Del Nido versus HTK cardioplegia for myocardial protection during adult complex valve surgery: a retrospective study.

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK. METHODS: The perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively. RESULTS: Of the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened. CONCLUSIONS: DN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.

Unusual origins of cardiac insufficiency: a case of iliac arteriovenous fistula post-spinal disc surgery.

In this case report, we present the unique and intriguing case of a 57-year-old man who experienced exertional palpitations and shortness of breath for 5 years. He was diagnosed with idiopathic heart failure three years ago, leading to diuretic treatment. Physical examination revealed notable left lower extremity swelling, severe varicose veins, and cardiac murmurs. Echocardiography showed significant cardiac enlargement and severe functional mitral and tricuspid valve regurgitation. Computed tomography (CT) imaging uncovered a 10 mm left common iliac arteriovenous fistula, causing abnormal early filling of the inferior vena cava (IVC) and marked IVC dilation. Open surgical repair of the arteriovenous fistula resulted in symptom relief and improved cardiac function. This case underscores the importance of considering unusual causes in heart failure patients and highlights the value of early diagnosis and intervention in complex cardiac-vascular interactions.

Tubular expression of heat-shock protein 27 inhibits fibrogenesis in obstructive nephropathy.

Morphological changes that occur during kidney injury involve actin skeleton remodeling. Here we tested whether heat-shock protein 27 (HSP27), a small stress response protein involved in cytoskeletal remodeling, protects the kidney from tubulointerstitial fibrosis in obstructive nephropathy. Tubular cell HSP27 immunostaining was significantly increased in human kidneys with ureteropelvic junction obstruction, supporting the clinical relevance of our studies. To develop an animal model for mechanistic studies, we generated transgenic mice that specifically overexpress human HSP27 in renal tubules, under the kidney androgen-regulated protein promoter, and determined the effects of HSP27 overexpression on epithelial-to-mesenchymal transition and tubulointerstitial fibrosis following unilateral ureteral obstruction. This was associated with decreased fibrogenesis as evidenced by significant declines in phosphorylated p38MAPK, collagen III, α-smooth muscle actin, 4-hydroxynonenal, and reduced trichrome staining following obstruction. Notably, E-cadherin and ß-catenin remained at the cell membrane of tubular cells in transgenic mice with an obstructed ureter. Monocyte/macrophage infiltration, however, was not significantly affected in these transgenic mice. Thus, tubular HSP27 inhibits fibrogenesis in obstructive nephropathy. Further studies are needed to determine pathways regulating the interactions between HSP27 and the E-cadherin-ß-catenin complex.

Cholesteryl ester transfer protein TaqIB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population.

BACKGROUND: TaqIB polymorphism in the cholesteryl ester transfer protein (CETP) gene has been reported to be associated with serum high-density lipoprotein cholesterol (HDL-C) levels and longevity in several populations, but controversial results also arose probably due to racial/ethnic diversity. Bama is a remote and mountainous county located in the northwest of Guangxi, People's Republic of China, which has been well known for its longevity for centuries. The current study was to investigate the possible association of CETP TaqIB polymorphism with serum lipid levels and longevity in the Bama Zhuang population. METHODS: The CETP TaqIB genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism in 523 long-lived inhabitants (long-lived group, LG; aged 90-107 years) and 498 healthy controls without longevity family history (non-long-lived group, non-LG; aged 40-69 years) residing in Bama County. RESULTS: The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were higher but TG, HDL-C/LDL-C ratio and the prevalence of dyslipidemia were lower in LG than in non-LG (P < 0.001 for all). There were no differences in the allelic and genotypic frequencies between the two groups (P > 0.05). Serum HDL-C levels and HDL-C/LDL-C ratio in LG were different among the genotypes (P < 0.01 for each), the subjects with B2B2 and B1B2 genotyes had higher HDL-C levels and HDL-C/LDL-C ratio than the subjects with B1B1genotye, whereas the levels of TC and HDL-C in non-LG were different among/between the genotypes (P < 0.01 for each), the B2 allele carriers had lower TC and higher HDL-C levels than the B2 allele noncarriers. Serum TG and HDL-C levels and HDL-C/LDL-C ratio were correlated with genotypes in LG, whereas serum TC and HDL-C levels were associated with genotypes in non-LG (P < 0.05-0.001). CONCLUSIONS: The association of CETP TaqIB polymorphism and serum lipid profiles is different between LG and non-LG in the Chinese Bama Zhuang population. CETP TaqIB polymorphism might be one of the longevity-related genetic factors in this population.

