PqqF inhibits T6SS secretion by decreasing the pH in Serratia marcescens FS14.

Pyrroloquinoline quinone (PQQ) is a redox cofactor with numerous important physiological functions, and the type VI secretion system (T6SS) is commonly found in Gram-negative bacteria and plays important roles in physiological metabolism of the bacteria. In this study, we found that the deletion of pqqF enhanced the secretion of Hcp-1 in Serratia marcesens FS14 in M9 medium. Transcriptional analysis showed that the deletion of pqqF almost had no effect on the expression of T6SS-1. Further study revealed that the increased secretion of Hcp-1 was altered by the pH changes of the culture medium through the reaction catalyzed by the glucose dehydrogenases in FS14. Finally, we demonstrated that decreased pH of culture medium has similar inhibition effects as PQQ induced on the secretion of T6SS-1. This regulation mode on T6SS by pH in FS14 is different from previously reported in other bacteria. Therefore, our results suggest a novel pH regulation mode of T6SS in S. marcesens FS14, and would broaden our knowledge on the regulation of T6SS secretion.

Changes in Cerebral Blood Flow in Patients Who Receive Different Durations of Hemodialysis: An Arterial Spin Labeling MRI Study.

BACKGROUND AND PURPOSE: This study aimed to determine the changes in cerebral blood flow (CBF) in patients who received different durations of hemodialysis (HD) using arterial spin labeling magnetic resonance imaging. METHODS: The study included 46 patients who received HD and 24 demographically similar healthy controls (HCs). Patients who received HD were divided into three subgroups based on its duration: HD-1 (n=15, dialysis duration ≤24 months), HD-2 (n=16, dialysis duration >24 and ≤72 months), and HD-3 (n=15, dialysis duration ≥73 months). All subjects completed the Mini Mental State Examination and Montreal Cognitive Assessment tests, and the patients who received HD underwent laboratory tests. Group-level differences in the global and regional CBFs between patients who received HD and HCs were assessed. Correlation analysis was performed to evaluate the associations among CBF, clinical variables, and cognitive function. RESULTS: Compared with HCs, global and regional CBFs were significantly increased in the HD-1 and HD-2 groups (p<0.05), but there was no significant difference in the HD-3 group (p>0.05). However, compared with the HD-1 group, the HD-3 group had significantly decreased global and regional CBFs (p<0.05). The cognitive function was worse in patients who received long-term HD than in HCs. Increased dialysis duration and hemoglobin level were predictive risk factors for decreased CBF in patients who received long-term HD. CONCLUSIONS: Patients who received long-term HD with normal CBF had worse cognitive function, which may be related to increased dialysis duration.

Osteocalcin and Abdominal Aortic Calcification in Hemodialysis Patients: An Observational Cross-Sectional Study.

Objectives: To investigate the serum level of osteocalcin (OC), also known as bone Gla protein, in maintenance hemodialysis (MHD) patients and its correlation with abdominal aortic calcification (AAC). Methods: From July 2017 to February 2020, we enrolled 108 adult MHD patients. Routine fasting blood laboratory tests were performed before the start of the second hemodialysis in a week. Abdominal aortic calcification score (AACs) was assessed within 1 month. Pearson correlation and Logistic regression were used to analyze the data. Results: The OC level was 231.56 (25.92,361.33) ng/ml, elevating significantly in this group of MHD patients. It had a positive correlation with serum phosphorus (r = 0.511, P = 0.001), intact parathyroid hormone(iPTH) (r = 0.594, P = 0.0001), fibroblast growth factor 23(FGF23) (r = 0.485, P = 0.003) and a negative correlation with age(r = -0.356, P = 0.039). Based on the AACs, patients were divided into two groups. Serum OC level were higher in patients with AACs≥5 (p=0.032). A multiple logistics regression analysis revealed that age (odds ratio [OR]1.14, P=0.005) and OC(OR=1.10, P=0.008)were risk factors for high AACs(≥5). Conclusion: The study implicated that OC elevated significantly in this group of MHD patients.OC is positively correlated with phosphorus, iPTH, FGF23, and a negative correlation with age. OC was a risk factor for vascular calcification in this study, but this study did not classify osteocalcin as c-OC and unOC. Whether unOC is associated more directly with vascular calcification requires further study.

