ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective To observe the clinical efficacy of Fangxiang Wentong Powder(composed of Salviae Miltiorrhizae Radix et Rhizoma,Chuanxiong Rhizoma,Alpiniae Officinarum Rhizoma,Piper Longum,and Corydalis Rhizoma)acupoint application combined with Kuanxiong Aerosol in treating female patients with coronary slow flow(CSF)associated angina.Methods After sample size estimation,119 female inpatients diagnosed as CSF associated angina and differentiated as chest-qi obstruction with yang deficiency and cold accumulation syndrome of traditional Chinese medicine(TCM)were collected from the cardiovascular departments of the Third People's Hospital of Fujian University of Traditional Chinese Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Zhanjiang First Traditional Chinese Medicine Hospital,and Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2023 to March 2024.Using a table of random numbers,the patients were divided into a treatment group(84 cases)and a control group(35 cases)in a ratio of 5∶2.The control group was treated with Isosorbide Monomitrate Sustained-Release Capsules,while the treatment group was treated with application of Fangxiang Wentong Powder on acupoints of Danzhong(CV17),Gaohuang(BL43),and Xinshu(BL15),together with sublingual administration of Kuanxiong Aerosol.The treatment course for both groups covered 7 days.Before and after treatment,the changes in the simplified Seattle Angina Questionnaire(SAQ-7)scores,Chinese Quality of Life Questionnaire for Cardiovascular Patients(CQQC)scores,6-minute walking distance(6MWD),serum C-reactive protein(CRP)level,and white blood cell-to-mean platelet volume ratio(WMR)were observed.The TCM symptom efficacy was compared between the two groups,and adverse reactions were monitored.Results(1)There were 8 patients withdrew in the treatment group for failing in completing the questionnaires,and 2 patients withdrew in the control group for suffering headaches after taking nitrates.Eventually,109 patients completed the trial,including 76 in the treatment group and 33 in the control group.(2)After 7 days of treatment,the total effective rate for TCM symptom efficacy in the treatment group was 86.84%(66/76),and that in the control group was 72.73%(24/33).The intergroup comparison(tested by the chi-square test)showed that the TCM symptom efficacy in the treatment group was significantly superior to that in the control group.(3)After treatment,both groups showed improvements in the scores of activity limitation and angina frequency items of SAQ-7,and the treatment group also showed improvements in the scores of subjective satisfaction item of SAQ-7(P＜0.05).The treatment group's improvements in the scores of activity limitation,angina frequency,and subjective satisfaction items of SAQ-7 were significantly superior to those of the control group(P＜0.05).(4)After treatment,the CQQC scores in the treatment group was significantly improved(P＜0.05),while no significant improvement was observed in the control group(P＞0.05).The improvement of CQQC scores in the treatment group was significantly superior to that in the control group(P＜0.05).(5)After treatment,both groups showed improvements in 6MWD(P＜0.05),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05).(6)After treatment,the serum levels of inflammatory indicators of CRP and WMR in the treatment group were significantly improved(P＜0.05),while no significant improvements were presented in the control group(P＞0.05).The improvements in serum CRP level and WMR value in the treatment group were significantly superior to those in the control group(P＜0.05).(7)No adverse reactions were found in the treatment group,indicating high safety.Conclusion Fangxiang Wentong Powder acupoint application combined with Kuanxiong Aerosol is more effective than Isosorbide Monomitrate Sustained-Release Capsules,improving exercise tolerance,decreasing inflammatory factor levels,and improving the quality of life to some extent during the treatment of female patients with CSF.

