Antithrombin â ¢ is a Novel Predictor for Contrast Induced Nephropathy After Coronary Angiography.

BACKGROUND/AIMS: Antithrombin Ⅲ (AT Ⅲ) is an important endogenous anticoagulant and has strong anti-inflammatory properties. Low ATⅢ activity is considered to be a predictor of poor outcomes in several conditions, including acute kidney injury after cardiac surgery. However, the association between the ATⅢ level and the occurrence of contrast induced nephropathy (CIN) has not been elucidated. In this study, our aim was to identify the potential predictive value of ATⅢ for CIN. METHODS: We enrolled a total of 460 patients who underwent coronary angiography (CAG) from January 2015 to December 2016 in coronary care units (CCU). ATⅢ activity in plasma collected before CAG was measured and <75% was considered low activity according to reference values. A cross-sectional study on CIN after CAG was conducted and the risk factors were analyzed. CIN was diagnosed according to the KDIGO guideline. RESULTS: Of these 460 patients undergoing CAG, 125 (27.17%) progressed to CIN. The incidence of CIN was significantly higher in patients with low ATⅢ activity compared to patients with normal ATⅢ activity (Pearson's chi-squared test P=0.002). As ATⅢ activity declined, the prevalence of CIN progressively increased, with the highest value (58.8%) in patients with an ATⅢ activity <60%. Moreover, the ATⅢ activity was significantly lower in CIN patients than in non-CIN patients (84.43±16.3% vs. 92.14±13.94%, P<0.001). After multivariable analysis, ATⅢ activity <75% remained a significant independent predictor of CIN (OR 2.207,95%CI [1.29-3.777]; P=0.004) as well as baseline serum creatinine (OR 1.009,95%CI [1.001-1.016]; P=0.026). CONCLUSIONS: Patients with low ATⅢ activity had a higher risk of developing CIN after CAG. The initial ATⅢ activity may be a novel independent predictor for CIN.

Underestimated incidence of kidney disease in nonrenal outpatient.

BACKGROUND AND AIMS: Chronic kidney disease (CKD) has been regarded as a severe threaten to public health, a large percentage of CKD are secondary to other diseases. Serum creatinine is the most common marker of renal function, but it did not always reflect glomerular filtration rate (GFR) accurately. In order to investigate the prevalence of kidney disease in non-renal departments and to provide a basis for the prevention of kidney injury, the present study was conducted in several medical centers. METHODS: A total of 17,462 outpatients were selected randomly from the departments of cardiology, endocrinology, and neurology in 16 hospitals and the incidence of kidney disease was screened. Estimated GFR (eGFR) was calculated by using MDRD-formula. RESULTS: There are 5293 (30.1%) patients' eGFR above 90 mL/min/1.73m2 among all the subjects in non-renal departments, and 4055(23%) patients' eGFR lower than 60 mL/min/1.73 m2 including 80 patients whose eGFR were below 15 mL/min/1.73 m2. Furthermore, among 16616 subjects who have a normal SCr level, there are 3209 respondents' eGFR lower than 60 mL/min/1.73 m2. Moreover, individuals with hypertension or diabetes had a high prevalence of decreased renal function. CONCLUSIONS: This survey indicated kidney injury wildly existed in non-renal outpatients, and the incidence of CKD is underestimated.

Prognostic Value of Systemic Inflammation Score for Esophageal Cancer Patients Undergoing Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The link between inflammation and cancer survival has been the subject of substantial research. The goal of this review is to summarize the evidence on the prognostic value of systemic inflammation score (SIS) in esophageal cancer patients undergoing surgical intervention. METHODS: PubMed, Scopus, Embase, and Web of Science were searched for relevant articles published until 30th June 2022. We pooled adjusted data on overall survival (OS) and disease-free survival (DFS) using a random-effects meta-analysis model. The review was pre-registered on PROSPER (No. CRD42022340717). RESULTS: Eight studies were included. All studies were conducted either in China or Japan. Six studies showed that patients with SIS of 1-2 had poor OS as compared to those with scores of 0 (HR:1.42 95% CI: 1.24, 1.62 I2=25%). SIS of 1 (HR:1.45 95% CI: 1.18, 1.78 I2=0%) and 2 (HR:1.94 95% CI: 1.49, 2.53 I2=0%) were also associated with poor OS. Two studies compared the SIS score of 2 vs 0-1. Meta-analysis indicated that poor OS was associated with SIS of 2 (HR:1.80 95% CI: 1.25, 2.58). Data from three studies showed that the SIS score did not predict DFS (HR:1.40 95% CI: 0.82, 2.39 I2=91%). CONCLUSION: SIS can be a novel prognostic indicator for esophageal cancer patients undergoing surgical intervention. Higher SIS is associated with a poor OS, but it does not predict DFS. Future studies are needed to strengthen the current evidence.