Contributing factors to complications and surgical success in mouse kidney transplantation.

PURPOSE: Mouse kidney transplantation is a challenging technique for novice microsurgeons. Factors that affect transplant outcomes for a clinical surgeon starting microsurgery have not yet been investigated. MATERIALS AND METHODS: 110 consecutive mouse kidney transplants were performed over a 9-month period. Data were recorded, and surgical results and complication were analyzed. RESULTS: Three and thirty day survival rates improved from 0 (0/6) to 92.3 % (12/13) between months 1 and 9. Bleeding, arterial thrombosis, kidney failure and hydronephrosis were the most common causes of transplant failure. From month 1 to month 7, using the same surgical technique, practice significantly decreased the incidence of bleeding and increased the 3-day survival rate; however, it didn't significantly decrease the incidence of thrombosis, kidney failure, but improved the 30-day survival rate. From month 8, when surgical technique used on artery anastomosis switched from continuous suture to interrupted suture, surgical survival rate at 3 and 30 days improved significantly. Interestingly, ischemia time was not a significant factor determining the success of transplantation in this study. CONCLUSIONS: Practice is essential for novice microsurgeons, and the choice of surgical techniques significantly affects surgical results. The use of interrupted arterial sutures can significantly improve mouse kidney transplantation outcomes compared with continuous sutures. Ischemic time was not a factor in determining successful of kidney transplantation in mice in this study.

Proteomics-based identification of secreted protein dihydrodiol dehydrogenase as a novel serum markers of non-small cell lung cancer.

Identification of secreted proteins of lung cancer could provide new candidates of serum biomarkers for cancer diagnosis and prognosis evaluation. In this study, non-small cell lung cancer (NSCLC) cell line A549 was cultured. Proteins in the conditioned medium of A549 were recovered and the proteome analysis was subsequently performed. Secreted proteins of A549 were identified using mass spectrometry and database search. Fourteen human proteins were identified, including peptidyl-prolyl cis-trans isomerase A, manganese superoxide dismutase, peroxiredoxin 1, phosphatidylethanolamine-binding protein, glutathione S-transferase P, PGP9.5, alpha enolase, phosphoglycerate mutase 1, galectin-1 and dihydrodiol dehydrogenase (DDH). DDH was selected for further analysis using RT-PCR, immunoblotting, immunohistochemical staining and ELISA in NSCLC patients. Compared with normal lung tissues, higher DDH mRNA and protein expression level were found in 15 NSCLC cancer tissues (p<0.05). DDH overexpression was identified to be located in cytoplasm and cell membrane by immunohistochemical staining in NSCLC tissue. The serum level of DDH was significantly higher in NSCLC patients (n=64) than nonmalignant lung tumor (n=20) and healthy controls (n=20) (p<0.05). The results show that DDH was one of the secreted proteins in NSCLC. It can serve as a tissue marker and a novel serological marker of NSCLC. Identification of secreted proteins could be a feasible and effective strategy to search potential serum biomarkers of cancer.

Chest wall tumors: Diagnosis, treatment and reconstruction.

The aim of the present study was to determine a suitable procedure for the treatment of chest wall neoplasms with less potential risk and an increased rate of survival. Fifty patients with suspected chest wall malignancies were analyzed using various preliminary investigation tools. Whole-chest scanning was performed in all the patients. The patients were subsequently subjected to biopsies for further confirmation of the neoplasm. All such patients were then treated with a surgical approach and radiation therapy, with a follow-up period lasting up to six years. The majority of the patients showed improved survival rates relative to conventional therapies. The survival rates of patients suffering from osteosarcoma (78%) were higher those of patients with rhabdomyosarcoma (73%) and malignant small round cell tumors (64%). The survival and the mortality rates of the patients with synovial sarcoma and fibrosarcoma were the same. This study, which was conducted on a small group of patients, has provided guidance for further studies on tumors of the chest wall, which may, in turn, increase the longevity of affected patients.

COMT Val158Met polymorphism is associated with blood pressure and lipid levels in general families of Bama longevous area in China.

