Contrast-enhanced ultrasonography for early prediction of response of neoadjuvant chemotherapy in breast cancer.

Neoadjuvant chemotherapy (NAC) is widely accepted as a primary treatment for inoperable or locally advanced breast cancer before definitive surgery. However, not all advanced breast cancers are sensitive to NAC. Contrast-enhanced ultrasonography (CEUS) has been considered to assess tumor response to NAC as it can effectively reflect the condition of blood perfusion and lesion size. Therefore, this study aimed to evaluate the diagnostic performance of CEUS to predict early response in different regions of interest in breast tumors under NAC treatment. This prospective study included 82 patients with advanced breast cancer. Parameters of TIC (time-intensive curve) between baseline and after the first cycle of NAC were calculated for the rate of relative change (Δ), including Δpeak, ΔTTP (time to peak), ΔRBV (regional blood volume), ΔRBF (regional blood flow) and ΔMTT (mean transit time). The responders and non-responders were distinguished by the Miller-Payne Grading (MPG) system and parameters from different regions of tumors were compared in these two groups. For ROI 1(the greatest enhancement area in the central region of the tumor), there were significant differences in Δpeak1, ΔRBV1 and ΔRBF1 between responders and non-responders. For ROI 2 (the greatest enhancement area on edge of the tumor), there were significant differences in Δpeak2 and ΔRBF2 between the groups. The Δpeak1 and ΔRBF2 showed good prediction (AUC 0.798-0.820, p ≤ 0.02) after the first cycle of NAC. When the cut-off value was 0.115, the ΔRBF2 had the highest diagnostic accuracy and the maximum NPV. Quantitative TIC parameters could be effectively used to evaluate early response to NAC in advanced breast cancer.

Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/ß, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1ß occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1ß pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

Assessment of Prognostic Factors of Racial Disparities in Testicular Germ Cell Tumor Survival in the United States (1992-2015).

OBJECTIVE: Testicular germ cell tumors (TGCT) are the most common cancer among men aged 15 to 39 years. Previous studies have considered factors related to TGCT survival rate and race/ethnicity, but histological type of the diagnosed cancer has not yet been thoroughly assessed. METHODS: The data came from 42,854 eligible patients from 1992 to 2015 in the Surveillance Epidemiology and End Results 18. Frequencies and column percent by seminoma and nonseminoma subtypes were determined for each covariates. We used Cox proportional hazard regression to assess the impact of multiple factors on post-diagnostic mortality of TGCT. RESULTS: Black males were diagnosed at a later stage, more commonly with local or distant metastases. The incidence of TGCT in black non-seminoma tumors increased most significantly. The difference in survival rates between different ethnic and histological subtypes, overall survival (OS) in patients with non-seminoma was significantly worse than in patients with seminoma. The most important quantitative predictor of death was the stage at the time of diagnosis, and older diagnostic age is also important factor affecting mortality. CONCLUSION: Histological type of testicular germ cell tumor is an important factor in determining the prognosis of testicular cancer in males of different ethnic groups.

METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism.

Type 2 diabetes (T2D) is characterized by lack of insulin, insulin resistance and high blood sugar. However, the underlying mechanisms of insulin resistance during T2D development remains unclear. As the most common mRNAs modification, N6-Methyladenosine (m6A) is involved in many of pathological processes in aging disease. However, it remains unclear whether m6A is involved in T2D development and what is the regulatory mechanism. This study is aimed to illustrate the roles of m6A and its methyltransferase METTL3 in the regulation of blood glucose homeostasis and insulin sensitivity. The results showed that m6A methylated RNA level and its N6-methyladenosine methylase METTL3 were consistently up-regulated in the liver tissues from patients with T2D. Moreover, both m6A methylated RNA and METTL3 levels showed positive correlation with HOMA-IR and negative correlation with HOMA-ß. The m6A methylated RNA and METTL3 levels were also up-regulated in mouse with 16 weeks high-fat diet (HFD), compared with mice fed a standard chow diet (CD). Hepatocyte-specific knockout of METTL3 in mice fed a HFD improved insulin sensitivity and decreased fatty acid synthesis. Furthermore, mechanism analysis demonstrates that METTL3 silence decreased the m6A methylated and total mRNA level of Fatty acid synthase (Fasn), subsequently inhibited fatty acid metabolism. Adeno-associated virus mediated Fasn overexpression in METTL3 knockout mice abrogates the improved insulin sensitivity and decreased fatty acid synthesis. Collectively, these results reveal that RNA N6-methyladenosine methylase METTL3 inhibits hepatic insulin sensitivity via N6-methylation of Fasn mRNA and promoting fatty acid metabolism.