Effects of total parathyroidectomy treatment on parathyroid hormone levels, recurrent laryngeal nerve function, and the rate of infection complications of secondary hyperparathyroidism patients under image information health monitoring by magnetic resonance imaging.

In order to explore the application of computer information health monitoring technology in the evaluation of the treatment effect after total parathyroidectomy (T-PTX) for patients with Secondary Hyperparathyroidism (SHPT), preoperative magnetic resonance imaging (MRI) computer health monitoring technology was used to locate and diagnose the parathyroid glands. Autotransplantation were performed. The changes of total intact parathyroid hormone (iPTH) before and after surgery, serum Calcium (Ca), serum phosphorus (P), and alkaline phosphatase (ALP) were observed and recorded. The postoperative complications were observed. The postoperative recurrent laryngeal nerve injury was analyzed. The results showed that serum Ca, serum P, and iPTH of the patients were significantly decreased within 6 months after parathyroid gland resection compared with that before surgery (P < 0.05); however, there was no significant change in ALP level within one week after surgery (P > 0.05); after surgical treatment, the clinical symptoms of patients with bone pain, itchy skin, and restless leg syndrome were significantly decreased, and 2 cases of recurrent laryngeal nerve injury, and 1 case of new arrhythmia, with a complication rate of 7.14 %, which showed that MRI based on computer information technology had a good value in preoperative localization and diagnosis of the parathyroid gland in SHPT patients and lower the rate of postoperative infection and complications and the impairment of recurrent laryngeal nerve function.

Resibufogenin suppresses tumor growth and inhibits glycolysis in ovarian cancer by modulating PIM1.

Ovarian cancer is a common human malignancy of the female reproductive system. However, chemotherapy has been proven to have limited effectiveness in a majority of patients. Resibufogenin (RB) is a major active ingredient in cinobufacini, which has been used in the treatment of human malignancies as adjunct agents. This study was designed to examine the anti-cancer effect of RB and the underlying mechanisms in ovarian cancer. Our results showed that RB treatment resulted in cell death, cell cycle arrest, and apoptosis in ovarian cancer cells. The anti-growth and pro-apoptotic effects of RB were also validated in xenograft mice models. Proteomics analysis indicated that RB was able to alter the expressions of several genes, which were involved in the regulation of glycolysis. The suppression effect of RB in the glycolysis pathway of ovarian cancer cells was validated by decreased glucose consumption, lactate production, and extracellular acidification rate (ECAR). We proposed that PIM1 functioned as the key target that mediated the anti-cancer effect of RB against ovarian cancer cells. Our results have revealed that RB downregulated PIM1 in ovarian cancer cells and its downstream genes involved in glycolysis. Moreover, our results indicated that the anti-growth activities and suppressing effect of RB on glycolysis were enhanced significantly by PIM1 knockdown but was attenuated by ectopic PIM1 expression. This provided evidence to support the role of PIM1 in the anti-cancer activities of RB.

Evaluation of Intradialytic Hypertension Using Bioelectrical Impedance Combined With Echocardiography in Maintenance Hemodialysis Patients.

Although intra-dialytic hypertension (IDH) has been noted in clinical settings for many years, its pathogenesis remains unclear. In this cross-sectional study, we analyzed IDH incidence in our center and the correlation between postdialysis volume state and IDH. One hundred thirty-one maintenance hemodialysis (MHD) patients were enrolled in our study, and bioelectrical impedance (BIA) and echocardiography (ECG) were recorded. In addition, demographic data were collected, and laboratory examinations were conducted. The patients were grouped into four groups according to the change in systolic blood pressure (SBP) between predialysis and postdialysis. The incidence of IDH was 10.7%. The proportion of extracellular water to total body weight (ECW/TW), as evaluated by BIA, was significantly higher in the IDH group than in the other three groups both in pre-and post-dialysis. In particular, postdialysis SBP was highest in the highest tertile interval of ECW/TW. In addition, among the four groups, left ventricular volume (LVV) was highest in the IDH group. Binary logistic analyses revealed that predialysis SBP, postdialysis ECW/TW and LVV were independent risk factors of intradialytic hypertension. When predicting IDH, the AUC of the ROC curve was higher for ECW/TW combined with LVV (0.752, 95% CI 0.613-0.896) than for either LVV or ECW/TW alone. Our study further showed that post-dialysis volume expansion is an important factor for the development of IDH.

