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1.  HIRA Gene is Lower Expressed in the Myocardium of Patients with Tetralogy of Fallot 
Chinese Medical Journal  2016;129(20):2403-2408.
Background:
The most typical cardiac abnormality is conotruncal defects (CTDs) in patients with 22q11 deletion syndrome (22q11DS). HIRA (histone cell cycle regulator) gene, as one of the candidate genes located at the critical region of 22q11DS, was reported as possibly relevant to CTD in animal models. This study aimed to analyze the level of expression of the HIRA gene in tetralogy of Fallot (TOF) patients and the potential DNA sequence variations in the promoter region.
Methods:
The messenger RNA (mRNA) expression was examined with quantitative real-time polymerase chain reaction in 39 myocardial tissues of the right ventricular outflow tract (RVOT) from TOF patients and 4 myocardial tissues of RVOT from noncardiac death children. The protein expression was detected using immunohistochemistry in 12 TOF patients and 4 controls. A total of 100 TOF cases and 200 healthy controls were recruited for DNA sequencing.
Results:
The mRNA and protein expressions of the HIRA gene in the myocardium of the TOF patients were both significantly lower as compared to the controls (P < 0.05). Five single nucleotide polymorphisms (SNPs), including g.4111A>G (rs1128399), g.4265C>A (rs4585115), g.4369T>G (rs2277837), g.4371C>A (rs148516780), and g.4543T>C (rs111802956), were found in the promoter region of the HIRA gene. There were no significant differences of frequencies in these SNPs between the TOF patients and the controls (P > 0.05).
Conclusion:
The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.
doi:10.4103/0366-6999.191745
PMCID: PMC5072250  PMID: 27748330
Congenital Heart Defects; Gene Expression; HIRA; Single Nucleotide Polymorphism; Tetralogy of Fallot
2.  Algorithm of chest wall keloid treatment 
Medicine  2016;95(35):e4684.
Abstract
Keloids are common in the Asian population. Multiple or huge keloids can appear on the chest wall because of its tendency to develop acne, sebaceous cyst, etc. It is difficult to find an ideal treatment for keloids in this area due to the limit of local soft tissues and higher recurrence rate. This study aims at establishing an individualized protocol that could be easily applied according to the size and number of chest wall keloids.
A total of 445 patients received various methods (4 protocols) of treatment in our department from September 2006 to September 2012 according to the size and number of their chest wall keloids. All of the patients received adjuvant radiotherapy in our hospital. Patient and Observer Scar Assessment Scale (POSAS) was used to assess the treatment effect by both doctors and patients. With mean follow-up time of 13 months (range: 6–18 months), 362 patients participated in the assessment of POSAS with doctors.
Both the doctors and the patients themselves used POSAS to evaluate the treatment effect. The recurrence rate was 0.83%. There was an obvious significant difference (P < 0.001) between the before-surgery score and the after-surgery score from both doctors and patients, indicating that both doctors and patients were satisfied with the treatment effect.
Our preliminary clinical result indicates that good clinical results could be achieved by choosing the proper method in this algorithm for Chinese patients with chest wall keloids. This algorithm could play a guiding role for surgeons when dealing with chest wall keloid treatment.
doi:10.1097/MD.0000000000004684
PMCID: PMC5008580  PMID: 27583896
algorithm; chest wall; keloid; surgery
3.  Cardiac β2-Adrenergic Receptor Phosphorylation at Ser355/356 Regulates Receptor Internalization and Functional Resensitization 
PLoS ONE  2016;11(8):e0161373.
Previous studies have demonstrated that β2-adrenergic receptors (β2ARs) can be phosphorylated by G protein-coupled receptor kinases (GRKs) and protein kinase A (PKA), affecting β2AR internalization and desensitization. However, the exact physiological function of β2ARs in cardiomyocytes is unknown. In this study, we showed that neonatal mouse cardiomyocytes had different contraction and internalization responses to sustained or repeated, transient agonist stimulation. Specifically, short-time stimulation (10 min) with epinephrine or norepinephrine increased the cardiomyocyte contraction rate, reaching a maximum at 5 min, followed by a slow decline. When the agonist was re-added after a 60-min wash-out period, the increase in the cardiomyocyte contraction rate was similar to the initial response. In contrast, when cardiomyocytes were exposed continuously to epinephrine or norepinephrine for 60 min, the second agonist stimulation did not increase the contraction response. These results indicated that continuous β2AR stimulation caused functional desensitization. Phosphorylation of β2ARs at serine (Ser)355/356 GRK phosphorylation sites, but not at Ser345/346 PKA phosphorylation sites increased with continuous epinephrine stimulation for 60 min. Accordingly, β2AR internalization increased. Interestingly, β2AR internalization was blocked by mutations at the GRK phosphorylation sites, but not by mutations at the PKA phosphorylation sites. Furthermore, inhibition of β2AR dephosphorylation by okadaic acid, a phosphatase 2A inhibitor, impaired the recovery of internalized β2ARs and reduced the cardiomyocyte contraction rate in response to epinephrine. Finally, epinephrine treatment induced the physical interaction of β-arrestin with internalized β2ARs in cardiomyocytes. Together, these data revealed the essential role of the Ser355/356 phosphorylation status of β2ARs in regulating receptor internalization and physiological resensitization in neonatal cardiomyocytes to contraction functions.
