The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study.

PURPOSE: We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). METHODS: The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). RESULTS: 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6-19.8) in combined therapy and 8.2 months (95% CI, 5.7-10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1-5 BMs (HR = 1.808, P = 0.012). CONCLUSIONS: Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1-5 BMs reduce the risk of extracranial recurrence.

A nomogram for the prediction of renal outcomes among patients with idiopathic membranous nephropathy.

The early prediction of renal outcomes in patients with idiopathic membranous nephropathy (iMN) remains challenging. The present retrospective study evaluated patients with iMN confirmed by renal biopsy. An optimized Cox regression model and a nomogram were constructed for the early prediction of renal outcomes. A total of 141 patients who met the inclusion criteria were evaluated in the present study. In total 18 (12.8%) patients eventually progressed to the endpoint, 6 of whom developed end-stage renal disease, and one patient died during follow-up. The optimized model demonstrated that 24-h proteinuria [hazard ratio (HR) 1.24; 95% CI, 1.10-1.40; P-value <0.001] and chronic tubulointerstitial injury [referred to as grade 0, grade 1 (HR), 5.12; 95% CI, 1.33-19.75; P-value=0.02] or grade 2 (HR, 6.43; 95% CI, 1.35-30.59; P-value=0.02) were independent risk factors for a poor renal outcome. Patients with an estimated three-year renal survival rate (ETR) less than 0.87 had a high risk of a poor renal outcome. In addition, patients with an ETR of 0.87 to 0.98 more quickly developed a decreased estimated glomerular filtration rate after two years of follow-up. In the present study a nomogram for the early prediction of renal outcomes in patients with iMN was developed. This nonogram suggested that patients with an ETR of 0.87-0.98 should receive greater attention during follow-up.

Determination of Water Content of Nitrogen Containing Hydrogen Sulfide by Karl Fischer Coulometric Titration.

Measuring the water content in natural gas is important for safety; however, complex matrixes make the results inaccurate. Natural gas contains hydrogen sulfide (H2S), which react with iodine (I2), causing Karl Fischer coulometric titration (KFCT) to give higher results. The KFCT method for the determination of water content of nitrogen containing H2S was investigated. A chilled mirror hygrometer offered a reference water content to calibrate the KFCT. The interfering of H2S was reduced by subtracting I2 consumed by H2S according to the reaction mechanism of ISO 10101; however, the modified results remained higher. A possible reaction mechanism with a stoichiometry of H2S to I2 of 1:2.5 was proposed. The improved KFCT method had an error of water content no more than (3 + 2%·x) mg/kg (x, water content in mg/kg) and had the potential of online monitoring of natural gas.

Serum C3/C4 ratio is a novel predictor of renal prognosis in patients with IgA nephropathy: a retrospective study.

IgA nephropathy (IgAN) is an autoimmune disease associated with complement activation. It is unclear whether the ratio of serum C3 and C4 concentrations (C3/C4 ratio) can predict renal outcomes in IgAN patients. A total of 1503 patients diagnosed with IgAN via renal biopsy were recorded in this study. Poor renal outcomes were defined as > 50% decrease in the baseline estimated glomerular filtration rate (eGFR) or development of end-stage renal disease (ESRD) during follow-up. In total, 712 patients meeting the exclusion/inclusion criteria were selected, and the mean follow-up period was 40.6 (12.34) months. Patients with decreased C3/C4 ratios displayed significantly more severe clinical characteristics and renal pathological features and a higher proportion of poor renal outcomes and ESRD. The optimal multivariate Cox regression models identified the C3/C4 ratio (hazard ratio (HR) 0.63, 95% CI 0.5-0.9), serum uric acid (HR 1.58, 95% CI 1.2-2.2), serum creatinine (HR 1.3, 95% CI 1.1-1.6), systolic blood pressure (HR 1.57, 95% CI 1.2-2.0) and T score (relative to T0, T1: HR 1.96, 95% CI 1.1-3.7, T2: HR 3.03, 95% CI 1.6-5.9) as strong predictors of poor renal outcomes. Subgroup analysis showed that patients with low C3/C4 ratios benefited from glucocorticoids or other immunosuppressive agents (hazard ratio 0.30 and 0.18, 95% CI 0.13-0.72 and 0.07-0.46, respectively). Serum C3/C4 ratios may be an independent novel predictor of renal outcomes in IgAN patients. Decreased C3/C4 ratios suggest poor renal outcomes and the potential to benefit from aggressive immunosuppressive therapies.

