Children with type 1 diabetes in COVID-19 pandemic: Difficulties and solutions.

Children/adolescents with type 1 diabetes (T1D) require holistic approach and continuous care. However, the coronavirus disease 2019 (COVID-19) pandemic has made challenges for the T1D children and their caregivers, professionals, and the healthcare system. This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic. T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide, which deserves a public concern particularly in the COVID-19 pandemic. As reported in previous studies, T1D is a risk factor related to severe cases, while the virus may induce new-onset diabetes and serious complications. Moreover, restriction strategies influence medical availability and lifestyle, impact glycemic control and compilation management, and thus pose stress on families and health providers of youths with T1D, especially on those with certain fragile conditions. Therefore, special treatment plans are required for children provided by caregivers and the local health system. Latest health tools such as improved medical devices and telemedicine service, as well as a combined support may benefit in this period. This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic. Therefore, strategies are supposed to be formulated to mitigate the difficulties and stress among this group, particularly in the most at-risk population. Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations.

A Hepatocellular Carcinoma Patient with TSC1 Mutations Benefits from Treatment with Everolimus: A Case Report.

Hepatocellular carcinoma (HCC) has a high degree of malignancy and poor prognosis. Treatment options for patients with advanced HCC are limited. There is currently no evidence to approve the accumulation of targeted therapies for HCC to support the inhibition of the PI3K/Akt/mTOR signaling pathway as an effective therapeutic strategy. We report on a patient with advanced HCC carrying the TSC1 gene mutation who responded well to the mammalian target of rapamycin inhibitor everolimus. Computed tomography revealed tumor shrinkage and maintenance of partial remission after everolimus treatment for >12.3 months. To the best of our knowledge, this is the first clinical case report showing benefit from everolimus treatment in HCC patients with TSC1 gene mutations. Therefore, everolimus may be used as a potential targeted therapy for HCC with TSC1 gene mutation.

Clinical efficacy and safety of acupuncture treatment of TIC disorder in children: A systematic review and meta-analysis of 22 randomized controlled trials.

OBJECTIVE: To systematically evaluate the clinical efficacy and safety of acupuncture in the treatment of Tic Disorders (TD) in children, and to clarify the current evidence regarding the clinical application of acupuncture in the treatment of TD. METHODS: Randomized controlled trials (RCTs) comparing acupuncture treatment with pharmaceutical treatment for TD were included in this review. A comprehensive search of 6 electronic literature databases was conducted, and the retrieval date was from the establishment of the database to April 2020. The Cochrane Collaboration's bias risk assessment tool was used to evaluate the bias risk of the included literature, and adopted the Review Manager 5.3 was used for statistical analysis of the data in the included literature. RESULTS: A total of 22 RCTs (1668 participants) were included in this review. Meta-analysis indicated that acupuncture showed superior effects in the following aspects, including higher overall effective rate [RR = 1.20,95 % CI(1.09,1.20),P＜0.00001], significant reduction in Yale Global Tic Severity Scale (YGTSS) scores [MD=-2.79,95 %CI(-4.75,-0.82),P = 0.005], lower incidence of adverse effects [RR = 0.26,95 %CI(0.17,0.41),P＜0.00001], and reduced recurrence rate [RR = 0.28,95 %CI(0.17,0.46),P＜0.00001]. CONCLUSION: Acupuncture treatment alone is more effective in the treatment of TD than pharmaceutical treatment, as seen in the reduction of YGTSS scores, fewer adverse effects and lower recurrence rates.

Cryoballoon ablation for extrapulmonary vein targets.

PURPOSE OF REVIEW: Cryoballoon catheter can create large and contiguous lesions with stable contact during ablation. It has proven to be well tolerated and effective in pulmonary vein isolation. But atrial arrhythmias, including atrial fibrillation, atrial tachycardia, and atrial flutter (AFL), also relate to many extrapulmonary vein targets. It is necessary to understand the current evidence for the use of cryoballoon ablation for targets outside of pulmonary veins. RECENT FINDINGS: Studies have shown that the cryoballoon ablation can be used in extrapulmonary vein area, including left atrium roof, left atrial appendages, posterior left atrial wall, mitral isthmus, and right atrial appendage. The results indicate cryoballoon ablation is an effective and well-tolerated treatment option for the atrial arrhythmias in these locations outside of pulmonary vein when clinical necessary. SUMMARY: The cryoballoon ablation can safely and effectively perform contiguous linear lesions, structure isolations, and local ablation for targets outside of the pulmonary veins.