Balloon dilator controls massive bleeding during endoscopic ultrasound-guided drainage for pancreatic pseudocyst: A case report and review of literature.

Pancreatic pseudocyst (PPC), a common sequela of acute or chronic pancreatitis, was defined by the revised Atlanta classification as "a collection." Endoscopic ultrasound (EUS)-guided drainage is often considered a standard first-line therapy for patients with symptomatic PPC. This effective approach exhibits 90%-100% technical success and 85%-98% clinical success. Bleeding is a deadly adverse event associated with EUS-guided drainage procedures, and the bleeding rate ranges from 3% to 14%. Hemostasis involves conservative treatment, endoscopy, interventional radiology-guided embolization and surgery. However, few studies have reported on EUS-guided drainage with massive, multiple hemorrhages related to severe pancreatogenic portal hypertension (PPH). Thus, the aim of this case report was to present a case using a balloon dilator to achieve successful hemostasis for PPH-related massive bleeding in EUS-guided drainage of PPC. To our knowledge, this method has not been previously reported.

Gene methylation as a powerful biomarker for detection and screening of non-small cell lung cancer in blood.

DNA methylation has been reported to become a potential powerful tool for cancer detection and diagnosis. However, the possibilities for the application of blood-based gene methylation as a biomarker for non-small cell lung cancer (NSCLC) detection and screening remain unclear. Hence, we performed this meta-analysis to evaluate the value of gene methylation detected in blood samples as a noninvasive biomarker in NSCLC. A total of 28 genes were analyzed from 37 case-control studies. In the genes with more than three studies, we found that the methylation of P16, RASSF1A, APC, RARß, DAPK, CDH13, and MGMT was significantly associated with risks of NSCLC. The methylation statuses of P16, RASSF1A, APC, RARß, DAPK, CDH13, and MGMT were not linked to age, gender, smoking behavior, and tumor stage and histology in NSCLC. Therefore, the use of the methylation status of P16, RASSF1A, APC, RARß, DAPK, CDH13, and MGMT could become a promising and powerful biomarker for the detection and screening of NSCLC in blood in clinical settings. Further large-scale studies with large sample sizes are necessary to confirm our findings in the future.

[Infrared Spectra Characteristics of the Silicate Nickel Ores: A Comparison Study on Different Ore Samples from Indonesia and China].

The silicate nickel ores developed in the lateritic nickel deposit, from Kolonodale, Sulawesi Island, Indonesia, and Yuanjiang, Yunnan province, China, were selected for the present study. The X-ray diffraction and Fourier infrared spectra were used to analyze the mineralogical attribute of laterite nickel ores from two different places. The results show that these two different silicate nickel ores have unique infrared spectra characteristics individually, which contributes to the ore classification. The silicate nickel ores from Kolonodale deposit, Indonesia, can be classified as the serpentine type, the montmorillonite + serpentine type, and the garnierite type. While, the silicate nickel ores from Yuanjiang deposit, China, can be classified as the serpentine type and the talc + serpentine type. Moreover, the mineral crystallinity of Yuanjiang nickel ores is generally better than Kolonodale nickel ores. According to the advantage of infrared absorption spectra in distinguishing mineral polytypes, it can be determined that lizardite is the main mineral type in the silicate nickel ores of the two deposits, and there is no obvious evidence of chrysotile and antigorite's existence. The characteristic of infrared absorption spectra also shows that frequency change of OH libration indicates Ni (Fe) replacing Mg in the serpentine type nickel-bearing mineral, that is, OH libration of serpentine moves to higher frequency, with the proportion of Ni (Fe) replacing Mg increasing.

[Analysis of the survival in patients after surgical resection of thoracic esophageal cancer].

