Application of texture signatures based on multiparameter-magnetic resonance imaging for predicting microvascular invasion in hepatocellular carcinoma: Retrospective study.

BACKGROUND: Despite continuous changes in treatment methods, the survival rate for advanced hepatocellular carcinoma (HCC) patients remains low, highlighting the importance of diagnostic methods for HCC. AIM: To explore the efficacy of texture analysis based on multi-parametric magnetic resonance (MR) imaging (MRI) in predicting microvascular invasion (MVI) in preoperative HCC. METHODS: This study included 105 patients with pathologically confirmed HCC, categorized into MVI-positive and MVI-negative groups. We employed Original Data Analysis, Principal Component Analysis, Linear Discriminant Analysis (LDA), and Non-LDA (NDA) for texture analysis using multi-parametric MR images to predict preoperative MVI. The effectiveness of texture analysis was determined using the B11 program of the MaZda4.6 software, with results expressed as the misjudgment rate (MCR). RESULTS: Texture analysis using multi-parametric MRI, particularly the MI + PA + F dimensionality reduction method combined with NDA discrimination, demonstrated the most effective prediction of MVI in HCC. Prediction accuracy in the pulse and equilibrium phases was 83.81%. MCRs for the combination of T2-weighted imaging (T2WI), arterial phase, portal venous phase, and equilibrium phase were 22.86%, 16.19%, 20.95%, and 20.95%, respectively. The area under the curve for predicting MVI positivity was 0.844, with a sensitivity of 77.19% and specificity of 91.67%. CONCLUSION: Texture analysis of arterial phase images demonstrated superior predictive efficacy for MVI in HCC compared to T2WI, portal venous, and equilibrium phases. This study provides an objective, non-invasive method for preoperative prediction of MVI, offering a theoretical foundation for the selection of clinical therapy.

Analyses of microRNAs and transcriptomes in the midgut of Spodoptera litura feeding on Brassica juncea.

Spodoptera litura is a destructive agricultural pest in tropical and subtropical areas. Understanding the molecular mechanisms of S. litura adaptation to its preferred host plants may help identify target genes useful for pest control. We used high-throughput sequencing to characterize the expression patterns of messenger RNAs (mRNAs) and microRNAs (miRNAs) in the midgut of S. litura fed on Brassica juncea for 6 h and 48 h. A total of 108 known and 134 novel miRNAs were identified, 29 miRNAs and 237 mRNAs were differentially expressed at 6 h of B. juncea feeding, 26 miRNAs and 433 mRNAs were differentially expressed at 48 h. For the mRNAs, the up-regulated genes were mostly enriched in detoxification enzymes (cytochrome P450, esterase, glutathione S-transferase, uridine diphosphate-glucuronosyl transferase), while the down-regulated genes were mostly enriched in proteinases and immune-related genes. Furthermore, most detoxification enzymes begin to up-regulate at 6 h, while most digestion and immune-related genes begin to up- or down-regulate at 48 h. Eighteen and 37 differently expressed transcription factors were identified at 6 h and 48 h, which may regulate the functional genes. We acquired 136 and 41 miRNA versus mRNA pairs at 6 h and 48 h, respectively. Some down-regulated and up-regulated miRNAs were predicted to target detoxification enzymes and proteinases, respectively. Real-time quantitative polymerase chain reaction of nine randomly selected miRNAs and 28 genes confirmed the results of RNA-seq. This analyses of miRNA and mRNA transcriptomes provides useful information about the molecular mechanisms of S. litura response to B. juncea.

Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats.

BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM: To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS: IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of C-kit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB. RESULTS: WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-ß), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION: BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS.

Identification and profile of microRNAs in Xiang pig testes in four different ages detected by Solexa sequencing.