[Acupoint selection rules of acupuncture for cervical spondylotic radiculopathy based on data mining].

OBJECTIVE: To analyze the rules of acupoint selection in the acupuncture treatment of cervical spondylotic radiculopathy by data mining. METHODS: The randomized controlled trials (RCTs) regarding acupuncture for cervical spondylotic radiculopathy published from July 15 of 2009 to July 15 of 2019 were retrieved from databases of CNKI, VIP, Wanfang, SinoMed, PubMed and EMbase. A database was established with Microsoft Excel 2016. The frequency and total effective rate of high-frequency acupoints, meridians and acupoint combinations were analyzed, and the association rules of acupoints and meridians were analyzed by Apriori algorithm. RESULTS: A total of 87 RCTs were included, involving 104 acupoints with a total frequency of 921. Among them, the high-frequency acupoints were cervical Jiaji (EX-B 2, 87 times), Fengchi (GB 20, 70 times), Houxi (SI 3, 54 times), etc. The frequently-used acupoints were mainly distributed in the hand yangming large intestine meridian, the foot shaoyang gallbladder meridian and hand taiyang small intestine meridian. The frequently-used acupoint combination was Fengchi (GB 20)-cervical Jiaji (EX-B 2), and most of the combinations were acupoints at the proximal end and acupoints at the far and near end. With the analysis of association rules, 15 groups of acupoint association rules and meridian association rules were obtained. CONCLUSION: It is feasible to explore the acupoint selection and compatibility rules of acupuncture for cervical spondylotic radiculopathy by data mining. This study could provide corresponding reference for clinical treatment.

Outcomes of cryoballoon or radiofrequency ablation in symptomatic paroxysmal or persistent atrial fibrillation.

AIMS: To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF). METHODS AND RESULTS: Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was 'atrial arrhythmia recurrence', secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm2 (RFA) (P < 0.001). Follow-up duration was 441 (CBA) and 511 days (RFA) (P < 0.0001). Primary endpoint occurred in 30.7% (CBA) and 39.4% patients (RFA) [adjusted hazard ratio (adjHR) 0.85, 95% confidence interval (CI) 0.70-1.04; P = 0.12). In paroxysmal AF, CBA resulted in a lower risk of recurrence (adjHR 0.80, 95% CI 0.64-0.99; P = 0.047). In persistent AF, the primary outcome was not different between groups. Major adverse cardiovascular and cerebrovascular event rates were 1.0% (CBA) and 2.8% (RFA) (adjHR 0.53, 95% CI 0.26-1.10; P = 0.088). Re-ablations (adjHR 0.46, 95% CI 0.34-0.61; P < 0.0001) and adverse events during follow-up (adjHR 0.64, 95% CI 0.48-0.88; P = 0.005) were less common after CBA. Higher rehospitalization rates with RFA were caused by re-ablations. CONCLUSIONS: The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.

Laparoscopic splenectomy for littoral cell angioma of the spleen: A case report.

RATIONALE: Littoral cell angioma (LCA) is a rare primary vascular neoplasm of the spleen. It can be benign or malignant. Pathology and immunohistochemistry are the gold standards for the diagnosis of LCA. Therefore, splenectomy is recommended for the purpose of diagnosis and treatment, and subsequent follow-up is necessary. There are limited reports about LCA. Here, we present a case of a female patient with LCA undergoing laparoscopic splenectomy in order to provide clinical experience in LCA treatment. PATIENT CONCERNS: A 32-year-old female attended the outpatient Department of Hepatobiliary Surgery for follow-up of hepatic hemangiomas. The patient presented with intermittent abdominal distension, which was slightly under no obvious inducement. DIAGNOSIS: Physical examination found no signs of abdominal tenderness and rebound tenderness, and liver and spleen were impalpable. The contrast-enhanced computed tomography (CT) showed multiple space-occupying lesions in the spleen, mottled low-density lesions, multiple hypoattenuating nodules with no contrast enhancement on the arterious phase. Delayed contrast-enhanced helical CT scan displayed incomplete filling of hypodense splenic lesions. INTERVENTIONS: Given that it was uncertain whether it was a benign or a malignant tumor, a laparoscopic total splenectomy was performed. OUTCOMES: The final pathological diagnosis was LCA. Her postsurgical course was uneventful, and no surgery-related complications were found. No signs of recurrence were observed in the 16 months after the operation. LESSONS: LCA was a rare primary vascular neoplasm of the spleen, and laparoscopic splenectomy for LCA was safe and feasible, and postoperative course was uneventful. However, regular follow-up and long-time monitoring after splenectomy for LCA is recommended because of its potential malignant biological behavior.

