Long-term outcomes of combined transarterial chemoembolization and radiofrequency ablation versus RFA monotherapy for single hepatocellular carcinoma ≤3 cm: emphasis on local tumor progression.

PURPOSE: To compare the long-term outcomes of combined transarterial chemoembolization and radiofrequency ablation (TACE-RFA) with radiofrequency ablation (RFA) monotherapy for small (≤3 cm) hepatocellular carcinomas (HCCs). METHODS: A total of 248 patients with 329 HCC nodules who underwent TACE-RFA or RFA monotherapy as the only first-line treatment between January 2009 and December 2020 were included in this study. The technical success, complications, survival rate, and local tumor progression (LTP) rate were compared between the two treatments. RESULTS: The 1-, 3- and 5-year survival rates were similar between the two groups (98.7%, 93.0% and 75.9% vs 97.4%, 88.0% and 77.4%; p = 0.444). The 1-, 3-, and 5-year cumulative LTP rates were significantly lower in the TACE-RFA group than in the RFA monotherapy group (2.9%, 9.2%, and 13.8% vs. 5.2%, 17.0%, and 21.0%; p = 0.043). Subgroup analyses suggested that TACE-RFA showed significantly lower LTP rates than RFA monotherapy for small HCC with tumor size>2cm (p = 0.008), subphrenic location (p = 0.021), and perivessel (p = 0.030). Furthermore, HCC with well-defined lipiodol deposition in the TACE-RFA group showed better local tumor control than the small HCC in the RFA monotherapy group (p = 0.013). There was no significant difference in the technical success rates (p = 0.064) and complication rates (p = 0.952) between the two groups. CONCLUSIONS: TACE-RFA is superior to RFA monotherapy in providing local tumor control for small HCC with tumor size 2-3 cm in diameter, subphrenic location, perivessel and HCCs with well-defined lipiodol deposition by TACE before RFA.

Glenoid bony morphology along long diameter is associated with the occurrence of recurrent anterior shoulder dislocation: a case-control study based on three-dimensional CT measurements.

PURPOSE: The purpose of our study is to compare the anatomic parameters of proximal humerus, glenoid, and glenohumeral joint between patients with recurrent anterior shoulder dislocation (RASD) and patients without RASD with the assistance of three-dimensional (3D) CT scans. METHODS: Sixty patients were included in the study and divided into group RASD and group control. 3D-CT models of shoulder joint for each included patient were reconstructed and multiple anatomic parameters were measured. RESULTS: There were no statistically significant differences between the two groups in morphological parameters of humerus and glenohumeral joints. Long diameter of glenoid was 3.50 ± 0.34 cm for patients in group RASD and 3.31 ± 0.32 cm in group control (p = 0.039). There was a statistically significant difference in the ratio of long to short diameter of glenoid (p < 0.001). Ratio of humeral head height to glenoid long diameter (Hhh/Gld) was 1.02 ± 0.07 in group RASD, significantly lower than 1.09 ± 0.08 in group control (p = 0.001). Longitudinal depth of glenoid was significantly higher in group RASD (p = 0.013). CONCLUSION: The glenoid morphology along long diameter is closely correlated with the stability of glenohumeral joint, including glenoid long diameter and glenoid longitudinal depth. It is especially noteworthy that the value of Hhh/Gld decreases in patients with RASD. The difference of Hhh/Gld between the two groups reminds us that the correlation of bony structure along long diameter between glenoid and humeral head plays an important role in RASD.

Safety and Efficacy of Stent Graft Implantation for Malignant Superior Vena Cava Syndrome.

