A Study on the Molecular Mechanism of High Altitude Heart Disease in Children.

Objective: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD. Methods: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau. Results: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO. Conclusion: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.

Longitudinal Imaging of Liver Cancer Using MicroCT and Nanoparticle Contrast Agents in CRISPR/Cas9-Induced Liver Cancer Mouse Model.

INTRODUCTION: Micro-computed tomography with nanoparticle contrast agents may be a suitable tool for monitoring the time course of the development and progression of tumors. Here, we suggest a practical and convenient experimental method for generating and longitudinally imaging murine liver cancer models. METHODS: Liver cancer was induced in 6 experimental mice by injecting clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 plasmids causing mutations in genes expressed by hepatocytes. Nanoparticle agents are captured by Kupffer cells and detected by micro-computed tomography, thereby enabling longitudinal imaging. A total of 9 mice were used for the experiment. Six mice were injected with both plasmids and contrast, 2 injected with contrast alone, and one not injected with either agent. Micro-computed tomography images were acquired every 2- up to 14-weeks after cancer induction. RESULTS: Liver cancer was first detected by micro-computed tomography at 8 weeks. The mean value of hepatic parenchymal attenuation remained almost unchanged over time, although the standard deviation of attenuation, reflecting heterogeneous contrast enhancement of the hepatic parenchyma, increased slowly over time in all mice. Histopathologically, heterogeneous distribution and aggregation of Kupffer cells was more prominent in the experimental group than in the control group. Heterogeneous enhancement of hepatic parenchyma, which could cause image quality deterioration and image misinterpretation, was observed and could be due to variation in Kupffer cells distribution. CONCLUSION: Micro-computed tomography with nanoparticle contrast is useful in evaluating the induction and characteristics of liver cancer, determining appropriate size of liver cancer for testing, and confirming therapeutic response.

Optimization of Fermentation Conditions and Bench-Scale for Improvement of a Novel Glycoprotein GP-1 Production by Streptomyces kanasenisi ZX01.

GP-1 is a novel glycoprotein produced by Streptomyces kanasenisi ZX01 that was isolated from soil near Kanas Lake with significant bioactivity against tobacco mosaic virus. However, extremely low fermentation production has largely hindered further research and market applications on glycoprotein GP-1. In this study, response surface methodology was used to optimize fermentation conditions in a shake flask for higher glycoprotein GP-1 production. When the optimized fermentation conditions were inoculum volume of 6%, initial pH of 6.5, and rotating speed of 150 rpm, glycoprotein GP-1 production could reach 0.9253 mg/L, which was increased by 52.14% compared to the original conditions. In addition, scale-up fermentation was conducted in a 5-L bioreactor to preliminarily explore the feasibility for mass production of glycoprotein GP-1 in a large fermentor, obtaining GP-1 production of 2.54 mg/L under the same conditions, which was 2.75 times higher than the production obtained from a shake flask of 0.9253 mg/L. This work will be helpful to improve GP-1 production on a large scale and lay the foundations for developing it as a novel agent against plant virus.

Effects of Agitation, Aeration and Temperature on Production of a Novel Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on Volumetric Oxygen Transfer Coefficient.

The effects of temperature, agitation and aeration on glycoprotein GP-1 production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were systematically investigated. The maximum final GP-1 production was achieved at an agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of 30 °C. By using a dynamic gassing out method, the effects of agitation and aeration on volumetric oxygen transfer coefficient (kLa) were also studied. The values of volumetric oxygen transfer coefficient in the logarithmic phase increased with increase of agitation speed (from 14.53 to 32.82 h-1) and aeration rate (from 13.21 to 22.43 h-1). In addition, a successful scale-up from bench-scale to pilot-scale was performed based on volumetric oxygen transfer coefficient, resulting in final GP-1 production of 3.92, 4.03, 3.82 and 4.20 mg/L in 5 L, 15 L, 70 L and 500 L fermentors, respectively. These results indicated that constant volumetric oxygen transfer coefficient was appropriate for the scale-up of batch fermentation of glycoprotein GP-1 by Streptomyces kanasenisi ZX01, and this scale-up strategy successfully achieved 100-fold scale-up from bench-scale to pilot-scale fermentor.