doi:10.1371/journal.pone.0161373
PMCID: PMC4991819  PMID: 27541735
4.  Cholecystectomy is associated with higher risk of early recurrence and poorer survival after curative resection for early stage hepatocellular carcinoma 
Scientific Reports  2016;6:28229.
Although cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC), the association between cholecystectomy and prognosis of HCC patients underwent curative resection has never been examined. Through retrospective analysis of the data of 3933 patients underwent curative resection for HCC, we found that cholecystectomy was an independent prognostic factor for recurrence-free survival (RFS) of patients at early stage (BCLC stage 0/A) (p = 0.020, HR: 1.29, 95% CI: 1.04–1.59), and the 1-, 3-, 5-year RFS rates for patients at early stage were significantly worse in cholecystectomy group than in non-cholecystectomy group (80.5%, 61.8%, 52.0% vs 88.2%, 68.8%, 56.8%, p = 0.033). The early recurrence rate of cholecystectomy group was significantly higher than that of non-cholecystectomy group for patients at early stage (59/47 vs 236/333, p = 0.007), but not for patients at advanced stage (BCLC stage C) (p = 0.194). Multivariate analyses showed that cholecystectomy was an independent risk factor for early recurrence (p = 0.005, HR: 1.52, 95% CI: 1.13–2.03) of early stage HCC, but not for late recurrence (p = 0.959). In conclusion, cholecystectomy is an independent predictor for early recurrence and is associated with poorer RFS of early stage HCC. Removal of normal gallbladder during HCC resection may be avoided for early stage patients.
doi:10.1038/srep28229
PMCID: PMC4913319  PMID: 27320390
5.  UBAP2 negatively regulates the invasion of hepatocellular carcinoma cell by ubiquitinating and degradating Annexin A2 
Oncotarget  2016;7(22):32946-32955.
The ubiquitin-dependent proteasomal degradation of proteins controls signaling and cellular survival. In this study, we found that ubiquitin associated protein 2 (UBAP2) was significantly downregulated in hepatocellular carcinoma (HCC) tissues compared with adjacent normal tissues. Furthermore, higher expression of UBAP2 in cancer tissues was correlated with good prognosis in HCC patients. Knockdown of UBAP2 significantly enhanced the invasion and proliferation of HCC cells in vitro and promoted tumor growth in vivo, while enforced expression of UBAP2 impaired the aggressive ability and tumor growth of HCC cells. Mechanistically, UBAP2 formed a complex with Annexin A2 and promoted the degradation of Annexin A2 protein by ubiquitination, and then inhibited HCC progression. Collectively, UBAP2 appears as a novel marker for predicting prognosis and a therapeutic target for HCC.
doi:10.18632/oncotarget.8783
PMCID: PMC5078065  PMID: 27121050
hepatocellular carcinoma; ubiquitin associated protein 2; Annexin A2; ubiquitination; invasion
6.  The efficacy of postoperative radiotherapy in localized primary soft tissue sarcoma treated with conservative surgery 
Background
To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS) and to identify prognostic factors.
Methods and materials
Between January 2000 and July 2010, 220 consecutive patients with localized primary STS, who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis was applied to identify the prognostic factors.
Results
After a median follow-up of 68 months (range, 5–127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2 and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235–0.707, P = 0.001), with 5-year LFFS of 81.1 and 63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512, 95 % CI 0.296–0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034).
Conclusion
Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized primary STS. The efficacy of RT on survival warrants further prospective study.
