Comparison of Pharmacokinetics and Tissue Distribution Characteristics of Three Diterpenoid Esters in Crude and Prepared Semen Euphorbiae.

BACKGROUND: Semen Euphorbiae (SE) and Semen Euphorbiae Pulveratum (SEP) have a long history of medicinal use. SEP is the processed product of SE; both ancient and modern studies have shown that SEP has a lower toxicity compared to SE. To clarify the influence of processing on the pharmacological properties of SE and SEP, a study was carried out to compare the pharmacokinetics and distribution characteristics of three active compounds after oral administration of SE and SEP extracts. METHODS: A UPLC-MS/MS method was established to simultaneously determine the contents of Euphorbia factors L1, L2, and L3 in rat plasma and mouse tissues after an oral administration of crude and processed SE with approximately the same dosage. Plasma and heart, liver, spleen, lung, kidney, and colon tissue samples were treated with ethyl acetate and separated by gradient elution on a C18 column with a mobile phase of 0.1% formic acid and methanol. RESULTS: The established method had good selectivity, linear range, accuracy, precision, stability, matrix effect, and extraction recovery. The area under the concentration time curve, time to maximum concentration, maximum concentration, half-life of elimination, and mean retention time of plasma samples in SEP-treated group decreased, and the clearance in SEP-treated group increased. Moreover, the active component concentrations in colon, liver, and kidney tissues were more followed by those in the heart, lungs, and spleen. CONCLUSION: These results indicate that the processing could influence the pharmacokinetics and tissue distribution of Euphorbia factors L1, L2, and L3 after oral administration of crude and processed SE. The data obtained may lay a foundation for the clinical use of SE and for further study on the processing mechanism of SE.

Clinical nomogram for lymph node metastasis in pathological T1 esophageal squamous cell carcinoma: a multicenter retrospective study.

BACKGROUND: Endoscopic resection is increasingly used to treat pathological T1 (pT1) esophageal cancer (EC) patients. However, the procedures are limited by lymph node metastasis (LNM) and remain controversial. We aimed to construct a nomogram to predict the risk of LNM in patients with pT1 esophageal squamous cell carcinoma (ESCC). METHODS: A total of 243 patients with pT1 ESCC who underwent esophagectomy and lymph node dissection at two different institutes between February 2013 and June 2019 were analyzed retrospectively. Patients were categorized into the negative group and the positive group according to whether there was LNM. Risk factors for LNM were evaluated by univariate and multivariate analyses. The nomogram was used to estimate the individual risk of LNM. RESULTS: Forty-six (18.9%) of the 243 patients with pT1 ESCC exhibited LNM. The LNM rate in patients with stage T1a disease was 5.7% (5/88), and the rate in patients with stage T1b disease was 26.5% (41/155). Multivariable logistic regression analysis showed that tumor differentiation [odds ratio (OR) =1.942, 95% confidence interval (CI): 1.067-3.536, P=0.030], the T1 sub-stage (OR =4.750, 95% CI: 1.658-13.611, P=0.004), the preoperative alanine aminotransferase/aspartate aminotransferase ratio (LSR) (OR =5.371, 95% CI: 1.676-17.210, P=0.005), and the high-density lipoprotein cholesterol (HDL-C) level (OR =5.894, 95% CI: 1.917-18.124, P=0.002) were independent risk factors for LNM. The nomogram had relatively high accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.803 (95% CI: 0.732-0.873). The calibration curve showed that the predicted probability of LNM was in good agreement with the actual probability. CONCLUSIONS: Clinicopathological and hematological parameters of tumor differentiation, the T1 sub-stage, the preoperative LSR, and the HDL-C level may predict the risk of LNM in T1 ESCC. The risk of LNM can be predicted by the nomogram.

Long term results of pancreatectomy with portal-superior mesenteric vein resection for pancreatic carcinoma: a systematic review.

BACKGROUND/AIMS: Clinical benefit from pancreatectomy combined with portal vein/superior mesenteric resection in the pancreatic carcinoma with local venous invasion still remains controversial. The aim of this study was to review the overall outcome of the pancreatectomy combined with portal vein/superior mesenteric resection for pancreatic carcinoma with local venous invasion. METHODOLOGY: A systematic literature search (Medline, Embase, Cochrane Library, Biosis, Science Citation Index, Ovid Journals) was performed to identify all eligible articles from January 2000 to December 2009. The methodological quality of included studies on portal vein/superior mesenteric resection during pancreatectomy for pancreatic carcinoma was evaluated independently by 2 authors and 47 non-duplicated studies providing relevant data was found. Quantitative data on operation, perioperative results (blood loss, operative time, and length of hospital stay), mortality, morbidity, histopathology of resected specimens, adjuvant therapies, and overall outcome were extracted from included studies for systematic analysis. RESULTS: The median operating time was 480 (140-1340) min, blood loss 1420 (50-14280) ml and the length of hospital stay 16 (4-123) days. Operative mortality and postoperative morbidity rates ranged from 0 to 14.3 % and 6 % to 67 % with a median of 3.5 % and 33 %, respectively. Median survival was 15 months and ranged from 1.6 to 250 months, and 1-, 2-, 3- and 5-year survival rates ranged from 28.5 to 92, 6.7 to 81.1, 0 to 60.3 and 0 to 24 % with a media of 56.6, 31.5, 17 and 12 %, respectively. Specimen histopathology confirmed venous invasion, perineural invasion and lymphnodal involvement in 66.6,53 and 73%, respectively. CONCLUSIONS: In properly selected patients, pancreatectomy combined with portal vein/superior mesenteric resection is a feasible surgical procedure with a survival benefit for pancreatic carcinoma, and the systemic chemotherapy is indispensable as the common events of perineural invasion and lymphnodal involvement of the pancreatic carcinoma with local venous invasion.

Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer.

PURPOSE: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). METHODS: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. RESULTS: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. CONCLUSION: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.

[Suspension with repose system in the treatment of obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To introduce the treatment of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with Repose bone screw system and to evaluate the treating effect. METHODS: Thirty-two patients with severe OSAHS (Friedman classification II, III) were treated with tongue ablation + uvulopalatopharyngoplasty + hard palate shortening + Repose suspension. All patients were followed-up for 6 months. Apnea hypopnea index (AHI), lowest oxygen percent saturation (LSaO2), body mass index (BMI), vallecula epiglottic-lateral pharyngeal wall (V-LPW) and pharyngeal airway space (PAS) were used for the diagnosis and evaluation. RESULTS: The AHI in 32 patients reduced from (78.3 +/- 11.6)/h to (18.4 +/- 12.5)/h (x(-) +/- s), t = 13.5, P = 0.000. The LSaO2 increased from (0.632 +/- 0.007) to (0.794 +/- 0.006), t = 4.1, P = 0.000. The BMI was statistical indiscriminate. The V-LPW increased from (12.1 +/- 3.2) mm to (16.9 +/- 2.6) mm (t = 2.5, P = 0.014). PAS increased from (9.2 +/- 3.3) mm to (15.6 +/- 2.4) mm (t = 7.6, P = 0.000). The total effective rate was 93.8%. Three genioglossus stabilization patients complained about foreign body sensation in the mouth floor 3 - 7 days after procedures, which disappeared in 6 months. One genioglossus stabilization patients complained about mandibular osteomyelitis 3 months after procedures, which recovered after anti-inflammatory treatment for 5 days. One genioglossus stabilization patients appeared hypoglossia bleeding, which stopped after compression. One hyoid suspension patients showed haematoma of submandibular region and cured after incision and drainage. CONCLUSION: Repose system was an effective method, safe, simple, with few complications.