F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation.

Evaluation of 24-Hour Ambulatory Blood Pressure Monitoring in Patients with Chronic Kidney Disease with Normal Casual Blood Pressure.

This study evaluated 24-hour ambulatory blood pressure (ABP) monitoring in patients with chronic kidney disease (CKD) who had a normal casual blood pressure (CBP) of less than 140/90 mmHg. A total of 350 patients with CKD (Stages 1-5) and a normal CBP were included, and 24-hour ABPs were monitored. Of these patients, 147 patients (42.0%) exhibited increased mean ABP; 69 patients (19.7%) exhibited masked hypertension; 199 patients (56.9%) exhibited an abnormal BP mode (circadian rhythm disappearing); and 204 patients (58.3%) exhibited increased BP load. The 24-hour ABP and mean day and night BPs in patients with higher CBP were significantly higher than those in patients with normal CBP and healthy controls (P<0.01). Results indicate that abnormal BPs exist in patients with CKD who exhibit normal CBPs.

Impact of Pulmonary Vein Anatomy on Long-term Outcome of Cryoballoon Ablation for Atrial Fibrillation.

Variant pulmonary vein anatomy (PVA) has been reported to influence the recurrence of atrial fibrillation (AF) after radiofrequency ablation. However, the effects of PVA on AF in patients undergoing cryoballoon ablation (CBA) remain unknown. The present study aimed to examine the impact of PVA on the long-term outcome of CBA for AF. A total of 78 patients (mean age 60.7±10.9 years, 64.1% males) with symptomatic and drug-refractory paroxysmal AF were enrolled in the study. Left atrium (LA) and PVA acquired at computed tomography angiography (CTA) were reconstructed with CARTO® 3 SYSTEM. Patients were routinely evaluated by 24-hour Holter monitoring following CBA. Cox regression was used to detect the predictors of AF recurrence after CBA. The results showed abnormal PVA in 30 patients (38.5%) and 18 patients (23.1%) had left common PV (LCPV). Electrical pulmonary vein isolation was achieved in all patients. After a mean follow-up of 689.5±103.8 days, it was found that patients with abnormal PVA had similar AF recurrence rate to those with normal PVA (26.7% vs. 25.0%, P=0.54), and there was no significant difference in AF recurrence rate between LCPV patients and non-LCPV patients (33.7% vs. 23.3%, P=0.29). Cox regression analysis showed that AF duration (72.9±9.0 vs. 42.3±43.2 months, HR 1.001; 95%CI 1.003-1.014; P<0.001) and cryo-applications of right-side PVs (3.0±1.6 vs. 4.7±1.7, HR 0.661; 95% CI 0.473-0.925; P=0.016) were independent predictors of freedom from AF, but PVA was not identified as a predictor of long-term success. In conclusion, the variant PVA cannot significantly influence the long-term outcome of AF patients undergoing CBA; longer AF duration and less cryo-applications of right-side PVs are associated with higher AF recurrent rate.

Gestational age and childhood leukemia: A meta-analysis of epidemiologic studies.

