Gremlin Regulates Podocyte Apoptosis via Transforming Growth Factor-ß (TGF-ß) Pathway in Diabetic Nephropathy.

BACKGROUND Gremlin has been reported to be up-regulated in glomerular mesangial cells in diabetic nephropathy (DN). However, the regulation of gremlin in podocytes is still rarely reported. This study aimed to investigate the underlying mechanisms by which gremlin mediates the pathogenesis of DN via transforming growth factor-ß (TGF-ß) signaling pathways. MATERIAL AND METHODS Lentiviral and RNAi transfection were performed to increase and decrease gremlin expression in high-glucose conditions. Expression at the mRNA and protein level was detected by RT-qPCR and Western blotting. RESULTS The expression of gremlin was significantly higher in high-glucose (HG, 30mM) than normal-glucose (NG, 5.5 mM) conditions. The gremlin overexpression significantly suppressed the expression of nephrin and synaptopodin. The phosphorylation of canonical TGF-b signaling pathway components, including Smad2/3 and MKK, was increased in the gremlin-overexpressing group. In addition, the expression levels of Bax and cleaved caspase-3 were also higher in the gremlin-overexpressing group. TGF-ß pathway inhibitor (SB505124) significantly inhibited TGF-ß pathway activity and enhanced the expression of nephrin and synaptopodin. CONCLUSIONS These results indicate that gremlin can aggravate podocyte lesions through the TGF-ß signaling pathway, providing a novel therapeutic target for DN.

[Cardio-pulmonary exercise capacity in patients with lung cancers: a comparison study between video-assisted thoracoscopic lobectomy and thoracotomy lobectomy].

OBJECTIVE: To determine the effect of video-assisted thoracoscopic lobectomy on the pulmonary rehabilitation of patients with lung cancers. METHODS: Between September 2010 and December 2011, 138 patients. with lung cancers were treated with lobectomy: 68 using video-assisted thoracoscopic surgery (VATS) and 70 using thoracotomy. The preoperative and postoperative (7 d and 30 d) pulmonary functions and Cardio-pulmonary Exercise Capacities as well as postoperative (7 d and 30 d) DE Morton Index of the two groups of patients were assessed. The two groups of patients had similar in clinical characteristics. RESULTS: (1) Patients in the VATS group had greater FEV1 (1.64 +/- 0.21) L and PEF [(310.58 +/- 30.13) L/min] on the 7 d after operations than those with thoracotomy [FEV1 (1.34 +/- 0.11) L and PEF (270.18 +/- 25.67) L/min], P < 0.05. (2) Patients in the VATS group had lower fatigue index (0.27 +/- 0.08) and dyspnea index (0.28 +/- 0.17) on the 7 d after operations than those with thoracotomy (0.44 +/- 0.10 fatigue index and 0.39 +/- 0.09 dyspnea index), P < 0.05. (3) Patients in the VATS group had longer 6-min walking distance on the 7 d [(490.57 +/- 118.33) m] and 30 d [(524.32 +/- 140.87) m] after operations than those with thoracotomy [(395.07 +/- 100.19) m at 7 d and (471.10 +/- 118.57) m at 30 d], P < 0.05. (4) Patients in the VATS group had higher DE Morton index (74.58 +/- 16.23) on the 7 d after operations than those with thoracotomy (55.87 +/- 14.79), P < 0.05. CONCLUSION: VATS lobectomy for curative lung cancer resection appears to provide a superior functional health recovery compared with thoracotomy.

[Comparative study of direct digital radiography and film-screen radiography in diagnosis of asbestosis].