Sarcopenia in patients undergoing maintenance hemodialysis: incidence rate, risk factors and its effect on survival risk.

BACKGROUND: Sarcopenia is a degenerative syndrome mainly characterized by the atrophy of skeletal muscle, along with the decrease of muscle strength and function. However, there are currently few studies concerning sarcopenia in patients undergoing maintenance hemodialysis dialysis (MHD). This study was aimed to investigate the incidence of sarcopenia in MHD patients and its influencing factors, as well as its impact on survival risk. METHOD: All 131 MHD patients enrolled in our study were tested with bioelectrical impedance analysis (BIA) and grip strength. Demographic data was collected and anthropometric measurement and laboratory examination were conducted. RESULTS: The total incidence of sarcopenia within the 131 MHD patients was 13.7% and the incidence of sarcopenia in patients over 60 years was 33.3%. The dialysis duration, with or without diabetes, serum phosphorus and pre-albumin levels of sarcopenic patients were significantly different from those of non-sarcopenicones; the modified quantitative subjective global assessment (MQSGA) scores of sarcopenic patients were higher than those without sarcopenia. Multivariate analysis showed that dialysis duration, diabetes and serum phosphorus level were independent risk factors for sarcopenia in MHD patients. Kaplan-Meier survival analysis showed a one-year survival of 88.9% in sarcopenic patients, which was significantly lower than non-sarcopenic patients. CONCLUSION: The incidence of sarcopenia in MHD patients was high and increased gradually with age. Dialysis duration, diabetes, serum phosphorus level and malnutrition predisposed the patients to sarcopenia. One-year follow-up found that the mortality risk of sarcopenic patients was higher than that of non-sarcopenic patients.

Procyanidin B2 inhibits high glucose­induced epithelial­mesenchymal transition in HK­2 human renal proximal tubular epithelial cells.

Diabetic nephropathy (DN) is not only an important chronic complication of diabetes, but is also one of the predominant cause of renal failure. Previous studies have indicated that the process termed 'epithelial­mesenchymal transition' (EMT) results in fibrosis of renal tubular epithelial cells, and is key in DN. As an antioxidant, procyanidin B2 can inhibit cardiac fibrosis; however, whether it has an effect on the inhibition of renal fibrosis remains to be elucidated. The present study demonstrated that high glucose levels were able to activate EMT­associated changes, including the loss of E­cadherin and increase in α­smooth muscle actin (α­SMA), as determined by western blotting and immunofluorescence. Pre­treatment with procyanidin B2 reversed the high glucose­induced morphological changes, upregulated the expression of E­cadherin and downregulated the expression levels of vimentin and α­SMA. Furthermore, procyanidin B2 decreased the phosphorylation of small mothers against decapentaplegic (Smad)2, Smad3 and P38, and upregulated the expression of phosphorylated­Smad7. In conclusion, the results of the present study suggested that procyanidin B2 inhibited high glucose­induced EMT through the inhibition of transforming growth factor­ß/Smad and mitogen­activated protein kinase/P38 signaling pathways.

Application of total parathyroidectomy with auto-transplantation for uremia secondary hyperparathyroidism treatment.

