ObjectiveThis study aims to improve the management efficiency of zebrafish strains and zebrafish facilities and to transform the traditional management model that relies on manual labor. The goal is to promote a comprehensive transition from traditional manual operation to standardized, digitalized, automated, and refined management, thereby significantly improving management quality and work efficiency. MethodsThe research group independently developed the "Zebrafish Facility and Zebrafish Strain Automation Management System V1.0" (Software Copyright Registration No. 2021SR0236837), which comprehensively recorded all operational data of the zebrafish facilities and completed data on zebrafish strains. By combining in-depth mining of these data with management experience, management regulations were transformed into executable system instruction sets, and a full-process automated closed-loop management framework of "Monitoring–Analysis–Early Warning–Task Assignment–Execution–Recording" was established. ResultsThis management system has been operating stably for 5 years and has been successfully applied in 3 zebrafish facilities, cumulatively supporting 78 researchers and efficiently managing 1 108 plasmids and 1 123 zebrafish strains, among which 291 strains has been incorporated into zebrafish sperm bank management. A Likert scale survey of 28 core users covering 14 evaluation dimensions across 4 major categories showed average scores of 4.46–4.89, all far above the midpoint (3 points) of the scale, indicating that users gave high evaluations to all dimensions of the system. Meanwhile, the standard deviations of most dimensions were low (s ≤ 0.44), reflecting good consistency in user evaluations. ConclusionThis study integrates information technology, big data analysis, and modern management concepts to achieve a virtuous cycle of "data collection–analysis and execution–system optimization" in zebrafish facility management. It significantly improves management efficiency and refinement and promotes the development of management models toward automation.

ObjectiveTo investigate the value of predictive models established based on machine learning methods in predicting the risk of metabolic associated fatty liver disease （MAFLD）， and to analyze its key risk factors. MethodsA retrospective analysis was performed for the 50 variables of 2 168 healthy individuals who underwent physical examination in Department of Health Assessment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， from January 2021 to December 2024， including body composition， past history， and laboratory tests， and according to whether they were diagnosed with MAFLD or not， they were divided into MAFLD group with 265 individuals and non-MAFLD group with 1 903 individuals. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Randomly split the research data into a training set and a validation set in a 70% to 30% ratio. Predictive factors were screened from the training set data using univariate analysis， LASSO regression， and multivariate Logistic regression analysis. Predictive models were then constructed using seven machine learning methods： Logistic regression， decision tree， random forest （RF）， eXtreme gradient boosting， light gradient boosting machine， support vector machine， and artificial neural network. Model performance was evaluated by plotting receiver operating characteristic curve for the validation set and calculating the area under the curve （AUC）， sensitivity， specificity， and Youden index for each model. Furthermore， the SHapley Additive exPlanation （SHAP） method was used to analyze the contribution of variables in the optimal model. ResultsThe prevalence rate of MAFLD among the 2 168 subjects was 12.22% （265/2 168）. Smoking， diastolic blood pressure， phase angle， visceral fat area， muscle fat ratio， waist-to-hip ratio， aspartate aminotransferase， non-HDL-C/HDL-C ratio， triglyceride-glucose index， and gallstones were independent risk factors for MAFLD （all P<0.05）. The seven predictive models of support vector machine， eXtreme gradient boosting， decision tree， light gradient boosting machine， artificial neural network， RF， and Logistic regression had an AUC of 0.738， 0.754， 0.757， 0.786， 0.795， 0.796， and 0.815， respectively， in the validation set， among which the RF model had the best discriminatory ability （AUC=0.796， 95% confidence interval： 0.754 — 0.839）， with a sensitivity of 81.01%， a specificity of 63.16%， and a Youden index of 44.17%. The SHAP analysis showed that visceral fat area， waist-to-hip ratio， and diastolic blood pressure were the top three predictive factors in terms of importance. ConclusionThe RF model， constructed based on body composition and clinical indicators， has a good performance in predicting the risk of MAFLD， and its interpretability can help to identify high-risk individuals in the early stage in clinical practice.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

