Comparison of embryo quality and pregnancy outcomes for patients with low ovarian reserve in natural cycles and mildly stimulated cycles: a cohort study.

BACKGROUND: As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles. METHODS: This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles. RESULTS: The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00. CONCLUSION: Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.

In the realm of in-vitro fertilisation (IVF) treatment, women with low ovarian reserve often face the crucial decision of opting for natural or mildly stimulated cycles. This retrospective study, conducted between January 2017 and April 2021 at Guangdong Second Provincial General Hospital, delves into the impact of these cycles on pregnancy outcomes. Examining 478 natural cycles and 448 mildly stimulated cycles, the study reveals a notably higher pregnancy rate in the natural cycle group (51.8% vs. 40.1%). Additionally, natural cycles demonstrated higher rates of available embryos, high-quality embryos, and oocyte utilisation compared to their mildly stimulated counterparts. The findings suggest that natural cycles, with proper oocyte retrieval timing, could be a favourable choice for those with low ovarian reserve seeking IVF treatment.

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes.

Mammalian centromeres are generally composed of dispersed repeats and the satellites such as α-satellites in human and major/minor satellites in mouse. Transcription of centromeres by RNA polymerase II is evolutionary conserved and critical for kinetochore assembly. In addition, it has been found that the transcribed satellite RNAs can bind DNA repair proteins such as MRE11 and PRKDC, and excessively expressed satellite RNAs could induce genome instability and facilitate tumorigenesis. During the maturation of female oocyte, centromeres are critical for accurate segregation of homologous chromosomes and sister chromatids. However, the dynamics of oocyte centromere transcription and whether it associated with DNA repair proteins are unknown. In this study, we found the transcription of centromeres is active in growing oocytes but it is silenced when oocytes are fully grown. DNA repair proteins like Mlh1, Mre11 and Prkdc are found associated with the minor satellites and this association can be interfered by RNA polymerase II inhibitor α-amanitin. When the growing oocyte is in vitro matured, Mlh1/Mre11/Prkdc foci would release from centromeres to the ooplasm. If the oocytes are treated with Mre11 inhibitor Mirin, the meiosis resumption of growing oocytes with Mre11 foci can be suppressed. These data revealed the dynamic of centromeric transcription in oocytes and its potential association with DNA repair proteins, which provide clues about how oocytes maintain centromere stability and assemble kinetochores.

Simulated microgravity reduces quality of ovarian follicles and oocytes by disrupting communications of follicle cells.

Ovarian follicles are the fundamental structures that support oocyte development, and communications between oocytes and follicle somatic cells are crucial for oogenesis. However, it is unknown that whether exposure to microgravity influences cellular communications and ovarian follicle development, which might be harmful for female fertility. By 3D culturing of ovarian follicles under simulated microgravity (SMG) conditions in a rotating cell culture system, we found that SMG treatment did not affect the survival or general growth of follicles but decreased the quality of cultured follicles released oocytes. Ultrastructure detections by high-resolution imaging showed that the development of cellular communicating structures, including granulosa cell transzonal projections and oocyte microvilli, were markedly disrupted. These abnormalities caused chaotic polarity of granulosa cells (GCs) and a decrease in oocyte-secreted factors, such as Growth Differentiation Factor 9 (GDF9), which led to decreased quality of oocytes in these follicles. Therefore, the quality of oocytes was dramatically improved by the supplementations of GDF9 and NADPH-oxidase inhibitor apocynin. Together, our results suggest that exposure to simulated microgravity impairs the ultrastructure of ovarian follicles. Such impairment may affect female fertility in space environment.

Continuous light exposure influences luteinization and luteal function of ovary in ICR mice.

With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD). We used continuous light-exposed mice as a model to observe whether continuous light exposure may affect luteinization and luteal function. We showed that the level of progesterone in serum reduced (p < .001), the number of corpus luteum (CL) decreased (p < .01), and the expressions of luteinization-related genes (Lhcgr, Star, Ptgfr, and Runx2), clock genes (Clock and Per1), and Mt1 were downregulated (p < .05) in the ovaries of mice exposed to continuous light, suggesting that continuous light exposure induces defects in luteinization and luteal functions. Strikingly, injection of melatonin (3 mg/kg) could improve luteal functions in continuous light-exposed mice. Moreover, we found that, after 2 h of hCG injection, the level of pERK1/2 in the ovary decreased in the continuous light group, but increased in the melatonin administration group, suggesting that melatonin can improve LPD caused by continuous light exposure through activating the ERK1/2 pathway. In summary, our data demonstrate that continuous light exposure affects ovary luteinization and luteal function, which can be rescued by melatonin.

Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: A phase II study.

OBJECTIVE: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. BACKGROUND: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. METHODS: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3-week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. RESULTS: As of January 29, 2021, 31 patients were enrolled. The median follow-up was 5.1 months (range, 1.5-9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3-68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4-100). The median time to response was 1.4 months (95% CI, 1.3-1.4), the median duration of response was not reached, and the median progression-free survival was 6.3 months (95% CI, 4.9-not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment-emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

Effects of Body Weight and Waist Circumference on Balance Function in Overweight and Obese Adults / 中山大学学报(医学科学版)

ObjectiveTo explore the effects of body weight and waist circumference on static and dynamic balance function in overweight and obese adults. MethodsParticipants （n=103） were selected by cluster random sampling from the Hypoglycemic Weight Loss Clinic of the Endocrinology Department of the Third Affiliated Hospital of Sun Yat-sen University. All participants were assessed for basic data collection， biochemical test， body weight， waist circumference and height measurement， static balance function assessed by balance error scoring system （BESS） and dynamic balance function assessed by functional reach test （FRT）. The BESS score and FRT distance of all participants were compared among groups according to different BMI grades and WC grades. Multivariate linear regression was used to analyze the influencing factors of participants' dynamic and static balance functions. Results① With the increase of BMI grading， the BESS score showed an upward trend， and the difference between groups was statistically significant （P = 0.004）. The BESS score of normal WC patients was lower than that of central obesity patients （P < 0.001）， which indicated that compared with normal BMI， overweight and obese people had poor dynamic and static balance ability； ② With the BMI grading， the FRT distance increased， showing a downward trend （P < 0.001）. The FRT distance in normal WC patients was significantly higher than that in central obesity patients （P < 0.001）， which indicated that the static and dynamic balance ability of central obesity patients was worse than that of normal WC patients； ③ In BMI overweight group， the FRT distance decreased significantly with the increase of WC （P = 0.02）. The results showed that under the condition of no difference in BMI， Compared with normal WC， the dynamic and static balance ability of central obese patients was worse； ④ The influence of BESS score on BMI（B=4.12，P =0.027， 95% CI=0.48-7.75）and WC（B = 3.47，P = 0.046， 95% CI = 0.07 - 6.88）was significant. The influence of FRT distance on BMI（B = -5.68，P = 0.001， 95% CI = -8.95 - 2.41）and WC（B = -4.71，P = 0.003， 95% CI = -7.83 to -1.61）was significant， which indicated that the static and dynamic balance ability of obese people was worse with the increase of BMI， and the ability of dynamic and static balance of central obesity was worse than that of normal WC. ConclusionWaist circumference is an independent factor affecting the dynamic and static balance function of overweight and obese people. Under similar BMI， the dynamic balance function of central obese people is worse than that of people with normal waist circumference， leading to higher risk of falling.

Progress on the relationship between high-sugar diet and myopia development / 国际眼科杂志(Guoji Yanke Zazhi)

Myopia has become a major public health problem affecting the eye health of our nationals, especially adolescents, and is listed as one of the three major diseases in the world. The etiology of myopia is complex and it is currently considered to be mainly related to environmental factors and genetic factors. Dietary factors are less concerned, but it has been reported that there is a correlation between high-sugar diet and the occurrence and development of myopia. Studies have found that high-sugar diet can cause hyperinsulinemia, which mediates the increase of retinal insulin-like growth factor(IGF-1, IGF-2)expression level, and the decrease of insulin-like growth factor binding protein-3(IGFBP-3)expression level in scleral fibroblasts, thereby activating signal transduction and transcriptional activator protein 3(STAT3)signaling pathway, and then acting on scleral matrix metalloproteinases(MMP)/transforming growth factor-β(TGF-β)and other factors, resulting in a decrease in scleral extracellular matrix(ECM), eventually leading to scleral remodeling, eye axis growth and myopia. This article explores the relationship between high-sugar diet and the occurrence and development of myopia from the aspects of epidemiology and biological mechanisms by consulting relevant literature, and provides research directions for the prevention and control of myopia.