Accuracy of 2D and point shear wave elastography-based measurements for diagnosis of esophageal varices: a systematic review and meta-analysis.

PURPOSE The aim of this meta-analysis is to summarize the diagnostic accuracies of point shear wave elas- tography (pSWE) and two-dimensional (2D) SWE for esophageal varices (EV) and varices needing treatment (VNT). METHODS We conducted a systematic review and meta-analysis of diagnostic accuracy studies. We searched for studies reporting the EV and VNT diagnostic accuracy of pSWE and 2D SWE using PubMed Cen- tral, SCOPUS, MEDLINE, Embase, and Cochrane databases. STATA software"Midas"package was used for meta-analysis. RESULTS A total of 24 studies with 3867 patients were included in the review. Pooled score sensitivities of pSWE were 91% (95% CI, 80%-96%) for EV, and 94% (95% CI, 86%-97%) for VNT. Pooled score sensi- tivities of 2D SWE were 78% (95% CI, 69%-85%) for EV, and 79% (95% CI, 72%-85%) for VNT. Pooled score specificities of pSWE were 70% (95% CI, 60%-78%) for EV, and 59% (95% CI, 40%-75%) for VNT. Pooled score specificities of 2D SWE for EV were 79% (95% CI, 72%-85%) 72% (95% CI, 66%-77%) for VNT. We found significant heterogeneity for all the elastography-based measurements with the chi- square test results and an I2 statistic >75%. CONCLUSION Both pSWE and 2D SWE can diagnose EV and VNT with moderate diagnostic accuracy. Further large- scale setting-specific longitudinal studies are required to establish the best modality.

The significance of platelet activation in ankylosing spondylitis.

The objective of this study was to explore the significance of platelet activation in patients with ankylosing spondylitis (AS). Thirty-five AS patients and 15 normal controls were selected from November 2005 to October 2006. The number of CD62P- and CD63-positive cells were detected by flow cytometry. At the same time, the erythrocyte sedimentation rate (ESR), platelet count (PLT) and C-reactive protein (CRP) were determined in both groups. The percentage of CD62P-positive cell in AS patients (13.60 +/- 7.64%) was significantly higher than that in control group (2.78 +/- 1.04%; P < 0.01). The percentage of CD63-positive cell in AS patients (6.92 +/- 4.16%) was significantly higher than that in control group (4.13 +/- 1.85%; P < 0.05). The levels of CRP (20.18 +/- 23.17 mg/l), PLT (259.54 +/- 102.59 x 10(9)/l) and ESR (36.86 +/- 31.23 mm/h) in AS patients were higher than those in normal controls, respectively (3.21 +/- 2.18 mg/l, P < 0.01; 197.00 +/- 55.70 x 10(9)/l, P < 0.01; 12.25 +/- 5.05 mm/h, P < 0.05). Platelet activation may be a sign of AS exacerbation.

CD14-159 and -260 gene polymorphisms are associated with HBV-related cirrhotic injury in Chinese Han patients.

The present study aimed to investigate the association between TLR4 mutations (Asp299Gly and Thr399Ile) and CD14 polymorphisms (base pair -159 and -260) with HBV-related cirrhosis in Chinese Han patients. By use of a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis technique, we genotyped Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile and CD14-159 and -260 polymorphisms in 110 HBV-related cirrhotic patients and 110 healthy controls from the Chinese Han population. We found significant differences in the genotypes and allele frequencies of CD14-159 (but not -260) between healthy controls and liver cirrhotic patients, and both the CD14-159 and -260 genotypes were significantly different among Child-Pugh grades in cirrhotic patients. No TLR4 Asp299Gly and Thr399Ile mutations were detected in any cirrhotic patients or healthy controls in the Chinese Han population. These findings indicated that the polymorphisms of CD14, but not TLR4 Asp299Gly and Thr399Ile mutations, may be an important genetic factor for HBV-related cirrhotic injury in the Chinese Han population.