BACKGROUND: Secondary hyperparathyroidism (sHPT) is a common acquired disorder in patients with chronic renal failure. Despite the development of new therapeutic agents, a majority of patients will require parathyroidectomy. The aim of this study was to evaluate total parathyroidectomy with auto-transplantation of trace amounts of parathyroid tissue as a surgical option in uremia sHPT treatment. METHODS: Clinical data of 50 sHPT patients who underwent total parathyroidectomy with auto-transplantation between January 2011 and December 2013 were reviewed retrospectively. Symptoms such as bone pain and fractures, concentrations of intact parathyroid hormone (iPTH), levels of ionized calcium and serum phosphorus, and activity of alkaline phosphatase were recorded before and after parathyroidectomy. RESULTS: After operation, signs of pruritus, bone pain and muscle weakness was disappeared, iPTH level and serum phosphate concentration were declined markedly. No serious postoperative complications were observed. Follow-up observation was around 28 months. One female patient (2%) died 3 months after surgery due to heart failure, and another patient (2%) had persistent disease. All other patients recovered during the follow-up period. CONCLUSIONS: Total parathyroidectomy with auto-transplantation of trace amounts of parathyroid tissue was considered to be a feasible, safe and effective surgical option for the treatment of sHPT.

Minimally invasive surgery with spotlight work channel system in the treatment of lumbar disc herniation: a retrospective study of 21 cases.

A group of lumbar discherniation cases was treated with posterior discectomy and decompression with Spotlight working channel. We retrospectively studied these patients. To study and analyze the clinical efficacy and technical features of discectomy which is carried out with the Spotlight channel technology. The development of the minimally invasive spine surgery technology promotes new instruments and materials. For minimally invasive spine surgery in channel technology, the newly launched Depuy(Spine) working channel-Spotlight, which is a new generation of wide viewing angle, single-hole device for minimally invasive spine operations, has good prospects for clinical application. From March 2011 to March 2012, 21 patients who were diagnosed with lumbar disc herniation were treated with posterior discectomy and decompression with Spotlight working channel, then the lumbar and leg pain visual analogue scale (VAS) scores of before and after surgery and that of the follow-ups and the Oswestry Disability Index were analyzed. All patients were successfully operated, and also they received follow-ups for more than 1 year. The postoperative lumbar and leg pain VAS scores improved significantly compared with the preoperative ones (P < 0.05) and can effectively maintain (P > 0.05). The three time points of lumbar pain VAS were 7.80 ± 0.49, 1.51 ± 0.52 and 1.47 ± 0.59. The leg pain VAS were 7.53 ± 0.50, 1.58 ± 0.58 and 1.49 ± 0.67. During the follow-ups of the cases in this group, no case of disc herniation relapsed. Patients were satisfied with that. The Spotlight channel system is one of the surgical approaches to "minimally invasive spine technology with direct vision". It has a good range of surgical indications. It can be carried out flexibly and used widely, which means it will be easier for the surgeons to master.

The effect of continuous blood purification on the prognosis of cardiorenal syndrome patients.

To discuss the effect of continuous blood purification (CBP) on the prognosis of cardiorenal syndrome (CRS) patients. Twenty-seven patients were selected for this study, who had previously been treated at the Blood Purification Center of the General Hospital of Jinan Military Region from May 2007 to October 2010. All patients suffered from chronic heart failure and acute kidney injury. Using a non-invasive hemodynamics monitoring system, we observed the dynamic changes in their cardiac output (CO), systemic vascular resistance (SVR), thoracic fluid capacity (TFC), central venous pressure (CVP), urinary volume, and Acute Physiology and Chronic Health Evaluation II system (APACHEII) score. Individual measurements were obtained at 24 h, 48 h, 72 h, 96 h, and 120 h after CBP treatment. At the same time, levels of serum creatinine (Scr), cysteine proteinase inhibitor Cystatin C (CysC), high sensitivity C-reactive protein (hs-CRP), and serum sodium were observed. The fatality rate at 28 days was also recorded. After 24 h of CBP treatment, acidosis, CO, and disturbances in water and electrolyte levels were all improved. As well, concentrations of Scr and CysC were significantly decreased, and the levels of SVR, TFC, and CVP were also decreased. After 72 h of CBP treatment, hs-CRP levels and APACHE II scores were significantly lower (P < 0.01). From 72 to 120 h of CBP treatment, oliguria was resolved in 24 patients, with improved sensitivity to diuretics. The fatality rate at 28 days was 11.12 %. CBP treatment could improve myocardial function, shorten the oliguria period, decrease the fatality rate, and improve the prognosis of CRS patients.