To further understand the role of microRNA (miRNA) during testicular development, we constructed four small RNA libraries from the testes of the Chinese indigenous Xiang pig at four different ages, which were sequenced using high-throughput Solexa deep sequencing methods. It yielded over 23 million high-quality reads and 1,342,579 unique sequences. At two and three months of age, the proportion which represented miRNAs was the most abundant class of small RNAs, but it was gradually replaced by the category that represented piRNAs in adult testes. We identified 543 known and homologous conserved porcine miRNAs and 49 potential novel miRNAs. There were 306 known miRNAs which were co-expressed in four libraries. Six miRNAs and three potential novel miRNAs were validated in testes and sperms of Xiang pig by RT-qPCR method. Many clusters of mature miRNA variants were observed, in which let-7 family was the most abundant one. After comparison among libraries, 204 miRNAs were identified as being differentially expressed and likely involved in the development and spermatogenesis of pig testes. This work presented a general genome-wide expression profile of the testes-expressed small RNAs in different ages of pig testes. Our results suggested that miRNAs performed a role in the regulation of mRNAs in puberty pig testes while piRNAs likely functioned mainly in sexually mature pig testes.

Effect of microRNA-128 on cisplatin resistance of glioma SHG-44 cells by targeting JAG1.

This current study intends to investigate the effect of microRNA-128 (miR-128) on cisplatin (DDP) resistance in glioma SHG-44 cells. SHG-44/DDP cells were transfected with miR-128 antisense oligonucleotide (ASO) and assigned into blank, resistance, NC, anti-miR-128, miR-128 mimic, si-JAG1, and anti-miR-128 + si-JAG1 groups. qRT-PCR and Western blotting were employed for determining expression of miR-128, JAG1, Bax and Bcl-2. MTT assay, Giemsa staining, and flow cytometry were applied to detect DDP resistance, cellular morphology, and cell cycle, respectively. JAG1 is targeted and negatively regulated by miR-128. In in vitro experiments, compared with the blank group, the rest groups exhibited declined miR-28 and Bax expression, lowered cell inhibition rate and apoptosis rate, but elevated JAG1 and Bcl-2 expression with cells arrested in the S phase. Compared with the resistance group, the anti-miR-128 group showed decreasedBax expression along with a lowered cell inhibition rate and apoptosis rate, but increased JAG1 and Bcl-2 expression with reduced cells arrested in the S phase; while the miR-128 mimic group showed an opposite trend; the si-JAG1 group showed decreased Bcl-2 expression and reduced cells in the S phase. In in vivo experiments, compared with the resistance group, the tumor growth rate, tumor volume, and weight as well as JAG1 expression accelerated in the anti-miR-128 group; whereas the miR-128 mimic and si-JAG1 groups exhibited an opposite trend. Our findings demonstrated that miR-128 ASO transfection might down-regulate the expression of miR-128 in SHG-44/DDP and up-regulate the DDP resistance in SHG-44/DDP cells, providing a potential treatment target for glioma.

Microneurosurgery and subsequent gamma knife radiosurgery for functioning pituitary macroadenomas or giant adenomas: One institution's experience.

OBJECTIVE: Functioning pituitary macroadenoma and giant adenoma have large growth volumes and endocrinological abnormalities, requiring proper medical intervention. In this retrospective study, microneurosurgery and subsequent gamma knife radiosurgery (GKRS) is assessed for efficacy and safety for the treatment of functioning pituitary macroadenoma and giant adenoma. METHODS: Between January 2007 and December 2011, 59 patients with functioning pituitary macroadenoma (n=38) or giant adenoma (n=21) received microneurosurgical resection, and after three months, GKRS with average maximum radiation dose ∼42Gy (range 30-66.7Gy). The median follow-up time was 54.3 months (range 36-85 months). RESULTS: The combined treatment controlled tumor growth in 81.4% (48/59) of patients, and improved the endocrinological status in 64.4% (38/59). Complications included hypopituitarism and visual deterioration (22 and 7 patients, respectively). Large tumor size at presentation was a risk factor for tumor recurrence, but not age, gender, invasion, radiosurgical dose, pituitary hormone status or follow-up period. Better outcomes were achieved by patients with macroadenoma than giant adenoma. CONCLUSIONS: Combined microneurosurgery and GKRS are safe and effective for functioning pituitary macroadenomas or giant adenomas. Tumor control and endocrinological improvement were satisfactory, with minimal complications.

