Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. Decreased portal vein velocity is the most important risk factor for cirrhotic PVT, and the etiology and severity of liver cirrhosis, hemostasis status, and inflammatory and immune mechanisms may also be associated with the development of cirrhotic PVT. The natural history of cirrhotic PVT includes improvement, stabilization, progression, and recurrence. Non-occlusive PVT and improvement of liver function may be associated with spontaneous improvement of cirrhotic PVT. The impact of different occlusion degree of cirrhotic PVT on patients' prognosis is inconsistent. Non-occlusive PVT may not significantly affect patients' outcomes; occlusive PVT may increase the risk of death, and PVT involving the mesenteric veins may also lead to intestinal ischemia and infarction. Clinical management strategies for cirrhotic PVT include wait-and-see strategy (no intervention), anticoagulation, thrombolysis, and transjugular intrahepatic portosystemic shunt (TIPS). When the degree of PVT is less than 50% and the mesenteric veins are not involved, immediate intervention may not be required. Anticoagulation is the first-line choice for cirrhotic PVT requiring treatment. Thrombolysis and TIPS are mainly used for patients with contraindications of anticoagulation and those who do not respond to anticoagulation. This paper reviews the clinical assessment of cirrhotic PVT and its predictors, natural history, impact on prognosis, treatment, and prophylaxis.

Objective To explore the alternative value of internal jugular vein collapsibility index (IJVCI) and subclavian vein collapsibility index (SCVCI) used to substitute for inferior vena cava collapsibility index (IVCCI) in volume evaluation under spontaneous breathing and mechanical ventilation. Methods A total of 100 patients were selected who underwent elective surgery in the Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University from December 2020 to August 2021, the cyclic indicators of patients with different respiratory states were compared. According to the cut-off value of IVCCI, the patients were divided into hypovolemic group and non-hypovolemic group, and the cyclic indicators of the two groups were compared under different respiratory states. Pearson correlation analysis and Bland-Altman analysis were used to determine the relevance and consistency between IJVCI, SCVCI and IVCCI. ROC curve was used to analyze the efficiency of IJVCI and SCVCI in volume evaluation. Results Under mechanical ventilation condition, compared to spontaneous breathing condition, the SpO₂ of patients was obviously increased, and heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), IVCCI, IJVCI and SCVCI were significantly decreased (P<0.01). IJVCI and SCVCI in non-hypovolemic group were significantly lower than those in hypovolemic group under the condition of spontaneous respiration (P<0.001). Under the condition of mechanical ventilation, SBP in non-hypovolemic group was significantly increased than that in hypovolemic group (P<0.05), while IJVCI and SCVCI were significantly lower than those in hypovolemic group (P<0.001). Under the condition of spontaneous breathing and mechanical ventilation, there was a significant positive correlation and consistency between IJVCI and IVCCI (r=0.586, P<0.01; r=0.514, P<0.001), and that a significant positive correlation and consistency between SCVCI and IVCCI (r=0.385, P<0.01; r=0.521, P<0.01). The area under the ROC curve (AUC) of IJVCI and SCVCI for the diagnosis of hypovolemia was 0.828, 0.684, and the best cut-off value was 22.2%, 25.4% under the condition of spontaneous breathing. The AUC of hypovolemia diagnosed by IJVCI and SCVCI were 0.701, 0.773, and the best cut-off value was 19.8%, 13.2% under the condition of mechanical ventilation. Conclusion Both IJVCI and SCVCI can replace IVCCI for volume evaluation in different respiratory states, but the alternative value of IJVCI is higher in spontaneous breathing state while of SCVCI is higher in mechanical ventilation state for volume evaluation.

Infection is a common complication and leading cause of death in liver cirrhosis patients. In recent years, people gradually recognize the vital impact of infection, especially spontaneous bacterial peritonitis, on the course and prognosis of liver cirrhosis patients. Timely and effective empiric antibiotic therapy is particularly critical for the treatment of liver cirrhosis patients with bacterial infection. However, due to the spread of multidrug resistant bacteria and extensively drug-resistant bacteria, infection in cirrhosis has also become a difficult problem. At the same time, we have a clearer understanding on the pathogenesis of infection in cirrhosis. Novel therapeutic methods, such as intestinal microecological intervention and immunoregulatory therapy, have also become research hotspots recently. Establishing an effective treatment plan for liver cirrhosis patients with bacterial infections is the key to improve the survival rate and quality of life of these patients.