Clinical application of special fluoroscopy method in the treatment of distal radius fractures with volar locking plate / 中国骨伤

OBJECTIVE@#The relationship between the distal screws and the wrist articular surface was assessed by the additional lateral oblique fluoroscopic view during the operation, and the dorsal tangential view of the wrist was used to observe whether the distal screw penetrated the dorsal cortex, so as to evaluate the clinical efficacy of the volar locking plate in the treatment of distal radius fractures.@*METHODS@#From January 2020 to June 2021, 45 cases of fresh distal radius fractures were treated using the volar Henry's approach, including 20 males and 25 females, aged from 32 to 75 years old with an average of (52.4±8.1) years old. During the operation, they were divided into 2 groups according to the different intraoperative fluoroscopic views:the control group of 20 cases, treated with standard anteroposterior and lateral fluoroscopic view;25 cases in the observation group, additional lateral oblique fluoroscopic view and dorsal tangential view of the wrist were taken. The wrist joint function score and postoperative complications were evaluated at 6 weeks, 3 and 6 months after operation between two groups.@*RESULTS@#All 45 patients were followed up and the duration ranged from 6 to 14 months, with an average of (10.8±1.7) months, all patients achieved bone union and the incision healed well. The incidence of postoperative complications in the observation group was lower than that in the control group, and the difference was statistically significant (P<0.05). In terms of Gartland-Werley score of wrist joint function, the score of wrist function in the observation group was (4.58±1.31) at 6 weeks, (2.98±0.63) at 3 months and (1.95±0.65) at 6 months post-operatively, which were better than those in the control group (6.32±1.96) at 6 weeks, (3.63±0.76) at 3 months and (2.43±0.73) at 6 months. The difference was statistically significant (P<0.05). In the observation group, 7/25 cases(28%) were found to have screw penetration during the operation by additional lateral oblique and dorsal tangential radiograph fluoroscopic views of wrist.@*CONCLUSION@#The addition of lateral oblique and dorsal tangential during the operation could improve the accuracy of distal screw placement, reduce postoperative complications, and achieve early functional exercise.

Analyzing the relevant factors affecting the clinical outcome of periodontal regeneration surgery / 中华口腔医学杂志

Periodontitis can lead to periodontal tissue defect, tooth mobility and loss, which seriously affects the quality of life. Periodontal regeneration surgery is an important treatment method for repairing periodontal defects, and it is also the hotspot of current periodontal clinical and basic research. A comprehensive understanding of the factors affecting the efficacy of periodontal regenerative surgery can improve clinicians' periodontal treatment concepts, increases the predictability of treatment results, and enhances the level of clinical diagnosis and periodontal treatment. In order to instruct the clinicians, this article will explain the basic principles of periodontal regeneration and the key points of periodontal wound healing, and analyze the elements of periodontal regeneration surgery, which including the patient-related factors, local factors, surgical factors and regenerative material selection.

Completion rates of bundle treatment of among patients with sepsis shock in intensive care departments of hospitals in Jiangsu Province from 2016 to 2020 years / 中华内科杂志

Current clinical approaches for septic shock increasingly incorporate bundle treatment, a multi-component approach that uses a collection of tests and agents to assist in the identification and treatment of infection. The present study analyzed completion rates of 3 h and 6 h bundle treatment among patients with septic shock in intensive care units (ICUs) of hospitals in Jiangsu Province from 2016 to 2020, using data from the Jiangsu Provincial Intensive Care Medical Quality Control Center. Current approaches and factors affecting treatment completion were assessed.The completion rates of 3 h and 6 h bundle treatment in ICUs of all medical units in Jiangsu Province and in ICUs of hospitals of different levels were recorded. Analyses show that the completion rate of 3 h and 6 h bundle treatment for patients with septic shock in ICUs in Jiangsu Province increased year by year from 2016 to 2020.The completion rate of 3 h bundle treatment increased from 69.82% (3 604/5 162) to 82.47% (8 915/10 775) (all P<0.001). The completion rate of 6 h bundle treatment increased from 62.69% (3 236/5 162) to 72.54% (7 816/10 775) (all P<0.001). In addition, year by year, the completion rate of 3 h bundle treatment in ICUs in tertiary hospitals increased, from 69.80% (3 596/5 152) to 82.23% (7 375/8 969), while the completion rate of 6 h bundle treatment increased from 62.69% (3 230/5 152) to 72.18% (6 474/8 969) (all P<0.001). Completion rates in secondary hospitals also increased year by year, from 80.00% (8/10) to 85.27% (1 540/1 806) for 3 h treatment and from 60.00% (6/10) to 74.31% (1 342/1 806) (all P<0.001) for 6 h treatment. Completion rates for 3 h treatment in first-tier cities (83.99% (2 099/2 499)) and second-tier cities (84.68% (3 952/4 667)) was higher than in third-tier cities (79.36% (2 864/3 609)). The completion rate of 6 h bundle treatment gradually decreased in first-line (77.19% (1 929/2 499)), second-line (74.37% (3 471/4 667)), and third-line (66.94% (2 416/3 609)) cities (all P<0.001). The data collectively show that from 2016 to 2020, the completion rate of bundle treatment in septic shock patients in ICUs in Jiangsu Province improved significantly.