To see the possible relationship between COMT Val158Met polymorphism and blood pressure (BP) and serum lipid levels and its putative role in human longevity, we genotyped COMT Val158Met (rs4680) by PCR-RFLP for members from Bama long-lived families (BLF, n = 1538), Bama non-long-lived families (BNLF, n = 600), Pingguo (a county outside Bama region) long-lived families (PLF, n = 538) and Pingguo non-long-lived families (PNLF, n = 403) after anthropometric measures were collected and serum lipid levels were detected. The distribution of genotypes and alleles among four family groups was significantly different (all P < 0.01), with GA/AA genotype and minor allele A presenting more frequently in Bama population than Pingguo Population (P < 0.01). The systolic blood pressure (SBP), pulse pressure (PP), total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDL-C) levels of GG genotype carriers were dramatically higher than non-GG carriers in BNLF (P < 0.05); the SBP and PP levels of GG carriers were lower (P < 0.05) while TC, LDL-C level were higher (P < 0.01) than that of non-GG carriers in PLF; no difference in blood pressure and lipids were observed between genotypes in BLF and PNLF (P > 0.05). Correlation analyses revealed that COMT Val158Met was mainly correlated negatively with SBP, diastolic blood pressure (DBP) and LDL-C in BNLF and negatively with TC level in BLF, BNLF and PLF. These data suggest that COMT Val158Met polymorphism may have more impact on the modulation of BP and lipid profiles in the average families than in the long-lived families in Bama region. The association between this SNP and other phenotypes (e.g. cognition) and its roles in the longevity in Bama area thus warrant further investigation.

Mycophenolic acid may delay allograft fibrosis by inhibiting transforming growth factor-beta1-induced activation of Nox-2 through the nuclear factor-kappaB pathway.

BACKGROUND: We evaluated the role of renal tubular Nox-2 in the pathogenesis of epithelial-to-mesenchymal transition (EMT) in kidney allografts. METHODS: We examined this question in the human kidney allografts with interstitial fibrosis and tubular atrophy not otherwise specified (IFTANOS), in the Fisher to Lewis rat transplant model, and in the in vitro model of transforming growth factor-beta1-induced EMT in normal rat kidney epithelial cells (NRK52E). RESULTS: We first demonstrated that Nox-2 and alpha-smooth muscle actin (SMA) were increased in renal tubules from kidney transplant recipients on calcineurin inhibitors, mycophenolic acid (MPA), and prednisone with IFTANOS, suggestive of EMT (n=6). Next, we examined Nox-2 expression and fibrogenesis in syngeneic transplants, allogeneic transplants treated with MPA 40 mg/kg per 24 hr, and untreated allogeneic transplants for 6 months (n=14 in each group). Immunofluorescent and immunohistochemical studies for Nox-2, alpha-SMA, and E-cadherin showed that similar to patients with IFTANOS, rat allografts had greater tubulointerstitial staining for Nox-2 and alpha-SMA. MPA therapy prevented these changes. Immunoblot analyses examining Nox-2 signaling (phospho-nuclear factor [NF]-kappaB), redox signaling (phospho-smad2), and fibrosis (alpha-SMA and fibronectin) demonstrated that MPA treatment prevented the up-regulation of Nox-2, inhibited p-NF-kappaB and p-smad2, and down-regulated alpha-SMA and fibronectin levels. Finally, we examined Nox-2 signaling in vitro and confirmed that MPA inhibited phospho-NF-kappaB, Nox-2, phospho-smad2, and alpha-SMA during transforming growth factor-beta1-induced EMT of NRK52E cells while reducing Nox-2, vimentin, and fibronectin mRNA levels. CONCLUSIONS: MPA may down-regulate Nox-2 activation and EMT through the NF-kappaB pathway in the tubular epithelial cells, suggesting a novel role for this drug independent of its immunosuppressive properties.

[Expression and significance of Pin1 mRNA in circulating mononuclear cells from non-small cell lung cancer patients during perioperative period].