Objective To explore the risk factors of thrombotic events in trauma patients by using random forest algorithm. Methods The data of 255 trauma patients admitted to the intensive care unit from July 2016 to December 2021 were retrospectively analyzed. These patients were divided into thrombosis group and non-thrombosis group by propensity score matching and according to the occurrence of thrombosis after trauma. The risk factors of 24 clinical variables including age, gender, injury severity score (ISS), acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), white blood cell count, red blood cell count, platelet count, hemoglobin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, total protein, prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, fibrin degradation products, D-dimer, antithrombin 3, coagulation reaction time (CRT), clot formation rate, clot formation kinetics and maximum clot strength (maximal amplitude, MA) within 2 hours after admission were analyzed by random forest algorithm. The predictive values of the variables were evaluated by receiver operating characteristic (ROC) curve and verified by bootstrap method. Results One hundred and ten trauma patients were divided into thrombosis group (n=22) and non-thrombosis group (n=88) by propensity score matching. The results of random forest algorithms showed that high MA level was an important risk factor for thrombotic events after trauma(P<0.05). The area under ROC curve (AUC) of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.56-0.81, P<0.01), and the bootstrap method confirmed that the AUC of using MA value to predict thrombotic events in trauma patients was 0.70 (95%CI 0.57-0.80, P<0.01). When the cut-off value of MA was 63.3 mm, the sensitivity and specificity of the trauma patients suffering thrombotic events were 63.6% and 78.4%, respectively. Conclusion The high MA level is an important risk factor for thrombotic events in trauma patients.

Objective To investigate the action mechanism of Xibining decoction on mitigation of pain of knee osteoarthritis (KOA) through regulation of redox homeostasis of synoviocytes by carnitine palmitoyl transferase 1 (CPT1) enzyme. Methods Fibroblast-like synovial cells (FLS) were extracted from rats' knee joint and the optimal concentration of the freeze-dried powder of Xibining decoction on FLS was selected by CCK-8. Subsequently, the cells were divided into control group, KOA group and Xibining group. The inflammatory environment of KOA was induced by 5 μg/ml lipopolysaccharide (LPS) in the last two groups, and in Xibining group, 100 μg/ml Xibining were added and cultured for 24 hours. The mRNA and protein expressions of CPT1 and carnitine/organic cation transporters 1 (OCTN1) were detected by Real-time PCR and Western blotting. The activities of CPT1 and superoxide dismutase (SOD) and malondialdehyde (MDA) content were detected by assay kits. Reactive oxygen species(ROS) level was detected by a 2',7'-dichlorofluorescein diacetate assay. The dorsal root ganglion (DRG) neurons were extracted from rats and identified by βⅢ-tubulin and glial fibrillary acidic protein (GFAP) immunofluorescence. The neurons were divided into control group, KOA group and Xibining group, the FLS supernatants of the three groups were added to the DRG for 24 hours. The mRNA and protein expression of transient receptor potential A1 ion channel (TRPA1) were detected by Real-time PCR and Western blotting. Ca²⁺ influx in DRG neurons after TRPA1 opening was observed by Real-time fluorescent calcium imaging. ELISA assay was used to detect the content of calcitonin gene related peptide (CGRP) and substance P (SP) in DRG supernatant. Results The ideal freeze-dried powder of Xibining decoction concentration was identified as 100 μg/ml. Real-time PCR and Western blotting results showed that the expression levels of mRNA and protein in CPT1 and OCTN1 of Xibining group were significantly higher than those in KOA group (P<0.05). Compared with control group, the average fluorescence intensity and MDA contents increased significantly in KOA group [(5.52±0.78) AU vs. (26.46±2.07) AU; (2.77±0.03) nmol/ml vs. (3.13±0.02) nmol/ml] (P<0.05); the activities of CPT1 and SOD were significantly downregulated [(11.50±0.21) nmol/min vs. (4.98±0.02) nmol/min; (17.6±0.07) U/ml vs. (11.38±0.05) U/ml] (P<0.05). Compared with KOA group, the fluorescence intensity and MDA contents significantly decreased in Xibining group [(14.07±1.41) AU and (2.87±0.01) nmol/ml] (P<0.05), the activities of CPT1 and SOD [(7.94±0.21) nmol/min and (13.81±0.07) U/ml] were significantly upregulated (P<0.05). Compared with KOA group, after treatment with FLS supernatant in Xibining group, the mRNA and protein expression of TRPA1, and Ca²⁺ influx after TRPA1 opening were inhibited in DRG (P<0.05). In addition, the expression of CGRP and SP were also reduced in Xibining group [(19.93±1.2) ng/L vs. (30.19±1.58) ng/L, P<0.05; (84.23±1.26) ng/L vs. (123.16±2.95) ng/L, P<0.05]. Conclusion Xibining can regulate the local redox homeostasis of FLS through CPT1 enzyme, which can further influence the Ca²⁺ influx on the TRPA1 ion channel of DRG and reduce the secretion of pain factor to alleviate KOA pain.