Shenfu Injection alleviates sepsis-associated lung injury by regulating HIF-1α / 中国中药杂志

Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.

The Role of EO% and CRP in Risk Factors Analysis of Young Patients with Transfusion Related Adverse Reactions / 中山大学学报(医学科学版)

ObjectiveTo discuss the correlation between young patients’ adverse transfusion reaction and pre-transfusion C reactive protein （CRP） level and EO% （percentage of eosinophils） . MethodsThe observation group was chosen from among sixty-six young patients who experienced transfusion-related adverse events between January 2019 and December 2020. For each patient chosen to be included in the observation group， another patient from the same department， with the same disease and gender， who had been hospitalized in the same month and received the same type of blood product transfusion， but had not experienced any transfusion-related adverse effects， was chosen to be in the control group. We examined and compared their ages， transfusion experiences， allergy backgrounds， EO%， and CRP levels in peripheral blood prior to transfusion. A receiver operating characteristic （ROC） curve was used to examine the diagnostic value of EO% and CRP for transfusion-related adverse events. Simultaneously， a logistic analysis was performed on the risk factors for transfusion-related adverse events. ResultsPre-transfusion CRP was higher in patients with FNHTR in the observation group than it was in patients in the control group； pre-transfusion CRP was also higher in patients with ATR in the observation group than it was in patients in the control group. There were also statistically significant differences between these variables in the percentage of patients with transfusion history and pre-transfusion EO% （ P＜0.05）. For the transfusion of different blood types， there was statistical significance in the occurrence of ATR and FNHTR （ P＜0.05）. For the diagnosis of FNHTR， the CRP area under the ROC curve was 0.889， and the best cut-off value was 18.05 mg/L. For the diagnosis of ATR， the area under the ROC curve was 0.749， and the best cut-off values were 17.60 mg/L. ConclusionPre-transfusion C-reactive protein level is an independent risk factor for FNHTR and ATR in young patients； the predictive value of EO% for adverse blood transfusion reactions is insufficient.

Identification of anti-inflammatory components in Dioscorea nipponica Makino based on HPLC-MS/MS, quantitative analysis of multiple components by single marker and chemometric methods.

The rhizome of Dioscorea nipponica Makino (RDN) is a widely used herbal medicine, which has significant anti-inflammatory activities on various inflammatory diseases. However, the bioactive compositions responsible for the anti-inflammatory activity of RDN are still unknown. This study aimed to identify the anti-inflammatory bioactive compounds in RDN using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS), quantitative analysis of multiple components by single marker (QAMS) and chemometric methods. Firstly, an HPLC-Q/TOF-MS method was employed for identification of bioactive steroidal saponins in RND, and a total of twelve steroid saponins were identified. Then, QAMS method was employed to determine the contents of seven bioactive steroidal saponins, including protodioscin, protogracillin, methyl protodioscin, pseudoprotodioscin, pseudoprogracillin, dioscin and gracillin in RND samples using dioscin as the reference analyte. The anti-inflammatory effects of RDN samples were then evaluated by inhibition of NO production in LPS-induced RAW264.7 cells. Furthermore, chemometric methods, including Pearson correlation analysis and partial least squares regression (PLSR) were employed to investigate the correlations between chemical components and anti-inflammatory activities, and explore the potential anti-inflammatory bioactive compounds of RDN. The results indicated that protodioscin, dioscin and gracillin were selected as the major anti-inflammatory compounds in RND. The further verification experiments showed that protodioscin, dioscin and gracillin exhibited great inhibition on NO production with IC50 values (the half maximal inhibitory concentration) of 0.712 µM, 0.469 µM and 0.815 µM, respectively. They also significantly reduced the levels of TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. The present study provided evidences for the anti-inflammatory activity of RND and identification of the anti-inflammatory components in RDN.