Quantitative assessment of the association between HDMX polymorphism and sarcoma.

To investigate the effects of the HDMX polymorphism on sarcoma risk. Relevant studies were identified by searching the PubMed, Embase, and Web of Science databases. Data were extracted by two independent investigators. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a fixed-effects model to assess the association between the HDMX polymorphism and sarcoma risk. We also conducted heterogeneity test, sensitivity analysis, and publication bias test. A meta-analysis of four published case-control studies involving 1,115 subjects (379 cases and 736 controls) showed no statistical association between the HDMX polymorphism and sarcoma risk (ORTT vs. GG 0.88, 95 % CI 0.68-1.14, P heterogeneity 0.819; ORTT + TG vs. GG 0.95, 95 % CI 0.79-1.15, P heterogeneity 0.937; ORTT vs. TG + GG 0.82, 95 % CI 0.65-1.04, P heterogeneity 0.589; ORT allele vs. G allele 0.91, 95 % CI 0.79-1.05, P heterogeneity 0.727; ORTG vs. GG 0.95, 95 % CI 0.74-1.22, P heterogeneity = 0.869). This null result did not alter when data were stratified according to ethnicity. Our meta-analysis indicates that the HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.

Effect of IFN-γ and IL-4 levels on the expression of Fas and Bcl-2 in peripheral blood lymphocytes in hemodialysis patients.

To study the correlation between the levels of IFN-γ and IL-4 and the expression of Fas and Bcl-2 in peripheral blood lymphocytes (PBL) in hemodialysis patients, the indirect immune fluorescein labeling method of flow cytometry and solid sandwich enzyme-linked immunosorbent assay were performed for detecting the expression of Fas and Bcl-2 in PBL and the levels of IFN-γ and IL-4 in the serum of 30 hemodialysis patients, respectively. It was found that the expression of Fas in PBL and the level of IL-4 in the serum of hemodialysis patients were significantly higher (P < 0.01), whereas Bcl-2 in PBL and IFN-γ in the serum were significantly lower (P < 0.01) than those of the normal controls. According to statistical analysis, the expression of Fas in PBL had a negative correlation with the level of IFN-γ, but a positive correlation with IL-4 in the serum of hemodialysis patients. Contrarily, the expression of Bcl-2 had a positive correlation with IFN-γ, but a negative correlation with IL-4 in the serum of hemodialysis patients. These results suggest that hemodialysis patients have a suppressed secretion of Th1-associated cytokine IFN-γ, but an increased secretion of Th2-associated cytokines IL-4, and these two aspects may play an important role in the abnormal apoptosis of PBL and its accompanying immune deficiency.

Effects of genistein on secretion of extracellular matrix components and transforming growth factor beta in high-glucose-cultured rat mesangial cells.

The ideal treatment for diabetic nephropathy should slow the progress of renal failure, delay the initiation of dialysis, and protect residual renal function in patients receiving dialysis. Renal mesangial cells play an important role in these processes. In the current study, we investigated the effects of genistein on rodent renal mesangial cells cultured in a high-glucose environment. Since overexpression of the extracellular matrix (ECM) components (type IV collagen and fibronectin) and transforming growth factor beta (TGF-beta) have been previously implicated in the development of the renal glomerulus damage of diabetic nephropathy, we included these substances in our study. The results showed that high concentration of glucose (450 mg.dl(-1)) stimulated the synthesis of type IV collagen and fibronectin and the secretion of TGF-beta. These responses were attenuated by genistein (> or =5 micromol.l(-1)) in a dose- and time-dependent manner. In conclusion, we demonstrated that genistein could inhibit the secretion of ECM components and the expression of TGF-beta at both the protein and mRNA levels. These findings should be followed up by further studies and clinical trials to verify the potential therapeutic effects of genistein on diabetic nephropathy.