Tannins in Phyllanthus emblica L. improves cisplatin efficacy in lung cancer cells by boosting endoplasmic reticulum stress to trigger immunogenic cell death.

BACKGROUND: Lung cancer is one of the deadliest cancers world-wide and immunotherapy has been considered as a promising therapeutic strategy. Previously, our study found that tannins in Phyllanthus emblica L. (PTF) could inhibit the growth of tumor by activating the immune response in liver cancer, and also exhibited a cytotoxicity on human lung cancer cells A549, H460, H1703 in vitro. OBJECTIVE: To explore whether PTF inhibited the growth of lung cancer through its immune-regulating function and to clarify underlying mechanisms. METHODS: The induction of immunogenic cell death (ICD) were characterized by calreticulin exposure, extracellular ATP secretion, and High Mobility Group Box 1(HMGB1) release both in vivo using LLC-derived xenograft tumor model and in vitro using both mouse LLC and human A549 cancer cells. RESULTS: PTF inhibited lung cancer cells growth and tumorigenesis in vivo/vitro and promoted anti-tumor immune responses. We further found that PTF could induce ICD, which then activated Type I interferon responses and CXCL9/10-mediated chemotaxis. Mechanistically, PTF induced the formation of intracellular protein aggregates and following activation of PERK/ATF4/CHOP-dependent endoplasmic reticulum stress-related ICD. Moreover, PTF improved the antitumor efficacy of cisplatin by inducing ICD both in vitro and in vivo. Finally, we screened out 5 components from PTF, including gallocatechin, gallic acid, methyl gallate, ethyl gallate and ellagic acid, which could induce ICD in vitro and might be considered as the potential antitumor pharmacodynamic substances. CONCLUSION: In conclusion, PTF inhibits the growth of lung cancer by triggering ICD and remodeling the tumor microenvironment, suggesting that PTF may have promising prospects as an adjacent immunotherapy for cancers.

Phyllanthi Tannin Loaded Solid Lipid Nanoparticles for Lung Cancer Therapy: Preparation, Characterization, Pharmacodynamics and Safety Evaluation.

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 µg/mL and 20.74 µg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

Correction: Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Correction for 'Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration' by Shukai Wang et al., Food Funct., 2023, 14, 4607-4620, https://doi.org/10.1039/D2FO03685A.

Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Tumor-associated macrophages (TAMs) participate in tumorigenesis, growth, invasion as well as metastasis by facilitating an immunosuppressive tumor microenvironment. Reversing the pro-tumoral M2 phenotype of TAMs has become a hot spot in advancing cancer immunotherapy. In the current study, the content of Moringa oleifera leaf polysaccharides (MOLP) was determined and characterized, along with the anti-cancer mechanism of MOLP studied in a Lewis lung cancer (LLC) tumor-bearing mouse model and bone marrow-derived macrophages. The monosaccharide composition and gel permeation chromatography analyses show that MOLP are mainly composed of galactose, glucose, and arabinose, with approximately 17.35 kDa average molecular weight (Mw). In vivo studies demonstrate that MOLP convert TAMs from the immunosuppressive M2 phenotype to the antitumor M1 phenotype, thus inducing CXCL9 and CXCL10 expression and increasing T-cell infiltration in the tumor. Furthermore, macrophage depletion and T cell suppression demonstrated that the tumor suppressive effect of MOLP was reliant on reprogramming macrophage polarization and T cell infiltration. In vitro studies revealed that MOLP could induce the phenotypic switch from M2 macrophages to M1 by targeting TLR4. The current study highlights that MOLP are promising anticancer plant-derived polysaccharides with potential in modulating the immune microenvironment and have a bright application prospect in the immunotherapy of lung cancer.

Enhanced TSG stability through co-assembly with C3G: the mechanism behind processing Polygonum multiflorum Thunb with black beans via supramolecular analysis.

