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Percutaneous coronary intervention (PCI) is an important treatment strategy for patients with coronary artery disease. However, bleeding after PCI significantly increases the mortality risk. The search for prognostic predictors and optimal antiplatelet therapy for patients with high bleeding risk (HBR) after PCI has been a much researched upon topic in current cardiovascular research. However, there is no widely accepted prognostic model or recommended antiplatelet therapy for patients with PCI-HBR. In this trial, based on prospective multi-center database building, we will analyze the adverse prognostic predictors for patients with PCI-HBR, observe the types of antiplatelet drugs and duration of dual antiplatelet therapy in PCI-HBR patients, and compare the safety and feasibility of different antiplatelet regimens and treatment courses. The prognostic analysis and an appropriate antiplatelet strategy for patients with PCI and high bleeding risk (PPP-PCI) trial will help analyze bleeding risk factors in PCI-HBR patients and explore the appropriate antiplatelet treatment options. This study is registered with ClinicalTrials.gov (NCT05369442). The Research Ethics Committee of West China Hospital authorized this study (2022 Review #269). The trial results will be published in peer-reviewed journals and at conferences.

Abstract Aims/Introduction To evaluate the differences in cardiac autonomic function, cardiac structure and diastolic function between individuals with diabetic foot (DF) and those with diabetes but without DF. Materials and Methods A total of 413 individuals with DF and 437 without DF who underwent a 24‐h electrocardiogram Holter and a Doppler echocardiogram were included. The heart rate variability parameters to evaluate cardiac autonomic function, and the indices for the assessment of cardiac structure and left ventricular (LV) diastolic function, including left atrium, LV posterior wall thickness, interventricular septum and E/e′ ratio, were measured or calculated. Propensity score matching was used for the sensitivity analysis to minimize potential imbalance. Results In both the crude and propensity score matching analyses, significant differences were observed in heart rate variability between individuals with and without DF, as evidenced by lower standard deviation of the normal sinus interval, lower low‐frequency power/high‐frequency power ratio, lower standard deviation of the 5‐min average RR intervals, lower low‐frequency power, lower percentage of normal adjacent RR interval difference >50 ms, lower root mean square of successive RR interval differences and lower high‐frequency power (all P

Abstract Background Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey. Methods A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival. Results During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80–0.87) for the pre-frailty group, 0.68 (95% CI: 0.64–0.72) for the mild frailty group, and 0.52 (95% CI: 0.48–0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82–0.85). Stratified and sensitivity analyses suggested the robustness of the results. Conclusions The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.

Abstract The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P

Hypertension is one of the most common chronic diseases in older people, and the prevalence is on the rise as the global population ages. Hypertension is closely associated with many adverse health outcomes, including cardiovascular disease, chronic kidney disease and mortality, which poses a substantial threat to global public health. Reasonable blood pressure (BP) management is very important for reducing the occurrence of adverse events. Frailty is an age-related geriatric syndrome, characterized by decreased physiological reserves of multiple organs and systems and increased sensitivity to stressors, which increases the risk of falls, hospitalization, fractures, and mortality in older people. With the aging of the global population and the important impact of frailty on clinical practice, frailty has attracted increasing attention in recent years. In older people, frailty and hypertension often coexist. Frailty has a negative impact on BP management and the prognosis of older hypertensive patients, while hypertension may increase the risk of frailty in older people. However, the causal relationship between frailty and hypertension remains unclear, and there is a paucity of research regarding the efficacious management of hypertension in frail elderly patients. The management of hypertension in frail elderly patients still faces significant challenges. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. This review provides a brief overview of hypertension in frail older adults, especially for the management of BP in this population, which may help in offering valuable ideas for future research in this field.

BackgroundPrevious studies have shown social activity is associated with reduced risk of health outcomes. However, among older people (≥65 years) who were socially inactive at baseline, limited study explored whether increased participation in social activity in later life was associated with reduced risk of health outcomes; therefore, using the data from the Chinese Longitudinal Healthy Longevity Survey, the study was performed.MethodsThe study outcomes were 10-year all-cause mortality (sample number = 9,984) and 10-year heart diseases (sample number = 7,496). The exposure was the change of social activity frequency. Cox regression analysis was used for data analysis.ResultsDuring the follow-up, there were 6,407 all-cause mortalities and 1,035 heart diseases, respectively. Kaplan–Meier analysis demonstrated that cumulative incidences of all-cause mortality were significantly lower in participants with changes into more frequent social activity (log-rank p

