Portal vein thrombosis (PVT) is one of the most common complications of liver cirrhosis. The formation of PVT can increase the mortality rate of cirrhotic patients and adversely affect the successful implementation and prognosis of liver transplantation. A hypercoagulable state is a unique mechanism underlying PVT formation in cirrhotic patients. In recent years, the pathogenesis of PVT has gradually been elucidated, with specific mechanisms including the following aspects: systemic and local inflammatory responses lead to vascular endothelial cell dysfunction, thereby promoting the activation of the coagulation system; abnormal activation of the monocyte-macrophage system exacerbates local inflammation, enhancing platelet adhesion and aggregation, and facilitating thrombus formation; an imbalance between the coagulation and fibrinolytic systems results in a sustained hypercoagulable state; and intestinal microbiota dysbiosis induces inflammation and metabolic disturbances, thereby increasing the risk of PVT. This article summarizes the latest research progress on these key mechanisms and their interactions, providing new insights into the molecular and cellular mechanisms of PVT. It also offers directions for the early diagnosis of PVT and the exploration of novel intervention strategies in the future.

Atherosclerosis(As)is a chronic inflammatory disease associated with lipid deposition.Copper is con-sidered to be an important trace element and is closely related to the occurrence and development of As.Excessive accu-mulation of copper ions in cells can induce cell death,a new type of cell death named"cuproptosis".Under normal con-ditions,the body's copper metabolism can control the copper level in a stable range.When the disease occurs,copper ho-meostasis is destroyed,intracellular copper overload produces cytotoxicity,induces oxidative stress,inflammation,cell py-roptosis and cuproptosis,and promotes the occurrence and development of As.This article summarizes the relationship between copper levels and As,and discusses the mechanism of cuproptosis and the pathological mechanism of copper over-load promoting As from the perspective of the body's copper regulation,and reviews the relevant drug intervention,expec-ting to provide a new therapeutic target for As.

Gut microbiota dysbiosis is an avenue for the promotion of atherosclerosis (AS) and this effect is mediated partly via the circulating microbial metabolites. More microbial metabolites related to AS vascular inflammation, and the mechanisms involved need to be clarified urgently. Paeonol (Pae) is an active compound isolated from Paeonia suffruticoas Andr. with anti-AS inflammation effect. However, considering the low oral bioavailability of Pae, it is worth exploring the mechanism by which Pae reduces the harmful metabolites of the gut microbiota to alleviate AS. In this study, ApoE^-/- mice were fed a high-fat diet (HFD) to establish an AS model. AS mice were administrated with Pae (200 or 400 mg·kg^-1) by oral gavage and fecal microbiota transplantation (FMT) was conducted. 16S rDNA sequencing was performed to investigate the composition of the gut microbiota, while metabolomics analysis was used to identify the metabolites in serum and cecal contents. The results indicated that Pae significantly improved AS by regulating gut microbiota composition and microbiota metabolic profile in AS mice. We also identified α-hydroxyisobutyric acid (HIBA) as a harmful microbial metabolite reduced by Pae. HIBA supplementation in drinking water promoted AS inflammation in AS mice. Furthermore, vascular endothelial cells (VECs) were cultured and stimulated by HIBA. We verified that HIBA stimulation increased intracellular ROS levels, thereby inducing VEC inflammation via the TXNIP/NLRP3 pathway. In sum, Pae reduces the production of the microbial metabolite HIBA, thus alleviating the ROS/TXNIP/NLRP3 pathway-mediated endothelial inflammation in AS. Our study innovatively confirms the mechanism by which Pae reduces the harmful metabolites of gut microbiota to alleviate AS and proposes HIBA as a potential biomarker for AS clinical judgment.
Animals ; Mice ; Atherosclerosis/drug therapy* ; Diet, High-Fat ; Endothelial Cells ; Inflammation/drug therapy* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Reactive Oxygen Species

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Population genomics, an interdiscipline of genomics and population genetics, is booming in recent years with the rapid growth number of deciphered genomes and revolutionizes the understanding of bacterial population diversity and evolution dynamics. It also largely improves the prevention and control of infectious disease through providing more accurate genotyping and source-tracing results and more comprehensive characteristics of emerging pathogens. In this review, taking one of the best characterized bacteria, Escherichia coli, as model, we reviewed the phylogenetic relationship across its five major populations (designated A, B1, B2, D and E); and summarized researches on molecular mutation rate, selection signals, and patterns of adaptive evolution. We also described the application of population genomics in responding against large-scale outbreaks of E. coli O157:H7 and E. coli O104:H4. These results indicated that, although being a novel discipline, population genomics has played an important role in deciphering bacterial population structures, exploring evolutionary patterns and combating emerging infectious diseases.

Population genomics, an interdiscipline of genomics and population genetics, is booming in recent years with the rapid growth number of deciphered genomes and revolutionizes the understanding of bacterial population diversity and evolution dynamics. It also largely improves the prevention and control of infectious disease through providing more accurate genotyping and source-tracing results and more comprehensive characteristics of emerging pathogens. In this review, taking one of the best characterized bacteria, Escherichia coli, as model, we reviewed the phylogenetic relationship across its five major populations (designated A, B1, B2, D and E); and summarized researches on molecular mutation rate, selection signals, and patterns of adaptive evolution. We also described the application of population genomics in responding against large-scale outbreaks of E. coli O157:H7 and E. coli O104:H4. These results indicated that, although being a novel discipline, population genomics has played an important role in deciphering bacterial population structures, exploring evolutionary patterns and combating emerging infectious diseases.