A Case of Achieving Partial Remission with Sequential Treatment of Transarterial Chemoemoblization after Transarterial Radioembolization in Old Patient with Hepatocellular Carcinoma with Multiple Metastasis

The number of older adults with hepatocelluar carcinoma (HCC) has been increasing with longer life expectancy and earlier diagnosis and treatment. However, older patients have lesser function reserve of multiple organ systems, more disability rate. Therefore, the treatment of elderly HCC patients remains a challenge worldwide. Recently, studies suggests that the survival outcome of older patients may be comparable to that of younger patients and active treatment may achieve promising rates of local and systemic control in selected patients. Based on above suggestions, we herein offer our experience of a case achieved partial remission by sequential therapy of transarterial chemoembolization after transarterial radioemoblization in elderly HCC patient with multiple metastasis. Further study, maybe regarding a combination of locoregional and systemic treatment, is necessary on how to manage HCC in elderly patients.

Genome-Wide Analysis Reveals the Secondary Metabolome in Streptomyces kanasensis ZX01.

Streptomyces kanasensis ZX01 produces some antibiotics and a glycoprotein with antiviral activity. To further evaluate its biosynthetic potential, here we sequenced the 7,026,279 bp draft genome of S. kanasensis ZX01 and analyzed all identifiable secondary gene clusters for controlling natural products. More than 60 putative clusters were found in S. kanasensis ZX01, the majority of these biosynthetic loci are novel. In addition, the regulators for secondary metabolism in S. kanasensis ZX01 were abundant. The global regulator nsdA not only controls biosynthesis of some antibiotics, but also enhances production of glycoprotein GP-1 with antiviral activity. This study importantly reveals the powerful interplay between genomic analysis and studies of traditional natural product purification/production increasing.

A Case of Achieving Complete Remission with Combination of Sorafenib and Tegafur in Patients with Hepatocellular Carcinoma with Progression of Disease after Sorafenib Therapy

Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.

Sectional Localization of a Small Hepatocellular Carcinoma in the Right Hepatic Lobe by Computed Tomography: Comparison between the Conventional and Portal Vein Tracing Methods.

PURPOSE: To compare the accuracy of the conventional and portal vein tracing methods in the right hepatic lobe in multidetector computed tomography (MDCT). MATERIALS AND METHODS: This retrospective study included patients with hepatocellular carcinoma (HCC) lesions in the right hepatic lobe who underwent multiphasic MDCT and C-arm CT hepatic arteriography (C-arm CTHA) for chemoembolization. The accuracies of the conventional and portal vein tracing methods were evaluated using C-arm CTHA as the gold standard. RESULTS: A total of 147 patients with 205 HCC nodules were included. The C-arm CTHA could identify all the tumour-feeding arteries and consequently demonstrated that 120 lesions were located in the anterior section, 78 in the posterior section, and 7 in the border zone. The accuracy rates of conventional vs. portal vein tracing methods were 71.7 % vs. 98.3 % for the anterior section lesions, 67.9 % vs. 96.2 % for the posterior section, and 28.6 % vs. 57.1 % for the border zone. The portal vein tracing method was more accurate than the conventional method (P<0.001). CONCLUSIONS: The portal vein tracing method should be used for sectional localization of HCCs in the right lobe, because it predicts the location more accurately than the conventional method. KEY POINTS: • Portal tracing method is more accurate than conventional method for tumour localization. • The conventional method is especially inaccurate in right anteroinferior or posterosuperior quadrants. • Scissurae between right anterior and posterior section may not be vertical but tilted.

Locoregional Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) have a extremely poor prognosis. According to the Barcelona Clinic Liver Cancer guideline, sorafenib is a standard therapy in this situation, but many clinicians still select locoregional therapy (LRT) such as transarterial therapy, external beam radiation therapy (EBRT), even surgical resection (SR) or combination of LRTs because the survival improvement by sorafenib is unsatisfactory. Based on recent meta-analysis and prospective study, transarterial chemoembolization (TACE) and transarterial radioembolization seem to be effective and safe therapeutic option that have comparable outcome to sorafenib. Recently large nationwide studies demonstrated that SR can be a potentially curative treatment in selected patients. Hepatic arterial infusion chemotherapy (HAIC) can be also good option, especially in Child class B patients based on small volume prospective studies. Moreover, multidisciplinary strategies based on the combination of LRTs (SR plus TACE, TACE + EBRT, TACE + Sorafenib, HAIC + EBRT etc.) may improve survival of HCC patients with PVTT. Finally we discuss individualized and tailored treatment strategies for different clinical situations.