BACKGROUND: Patients with malignant superior vena cava syndrome (SVCS) usually require urgent treatments due to a high potential risk of early mortality. Stent implantation can rapidly improve the symptoms of SVCS, which may be beneficial to subsequent anti-tumor therapy. The aim of the study was to evaluate the clinical outcomes of stent graft implantation for the treatment of superior vena cava (SVC) obstruction caused by non-small cell lung carcinoma (NSCLC) with acute post-stenting occlusion. METHODS: Between October 2014 and December 2019, 16 patients were selected for stent graft implantation. Technical success and clinical efficacy were assessed. Stent patency and patient survival rates, as well as the complications were analyzed. RESULTS: There were 17 stent grafts implanted in 16 patients. The technical success was 100%. The residual stenosis after initial implantation was 64.0 ± 9.0%. The stent expanded to an optimal size in 5.5 ± 2.2 days after the initial deployment. Migration occurred when deploying of the stent graft in one patient; this stent graft was successfully stabilized by a second one. No other complications related to the procedure were found except one migration. At 1, 3, 6, 9 and 12 months, the cumulative survival rates were 100%, 75%, 56%, 19% and 0%, respectively. The mean OS was 173 days. The median survival was 166 days. CONCLUSIONS: Stent graft can be safely used in patients with SVC obstruction with a good long-term patency rate.

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial.

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%). Conclusions and Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.

Long-term outcomes after partial patellectomy in comminuted fractures - a clinical study.

PURPOSE: The purpose of this study was to evaluate the long-term clinical and radiographic outcomes of partial patellectomy (PP) in patients with patella comminuted distal pole fractures. METHODS: Seventeen patients who were diagnosed with patella comminuted distal pole fractures and underwent PP procedures were retrospectively included between January 1995 and January 2005. We collected patient demographics and data on the mechanism of injury, time to surgery, fracture type, follow-up time, and post-operative complications (infection, patellofemoral arthritis, and stiffness). At the final follow-up, functional outcome was evaluated by the range of motion (ROM) and the Bostman Scoring System. Quadriceps strength was evaluated by using an isokinetic dynamometer to measure peak torque, and patellar height was evaluated by the Insall-Salvati (IS) ratio in lateral knee radiographs. The average follow-up period was 14.6 years (range, 11-19 years). RESULTS: We analyzed 17 patients (AO/OTA 34-A1), with an average age of 59.8 years (range, 43-76 years). According to the Bostman grading scales, final functional outcomes were excellent in 11 (64.7%) and good in six (35.3%) patients. All patients had full knee extension, and the average ROM was 125.1° (range, 121.4-129.3°). The average peak torque of the injured knee was 103.2 ± 9.7 Nm, and that of the uninjured opposite side was 108.3 ± 7.6 Nm, with no significant difference (p > 0.05). Furthermore, no postoperative complications, such as infection, posttraumatic osteoarthritis, or stiffness, were observed. Compared to the uninjured knee, the IS ratio of the injured knee was 0.76 ± 0.13, indicating that the patellar height was decreased, which meant patella baja. CONCLUSIONS: The PP procedure for patella comminuted distal pole fractures is a safe, simple, and reliable technique that can provide good long-term clinical outcomes even with decreased patellar height and could be a satisfactory alternative treatment option when anatomical reduction is difficult.

Concordance between treatment recommendations provided by IBM Watson for Oncology and a multidisciplinary tumor board for breast cancer in China.

OBJECTIVE: Watson for Oncology (WFO), an artificial intelligence from IBM Corporation, can provide a treatment plan by analyzing patient's disease characteristics. The present study was performed to examine the concordance between treatment recommendations proposed by WFO and the multidisciplinary tumor board at our center. The aim was to explore the feasibility of using WFO for breast cancer cases in China and to ascertain the ways to make WFO more suitable for Chinese patients with breast cancer. METHODS: Data from 302 breast cancer patients treated at the Second Affiliated Hospital of Xi'an Jiaotong University between October 2016 and February 2018 was retrieved and retrospectively analyzed by WFO. The recommendations were divided into 'recommended', 'considered' and 'not recommended' groups. Results were considered concordant when oncologists' recommendations were categorized as 'recommended' or 'for consideration' by WFO. RESULTS: The concordance rate of 200 subjects with postoperative adjuvant therapy was 77%. However, the rate was 27.5% in the remaining 102 cases with metastatic disease receiving either first-line or no treatment. Further analysis demonstrated that inconsistencies were mainly due to different choices of chemotherapy regimens. Subgroup study indicates that tumor stage, receptor status and age also had influences at the concordance rate. CONCLUSION: The results of this study suggest that WFO is a promising artificial intelligence system for the treatment of breast cancer. These findings can also serve as a reference framework for the inclusion of artificial intelligence in the ongoing medical reform in China.