Characterization of phenolics and discovery of α-glucosidase inhibitors in Artemisia argyi leaves based on ultra-performance liquid chromatography-tandem mass spectrometry and relevance analysis.

Artemisia argyi leaves (AAL) has been widely used as herbal medicine and food supplement and in China and other Asian countries. The aim of this work is to qualitative and quantitative characterization of phenolic compounds in AAL and screening of natural product inhibitors of α-glucosidase from AAL. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was employed to rapid and comprehensive identification of phenolic compounds in AAL, and a total of thirty-three phenolic compounds were identified. High performance liquid chromatography with diode array detection (HPLC-DAD) was established and validated to simultaneously determinate ten main bioactive phenolics compounds in different batches of AAL samples. Meanwhile, the inhibitory capacities of different batches of AAL samples on α-glucosidase were evaluated. Then, relevance analysis, including grey relational analysis and Pearson correlation analysis were employed to investigate the correlations between the contents of phenolic compounds and α-glucosidase inhibitory activities, and discover the α-glucosidase inhibitors in AAL. The relevance analysis results indicated that three phenolic compounds, 3-caffeoylquinic acid, 3,4-dicaffeoylquinic acid and 3,5-dicaffeoylquinic acid could be potential α-glucosidase inhibitors in AAL. Moreover, the α-glucosidase inhibitory activities of the three phenolic compounds were validated by in vitro and in vivo experiments. The possible inhibiting effect of the three phenolic compounds on α-glucosidase was also explored by molecular docking analysis, and the results indicated that the binding of the three α-glucosidase inhibitors to α-glucosidase mainly by hydrogen bonds, hydrophobic forces and ionic bonds. The present research provided a deep insight into phenolic compounds and α-glucosidase inhibitory activities of AAL, and discovered the α-glucosidase inhibitors in AAL.

Chemical comparison and discrimination of two plant sources of Angelicae dahuricae Radix, Angelica dahurica and Angelica dahurica var. formosana, by HPLC-Q/TOF-MS and quantitative analysis of multiple components by a single marker.

INTRODUCTION: Angelica dahurica(BZ) and Angelica dahurica var. formosana(HBZ) are two plant sources of Angelicae dahuricae Radix. Although BZ and HBZ are commonly used herbal medicines with great medicinal and dietary values, study on their phytochemicals and bioactive compositions is limited. OBJECTIVE: To compare the chemical compositions of BZ and HBZ and find the chemical makers for discrimination and quality evaluation of the two botanical origins of Angelicae dahuricae Radix. METHODOLOGY: A high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established for chemical profiling of BZ and HBZ. Then, a quantitative analysis of multiple components by a single marker method was developed for simultaneous determination of nine bioactive coumarins (xanthotoxol, oxypeucedanin hydrate, byakangelicin, xanthotoxin, bergapten, oxypeucedanin, phellopterin, imperatorin and isoimperatorin). Moreover, chemometrics were performed to compare and discriminate BZ and HBZ samples. RESULTS: A total of 30 coumarins compounds were identified, and the chemical compositions in BZ and HBZ were quite similar. The quantitative analysis showed that there were significant differences in the contents of bioactive coumarins, and the chemometric analysis indicated five coumarins (xanthotoxol, xanthotoxin, bergapten, phellopterin and isoimperatorin) were responsible for the significant differences between BZ and HBZ, which could be used as chemical markers to distinguish the two original plant sources of Angelicae dahuricae Radix. CONCLUSION: The present work provided useful information for understanding the chemical differences between BZ and HBZ and also provided feasible methods for quality evaluation and discrimination of herbal medicines originating from multiple botanical sources.

[Dynamic changes of volatile components in Forsythia suspensa at different harvest periods based on GC-MS and chemometrics analysis].

