OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice. METHODS: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl₄ to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting. RESULTS: Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs. CONCLUSIONS LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals ; Signal Transduction/drug effects* ; Mice ; Nucleotidyltransferases/metabolism* ; Mice, Inbred C57BL ; Acute-On-Chronic Liver Failure/etiology* ; Membrane Proteins/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Liver/metabolism* ; Disease Models, Animal ; Interferon Regulatory Factor-3/metabolism* ; Interleukin-6/metabolism* ; Male

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)erve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

Objective:To investigate the potential guiding role of fractional flow reserve(FFR) in surgical revascularization by comparing the relationship between coronary fractional flow reserve(FFR) and blood flow pattern status of bypass graft.Methods:A total of 86 patients with coronary artery disease between March 2016 to October 2019 were included in the study, with 59 males and 27 females; the age ranged from 42 to 77 years old, with an average of(58±12) years old. According to the measured FFR value of the left anterior descending artery, they were divided into severe ischemic group(FFR<0.75), boundary group(0.75≤FFR<0.80) and mild ischemic group(FFR≥0.80). Transit time flow meter(TTFM) was used to evaluate the blood flow status of the bridge vessel from the left internal thoracic artery to the left anterior descending coronary artery.Results:Mean graft flow(MGF) was measured at(21.24±5.71)ml/min, (18.25±7.72)ml/min, (16.47±7.83)ml/min in severe ischemic group, boundary group and mild ischemic group. The results of mean pulsatility index(PI) was 2.58±0.96, 3.14±1.19 and 3.53±1.34, the ratio of diastolic flow during the entire graft flow was 0.63±0.10, 0.55±0.11 and 0.53±0.11, patients appeared systolic reverse flow was 2 cases(3.6%), 3 cases(18.8%) and 3 cases (20.0%), respectively. There were statistically significant differences in MGF( P=0.027)、PI( P=0.007)、the ratio of DF( P=0.001) and the quantity of patients appeared systolic reverse flow( P=0.027) between the three groups. Conclusion:Due to increasing severity of coronary artery stenosis, MGF and the ratio of diastolic flow increased, and there appears to be an decreased PI and quantity of patients appeared systolic reverse flow. The chance of bypass graft occlusion may increase for the near and middle term in mild to moderate functional coronary artery stenosis(FFR≥0.75). For patients with severe functional coronary artery stenosis(FFR<0.75), it can obtain satisfactory flow parameters and ideal clinical outcomes.

Objective Metabolites produced by metabolic imbalance such as free fatty acids and lipopolysaccharides can result in a state of chronic low-grade inflammation, or metabolic inflammation, which plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders are closely related with the metabolic inflammation, which always coexist. Therefore, we proposed the concept ofmetabolic inflammatory syndrome ( MIS). According to our study, patients with two or more metabolic disorders above could be diagnosed as MIS. The current research is aimed to investigate the prevalence of MIS and its components, and to compare the clinical values of MIS and metabolic syndrome ( MS) . Methods 2 001 in patients with type 2 diabetes from 6 hospitals in Shanghai were recruited in the current multi-center cross-sectional study. The diagnostic rates of MIS and MS and their components of both syndromes were compared. Results In the patients with type 2 diabetes, the detective rate of MIS was 96. 2%, which was higher than that of MS (71. 3%). Among 4 components of MIS, atherosclerosis showed the highest detective rate (75.6%). MIS[OR=2.252(95%CI1.026-4.942),P=0.043],atherosclerosis[OR=2.726(95% CI1.953-3. 804),P<0. 001], and MS[OR=1. 915 (95%CI 1. 444-2. 540),P<0. 01] were the risk factors of coronary heart disease. Conclusion With atherosclerosis, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity as its 4 components, MIS has a high detective rate in patients with metabolic disorders, and seems to be more sensitive than MS to distinguish inflammation-related metabolic diseases. The concept of MIS will promote the screening and prevention of atherosclerosis in its early stage.

Objective To explore the clinical effect of autologous fat grafting in frontotemporal augmentation.Methods The fat granule was harvested from patient's abdomen or both medial knees by a multi-holed liposuction cannula attached to a syringe with negative pressure.Then the syringe was held vertically with the open end pointing downward until the fat and fluid were separated.The aqueous layer at the bottom and the oil layer on the top were discarded.The fat without being washed was directly transferred into 2 ml syringes and injected into bilateral temple and frontal depression area with a multi-plane,multi-tunnel,multi-point approach.The volume of injection was over 20％-30％.From March 2010 to March 2013,117 patients underwent this procedure.Results In all the 117 cases,there were no complications such as hematoma,induration,and infection.There were 11 cases (11.4％) in temple and 13 cases (20.0％) in frontal region achieved aesthetically-acceptable results after the second treatment.There was no statistically significant difference in secondary operation rates between the temple group and the frontal grouup (x2 =2.229,P＞0.05).Based on the followup for 3-36 months on all 117 cases,satisfactory results were obtained with improved frontotemporal contour and skin texture.The volume retention of transplanted fat was estimated between 60％ and 80％,which was based on subjective analysis of photographs.Conclusions Autologous fat grafting in frontotemporal depression is a convnient technique with reliable clinical results.It is also an optimal and safe method for facial rejuvenation and contouring remodeling.

Objective To investigate the relationship between heme oxygenase-1 (HO-1),glutathione S-transferase (GST) and cerebral atherosclerosis.Methods Cerebralvascular status was assessed with color flow Doppler sonography,transcranial Doppler (TCD),magnetic resonance angiography (MRA)or/and digital subtraction angiography (DSA) in patients with cerebral atherosclerosis (mild,moderate,and severity).Serum HO-1 and GST were measured with enzyme-linked immunosorbent assay (ELISA).Results In comparison between case and control groups,there was significant difference in age,hypertension,cerebral infarction,uric acid,and HO-1 (P =0.041,0.008,0.000,0.036,and 0.001).The level of serum HO-1 in the severe atherosclerosis was lower than that in the mild and moderate atherosclerosis (P =0.000 and 0.002).Logistic regression was used to find the association of HO-1 and the degree of cerebral atherosclerosis (P =0.000).Conclusions HO-1 might be related to cerebral atherosclerosis.