Relationship between Serum Soluble Klotho Protein and Coronary Artery Calcification and Prognosis in Patients on Maintenance Hemodialysis.

BACKGROUND: We aimed to investigate the relationship between serum soluble Klotho protein (sKlotho) level and coronary artery calcification (CAC) as well as prognosis in patients with maintenance hemodialysis (MHD). METHODS: Overall, 128 adult patients with end-stage renal failure treated with MHD were collected in the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Zhejiang Province, China in 2013. Serum sKlotho was detected by ELISA and coronary artery calcification was measured by multi-slice spiral computed tomography (MSCT). With 36 months' follow-up, death notes such as cause of death and death time were recorded. RESULTS: Patients were divided into low sKlotho group and high sKlotho group. Age, blood phosphorus level, hypertension incidence and incidence of diabetes mellitus of the patients in low sKlotho group was significantly higher than that of high sKlotho group (P<0.05). The coronary artery calcification score (CACs) of patients in high sKlotho group was significantly lower than that of low sKlotho group (P<0.001). Logistic regression showed that the decrease of sKlotho level (P<0.001) was an independent risk factor for CAC progression. The mortality of the patients in low sKlotho group was higher than that of high sKlotho group. Kaplan-Meier survival curve had shown that survival time of the patients in low sKlotho group was significantly lower than that of high sKlotho group (P<0.05). CONCLUSION: SKlotho can increase the degree of CAC. Although MHD patients with low sKlotho level had shorter survival time, sKlotho is not an independent risk factor in prediction of prognosis of MHD patients.

Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients.

OBJECTIVE: The correlation of serum fibroblast growth factor 23 (FGF-23) and Klotho protein levels with bone mineral density (BMD) in maintenance hemodialysis (MHD) patients was analyzed. METHODS: Between January 2015 and November 2015, 125 MHD patients in our hospital were enrolled. Dual-energy X-ray absorptiometry was used to examine the BMD in the femoral neck and lumbar spine of MHD patients. The patients were divided into three groups: a normal bone mass group, an osteopenia group, and an osteoporosis group. An ELISA was performed to measure serum FGF-23, Klotho protein, and 1,25(OH)2VitD3 levels. Other parameters, including calcium (Ca), phosphorus (P), and parathyroid hormone, were also measured. RESULTS: Of the 125 MHD patients, 82.40% of patients had femoral neck osteopenia, and 56.00% of patients had lumbar spinal osteopenia. The serum FGF-23 level was highest in the osteoporosis group. However, there was no significant difference in serum FGF-23 levels among the three groups, depending on femoral neck and lumbar spinal BMD (P > 0.05). Spearman's correlation analysis also pointed to a lack of correlation between serum FGF-23 levels and BMD. Among the three groups, there were significant differences in serum Klotho protein levels and femoral neck BMD (P < 0.05). Serum Klotho protein levels in the osteoporosis group were clearly lower than those in the normal bone mass group and osteopenia group (P < 0.05). Similarly, serum Klotho protein levels were significantly lower in those with lumbar spinal osteopenia as compared with those in the normal group. There was a positive correlation between serum Klotho protein levels and BMD and T values for the femoral neck and lumbar spine. The results of a multiple linear regression analysis revealed that the serum Klotho protein level was one of the main factors affecting BMD in MHD patients. CONCLUSIONS: The serum level of FGF-23 was not correlated with a change in BMD of MHD patients, whereas the serum Klotho protein level was associated with the degree of BMD. A high Klotho protein level may decrease the severity of chronic kidney disease and mineral bone disorder (CKD-MBD) in MHD patients with low BMD.

Renal outcomes in primary IgA nephropathy patients with segmental glomerular necrosis: a case-control study.