Objective To explore the effect of miR-491-5p on the apoptosis of trophoblast cells induced by hypoxia and the process of preeclampsia. Methods Human trophoblast cells were divided into control group, hypoxia group, hypoxia+miR-491-5p mimic group and hypoxia+miR-491-5p inhibit group. Cell viability staining was used to detect hypoxia-induced trophoblast cell apoptosis. qRT-PCR was used to detect the expression of miR-491-5p in hypoxia-induced trophoblast cells; TargetScan database to predict miR-491-5p target; Detection of dual-luciferase reporter gene was used to confirm the targeting relationship between miR-149-5p and BCL2l2; miR-491-5p mimic and inhibitor single-stained embryonic trophoblast cells, qRT-PCR was used to detect the expression of miR-491-5p. Western blotting was used to detect changes of BCL2l2 expression in trophoblast after overexpression and inhibition of miR-491-5p; cell viability staining, Western blotting, and flow cytometry to detect trophoblast apoptosis. Results Compared with control group, the hypoxia group had significantly increased cell apoptosis and increased expression of miR-491-5p (2.784±0.214 vs. 1.000±0.000, P<0.01); bioinformatics detection and dual luciferase detection report experiments showed that miR-491-5p can targete and regulate BCL2l2 expression. Compared with control group, the miR-491-5p content in hypoxia+miR-491-5p mimic group was significantly increased (7659.300±191.300 vs. 5.467±0.503, P<0.05), while that in miR-491-5p inhibit group was the opposite (0.139±0.022 vs. 0.323±0.035, P<0.01). Compared with hypoxia group, the apoptosis rate of trophoblast cells was decreased (11.56%±0.452% vs. 16.67%±0.750%, P<0.01), the expressions of BCL2L2 (0.702±0.047 vs. 0.312±0.007, P<0.001) and Bcl-2 (0.752±0.055 vs. 0.415±0.005, P<0.01) were increased, and the expression of Bax (1.221±0.066 vs. 1.652±0.085, P<0.01) was decreased in hypoxia+miR-491-5p inhibit group; but in hypoxia+miR-491-5p mimic group, the apoptosis rate was increased (23.54%±1.233% vs. 16.67%±0.750%, P<0.001), the contents of BCL2L2 (0.211±0.013 vs. 0.312±0.007, P<0.01) and Bcl-2 (0.203±0.011 vs. 0.415±0.005, P<0.001) was decreased, and Bax (2.362±0.284 vs. 1.652±0.085, P<0.01) expression was increased. Conclusions miR-491-5p might negatively regulates the expression of BCL2L2, increases the apoptosis of trophoblast cells induced by hypoxia and accelerates the development of preeclampsia.

Objective To explore the role of mitochondrial copy number (MCN) of embryos in the outcome of embryo transfer in patients with poor ovarian response (POR) and the correlation with mother's age, embryonic karyotype and blastocyst grade. Methods A retrospective analysis was performed of 75 patients with normal ovarian reserve (NOR) and 74 patients with POR who underwent in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidies (PGT-A) in the Sixth Medical Center of Chinese PLA General Hospital from September 2018 to October 2020. The blastocysts obtained after IVF were biopsied(NOR group: 205; POR group: 135), and 116 and 44 euploid blastocysts were obtained, respectively. The MCN of embryos in different clinical outcomes of each group were analyzed and compared, and the correlations of embryo MCN with maternal age, embryo karyotype and blastocyst grade were analyzed by multiple linear regression analysis. Results The mean MCN of biopsy blastocysts and euploid blastocysts were lower in POR group than those in NOR group with statistically significant difference (biopsy blastocysts: 267.4±174.0 vs. 319.0±264.8, P<0.05; euploid blastocysts: 216.0±95.7 vs. 305.4±273.2, P<0.01). Regardless POR group or NOR group, the MCN of early aborted embryos was higher than that of live embryos with statistically significant difference(POR group: 303.3±95.4 vs. 158.9±36.3, P<0.01; NOR group: 486.0±356.7 vs. 258.0±137.9, P<0.05). Multiple linear regression analysis showed the MCN of embryos in POR and NOR groups had no correlation with embryo karyotype and blastocyst grade, but was positively correlated with the mother's age (POR group: β=0.185, P=0.035; NOR group: β=0.215, P=0.002). Conclusion Higher MCN may be more likely to cause early miscarriage in POR patients, and the embryonic MCN was correlated with maternal age.