A Case of Achieving Complete Remission with Stereotactic Body Radiation Therapy in Patients with Hepatocellular Carcinoma with Macrovascular Invasion after Repeated Transarerial Chemoembolization

Transarterial chemoembolization (TACE) is the worldwide procedure performed for patients with various stage hepatoceullar carcinoma (HCC), but is not yet considered as curative treatment because of relatively high local recurrence rate. Moreover, many clinicians frequently experience treatment failure (incomplete necrosis or stage progression etc.) after repeated TACE, but no clear guidelines have been recommended about salvage treatment modalities for this situation. Recently, studies for combination of radiation therapy and TACE for HCC with TACE refractoriness have been tried and reported better therapeutic efficacy. Based on above suggestions, we herein offer our experience of a patient with macrovascular invasion developed after repeated TACE that achieve complete remission by stereotactic body radiation therapy. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage HCC patients with TACE refractoriness.

A Case of Achieving Complete Remission with Combination of Stereotac-tic Body Radiation Therapy and Transarterial Chemoemoblization in Pa-tients with 4.8 cm Sized Infiltrative Hepatocellular Carcinoma with Arte-riovenous Shunt

Infiltrative hepatocellular carcinoma (HCC) patients have a poor prognosis because most patients present with advanced disease. Although tumor size is small, ablation therapy is difficult because it is difficult to delineate tumor boundary and tumor often combined vascular invasion. Therefore many clinicians still try locoregional therapy (LRT) such as transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT and sorafenib in this situation. Stereotactic body radiation therapy (SBRT) is new technology providing very highly conformal ablative radiation dose and is expected to salvage modality for HCC showed incomplete response of TACE due to combined arteriovenous (AV) shunts. Based on above suggestions, we herein offer our experience of a complete remission of tumor by combination of SBRT and TACE in a patient with infiltrative HCC. Further study, maybe regarding a combination of locoregional and systemic therapy is necessary on how to manage infiltrative HCC with AV shunts.

Selective embolization for hypervascular metastasis from differentiated thyroid cancer: a case series.

INTRODUCTION: The technique of selective embolization has been applied for years in the treatment of vascular anomalies, severe hemorrhage, and for benign and malignant tumors. Some hypervascular skeletal metastases are prone to massive hemorrhage. CASE PRESENTATION: We describe the cases of two patients with thyroid carcinoma presenting with neuromuscular symptoms due to large skeletal metastases in the shoulder and sternum respectively. Pre-operative percutaneous selective catheterizations of the arteries feeding the metastatic tumors were performed, followed by infusion of gelfoam. The procedures were technically successful in both patients without adverse effects or bleeding. Complete resections of the skeletal metastases were then performed without substantial bleeding. CONCLUSION: Selective embolization is an effective treatment for bony metastases from thyroid cancer.

Ultrasound and fluoroscopy-guided placement of central venous ports via internal jugular vein: retrospective analysis of 1254 port implantations at a single center.

OBJECTIVE: To assess the technical success and complication rates of the radiologic placement of central venous ports via the internal jugular vein. MATERIALS AND METHODS: We retrospectively reviewed 1254 central venous ports implanted at our institution between August 2002 and October 2009. All procedures were guided by using ultrasound and fluoroscopy. Catheter maintenance days, technical success rates, peri-procedural, as well as early and late complication rates were evaluated based on the interventional radiologic reports and patient medical records. RESULTS: A total of 433386 catheter maintenance days (mean, 350 days; range 0-1165 days) were recorded. The technical success rate was 99.9% and a total of 61 complications occurred (5%), resulting in a post-procedural complication rate of 0.129 of 1000 catheter days. Among them, peri-procedural complications within 24 hours occurred in five patients (0.4%). There were 56 post-procedural complications including 24 (1.9%, 0.055 of 1000 catheter days) early and 32 (2.6%, 0.074 of 1000 catheter days) late complications including, infection (0.6%, 0.018 of 10000 catheter days), thrombotic malfunction (1.4%, 0.040 of 1000 catheter days), nonthrombotic malfunction (0.9%, 0.025 of 1000 catheter days), venous thrombosis (0.5%, 0.014 of 1000 catheter days), as well as wound problems (1.1%, 0.032 of 1000 catheter days). Thirty six CVPs (3%) were removed due to complications. Bloodstream infections and venous thrombosis were the two main adverse events prolonging hospitalization (mean 13 days and 5 days, respectively). CONCLUSION: Radiologic placement of a central venous port via the internal jugular vein is safe and efficient as evidenced by its high technical success rate and a very low complication rate.