OBJECTIVE: An increasing amount of evidence shows that childhood leukemia is initiated in utero. Birth characteristics initiated in utero, such as gestational age, may play a role in leukemogenesis. The purpose of our meta-analysis is to explore the association between gestational age and childhood leukemia. METHODS: Relevant studies up to 21 April 2017 were collected by searching PubMed and EMBASE databases. Subgroup analysis, sensitivity analysis and publication bias assessment were conducted. RESULTS: A total of 13 studies were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for preterm birth and postterm birth were 1.06 (0.98, 1.13) and 1.01 (0.90, 1.13) for childhood leukemia, 1.04 (0.97, 1.11) and 1.03 (0.95, 1.12) for acute lymphocytic leukemia (ALL), 1.20 (1.00, 1.44) and 1.20 (1.00, 1.43) for acute myeloid leukemia (AML), compared with full-term birth. Study type and study region were the reasons behind the heterogeneity. In subgroup analyses, the summary ORs with 95% CI for childhood leukemia and ALL were 1.23 (1.07, 1.41) and 1.21 (1.06, 1.39) for postterm birth in cohort studies. No significant changes in sensitivity analyses and no publication bias were observed in our analysis. CONCLUSION: Our results suggest that both preterm and postterm infants have an elevated risk of developing AML. In addition, postterm birth increased the risk of childhood leukemia and ALL in cohort studies. However, more studies are warranted to validate these results and explore the biologic mechanisms underlying these relationships.

Recurrence of Barcelona Clinic Liver Cancer Stage A Hepatocellular Carcinoma After Hepatectomy.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely used to classify hepatocellular carcinoma (HCC). This study was performed to investigate the prognostic factors for patients with BCLC stage A HCC after R0 hepatectomy. METHODS: A total of 592 patients with BCLC stage A HCC following R0 hepatectomy from 1997-2012 were enrolled in this study. Kaplan-Meier analysis and Cox regression were used to analyze the risk factors associated with recurrence. Receiver operating characteristic curves were used to establish a new scoring system to evaluate the independent risk factors for recurrence. Furthermore, subgroup analyses were performed to evaluate surgical margins on tumor recurrence between the anatomic and nonanatomic resection group. RESULTS: Independent risk factors for BCLC stage A HCC recurrence were preoperative alanine transaminase >40U/L, liver cirrhosis, surgical margin <5mm, nonanatomic resection and maximum tumor diameter >5cm. Based on these 5 risk factors, we established a new scoring system, named "HCC recurrence scoring system." Patients with a high score (≥3 points, 1 point for each factor) composed the high recurrence risk group. Moreover, the subgroup analyses demonstrated that different surgical margins had no significant effect on tumor recurrence in the anatomic resection group (P = 0.408), while it had a significant effect in the nonanatomic resection group (P = 0.000). CONCLUSIONS: For patients with BCLC stage A with scores ≥3 points, close postoperative follow-up and positive measures to prevent recurrence are particularly important. Anatomic resection is preferred for patients with BCLC stage A. Adequate surgical margins are necessary for patients with poor liver function.

Cryoballoon ablation in Chinese patients with paroxysmal atrial fibrillation: 1-year follow-up.

OBJECTIVES: We assessed the effectiveness and safety of cryoballoon ablation (CBA) in the Chinese population with paroxysmal atrial fibrillation (AF) with a 1-year follow-up and determined the association of early recurrence of atrial tachyarrhythmias (ERAT) with late recurrence (LR). METHODS: A total of 114 patients (age 61 ± 10 years, 78 males) with paroxysmal AF who underwent CBA were consecutively enrolled. After procedures, patients were observed for 3 days with continuous electrocardiogram monitoring in the hospital with routine follow-up visits at 3 months, 6 months, and 1 year. Documented atrial tachyarrhythmia >30 seconds was defined as recurrence. ERAT was defined as any recurrence during the first 3 months, and LR was recurrence between 3 and 12 months. RESULTS: With the first 3 months as blanking period, 76% of patients were free of LR at 12 months. Five patients (4%) experienced complications, including phrenic nerve palsy, stroke, and groin complications. Forty-five percent of patients had ERAT in the first 3 months and 31% of patients had ERAT in the first 3 days. Patients with ERAT had higher LR rate (LRR) than those without ERAT (43% vs 8%, P < 0.001). The LRR of patients with ERAT only in the first 3 days was lower than those with ERAT both in the first 3 days and in 4-90 days (29% vs 64%, P = 0.036). CONCLUSIONS: CBA was an effective and safe treatment option for paroxysmal AF. Patients with ERAT had higher LRR after CBA of AF. The time when ERAT occurred had an impact on LRR.

Regulation of cardiac CACNB2 by microRNA-499: Potential role in atrial fibrillation.