Forsythiae Fructus is the dried fruit of Forsythia suspensa and the volatile compounds are its main bioactive components. According to the different harvest periods, F. suspensa can be divided into Qingqiao(mature F. suspensa) and Laoqiao(ripe F. suspensa). To investigate dynamic changes of volatile components in Qingqiao and Laoqiao samples collected at different periods, the present study extracted and analyzed the total volatile oils in Qingqiao and Laoqiao samples(four harvest periods for Qingqiao and two for Laoqiao) by steam distillation method. The results indicated that the content of volatile oils in F. suspensa samples at different harvest periods was significantly different. The content of volatile oils in Qingqiao samples(except those harvested in the first period) was higher than that of Laoqiao, and the content of volatile oils in both Qingqiao and Laoqiao increased with the harvest period. Furthermore, volatile compounds in F. suspensa were qualitatively analyzed by the gas chromatography-mass spectrometry(GC-MS), and 28 volatile compounds were identified. Chemometrics analyses including principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) were further applied to explore differential markers and dynamic changes of volatile components in Qingqiao and Laoqiao samples at different harvest periods. Finally, four volatile compounds, including α-pinene, sabinene, ß-pinene, and 4-terpenol were selected as potential differential markers. The relative content of α-pinene and 4-terpenol was consistent with that of total volatile oils in the changing trend.

Correction: Chromosomal variants accumulate in genomes of the spontaneous aborted fetuses revealed by chromosomal microarray analysis.

[This corrects the article DOI: 10.1371/journal.pone.0259518.].

Analysis of chemical constituents in ethyl acetate extract of Taxilli Herba by UPLC-Q-Exactive-MS and screening of potential xanthine oxidase inhibitors / 中国中药杂志

The present study analyzed and identified the chemical constituents from ethyl acetate(EA) extract of Taxilli Herba with UPLC-Q-Exactive-MS and screened active xanthine oxidase(XO) inhibitors with HPLC. The analysis was performed on an Hypersil GOLD C_(18) reversed-phase column(2.1 mm×50 mm, 1.9 μm), with the mobile phase of water containing 1% formic acid(A) and methanol(B) under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 5 μL. ESI source was used for MS and the compounds were collected in positive and negative ion modes. Xcalibur 4.1 was used to analyze the retention time, accurate relative molecular weight, and fragmentation of the compounds. The inhibitory activity of some known compounds on XO was screened by HPLC. Thirty chemical constituents were identified, including phenolic acids and flavonoids by experimental data combined with information of standards, data reported previously, and databases, such as MzCloud and ChemSpider. The activities of 10 chemical components were screened. Gallic acid and naringenin chalcone had strong inhibitory activities on XO with IC_(50) of 57 μg·mL~(-1) and 108 μg·mL~(-1). UPLC-Q-Exactive-MS allows the accurate, rapid, and comprehensive identification of main chemical constituents from Taxilli Herba. Gallic acid and naringenin chalcone may be the active components of XO inhibitors.

Pharmacological Effect and Mechanism of Andrographolide： A Review / 中国实验方剂学杂志

Andrographolide， a diterpene lactone， is the important material basis for the pharmacological effect of the Chinese medicinal Andrographis paniculata （Burm.f.）Nees. Modern pharmacological research has shown that andrographolide has many pharmacological activities such as anti-inflammation， bacteriostat， anti-virus， anti-tumor， protecting liver， promoting the function of gallbladder， and protecting the cardiovascular system and nervous system. It has significant anti-inflammatory activity which involves multiple targets. To be specific， it can inhibit nuclear factor-κB （NF-κB）， signal transduction and activator of transcription 3 （STAT3）， and other signaling pathways， reduce the synthesis and release of downstream inflammatory mediators， and regulate oxidative stress and immune response to achieve anti-inflammatory effect on various inflammatory diseases. At the same time， it suppresses a variety of tumor cells by inhibiting tumor cell proliferation， blocking cell cycle， and inducing tumor cell apoptosis. Its anti-tumor mechanism involves cellular signaling pathways such as Notch， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， NF-κB， and secreted glycoprotein/β-catenin （Wnt/β-catenin）. In addition， it can also alleviate diabetes by regulating glucose metabolism. According to related research， it often exerts pharmacological effects through multiple pathways and multiple targets， but the specific targets are unclear. Therefore， this article summarizes the relevant studies on the pharmacological effects and mechanisms of andrographolide in the past three years and puts forward the future research directions， which is expected to serve as a reference for the further in-depth research and development and utilization of andrographolide.