Elucidating the underlying mechanism of the processing of Chinese herbal medicine (CHM) is crucial and also challenging for the modernization of Traditional Chinese Medicine (TCM). Herein, inspired by the traditional method for processing the Chinese herb Polygonum multiflorum (PM) Thunb with excipient black beans, the representative herbal components trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-D-glucopyranoside (TSG) and cyanidin-3-O-ß-glucoside (C3G) from each herbal medicine were selected to investigate the processing mechanism at the supramolecular level. The co-assemblies of TSG/C3G were found to be formed, and their structure was characterized by electronic microscopy and a small angle X-ray scattering (SAXS) technique. In addition, the supramolecular interactions between TSG and C3G were fully probed with UV-Vis, fluorescence, XRD, and NMR spectroscopy. Molecular dynamics were further performed to simulate the assembly processes of TSG and C3G. Notably, the formation of TSG/C3G co-assemblies was found to significantly enhance the stability of TSG against light, Fe3+, and simulated intestinal fluids. The co-assembly of TSG and C3G that leads to supramolecular aggregates discovered here may imply the underlying mechanism of processing PM with black beans. Our results may also suggest that a new effective form of TCM is supramolecular aggregates rather than each component.

Association between short inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.

OBJECTIVE: To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery. METHODS: This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery. RESULTS: Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26). CONCLUSIONS: The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.

Human Amniotic Fluid Stem Cells Exert Immunosuppressive Effects on T Lymphocytes in Allergic Rhinitis.

AIM: The study aims to investigate the immunomodulatory effect of Amniotic fluid stem (AFS) cells to Th2-skewed allergic rhinitis (AR) on T-lymphocyte proliferation, viability, activation and cytokine production. BACKGROUND: AFS cells can suppress peripheral blood mononuclear cells (PBMCs) proliferation and display immunomodulatory properties, but AFS cells' immunoregulation on AR has not been defined. METHODS: Human AFS cells were derived from magnetic cell sorting and co-cultured with PBMCs from AR patients stimulated by phytohemagglutinin (PHA). The AFS cells-associated suppressive proliferation was analyzed using CellTrace™ Violet assay; the T lymphocytes proliferation, viability, activation and the Foxp3+ Treg cells were determined by flow cytometry; cytokine levels were measured using an enzyme- linked immunosorbent assay. RESULTS: We determined that AFS cells significantly inhibited PHA-induced CD3+ T lymphocyte proliferation at the ratio higher than 1:50 (AFS cells: PBMCs) (P<0.05); AFS cells obviously increased the T lymphocytes viability (P<0.01), inhibited the apoptosis of T lymphocytes (P<0.001), compared to PBMCs alone; AFS cells suppressed CD3+CD25+ T lymphocytes activated by PHA (P<0.05); AFS cells significantly promote Treg cells expansion in house dust mite (HDM)-stimulated PBMCs from AR patients (P<0.05). Compared with HDM-stimulated PBMCs, AFS cell co-culture predominantly decreased IL-4 level (P<0.05), but increased IFN-γ and IL-10 levels (P<0.01). CONCLUSION: AFS cells modulate the T-cells' immune imbalance towards Th2 suppression in AR, which can be used as a new cell banking for allergic airway diseases.

The Therapeutic Effect and the Potential Mechanism of Flavonoids and Phenolics of Moringa oleifera Lam. Leaves against Hyperuricemia Mice.

The aim of this study is to evaluate the anti-hyperuricemia effect and clarify the possible mechanisms of flavonoids and phenolics of MOL (MOL-FP) in mice. Hyperuricemia mice were generated via intraperitoneal (i.p.) administration of potassium oxonate (PO) and oral gavage (p.o.) of hypoxanthine (HX). Serum uric acid (UA), weight, serum XO activity, hepatic XO activity, urea nitrogen (BUN), creatinine (CRE), serum AST level, serum ALT level, mRNA expression of renal urate-anion transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), organic anion transporters 3 (OAT3), and ATP-binding cassette transporter G2 (ABCG2) were determined. The molecular docking was conducted using AutoDock Vina 1.2.0 to screen potential XO inhibitors in MOL-FP. Serum metabolomics was established to collect the metabolic profiles of mice and explore the metabolic changes that occurred after MOL-FP treatment. MOL-FP could notably reduce the serum UA level of hyperuricemia mice by inhibiting XO activity and regulating renal urate transporters. Molecular docking studies indicated that 5-p-coumaroylquinic acid, 3-p-coumaroylquinic acid, and catechin could be potential XO inhibitors. Besides, MOL-FP prevented the pathological process of hyperuricemia by regulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism.