The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499. We found that CACNB2, an important subunit of the LTCC, is also a target of miR-499. We hypothesize that miR-499 plays an important role in AF electrical remodeling by regulating the expression of CACNB2 and the LTCC. In atrial tissue from patients with permanent AF, CACNB2 was significantly downregulated by 67% (n = 4, p < 0.05) compared to those from patients with no history of AF. Transfection of miR-499 mimic into HL-1 cells, a mouse hyperplastic atrial cardiac myocyte cell-line, resulted in the downregulation of CACNB2 protein expression, while that of miR-499 inhibitor upregulated CACNB2 protein expression. Binding of miR-499 to the 3' untranslated region of CACNB2 was confirmed by luciferase reporter assay and by the increased presence of CACNB2 mRNA in Argonaute pulled-down microRNA-induced silencing complexes after transfection with the miR-499 mimic. In addition, downregulation of CACNB2 resulted in the downregulation of protein levels of the pore-forming α-subunit (CACNA1C). In conclusion, upregulation of atrial miR-499 induces the downregulation of CACNB2 expression and may contribute to the electrical remodeling in AF.

Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection: a matched study.

BACKGROUND: Hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear. METHODS: We compared the prognoses of 110 HCC patients without BDTT (group A) to 22 cases with BDTT (group B). The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Additionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors. RESULTS: The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively (P=0.043). The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gamma-glutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage III-IV was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage I-II after R0 resection (hazard ratio=6.056, P=0.014). Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage III-IV were independent risk factors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection (31.0 vs 4.0 months, P=0.007). CONCLUSIONS: R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.

Hepatic falciform ligament clear cell myomelanocytic tumor: A case report and a comprehensive review of the literature on perivascular epithelioid cell tumors.

BACKGROUND: The objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature. CASE PRESENTATION: Clear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+). CONCLUSION: Hepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.

Use of Cytokeratin-19 Concentration to Assess Early Recurrence and Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma following Radical Resection in Patients with a Low Serum Alpha-Fetoprotein Concentration.

Cytokeratin 19 (CK-19) is a prognostic indicator of recurrence and metastasis of hepatocellular carcinoma (HCC) following radical resection. To investigate the role of CK-19 in assessment of early recurrence and prognosis in patients with hepatitis B virus (HBV)-related HCC following radical resection. In total, 235 patients with HBV-related HCC (age, 15-82 years; mean age, 54 ± 10 years) undergoing radical resection were screened for inclusion from January 2005 to December 2010. Malignant tissues and adjacent non-malignant tissues were sampled during surgery, and CK-19 and Ki-67 expression was determined by tissue microarray and immunohistochemistry. CK-19 mRNA levels in 30 randomly selected frozen HCC specimens were examined by reverse transcription polymerase chain reaction from January 2011 to June 2011. Correlations of CK-19 and Ki-67 expression with tumor recurrence, metastasis, disease-free survival (DFS), and overall survival (OS) were analyzed. Elevated CK-19 expression was correlated with early recurrence (P = 0.001), shorter DFS (P = 0.001), and reduced OS (P = 0.010). CK-19 expression was correlated with the Ki-67 index (P = 0.037), histological differentiation (P = 0.016), focal number (P = 0.044), and blood vessel tumor embolism (P = 0.002). Patients with metastasis within 1 year exhibited stronger CK-19 expression than did patients without metastasis (P < 0.05). Furthermore, early recurrence was associated with elevated CK-19 mRNA levels (χ2 = 5.761, P = 0.016).When confirmed by a low alpha-fetoprotein concentration (<400 µg/L), CK-19 expression in surgical biopsy specimens taken from patients with HCC during radical resection is an additional valuable indicator of early recurrence, distant metastasis, and poor prognosis in HBV-positive patients.

EphB4 forward-signaling regulates cardiac progenitor development in mouse ES cells.