Abstract Background Few studies have investigated the association between changes in frailty status and all-cause mortality, inconsistent results were reported. What’s more, studies that evaluated the effect of changes of frailty on cardiovascular death in older population are scanty. Therefore, the present study aims to investigate the association of such changes with the risk of all-cause mortality and cardiovascular death in older people, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Methods A total of 2805 older participants from two consecutive waves (i.e. 2011 and 2014) of the CLHLS were included for analysis. Based on the changes in frailty status from wave 2011 to wave 2014, participants were categorized into 4 subgroups, including sustained pre/frailty, robustness to pre/frailty, pre/frailty to robustness and sustained robustness. Study outcomes were all-cause mortality and cardiovascular death, and Cox regression analysis examined the association of changes in frailty status with outcomes. Results From wave 2011 to wave 2014, 33.2% of the participants had frailty transitions. From wave 2014 to wave 2018, there were 952 all-cause mortalities and 170 cardiovascular deaths during a follow-up of 9530.1 person-years, and Kaplan-Meier analysis demonstrated that cumulative incidences of the two outcomes were significantly lower in more robust participants (all log-rank p < 0.001). Compared with the subgroup of sustained pre/frailty, the fully adjusted HRs of all-cause mortality were 0.61 (95% CI: 0.51–0.73, p < 0.001), 0.51 (95% CI: 0.42–0.63, p < 0.001) and 0.41 (0.34–0.49, p < 0.001) in the subgroup of robustness to pre/frailty, the subgroup of pre/frailty to robustness, and the subgroup of sustained robustness, respectively. The fully adjusted HRs of cardiovascular death were 0.79 (95% CI: 0.52–1.19, p = 0.256) in the subgroup of robustness to pre/frailty, 0.45 (95% CI: 0.26–0.76, p = 0.003) in the subgroup of pre/frailty to robustness and 0.51 (0.33–0.78, p = 0.002) in the subgroup of sustained robustness when comparing to the subgroup of sustained pre/frailty, respectively. Stratified analysis and extensive sensitivity analyses revealed similar results. Conclusions Frailty is a dynamic process, and improved frailty and remaining robust are significantly associated with lower risk of all-cause mortality and cardiovascular death in older people.

Panax notoginseng is a highly valued perennial medicinal herb plant in Yunnan Province, China, and the taproots are the main medicinal parts that are rich in active substances of P. notoginseng saponins. The main purpose of this study is to uncover the physiological and molecular mechanism of Panax notoginseng saponin accumulation triggered by methyl jasmonate (MeJA) under arbuscular mycorrhizal fungi (AMF) by determining physiological indices, high-throughput sequencing and correlation analysis. Physiological results showed that the biomass and saponin contents of P. notoginseng, the concentrations of jasmonic acids (JAs) and the key enzyme activities involved in notoginsenoside biosynthesis significantly increased under AMF or MeJA, but the interactive treatment of AMF and MeJA weakened the effect of AMF, suggesting that a high concentration of endogenous JA have inhibitory effect. Transcriptome sequencing results indicated that differential expressed genes (DEGs) involved in notoginsenoside and JA biosynthesis were significantly enriched in response to AMF induction, e.g., upregulated genes of diphosphocytidyl-2-C-methyl-d-erythritol kinases (ISPEs), cytochrome P450 monooxygenases (CYP450s)_and glycosyltransferases (GTs), while treatments AMF-MeJA and salicylhydroxamic acid (SHAM) decreased the abundance of these DEGs. Interestingly, a high correlation presented between any two of saponin contents, key enzyme activities and expression levels of DEGs. Taken together, the inoculation of AMF can improve the growth and saponin accumulation of P. notoginseng by strengthening the activities of key enzymes and the expression levels of encoding genes, in which the JA regulatory pathway is a key link. This study provides references for implementing ecological planting of P. notoginseng, improving saponin accumulation and illustrating the biosynthesis mechanism.

