycline group[OR=0.20,95% CI=(0.11,0.39),P<0.000 01].In terms of safety,the incidence of adverse events between the two groups was comparable and statistically non-significant[RR=0.47,95% CI=(0.20,1.07),P=0.07].However,the nephrotoxicity was significantly lower in the CAZ-AVI group than in the control group[OR=0.36,95% CI=(0.21,0.64),P=0.000 5].Conclusion Based on the findings of the current study,CAZ-AVI offers potential clinical advantages in the treatment of CRE bloodstream infections by improving clinical cure rates and reducing mortality rates.

Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.

Objective:To explore the application and clinical efficacy of functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium in the surgery of lung cancer brain metastases.Methods:Forty patients with lung cancer and brain metastasis admitted to the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2020 to January 2024 were collected as the observation group. Another 40 patients with lung cancer brain metastases who underwent microscopic resection at Inner Mongolia Autonomous Region People's Hospital from January 2016 to December 2019 were selected as the control group. All patients received head CT examination, head MRI examination, MRI enhanced sequence and MRA, MRV and DWI sequence scanning before operation. Functional neural navigation system was used to perform preoperative multi-modal image fusion to realize three-dimensional display of tumor lesions, and display the position relationship between tumor and functional areas, conduction bundles and large blood vessels, so as to make preoperative navigation plan. After conducting a fluorescein sodium allergy test on the patient before surgery, a small dose of fluorescein sodium (2 mg/kg) was intravenously injected during the operation. During the operation, neuro navigation was combined with fluorescein sodium to perform tumor resection by displaying the boundary between tumor tissue and normal brain tissue under a Pentero 900 Zeiss microscope 560 fluorescence mode. Both groups collected tumor tissue samples for pathological classification and immunohistochemical analysis, comparing and analyzing differences in tumor resection degree, postoperative occurrence of new neurological dysfunction, postoperative muscle strength improvement, changes in KPS scores before and after surgery, and the occurrence of complications. The metric data that conforms to normal distribution is represented by xˉ± s, and the comparison of means between two groups is conducted using independent sample t-test. Calculate the percentage based on the count data, and compare the inter group rates using the χ2 test. P<0.05 indicates statistical significance of the difference. Results:Compared with the control group, the total tumor resection rate of observation group (75.0% (30/40) ) and KPS score of 3 months after surgery (82.5% (33/40)) were better than those of the control group (52.5% (21/40) and 60% (24/40)), and the differences were statistically significant ( χ2 value was 4.94 and 4.38, P values were 0.026 and 0.036). The rate of postoperative new neurological dysfunction in the observation group (22.5% (9/40)) was lower than that in the control group (45.0% (18/40)), and the difference between the two groups was statistically significant ( χ2=4.53, P=0.033). The length of hospital stay ((21.48±3.23) days), operation time ((216.65±56.76) points) and complication rate (37.5% (15/40)) in observation group were lower than those in control group ((22.43±2.34) days, (225.62±37.68) points, 45.0% (18/40)). However, the difference was not statistically significant ( t/ χ2 values were 1.51, 0.83, and 0.46, respectively; P values were 0.136, 0.408, and 0.496, respectively). The 12-month survival rate of observation group (67.5%(27/45) respectively was significantly higher than that of control group (40.0%(16/40) respectively, and the difference was statistically significant ( χ2=6.08, P=0.014). Conclusion:Functional neural navigation multimodal image fusion technology combined with intraoperative fluorescein sodium can accurately locate the tumor and determine the boundary relationship between the tumor and normal brain tissue during lung cancer brain metastasis surgery, improve tumor resection rate, enhance patient quality of life, and ultimately improve patient prognosis without increasing the risk of related complications.

Objective: To explore the longitudinal correlation between smartphone multitasking and depressive symptoms, so as to provide an evidence based basis for promoting the mental health of college students. Methods: A total of 967 college students were recruited from one university in Taiyuan, Chongqing, and Shenzhen cities, China, by using multi stage randomized cluster sampling from October to December 2021 at baseline, and a follow up survey was conducted in May 2022. Smartphone multitasking behaviors were assessed by means of the Assessment of Smartphone Multitasking for Adolescents (ASMA), and depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) among college students. Chi square tests were performed to compare the differences in depressive symptoms between different groups of demographic characteristics, and binary Logistic regression models were employed to analyze the associations between smartphone multitasking and depressive symptoms among college students. Results: The rates of depressive symptoms among college students at baseline and follow up were 35.2% and 42.3%, respectively. Compared to the low level smartphone multitasking index group at baseline, the moderate and high level groups were more likely to experience depressive symptoms at baseline (moderate level group: OR=1.74, 95%CI =1.22-2.50, high level group: OR=2.77, 95%CI =1.94-3.95) and followup (moderate level group: OR=1.41, 95%CI =1.01-1.95, high level group: OR=1.64, 95%CI =1.17-2.29) ( P <0.05). In addition, compared to the persistently low smartphone multitasking index, increased risk of depressive symptoms was associated with maintaining a moderate to high ( OR=2.94, 95%CI =1.83-4.71), and a higher ( OR=2.07, 95%CI =1.31-3.27) or lower smartphone multitasking index ( OR=2.02, 95%CI =1.27-3.19) ( P <0.05). Moreover, higher smartphone multitasking index scores were positively associated with the risk of new-onset depressive symptoms at follow up ( OR=1.87, 95%CI=1.07-3.27, P <0.05). Conclusions Smartphone multitasking behaviors are find to be associated with an increased risk of depressive symptoms in college students. There is a need to reduce smartphone multitasking in order to decrease depressive symptoms and promote students mental health.

Objective: To explore the association among neck-shoulder pain (NSP), low back pain (LBP) and co occurring symptoms with mental sub health in adolescents, so as to provide evidence for improving physical and mental health of adolescents. Methods: Stratified cluster random sampling method was used to select 7 986 students from 12 middle and high schools in Shenzhen, Nanchang, and Shenyang cities from October to December 2019. The Assessment of Spinal Health of Youth (ASHY) and the Brief Instrument on Psychological Health of Youth (BIOPHY) were used to assess NSP, LBP and mental sub health. Binary Logistic regression model was used to analyze the association between NSP, LBP and co occurring symptoms with mental sub health in adolescents. Results: The detection rates of adolescents with NSP, LBP and co occurring symptoms and mental sub health were 9.1% , 9.8%, 9.5%, and 10.0%, respectively. The co occurring rate of neck shoulder pain, low back pain and mental sub health was 3.2%. After adjusting for confounding variables such as gender, age, being an only child, family residence, and parental education level, NSP ( OR=6.01, 95%CI =5.02-7.19), LBP ( OR=5.08, 95%CI =4.25-6.07), and co occurring symptoms ( OR= 5.96 , 95%CI =4.98-7.12) in adolescents were positively correlated with mental sub health risk ( P <0.01). Stratifying the gender, boys with NSP, LBP and co occurring symptoms ( OR =6.84, 5.80, 6.74)had a higher risk of mental sub health compared to girls ( OR =5.52, 4.65, 5.49) ( P <0.01). Conclusions NSP, LBP and co occurring symptoms in adolescents are associated with mental sub health. The mental health status of boys is more affected by NSP, LBP and their co occurring symptoms. Measures should be taken to improve spinal health in adolescents to reduce the incidence of mental sub health.