Bevacizumab treatment for newly diagnosed glioblastoma: Systematic review and meta-analysis of clinical trials.

High-grade glioma is a richly neovascularized brain solid tumor with a poor prognosis. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial cell proliferation and angiogenesis, which has shown clinical efficacy in recurrent glioblastoma. MEDLINE/PubMed, EMBASE and Web of Science databases were searched for relevant studies that compared bevacizumab plus combined radiotherapy/temozolomide (RT/TMZ) with RT/TMZ alone in newly diagnosed glioblastoma (GBM). Of all the studies identified, three comparative trials were included in the systematic review. All three enrolling trials, including a total of 1,738 patients, investigated bevacizumab or placebo plus combined RT/TMZ treatment in glioblastoma. The result showed no increased overall survival (OS) (pooled hazard ratio (HR), 1.04; 95% confidence interval (CI), 0.84-1.29; P=0.71) but increased progression-free survival (HR, 0.74; 95% CI, 0.62-0.88; P=0.0009). However, the two randomized double-blind placebo-control trials exemplified a high rate of adverse events of the bevacizumab compared with the placebo group while discrepant points were noted in term of quality-of-life outcome. Additionally, bevacizumab plus RT/TMZ did not increase the 6-month survival rate [odd ratios (ORs), 0.65; 95% CI, 0.37-1.13; P=0.13). Overall, addition of bevacizumab to radiotherapy-temozolomide treatment may be an effective therapy strategy for improving progression-free survival. OS and the 6-month survival rate was not prolonged and there was questionable efficacy of bevacizumab on the quality-of-life of glioblastoma patients, thus further clinical trials should be performed.

[Diagnosis and Treatment of the First Imported Case of Plasmodium knowlesi Infection in China].

Objective: To diagnose and treat the first imported active case of Plasmodium knowlesi infection in China. Methods: The clinical information of the patient was collected. Microscopy of blood smear was conducted after Giemsa staining. Genomic DNA was extracted from blood, and PCR was conducted to amplify rDNA. The PCR products were sequenced and analyzed with BLAST Results: The patient returned from a one-week tour in a tropical rain forest in Malaysia. The first disease attack occurred in Guangzhou on Oct. 16, 2014, with fever, shivering and sweating. The patient was initially diagnosed as malaria and hospitalized on Oct. 26, 2014. Microscopic observation revealed typical forms of P. knowlesi in blood smear. The red blood cells became enlarged, with big trophozoites appearing as a ring with dual cores and dark brown malaria pigment. The trophozoites were slightly bigger and thicker than P. falciparum. The schizont had 6-8 merozoites, with obvious brown malaria pigment. PCR resulted in a specific band of 1 099 bp. BLAST analysis showed that the sequence of the PCR product was 99% homologous to P. knowlesi (acession No. AM910985.1, L07560.1 and AY580317.1). The patient was diagnosed as P. knowlesi infection, and was then given an 8-day treatment with chloroquine and primaquine, together with dihydroartemisinin piperaquine phosphate tablet. The patient was discharged after recovery on Oct. 28, 2014. Conclusion: According to the clinical symptoms, epidemiological history and laboratory test, the patient has been confirmed as P. knowlesi infection. It may also be the first active case of knowlesi malaria reported in China.

Evaluation of inapparent dengue infections during an outbreak in Southern China.