Objective To explore the factors influencing hospitalized new-onset overt hepatic encephalopathy (OHE) in hospitalized patients with hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF), and to construct an individualized risk prediction model. Methods A total of 310 HBV-ACLF patients admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from December 2016 to December 2020 were selected, and divided into non-hepatic encephalopathy group(n=236), hepatic encephalopathy group (n=74) according to whether OHE occurred after admission. The general data, laboratory test indicators, and model of end-stage liver disease (MELD) scores were compared between the two groups; univariate and multivariate logistic regressions were used to analyze the factors influencing the hospitalized new-onset OHE in HBV-ACLF patients after admission. A nomogram model was constructed with the influencing factors. The receiver operating characteristic (ROC)curve and the calibration curve was used to evaluate the discrimination and calibration of the model, and decision curve analysis(DCA) was used to evaluate the clinical validity of the model. Results Compared with the non-hepatic encephalopathy group, the baseline international normalized ratio [2.71(2.20, 3.44) vs. 1.98(1.70, 2.55)], serum alanine aminotransferase [987.50(450.50,1538.00) U/L vs. 561.00(191.00, 1090.50) U/L], blood aspartate aminotransferase [830.00(257.75, 1518.25) U/L vs. 381.00(153.50, 872.00) U/L], plasma Ammonia [71.75(57.75, 109.50) μmol/L vs. 57.00(41.80, 79.60) μmol/L], white blood cell count [7.93(6.43, 9.74)×10⁹/L vs. 6.62(5.33, 8.16)×10⁹/L], hemoglobin [136.50 (126.25, 151.50) g/L vs. 126.00(115.00,143.00) g/L], and the proportion of patients in intermediate and advanced stages (56.8% vs. 23.3%) of the hepatic encephalopathy group were higher, the difference was statistically significant; the alpha-fetoprotein level was lower [56.33(23.61, 139.03) ng/L vs. 88.25(31.32, 216.88) ng/L, P=0.033], the difference was statistically significant (P<0.001). The results of multivariate logistic regression analysis showed that baseline international normalized ratio (OR=2.56, 95%CI 1.61-4.30, P<0.001), age (OR=1.06, 95%CI 1.02-1.10, P=0.003), plasma ammonia (OR=1.02, 95%CI 1.01-1.03, P=0.005), blood white blood cell count (OR=1.24, 95%CI 1.07-1.43, P=0.003), hemoglobin (OR=1.03, 95%CI 1.00-1.05, P=0.026) were the independent influencing factors of hospitalized new-onset OHE in HBV-ACLF patients. The area under the ROC curve (AUC) of the nomogram model established in this study was 0.848(95%CI 0.798-0.897), and the MELD model was 0.723(95%CI 0.654-0.793). The maximum bias (Emax)=0.143 and the minimum bias (Eavg=0.041 between the nomogram model and the ideal model, the model has a good degree of discrimination,S:p=0.676. Through the calibration test, the model predicted value is consistent with the actual value. The performance was good, the decision curve showed that the threshold was in the range of 0.05 to 1.0, and the net benefit rate of the nomogram model was higher than that of the MELD model. Conclusions Age, international normalized ratio, white blood cell count, plasma ammonia, and hemoglobin are the factors influencing hospitalized new-onset OHE in HBV-ACLF patients. Nomogram constructed from five independent influencing factors can more accurately predict the risk of hospitalized new-onset OHE in this population, thus having a good clinical application value.