Electronic supplementary material
The online version of this article (doi:10.1186/s13014-016-0605-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s13014-016-0605-y
PMCID: PMC4766748  PMID: 26911328
Soft tissue sarcoma; Surgery; Radiotherapy; Local recurrence; Overall survival
7.  Generation and characterization of a tetraspanin CD151/integrin α6β1-binding domain competitively binding monoclonal antibody for inhibition of tumor progression in HCC 
Oncotarget  2016;7(5):6314-6322.
Our previous studies revealed that tetraspanin CD151 plays multiple roles in the progression of hepatocellular carcinoma (HCC) by forming a functional complex with integrin α6β1. Herein, we generated a monoclonal antibody (mAb) that dissociates the CD151/integrin α6β1 complex, and we evaluated its bioactivity in HCCs. A murine mAb, tetraspanin CD151 (IgG1, called CD151 mAb 9B), was successfully generated against the CD151-integrin α6β1 binding site of CD151 extracellular domains. Co-immunoprecipitation using CD151 mAb 9B followed by Western blotting detected a 28 kDa protein. Both immunofluorescent and immunohistochemical staining showed a good reactivity of CD151 mAb 9B in the plasma membrane and cytoplasm of HCC cells, as well as in liver cells. In vitro assays demonstrated that CD151 mAb 9B could inhibit neoangiogenesis and both the mobility and the invasiveness of HCC cells. An in vivo assay showed that CD151 mAb 9B inhibited tumor growth potential and HCC cells metastasis. We successfully produced a CD151 mAb 9B targeting the CD151/integrin α6β1-binding domain, which not only can displayed good reactivity to the CD151 antigen but also prevented tumor progression in HCC.
doi:10.18632/oncotarget.6833
PMCID: PMC4868758  PMID: 26756217
hepatocellular carcinoma; tetraspanin CD151; integrin α6β1; monoclonal antibody; therapeutical agent
8.  Early Outcomes of Primary Total Hip Arthroplasty for Osteonecrosis of the Femoral Head in Patients with Human Immunodeficiency Virus in China 
Chinese Medical Journal  2015;128(15):2059-2064.
Background:
Studies have reported that patients with human immunodeficiency virus (HIV) have a high incidence of osteonecrosis of the femoral head (ONFH). Total hip arthroplasty (THA) is an effective management of ONFH. However, little data exist regarding the use of THA for the HIV patients with ONFH in China. This study reviewed the outcomes of HIV-positive patients who underwent THA for ONFH, compared with HIV-negative individuals.
Methods:
The patients who underwent THA for ONFH from September 2012 to September 2014 in Beijing Ditan Hospital, Capital Medical University were retrospectively studied. Twenty-eight HIV-positive patients and 35 HIV-negative patients underwent 48 THAs and 45 THAs with cementless components, respectively. Medical records and follow-up data were reviewed. Harris Hip Score (HHS) was applied to evaluate the pain and function of the hips before and after THA. Complications such as wound healing, surgical site infection, deep venous thrombosis, pulmonary embolism, sepsis, mortality, and complications from the prosthesis were reviewed. The operation time, blood loss, and hospital stay were compared between the two groups.
Results:
The mean follow-up period was 19.5 ± 5.8 months (ranging from 6 to 30 months). The mean age of the HIV-positive patients with osteonecrosis at the time of surgery was 35 years old, which was significantly lower than that of the HIV-negative group (42 years old) (P < 0.05). The HIV-positive patients underwent surgery a mean of 2.5 years after their original symptoms, which was significantly shorter than the HIV-negatives’ (mean 4 years) (P < 0.05). Among HIV-positive patients, the prevalence of being male and rate of bilateral procedures were significantly higher than those in the HIV-negative group (P < 0.05). The operation time in HIV-positive patients was significantly longer than that in HIV-negative patients (P < 0.05). There were no significant differences in blood loss or hospital stay between the two groups (P > 0.05). The HHSs of two groups significantly improved after THAs (P < 0.05), without significant difference between two groups. No wound complication, sepsis, mortality, prosthesis complication, and occupational exposure occurred, except for two cases of heterotopic ossification and one case of humeral head necrosis.
Conclusions:
ONFH is more likely to occur bilaterally in younger HIV-positive males. The development of osteonecrosis seems faster in HIV-positive patients than in HIV-negative patients. This should be cautionary for asymptomatic HIV-positive patients with low viral RNA level and in the primary HIV stage. Despite longer operation times in the HIV-positive patients than in the HIV-negative patients, THA is still a safe and efficient approach to treat ONFH in HIV-positive patients. The incidence of complications is much lower than previously reported. However, the long-term follow-up is needed.
doi:10.4103/0366-6999.161364
PMCID: PMC4717963  PMID: 26228219
Arthroplasty; Harris Hip Score; Hip; Human Immunodeficiency Virus Infections; Osteonecrosis of the Femoral Head; Outcomes
9.  TMPRSS4 facilitates epithelial-mesenchymal transition of hepatocellular carcinoma and is a predictive marker for poor prognosis of patients after curative resection 
Scientific Reports  2015;5:12366.
