Kank1 and Ki67 expression are associated with poor prognosis in human pulmonary adenocarcinoma.

KN motif and ankyrin repeat domains 1 (Kank1) and ki67 are associated with tumorigenesis and progression. This paper researched the expression of Kank1 and Ki67 and their clinicopathologic significance in pulmonary adenocarcinoma (PA). We monitored the expression of KanK1 and ki67 in 94 cases of human PA and 31 cases of paracancerous tissue by the immunohistochemical method. The results showed that Kank1 protein was detected in 74.2% (41/94) of PA tissues, and they were associated with differentiation (P = 0.025) and lymphatic metastasis (P = 0.002). Kaplan-Meier analysis suggested that patients with low Kank1 expression had shorter overall survival in PA (P = 0.020). Ki67 protein was detected in 79.8% (75/94) of PA tissues, and they were associated with differentiation (P < 0.001), TNM classification (P = 0.007), and lymphatic metastasis (P = 0.044). Furthermore, Kaplan-Meier analysis showed that patients with overexpression of Ki67 had shorter overall survival (P = 0.014). Cox multivariate analysis showed that tumor differentiation, TNM classification, lymphatic metastasis, Kank1, and ki67 expression were independent factors for prognosis of PA (P = 0.012, 0.016, 0.007, 0.021 and P = 0.003 respectively). In conclusion, compared with paracancerous tissues, Kank1 had low expression, while Ki67 was overexpressed in PA. They are closely related to its occurrence and development, and the prognosis of patients with low expression of Kank1 or overexpression of ki67 was poor in PA. Kank1 and Ki67 can be helpful for diagnosing and detecting the prognosis of patients with PA.

Genetic Polymorphisms Predisposing the Interleukin 6-Induced APOBEC3B-UNG Imbalance Increase HCC Risk via Promoting the Generation of APOBEC-Signature HBV Mutations.

PURPOSE: APOBEC3-UNG imbalance contributes to hepatitis B virus (HBV) inhibition and somatic mutations. We aimed to explore the associations between hepatocellular carcinoma (HCC) risk and genetic polymorphisms predisposing the imbalance.Experimental Design: Genetic polymorphisms at APOBEC3 promoter and UNG enhancer regions were genotyped in 5,621 participants using quantitative PCR. HBV mutations (nt.1600-nt.1945, nt.2848-nt.155) were determined by Sanger sequencing. Dual-luciferase reporter assay was applied to detect the transcriptional activity. Effects of APOBEC3B/UNG SNPs and expression levels on HCC prognosis were evaluated with a cohort of 400 patients with HCC and public databases, respectively. RESULTS: APOBEC3B rs2267401-G allele and UNG rs3890995-C allele significantly increased HCC risk. rs2267401-G allele was significantly associated with the generation of APOBEC-signature HBV mutation whose frequency consecutively increased from asymptomatic HBV carriers to patients with HCC. Multiplicative interaction of rs2267401-G allele with rs3890995-C allele increased HCC risk, with an adjusted OR (95% confidence interval) of 1.90 (1.34-2.81). rs2267401 T-to-G and rs3890995 T-to-C conferred increased activities of APOBEC3B promoter and UNG enhancer, respectively. IL6 significantly increased APOBEC3B promoter activity and inhibited UNG enhancer activity, and these effects were more evident in those carrying rs2267401-G and rs3890995-C, respectively. APOBEC3B rs2267401-GG genotype, higher APOBEC3B expression, and higher APOBEC3B/UNG expression ratio in HCCs indicated poor prognosis. APOBEC-signature somatic mutation predicts poor prognosis in HBV-free HCCs rather than in HBV-positive ones. CONCLUSIONS: Polymorphic genotypes predisposing the APOBEC3B-UNG imbalance in IL6-presenting microenvironment promote HCC development, possibly via promoting the generation of high-risk HBV mutations. This can be transformed into specific prophylaxis of HBV-caused HCC.

Clinical characteristics and prognosis of ground-glass opacity nodules in young patients.