Tannins in Terminalia bellirica inhibits hepatocellular carcinoma growth via re-educating tumor-associated macrophages and restoring CD8+T cell function.

Tumor-associated macrophages (TAMs) are the major immunosuppressive components infiltrating the tumor microenvironment (TME). Targeting TAMs has emerged as a promising strategy to remodel immunosuppressive TME and enhance T-cell mediated anti-tumor immunity for cancer therapy. In this study, we investigate the effect and mechanism of total tannin fraction of Terminalia bellirica (Gaertn.) Roxb. (TB-TF) against hepatocellular carcinoma (HCC) using established Hepa1-6 orthotopic mouse model and murine bone marrow derived macrophage polarization model. Here we showed that TB-TF significantly inhibited orthotopic tumor growth and promoted the polarization of M2-TAMs toward the anti-tumor M1 phenotype in vivo. Further studies showed that TB-TF reversed tumor-conditioned medium induced M2 polarization of macrophages as indicated by increased expression of TNF-α, IL-1ß, and iNOS, and decreased expression of Arg-1, thereby re-educating macrophages co-cultured with tumor-conditioned medium into M1 phenotype. In addition, we found that TB-TF also promoted T cell infiltration mediated by chemokines such as CCL5 and CXCL10, and restored the cytotoxic function of CD8+T cells as evidenced by upregulated expression of Granzyme B, Perforin, and IFN-γ. Our data suggest TB-TF as a promising anti-cancer agent, mediates its anti-tumor effects via remodeling the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy for hepatocellular carcinoma.

Antidepressant-Like Effect and Mechanism of Ginsenoside Rd on Rodent Models of Depression.

Background: There is growing evidence to suggest that ginsenoside Rd (GRd) has a therapeutic effect on depression, but the specific mechanisms behind its activity require further study. Objective: This study is designed to investigate the antidepressant-like effect and underlying mechanisms of GRd. Methods: In this study, the behavioral despair mouse model of depression and chronic unpredictable mild stress (CUMS) rat model of depression were established to explore the effects of GRd on depression-like behavior and its underlying mechanisms. Behavioral tests were used to evaluate the replication of animal models and depression-like behaviors. The hypoxia-inducible factor-1α (HIF-1α) blocker 2-methoxyestradiol (2-ME) was injected to determine the role of HIF-1α in the antidepressant-like effect of GRd. In addition, molecular biology techniques were used to determine the mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators, that is synapsin 1 (SYN 1) and postsynaptic density protein 95 (PSD 95). In silico binding interaction studies of GRd with focused target proteins were performed using molecular docking to predict the affinity and optimal binding mode between ligands and receptors. Results: Our data show that GRd significantly reversed depression-like behavior and promoted mRNA and protein expression of HIF-1ɑ signaling pathway and synaptic plasticity-related regulators. However, the antidepressant-like effect of GRd disappeared upon inhibition of HIF-1α expression following administration of 2-ME. Furthermore, molecular docking results showed that GRd possessed significant binding affinity for HIF-1α, VEGF, and VEGFR-2. Conclusion: Our results show that GRd exhibits significant antidepressant-like effect and that HIF-1α signaling pathway is a promising target for the treatment of depression.

Ginsenoside Rb1 prevents lipopolysaccharide-induced depressive-like behavior by inhibiting inflammation and neural dysfunction and F2 elicits a novel antidepressant-like effect: A metabolite-based network pharmacology study.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory responses are associated wieh the pathophysiology of depression. Ginsenoside Rb1 (Rb1) exerts antidepressant effect, but the relationship between its activity and inflammation remains unclear. AIM OF THE STUDY: In this study, the antidepressant-like effect and underlying mechanisms of Rb1 were been investigated. MATERIALS AND METHODS: The neuroinflammatory mouse model of lipopolysaccharide (LPS)-induced acute depression-like behavior was employed to detect the action of Rb1. An integrative strategy combining the identification of prototype (Rb1) and its metabolites in vivo with network pharmacology analysis was used to explore therapeutic mechanisms of these ingredients. The putative targets and signalings were experimentally validated. The antidepressant-like effect of F2, the metabolite of Rb1, was firstly evaluated. RESULTS: Rb1 significantly ameliorated LPS-induced depressive-like behavior. Rb1 and its metabolites (Rd, F2, compound K, Rh2, Rg3, PPD) were identified and then a disease-component-target network was established. Experimental validation showed that Rb1 inhibited peripheral and hippocampal inflammation via MAPK/NF-κB signaling. In inflammatory-mediated depression state, Rb1 improved impaired glucocorticoid receptor, suppressed indoleamine 2,3-dioxygenase activity, increased 5-HT level and 5-HT1A receptor expression. Additionally, F2 was firstly discovered to exert antidepressant-like effect, and it existed higher activity than Rb1 against depression. CONCLUSION: The study highlighted the potential of Rb1 and F2 as healthy supplement or agent for inflammation-induced depression.