Objective To investigate the value of liver fatty acid-binding protein(L-FABP)in predicting the severity and short-term prognosis of patients with acute-on-chronic liver failure(ACLF).Methods A total of 149 patients with ACLF were selected from a prospective multicenter cohort assessing the platelet function of ACLF patients,and according to the 28-day prognosis after admission,they were divided into survival group with 97 patients and death group with 52 patients.The patients were analyzed in terms of sex,age,etiology,and blood routine,biochemical parameters,and organ failure status within 24 hours after admission,and the level of L-FABP in urine and blood was measured.The independent-samples t test was used for comparison of normally distributed continuous data between two groups,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups;the chi-square test was used for comparison of categorical data between two groups.The Spearman test was used to evaluate the correlation between urinary L-FABP and indicators for liver failure.The receiver operating characteristic(ROC)curve was plotted to assess the value of CLIF-OFs,MELD score,and urinary L-FABP in predicting the short-term prognosis of ACLF patients;the Kaplan-Meier analysis was used to evaluate short-term mortality in the high urinary L-FABP group and the low urinary L-FABP group;the Cox proportional hazards model was used to investigate the association of each factor with the short-term prognosis of ACLF.Results There were significant differences between the two groups in white blood cell count,serum total bilirubin(TBil),international normalized ratio,CLIF-OFs,MELD score,urinary L-FABP level,and the proportion of patients with cerebral failure,liver failure,coagulation failure,renal failure,or respiratory failure(all P<0.05).The Spearman correlation analysis showed that urinary L-FABP was significantly positively correlated with serum TBil(r=0.225,P=0.006).Urinary L-FABP level had an area under the ROC curve of 0.804(95%confidence interval[CI]:0.729-0.865,P<0.001)and a cut-off value of 4.779 μg/dL,with a sensitivity of 73.08%,a specificity of 73.91%,and a Youden index of 0.469 9.The Kaplan-Meier survival analysis showed that compared with the low urinary L-FABP group(urinary L-FABP≤4.779 μg/dL),the high urinary L-FABP group(urinary L-FABP>4.779 μg/dL)had a significantly lower 28-day survival rate(P<0.001).The Cox proportional hazards model analysis showed that serum TBil(hazard ratio[HR]=1.003,95%CI:1.001-1.004,P<0.05),CLIF-OFs(HR=2.283,95%CI:1.814-2.873,P<0.05),and high urinary L-FABP level(HR=4.568,95%CI:2.424-8.608,P<0.05)were independent risk factors for the short-term prognosis of ACLF.Conclusion High urinary L-FABP level can be used as a clinical indicator for predicting the short-term prognosis of ACLF,and further studies with larger sample sizes are needed to evaluate its predictive value.

Objective:To study the protective effects and mechanism of Melastoma sanguineum Sims fruit extract (MSE) on chronic chemical liver injury induced by ethanol, acetaminophen and carbon tetrachloride in mice; To discuss it mechanism.Methods:Totally 96 mice were divided into normal control group, ethanol model group, ethanol+bifendate control group and ethanol+MSE high-, medium- and low-dosage groups, APAP model group, APAP+bifendate control group and APAP+MSE high-, medium- and low-dosage groups, CCl 4 model group, CCl 4+bifendate control group and CCl 4+MSE high-, medium- and low-dosage groups, with 6 mice in each group. Except for the normal control group, the other groups were respectively prepared for the ethanol model, the APAP model and the CCl 4 model. The mice in the MSE high-, medium- and low-dosage groups were intragastrically administrated with 10, 5 and 2.5 g/kg of MSE, respectively; the bifendate control group was intraperitoneally injected with 15 mg/ml bifendate solution at 75 mg/kg; the normal control group was intraperitoneally injected with equal volume of normal saline/peanut oil solution once a day for 25 consecutive days. The levels of GPT, GOT and total bilirubin (TBIL) in serum were detected; the activities of SOD and GSH-Px and the content of MDA in liver tissue were detected; the mRNA expressions of TNF-α, IL-6, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) were detected by qRT-PCR; the protein expressions of cytochrome P450 CYP1A1, CYP1A2, and CYP3A in liver tissue were detected by Western blot; the pathological changes of the liver tissue were observed by HE staining. Results:Compared with the corresponding ethanol, APAP and CCl 4 model groups, the serum GPT, GOT and TBIL levels of mice in the ethanol+bifendate control group and ethanol+MSE high- and medium-dosage groups, the APAP+bifendate control group and APAP+MSE high- and medium-dosage groups, and the CCl 4+bifendate control group and CCl 4+MSE high- and medium-dosage groups decreased ( P<0.01 or P<0.05), the activities of SOD and GSH-Px in the liver tissue increased ( P<0.01 or P<0.05), and the MDA level decreased ( P<0.01 or P<0.05), and the mRNA levels of IL-6 and TNF-α decreased ( P<0.01); the mRNA levels of ADH and ALDH in the ethanol+MSE high-, medium-, and low-dosage groups decreased ( P<0.01). Compared with the APAP model group, the expressions of CYP1A1 and CYP1A2 in the APAP+MSE groups increased ( P<0.01), and the expression of CYP3A protein decreased ( P<0.05); compared with the CCl 4 model group, the expressions of CYP1A1, CYP1A2 and CYP3A proteins in the CCl 4+MSE groups decreased ( P<0.05). Conclusion:MSE has a protective effect on chronic chemically-induced liver injury induced by ethanol, APAP, and CCl 4 in mice, and its mechanism may be related to antioxidant stress, inhibition of inflammatory response, and regulation of the expression of cytochrome P450-related enzymes.

