Objective To explore the risk factors for portal vein thrombosis(PVT)in patients with cirrhosis in the decompensated stage and construct a risk prediction model for PVT so as to improve the early diagnosis rate of decompensated liver cirrhosis PVT.Methods The clinical data of patients with cirrhosis in the decompensated stage admitted to Department of Gastroenterology,The First Affiliated Hospital of Xi'an Jiaotong University between June 2018 and June 2023 were collected and divided into cirrhosis PVT group(n=135)and cirrhosis non-PVT group(n=225)according to whether or not portal vein thrombosis was formed.We made a univariate analysis of the general data,laboratory indexes,liver function scores and imaging findings of the patients in the two groups,and indexes with statistically significant differences were included in binary Logistic regression for multifactorial analysis to screen out independent risk factors.A predictive model of binary Logistic regression was established based on the independent risk factors.The clinical data of the validation set were incorporated into the model,the accuracy of the prediction model was evaluated by receiver operating curve(ROC),and the practicability of the model was evaluated by consistency curve to complete the validation and evaluation of the constructed prediction model.Internal stability of the model was verified with Bootstrap method.Finally,R software(4.3.1)was used to draw a nomogram of the prediction model to visualize the model.Results Univariate analysis revealed statistically significant differences between patients in the PVT and non-PVT groups in the following five aspects:history of splenectomy,history of endoscopic varicose vein treatment,portal vein diameter,and neutrophil-to-lymphocyte ratio(P＜0.05).Binary Logistics regression analysis showed that a history of splenectomy(P=0.002,OR=3.012,95％CI:1.500-6.047),a history of endoscopic varicose vein treatment(P=0.001,OR=2.276,95％CI:1.400-3.698),widening of portal vein diameter(P=0.007,OR=1.942,95％CI:1.202-3.136),increased neutrophil-to-lymphocyte ratio(P=0.009,OR=1.886,95％CI:1.170-3.041),and elevated D-dimer(P＜0.001,OR=3.725,95％CI:2.149-6.485)were independent risk factors for the formation of portal vein thrombosis in patients with cirrhosis in the decompensated stage of cirrhosis chemically presented(P＜0.05).The area under the ROC curve of the predictive model and the model after internal validation was 0.760 and 0.7494,respectively.The model still had good prediction ability and accuracy in the verification set.Conclusion A history of splenectomy,history of endoscopic varicose vein treatment,widening of portal vein diameter,increased neutrophil-to-lymphocyte ratio,and elevated D-dimer concentration are independent risk factors for the formation of portal vein thrombosis in patients with decompensated cirrhosis.The Logistic prediction model and visual nomogram constructed based on the above independent risk factors have a good ability to predict the occurrence of PVT in patients with decompensated cirrhosis and have important clinical guiding significance for early screening patients with PVT in decompensated cirrhosis.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.

Objective To construct a model for predicting the risk of essential hypertension accompanied by left ventricular hypertrophy using machine learning algorithms based on pulse diagram parameters;To explore its clinical application value.Methods A total of 295 patients with essential hypertension who were hospitalized in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai Hospital of Traditional Chinese Medicine and Shanghai Hospital of Integrated Traditional Chinese and Western Medicine were selected from July 2020 to May 2021 and July 2023 to July 2024.According to the echocardiographic results,the selected research subjects were divided into the essential hypertension with left ventricular hypertrophy group(referred to as the"LVH group")and the essential hypertension without left ventricular hypertrophy group(referred to as the"non-LVH group").The general data and clinical biochemical indicators were collected,and the pulse diagram parameters of the patients were detected using the SMART-I type TCM digital pulse analyzer.A clinical prediction model was constructed based on decision tree,support vector machine and extreme gradient boosting model algorithms.The predictive performance of the model was evaluated in terms of discrimination,calibration and clinical prediction ability by using the receiver operating characteristic(ROC)curve,calibration curve and decision curve analysis respectively.The influence of each predictive factor on the risk of LVH in essential hypertension was explained based on the SHAP algorithm.Results Compared with the non-LVH group,the BMI,the proportion of males,drinkers and smokers was lower in the LVH group,with statistical significance(P<0.05);the thickened ventricular wall,left ventricular internal dimension enlargement,left common carotid artery intima-media thickness and high density lipoprotein cholesterol were higher in the LVH group than in the non-LVH group(P<0.05);the left common carotid peak systolic velocity,left common carotid resistance index,serum uric acid and serum creatinine were lower in the LVH group than in the non-LVH group(P<0.05).The pulse diagram parameters T4,T,W1,W2,H3/H1 and H4/H1 were higher in the LVH group than in the non-LVH group(P<0.05).The areas of the ROC curves of the models constructed by the three types of machine learning algorithms were 0.887,0.962 and 0.873 respectively,indicating that the model had good discrimination and certain diagnostic efficacy.The calibration curve suggested that the prediction accuracy of the model was average;the clinical decision curve showed that XGBoost model has a higher net benefit.Conclusion The interpretable model constructed based on pulse diagram parameters and machine learning algorithms can be used as a reliable tool for predicting the risk of essential hypertension with LVH.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.

The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

AIM To investigate the clinical effects of Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment on patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency.METHODS Sixty patients were randomly assigned into control group(30 cases)for 24-week intervention of non-immunosuppressive treatment,and observation group(30 cases)for 24-week intervention of both Mahuang Fuzi Xixin Decoction and non-immunosuppressive treatment.The changes in clinical effects,TCM syndrome effects,TCM syndrome score,24 h UTP,ALB,eGFR,Nephrin,Podocin and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate and TCM syndrome effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome score,24 h UTP,Nephrin,Podocin(P＜0.05),and increased ALB(P＜0.05),especially for the observation group(P＜0.05).No obvious adverse reactions occured in the two groups.CONCLUSION For the patients with focal segmental glomerulosclerosis due to Spleen-Kidney Yang Deficiency,Mahuang Fuzi Xixin Decoction combined with non-immunosuppressive treatment can improve TCM syndromes,whose action mechanism may be contribute to the alleviation of podocyte injury.

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

[Objective]To detect the sensitivity of multidrug-resistant Acinetobacter baumannii(MDRAB)to berberine and investigate the effect of berberine on its resistance.[Methods]Sixty clinical strains of MDRAB obtained from Microbiology Laboratory of Zhejiang Provincial Hospital of Traditional Chinese Medicine between January and December 2023 were utilized.Microbroth dilution was used to measure the minimum inhibitory concentration(MIC)of berberine against MDRAB.Protein profiles of both the original and passaged strains were examined through matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS),carbapenemase related genes were detected simultaneously.[Results]The MIC values of 60 MDRAB strains to berberine were all more than or equal to 5 mg·mL-1.After the action of berberine,MALDI-TOF MS analysis of the two groups of strains revealed that the peaks at mass-to-charge ratios of 6 644.47,12 297.67,and 16 985.72 were characteristic peaks with significant differences between the two groups.The detection rate of carbapenemase imipenemase metallo-β-lactamase(IMP)genes decreased from 34.2％to 10.5％,with a statistically significant difference(P＜0.05).[Conclusion]When used alone,berberine has very limited ability to directly inhibit or kill MDRAB;berberine can reverse the drug resistance mechanism of MDRAB by altering the expression of MDRAB proteins and IMP genes of carbapenemases,providing a new approach for the clinical treatment of MDRAB infections.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.