ObjectiveTo investigate the effects and mechanisms of Fangji Fulingtang （FFD） on mitochondrial function in the mouse model of myocardial fibrosis （MF）. MethodsSixty SPF-grade male C57BL/6J mice were randomly allocated into six groups （n=10 per group）： control， model， low-dose， medium-dose， and high-dose （3.315， 6.63， and 13.26 g·kg^-1， respectively） FFD， and captopril （20 mg·kg^-1）. MF was induced by subcutaneous injection of isoproterenol （10 mg·kg^-1·d^-1） in other groups except the control group for 14 consecutive days， with simultaneous gavage of corresponding drugs. Left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured by echocardiography. Serum levels of creatine kinase-MB （CK-MB）， cardiac troponin I （cTnI）， N-terminal pro-brain natriuretic peptide （NT-pro BNP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were determined by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） levels were measured by biochemical assays. Reactive oxygen species （ROS） were detected by dihydroethidium （DHE） fluorescence staining. Hematoxylin-eosin （HE）， Masson's trichrome， and wheat germ agglutinin （WGA） staining were performed to evaluate myocardial structure and fibrosis. Mitochondrial ultrastructure and function were assessed by transmission electron microscopy， adenosine triphosphate （ATP） colorimetric assay， and JC-1 fluorescence staining. The protein levels of phosphorylated adenosine monophosphate-activated protein kinase α subunit （p-AMPKα）， AMPKα， peroxisome proliferator-activated receptor gamma coactivator-1α （PGC-1α）， mitofusin 2 （MFN2）， pyruvate kinase M2 isoform （PKM2）， lactate dehydrogenase A （LDHA）， and hypoxia-inducible factor 1 alpha （HIF-1α） were analyzed by Western blot. ResultsCompared with the control group， the model group exhibited decreased LVEF and LVFS， increased heart weight index and heart weight-to-tibia length ratio （P<0.01）， elevated levels of myocardial injury markers （CK-MB， cTnI， and NT-pro BNP）， inflammatory cytokines （TNF-α， IL-1β， and IL-6）， and MDA， along with reduced SOD and GSH levels （P<0.01）. Enhanced interstitial collagen deposition and cardiomyocyte hypertrophy were observed in the model group （P<0.01）. Transmission electron microscopy and JC-1 staining revealed mitochondrial swelling， crista disruption， decreased ATP content， and reduced red/green fluorescence ratio in the model group （P<0.01）. Western blot analysis demonstrated downregulation of p-AMPKα， PGC-1α， and MFN2 and upregulation of PKM2， LDHA， and HIF-1α in the model group （P<0.01）. Compared with the model group， treatment with FFD or captopril improved LVEF and LVFS， reduced heart weight index and heart weight-to-tibia length ratio （P<0.05， P<0.01）， lowered the serum levels of CK-MB， cTnI， NT-pro BNP， TNF-α， IL-1β， IL-6， and MDA， increased the SOD and GSH levels （P<0.05， P<0.01）， attenuated the myocardial fibrosis and cardiomyocyte hypertrophy （P<0.01）， and restored the mitochondrial ultrastructure. The medium and high-dose FFD groups as well as the captopril group showed increased ATP production and red/green fluorescence ratio （P<0.05， P<0.01）. Furthermore， FFD upregulated the expression of p-AMPKα and PGC-1α while downregulating the expression of LDHA and HIF-1α （P<0.05， P<0.01）. ConclusionFFD activates the AMPK/PGC-1α/MFN2 signaling pathway and inhibits the PKM2/LDHA/HIF-1α axis to restore mitochondrial function and energy metabolic homeostasis， thereby attenuating isoproterenol-induced myocardial fibrosis.