The significance of platelet activation in rheumatoid arthritis.

We evaluated the significance of platelet activation in patients with rheumatoid arthritis (RA). The expression of CD62P and CD63 by platelets was determined using flow cytometry in 18 active RA patients, 10 remission RA and 15 normal controls. Meanwhile, the erythrocyte sedimentation rate (ESR) and C-reactive protein was also determined in all groups. The expression of CD62P in active RA patients (11.88 +/- 2.47%) was significantly higher than that in remission RA group (2.85 +/- 1.60%; P < 0.01) and control group (2.78 +/- 1.04%; P < 0.01). The expression of CD63 in active RA patients (9.90 +/- 3.02%) was significantly higher than that in remission RA group (4.11 +/- 2.00%; P < 0.01) and control group (4.13 +/- 1.85%; P < 0.01). The level of CRP (54.33 +/- 23.35 mg/l) and ESR (86.06 +/- 33.67 mm/h) in active RA patients was higher than that in remission RA group (2.55 +/- 1.01 mg/l, 14.70 +/- 4.57 mm/h; P < 0.01 for both) and normal control group (3.21 +/- 2.18 mg/l, 12.25 +/- 5.05 mm/h; P < 0.01 for both). There was a positive correlation between CD62P and ESR (r = 0.5224, P < 0.01) and also a positive correlation between CD62P and CRP (r = 0.7048, P < 0.01) as well as between CD63 and ESR (r = 0.4476, P < 0.05) but no correlation between CD63 and CRP. Platelet activation may be a sign of RA exacerbation.

[Study on the expressions and roles of renal heat shock protein 72 and Toll-like receptor 4 in hepatorenal syndrome in rat].

OBJECTIVE: To explore the expressions and roles of renal heat shock protein 72(HSP72) and Toll-like receptor 4(TLR4) during development of hepatorenal syndrome in rat. METHODS: Following bile duct ligation (BDL), a biliary cirrhosis and hepatorenal syndrome rat model was reproduced. The blood, the renal and hepatic tissues of the rats were examined at 1, 2, 4 and 6 weeks (6 rats were used in each week) after BDL. Blood was withdrawn from the femoral vein and centrifuged. The plasma concentrations of alanine aminotransferase (ALT), total bilirubin (TBil), blood urea nitrogen (BUN) and creatinine (Cr) were measured, and those of the HSP72 and tumor necrosis factor-alpha (TNF-alpha) were assessed with enzyme linked immunosorbent assay (ELISA). After weighing liver and kidney and expressions of HSP72 and TLR4 in renal tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. All data were compared with control group (C group). RESULTS: The plasma levels of ALT, TBil at each week and of BUN, Cr at 4 and 6 weeks were increased significantly (all P<0.05). The concentration of plasma HSP72 and the expressions of renal HSP72 mRNA and protein were lower (especially at 4 and 6 weeks, both P<0.01) in BDL rats compared with sham operation rats. But the plasma TNF-alpha levels and renal TLR4 (mRNA and protein) expressions were significantly higher than those of sham operation rats (all P<0.01). CONCLUSION: Decreased expression of renal HSP72 may contribute to activate the TLR4- initiating inflammatory signal pathway, attributing partly to the pathogenesis of hepatorenal syndrome in biliary cirrhosis.

Role of ultrasound and microbubble-mediated heat shock protein 72 siRNA on ischemia-reperfusion liver injury in rat.

