Radiomics and nomogram of magnetic resonance imaging for preoperative prediction of microvascular invasion in small hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) of small hepatocellular carcinoma (sHCC) (≤ 3.0 cm) is an independent prognostic factor for poor progression-free and overall survival. Radiomics can help extract imaging information associated with tumor pathophysiology. AIM: To develop and validate radiomics scores and a nomogram of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in sHCC. METHODS: In total, 415 patients were diagnosed with sHCC by postoperative pathology. A total of 221 patients were retrospectively included from our hospital. In addition, we recruited 94 and 100 participants as independent external validation sets from two other hospitals. Radiomics models of Gd-EOB-DTPA-enhanced MRI and diffusion-weighted imaging (DWI) were constructed and validated using machine learning. As presented in the radiomics nomogram, a prediction model was developed using multivariable logistic regression analysis, which included radiomics scores, radiologic features, and clinical features, such as the alpha-fetoprotein (AFP) level. The calibration, decision-making curve, and clinical usefulness of the radiomics nomogram were analyzed. The radiomic nomogram was validated using independent external cohort data. The areas under the receiver operating curve (AUC) were used to assess the predictive capability. RESULTS: Pathological examination confirmed MVI in 64 (28.9%), 22 (23.4%), and 16 (16.0%) of the 221, 94, and 100 patients, respectively. AFP, tumor size, non-smooth tumor margin, incomplete capsule, and peritumoral hypointensity in hepatobiliary phase (HBP) images had poor diagnostic value for MVI of sHCC. Quantitative radiomic features (1409) of MRI scans) were extracted. The classifier of logistic regression (LR) was the best machine learning method, and the radiomics scores of HBP and DWI had great diagnostic efficiency for the prediction of MVI in both the testing set (hospital A) and validation set (hospital B, C). The AUC of HBP was 0.979, 0.970, and 0.803, respectively, and the AUC of DWI was 0.971, 0.816, and 0.801 (P < 0.05), respectively. Good calibration and discrimination of the radiomics and clinical combined nomogram model were exhibited in the testing and two external validation cohorts (C-index of HBP and DWI were 0.971, 0.912, 0.808, and 0.970, 0.843, 0.869, respectively). The clinical usefulness of the nomogram was further confirmed using decision curve analysis. CONCLUSION: AFP and conventional Gd-EOB-DTPA-enhanced MRI features have poor diagnostic accuracies for MVI in patients with sHCC. Machine learning with an LR classifier yielded the best radiomics score for HBP and DWI. The radiomics nomogram developed as a noninvasive preoperative prediction method showed favorable predictive accuracy for evaluating MVI in sHCC.

OsPHT1;3 Mediates Uptake, Translocation, and Remobilization of Phosphate under Extremely Low Phosphate Regimes.

Plant roots rely on inorganic orthophosphate (Pi) transporters to acquire soluble Pi from soil solutions that exists at micromolar levels in natural ecosystems. Here, we functionally characterized a rice (Oryza sativa) Pi transporter, Os Phosphate Transporter-1;3 (OsPHT1;3), that mediates Pi uptake, translocation, and remobilization. OsPHT1;3 was directly regulated by Os Phosphate Starvation Response-2 and, in response to Pi starvation, showed enhanced expression in young leaf blades and shoot basal regions and even more so in roots and old leaf blades. OsPHT1;3 was able to complement a yeast mutant strain defective in five Pi transporters and mediate Pi influx in Xenopus laevis oocytes. Overexpression of OsPHT1;3 led to increased Pi concentration both in roots and shoots. However, unlike that reported for other known OsPHT1 members that facilitate Pi uptake at relatively higher Pi levels, mutation of OsPHT1;3 impaired Pi uptake and root-to-shoot Pi translocation only when external Pi concentration was below 5 µm Moreover, in basal nodes, the expression of OsPHT1;3 was restricted to the phloem of regular vascular bundles and enlarged vascular bundles. An isotope labeling experiment with 32P showed that ospht1;3 mutant lines were impaired in remobilization of Pi from source to sink leaves. Furthermore, overexpression and mutation of OsPHT1;3 led to reciprocal alteration in the expression of OsPHT1;2 and several other OsPHT1 genes. Yeast-two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays all demonstrated a physical interaction between OsPHT1;3 and OsPHT1;2. Taken together, our results indicate that OsPHT1;3 acts as a crucial factor for Pi acquisition, root-to-shoot Pi translocation, and redistribution of phosphorus in plants growing in environments with extremely low Pi levels.

A 41-gene signature derived from breast cancer stem cells as a predictor of survival.

PURPOSE: The aim of this study was to evaluate the ability of a 41-gene signature derived from breast cancer stem cells (BCSCs) to estimate the risk of metastasis and survival in breast cancer patients. METHODS: The centroid expression of the 41-gene signature derived from BCSCs was applied as the threshold to classify patients into two separate groups--patients with high expression (high-EL) of the prognostic signature and patients with low expression (low-EL). The predictive ability of the 41-gene signature was evaluated by Cox regression model and was compared against other popular tests, such as Oncotype and MammaPrint. RESULTS: Our results showed that the 41-gene prognostic signature was significantly associated with age (P = .0351) and ER status (P = .0095). The analysis indicated that patients in the high-EL group had a worse prognosis than those in the low-EL group in terms of both overall survival (OS: HR, 2.05, P = .009) and distant metastasis-free survival (DMFS: HR, 2.24, P = .002). Additionally, the 41-gene signature was an independent risk factor and separates patients based on estrogen receptor status. While comparable to Oncotype, the analysis demonstrated that the 41-gene signature had a better prognostic value in predicting DMFS and OS than AOL, NPI, St. Gallen, Veridex, and MammaPrint. CONCLUSIONS: This study confirms the utility of the 41-gene signature and adds to the growing evidence that gene expression signatures of BCSCs have clinical potential to predict patient outcome and aid in treatment choice.

[Therapeutic effect of Chinese herbal medicines for nourishing blood and reinforcing shen in treating patients with anovulatory sterility of shen-deficiency type and its influence on the hemodynamics in ovarian and uterine arteries].

OBJECTIVE: To observe the clinical therapeutic effect of Nuzhen Yunyu Decoction (NYD, a Chinese recipe for nourishing blood and reinforcing Shen) and its influence on the hemodynamic parameters in ovarian and uterine arteries. METHODS: Sixty-eight patients were randomly divided into two groups at the ratio of 2:1, 45 in the TCM group treated with Chinese medicine and 23 in the control group treated with clomiphene citrate. Menstrual cycle were taken as the indexes for clinical observation; basal body temperature, cervical mucus, vaginal exfoliative cells, serum hormones and B ultrasonic examination were taken as the indexes for ovulation and pregnancy assessment. The hemodynamic parameters of uterus and ovary were determined by using color Doppler ultrasonography, and the growth of follicles and ovulation, thickness of uterine endometrium were also monitored continuously. RESULTS: Results of 3 cycles treatment and 1 year follow-up study showed that the ovulation promoting rate, pregnancy rate and abortion rate in the two groups were similar, but the treated group showed better effects than that of control group, in such aspects as regulating menstruation, promoting growth and development of follicle, strengthening endometrium, improving blood supply and circulation of uterine and ovary (P < 0.05, P < 0.01). CONCLUSION: NYD has the effects of ovulation promotion and holistic regulation of reproductive system.