This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Tandem Mass Spectrometry/methods* ; Sleep Initiation and Maintenance Disorders/metabolism* ; Mice ; Network Pharmacology ; Male ; Chromatography, High Pressure Liquid ; Humans ; Protein Interaction Maps/drug effects* ; Sleep/drug effects* ; Female ; Adult

OBJECTIVE: To compare clinical effects of external fixation and minimally invasive percutaneous plate osteosynthesis (MIPPO) after external fixation in treating open fractures of tibial shaft. METHODS: From January 2020 to June 2022, 151 patients with open fracture of tibial shaft treated with external fixation stenting were divided into external fixation group and combined group according to different surgical methods. There were 81 patients in external fixation group, including 48 males and 33 females, aged from 21 to 68 years old with an average of (42.58±7.44) years old;according to Gustilo classification, 49 patients with typeⅡ, 32 patients with type ⅢA;the time from injury to treatment ranged from 2.5 to 10 h with an average of (4.25±0.74) h;external fixed stenting was performed. There were 70 patients in combined group, including 42 males and 28 females, aged from 20 to 69 years old with an average of (41.39±7.02) years old;35 patients with type Ⅱ and 35 patients with type ⅢA according to Gustilo classification;the time from injury to treatment ranged from 3 to 9 h with an average of (4.31±0.85) h;MIPPO treatment was performed after external fixed stenting. The time of callus formation, fracture healing and complications were compared between two groups. Rasmussen score and Hospital for Special Surgery (HSS) score were used to evaluate functional recovery of knee joint at 6 months after operation. RESULTS: Both groups were followed up for 6 to 13 months with an average of (10.17±2.33) months. The time of callus formation and fracture healing were (13.98±4.02) d and (70.26±12.15) d in combined group, and (18.56±4.37) d and (79.87±15.41) d in external fixation group, respectively. Combined group was better than external fixation group in the time of callus formation and fracture healing (P<0.05). At six months after operation, Rasmussen and HSS scores in combined group were (26.79±3.11) and (83.36±9.44), which were higher than those in external fixation group (24.51±4.63) and (79.63±8.46) (P<0.05). In external fixation group, there were 2 patients with incision infection, 2 patients with nail tract infection, 1 patient with stent loosening, fracture displacement, delayed union and malunion, and 1 patient with biocompatibility reaction in combined group, with statistical significance between two groups (P<0.05). CONCLUSION MIPPO could accelerate callus formation and fracture healing, improve knee function, improve clinical effects and reduce complications in patients with open tibial shaft fractures after external and external fixation.
Humans ; Male ; Female ; Middle Aged ; Adult ; Aged ; Tibial Fractures/physiopathology* ; Fracture Fixation, Internal/methods* ; Retrospective Studies ; Bone Plates ; External Fixators ; Fractures, Open/physiopathology* ; Stents ; Young Adult

PURPOSE: Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT). METHODS: Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference. RESULTS: There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 - 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT. CONCLUSION The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Humans ; Venous Thrombosis/etiology* ; Male ; Female ; Middle Aged ; Lower Extremity/blood supply* ; Retrospective Studies ; Adult ; Aged ; Age Factors ; Sex Factors ; Risk Factors ; Acute Disease ; Incidence ; Aged, 80 and over ; Young Adult ; Adolescent

To enhance the trustworthiness,security,and convenience of research data management and pro-mote the deep utilization of clinical research data,it introduces core technologies such as data sandboxing,ze-ro-trust architecture,elastic resource scheduling in cloud computing,and data lakes to construct a clinical research trusted data space with trusted management,resource interaction,and value co-creation capabilities.This trusted data space provides a secure and efficient platform for data processing and analysis through strict network access control,dynamic authentication,data anonymization,and digital watermarking technologies.It ensures the secure flow and precise traceability of research data throughout its lifecycle,effectively facilitating resource interaction and value co-creation.The implementation offers a valuable technical reference and practical guidance for other hospitals aiming to build trusted research data platforms.

