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Background: To date, few studies have evaluated the impact of lobectomy versus sublobar resection for early small cell lung cancer (SCLC). We investigated the survival rates of patients with pathological stage T1‐2N0M0 SCLC who underwent lobectomy or sublobar resection. Methods: We identified 548 SCLC patients in the Surveillance, Epidemiology, and End Results database who underwent lobectomy or sublobar resection. Propensity score matching (PSM) and Cox regression analysis were used to adjust for baseline characteristics. Results: The three‐year overall survival (OS) of patients treated with lobectomy (n = 376, 60%) was significantly higher than those treated with sublobar resection (n = 172, 38%). PSM and Cox multivariable analysis further confirmed this result (hazard ratio [HR] 0.543, 95% confidence interval [CI] 0.421–0.680; P < 0.001). The three‐year OS of patients treated with segmentectomy (n = 24, 54%) and wedge resection (n = 148, 36%) was not significantly different (HR 0.639, 95% CI 0.393–1.039; P = 0.071). Based on PSM analysis, segmentectomy conferred a superior survival advantage to patients relative to wedge resection (HR 0.466, 95% CI 0.221–0.979; P = 0.040). Conclusion: Lobectomy correlated with superior survival. For patients in which lobectomy is unsuitable, prognosis following segmentectomy appears to be better than after wedge resection. [ABSTRACT FROM AUTHOR]

Bupleuri radix and liquorice are commonly used as a hepatoprotectants. Their main effective ingredients are triterpenoid saponins. It is known that the saponins in liquorice and Bupleuri radix not only promote the metabolism of sugar and lipids but also have anti‐inflammatory functions and hepatoprotective effect. However, the complexity of these compounds results in difficulty in studying their pharmacodynamics and mechanism. In this study, glycosides were the main components that were identified and selected as the main research object. First, the mass spectrometry information of the main chemical components in liquorice and Bupleuri radix were collected from the literature. The characteristic fragments and neutral losses were summarized according to typical cleavage methods. Second, the samples were analysed using ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry, and characteristic fragment filters and neutral loss filters were successfully applied to screen 18 saponins from Bupleuri radix and 23 saponins and nine flavonoid glycosides from liquorice. Rapid classification and identification of the main components in Bupleuri radix and liquorice were finally achieved. This method promoted the development of chemical components in Bupleuri radix and liquorice, and provided a new way for screening, classifying, and identifying target components in complex samples of metabolomics and pharmacokinetics. [ABSTRACT FROM AUTHOR]

Background/Aims: The mechanistic target of rapamycin (mTOR) signaling pathway is essential for angiogenesis and embryonic development. DEP domain-containing mTOR-interacting protein (DEPTOR) is an mTOR binding protein that functions to inhibit the mTOR pathway In vitro experiments suggest that DEPTOR is crucial for vascular endothelial cell (EC) activation and angiogenic responses. However, knowledge of the effects of DEPTOR on angiogenesis in vivo is limited. This study aimed to determine the role of DEPTOR in tissue angiogenesis and to elucidate the molecular mechanisms. Methods:Cre/loxP conditional gene knockout strategy was used to delete the Deptor gene in mouse vascular ECs. The expression or distribution of cluster of differentiation 31 (CD31), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1α) were detected by immunohistochemical staining or western blot. Tube formation assay was used to measure angiogenesis in vitro. Results:Deptor knockdown led to increased expression of CD31, VEGF and HIF-1α in heart, liver, kidney and aorta. After treatment with rapamycin, their expression was significantly down regulated. In vitro, human umbilical vein endothelial cells (HUVECs) were transfected with DEPTOR-specific small interfering RNA (siRNA), which resulted in a significant increase in endothelial tube formation and migration rates. In contrast, DEPTOR overexpression markedly reduced the expression of CD31, VEGF and HIF-1α. Conclusions: Our findings demonstrated that deletion of the Deptor gene in vascular ECs resulted in upregulated expression of CD31 and HIF-1α, and further stimulated the expression of VEGF which promoted angiogenesis, indicating that disruption of normal angiogenic pathways may occur through hyperactivation of the mTORC1/HIF-1α/VEGF signaling pathway. [ABSTRACT FROM AUTHOR]