Objective To explore the phenotypes of erythroblastic island-like (EBI-like) macrophages during erythroid differentiation from human embryonic stem cells in vitro and the function of EBI-like macrophages in the differentiation of erythroid. Methods To study the function of EBI- like macrophages in the differentiation of erythroid, we used the Spin-EB method to induce human embryonic stem cells (hESCs) to differentiate into red blood cells. The expression of specific surface markers of erythrocytes and macrophages and the cell morphology were tested by flow cytometry and imaging flow cytometry. Multiple gene expressions were detected by qRT-PCR. An immunofluorescence assay was used to identify the phenotype of EBI-like macrophages. Results Erythroid cells were induced by embryonic stem cells in vitro. Giemsa staining revealed that EBI-like structures derived from the hESCs were similar to natural EBI. Immunofluorescence staining confirmed that the erythroid cells (CD235a) were surrounded by macrophages (CD68); CD45⁺CD235a⁺CD163⁺CD169⁺CD106⁺ EBI-like macrophage (0.092%±0.013%) resembles in vivo EBI macrophage. Imaging flow cytometry observed that CD45⁺CD235a⁺CD163⁺CD106⁺CD169⁺ EBI-like macrophages were surrounded by CD235a⁺ erythroid cells. The proportion of induced CD71⁺CD235a⁺ cells was 37.37%±1.68% after removing the EBI structure, which was significantly lower than the untreated group (46.97%±4.16%). We found that central macrophages of EBI-like may play a role in promoting erythroid differentiation through the interaction of CD169 and CD43. Conclusions EBI-like structure in the erythroid induction system of hESCs is similar to the natural EBI. The central EBI-like macrophages maybe promote the differentiation of erythrocytes in vitro through the interaction of CD169 and CD43. We provided a theoretical and practical reference for optimizing the erythroid induction system in vitro.

Objective To explore the molecular mechanism of a classic traditional Chinese medicine compatibility combination of Astragalus membranaceus (A.m) and Angelica sinensis (A.s) in treatment of diabetes mellitus with cardiovascular complications. Methods The BATMAN database was used to analyze A.m and A.s respectively. The chips data related to diabetes mellitus with cardiovascular complications were retrieved from GEO database. The differential genes were analyzed by GEO2R to construct the protein-protein interaction (PPI) network, and the key target genes of A.m-A.s were obtained by topology, and DAVID database was used for gene ontology (GO) and KEGG pathway enrichment analysis of key genes. A total of 20 SD rats were randomly divided into healthy control group, diabetes mellitus complicated with cardiovascular complications group, metformin group, and A.m-A.s group (5 each). All the rats except those in HC group were fed with high fat and high sugar feeds, and used to establish the model of diabetes mellitus with cardiovascular complications. The expressions of PI3K and Akt3 in cardiomyocytes of the rats in each group were observed. Results (1) A total of 1332 target genes related to A.m-A.s combination were analysis obtained from BATMAN database, and 3 chip data files related to diabetes with cardiovascular diseases (GSE26887, GSE43950 and GSE46262)were retrieved from GEO database including 2759 differential genes screened by GEO2R analysis and 247 key genes of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications. (2) The protein-protein interaction (PPI) network diagram of key targets was constructed by STRING database, and the "A.m-A.s- active ingredients-targets" network was constructed by Cytoscape 3.7.2. The functional enrichment analysis with DAVID database showed that the biological process of A.m-A.s in treatment of diabetes mellitus and cardiovascular complications was mainly concentrated in positive and negative regulation of RNA polymerase II promoter transcription, redox process, signal transduction, apoptosis process, inflammatory reaction, and positive regulation of cell proliferation, etc. The signaling pathways mainly include metabolic pathway, cancer pathway, TNF signaling pathway, cAMP signaling pathway, cGMP-PKG signaling pathway, PI3K-Akt signaling pathway, non-alcoholic fatty liver disease pathway, and insulin resistance pathway and so on. (3) The animal model experiment with SD rats in vivo of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications suggested that, compared with healthy control group, the expressions of PI3K and Akt3 decreased in cardiomyocytes of the untreated model group, and the difference was statistically significant (P<0.05, P<0.01); the expressions of PI3K in the treatment groups were higher than that in the model group, but lower than that in the healthy control group, and the difference was statistically significant (P<0.01). Conclusion The characteristics of A.m-A.s combination in treatment of diabetes mellitus with cardiovascular complications are "multi-components, multi-targets and multi-pathways", and multiple key genes and signal pathways can play important roles. Further research is expected to broaden the ideas of diagnosis and treatments of diabetes with traditional Chinese medicine.