Negligible transcriptome and metabolome alterations in RNAi insecticidal maize against Monolepta hieroglyphica.

KEY MESSAGE: RNAi-based genetically modified maize resistant to Monolepta hieroglyphica (Motschulsky) was demonstrated with negligible transcriptome and metabolome alterations compared to its unmodified equivalent. As one of the most prevalent insect pests afflicting various crops, Monolepta hieroglyphica (Motschulsky) causes severe loss of agricultural and economic productivity for many years in China. In an effort to reduce damages, in this study, an RNA interference (RNAi)-based genetically modified (GM) maize was developed. It was engineered to produce MhSnf7 double-stranded RNAs (dsRNAs), which can suppress the Snf7 gene expression and then lead M. hieroglyphica to death. Field trail analysis confirmed the robustly insecticidal ability of the MhSnf7 GM maize to resist damages by M. hieroglyphica. RNA sequencing analysis identified that only one gene was differentially expressed in the MhSnf7 GM maize compared to non-GM maize, indicating that the transcriptome in MhSnf7 GM maize is principally unaffected by the introduction of the MhSnf7 dsRNA expression vector. Likewise, metabolomics analysis identified that only 8 out of 5787 metabolites were significantly changed. Hence, the integration of transcriptomics and metabolomics demonstrates that there are negligible differences between MhSnf7 GM maize and its unmodified equivalent. This study not only presents a comprehensive assessment of cellular alteration in terms of gene transcription and metabolite abundance in RNAi-based GM maize, but also could be used as a reference for evaluating the unintended effect of GM crops.

Spontaneous rupture of enormous renal angiomyolipoma in a pregnant tuberous sclerosis patient: a rare case.

BACKGROUND: Renal angiomyolipoma (RAML) is a rare benign kidney tumour comprised of adipose tissue, smooth muscle, and blood vessels. It can cause fatal complications if it ruptures. Although there have been reports of RAMLs rupturing, it is unusual to see RAMLs rupture during pregnancy, especially in pregnant women with tuberous sclerosis (TSC). Moreover, we reported a rare complication after selective arterial embolization (SAE) for the first time, which called aseptic liquefaction necrosis. CASE PRESENTATION: The case is a 16-week-pregnant woman with TSC who presented with severe flank pain, which was secondary to the rupture of a large, previously unknown RAML. This was confirmed by emergency computed tomography and successfully treated with selective arterial embolization after the patient received counselling and provided prior informed written consent for medical termination of pregnancy (MTP). The patient underwent abortion 3 weeks after the SAE. The patient required drainage 2 months after the SAE because of aseptic liquefaction necrosis. During follow-up, the patient's lesion remained stable. CONCLUSION: RAML rupture is a rare but rather serious complication in pregnant tuberous sclerosis patients. Selective arterial embolization (SAE) should be performed immediately, and the status of the pregnancy needs to be assessed by a multidisciplinary team. We also report for the first time the rare complication of aseptic liquefaction necrosis after SAE of RAML, for which percutaneous drainage is effective.

Changes in the gut microbiota during and after commercial helium-oxygen saturation diving in China.

OBJECTIVES: The influence of commercial helium-oxygen saturation diving on divers' gut microbiotas was assessed to provide dietary suggestion. METHODS: Faecal samples of 47 divers working offshore were collected before (T1), during (T2) and after (T3) saturation diving. Their living and excursion depths were 55-134 metres underwater with a saturation duration of 12-31 days and PaO2 of 38-65 kPa. The faecal samples were examined through 16S ribosomal DNA amplicon sequencing based on the Illumina sequencing platform to analyse changes in the bacteria composition in the divers' guts. RESULTS: Although the α and ß diversity of the gut microbiota did not change significantly, we found that living in a hyperbaric environment of helium-oxygen saturation decreased the abundance of the genus Bifidobacterium, an obligate anaerobe, from 2.43%±3.83% at T1 to 0.79%±1.23% at T2 and 0.59%±0.79% at T3. Additionally, the abundance of some short-chain fatty acid (SCFA)-producing bacteria, such as Fusicatenibacter, Faecalibacterium, rectale group and Anaerostipes, showed a decreased trend in the order of before, during and after diving. On the contrary, the abundance of species, such as Lactococcus garvieae, Actinomyces odontolyticus, Peptoclostridium difficile, Butyricimonas virosa, Streptococcus mutans, Porphyromonas asaccharolytica and A. graevenitzii, showed an increasing trend, but most of them were pathogens. CONCLUSIONS: Occupational exposure to high pressure in a helium-oxygen saturation environment decreased the abundance of Bifidobacterium and some SCFA-producing bacteria, and increased the risk of pathogenic bacterial infection. Supplementation of the diver diet with probiotics or prebiotics during saturation diving might prevent these undesirable changes.