Rhizoma Anemarrhenae, a famous traditional Chinese medicine (TCM), is the dried rhizome of Anemarrhena asphodeloides Bge. (Anemarrhena Bunge of Liliaceae). The medicine presents anti-inflammatory, antipyretic, sedative, and diuretic effects. The chemical constituents of Rhizoma Anemarrhenae are complex and diverse, mainly including steroidal saponins, flavonoids, phenylpropanoids, benzophenones, and alkaloids. In this study, UPLC-Q-TOF/MS was used in combination with data postprocessing techniques, including characteristic fragments filter and neutral loss filter, to rapidly classify and identify the five types of substances in Rhizoma Anemarrhenae. On the basis of numerous literature reviews and according to the corresponding characteristic fragments produced by different types of compounds in combination with neutral loss filtering, we summarized the fragmentation patterns of the main five types of compounds and successfully screened and identified 32 chemical constituents in Rhizoma Anemarrhenae. The components included 18 steroidal saponins, 6 flavonoids, 4 phenylpropanoids, 2 alkaloids, and 2 benzophenones. The method established in this study provided necessary data for the study on the pharmacological effects of Rhizoma Anemarrhenae and also provided the basis for the chemical analysis and quality control of TCMs to promote the development of a method for chemical research on TCMs. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl4, oil or CCl4+ rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl4− induced liver fibrosis and the rapamycin prevent its occurance. [ABSTRACT FROM AUTHOR]

There have been paradoxical findings regarding the expression of DEP domain-containing mTOR-interacting protein (DEPTOR) and its role in predicting prognosis in esophageal squamous cell carcinoma (ESCC). Here we show that DEPTOR expression was significantly increased in tumor tissues and predicted good survival in early stage ESCC patients but not in advanced stage patients. In vitro，our studies showed that ESCC cell lines could be classified into relatively high and low DEPTOR-expressing subgroups according to esophageal squamous epithelial cell line Het-1A.In our study, different levels of DEPTOR expression absolutely determined the response to chemotherapy. In relatively low-expressing cell lines, DEPTOR increased chemotherapy sensitivity via deactivation of the AKT pathway. In relatively high-expressing cell lines, DEPTOR increased cell survival and chemoresistance by strong feedback activation of the IRS1-PI3K-AKT-survivin pathway that occurred after downregulation of ribosomal protein S6 kinase (S6K). Collectively, our findings highlight the dichotomous nature of DEPTOR functions in modulating chemotherapy sensitivity in different ESCC cells. [ABSTRACT FROM AUTHOR]

Background: The correlation between the number of examined lymph nodes (ELNs) and lung cancer-specific survival (LCSS) of stage IA non-small cell lung cancer (NSCLC) patients, who underwent sublobar resection in which lymph node (LN) sampling was relatively restricted as compared with standard lobectomy remains unclear., Methods: Patients from the Surveillance, Epidemiology, and End Results database with stage IA NSCLC who underwent sublobar resection were categorized based on ELN count (1-6 vs. ≥7; the cut point 7 was identified by Cox model)., Results: Collectively, 3,219 patients with a median follow-up time of 37 months were included in this study (G1: 1-6 ELN, n=2,410; G2: ≥7 ELN, n=809). The 5-year LCSS rate of the G1 and G2 cohorts were 75% and 83%, respectively. Cox analysis suggested that the LCSS of G1 cohort patients was lower as compared with the G2 cohort [hazard ratio (HR) =1.530; 95% confidence interval (CI): 1.240-1.988, P<0.001). Propensity score analysis also showed decreased survival of the matched G1 cohort (HR =1.499; 95% CI: 1.176-1.911; P=0.001)., Conclusions: The data suggested the ELNs ≤6 were associated with poor prognoses. Adequate LN sampling is essential even for stage IA NSCLC patients undergoing sublobar resection.

Schisandra chinensis (known in Chinese as WuWeiZi, WWZ) has observable effects such as astringing the lung to stop coughs, arresting sweating, preserving semen and preventing diarrhea. The major components of WWZ include lignans, triterpenoids, organic acids and fatty acids. In this paper, a reliable method for the rapid identification of multiple components in WWZ by their characteristic fragments and neutral losses using UPLC-Q-TOF/MS technology was developed. After review of the literature and some reference experiments, the fragmentation pattern of several compounds were studied and summarized. Then, according to the corresponding characteristic fragments coupled with neutral losses in the positive or negative ion mode produced by different types of substances a rapid identification of target compounds was achieved. Finally, a total of 30 constituents of WWZ were successfully identified, including 15 lignans, nine triterpenoids, three organic acids and three fatty acids. The method established in this study not only provides a comprehensive analysis of the chemical ingredients of WWZ, providing a basis for further phytochemical studies on WWZ but also provides a more efficient way to solve the problem of identification of complex chemical constituents in traditional Chinese medicines., Competing Interests: The authors declare no conflict of interest.