Few studies evaluating inapparent dengue virus (DENV) infections have been conducted in China. In 2013, a large outbreak of DENV occurred in the city of Zhongshan, located in Southern China, which provided an opportunity to assess the clinical spectrum of disease. During the outbreak, an investigation of 887 index case contacts was conducted to evaluate inapparent and symptomatic DENV infections. Post-outbreak, an additional 815 subjects from 4 towns with, and 350 subjects from 2 towns without reported autochthonous DENV transmission, as determined by clinical diagnosis, were evaluated for serological evidence of dengue IgG antibodies. Between July and November 2013, there were 19 imported and 809 autochthonous dengue cases reported in Zhongshan. Of 887 case contacts enrolled during the outbreak, 13 (1.5%) exhibited symptomatic DENV infection, while 28 (3.2%) were inapparent. The overall I:S ratio was 2.2:1 (95% CI: 1.1-4.2:1). Post-outbreak serological data showed that the proportion of DENV IgG antibody detection from the 4 towns with and the 2 towns without reported DENV transmission was 2.7% (95% CI: 1.6%-3.8%) and 0.6% (95% CI: 0-1.4%), respectively. The I:S ratio in the 3 towns where clinical dengue cases were predominately typed as DENV-1 was 11.0:1 (95% CI: 3.7-∞:1). The ratio in the town where DENV-3 was predominately typed was 1.0:1 (95% CI: 0.5-∞:1). In this cross-sectional study, data suggests a high I:S ratio during a documented outbreak in Zhongshan, Southern China. These results have important implications for dengue control, implying that inapparent cases might influence DENV transmission more than previously thought.

Pulmonary nodules in liver transplant candidates with hepatocellular carcinoma: Imaging characteristics and clinical outcomes.

No guidelines exist for the management of pulmonary nodules in patients with hepatocellular carcinoma (HCC) who are being evaluated for liver transplantation. The 172 patients with HCC who were listed for liver transplant at our institution received both pretransplant chest computed tomography (CT) and follow-up CT. Pulmonary nodules on CT were characterized and followed on subsequent scans by a blinded radiologist, with a consensus review with a second radiologist being performed for equivocal cases. Nodule characteristics and outcomes were examined with chi-square tests, and the posttransplant survival of patients with different nodule outcomes was compared. Cumulative probabilities of waiting-list removal for nontransplant patients and cumulative probabilities of undergoing transplantation for all patients were also compared between patients with and without pulmonary nodules. Of all the patients, 76.2% had at least 1 pulmonary nodule on pretransplant CT, with 301 total nodules characterized; 2.7% of nodules represented HCC metastases, 1.0% represented other bronchopulmonary malignancies, and 2.7% represented infections. None of the malignant nodules exhibited a triangular/lentiform shape or calcifications. There were no statistically significant differences in pulmonary nodule outcomes between patients who underwent transplantation and those who did not undergo transplantation. No significant differences in posttransplant survival were found between patients with different nodule outcomes. There was also no significant difference between patients with and without nodules in the cumulative probabilities of waiting-list removal. However, the cumulative probability of undergoing liver transplantation was borderline significantly higher in patients without pulmonary nodules. In conclusion, despite the low prevalence of malignant nodules, all pulmonary nodules besides triangular/lentiform-shaped or calcified nodules should be followed with serial CT while the patient is on the transplant list, with biopsy performed for new and/or enlarged nodules. Both malignancy and active infection must be excluded when one is confronted with enlarged pulmonary nodules. Clinicians should also be aware of the possibility of reactivation of a granulomatous infection after transplantation.

Cardiophrenic lymph nodes in liver transplant candidates with hepatocellular carcinoma: imaging characteristics and post-transplant outcomes.