Objective To derive a questionnaire to assess the risk of developing motor complications through a 3-year prospective investigation on 71 patients of Parkinson' s disease (PD) in the out clinic at our hospital.Methods Three years after the first assessment,71 PD out patients were reassessed using various scales,including Unified Parkinson Disease Rating Scale,Hoehn-Yahr grade,Mini Mental State Exam,Hamilton Depression Scale and Hamilton Anxiety Scale.Results The incidence of motor complications was 43.6％ (31/71).Logistic regression analysis showed that the prognostic factors for motor fluctuation were age of onset ≤ 54 (OR =6.4,95％ CI 1.7-24.5,P =0.006),the occurrence of swallowing difficulty (OR =3.8,95 ％ CI 1.0-14.1,P =0.04) and depression (OR =4.0,95 ％ CI 1.1-13.7,P =0.03),and the prognostic factors for dyskinesia were age of onset ≤54 (OR =48.5,95％ CI 1.9-121.0,P:0.02),the occurrence of falling (OR =64.1,95％ CI 2.9-142.2,P =0.008) and the daily levodopa dosage ＞ 600 mg(OR =17.5,95％ CI 1.1-276.2,P =0.04).Based on the regression model,the assessment questionnaire for motor complicationsincludes the followings:the questionnaire for motor fluctuations:the age of onset ≤54,2 points; the occurrence of swallowing difficulty,1 point; the occurrence of depression,1 point; the questionnaire for dyskinesia:the onset age ≤54,2 points; the occurrence of falling,3 points; daily levodopa dosage ＞ 600 mg,2 points.In all patients in this study,21.7％ (10/46) was asscssed to a total scorc of 0-1 which is associated with a low risk of motor fluctuation,8/16 had a score of 2 which is associated with intermediate risk and 8/9 got a score of 3-4 associated high risk; 10.2％ (5/49) had a score of 0-2,a low risk of dyskinesia,4/13 had a score of 3-4,a intermediate risk and 7/9 got a score of 5-7 which is associated with a high risk.Conclusions Age onset ≤54,the occurrence of swallowing difficulty,falling and depression,daily levodopa dosage ＞ 600 mg were considered to be the prognostic factors of motor complications in PD.The questionnaire may help to stratify PD patients into low-risk,medium-risk and high-risk groups for motor complications and the higher the score in the questionnaire is related to the higher risk of motor complications.

Objective To improve self-management of diabetics with role lack.Methods A total of 121 diabetics with role lack were enrolled and received mass education and individual counseling.Serum levels of glucose and lipid profiles and body mass index (BMI) were assessed and compared before and after intervention by using paired t test.Results Knowledge on diabetes ( 79.37 ± 12.45 vs 31.69 ± 9.36,t =2.860,P ＜ 0.05) and self-management skills ( 9.21 ± 2.85 vs 4.43 ± 1.72,t =2.812,P ＜ 0.05 ) were significantly improved after receiving health education,although fasting plasma glucose [ ( 6.3 ± 1.8 ) vs (8.1 ±2.1) mmol/L,t =2.736,P ＜0.05],2-h postprandial blood glucose [(8.1 ±3.7) vs (12.8 ±4.1)mmol/L,t =3.549,P ＜ 0.05 ],glycosylated hemoglobin Alc [ (6.4 ± 2.5 ) ％ vs (7.1 ± 2.7 ) ％,t =2.603,P ＜ 0.05 ],total cholesterol [ ( 5.2 ± 2.3 ) vs ( 6.3 ± 2.4 ) mmol/L,t =2.036,P ＜ 0.05 ],triglyceride [(1.7±0.7) vs (2.4±0.8) mmol/L,t=2.368,P＜0.05] and BMI [(25.6±6.2) vs (27.3±6.5)kg/m2,t =2.546,P ＜ 0.05 ] were largely decreased.Conclusion Health education could improve selfmanagement and cure of diabetic patient with role lack.

Objective To assess the development,progression and change of nonmotor symptoms in patients with Parkinson' s disease and its impact on patients' quality of life.Methods Eighty-seven consecutive patients with idiopathic Parkinson' s disease were studied.Parkinsonian status was assessed at baseline and 3 years follow-up using Unified Parkinson' s Disease Rating Scale (UPDRS) part Ⅲ & Ⅳ,Nonmotor Symptoms Questionnaire (NMSQuset),Parkinson-related quality of life (PDQ) scales.Paired ttest,Chi-square test,Spearman rank order correlation and hierarchical regression of the major statistical procedures were employed.Results At 3 years follow-up,compared to baseline,the UPDRS Ⅲ score (22.21 ±11.31 vs 30.49± 11.68),UPDRS Ⅳ score(1.00±1.54 vs 2.94±3.12),NMS score (7.98±3.96 vs 12.35 ± 5.12) and PDQ score (28.11 ± 22.88 vs 36.65 ± 26.95) were significantly higher ( t =- 5.54,- 5.75,- 6.46,- 5.29,all P =0.000,respectively).The aggravation of motor and nonmotor symptoms caused the decline of quality of life.The prevalence of constipation,problem of remembenng thing,nocturia ranked tops,and depression,and anxiety were still in the middle,compared with baseline.The prevalence of pains,sweating,dribbling,sense of incomplete emptying etc were significantly increased during the follow-up,△R2 were 21.6％ and 23.4％ respectively,resulting in the deterioration of quality of life.Conclusions PD nonmotor symptoms appear from the early stage.The motor and nonmotor symptoms aggravate over time.