Fingerprinting is widely and commonly used in the quality control of traditional Chinese medicine (TCM) injections. However, current studies informed that the fingerprint similarity evaluation was less sensitive and easily generated false positive results. For this reason, a novel and practical chromatographic "Fingerprint-ROC-SVM" strategy was established by using KuDieZi (KDZ) injection as a case study in the present article. Firstly, the chromatographic fingerprints of KDZ injection were obtained by UPLC and the common characteristic peaks were identified with UPLC/Q-TOF-MS under the same chromatographic conditions. Then, the receiver operating characteristic (ROC) curve was used to optimize common characteristic peaks by the AUCs value greater than 0.7. Finally, a support vector machine (SVM) model, with the accuracy of 97.06%, was established by the optimized characteristic peaks and applied to monitor the quality of KDZ injection. As a result, the established model could sensitively and accurately distinguish the qualified products (QPs) with the unqualified products (UPs), high-temperature processed samples (HTPs) and high-illumination processed samples (HIPs) of KDZ injection, and the prediction accuracy was 100.00%, 93.75% and 100.00%, respectively. Furthermore, through the comparison with other chemometrics methods, the superiority of the novel analytical strategy was more prominent. It indicated that the novel and practical chromatographic "Fingerprint-ROC-SVM" strategy could be further applied to facilitate the development of the quality analysis of TCM injections., Competing Interests: The authors declare no conflict of interest.

Although many advances have been made in understanding the pathogenesis of liver fibrosis, few options are available for treatment. Casticin, one of the major flavonoids in Fructus Viticis extracts, has shown hepatoprotective potential, but its effects on liver fibrosis are not clear. In this study, we investigated the antifibrotic activity of casticin and its underlying mechanism in vivo and in vitro . Male mice were injected intraperitoneally with carbon tetrachloride (CCl 4 ) or underwent bile duct ligation (BDL) to induce liver fibrosis, followed by treatment with casticin or vehicle. In addition, transforming growth factor-β1(TGF-β1)-activated LX-2 cells were used. In vivo experiments showed that treatment with casticin alone had no toxic effect while significantly attenuating CCl 4 -or BDL-induced liver fibrosis, as indicated by reductions in the density of fibrosis, hydroxyproline content, expression of α-SMA and collagen α1(I) mRNA. Moreover, casticin inhibited LX2 proliferation, induced apoptosis in a time- and dose-dependent manner in vitro . The underlying molecular mechanisms for the effect of casticin involved inhibition of hepatic stellate cell (HSC) activation and reduced the expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 resulting from blocking TGF-β1/Smad signaling, as well as increased the apoptosis of HSCs. The results suggest that casticin has potential benefits in the attenuation and treatment of liver fibrosis., Competing Interests: CONFLICTS OF INTEREST The authors do not have any disclosures to report.

Hepatic stellate cells are of mesenchymal cell type located in the space of Disse. Upon liver injury, HSCs transactivate into myofibroblasts with increase in expression of fibrillar collagen, especially collagen I and III, leading to liver fibrosis. Previous studies have shown mTOR signaling is activated during liver fibrosis. However, there is no direct evidence in vivo. The aim of this study is to examine the effects of conditional deletion of TSC1 in mesenchymal on pathogenesis of liver fibrosis. Crossing mice bearing the floxed TSC1 gene with mice harboring Col1α2-Cre-ER(T) successfully generated progeny with a conditional knockout of TSC1 (TSC1 CKO) in collagen I expressing mesenchymal cells. TSC1 CKO and WT mice were subjected to CCl 4 , oil or CCl 4 + rapamycin treatment for 8 weeks. TSC1 CKO mice developed pronounced liver fibrosis relative to WT mice, as examined by ALT, hydroxyproline, histopathology, and profibrogenic gene. Absence of TSC1 in mesenchymal cells induced proliferation and prevented apoptosis in activated HSCs. However, there were no significant differences in oil-treated TSC1 CKO and WT mice. Rapamycin, restored these phenotypic changes by preventing myofibroblasts proliferation and enhancing their apoptosis. These findings revealed mTOR overactivation in mesenchymal cells aggravates CCl 4 - induced liver fibrosis and the rapamycin prevent its occurance.