BACKGROUND: No guidelines exist for the management of cardiophrenic lymph nodes in patients with hepatocellular carcinoma (HCC) being evaluated for liver transplantation. METHODS: One hundred and seventy-eight patients with HCC listed for liver transplant received both pre-transplant computed tomography (CT) and follow-up CT scans. Enlarged cardiophrenic lymph nodes on CT were characterized and followed on subsequent scans; lymph node outcomes were assigned to "reduced" and "not reduced" categories. Tumor and patient characteristics were also recorded. RESULTS: Seventy-one of one hundred and seventy-eight patients (39.9%) had at least one cardiophrenic lymph node larger than 8 mm in diameter on pre-transplant CT. One hundred and sixty-six total lymph nodes were characterized. Six lymph nodes (3.6%) in two patients increased in size on follow-up imaging; all six cardiophrenic lymph nodes were presumed to represent metastases. There was a statistically significant reduction in lymph node size in patients who were transplanted vs. those who were not transplanted. Furthermore, a statistically significant association was found between increasing Model for End-Stage Liver Disease score and lymph node size reduction. There were no significant differences in post-transplant survival between patients with different lymph node outcomes. CONCLUSION: In the absence of metastatic disease in other sites, these lymph nodes are probably reactive; further workup is likely not necessary.

Racial and socioeconomic disparities in incidence of hospital-acquired complications following cerebrovascular procedures.

BACKGROUND: Patients with cerebrovascular disease undergo complex surgical procedures, often requiring prolonged inpatient hospitalization. Previous studies have demonstrated associations between racial/demographic factors and clinical outcomes in patients undergoing cerebrovascular procedures (CVPs). The Centers for Medicare and Medicaid Services have published a series of 11 hospital-acquired conditions (HACs) deemed "reasonably preventable" for which related costs of treatment are not reimbursed. We hypothesize that race and payer status disparities impact HAC frequency in patients undergoing CVPs and that HAC incidence is associated with length of stay and hospital costs. OBJECTIVE: To assess health disparities in HACs among the cerebrovascular neurosurgical patient population. METHODS: Data were collected from the Nationwide Inpatient Sample (NIS) database from 2002 to 2010. CVPs and HACs were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic and procedure codes. HAC incidence was evaluated according to demographics including race, payer status, and median zip code income via multivariable analysis. Secondary outcomes of interest included length of stay and resulting inpatient charges. RESULTS: From 2002 to 2010, there were 1 290 883 CVP discharges with an HAC rate of 0.5%. Significant disparities in HAC frequency existed according to ethnicity and insurance provider. Minorities and Medicaid patients had increased frequency of HACs (P < .05), as well as prolonged length of stay and higher inpatient costs (P < .05). CONCLUSION: HAC incidence is associated with racial and socioeconomic factors in patients who undergo CVPs. Awareness of these disparities may lead to improved processes and protocol implementation, which might help to decrease the frequency of these potentially avoidable events.

Image coregistration: quantitative processing framework for the assessment of brain lesions.

The quantitative, multiparametric assessment of brain lesions requires coregistering different parameters derived from MRI sequences. This will be followed by analysis of the voxel values of the ROI within the sequences and calculated parametric maps, and deriving multiparametric models to classify imaging data. There is a need for an intuitive, automated quantitative processing framework that is generalized and adaptable to different clinical and research questions. As such flexible frameworks have not been previously described, we proceeded to construct a quantitative post-processing framework with commonly available software components. Matlab was chosen as the programming/integration environment, and SPM was chosen as the coregistration component. Matlab routines were created to extract and concatenate the coregistration transforms, take the coregistered MRI sequences as inputs to the process, allow specification of the ROI, and store the voxel values to the database for statistical analysis. The functionality of the framework was validated using brain tumor MRI cases. The implementation of this quantitative post-processing framework enables intuitive creation of multiple parameters for each voxel, facilitating near real-time in-depth voxel-wise analysis. Our initial empirical evaluation of the framework is an increased usage of analysis requiring post-processing and increased number of simultaneous research activities by clinicians and researchers with non-technical backgrounds. We show that common software components can be utilized to implement an intuitive real-time quantitative post-processing framework, resulting in improved scalability and increased adoption of post-processing needed to answer important diagnostic questions.