OBJECTIVE: To explore the ultrasound-guided gene transfection as well as the role of heat shock protein 72 (HSP72) siRNA combined with ultrasound micro-bubble contrast agents on rat hepatic ischemia-reperfusion injury. METHODS: 72 SD rats were divided into non-surgery group (group N), sham-operation group (group P) and liver ischemia-reperfusion groups (I/R). In each group, rats were further divided into 4 subgroups according to the different intravenous treatment: 220 ul saline solution (group A); 20 ul HSP72 siRNA plasmid vector + 200 ul saline solution (group B); 20 ul HSP72 siRNA plasmid vector + 200 ul ultrasound microbubble contrast agent (group C); 20 ul HSP72 siRNA plasmid vector + 200 ul ultrasound microbubble contrast agent + ultrasonic irradiation target region with MI1.0 (group D). RESULTS: Certain degree hepatic tissue injury was observed in rats of group I/R A, B and C. The expressions of liver tissue HSP72 mRNA and HSP72 protein and the concentrations of peripheral blood HSP72, ALT and TNF-α were significantly increased at each I/R subgroup (vs group N and group P, P < 0.01). Among them, the plasma concentrations of ALT, HSP72, and TNF-α and the liver tissue expressions of HSP72 mRNA and HSP72 protein at group A were significantly higher than groups B, C and D (P < 0.01). And group D was significantly lower than that of group A, B and C (P < 0.01). CONCLUSION: The liver tissue expressions of HSP72 mRNA and HSP72 protein and the liver injury degree of ischemia-perfusion were significantly reduced after the HSP72 siRNA was combined with micro-bubble and radiated directionally by ultrasound.

[The experimental study on the expression of toll-like receptor 2 in fulminant hepatic failure].

OBJECTIVE: In order to explore the role of toll-like receptors 2 (TLR2) in initiating inflammatory response, the expression of TLR2 of the liver and IL-18, TNF-alpha and IFN-gamma of plasma in fulminant hepatic failure was analysed. METHODS: D-galactosamine (D-Gal, 900 mg/kg) and lipopolysaccharide (LPS, 10 microg/kg) were administered intraperitoneally into the BALB/C mice. To evaluate the hepatic injury, serum transaminase (ALT and AST) and plasma IL-18, TNF-alpha and IFN-gamma were determined and the mortality was observed at various time points following the intraperitoneal injection. The level of TLR2 mRNA was measured by semiquantitative RT-PCR. The protein expression of TLR2 in the liver was detected by immunohistochemistry. The data was analyzed by SAS software. RESULTS: After 4 hours of intraperitoneal injection of D-Gal/LPS, the serum transaminase and plasma IL-18, TNF-alpha and IFN-gamma levels were elevated. The treated mice began to die at 7 hours. The mortality reached up to 80% at 10 h. TLR2 mRNA was expressed at a low level in liver tissues of normal mice, while it was significantly increased and maintained at a higher level following intraperitoneal injection with D-Gal/LPS. The expression of TLR2 protein was similar to that of the TLR2 mRNA, and the expression of TLR2 mRNA was positively correlated with the concentration of plasma IL-18, TNF-alpha and IFN-gamma (r=0.36, P=0.02; r = 0.48, P 0.003; r = 0.72, P<0.001) at different time points. CONCLUSIONS: Our results showed that TLR2 was involved in initiating and inducing the expression of proinflammation cytokines in this model of fulminant hepatic failure. The results suggest that adjusting the expression of TLR2 might be a new strategy in preventing the development of infectious diseases

Correlation analysis of peripheral DPYD gene polymorphism with 5-fluorouracil susceptibility and side effects in colon cancer patients.

OBJECTIVE: To investigate the correlation of peripheral DPYD gene polymorphism with 5-fluorouracil (5-FU) susceptibility and side effect in patients with colon cancer. METHODS: The total DNA of peripheral mononuclear cells was extracted in 100 cases of colon cancer patients. Quantitative PCR was conducted to measure DPYD gene 14G1A, A1627G, T85C 3 loci polymorphism, and analyze the correlation of 5-FU susceptibility, side effects with DPYD gene polymorphism. RESULTS: Mutations were detected at position 14G1A (mutation rate 14%), A1627G (mutation rate 11%), and T85C (mutation rate 17%). The effective rate of 3 loci of wild type was significantly higher than that of mutant type (P < 0.05). With respect to side effects such as myelosuppression, hand-foot syndrome, diarrhea, and gastrointestinal reactions, the incidence in mutation type was significantly higher than that in the wild type (P < 0.05). CONCLUSION: DPYD gene polymorphism plays a guiding role in predicting efficacy and toxicity of 5-FU, which can be used as an important reference index of 5-FU individualized administration scheme.