OBJECTIVE: To evaluate the feasibility of direct digital radiography (DDR) in the diagnosis of asbestosis, and to analyze the difference and similarity between DDR and film-screen radiography (FSR) in terms of the radiographic features of asbestosis. METHODS: A total of 60 cases of asbestosis underwent FSR and DDR of the chest in the same day. The FSR and DDR findings were compared with respect to shapes and profusion of small opacities, pleural abnormality, and diagnostic stages. RESULTS: The patients showed "s", "t", and "p" small opacities on chest images, with irregular "s" and "t" ones predominating (FSR: 95.0%; DDR: 91.7%). The small opacities were widely distributed in six lung zones, especially in middle and lower zones. The shapes and distribution of small opacities did not differ significantly between FSR and DDR findings (P > 0.05). For all the 60 cases, the two radiographies demonstrated a concordance rate of 64.2% (231/360) for the profusion of small opacities in lung zones (κ = 0.62, 95%CI: 0.54 ∼ 0.69), and for the 43 cases (258 lung zones) who displayed identical small opacity shapes on the two radiographies, the concordance rate was 81.0% (209/258) (κ = 0.79, 95%CI: 0.72 ∼ 0.87). FSR revealed 10 cases (16.7%) of pleural thickening, compared to 12 cases (20.0%) on DDR (P > 0.05). FSR revealed 53 cases (88.3%) of stage I asbestosis and 7 cases (11.7%) of stage II asbestosis, compared to 51 cases (85.0%) and 9 cases (15.0%) on DDR (P > 0.05). There was no significant difference in diagnostic stages between the two radiographies (P > 0.05), demonstrating a concordance rate of 93.3% (56/60) (κ = 0.71, 95%CI: 0.45 ∼ 0.98). CONCLUSION: DDR is similar to FSR in determining the shapes, distribution, and profusion of small opacities, pleural abnormality, and diagnostic stages.

Value of Peak Expiratory Flow Rate in Evaluating Cough Ability in Patients Undergoing Lung Surgery.

Introduction: Postoperative ineffective cough is easy to occur after thoracic surgery, and it is also a risk factor for postoperative pulmonary complications (PPCs). Objectives: To explore the value of peak expiratory flow rate (PEF) in evaluating cough ability in patients undergoing lung surgery and evaluate the effectiveness of chest wall compression during the expiratory phase by PEF. Methods: From September 2020 to May 2021, the researchers collected the data of patients who underwent lung surgery. Eventually, 153 patients who met the criteria were included, 102 cases were included in the effective cough group and 51 cases were included in the ineffective cough group. The receiver working curve (ROC curve) was used to analyze whether PEF could evaluate cough ability. At the same time, the researchers collected the pulmonary function data of the first 30 patients of the ineffective cough group while compressing the chest wall during the expiratory phase to evaluate the effectiveness of chest wall compression. Results: The area under the curve (AUC) of postoperative PEF to evaluate the postoperative cough ability was 0.955 (95% CI: 0.927-0.983, P < 0.001). The values of PEF (127.17 ± 34.72 L/min vs. 100.70 ± 29.98 L/min, P < 0.001, 95% CI: 18.34-34.59) and FEV1 (0.72 (0.68-0.97) L vs. 0.64 (0.56-0.82) L, P < 0.001) measured while compressing the chest wall were higher than those without compression. Conclusions: PEF can be used as a quantitative indicator of cough ability. Chest wall compression could improve cough ability for patients who have ineffective cough.

Protective effects of the calcium-channel blocker flunarizine on crush injury of sciatic nerves in a rat model.

BACKGROUND: Neural damage can be mitigated by calcium-channel blockers (CCBs). However, the mechanism of action of CCBs is not yet fully understood. Objective : To investigate the mechanism of action and efficacy of CCB, flunarizine in restoring neural function after crush injury to the nerves. MATERIALS AND METHODS: The sciatic nerves of rats were crushed using pincers to establish the model for crush injury. Two hundred and eighty-eight Sprague-Dawley (SD) rats were randomly divided into sham-operated, saline, and low-dose flunarizine and high-dose flunarizine (FI and FII) groups. The expression of the protein c-fos in the dorsal root ganglia (DRG) after crush injury to the sciatic nerves was investigated by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The effect of flunarizine on c-fos expression and its efficacy in restoring neural function was evaluated. RESULTS: The c-fos messenger ribonucleic acid (mRNA) and protein expression in FI and FII groups was significantly lower than in the saline group and was the least in the FII group. Nerve-conduction velocity was increased in the order of: saline < FI< FII< sham-operated. There was no significant difference in the nerve-conduction velocity in the sham-operated and FII groups (P>.05). CONCLUSIONS: When administered after crush injury to peripheral nerves, flunarizine may protect neurons with lesions from further damage and improve neural function by downregulating c-fos expression.

Cardiopulmonary exercise testing screening and pre-operative pulmonary rehabilitation reduce postoperative complications and improve fast-track recovery after lung cancer surgery: A study for 342 cases.