BACKGROUND AND OBJECTIVE: The catalytic reaction of Pin1 (peptidylprolyl cis/trans isomerase NIMA-interacting 1) is a signal pathway for changing the functions of phosphorylated proteins, which plays an important role in tumorigenesis. Pin1 is called the catalytic molecule for tumorigenesis. This study was to detect the expression of Pin1 mRNA in blood samples from non-small cell lung cancer (NSCLC) patients, and explore its significance. METHODS: Twenty-six NSCLC patients who underwent radical resection were assigned to pulmonary artery first ligation group (PA-first group) and pulmonary vein first ligation group (PV-first group). The blood samples were collected before operation (after anesthesia), during operation from the proximal part and distal part of the pulmonary vein when it was ligated, and at 7 days later. Additionally, ten patients with benign lung disease who underwent resection served as disease control, and ten healthy subjects served as negative control. The expression of Pin1 in the blood samples was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The mRNA level of Pin1 was obviously higher in blood samples from NSCLC patients than in those from benign lung disease patients and healthy subjects: it in NSCLC group was 1.69-34.78 times of that in negative control group. It was associated with lymph node metastasis and clinical stage of NSCLC (p=0.043, p=0.038). The mRNA level of Pin1 was significantly higher in the distal part of the pulmonary vein than in the proximal part (p=0.019), and was significantly lower at 7 days after operation than before operation (p=0.031). There was no significant difference between PA-first group and PV-first group (p=0.082, p=0.106). CONCLUSION: Pin1 is overexpressed in circulation of NSCLC, and may be used as a tumor marker or as a target for cancer therapy.

Contributing factors to complications and surgical success in mouse kidney transplantation

PURPOSE: Mouse kidney transplantation is a challenging technique for novice microsurgeons. Factors that affect transplant outcomes for a clinical surgeon starting microsurgery have not yet been investigated. MATERIALS AND METHODS: 110 consecutive mouse kidney transplants were performed over a 9-month period. Data were recorded, and surgical results and complication were analyzed. RESULTS: Three and thirty day survival rates improved from 0 (0/6) to 92.3% (12/13) between months 1 and 9. Bleeding, arterial thrombosis, kidney failure and hydronephrosis were the most common causes of transplant failure. From month 1 to month 7, using the same surgical technique, practice significantly decreased the incidence of bleeding and increased the 3-day survival rate; however, it didn't significantly decrease the incidence of thrombosis, kidney failure, but improved the 30-day survival rate. From month 8, when surgical technique used on artery anastomosis switched from continuous suture to interrupted suture, surgical survival rate at 3 and 30 days improved significantly. Interestingly, ischemia time was not a significant factor determining the success of transplantation in this study. CONCLUSIONS: Practice is essential for novice microsurgeons, and the choice of surgical techniques significantly affects surgical results. The use of interrupted arterial sutures can significantly improve mouse kidney transplantation outcomes compared with continuous sutures. Ischemic time was not a factor in determining successful of kidney transplantation in mice in this study.

Proteomic analysis of secreted proteins of non-small cell lung cancer.

BACKGROUND & OBJECTIVE: Secreted proteins from cancer cells may be potential serologic biomarkers of cancer. It's important to globally identify secreted proteins of cancer cells. This study was to identify secreted proteins of lung cancer cells. METHODS: Proteins in the conditioned medium of non-small cell lung cancer (NSCLC) cell line A549 was collected and the proteome analysis was subsequently performed. Specific protein spots in A549 cells were identified by peptide mass fingerprints using mass spectrometry and through searching database. The expression of identified secreted proteins was detected by reverse transcription-polymerase chain reaction (RT-PCR) in 15 specimens of NSCLC tissue and paired distant lung tissue. Manganese superoxide dismutase (Mn-SOD) activity in serum and conditioned medium was detected by spectrophotometry. RESULTS: Fourteen secreted proteins were identified, which included peptidyl-prolyl cis-trans isomerase A (PPIA), Mn-SOD, peroxiredoxin 1 (PDX1), phosphatidylethanolamine binding protein (PEBP), glutathione S-transferase P (GSTP1-1), glucose-dependent insulinotropic protein receptor (GIPR), ubiquitin carboxyl-terminal hydrolase isozyme L1 (PGP9.5), alpha enolase (ENO1), dihydrodiol dehydrogenase (DDH), phosphoglycerate mutase 1 (PGAM1), galectin-1 (GAL1). PPIA, DDH, PGAM1, PDX1, PGP9.5, ENO1, and PEBP were overexpressed in cancer tissues. Higher level of Mn-SOD activity was detected in conditioned medium than in control. Serum Mn-SOD activity was significantly higher in NSCLC patients than in healthy controls (P<0.01). CONCLUSIONS: Multiple secreted proteins of A549 cells were identified in this study and the overexpression of ENO1 and PEBP in NSCLC was revealed for the first time. Mn-SOD is secreted serologic marker of NSCLC. The results presented here would provide clues to identify new serologic biomarkers of NSCLC.