Quality of Life, Adverse Events, and Reintervention Outcomes after Laparoscopic Radiofrequency Ablation for Symptomatic Uterine Fibroids: A Meta-Analysis.

In this review, we assessed the short-term (3 and 6 months) and long-term (12, 24, and 36 months) symptom relief and quality of life improvement, procedure-related adverse event rate, reintervention rate, and days missed from work after laparoscopic radiofrequency ablation. Using MeSH keywords "uterine fibroid" and "ablation technique," a systematic search was performed in PubMed, Ovid, Embase, Cochrane Library, and Clinicaltrials.gov. Studies consisting of uterine fibroid symptoms and quality of life scores were considered eligible. Both comparative and noncomparative studies were included. Using a random-effects model, a meta-analysis was performed. Eight studies with a total of 581 patients were finally included in our review. Based on validated questionnaires, quality of life improved significantly until 36 months after laparoscopic radiofrequency ablation therapy, with a maximum improvement (Health-Related Quality of Life [HRQL] questionnaire score of +41.64 [95% confidence interval (CI), 38.94-44.34] and a transformed Symptom Severity Score [tSSS] of -39.37 [95% CI, 34.70-44.04]) at 12 months after laparoscopic radiofrequency ablation. All subscales of quality of life improved significantly, and most of the changes remained stable in long-term follow-up. The overall reintervention rate was 4.39% (95% CI, 1.60%-8.45%), and the median uterine volume reduction was 69.17 cm³ (95% CI, 35.87-102.46 cm³).The overall procedure-related adverse events rate was 1.78% (95% CI, 0.62%-3.53%), and patients missed an average of 4.35 days (95% CI, 2.55-6.15 days) of work. In conclusion, laparoscopic radiofrequency ablation therapy is an efficacious way to treat small-sized and nonpedunculated symptomatic uterine fibroids, providing stable long-term symptom relief and quality of life improvement with a low risk of adverse events and reintervention and just a few days of missed work.

Diagnostic criteria of periprosthetic joint infection: a prospective study protocol to validate the feasibility of the 2018 new definition for Chinese patients.

BACKGROUND: Periprosthetic joint infection (PJI) is a challenging complication following total joint arthroplasty (TJA), and the diagnostic criteria remains controversial. The 2018 new definition proposed in May 2018 consists of new diagnostic criteria for PJI. We conducted a retrospective study and demonstrated that the new definition could improve the diagnostic efficiency in Chinese patients. However, missing data led to bias in the previous retrospective study. Therefore, this prospective study is designed to further validate the feasibility of 2018 new definition (and its modified version) for Chinese patients. METHODS/DESIGN: This is a single-centre, prospective diagnostic study with 1 year of follow-up. The patients enrolled in the trial will be divided into a PJI group and an Aseptic group based on the eligibility criteria. We will recruit at least 70 patients for each group from October 2019 to October 2020. Blood samples, synovial fluid samples and intraoperative variables of all the included patients will be collected to assess various indicators. We will integrate the results of the various tests and examine the diagnostic efficiency (sensitivity and specificity) of five diagnostic criteria. DISCUSSION: We design the prospective study in the hope of reducing the bias caused by missing data. Therefore, the prospective study will further support the conclusion of our preceding retrospective study. The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: Through this prospective study, we will validate the feasibility of the 2018 new PJI definition (and its modified version) for Chinese patients and determine the optimal method of PJI diagnosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025395. Registered on 25 August 2019.

MiR-429 suppresses neurotrophin-3 to alleviate perineural invasion of pancreatic cancer.