The renal prognosis and treatment of primary IgA nephropathy (IgAN) patients with segmental glomerular necrosis (SGN) remain controversial. Patients with primary IgAN confirmed by renal biopsy were enrolled. Patients with SGN on renal biopsy were selected as the necrosis group, and a propensity score matching method was used to match a control group according to age, gender, weight, height and follow-up time. A total of 825 IgAN patients were enrolled in the present study. Seventy-three (8.8%) patients with SGN were selected as the necrosis group, and 292 patients without SGN were matched as the control group. Compared to the control group, a significantly increased serum fibrinogen level (3.97 g/L vs 3.54 g/L, P=.002) and proportion of patients with macroscopic hematuria (35.6% vs 14.7%, P<.001) was observed in the necrosis group. According to the new IgA pathological classification system, crescent formation was more pronounced in the necrosis group (P=.001). The average estimated glomerular filtration rate was obviously higher in the necrosis group and decreased more slowly during follow-up. However, the time-averaged urine protein-to-creatinine ratio remained low in the necrotic group, whereas it gradually increased in the control group. SGN suggests an active renal inflammatory state, but it was not an independent risk factor for a poor renal outcome in patients treated with immunosuppressive therapy. Furthermore, patients with SGN had a more stable renal function and low urinary protein excretion during follow-up, which may be attributable to aggressive immunotherapy.

Elevated serum fibrinogen level is an independent risk factor for IgA nephropathy.

BACKGROUND: IgA nephropathy is a primary cause of renal failure, and inflammation and renal fibrosis are the main mechanisms leading to kidney damage. The serum fibrinogen level is closely related to inflammatory states, but its relationship to the prognosis of IgA nephropathy (IgAN) is unclear. MATERIALS AND METHODS: 1053 patients diagnosed with IgAN after renal biopsy were enrolled from two Nephrology Departments. Demographic and clinical data and histopathological features were collected. The patients were divided into four groups (Q1-Q4) according to the serum fibrinogen levels at the time of renal biopsy, and the relationships of serum fibrinogen levels with other risk factors and the prognosis of IgAN were investigated. RESULTS: 672 patients with proven primary IgAN were included in this study, which included a median follow-up of 36 months. Patients with higher serum fibrinogen levels had elevated serum creatinine levels, 24-hour urinary protein, and blood pressure compared with patients with the lowest levels of serum fibrinogen as well as severe renal damage at the time of renal biopsy. Univariate and multivariate Cox regression analyses confirmed that the serum fibrinogen level at the time of renal biopsy was significantly related to the prognosis of patients with IgAN. CONCLUSIONS: In patients with IgAN, an elevated serum fibrinogen level at the time of renal biopsy is associated with poor renal outcomes, which suggests the need for more aggressive early interventions. Greater benefits of aggressive treatments were observed in patients with higher serum fibrinogen levels.

Increased C4 and decreased C3 levels are associated with a poor prognosis in patients with immunoglobulin A nephropathy: a retrospective study.

BACKGROUND: An association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy (IgAN) remains controversial. METHODS: We conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN. Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from the Second Affiliated Hospital of Wenzhou Medical College, China, and various parameters were documented during follow-up until 2015. The definition of the primary endpoint was a decrease of estimated glomerular filtration rate (eGFR) more than 30% from their baseline levels. RESULTS: A total of 403 patients (55.3% female, average 33.7 months of follow-up) were identified and enrolled, with the primary endpoint occurring in 39 (9.8%) patients. Among the patients selected, 202 (50.1%) received corticosteroid treatment alone or in combination with another immunosuppressant (GS group), while others did not receive immunosuppressive treatment (non-GS group). The incidence of the primary endpoint was slightly lower in the GS group compared to the non-GS group (7.0% versus 12.6%, p = 0.06). Multivariate Cox proportional-hazard regression analyses, adjusting for age, systolic and diastolic blood pressure, 24-h urine protein, and immunosuppressive therapy, showed that serum complement 4 (C4) levels (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.8, p < 0.001) and serum complement 3 (C3) levels (HR 0.6, 95% CI 0.2-0.6, p < 0.001) were significantly associated with a poor prognosis among patients with IgAN. CONCLUSIONS: We demonstrated that an increase in serum C4, as well as a decrease in C3, was an important outcome determinant for patients with IgAN. Testing serum C3 and C4 levels might assist in predicting renal outcomes among these patients.

Brazilin Ameliorates Diabetic Nephropathy and Inflammation in db/db Mice.