BACKGROUND: The detection rate of ground-glass opacity (GGO) in young patients has increased year by year with the increasingly widespread use of high-resolution computed tomography (HRCT) and the increased resolution of HRCT imaging. However, no scholars have reported the clinical characteristics and prognosis of GGO in young patients systematically. The purpose of this study is to investigate the clinical characteristics and prognosis presenting as GGO in young patients. METHODS: Clinical data of 127 young patients who were diagnosed as GGO and who underwent video-assisted thoracoscopic surgery (VATS) and had routine pathological examination were collected from January 2016 to January 2017. Nodules were classified according to benign and malignant: 26 benign nodules (Group A) and 115 malignant nodules (Group B). The pathological types, nodules size, surgical methods were analyzed, and the clinical characteristics and prognosis were evaluated. RESULTS: The results of pathological examination of 91 pure ground-glass opacities (pGGOs) revealed 16 adenocarcinoma in situs (AISs), 42 micro invasive adenocarcinomas (MIAs), 13 invasive adenocarcinomas (IAs), 8 atypical adenomatous hyperplasias (AAHs), 1 inflammatory granuloma, 2 pulmonary inflammatory pseudotumors (IPTs) and 9 other benign nodules. The results of pathological examination of 50 mixed ground-glass opacities (mGGOs) revealed 6 AISs, 29 MIAs, 9 IAs, 1 AAH, 2 inflammatory granulomas and 3 other benign nodules. All patients had no lymph nodes invasion. The rates of perioperative complications were 6.30%, compared to 7.63% for long-term complications. None of the patients with GGO experienced a recurrence and death [2-year recurrence-free survival (RFS), 100%; 2-year overall survival (OS), 100%]. CONCLUSIONS: The GGO in young patients that received VATS has a high proportion of malignant, its prognosis is satisfied.

Endobronchial ultrasound-guided transbronchial needle aspiration can improve the diagnostic accuracy of positron emission tomography/computed tomography in hilar and/or mediastinal lymphadenopathy.

CONTEXT: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and positron emission tomography/computed tomography (PET/CT) are the two most extensively used methods for the diagnosis and staging of lung cancer. AIMS: The present study was designed to compare the diagnostic performance of EBUS-TBNA with that of PET/CT in patients with hilar and/or mediastinal lymphadenopathy. SETTINGS AND DESIGN: We compared the accuracy of EBUS-TBNA with that of PET/CT in the diagnosis of hilar and/or mediastinal lymphadenopathy and evaluated the diagnostic utility of EBUS-TBNA in patients with PET/CT false-positive and false-negative findings. METHODS: This study retrospectively analyzed 85 patients with hilar and/or mediastinal lymphadenopathy who underwent EBUS-TBNA and PET/CT between January 2014 and December 2017. The accuracy of EBUS-TBNA histopathology and cytopathology was evaluated and compared with PET/CT scan findings. RESULTS: The diagnostic accuracy of EBUS-TBNA combined with PET/CT was significantly higher than that of the single diagnostic method (P < 0.001). Among PET/CT-negative lymph nodes, 4 of 9 (44.4%) malignant lymph nodes were identified by EBUS-TBNA. Among PET/CT-positive lymph nodes, 43 of 47 (91.5%) benign lymph nodes were diagnosed by EBUS-TBNA. CONCLUSIONS: EBUS-TBNA combined with PET/CT could effectively reduce false-positive and false-negative rates in the diagnosis of hilar and mediastinal lymphadenopathy, which might provide accurate staging, determine optimum therapeutic strategy and improve survival in patients with lung cancer.

A genetic polymorphism affects the risk and prognosis of renal cell carcinoma: association with follistatin-like protein 1 expression.

Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2.004 (95% confidence internal [CI] = 1.190-3.375). Multivariate Cox regression analysis in 309 of 417 cases showed that rs1259293 genotype (CC vs TT + CT) independently predicted an unfavorable prognosis, with a hazard ratio of 2.531 (95% CI = 1.052-6.086). Expression of FSTL1 was significantly higher in adjacent renal tissues than in tumors, and significantly higher in the tissues with rs1259293 TT genotype than in those with rs1259293 TC+CC genotypes. rs1259293 C allele might generate a CTCF binding site that blocks trans-activation of FSTL1 expression. Our results indicate that rs1259293 is associated with an increased risk and unfavorable postoperative prognosis of RCC, possibly by down-regulating FSTL1 expression in renal tissues.