Perineural invasion (PNI) potentially increases the risk of relapse and abdominal pain in patients with pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms of PNI of PDAC is incompletely revealed. Our study aimed to investigate roles of miR-429 in modulating PNI in PDAC. We found that miR-429 was downregulated in PDAC cancer tissues and was profoundly decreased in tissues with PNI. It was reduced in nine of the ten examined pancreatic cancer cell lines. MiR-429 mimics restored its cellular expressions in MIA PaCa-2 and BxCP3 cells and significantly suppressed cell viability and invasion of the cancer cells. The online bioinformatic software predicted that neurotrophin-3 (NT-3) was a potential target gene of miR-429. It was showed that NT-3 mRNA elevated in PC cancer tissues, especially in patients presenting PNI. MiR-429 upregulation substantially suppressed the NT-3 mRNA and secretion in cancer cells. Also, the dual luciferase reporter assays confirmed the interaction between miR-429 and NT-3. When co-culturing the two PDAC cells with PC-12 cells, the invaded cell counts significantly increased comparing with the sole culture of cancer cells. However, miR-429 mimic transfection or NT-3 blocking retarded the cancer invasion in the co-culture system. Besides, we found that cancer cells conditioned medium (CM) treatment significantly increased the neurite outgrowth percentage in PC-12 cells, which was suppressed by culturing with CM from miR-429 mimics-transfected cells. In the CM cultured PC-12 cells, NT-3 receptor TrkC as well as pain-related proteins TRPV1 and TRPV2 significantly elevated. Collectively, miR-429 potentially suppressed neurotrophin-3 to alleviate PNI of PDAC.

Berberine alleviates the cerebrovascular contractility in streptozotocin-induced diabetic rats through modulation of intracellular Ca²âº handling in smooth muscle cells.

BACKGROUND: Vascular dysfunction is a distinctive phenotype in diabetes mellitus. Current treatments mostly focus on the tight glycemic control and few of these treatments have been designed to directly recover the vascular dysfunction in diabetes. As a classical natural medicine, berberine has been explored as a possible therapy for DM. In addition, it is reported that berberine has an extra-protective effect in diabetic vascular dysfunction. However, little is known whether the berberine treatment could ameliorate the smooth muscle contractility independent of a functional endothelium under hyperglycemia. Furthermore, it remains unknown whether berberine affects the arterial contractility by regulating the intracellular Ca(2+) handling in vascular smooth cells (VSMCs) under hyperglycemia. METHODS: Sprague-Dawley rats were used to establish the diabetic model with a high-fat diet plus injections of streptozotocin (STZ). Berberine (50, 100, and 200 mg/kg/day) were intragastrically administered to control and diabetic rats for 8 weeks since the injection of STZ. The intracellular Ca(2+) handling of isolated cerebral VSMCs was investigated by recording the whole-cell L-type Ca(2+) channel (CaL) currents, assessing the protein expressions of CaL channel, and measuring the intracellular Ca(2+) in response to caffeine. Our results showed that chronic administration of 100 mg/kg/day berberine not only reduced glucose levels, but also inhibited the augmented contractile function of cerebral artery to KCl and 5-hydroxytryptamine (5-HT) in diabetic rats. Furthermore, chronic administration of 100 mg/kg/day berberine significantly inhibited the CaL channel current densities, reduced the α1C-subunit expressions of CaL channel, decreased the resting intracellular Ca(2+) ([Ca(2+)]i) level, and suppressed the Ca(2+) releases from RyRs in cerebral VSMCs isolated from diabetic rats. Correspondingly, acute application of 10 µM berberine could directly inhibit the hyperglycemia-induced CaL currents and suppress the hyperglycemia-induced Ca(2+) releases from RyRs in cerebral VSMCs isolated from normal control rats. CONCLUSIONS: Our study indicated that berberine alleviated the cerebral arterial contractility in the rat model of streptozotocin-induced diabetes via regulating the intracellular Ca(2+) handling of smooth muscle cells.

SH3GL1 inhibition reverses multidrug resistance in colorectal cancer cells by downregulation of MDR1/P-glycoprotein via EGFR/ERK/AP-1 pathway.