Hyperglycemia and inflammation play important roles in the pathogenesis of diabetic nephropathy (DN). Brazilin might be an effective pharmacological agent against hyperglycemia and inflammation. In our present study, we explored whether brazilin mitigated pathological progression, inflammation, and extracellular matrix (ECM) accumulation in a mouse model of diabetic nephropathy. Brazilin reduced aggravated biochemical indices of DN (proteinuria and the serum glucose level) and renal hypertrophy. Brazilin also improved renal morphology and inhibited macrophage infiltration, as manifested by different pathological staining methods. Brazilin reduced the levels of pro-inflammatory cytokines and CD68, a macrophage marker, in the kidney cortex, as revealed by both RT-PCR and western blotting experiments. Furthermore, brazilin significantly downregulated the serum levels of pro-inflammatory cytokines and chemokines. Interestingly, brazilin significantly upregulated the levels of the anti-inflammatory factor IL-10, and prevented ECM accumulation. Brazilin reduced nuclear translocation of the NF-κB p65 subunit both in vitro and in vivo. Thus, brazilin might be a useful treatment for DN, through mitigating hypoglycemia, inflammation, and ECM accumulation.

Chlorogenic Acid Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting TLR4/NF-κB Signal Pathway.

Chlorogenic acid (CGA), a polyphenolic compound, exists widely in medicinal herbs, which has been shown a strong antioxidant and anti-inflammatory effect. This study investigated the protective effects and mechanism of CGA on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Treatment of CGA successfully ameliorates LPS-induced renal function and pathological damage. Moreover, CGA dose-dependently suppressed LPS-induced blood urea nitrogen (BUN), creatinine levels, and inflammatory cytokines TNF-α, IL-6, and IL-1ß in serum and tissue. The relative proteins' expression of TLR4/NF-κB signal pathway was assessed by western blot analysis. Our results showed that CGA dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. CGA also suppressed LPS-induced TNF-α, IL-6, and IL-1ß production both in serum and kidney tissues. Furthermore, our results showed that CGA significantly inhibited the LPS-induced expression of phosphorylated NF-κB p65 and IκB as well as the expression of TLR4 signal. In conclusion, our results provide a mechanistic explanation for the anti-inflammatory effects of CGA in LPS-induced AKI mice through inhibiting TLR4/NF-κB signaling pathway.

The attenuation of chlorogenic acid on oxidative stress for renal injury in streptozotocin-induced diabetic nephropathy rats.

The present study was undertaken to investigate whether chlorogenic acid (CGA) could protect kidney function against oxidative stress in the diabetic nephropathy (DN) rats. The treatment with CGA could decrease significantly the levels of blood glucose, blood urea nitrogen and serum creatinine in DN rats. Moreover, CGA significantly increased the activity of superoxide dismutase, glutathione peroxidase, and catalase. Moreover, the level of lipid peroxidation malondialdehyde was reduced markedly after CGA administration. Immunohistochemical analysis also showed that CGA downregulated significantly cyclooxygenase-2 protein expression in renal tissue, which is considered as one of the major pathogeneses of oxidative stress. Furthermore, we demonstrated that CGA could block the expression of activating transcription factor-6, C/EBP homology protein and the phosphorylation of eukaryotic initiation factor 2α and double stranded RNA-activated protein kinase-like endoplasmic reticulum kinase. In addition, we attempted to detect the presence of diabetic renal tissues apoptosis-related proteins. Our data provided evidence to support this fact that CGA attenuated oxidative stress in streptozocin-induced DN rats. Its molecular mechanism may inhibit the endoplasmic reticulum-stress response in DN.

Effect of angiogenesis inhibitor SU6668 in combination with 5-Fu on liver metastasis from transplantation tumors of human colorectal cancer in nude mice.

This study was to investigate inhibiting effect of angiogenesis inhibitor SU6668 in combination with 5-Fu on liver metastasis from human colon cancer. Results showed that metastasis rates in SU6668+5-Fu group, SU6668 group, 5-Fu group decreased obviously (P<0.01). Compared with 5-Fu group and control group, microvessel density significantly decreased in SU6668+5-Fu group and SU6668 group (P<0.05). Vascular endothelial growth factor and base fibroblast growth factor reduced obviously in SU6668+5-Fu group, SU6668 group and 5-Fu group compared with control group, and there were significant differences among SU6668+5-Fu group, SU6668 group and 5-Fu group (P<0.05). Thus, SU6668 can inhibit liver metastasis from colorectal cancer through anti-angiogenesis, and it would have a synergistic effect in combination with 5-Fu. Therefore, SU6668 combined with 5-Fu could be considered as a safe and effective antitumor strategy.