Eph receptor (Eph)-ephrin signaling plays an important role in organ development and tissue regeneration. Bidirectional signaling of EphB4-ephrinB2 regulates cardiovascular development. To assess the role of EphB4-ephrinB2 signaling in cardiac lineage development, we utilized two GFP reporter systems in embryonic stem (ES) cells, in which the GFP transgenes were expressed in Nkx2.5(+) cardiac progenitor cells and in α-MHC(+) cardiomyocytes, respectively. We found that both EphB4 and ephrinB2 were expressed in Nkx2.5-GFP(+) cardiac progenitor cells, but not in α-MHC-GFP(+) cardiomyocytes during cardiac lineage differentiation of ES cells. An antagonist of EphB4, TNYL-RAW peptides, that block the binding of EphB4 and ephrinB2, impaired cardiac lineage development in ES cells. Inhibition of EphB4-ephrinB2 signaling at different time points during ES cell differentiation demonstrated that the interaction of EphB4 and ephrinB2 was required for the early stage of cardiac lineage development. Forced expression of human full-length EphB4 or intracellular domain-truncated EphB4 in EphB4-null ES cells was established to investigate the role of EphB4-forward signaling in ES cells. Interestingly, while full-length EphB4 was able to restore the cardiac lineage development in EphB4-null ES cells, the truncated EphB4 that lacks the intracellular domain of tyrosine kinase and PDZ motif failed to rescue the defect of cardiomyocyte development, suggesting that EphB4 intracellular domain is essential for the development of cardiomyocytes. Our study provides evidence that receptor-kinase-dependent EphB4-forward signaling plays a crucial role in the development of cardiac progenitor cells.

Expression of human leukocyte antigen-G and acute rejection in patients following liver transplantation.

Acute liver rejection is one of the most severe complications that may affect the liver transplantation procedure. Thus, one of the most important focal points in the field of liver transplantation research is to discover a non-invasive or less-invasive method of diagnosing and predicting cases of acute liver rejection. In the present study, 59 tissue samples, including blood and liver tissues, were collected from patients who underwent liver transplantation between March 2005 and November 2009. The patients were divided into acute rejection and no rejection groups, the latter of which was further divided into normal and abnormal liver function groups. The samples were assayed by enzyme-linked immunosorbent assay and immunohistochemistry methods. The results were analyzed and a receiver operating characteristic (ROC) curve was plotted. The area under the ROC curve and the sensitivity and specificity of the cut-off point were analyzed statistically. The results indicated that the expression level of human leukocyte antigen-G (HLA-G) in the serum and liver samples in the acute rejection group was markedly lower than that in the no rejection group (P<0.001 and P=0.004, respectively). Furthermore, in the no rejection group, no statistically significant difference was identified in the level of HLA-G between patients with normal or abnormal liver function (P=0.0593). The area under the ROC curve was 0.805. When 2.41 U/ml HLA-G was considered as the cut-off point for the diagnosis of acute liver rejection, the sensitivity and specificity were 72.7 and 83.8%, respectively. In conclusion, in the present study, a high expression of the HLA-G was shown to correlate with a reduced occurrence of acute liver rejection. HLA-G may thus be an effective factor for the diagnosis and prediction of acute liver rejection.

Is right ventricular mid-septal pacing superior to apical pacing in patients with high degree atrio-ventricular block and moderately depressed left ventricular function?

OBJECTIVE: We are aimed to investigate whether right ventricular mid-septal pacing (RVMSP) is superior to conventional right ventricular apical pacing (RVAP) in improving clinical functional capacity and left ventricular ejection fraction (LVEF) for patients with high-degree atrio-ventricular block and moderately depressed left ventricle (LV) function. METHODS: Ninety-two patients with high-degree atrio-ventricular block and moderately reduced LVEF (ranging from 35% to 50%) were randomly allocated to RVMSP (n=45) and RVAP (n=47). New York Heart Association (NYHA) functional class, echocardiographic LVEF, and distance during a 6-min walk test (6MWT) were determined at 18 months after pacemaker implantation. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Compared with baseline, NYHA functional class remained unchanged at 18 months, distance during 6MWT (485 m vs. 517 m) and LVEF (36.7% vs. 41.8%) were increased, but BNP levels were reduced (2352 pg/ml vs. 710 pg/ml) in the RVMSP group compared with those in the RVAP group, especially in patients with LVEF 35%-40% (for all comparisons, P<0.05). However, clinical function capacity and LV function measurements were not significantly changed in patients with RVAP, despite the pacing measurements being similar in both groups, such as R-wave amplitude and capture threshold. CONCLUSIONS: RVMSP provides a better clinical utility, compared with RVAP, in patients with high-degree atrioventricular block and moderately depressed LV function whose LVEF levels ranged from 35% to 40%.