Multidrug resistance is one of the major reasons colorectal cancer (CRC) chemotherapy-based treatments fail, and novel biologically based therapies are urgently needed. Src homology 3 (SH3)-domain GRB2-like protein 1 (SH3GL1) is a membrane-bound protein which was found to be involved in tumor formation, progression, and metastasis. In this study, immunohistochemistry staining, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis revealed a high expression of SH3GL1 in human CRC tumor specimens and several CRC cells resistant to chemotherapeutics. Cell Counting Kit-8 (CCK-8) assay showed that transfection of pCDNA3.1(+)-SH3GL1 increased while transfection of SH3GL1 siRNA decreased cell viability in response to 5-fluorouracil (5-FU) treatment (P < 0.05). Further studies indicated that transfection of SH3GL1 siRNA significantly downregulated multidrug resistance protein 1 (MDR1)/P-glycoprotein expression (P < 0.05), decreased MDR1 promoter activity and activator protein-1 (AP-1) binding activity (P < 0.05), and inhibited the activation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling (P < 0.05) in CRC cells resistant to chemotherapeutics. Transfection of pCDNA3.1(+)-SH3GL1 caused the opposite effect. Additionally, pre-treatment with either EGFR kinase inhibitor PD153035 or ERK1/2 kinase inhibitor PD98059 in HCT116/5-FU cells partly inhibits P-glycoprotein expression and AP-1 binding activity (P < 0.05). In conclusion, we confirmed that inhibition of SH3GL1 reverses multidrug resistance through declining P-glycoprotein expression via the EGFR/ERK/AP-1 pathway.

miR-383 inhibits hepatocellular carcinoma cell proliferation via targeting APRIL.

Mounting evidence has shown that microRNAs (miRNAs), a class of small non-coding RNAs, are frequently deregulated in human malignancies and have pivotal roles in diverse biological processes including cancer cell proliferation. Herein, we investigated the expression pattern of miR-383 in 64 hepatocellular carcinoma (HCC) tissues and 4 HCC cell lines and found that miR-383 was downregulated in HCC tissues and cell lines. Moreover, miR-383 expression in HCC was significantly correlated with tumor size and tumor-node-metastasis (TNM) stage. Kaplan-Meier analysis showed that decreased miR-383 expression was associated with poor overall survival of HCC patients. In addition, Cox regression analysis indicated that miR-383 was an independent prognostic factor for HCC patients. Then, functional studies demonstrated that ectopic miR-383 expression could significantly suppress the in vitro proliferation of HCC cells, as well as induce cell cycle arrest and cell apoptosis. Luciferase reporter assay further identified that a proliferation-inducing ligand (APRIL), a member in the tumor necrosis factor (TNF) superfamily, was a novel target gene for miR-383. Subsequent investigation revealed that miR-383 expression was inversely correlated with APRIL messenger RNA (mRNA) expression in HCC tissues. Besides, recombinant human APRIL (rhAPRIL) could rescue HCC cell proliferation inhibited by miR-383. Taken together, our present study provided the first evidence that miR-383 was decreased in HCC and associated with tumor progression and prognosis of HCC patients. Furthermore, our findings confirmed that miR-383 might inhibit HCC cell proliferation partially via downregulating APRIL expression. Thus, this study might provide a promising strategy by targeting with the miR-383-APRIL axis in the treatment of HCC.

Significance of the ADC ratio in the differential diagnosis of breast lesions.

