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.

Objective To systematically evaluate the predictive models for re-admission in patients with heart failure (HF) in China. Methods Studies related to the risk prediction model for HF patient re-admission published in The Cochrane Library, PubMed, EMbase, CNKI, and other databases were searched from their inception to April 30, 2024. The prediction model risk of bias assessment tool was used to assess the risk of bias and applicability of the included literature, relevant data were extracted to evaluate the model quality. Results Nineteen studies were included, involving a total of 38 predictive models for HF patient re-admission. Comorbidities such as diabetes, N-terminal pro B-type natriuretic peptide/brain natriuretic peptide, chronic renal insufficiency, left ventricular ejection fraction, New York Heart Association cardiac function classification, and medication adherence were identified as primary predictors. The area under the receiver operating characteristic curve ranged from 0.547 to 0.962. Thirteen studies conducted internal validation, one study conducted external validation, and five studies performed both internal and external validation. Seventeen studies evaluated model calibration, while five studies assessed clinical feasibility. The presentation of the models was primarily in the form of nomograms. All studies had a high overall risk of bias. Conclusion Most predictive models for HF patient re-admission in China demonstrate good discrimination and calibration. However, the overall research quality is suboptimal. There is a need to externally validate and calibrate existing models and develop more stable and clinically applicable predictive models to assess the risk of HF patient re-admission and identify relevant patients for early intervention.

Retinal vein occlusion(RVO)is the second most common blinding retinal vascular disease, and its secondary macular edema(ME)is an important cause of visual function impairment in patients. Intravitreal injection of anti-vascular endothelial growth factor(VEGF)drugs serves as the first-line treatment, yet it is confronted with such issues as the need for repeated injections and non-response in some patients. Imaging and laboratory biomarkers play a crucial role in the early accurate diagnosis, prediction of disease progression, and evaluation of visual prognosis of RVO-ME. This study systematically reviews the research progress of imaging and laboratory biomarkers related to the prognosis of RVO-ME after anti-VEGF treatment in recent years, covering imaging biomarkers like central retinal thickness and ellipsoid zone integrity, as well as laboratory biomarkers such as serum APLN and aqueous humor IL-6. It summarizes the associations between different biomarkers and the prognosis of anti-VEGF therapy, aiming to provide a basis for the early accurate assessment and optimization of individualized treatment for RVO-ME patients, which holds significant clinical reference value.

Objective:To explore the correlation of early urinary continence(UC)after laparoscopic radical prostatectomy(LRP)with relevant preoperative MRI parameters of the urinary tract structure and provide some theoretical evidence for screening the high-risk population with postoperative urinary incontinence.Methods:This study included 49 PCa patients aged 50-78 years trea-ted by LRP in Beijing Tongren Hospital from January 2015 to February 2021,and all followed up for 12 months.We collected the com-plete baseline data on the patients,the clinical data possibly related to early postoperative UC,the MRI anatomical parameters associat-ed with UC,and the data on the recovery of early postoperative UC.We recorded the number of urinary pads used,submitted the data obtained to SPSS 23.0 statistical analysis,and identified the possible relevant factors by univariate correlation analysis,followed by R40.3 or SPSS 23.0 multivariate logistic regression analysis of the included factors and the results of UC.Results:MRI images mani-fested that the prostate anteroposterior diameter averaged(4.0±1.11)cm,the transverse diameter(4.6±0.83)cm,the cephalo-caudal diameter 2.4-6.4 cm,the membranous urethral length(MUL)(13.16±3.52)mm,and the thickness of the urethral rhab-dosphincter(URS)1.08-4.37 mm.Multivariate analysis showed that age was significantly correlated with the recovery of UC at 1 month after LRP(P=0.035,OR=0.16),and so was the URS thickness at 3 months(P=0.011,OR=0.02),9 months(P=0.014,OR=0.039)and 12 months(P=0.014,OR=0.039).Urinary incontinence with the URS thickness ≤1.6 mm at 12 months after operation was found of a high severity(P=0.010,OR[95％CI]=0.858-6.240).The MUL was positively correla-ted with the recovery of UC at 9 months(P=0.024,OR=0.508)and 12 months(P=0.024,OR=0.508)postoperatively.Correlation analysis revealed that the prostate volume,prostate diameter and other factors included in this study were not significantly correlated to postoperative UC.Conclusion:The thickness of the URS is positively correlated with the recovery of early UC,the thinner the URS,the severer the UC,and so is MUL.Age is an independent risk factor for the recovery of UC at 1 month after LRP.These findings need to be further verified by more prospective studies with long-term follow-ups.