Right gastric venous drainage: angiographic analysis in 100 patients.

OBJECTIVE: To evaluate the pattern of right gastric venous drainage by use of digital subtraction angiography. MATERIALS AND METHODS: A series of 100 consecutive patients who underwent right gastric arteriography during transcatheter arterial chemoembolization for hepatocellular carcinoma were included in this study. Angiographic findings were retrospectively analyzed with respect to the presence or absence of the right and aberrant gastric veins, multiplicity of draining veins, aberrant right gastric venous drainage sites, and the termination pattern of aberrant right gastric veins (ARGVs). We also compared the relative size of the right and left gastric veins. RESULTS: A total of 49 patients collectively had 66 ARGVs. The common drainage sites for the ARGVs included the hepatic segment IV (n = 35) and segment I (n = 15). The termination pattern of ARGV could be classified into 4 different types. The most common type was termination as a superficial parenchymal blush formation in small areas without demonstrable portal branches. A statistically significant difference was found for the dominancy of the right gastric vein in gastric venous drainage between the two groups with or without ARGV (p < 0.05, Fisher's exact test). In the group of patients without ARGV (n = 51), the right gastric vein was equal to (n = 9) or larger than (n = 17) the left gastric vein in 26 patients (26 of 51, 51%). CONCLUSION: The incidence of ARGV is higher than expected with four distinct types in its termination pattern. The right gastric vein may play a dominant role in gastric venous drainage.

Ultrasound and Fluoroscopy-Guided Placement of Central Venous Ports via Internal Jugular Vein: Retrospective Analysis of 1254 Port Implantations at a Single Center

OBJECTIVE: To assess the technical success and complication rates of the radiologic placement of central venous ports via the internal jugular vein. MATERIALS AND METHODS: We retrospectively reviewed 1254 central venous ports implanted at our institution between August 2002 and October 2009. All procedures were guided by using ultrasound and fluoroscopy. Catheter maintenance days, technical success rates, peri-procedural, as well as early and late complication rates were evaluated based on the interventional radiologic reports and patient medical records. RESULTS: A total of 433386 catheter maintenance days (mean, 350 days; range 0-1165 days) were recorded. The technical success rate was 99.9% and a total of 61 complications occurred (5%), resulting in a post-procedural complication rate of 0.129 of 1000 catheter days. Among them, peri-procedural complications within 24 hours occurred in five patients (0.4%). There were 56 post-procedural complications including 24 (1.9%, 0.055 of 1000 catheter days) early and 32 (2.6%, 0.074 of 1000 catheter days) late complications including, infection (0.6%, 0.018 of 10000 catheter days), thrombotic malfunction (1.4%, 0.040 of 1000 catheter days), nonthrombotic malfunction (0.9%, 0.025 of 1000 catheter days), venous thrombosis (0.5%, 0.014 of 1000 catheter days), as well as wound problems (1.1%, 0.032 of 1000 catheter days). Thirty six CVPs (3%) were removed due to complications. Bloodstream infections and venous thrombosis were the two main adverse events prolonging hospitalization (mean 13 days and 5 days, respectively). CONCLUSION: Radiologic placement of a central venous port via the internal jugular vein is safe and efficient as evidenced by its high technical success rate and a very low complication rate.

Right Gastric Venous Drainage: Angiographic Analysis in 100 Patients

OBJECTIVE: To evaluate the pattern of right gastric venous drainage by use of digital subtraction angiography. MATERIALS AND METHODS: A series of 100 consecutive patients who underwent right gastric arteriography during transcatheter arterial chemoembolization for hepatocellular carcinoma were included in this study. Angiographic findings were retrospectively analyzed with respect to the presence or absence of the right and aberrant gastric veins, multiplicity of draining veins, aberrant right gastric venous drainage sites, and the termination pattern of aberrant right gastric veins (ARGVs). We also compared the relative size of the right and left gastric veins. RESULTS: A total of 49 patients collectively had 66 ARGVs. The common drainage sites for the ARGVs included the hepatic segment IV (n = 35) and segment I (n = 15). The termination pattern of ARGV could be classified into 4 different types. The most common type was termination as a superficial parenchymal blush formation in small areas without demonstrable portal branches. A statistically significant difference was found for the dominancy of the right gastric vein in gastric venous drainage between the two groups with or without ARGV (p < 0.05, Fisher's exact test). In the group of patients without ARGV (n = 51), the right gastric vein was equal to (n = 9) or larger than (n = 17) the left gastric vein in 26 patients (26 of 51, 51%). CONCLUSION: The incidence of ARGV is higher than expected with four distinct types in its termination pattern. The right gastric vein may play a dominant role in gastric venous drainage.