TMPRSS4 (Transmembrane protease serine 4) is up-regulated in a broad spectrum of cancers. However, little is known about the biological effects of TMPRSS4 on hepatocellular carcinoma (HCC) and the related mechanisms. In the present study, we found that overexpression of TMPRSS4 significantly promoted the invasion, migration, adhesion and metastasis of HCC. Further more, TMPRSS4 induced EMT of HCC, which was mediated via snail and slug as a result of Raf/MEK/ERK1/2 activation, and inhibition of ERK1/2 activation by its inhibitor was associated with reduced cell invasion and reversion of EMT. In addition, we demonstrated that TMPRSS4 remarkably suppressed the expression of RECK, an inhibitor of angiogenesis, and drastically induced tumor angiogenesis and growth. More important, in clinical HCC specimens, TMPRSS4 expression was significantly correlated with tumor staging and was inversely correlated with E-cadherin and RECKS expression. Expression of TMPRSS4 is significantly associated with HCC progression and is an independent prognostic factor for postoperative worse survival and recurrence. In conclusion, TMPRSS4 functions as a positive regulator of Raf/MEK/ERK1/2 pathway and promotes HCC progression by inducing EMT and angiogenesis. The increase of TMPRSS4 expression may be a key event for HCC progression and may be regarded as a potential prognostic marker for HCC.
doi:10.1038/srep12366
PMCID: PMC4507176  PMID: 26190376
10.  A Systemic Review of Autologous Fat Grafting Survival Rate and Related Severe Complications 
Chinese Medical Journal  2015;128(9):1245-1251.
Objective:
Clinical application of autologous fat grafting (AFG) is quickly expanding. Despite the widely acceptance, long-term survival rate (SR) of AFG remains a question not yet solved. Meanwhile, although rare, severe complications related to AFG including vision loss, stroke even death could be seen in the literature.
Data Sources:
A comprehensive research of PubMed database to June 2013 was performed according to guidelines of the American Society of Plastic Surgeons Fat Graft Task Force Assessment Methodology. Articles were screened using predetermined inclusion and exclusion criteria.
Study Selection:
Data collected included patient characteristics, surgical technique, donor site, recipient site, graft amount, and quantified measurement methods. Patient cohorts were pooled, and SR was calculated. All the severe complications were also summarized according to the different clinical characteristics.
Results:
Of 550 articles, 16 clinical articles and 10 animal studies met the inclusion criteria and provided quantified measurement methods. Totally, 596 patients were included. SR varied from 34% to 82% in breast and 30–83% in the facial area. Nude mice were applied to investigate human fat grafting SR (38.3–52.5% after 15 weeks). Rabbits were commonly used to study animal AFG SR (14.00–14.56% after 1-year). Totally, 21 severe complications were reported, including death (2), stroke (10), vision loss (11, 8 of which accompanied with stroke), sepsis (3), multiple abscess (1) and giant fat necrotic cyst (2). Ten of these complications happened within 10 years.
Conclusions:
There is no unified measurement method to evaluate fat graft SR until now and no clinical evidence to show better SR according to different donor and recipient cite. Body mass index change between pre- and postoperation may be the bias factor in evaluating fat SR. Fat embolisms of the ophthalmic artery and the middle cerebral artery are the most severe complication of AFG and still lack of effective treatment.