Objective To construct a symptom network in patients with acute type A aortic dissection(ATAAD),so as to provide theoretical basis for the screening of dissection ATAAD during emergency pre-screening triage.Methods There were 433 patients diagnosed with ATAAD during 2019 to 2023 in an emergency department of a tertiary hospital in Wuhan.Their basic information and medical records were reviewed by self-designed data questionnaire.UCINET6.0 software was used to construct a symptom network,analyze the centrality index and determine the core symptoms.Symptom distribution of patients with positive and negative blood pressure in extremities was analyzed in the further.Results The most common symptoms in patients with type A aortic dissection were chest pain(77.37％),back pain(42.96％),and sweating(29.79％).In the symptom network,chest pain had the highest degree(rs=659).The closeness of chest pain,chest tightness,shortness of breath,back pain,nausea and vomiting,limb numbness and fatigue were same(rc=93.33).Fatigue has the highest betweenness(rb=13.69).Patients with positive limbs blood pressure mainly reported chest pain(70.17％),back pain(44.96％),and nausea and vomiting(19.33％),while those with negative limb blood pressure mainly reported chest pain(63.64％),back pain(63.64％),and orosphyalgia(39.40％).Orosphyalgia had the highest degree(rs=20).Conclusion The symptoms of ATAAD are complex and varied in patients.During triage,nurses should measure the limb blood pressure when patients complained chest pain alone or when combined with other hypoperfusion symptoms,such as back pain,chest tightness,sweating,near-death sensation,and shortness of breath.Aortic dissection cannot be ruled out in patients with negative blood pressure when they had chest pain,back pain or orosphyalgia.

Objective:To investigate the correlation between blood lipid levels and arterial stiffness in middle-aged and elderly Han Chinese individuals with angiotensin-converting enzyme(ACE)gene I/D polymorphism in Beijing.Methods:This was a cross-sectional study.The Han Chinese residents, aged 45 years and above, from Haidian District of Beijing, were recruited for the survey from May to August 2022.Based on the inclusion and exclusion criteria, 356 subjects were included, of which 100(28.09%)were male and 256(71.91%)were female.According to the population division criteria proposed by the World Health Organization, the subjects were divided into 253 cases in the middle-aged group[45-59 years old, median age 52.5(49.0, 56.0)years]and 103 cases in the elderly group[60-89 years old, median age 63.0(61.0, 65.0)years].Subjects were tested for ACE genotyping, lipids and brachial-ankle pulse wave velocity(baPWV).Lipid indices included triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).Results:In the middle-aged group, there were no significant differences in plasma levels of TC, TG and HDL-C between individuals with the DD genotype and those with the ID/Ⅱ genotype(all P>0.05).Similarly, in the elderly group, no significant differences were observed in plasma TC, TG, and HDL-C levels between individuals with the DD genotype and those with the ID/Ⅱ genotype(all P>0.05).In the middle-aged group, plasma LDL-C levels were significantly higher in the DD phenotype than in the ID/Ⅱ phenotype( Z=-2.483, P=0.013), while there was no significant difference in plasma LDL-C levels between the two phenotypes in the elderly group( Z=-0.935, P=0.350).There were no significant differences in baPWV between the DD and ID/Ⅱ phenotypes in both the middle-aged and elderly groups( Z=-0.104, -1.490, P=0.917, 0.136).In the elderly group, plasma TG levels were positively correlated with baPWV in the DD phenotype( r=0.590, P=0.016).In the middle-aged group, plasma TG levels were positively correlated with baPWV in the ID/Ⅱ phenotype( r=0.158, P=0.019), while plasma HDL-C levels were negatively correlated with baPWV( r=-0.174, P=0.009). Conclusions:Among middle-aged and elderly individuals with different ACE gene I/D polymorphisms, there are differences in blood lipid indicators sensitive to arterial stiffness.For middle-aged individuals with the ID/Ⅱ phenotype, arterial stiffness is more sensitive to high TG and low HDL-C levels, whereas for elderly individuals with the DD phenotype, arterial stiffness is more sensitive to high TG levels.These findings offer an experimental foundation for tailored blood lipid management strategies across diverse populations, aiming to maintain cardiovascular health and reduce the occurrence of cardiovascular diseases.