Prenatal diagnosis of Meier-Gorlin syndrome 7: a case presentation.

BACKGROUND: Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES). CASE PRESENTATION: Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction. CONCLUSIONS: It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.

Tannins in Terminalia bellirica inhibit hepatocellular carcinoma growth by regulating EGFR-signaling and tumor immunity.

The fruits of Terminalia bellirica (Gaertn.) Roxb. (TB) are used as a multi-use therapeutic herbal product in the Tibetan medicinal system and are prescribed as a general health tonic in the traditional Ayurvedic medicinal system. It has been demonstrated that these fruits have a variety of pharmacological activities, including anti-tumor, anti-oxidative, anti-inflammatory, hepatoprotective and immunoregulatory effects, etc. However, the therapeutic effects of tannins in TB on HCC and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the anti-tumor effect of tannins in TB by employing a H22 xenograft mouse model and by performing cell-based in vitro studies with the assistance of the network pharmacology analysis. The crude extract of TB was purified to yield total tannin fraction (TB-TF), and our results found that TB-TF significantly inhibited the tumor growth of H22 xenografts in mice by inducing apoptosis and reducing angiogenesis. A total of 90 compounds were then identified in TB-TF by UPLC-MS/MS, and 27 were found in serum after oral administration of TB-TF in mice. The network pharmacology analysis based on these absorbed components was performed and, along with experimental evidence, it revealed that the ERBB, PI3K-Akt, and MAPK signaling pathways may be involved in the anti-tumor effect of TB-TF on HCC. Furthermore, we suggested that TB-TF effectively modulated the immunosuppressive tumor microenvironment in H22 xenograft mice. In summary, our study demonstrated that TB-TF could be developed as a functional food, which is not only a promising anti-cancer reagent but also a potential candidate with bright prospects for the emerging trends of immunotherapy for HCC.

Probability of severe postpartum hemorrhage in repeat cesarean deliveries: a multicenter retrospective study in China.

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

Phytochemical Analysis Using UPLC-MSn Combined with Network Pharmacology Approaches to Explore the Biomarkers for the Quality Control of the Anticancer Tannin Fraction of Phyllanthus emblica L. Habitat in Nepal.

Phyllanthus emblica L. is widely used in traditional Tibetan medicine for its therapeutic effects on treating liver, kidney, and bladder problems. We have reported that the tannin fraction has a good anti-hepatocellular carcinoma effect, but its active ingredients are not clear. This study was to find the active ingredients of the tannin fraction using UPLC-MSn and network pharmacology. First of all, the UPLC-MSn method was employed to obtain high-resolution mass spectra of different components, and 110 compounds were obtained. Then a network pharmacology method was used to find biomarkers for quality control. Network pharmacology results showed that gallic acid, punicalagin A, punicalagin B, methyl gallate, geraniin, corilagin, chebulinic acid, chebulagic acid, and ellagic acid should be the biomarkers of the tannin fraction. Furthermore, 9 components were detected in the serum, which also proved that they could be biomarkers, because we generally believe that the ingredients which are absorbed into the blood are effective. In the end, a simple method for simultaneously determining the contents of the 9 compounds was constructed by HPLC-DAD. This research established a new method to find biomarkers of traditional Chinese medicine. This is of great significance to improving the quality standards of Tibetan medicine.

Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis.