[The water content reference material of water saturated octanol].

The national standards of biofuels specify the technique specification and analytical methods. A water content certified reference material based on the water saturated octanol was developed in order to satisfy the needs of the instrument calibration and the methods validation, assure the accuracy and consistency of results in water content measurements of biofuels. Three analytical methods based on different theories were employed to certify the water content of the reference material, including Karl Fischer coulometric titration, Karl Fischer volumetric titration and quantitative nuclear magnetic resonance. The consistency of coulometric and volumetric titration was achieved through the improvement of methods. The accuracy of the certified result was improved by the introduction of the new method of quantitative nuclear magnetic resonance. Finally, the certified value of reference material is 4.76% with an expanded uncertainty of 0.09%.

[Effect of stromal cell-derived factor-1 and its receptor CXCR4 on liver metastasis of human colon cancer].

OBJECTIVE: To investigate the effect of chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 on liver metastasis of human colon cancer. METHODS: Expression of CXCR4 in different colon cancer cell lines and SDF-1 in different tissues were detected by using Western-blot technique. Effect of SDF-1 and anti-CXCR4 monoclonal antibody (McAb) on proliferation and migration of HT-29 cells were measured using MTT methods. Model mimicking liver metastasis of human colon cancer was established by injecting HT-29 cells intrasplenically into BALB/C nude mice. Mice were randomly divided into AMD3100 treated group and control group. Liver metastatic rate and tumor foci were measured 7 weeks after. RESULTS: HT-29 cells expressed higher level of CXCR4 protein, and liver tissue expressed higher level of SDF-1 protein. Compared with the control, SDF-1 could significantly induced the proliferation and migration of the HT-29 cells, and anti-CXCR4 McAb could inhibited both functions of SDF-1. The liver metastasis rate in the control group was 100%, and it was 40% in the AMD3100 treating group (P < 0.05). The mean liver metastasis number also significantly decreased by AMD3100 (7.8 +/- 2.6 vs 22.4 +/- 8.6, P < 0.05). CONCLUSIONS: SDF-1/CXCR4 biological axis play an important role in liver metastasis of human colon cancer. Arrest of CXCR4 can inhibit liver metastasis of colon cancer through blocking cell proliferation and migration induced by SDF-1.

Aberrant expression of SPARC and its impact on proliferation and apoptosis in ADPKD cyst-lining epithelia.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) results from a combination of environmental and genetic factors. Secreted protein acidic and rich in cysteine (SPARC) can be expressed by many different cell types and is associated with development, remodelling, cell turnover and tissue repair. The analysis of SPARC would help evaluate the effect of the unique matricellular glycoprotein on renal disease progression in ADPKD. METHODS: The concentration of SPARC was measured with an enzyme-linked immunosorbent assay (ELISA); distribution and expression levels were measured with in situ hybridization, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and western blot assays. Apoptosis was assessed by morphological observation and fluorescence-activated cell sorting (FACS) apoptosis index (AI) analysis. Cell cycle phase was examined by FACS analysis. Cell proliferation was studied using bromodeoxyuridine (BrdU) incorporation ELISA. RESULTS: The SPARC level in the renal cyst fluid of patients with ADPKD was greater than that in patients with simple renal cyst (SRC), and also greater than that found in the plasma and urine of patients with either ADPKD or SRC and normal subjects. SPARC mRNA and protein levels in polycystic renal tissue were greater than that in normal renal tissue. Additionally, SPARC could inhibit cyst-lining epithelial cell proliferation, bring about cell cycle arrest in the G0/G1 phase and induce apoptosis in vitro. SPARC treatment resulted in decreased mRNA levels of PCNA (proliferating cell nuclear antigen), MCM2 (minichromosome maintenance protein 2), ClnD1 and Bcl-2, but an increased mRNA level of p21(Waf1) in cyst-lining epithelial cells. CONCLUSION: Our findings suggest that the increased SPARC expression in ADPKD renal tissue may provide negative feedback in ADPKD patients.