ABSTRACT:Panax notoginseng (Sanqi) is a cardiovascular herb containing ginsenosides that are believed to be responsible for the therapeutic effects of Sanqi. The aim of this study was to evaluate rat exposure to ginsenosides after oral administration of Sanqi extract and to identify the key factors affecting their absorption and disposition. Ginsenosides were administered to rats, either in the form of Sanqi extract or as pure chemicals. The ginsenosides Ra 3 , Rb 1 , Rd, Re, Rg 1 , and notoginsenoside R 1 were the major saponins present in the herbal extract. Systemic exposure to ginsenosides Ra 3 , Rb 1 , and Rd after oral administration of the extract was significantly greater than that to the other compounds. Considerable colonic deglycosylation of the ginsenosides occurred, but the plasma levels of deglycosylated metabolites were low in rats. Poor membrane permeability and active biliary excretion are the two primary factors limiting systemic exposure to most ginsenosides and their deglycosylated metabolites. In contrast with other ginsenosides, biliary excretion of ginsenosides Ra 3 and Rb 1 was passive. Meanwhile, the active biliary excretion of ginsenoside Rd was significantly slower than that of other saponins. Slow biliary excretion, inefficient metabolism, and slow renal excretion resulted in long-circulating and thus relatively high exposure levels for these three ginsenosides. For these reasons, plasma ginsenosides Ra 3 , Rb 1 , and Rd were identified as pharmacokinetic markers for indicating rat systemic exposure to Sanqi extract. This is a systematic investigation of the absorption and disposition of ginsenosides from an herb, the information gained from which is important for linking Sanqi administration to its medicinal effects.

BackgroundHypertension and the triglyceride and glucose index both have been associated with insulin resistance; however, the longitudinal association remains unclear. This study was designed to investigate the longitudinal association between the triglyceride and glucose index and incident hypertension among the Chinese population.MethodsWe studied 4686 subjects (3177 males and 1509 females) and followed up for 9 years. The subjects were divided into four groups based on the triglyceride and glucose index. Univariate and multivariate Cox regression models were used to analyse the risk factors of hypertension.ResultsAfter 9 years of follow-up, 2047 subjects developed hypertension. The overall 9-year cumulative incidence of hypertension was 43.7%, ranging from 28.5% in quartile 1 to 36.9% in quartile 2, 49.2% in quartile 3 and 59.8% in quartile 4 (p for trend < 0.001). Cox regression analyses indicated that higher triglyceride and glucose index was associated with an increased risk of subsequent incident hypertension.ConclusionThe triglyceride and glucose index can predict the incident hypertension among the Chinese population.

Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.

The incidence rate of thyroid cancer has been rising rapidly in recent decades, but its trend remains unclear. To investigate this, we analyzed the database of SEER 13, 1992-2012 in USA, with a particular focus on conventional papillary thyroid cancer (CPTC) and follicular-variant PTC (FVPTC). Of the 75,992 thyroid cancers, 61.3% were CPTC, and 25.7% were FVPTC, and their incidence rates (IRs) were both significantly increased from 1992 to 2012 (P all <0.001), with CPTC being 2.4-time FVPTC (P<0.001) and the overall average annual percent change (AAPC) of incidence being 6.3% in the former and 5.3% in the latter. IRs were increased in all thyroid cancers, albeit most dramatically in PTC, in virtually all ethnic/demographic groups in recent two decades, but the incidence trends varied among different thyroid cancers, particularly differentiable between CPTC and FVPTC. For example, joinpoint analyses revealed that the APC of CPTC before 1996 was 1.5% (P>0.05), which jumped to 6.8% (P<0.05) after 1996, while the APC of FVPTC before 2000 was 6.6% (P<0.05), which dropped to 4.8% (P<0.05) after 2000. IRs and incidence trends of PTC were uneven among different ethnic/demographic groups, as exemplified by the lower IRs of both PTC variants in the black females than non-Hispanic white females but higher AAPCs of incidence in the former than the latter. Interestingly, the data also suggest that the incidence rise of PTC is becoming plateaued in the most recent two years. These novel observations are helpful in understanding the incidence and incidence trends of thyroid cancer.