Ginseng, the root and rhizome of Panax ginseng C. A. Mey., is a famous herbal medicine, and its major ginsenosides exert beneficial effects on nonalcoholic fatty liver disease (NAFLD). Due to the multicomponent and multitarget features of ginsenosides, their detailed mechanisms remain unclear. This study aimed to explore the role of ginsenosides on NAFLD and the potential mechanisms mediated by the gut microbiota and related molecular processes. C57BL/6J mice were fed a high-fat diet (HFD) supplemented or not supplemented with ginsenoside extract (GE) for 12 weeks. A strategy that integrates bacterial gene sequencing, serum pharmacochemistry and network pharmacology was applied. The results showed that GE significantly alleviated HFD-induced NAFLD symptoms in a dose-dependent manner. Furthermore, GE treatment modulated the HFD-induced imbalance in the gut microbiota and alleviated dysbiosis-mediated gut leakage and metabolic endotoxemia. Additionally, 20 components were identified in the mouse plasma after the oral administration of GE, and they interacted with 82 NAFLD-related targets. A network analysis revealed that anti-inflammatory effects and regulation of the metabolic balance might be responsible for the effects of GE on NAFLD. A validation experiment was then conducted, and the results suggested that GE suppressed NF-κB/IκB signaling activation and decreased the release and mRNA levels of proinflammatory factors (TNF-α, IL-1ß and IL-6). Additionally, GE promoted hepatic lipolytic genes (CPT-1a), inhibited lipogenic genes (SREBP-1c, FAS, ACC-1) and improved leptin resistance. These findings imply that the benefits of GE are involved in modulating the gut microbiota, enhancing the gut barrier function, restoring the energy balance, and alleviating metabolic inflammation. Moreover, GE might serve as a potential agent for the prevention of NAFLD through the integration of prebiotic, anti-inflammatory and energy-regulatory effects.

Fast discrimination and quantification analysis of Curcumae Radix from four botanical origins using NIR spectroscopy coupled with chemometrics tools.

Curcumae Radix (Yujin) is a multi-origin herbal medicine with excellent clinical efficacy. For fast discrimination and quantification analysis of Yujin from four botanical origins (Guiyujin, Huangyujin, Lvyujin and Wenyujin), near infrared (NIR) spectroscopy combined with chemometrics tools was employed in this study. Based on NIR data, principal component analysis (PCA) could only realize the separation between Guiyujin and Wenyujin samples, and the partial least squares-discrimination analysis (PLS-DA), support vector machine (SVM) and k-nearest neighbors (KNN) models achieved the complete discrimination of the four species of Yujin with 100% accuracy. Moreover, the method for the simultaneous determination of six bioactive compounds in Yujin was developed by HPLC. Germacrone, curdione and curcumenol could be found in all samples, and curcumin, demethoxycurcumin and bisdemethoxycurcumin were only observed in Huangyujin samples. Then, the support vector machine regression (SVMR) model for the prediction of germacrone content was successfully constructed. And the coefficients of determination were 0.88 and 0.89 for calibration and validation sets, respectively. The present work proposes a quick, economic and reliable method for the discrimination of Yujin from four botanical origins and the prediction of germacrone content, which will contribute to its quality control researches.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

A Comprehensive Review of the Structure Elucidation of Tannins from Terminalia Linn.

OBJECTIVES: Tannins with complex structures are important plant resources, which are abundant in the genus Terminalia. Various Terminalia species have been playing an important role in traditional medicine system. A systematic scoping review of Terminalia Linn. research literature for tannins was conducted to summarize the structures of tannins and analysis fragmentation pathway characteristics, which could provide references for the structural analysis of tannins from Terminalia Linn. METHODS: After an update of the literature search up to September 2018, the terms of Terminalia in all publications were analyzed. Electronic searches were conducted in scifinder and PubMed, and the information from 197 articles in all with regard to the tannin structure study was extracted. RESULTS: The compounds of 82 tannins from the genus Terminalia were reviewed. According to the structural differences, they can be divided into three categories, hydrolysable tannins, condensed tannins, and complex tannins, respectively. The fragmentation pathways of 46 identified tannins were analyzed, and the fragmentation rules of tannins were speculated according to different types. CONCLUSION: This review has attracted attention to the active substances in this species such as the tannins summarized in further study. How to improve the extraction and purification technology of tannins from genus Terminalia is an urgent problem to be solved.