BACKGROUND: An evaluation of cardiopulmonary exercise testing (CPET) screening and pre-operative pulmonary rehabilitation in reducing postoperative complications and improving fast-track recovery in high-risk patients who undergo resection for lung cancer. METHODS: Of 342 potential lung cancer cases, 142 high-risk patients were finally divided into two groups: group R (n = 71) underwent an intensive pre-operative pulmonary rehabilitation program (PRP), followed by lobectomy; group S (n = 71) underwent only lobectomy with conventional management. Postoperative complications, average days in hospital, postoperative days in hospital, and cost were analyzed. RESULTS: The 142 high-risk patients were screened by smoking history and CPET. Sixty-eight patients had bronchial hyperresponsiveness (BHR) and 47 patients had peak expiratory flow <250 L/minute by CPET. The rate of postoperative total complications in group R (16.90%) was significantly lower than in group S (83.31%) (P = 0.00), as was the rate of postoperative pulmonary complications PPC: group R (12.81%) versus S (13.55%) (P = 0.009); the PPC in the left lung (17.9%) was higher than in the right lung (2.3%) (P = 0.00). The average days in hospital in group S was significantly higher than in group R (P = 0.03). There was no difference between groups in average hospital cost (P = 0.304). CONCLUSION: Pre-operative screening using CPET is conducive to identifying high-risk patients for lung resection. Pre-operative pulmonary rehabilitation is helpful to reduce postoperative complications and improve fast-track recovery.

Vasoactive agent buflomedil up-regulated expression of vascular endothelial growth factor in a rat model of sciatic nerve crush injury.

OBJECTIVES: To study the effect of Buflomedil on the morphological repair on crush injury of sciatic nerve and also the expression of vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: Rat sciatic nerves were crushed by pincers. All of the 400 Sprague Dawley rats were randomly divided into: Sham-operated; saline; saline + VEGF-antibody; Buflomedil; and Buflomedil + VEGF antibody groups. The expression of VEGF in dorsal root ganglia (DRGs), following crush injury to sciatic nerves, was studied by RT-PCR, immunohistochemistry. The effects of Buflomedil on expression of VEGF and repair of neural pathology were also evaluated. RESULTS: VEGF mRNA was significantly increased in Buflomedil and Buflomedil + VEGF-antibody groups, compared with other groups. The number of VEGF-positive neurons was significantly increased in the Buflomedil and the saline groups. Besides, Buflomedil also caused less pathological changes in DRGs. CONCLUSIONS: The vasoactive agent Buflomedil may decrease the pathological lesion and improve the functional rehabilitation of peripheral nerves, which may correlate to upregulation of the expression of VEGF, following crush injury to the peripheral nerves.

Elevated serum glucose-6-phosphate isomerase correlates with histological disease activity and clinical improvement after initiation of therapy in patients with rheumatoid arthritis.

OBJECTIVE: To determine serum glucose-6-phosphate isomerase (GPI) concentrations in patients with rheumatoid arthritis (RA), and to test whether they correlate with objective measures of disease activity. METHODS: Sera from 116 patients with RA, 69 patients with non-RA rheumatic diseases, and 101 healthy controls were analyzed. Levels of soluble serum GPI were measured by ELISA. Histological disease activity was determined with the synovitis score in synovial needle biopsies from 58 of the 116 patients with RA. Thirty-one of the 58 synovium samples were stained for CD68, CD3, CD20, CD38, CD79a, and CD34 by immunohistochemistry. Demographic data were collected, as well as serological and clinical variables that indicate RA disease activity, for Spearman correlation analysis. RESULTS: Serum GPI level correlated positively with the synovitis score (r = 0.278, p = 0.034). Significantly higher soluble GPI levels were detected in the RA sera compared with sera from healthy controls and the non-RA disease controls (2.25 ± 2.82 vs 0.03 ± 0.05 and 0.19 ± 0.57 µg/ml, respectively; p < 0.0001). The rate of serum GPI positivity was significantly higher in the RA patients than in the non-RA disease controls (64.7% vs 10.1%; p < 0.0001). Spearman analysis showed no significant correlation between serum GPI level and Disease Activity Score in 28 joints at baseline. After initiation of antirheumatic treatments, GPI levels decreased significantly (2.81 ± 3.12 vs 1.44 ± 2.09 µg/ml; p = 0.016), paralleling improvement of the disease activity indices. CONCLUSION: Elevated serum GPI may be involved in the synovitis of RA and may prove useful as a serum marker for disease activity of RA.