Noncontrast chest computed tomography immediately after transarterial chemoembolization in patients with hepatocellular carcinoma: clinical benefits and effect of radiation reduction on image quality in low-dose scanning.

PURPOSE: To evaluate the clinical benefits of noncontrast chest computed tomography (CT) immediately after transarterial chemoembolization in patients with hepatocellular carcinoma and to assess the effect of radiation reduction on image quality in low-dose scanning. MATERIALS AND METHODS: From June to October 2010, we performed standard-dose, noncontrast chest CTs immediately after transarterial chemoembolization in 160 patients and low-dose CTs in 88 patients. We reviewed the entire noncontrast chest CTs and follow-up CTs to reveal the clinical benefits of CT evaluation immediately after transarterial chemoembolization. Using two independent readers, we also retrospectively evaluated the radiation dose and image quality in terms of the image noise, contrast between the liver parenchyma and iodized oil and diagnostic acceptability for the evaluation of treatment response after transarterial chemoembolization. RESULTS: In 5.2% of the patients, additional treatment was performed immediately after the interpretation of the noncontrast chest CT, and additional pulmonary lesions were found in 8.5% of the patients. The measured mean dose-length product for the low-dose scanning was 18.4% of that of the standard-dose scanning. The image noise was significantly higher with the low-dose scanning (p<0.001). However, all of the low-dose CT scans were diagnostically acceptable, and the mean scores for the subjective assessments of the contrast and diagnostic acceptability showed no significant differences for either reader. CONCLUSION: A noncontrast chest CT immediately after transarterial chemoembolization has some clinical benefits for immediate decision making and detecting pulmonary lesions. Low-dose, noncontrast chest CTs immediately after transarterial chemoembolization consistently provide diagnostically acceptable images and information on treatment response in patients who have undergone transarterial chemoembolization.

Data analysis of iodine level in iodized salt from monitoring sites in Tibet in 2008 / 中国地方病学杂志

Objective To know the quality of iodized salt and the current situation of the salt coverage in Tibet,and to provide scientific basis for proposing proper prevention and control measures to Iodine dificiency disorders(IDD). Methods In 2008, according to the "Sampling Methods of the Main Products in the Salt Industry",one batch fifteen salt samples were collected in iodized salt processing factory in Tibet. Five townships were chosen in each county based on 5 different directions of east, south, west, north and center. If the monitoring county has less than five townships, then all of the townships were sampled. In each township, four villages were selected withrandom sampling and importance sampling. In each township, 15 households were selected for salt collection. Results A batch of 15 salt samples in a salt processing plant were tested, and all of them were qualified with salt iodine(34.6±1.58) mg/kg. A total of 21 107 edible salt samples were tested, and 11 203 of them were qualified iodized salt. These results meant that the provincial iodized salt coverage rate was 53.08%. Shannan iodized salt coverage rate was 94.31% (3395/3600) which was the highest in Tibet. Those of Nagqu, Changdu, Ngari were lower, they were 29.84% (897/3006), 24.94% (823/3300) and 17.08% (205/1200), respectively. Conclusions The quality of iodized salt in Tibet is up to the national standard, but the coverage rate of iodized salt is very low.We suggest that the strategy should be carried out according to the national overall program strategy and supplement iodized oil capsule for special groups.

Giant cell tumor of soft tissue: a case with atypical US and MRI findings.

We report the case of a giant cell tumor with diffuse interstitial hemorrhaging and unusually prominent cystic components in the soft tissue of the thigh which has not been reported previously. Magnetic resonance image (MRI), showed signal intensity typical of a giant cell tumor. However, because of its conspicuous large well-circumscribed cystic components, the differential diagnoses, based on the image findings from an ultrasonography (US) and MRI, were complicated epidermoid cyst, cystic change of a neurogenic tumor, and a parasitic cyst.

Granulocytic sarcoma presenting with necrotic cervical lymph nodes as an initial manifestation of childhood leukaemia: imaging features.

We present two cases of granulocytic sarcoma of the cervical lymph nodes with central necrosis as an initial manifestation of childhood leukaemia, focusing on the imaging features. Recognition of the CT and MR imaging findings of granulocytic sarcoma involving the cervical lymph nodes assists the differential diagnosis of noninfective lymphadenopathy in children.