Objective:To identify the key genes involved in the development and progression of prostate cancer(PCa)and those associated with the prognosis of the malignancy.Methods:We obtained the single-cell sequencing data on 4 cases of PCa from the GSE156632 database.Using R language and the Seurat package,we performed cell clustering and annotation,selected the subpop-ulations of epithelial cells for differential analysis after quality control and cell type identification,and conducted enrichment analysis of the identified differential genes using the Hiplot website.Then we downloaded the single nucleotide polymorphism(SNP)loci corre-sponding to the expression quantitative trait loci(eQTL)of these genes from the UK Biobank(UKB)database,and the clinical data and corresponding gene expression data on PCa patients from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO),followed by univariate COX regression analysis of the impact of the genes on the prognosis of the patients after Mendelian ran-domization.Results:A total of 1 566 genes were identified and subjected to enrichment analysis,which indicated that the differenti-al genes might be enriched in the Ras,apoptosis and oxidative phosphorylation signaling pathways.Subsequent Mendelian randomiza-tion revealed 74 potential causal genes among the 1 566 genes,and univariate COX regression analysis of the 74 genes identified 4 pos-sibly related genes FAM3B,JUNB,TMEM59,and KRT5.Comparison of the results of Mendelian randomization and univariate COX regression showed that KRT5 might be the most important gene influencing PCa.Conclusion:FAM3B,JUNB,TMEM59 and KRT5 may play a role in the progression of PCa,and KRT5 may potentially serve as a prognostic predictor and therapeutic target for the malig-nancy.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Based on the views of FAN's Eight Dynamic-Static Sequential Methods,Professor FAN Guan-Jie believes that the obesity has the pathological factor of blood stasis in addition to qi deficiency and phlegm-damp.The compatibility of blood-activating and stasis-removing drugs for the treatment of obesity is accorded to the progression of the disease.In the clinic,Crataegi Fructus associated medicinal cluster of activating blood and removing stasis is usually recommended.The medicinal cluster is with Crataegi Fructus as the chief medicinal,and is compatible with drug pairs of Salviae Miltiorrhizae Radix et Rhizoma-Carthami Flos and Moutan Cortex-Paeoniae Radix Rubra.Crataegi Fructus associated medicinal cluster is able to treat qi and blood simultaneously,mainly aimed at removing blood stasis,supplemented by nourishing blood,promoting qi and blood movement,and invigorating spleen and stomach,which has the features of simultaneous dispersing and astringency,and proper combination of static therapy and dynamic therapy,and is suitable for obese patients with blood stasis obstruction in the vessels.

Objective To conduct basic research on the structure and function of the heart in cynomolgus monkeys older than 10 years to provide data for animal selection in elderly disease research.Methods A total of 144 cynomolgus monkeys＞10 years old were selected as research subjects,including 37 females and 66 males in the 10～15 years group,and 21 females and 20 males in the 16～20 years group.Basic data on cardiac structure and function in middle-aged and elderly cynomolgus monkeys were obtained through comparative analysis of general indicators(body mass index,blood pressure,and heart rate),blood biochemical indicators(blood glucose,blood lipids,and ion indicators),and cardiac structure and function indicators.Results General indicators for the 10～15 years and 16～20 years groups were compared.As age increased,the blood pressure and heart rate of female and male monkeys increased,and there was a significant difference in blood pressure changes between male monkeys.A comparison of two sets of blood biochemical indicators showed that,as age increased,blood glucose,triglycerides,total cholesterol,low-density lipoprotein cholesterol,blood calcium,blood sodium,and blood potassium increased,while lactate dehydrogenase decreased,in female and male monkeys.Among these,blood glucose,triglycerides(males),total cholesterol,high-density lipoprotein cholesterol(males),low-density lipoprotein cholesterol(males),blood calcium,blood sodium,blood potassium,and lactate dehydrogenase showed significant changes.A comparison of cardiac contractile function between the two groups showed that,as age increased,the anterior and posterior diameters of the left atrium significantly decreased in both female and male monkeys.Female monkeys showed a significant decrease in the interventricular septal end systolic diameter,left ventricular end diastole and systolic diameters,left ventricular end diastolic and systolic volumes,and left ventricular mass index,while no significant changes were seen in male monkeys.A comparison of diastolic function between the two groups showed that,as age increased,the late diastolic velocity of the mitral valve decreased significantly in male monkeys,while the early diastolic velocity of the left ventricular sidewall increased significantly in female monkeys.Correlation analysis was conducted between the metabolic indicators and the cardiac structure and function indicators of female and male monkeys.The correlations between metabolic indicators and cardiac structure and function indicators were weak in female monkeys,for which the maximum absolute Γ value did not exceed 0.39.However,the correlations between metabolic indicators and cardiac structure and function indicators were relatively strong in male monkeys,for which the maximum absolute Γ value reached 0.66.Conclusions Based on ultrasound analysis combined with metabolic indicators,the heart function of cynomolgus monkeys was studied,and basic data related to the structure and function of the heart in middle-aged and elderly cynomolgus monkeys were obtained.As age increased,blood glucose and lipid indicators increased in cynomolgus monkeys,while cardiac systolic and diastolic functions show a downward trend,similar to changes in middle-aged and older adult human populations.These data provide support for animal selection in research on age-related diseases related to heart function.

Objective:To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU).Methods:A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO 2/FiO 2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO 2/FiO 2 before and after prone position in patients with severe pneumonia. Results:Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55, 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio ( OR) = 0.946, 95% confidence interval (95% CI) was 0.912-0.980, P = 0.002] and Lac ( OR = 0.563, 95% CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival ( OR = 2.551, 95% CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO 2/FiO 2 at different time points in prone position showed that PaO 2/FiO 2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position ( r = 0.565, P < 0.001). Conclusions:The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.