OBJECTIVE: To investigate the prognostic factors and influence of the number of lymph node metastases on survival and UICC-TNM classification in patients with thoracic esophageal cancer after curative resection. METHODS: From 1985 to 1990, 1224 patients were surgically treated for thoracic esophageal cancer. The patients who died within 30 days after operation were not included in this study. Fifteen factors possibly influencing survival of these patients were selected and analyzed. A multivariate analysis of these individual variables was performed by Cox proportional hazard model. According to the number of lymph node metastases (0, 1 and > or = 2), a new modification of the TNM classification was suggested: stage IIa (T2N0M0 and T3N0M0), stage IIb [T1N1M0 and T2N1(1)M0], stage IIIa [T2N1 (2)M0 and T3N1 (1) M0] and stage IIIb [T3N1 (2) M0 and T4N any M0]. RESULTS: According to multivariate analysis, lymph node metastases, depth of invasion, location of tumor, histological classification and length of the tumor were of prognostic significance (P < 0.01). There was obvious correlation between the rate of lymph node metastasis and the depth of invasion, length of tumor and grade of differentiation. The 5-year survival rate of the patients with 0, 1 and > or = 2 positive metastatic lymph nodes was 59.1%, 32.0% and 8. 9%, respectively. The 5-year survival rate of the patients with stage T2N1 M0 and stage T3N1 M0 was significantly higher in those with only one lymph node involved than in those with two or more lymph nodes involved (43.1% vs. 18.0% and 28.0% vs. 9.6%, P < 0.01). The 5-year survival rate of the modified stage IIa, IIb, IIIa and IIIb was 56.5%, 43.9%, 25.6% and 11.1%, respectively, with a statistically significant difference among different stages (P < 0.01). CONCLUSION: The lymph node metastasis is the most important prognostic factor for thoracic esophageal cancer after resection. The major influencing factors of lymph node metastasis are the depth of invasion, length of tumor and grade of differentiation. Therefore, the lymphadenectomy along with esophagectomy and subsequently combined modality therapy against lymph node metastasis is necessary to improve the 5-year survival rate. Our proposed new classification based on number of lymph node metastases (0, 1, > or = 2 positive nodes) is more applicable because it can well reflect the correlation between lymph node metastasis and the survival, and provides evidence for the modification of the currently used UICC TNM staging system for surgically treated thoracic esophageal cancer.

[Impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma].

OBJECTIVE: To study the impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma. METHODS: Data collected from 120 patients with locally advanced mid-low rectal cancer (T2-4 and/or N1-2M0) treated from January 2005 to June 2008 was investigated. The patients were divided into two groups: the study group (n=54) was treated with neoadjuvant therapy (preoperative radiation with a total dosage of 50 Gy and synchronous 5-Fu-based chemotherapy) followed by radical tumor resection 4-6 weeks after;the control group (n=66) underwent primary surgery without neoadjuvant therapy. The clinical stage was evaluated before and after neoadjuvant therapy. The total lymph nodes yields, as well as the tumor-positive lymph nodes of each resected specimen was compared between the two groups statistically. RESULTS: Clinical downstage was achieved in 30 cases (56%) in study group after neoadjuvant therapy. The number of total lymph nodes and positive lymph nodes harvested from each resected specimen in the control group were 14+/-7 and 2.2+/-3.7, meanwhile those were 9+/-6 and 0.7+/-2.4 in study group, which were all significantly lower than those in control group (P<0.01). CONCLUSIONS: Preoperative radiotherapy combined with chemotherapy can downstage the tumor and reduce the retrieval rate of total lymph nodes and positive lymph nodes in locally advanced rectal cancer. It is necessary to retrieve as many lymph nodes as possible for it has some prognostic significance for the patients.

The effects of Chinese herb Angelica in focal cerebral ischemia injury in the rat.

This experiment was designed to study the therapeutic mechanisms of Angelica on the focal cerebral ischemia injury of the rat. The ischemic area was determined by TTC stain. And terminal deoxynucleotidyl transferase (TDT) mediated DUTP-biotin nick end labeling (TUNEL) method was applied to detect neuronal apoptosis. The expressions of Bcl-2 and Bax proteins were observed by immunohistochemical staining methods. Results show that the treatment with angelica reduced the volume of cerebral infarction (p < 0.05), and that the number of neuronal apoptosis cells decreased significantly (p < 0.01). Also the expression level of Bax protein decreased (p < 0.01). These results suggest that Angelica can reduce the number of apoptosis cells by decreasing the expression of Bax protein. This is maybe one of the mechanisms of the therapeutic effect of Angelica on focal cerebral ischemia injury.