Objective:To evaluate the early assessment of hepatocardiac integration based on ultrasonic elasticity and blood flow vector imaging (VFM) technology, in conjunction with unsupervised cluster analysis and supervised machine learning methods.Methods:An observational research design without any intervention was adopted from December 2021 to September 2022, 45 patients with liver cirrhosis, 43 patients with liver fibrosis, and 42 healthy volunteers were selected from the First Affiliated Hospital of Harbin Medical University. Liver combined elasticity technology and VFM technology were used to obtain information on the liver and heart of the subjects, respectively. The acquired data were standardized, and then clustered using topological data analysis (TDA) technology on the processed data. Subsequently, the clustering results were evaluated based on statistical analysis, and finally, supervised multi-classification tasks were realized through machine learning methods.Results:Patients were stratified into five distinct groups based on a network of patient similarities. The average characteristics of each group were as follows: Group 1 exhibited the most severe hepatocardiac conditions relative to the other groups. Groups 2 and 3 displayed moderately severe conditions.In contrast, Group 4 comprised entirely of healthy controls, all of whom presented with normal hepatocardiac function. Group 5 presented a unique case among the categories.Participants in this group showed poor liver conditions. However, according to the guidelines for cardiac diastolic function assessment, their heart function was generally unremarkable, with only a minority of indicators deviating significantly. Support Vector Machine (SVM), Random Forest Tree (RFT), and Multilayer Perceptron (MLP) were employed for multi-classification tasks on the test dataset. The average accuracies achieved by these models were 70%, 81%, and 84%, respectively.Conclusions:By combining liver combined ultrasonic elasticity, cardiac VFM technology and TDA technology to construct a patient similarity network, we successfully identified patients with liver fibrosis who did not show abnormalities in conventional cardiac indicators but may have potential abnormal cardiac function, which has important implications for guiding the selection of clinical intervention measures, and optimizing patient management stratification.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To explore the protective mechanism of transdifferentiation of glomerular endothelial cells based on the differentiated embryonic chondrocyte gene 2 (DEC2) via the TGF-β/ROCK1 signaling pathway. Methods The 24 mice were randomly divided into sham group, UUO group, UUO combined with vector group and UUO combined with DEC2 group, with 6 mice in each group. A unilateral ureteral obstruction (UUO) model was established in each group, except for the sham group. In the UUO combined with vector group and UUO combined with DEC2 group, 10 μL (10⁸ PFU) of vector or DEC2 was injected into each kidney on day 0 (immediately after UUO) under the guidance of the ultrasound system. The mice were sacrificed 14 days after the operation, and the kidneys were collected for histological examination and Western blot analysis: HE staining was used to observe the histological changes of kidneys, Masson staining to observe the renal fibrosis, and Western blot analysis to detect the protein expression. In vitro, normal human glomerular endothelial cells (GEnCs) was selected as the research objects. GEnCs stimulated with TGF-β were treated with ROCK1 inhibitor Y-27632 or DEC2 transfection. Western blot analysis was used to detect the expression of ROCK1, α-SMA, DEC2 and E-cadherin in GEnC exposed to transforming growth factor β (TGF-β). The localization of ROCK1 and DEC2 in GEnCs cells was detected by immunofluorescence cytochemistry. The relationship between the ROCK1 and DEC2 was confirmed by co-immunoprecipitation. Results Compared with the sham group, the UUO groups showed significant renal fibrosis and collagen accumulation on the 14th day. In the UUO groups, the expression of DEC2 and E-cadherin in the kidney tissue of the mice was significantly reduced, and the expression of α-SMA significantly increased. Compared with the UUO combined with vector group, the kidney fibrosis and collagen accumulation in the UUO combined with DEC2 group decreased, and the expression of ROCK1 and α-SMA decreased and the expression of DEC2 and E-cadherin increased in the kidney tissue. TGF-β enhanced the expression of ROCK1 and α-SMA in GEnCs cells in a time-dependent manner, and the levels of DEC2 and E-cadherin decreased. Treatment with the ROCK1 inhibitor Y-27632 partially abrogated the TGF-β-induced increase in the expression of ROCK1 and α-SMA and decrease in the expression of DEC2 and E-cadherin. In addition, transfection of GEnCs cells with DEC2 before TGF-β stimulation reduced the expression of ROCK1 and α-SMA, and increased the expression of DEC2 and E-cadherin. Immunofluorescence cytochemical staining showed that DEC2 co-localized with ROCK1 in GEnCs, and the co-immunoprecipitation showed that DEC2 and ROCK1 pulled down each other. Conclusions DEC2 is down-regulated in fibrotic renal tissue, while up-regulated DEC2 inhibits epithelial myofibroblast transdifferentiation and renal fibrosis of GEnC by blocking TGF-β/ROCK1 signaling pathway.