BACKGROUND: Magnetic resonance imaging (MRI) has high sensitivity but low specificity for breast cancer, and consequently, new techniques to improve the specificity of breast MRI in diagnosing breast cancer are under development. PURPOSE: To assess the ability of the apparent diffusion coefficient (ADC) compared with the ADC ratio (ADCr) to differentially diagnose benign compared with malignant breast lesions. MATERIAL AND METHODS: Forty-eight women with breast lesions (average age, 45 years) underwent MRI scanning including T1-weighted dynamic contrast-enhanced (DCE) scanning and diffusion-weighted imaging (DWI). The average ADC and ADCr values for both lesions and pectoralis major muscles (ADCrmuscle and ADCrmuscle) were measured in patients with malignant (n = 25) and benign (n = 23) breast lesions. The ADCr of the contralateral breast (ADCr contralateral) was also evaluated. All histology was confirmed by pathological analysis of biopsied tissue. ADC and ADCr values were analyzed using receiver-operating characteristic (ROC) curves. RESULTS: For benign lesions compared with malignant lesions, lesion-side ADC was 1.45 vs. 1.05, respectively (P < 0.001), normal-side ADC was 1.82 vs.1.64 (P = 0.002), ADCrmuscle was 1.35 vs. 0.9 (P < 0.001), and ADCrcontralateral was 0.79 vs. 0.64 (P = 0.001). ADCrmuscle showed higher sensitivity (82.61%) and specificity (96.00%) than ADCrcontralateral (60.87% and 92.00%, respectively) and ADC (69.57% and 96.00%) for discriminating malignant from benign lesions. The AUC using ADCrmuscle had higher discriminatory power (0.92, P < 0.001) for malignant versus benign breast lesions compared with either ADC (0.82, P < 0.001) or ADCrcontralateral (0.78, P = 0.001). CONCLUSION: The ADCrmuscle value showed higher sensitivity and specificity and improved diagnostic accuracy compared with either ADC or ADCrcontralateral in differentiating benign from malignant breast lesions.

Saikosaponin-D enhances radiosensitivity of hepatoma cells under hypoxic conditions by inhibiting hypoxia-inducible factor-1α.

BACKGROUND: Our previous study revealed that the combination of Saikosaponin-d ( SSd) and radiation is more effective in the treatment of liver cancer than the application of either of these monotherapeutic methods. However, the molecular mechanisms of the radiosensitizing effect of SSd on liver cancer remained ill defined. METHODS: Cells were treated with different interventions; afterward, cell viability, apoptosis, and cell survival of SMMC-7721 and HepG2 hepatoma cells were examined. Xenograft tumor models were established by subcutaneously injecting SMMC-7721 cells. The molecular mechanism was assessed by western blot. RESULTS: SSd dose-dependently increased radiosensitivity of hepatoma cells under hypoxic condition. The growth inhibitory effect of the combined treatment was correlated with cell apoptosis. Further mechanistic analysis indicated that SSd induced the upregulation of p53 and Bax as well as the downregulation of Bcl-2 by attenuating HIF-1α expression under hypoxic condition. These effects were enhanced when the HIF-1α inhibitor PX-478 was introduced. In vivo data also presented a more significant suppression of tumor xenograft growth from the combined therapy than from either of the monotherapeutic methods. CONCLUSIONS: Our study provides evidence for a radiosensitizing effect of SSd on hepatoma cells under hypoxic conditions by inhibiting HIF-1α expression. Thus, SSd can be used as a potential sensitizer in hepatoma radiotherapy. © 2014 S. Karger AG, Basel.

Functional promoter -765 G > C variant in COX-2 gene is associated with the susceptibility of breast cancer in Chinese Han women.

BACKGROUND: Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women. METHODS: In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression. RESULTS: Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism. CONCLUSIONS: Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.

[Preparation and investigation of MRI-traceable Eudragit-E liquid embolic agent].

OBJECTIVE: To develop and investigate the properties of MRI-traceable Eudragit-E liquid embolic agent (MR-E). METHODS: Polyethylene glycol-modified superparamagnetic iron oxides (PEG-SPIO) was synthesized by chemical co-precipitation method. MR-E was prepared by mixing PEG-SPIO and Eudragit-E liquid embolic agent homogeneously. An in vitro MR phantom study was carried out to measure MR traceability of MR-E and to determine the concentration of PEG-SPIO for further studies. The microcatheter deliverability and sol-gel transition process of MR-E were investigated. MR-E was injected into the kidney of a Japanese white big ear rabbit via an angiographic microcatheter, and detected by MRI. RESULTS: A PEG-SPIO concentration of 2 g/L was considered to be suitable for further studies. MR-E was injected through the microcatheter without any difficulty. MR-E instantly solidified on release into saline. Then 0.2 mL of MR-E effectively embolized distal renal arteries, and MR-E could be detected by MRI in the embolized kidney. CONCLUSION: MR-E seems to be a promising MRI-traceable liquid embolic agent.