[Immunophenotypic features of acute myeloid leukemia with AML-1/ETO fusion gene].

AML-1/ETO fusion gene is the frequent genetic lesion described in FBA M(2) type acute myeloid leukemia (AML-M(2)) and is associated with a favourable prognosis. In spite of its potential clinical relevance, this subtype leukemia usually would be undetected with conventional cytology procedures, and easily confused with acute promyelocyte leukemia (APL) in morphology. In order to investigate the immunophenotypic characteristics of bone marrow cells in AML-M(2) patients with AML-ETO gene rearrangement classified by FAB, immunophenotype of bone marrow cells in 17 AML-M(2) patients with AML-1/ETO(+) confirmed by fluorescence in situ hybridization was analyzed by using flow cytometry as compared with immunophenotype in 34 APL patients with AML-1/ETO(-). The results showed that population of blast cells (15.89% - 68.53%) and population of more heterogeneous myeloid cells were detected with right-angle scatter in 17 patients with AML-1/ETO(+), i.e. AML-M(2) by FAB classification. The blast cells expressed stem cell associated antigens CD34, HLA-DR and myeloid antigens CD33, CD13, MPO. The mean fluorescent intensity of CD33 in M(2)/ETO(+) patients was significantly lower than that in APL patients (121 +/- 92 vs 845 +/- 523, P<0.001), meanwhile positive expression rates of HLA-DR, CD19 and CD34(+)CD56(+) in M(2)/ETO(+) patients were significantly higher than that in APL patients (100%, 88.24%, 100% vs 27.27%, 8.82%, 0%, P<0.001), expression rate of CD9 in M(2)/ETO(+) patients was significantly lower than that in APL patients (P<0.001). In patients with M(2)/ETO(+) (AML-M(2)), the pattern of CD15/CD11b expression was seen as granulocytic differentiation with immature events showing CD15(+)CD11b(-) and more mature CD15(+)CD11b(+) populations, the expression of mature granulocytes CD10 was negative and similar to APL in expression figure. The granulocytes expressed CD56 in 17 patients with M(2)/ETO(+) (17/17, 100%) and its expression rate was significantly higher than that in patients with M(3) (6/34, 17.56%). It is concluded that AML-M(2) with AML-1/ETO gene rearrangement was confirmed to express an exclusive immunophenotype that shows highly predictive value for the cytogenetic pattern, and the multiparametric flow cytometry with FISH provides a technical approach to easily distinguish leukemia subtype M(2)/ETO(+) from APL.

[Significance of quantitative detection of bcr-abl mRNA in chronic myeloid leukemia patients after allogeneic hematopoietic stem cell transplant].

The objective of this study was to analyze the level of bcr-abl mRNA in peripheral blood (PB) after allogeneic stem cell transplantation (allo-SCT) in chronic myeloid leukemia patients, providing a experimental basis for diagnosing early relapse. bcr-abl mRNA levels in 78 PB and bone marrow (BM) samples from 15 CML patients after allo-SCT were detected by using real-time quantitative PCR. The results indicated that levels of bcr-abl mRNA before transplantation were high (median 29.303%) and decreased greatly (median 0) at the first month after allo-SCT. During the first year after allo-SCT, the patterns of serial bcr-abl transcripts varied in number, but the overall bcr-abl transcript levels significantly decreased at 6 months after allo-SCT. Majority of patients with undetectable or very low levels of bcr-abl mRNA were monitored after 1 year following transplantation. The hematological features of BM and PB in all detected patients remained normal. PB and BM bcr-abl values were not different significantly and had the similar trend of changes. It is concluded that the bcr-abl mRNA levels in CML patients change greatly early after allograft. Serial monitoring measurements for bcr-abl mRNA contribute to understanding the trend of change and effect of transplantation, also can be a guidance for starting therapy. But detectable levels of bcr-abl mRNA during the first 6 months do not indicate relapse. Measurements of bcr-abl mRNA of PB may be more suitable for routine monitoring long-term disease status in CML after allo-HSCT.