Humans ; Animals ; Mice ; Cell Transdifferentiation ; Chondrocytes ; Endothelial Cells ; Cadherins ; Signal Transduction ; rho-Associated Kinases

OBJECTIVE To explore the effects of irbesartan（Irb）combined with 5-fluorouracil（5-FU）on the proliferation and extracellular signal-regulated kinase （ERK）/peroxidase proliferator-activated receptor γ（PPARγ）signaling pathway of Lewis lung cancer cells. METHODS Lewis lung cancer cells from mice were divided into normal control （NC）group，Irb low-dose （LD）group（1×10－3 mmol/L），Irb high-dose （HD）group（1×10－1 mmol/L），5-FU group （10 μmol/L），Irb LD+ 5-FU group （Irb 1×10－3 mmol/L+5-FU 10 μmol/L）and Irb HD+ 5-FU group （Irb 1×10－1 mmol/L+5-FU 10 μmol/L）. MTT method was used to measure the activity of cell proliferation in each group. Plate colony formation experiment was used to determine the number of cell colonies formed in each group ；Western blot method was used to detect the expression levels of proliferating cell nuclear antigen （PCNA），p53，ERK1/2，p-ERK1/2 and PPAR γ protein in each group. RESULTS Compared with the NC group ，the cell proliferation activity ，the number of colonies formed and the protein levels of PCNA ，p-ERK1/2，and PPARγ were significantly reduced in the other five groups ，and the protein level of p 53 was significantly increased （P＜0.05）；the protein expression of ERK1/2 had no significant difference （P＞0.05）. The changes of above indexes in Irb LD+ 5-FU group and Irb HD+ 5-FU group were more significant than Irb LD group ，Irb HD group and 5-FU group （P＜0.05）. CONCLUSIONS Irb combined with 5-FU can inhibit the proliferation of Lewis lung cancer cell ，and the effect is better than that of the two alone. The mechanism may be related to the inhibition of ERK/PPARγ signal pathway.

Objective:To explore the lesion characteristics and predictors of invasive coronary angiography (ICA)-verified obstructive lesions with fractional flow reserve (FFR)>0.80, that is, anatomy-function mismatch.Methods:A total of 515 obstructive vessels in 419 coronary disease patients from 11 Chinese medical centers undergoing coronary CT angiography and ICA and FFR were retrospectively analyzed. All vessels had one target lesion with diameter stenosis ≥50 % by ICA. There were 229 vessels in the match group (FFR≤0.80) and 286 vessels in the mismatch group (FFR>0.80). The lesion characteristics including lesion territory, the distance of the coronary artery ostium to the proximal end of the lesion, minimum lumen area, reference lumen area, plaque length and burden, plaque volume and component volume, remodeling index and plaque morphological complexity were measured and compared between the two groups. Optimal thresholds of quantitative plaque characteristics were defined by Yoden index. Logistic regression analysis was used to analyze the predictors of anatomy-function mismatch. Area under receiver operating characteristic curve (AUC) was used to analyze the ability of different lesion features to predict mismatched lesions.Results:The coronary stenosis, plaque burden and length, plaque volume (including each component volume) in the mismatch group were smaller than those in the match group, and FFR, minimum lumen area were larger (all P<0.05). Left anterior descending artery (LAD) lesion and severe complex plaque were more common in the match group than the mismatch group with a statistically significant difference. Univariate logistic regression analysis showed that LAD lesion, minimum lumen area>4 mm 2, plaque burden and length, plaque calcification volume<27 mm 3, plaque lipid volume<30 mm 3, plaque fiber volume<150 mm 3 and plaque morphological complexity were predictiors of anatomic function mismatched lesions; Multivariate logistic regression showed that the minimum lumen area>4 mm 2 (OR=3.371, 95%CI 1.903-5.973, P<0.001), plaque lipid volume<30 mm 3 (OR=3.014, 95%CI 1.691-5.373, P<0.001), plaque morphological complexity (mild OR=17.772, 95%CI 8.072-39.128, P<0.001, moderate OR=6.383, 95%CI 3.739-10.896, P<0.001) were independent predictors of mismatched lesions. The AUC of the model based on the minimum lumen area, plaque lipid volume and morphological complexity was 0.824, which was superior to either of the plaque feature alone ( P<0.001). Conclusions:The minimum lumen area, lipid volume and plaque morphological complexity are independent predictors of the anatomical-functional mismatch lesions, and the combination can significantly improve the prediction value.

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.