doi:10.4103/0366-6999.156142
PMCID: PMC4831554  PMID: 25947410
Autologous Fat Grafting; Complication; Fat Survival
11.  Postoperative adjuvant transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond the Milan criteria: a retrospective analysis 
Objective: To clarify the value of postoperative adjuvant transcatheter arterial chemoembolization (TACE) for resectable multiple hepatocellular carcinoma beyond the Milan criteria. Background: Patients with multiple HCC have been shown to have a worse survival after a partial hepatectomy (PH) because of the high incidence of intrahepatic tumor recurrence. Postoperative adjuvant TACE is an optional strategy for HCC patients with a high recurrence risk. Its effects and range of applications are debatable. Methods: This retrospective study enrolled 135 HCC patients with resectable multiple hepatocellular carcinoma beyond the Milan criteria, and those patients underwent a hepatectomy with/without postoperative adjuvant TACE from Jan. 2004 to Dec. 2008. The patients were divided to the PH cohort or the PH+TACE cohort. The prognosis measures were the disease-free survival (DFS) and overall survival (OS) from the date of treatment. Univariate and multivariate analyses were used to assess the prognostic factors associated with DFS and OS, using the Cox proportional hazards model. Results: The 1-, 2-, and 5-year DFS and OS for the PH+TACE group differed significantly from the PH group (p = 0.004, p = 0.002, respectively). Multivariate analysis revealed that the significant independent risk factors associated with the DFS and OS were postoperative TACE treatment (p = 0.002, p = 0.001, respectively) and the number of tumors (p = 0.006, p = 0.037, respectively). Conclusions: Our results show that postoperative adjuvant treatment resulted in delayed intrahepatic recurrence and better survival for patients with resectable multiple hepatocellular carcinoma beyond the Milan criteria. Postoperative adjuvant TACE should be regarded as a common strategy for patients with resectable multiple HCC beyond the Milan criteria.
PMCID: PMC4300716  PMID: 25628953
TACE; multiple hepatocellular carcinoma; Milan criteria; recurrence; prognosis
12.  Crystal structure of aqua­chlorido­bis­(2-eth­oxy-6-formyl­phenolato-κ2 O 1,O 6)iron(III) aceto­nitrile hemisolvate 
In both complex mol­ecules in the asymmetric unit, the FeIII ion has a distorted O5Cl octa­hedral coordination environment defined by two bidentate 2-eth­oxy-6-formyl­phenolato ligands, one Cl atom and one water mol­ecule. In the crystal, O—H⋯O hydrogen bonds link the two independent mol­ecules to form a dimer while the solvent mol­ecule is linked to the complex mol­ecule by a weak C—H⋯O hydrogen bond. Further weak C—H⋯O inter­actions along with weak C—H⋯Cl hydrogen bonds link the components into chains parallel to [001].
In the title compound, [Fe(L)2Cl(H2O)]·0.5CH3CN, (HL is 3-eth­oxy-2-hy­droxy-benzaldehyde, C9H10O3), there are two independent complex mol­ecules and one aceto­nitrile solvent mol­ecule in the asymmetric unit. In each complex mol­ecule, the FeIII ion has a distorted O5Cl octa­hedral coordination environment defined by two bidentate 2-eth­oxy-6-formyl­phenolato ligands, one Cl atom and one water mol­ecule. In the crystal, O—H⋯O hydrogen bonds link the two independent mol­ecules to form a dimer. The solvent mol­ecule is linked to the complex mol­ecule by a weak C—H⋯O hydrogen bond. Further weak C—H⋯O inter­actions along with weak C—H⋯Cl hydrogen bonds link the components into chains parallel to [001].
doi:10.1107/S1600536814021205
PMCID: PMC4257307  PMID: 25484720
crystal structure; solvothermal synthesis; Fe(III) complex; dimer; hydrogen bonding.
13.  Incidence of pocket hematoma after electrophysiological device placement: dual antiplatelet therapy versus low-molecular-weight heparin regimen 
Background
Given the increasing number of patients who require dual antiplatelet (DAP) therapy and electrophysiological device (EPD) placement, perioperative antiplatelet management is a current challenge. In this study, we investigated the incidence of pocket hematoma formation after EPD placement in patients undergoing DAP therapy or an alternative low-molecular-weight heparin (LMWH) regimen.
Methods
This clinical observational study was performed from July 2010 to July 2012. In total, 171 patients were enrolled in the analysis after meeting the inclusion criteria. These patients were divided into two groups: 86 patients were treated with DAP therapy at the time of device implantation, and the DAP therapy was discontinued for 5 to 7 days and replaced with enoxaparin before device implantation in the other 85 patients. Adenosine phosphate (ADP)-mediated platelet aggregation and arachidonic acid-induced platelet aggregation were tested preoperatively. We compared the incidence of pocket hematoma between the two groups and the association of pocket hematoma development with ADP-mediated platelet aggregation and arachidonic acid-induced platelet aggregation.