Hypothermia improves disease manifestations in SMA mice via SMN augmentation.

Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by a deficiency of survival motor neuron (SMN) protein. In this study, we evaluated the efficacy of intermittent transient hypothermia in a mouse model of SMA. SMA mice were exposed to ice for 50 s to achieve transient hypothermia (below 25°C) daily beginning on postnatal day 1. Neonatal SMA mice (Smn(-/-)SMN2(+/-)) who received daily transient hypothermia exhibited reduced motor neuron degeneration and muscle atrophy and preserved the architecture of neuromuscular junction when compared with untreated controls at day 8 post-treatment. Daily hypothermia also prolonged the lifespan, increased body weight and improved motor coordination in SMA mice. Quantitative polymerase chain reaction and western blot analyses showed that transient hypothermia led to an increase in SMN transcript and protein levels in the spinal cord and brain. In in vitro studies using an SMN knockdown motor neuron-like cell-line, transient hypothermia increased intracellular SMN protein expression and length of neurites, confirming the direct effect of hypothermia on motor neurons. These data indicate that the efficacy of intermittent transient hypothermia in improving outcome in an SMA mouse model may be mediated, in part, via an upregulation of SMN levels in the motor neurons.

Influence of laparoscopy vs. laparotomy on bacterial translocation and systemic inflammatory responses in a porcine model with peritonitis.

BACKGROUND: This study aimed to compare the effects of laparoscopy vs. laparotomy on bacterial translocation and immunologic responses in a porcine model with peritonitis caused by small bowel injuries (SBIs). METHODS: Pigs with SBIs were first established, assigned into either the laparoscopy group or the laparotomy group, and then received surgical intervention. During 72 hours (72 hr) observation period, blood, and tissues of different organs were obtained for bacterial cultures; endotoxin and peripheral leukocyte were determined; serum levels of IL-6, TNF-α, and CRP were measured. RESULTS: Blood cultures confirmed systemic bacteremia in all animals and the endotoxin level was comparable between groups at 24 hr after surgery. However, two days later, positive bacteremia was only detected in four pigs following laparoscopy and five following laparotomy. Eight and four pigs during laparoscopy (seven and six pigs during laparotomy) had translocated bacteria in mesenteric lymph nodes (MLN) and liver. The 72 hr later, bacteria in MLN, liver, lung, and kidney was found in 2, 1, 2, and 0 pig after laparoscopy, respectively (3, 2, 2, and 1 pig after laparotomy). The peripheral blood monocytes (PBMC) counts remained at a much lower level after laparoscopy than after laparotomy. Serum IL-6, TNF-α, and CRP increased notably after both procedures when compared to preoperative levels. However, significantly faster and lower regression of IL-6, TNF-α, and CRP were observed in the laparoscopy group. CONCLUSION: Compared with laparotomy, laparoscopy does not result in increased bacterial translocation, but decrease IL-6, TNF-α, and CRP release.

Is laparoscopy equal to laparotomy in detecting and treating small bowel injuries in a porcine model?