Results
The incidence of pocket hematoma in the patients who continued DAP was lower than that in the patients who replaced the dual antiplatelet regimen with LMWH (3.49% vs. 16.47%, respectively; X2 = 6.66, P < 0.01). Among the patients who continued DAP therapies, the rate of ADP-mediated platelet aggregation inhibition in patients with pocket hematomas was higher than that in patients without pocket hematomas. None of the patients undergoing DAP or enoxaparin therapy developed pocket infection, thromboembolic events, or other serious complications. Multiple logistic regression analysis revealed that LMWH therapy was an independent risk factor for the development of pocket hematoma (RR = 0.054, 95%CI = 0.012–0.251). Furthermore, patients undergoing LMWH therapy were 5.1-fold more likely to develop pocket hematomas than were DAP-treated individuals.
Conclusion
Continuance of DAP therapy does not increase the risk of pocket hematoma formation after EPD placement.
doi:10.11909/j.issn.1671-5411.2014.03.013
PMCID: PMC4178510  PMID: 25278967
Antiplatelet drug; Hematoma; Low-molecular-weight heparin; Electrophysiological device
14.  Comprehensive Multiple Molecular Profile of Epithelial Mesenchymal Transition in Intrahepatic Cholangiocarcinoma Patients 
PLoS ONE  2014;9(5):e96860.
Background
The aim of this study is to investigate the expression profile of multiple epithelial mesenchymal transition (EMT)-related molecules in intrahepatic cholangiocarcinoma (ICC) and the related prognostic significance.
Methods
Immunohistochemistry was performed to determine the expression of E-cadherin, Vimentin, Snail, slug and β-catenin in a tissue microarray consisting of tumor tissues of 140 ICC patients undergoing curative resection. The correlation between the expression of these molecules and the clinicopathological characteristics of ICC patients was analyzed, and their prognostic implication was evaluated.
Results
Reduced E-cadherin and increased Vimentin expression, the characteristic changes of EMT, identified in 55.0% and 55.7% of primary ICCs, respectively, were correlated with lymphatic metastasis and poorer overall survival (OS) and disease-free survival (DFS) of ICCs. The overexpression of snail and nonmembranous β-catenin, which are the major regulators of the EMT, were identified in 49.2% and 45.7% of primary ICCs, while little slug expression was detected in ICCs. Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss. The overexpression of snail predicted worse OS and DFS. Snail overexpression correlated with the down-regulation of E-cadherin and the up-regulation of Vimentin. Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.
Conclusions
These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.
doi:10.1371/journal.pone.0096860
PMCID: PMC4016113  PMID: 24816558
15.  Increased Peripheral Proinflammatory T Helper Subsets Contribute to Cardiovascular Complications in Diabetic Patients 
Mediators of Inflammation  2014;2014:596967.
Background. Coronary atherosclerotic heart disease (CHD) is one of the major concerns in type 2 diabetes (T2D). The systemic chronic inflammation has been postulated to bridge the increased risk of cardiovascular disease and T2D. We formulated that increased peripheral proinflammatory T helper subsets contributed to the development of cardiovascular complications in diabetic patients. Methods. The frequencies of peripheral total CD4+ T helper cells, proinflammatory Th1, Th17, and Th22 subsets were determined by flow cytometry in diabetic patients with or without CHD (n = 42 and 67, resp.). Results. Both peripheral frequencies and total numbers of Th1, Th17, and Th22 cells were further increased in diabetic patients with CHD. Logistic regression and categorical cross-table analysis further confirmed that increased proinflammatory Th subsets, especially Th22, were independent risk factors of cardiovascular complication in diabetes. Elevated Th subsets also correlated with increased CRP levels and the atherogenic index of plasma. Moreover, Th1 frequency and Th22 numbers demonstrated remarkable potential in predicting CHD in diabetes. Conclusions. Increased peripheral proinflammatory T helper subsets act in concert and contribute to the increased prevalence of diabetic cardiovasculopathy. The recently identified Th22 cells might play an independent role in CHD and represent a novel proxy for cardiovascular risks in diabetes.
doi:10.1155/2014/596967
PMCID: PMC3997161  PMID: 24803740
16.  Marjolin’s ulcer: a preventable malignancy arising from scars 
Background
Marjolin’s ulcer (MU) is a rare malignancy arising from various forms of scars. This potentially fatal complication typically occurs after a certain latency period. This article attempts to reveal the importance of the latency period in the prevention and early treatment of the malignancy.
Methods
A retrospective review of 17 MU patients who underwent surgical procedures between June of 2005 and December 2011 was conducted. Etiology of injuries, latency period, repeated ulceration, and outcomes were recorded. This observational report reveals characteristics of patients who develop MU.
Results
An incidence of 0.7% of MU was found amongst patients complaining of existing scars in our study; burns and trauma were the most common etiology of MU. The mean latency period was 29 years (SD = 19) and the mean post-ulceration period was 7 years (SD = 9). Statistical analysis revealed a negative correlation between the age of patients at injury and the length of latency period (r = −0.8, P <0.01), as well as the lengths of pre-ulceration and post-ulceration periods (r = −0.7, P <0.01).
Conclusions
Patients experience different lengths of pre- and post-ulceration periods during the latency period. Younger patients tend to have a longer latency period. Skin breakdown on chronic scars and chronic unhealed ulcers are two main sources of MU. MU may be preventable with a close surveillance of the ulcer during the latency period.
doi:10.1186/1477-7819-11-313
PMCID: PMC3896958  PMID: 24341890
Marjolin’s ulcer; Squamous cell carcinoma
17.  Tris[4-bromo-2-(methyl­imino­meth­yl)phenolato-κ2 N,O]cobalt(III) 
In the title compound, [Co(C8H7BrNO)3], the CoIII ion is coordinated in a slightly distorted octa­hedral environment by three N atoms and three O atoms from three bidentate 4-bromo-2-(methyl­imino­meth­yl)phenolate ligands. The dihedral angles between the benzene rings are 82.6 (2), 57.1 (2) and 62.9 (2)°. In the crystal, mol­ecules are linked by pairs of weak C—H⋯Br hydrogen bonds, forming inversion dimers.
doi:10.1107/S1600536813027591
PMCID: PMC3884257  PMID: 24454033
18.  Nipple Retractor to Correct Inverted Nipples 
Breast Care  2011;6(6):463-465.
Background
Inverted nipples are a common problem and a challenging clinical condition to repair. Multiple methods have been reported to correct inverted nipples, most of which will destroy breastfeeding function.
Patients and Methods
We have designed a simple nipple retractor to correct inverted nipples. A total of 53 patients with 95 inverted nipples underwent an operation in which the nipples were retracted into a normal position and fixated with the nipple retractor and wires under local anesthesia. Nipple retractors were to be worn for 6 months. Postoperatively, the patients were invited to follow-up on the 1st day, the 7th day, after 1 month, 3 months and 6 months, and yearly thereafter. Wire adjustments were performed as needed. Mean follow-up was 11.9 months (range 8–18 months).
Results
Improvement occurred in all patients and was sustained in all cases throughout the follow-up period. The total complication rate was 5.26% (5/95). The main complications included depigmentation (2.11%, 2/95), areolar ulcer (2.11%, 2/95), and wire dislocation (1.05%, 1/95).
Conclusion
The nipple retractor is a simple tool with which severely inverted nipples can be successfully corrected with a low complication rate. Close follow-up and careful postoperative care are important to avoid complications.
doi:10.1159/000335221
PMCID: PMC3290018  PMID: 22419901
Inverted nipple; Surgery; Nipple retractor
19.  Cysteamine increases expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets 
AIM: To determine the in vivo and in vivo effects of cysteamine (CS) on expression and activity of H+-K+-ATPase of gastric mucosal cells in weaning piglets.
METHODS: Eighteen litters of newborn Xinhuai piglets were employed in the in vivo experiment and allocated to control and treatment groups. From 12 d of age (D12), piglets in control group were fed basal diet, while the treatment group received basal diet supplemented with 120 mg/kg CS. Piglets were weaned on D35 in both groups. Six piglets from each group (n = 6) were slaughtered on D28 (one week before weaning), D35 (weaning), D36.5, D38, D42, and D45 (36 h, 72 h, one week and 10 d after weaning), respectively. Semi-quantitative RT-PCR was performed to determine the levels of H+-K+-ATPase mRNA in gastric mucosa. H+-K+-ATPase activity in gastric mucosa homogenate was also determined. Gastric mucosal epithelial cells from piglets through primary cultures were used to further elucidate the effect of CS on expression and activity of H+-K+-ATPase in vivo. Cells were treated for 20 h with 0.001, 0.01, and 0.1 mg/mL of CS (n = 4), respectively. The mRNA expression of H+-K+-ATPase and somatostatin (SS) as well as the H+-K+-ATPase activity were determined.