AIM: To evaluate the safety and effectiveness of laparoscopy compared with laparotomy for diagnosing and treating small bowel injuries (SBIs) in a porcine model. METHODS: Twenty-eight female pigs were anesthetized and laid in the left recumbent position. The SBI model was established by shooting at the right lower quadrant of the abdomen. The pigs were then randomized into either the laparotomy group or the laparoscopy group. All pigs underwent routine exploratory laparotomy or laparoscopy to evaluate the abdominal injuries, particularly the types, sites, and numbers of SBIs. Traditional open surgery or therapeutic laparoscopy was then performed. All pigs were kept alive within the observational period (postoperative 72 h). The postoperative recovery of each pig was carefully observed. RESULTS: The vital signs of all pigs were stable within 1-2 h after shooting and none of the pigs died from gunshot wounds or SBIs immediately. The SBI model was successfully established in all pigs and definitively diagnosed with single or multiple SBIs either by exploratory laparotomy or laparoscopy. Compared with exploratory laparotomy, laparoscopy took a significantly longer time for diagnosis (41.27 ± 12.04 min vs 27.64 ± 13.32 min, P = 0.02), but the time for therapeutic laparoscopy was similar to that of open surgery. The length of incision was significantly reduced in the laparoscopy group compared with the laparotomy group (5.27 ± 1.86 cm vs 15.73 ± 1.06 cm, P < 0.01). In the final post-mortem examination 72 h after surgery, both laparotomy and laparoscopy offered a definitive diagnosis with no missed injuries. Postoperative complications occurred in four cases (three following laparotomy and one following laparoscopy, P = 0.326). The average recovery period for bowel function, vital appearance, and food re-intake after laparoscopy was 10.36 ± 4.72 h, 14.91 ± 3.14 h, and 15.00 ± 7.11 h, respectively. All of these were significantly shorter than after laparotomy (21.27 ± 10.17 h, P = 0.004; 27.82 ± 9.61 h, P < 0.001; and 24.55 ± 9.72 h, respectively, P = 0.016). CONCLUSION: Compared with laparotomy, laparoscopy offers equivalent efficacy for diagnosing and treating SBIs, and reduces postoperative complications as well as recovery period.

Imbalance of circulating T-lymphocyte subpopulation in COPD and its relationship with CAT performance.

Chronic obstructive pulmonary disease (COPD) is associated with systemic effects, and T-cell-mediated immunity was involved in the COPD. COPD Assessment Test (CAT) could provide a valid, reliable, and standardized measure of COPD health status. The objective of this study was determination of lymphocyte subpopulation in patients with stable COPD (n = 52) and to ascertain if a relationship existed between T-lymphocyte subpopulation and CAT performance. The stable COPD patients were assessed with CAT, and divided into four groups with score >30 (n = 8), 20< score ≤30 (n = 16), 10< score ≤20 (n = 20), and score ≤10 (n = 8). Spearman's rank correlation was used to determine the relationship between proportion of T lymphocyte and CAT score. We found an elevated proportion of CD8(+) cells in COPD patients of the group with score >30 compared to other groups. Proportion of CD4(+) cells was significantly lower in the groups with score >30 and 20< score ≤30 when compared to groups with 10< score ≤20 and score ≤10. The CD4(+) :CD8(+) ratio was also significantly lower in the groups with score >30 and 20< score ≤30. Of note are the correlations of proportion of CD8(+) cells and CD4(+) :CD8(+) ratio with CAT performance when score >20. No correlations existed between proportion of CD4(+) , CD8(+) cells, CD4(+) :CD8(+) ratio, and CAT performance when score ≤20. Our results show that the determinants of T-lymphocyte subpopulation in COPD patients were value to assess physical conditions. We considered CD4(+) and CD8(+) T lymphocytes to be a representative and stable parameter in grading of health status in COPD patients.

[Identification of marsdeniae tenacissimae caulis and its adulterants by RAPD].

OBJECTIVE: To identify Marsdeniae Tenacissimae Caulis and its adulterants by RAPD (random amplified polymorphic DNA) and analyze the gene homology of Marsdeniae Tenacissimae Caulis from various habitats. METHODS: General DNA was isolated from Marsdeniae tenacissimae Caulis which were from seven various habitats and its six adulterants by CTAB, the twenty RAPD was used to identify them. RESULTS: Random primer 285 (GGG AAC CCT T) could amplify the gene of Marsdeniae tenacissimae Caulis from various habitats stablely, Marsdeniae tenacissimae Caulis and its adulterants could be identified by primer E01 (CCC AAG GTC C) effectively. CONCLUSION: The method of RAPD can be used to identify Marsdeniae Tenacissimae Caulis and its adulterants, the gene of Marsdeniae tenacissimae Caulis from various habitats have homology.