RESULTS: in vivo, both mRNA expression and activity of H+-K+-ATPase in gastric mucosa of control group exhibited a trend to increase from D28 to D45, reaching a peak on D45, but did not show significant age differences. Furthermore, neither the mRNA expression nor the activity of H+-K+-ATPase was affected significantly by weaning. CS increased the mRNA expression of H+-K+-ATPase by 73%, 53%, 30% and 39% on D28 (P = 0.014), D35 (P = 0.017), D42 (P = 0.013) and D45 (P = 0.046), respectively. In accordance with the mRNA expression, H+-K+-ATPase activities were significantly higher in treatment group than in control group on D35 (P = 0.043) and D45 (P = 0.040). In vivo, CS exhibited a dose-dependent effect on mRNA expression and activity of H+-K+-ATPase. Both H+-K+-ATPase mRNA expression and activity in gastric mucosal epithelial cells were significantly elevated after 20 h of exposure to the moderate (H+-K+-ATPase expression: P=0.03; H+-K+-ATPase activity: P = 0.014) and high concentrations (H+-K+-ATPase expression: P=0.017; H+-K+-ATPase activity: P = 0.022) of CS. Significant increases in SS mRNA expression were observed to accompany the elevation of H+-K+-ATPase expression and activity induced by the moderate (P = 0.024) and high concentrations (P = 0.022) of CS. Low concentration of CS exerted no effects either on expression and activity of H+-K+-ATPase or on SS mRNA expression in cultured gastric mucosal epithelial cells.
CONCLUSION: No significant changes are observed in mRNA expression and activity of H+-K+-ATPase in gastric mucosa of piglets around weaning from D28 to D45. CS increases expression and activity of gastric H+-K+-ATPase in vivo and in vivo. SS is involved in mediating the effect of CS on gastric H+-K+-ATPase expression and activity in weaning piglets.
doi:10.3748/wjg.v11.i42.6707
PMCID: PMC4355770  PMID: 16425370
Cysteamine; Weaning piglets; H+-K+-ATPase; Gastric mucosal cells; Somatostatin
20.  Developmental patterns of GHr and SS mRNA expression in porcine gastric tissue 
AIM: The present study was aimed to investigate the developmental patterns of growth hormone receptor (GHr) and somatostatin (SS) mRNA expression in porcine gastric tissue and its relationship with gastric growth and gastric functional development.
METHODS: Erhualian and Large White boars were selected randomly and sampled at birth (D0), 3, 20, 30, 90, 120 and 180 days of age respectively, meanwhile the bodyweight and gastric weight were recorded. The single tube semi-quantitative RT-PCR was applied in this experiment to investigate the developmental patterns of gastric GHr and SS mRNA expression, the correlations between the patterns of mRNA expression and the relative gastric weight (ratio of gastric weight to bodyweight) and the pepsin contents in gastric mucous membrane were analyzed. In order to further elucidate the effect of GH on gastric function, the primary cultures of gastric fundic mucosal cells were treated with 2 ng/ml, 20 ng/ml and 200 ng/ml of rpGH for 18 hrs respectively, and the pepsin contents in culture medium were measured.
RESULTS: The expression of GHr mRNA was high at birth, followed by a significant decrease at 3 days of age (D3) in both breeds. In Large White boars, the expression of GHr mRNA reached a peak at D90 and remained a plateau afterward. In Erhualian pigs, however, a slight yet significant increase occurred at D30 reaching a level that was kept constant thereafter. From birth to D30, the expression of GHr mRNA in gastric tissue was higher in Erhualian boars than that in Large White boars, but from D90 to D180, the higher expression of GHr mRNA was found in Large White boars. The gastric GHr mRNA expression was significantly correlated with the relative gastric weight (r = 0.541, P < 0.05) and pepsin content in gastric mucosa (r = 0.625, P < 0.05) respectively.
The gastric SS mRNA expression was high at birth (Erhualian 1.59, Large White 0.80), but dropped significantly at D3 (Erhualian 0.95, Large White 0.19, P < 0.05), a stepwise increase was followed thereafter until a peak at D30 (Erhualian 1.71, Large White 0.95) In general, Erhualian pigs expressed higher levels of SS mRNA in gastric tissue as compared with Large White pigs at the same age (P < 0.05). No significant correlations between SS mRNA and relative gastric weight or pepsin content were found.
In vitro, 2 ng/ml of rpGH elicited significant increase in pepsin secretion from primary cultures of gastric mucosal cells (P < 0.05), and no responses were observed at 20 ng/ml and 200 ng/ml.
CONCLUSION: The results suggested that: 1, GHr and SS mRNA in porcine stomach are expressed according to strain specific developmental patterns; 2, GH acts directly at the gastric tissue and regulates the structural and functional growth of stomach.
doi:10.3748/wjg.v9.i5.1058
PMCID: PMC4611372  PMID: 12717856

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