Abstract Background Albumin to fibrinogen ratio (AFR), a new inflammatory marker, has emerged as a useful indicator to predict adverse outcomes for several diseases. However, whether AFR could be a new useful indicator to predict mortality in HCM patients remains to be evaluated. The study explored the predictive value of AFR for HCM-related death in adult HCM patients. Methods A total of 404 HCM patients were eventually enrolled in the study according to the inclusion criteria. Patients were divided into two groups based on the median of baseline AFR. The association between AFR and HCM-related death was analyzed. Results During a median follow-up of 4.75 years, HCM-related death was observed in 45 patients (11.1%). The incidence of HCM-related death was significantly higher in the low AFR group (log-rank p

This paper proposed a two-dimensional steady-state field prediction approach that combines B-spline functions and a fully connected neural network. In this approach, field data, which are determined by corresponding control vectors, are fitted by a selected B-spline function set, yielding the corresponding best-fitting weight vectors, and then a fully connected neural network is trained using those weight vectors and control vectors. The trained neural network first predicts a weight vector using a given control vector, and then the corresponding field can be restored via the selected B-spline set. This method was applied to learn and predict two-dimensional steady advection–diffusion physical fields with absorption and source terms, and its accuracy and performance were tested and verified by a series of numerical experiments with different B-spline sets, boundary conditions, field gradients, and field states. The proposed method was finally compared with a generative adversarial network (GAN) and a physics-informed neural network (PINN). The results indicated that the B-spline neural network could predict the tested physical fields well; the overall error can be reduced by expanding the selected B-spline set. Compared with GAN and PINN, the proposed method also presented the advantages of a high prediction accuracy, less demand for training data, and high training efficiency.

Panax notoginseng is a highly valued perennial medicinal herb in China and is widely used in clinical treatments. The main purpose of this study was to elucidate the changes in the composition of P. notoginseng saponins (PNSs), which are the main bioactive substances, triggered by arbuscular mycorrhizal fungi (AMF) via ultrahigh-performance liquid chromatography–electrospray ionization–tandem mass spectrometry (UPLC–ESI–MS/MS). A total of 202 putative terpenoid metabolites were detected, of which 150 triterpene glycosides were identified, accounting for 74.26% of the total. Correlation analysis, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS–DA) of the metabolites revealed that the samples treated with AMF (group Ce) could be clearly separated from the CK samples. In total, 49 differential terpene metabolites were identified between the Ce and CK groups, of which 38 and 11 metabolites were upregulated and downregulated, respectively, and most of the upregulated differentially abundant metabolites were mainly triterpene glycosides. The relative abundances of the two major notoginsenosides (MNs), ginsenosides Rd and Re, and 13 rare notoginsenosides (RNs), significantly increased. The differential saponins, especially RNs, were more easily clustered into one branch and had a high positive correlation. It could be concluded that the biosynthesis and accumulation of some RNs share the same pathways as those triggered by AMF. This study provides a new way to obtain more notoginsenoside resources, particularly RNs, and sheds new light on the scientization and rationalization of the use of AMF agents in the ecological planting of medicinal plants.

Abstract Background The detection of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer is critical for tyrosine kinase inhibitor therapy. EGFR detection requires tissue samples, which are difficult to obtain in some patients, costing them the opportunity for further treatment. To realize EGFR mutation prediction without molecular detection, we aimed to build a high-accuracy deep learning model with only haematoxylin and eosin (H&E)-stained slides. Methods We collected 326 H&E-stained non-small cell lung cancer slides from Beijing Chest Hospital, China, and used 226 slides (88 with EGFR mutations) for model training. The remaining 100 images (50 with EGFR mutations) were used for testing. We trained a convolutional neural network based on ResNet-50 to classify EGFR mutation status on the slide level. Results The sensitivity and specificity of the model were 76% and 74%, respectively, with an area under the curve of 0.82. When applying the double-threshold approach, 33% of the patients could be predicted by the deep learning model as EGFR positive or negative with a sensitivity and specificity of 100.0% and 87.5%. The remaining 67% of the patients got an uncertain result and will be recommenced to perform further examination. By incorporating adenocarcinoma subtype information, we achieved 100% sensitivity in predicting EGFR mutations in 37.3% of adenocarcinoma patients. Conclusions Our study demonstrates the potential of a deep learning-based EGFR mutation prediction model for rapid and cost-effective pre-screening. It could serve as a high-accuracy complement to current molecular detection methods and provide treatment opportunities for non-small cell lung cancer patients from whom limited samples are available.

Objectives: To investigate the association between duration of disability in activity of daily living (ADL) and overall survival in older individuals. Design: A prospective cohort study. Setting: Community-based data from Chinese Longitudinal Healthy Longevity Survey. Participants: In total, 13,560 participants without ADL disability and 2772 participants with ADL disability at baseline were included. Measurements: ADL disability was assessed using Katz index scale, which included six essential ADLs: dressing, bathing, transferring, toileting, continence, and eating. Dependence of each item was scored on a scale of 1, the maximum total score was 6. At baseline, duration of ADL disability was defined as the maximum duration among the six items. The study outcome was overall survival. Accelerated failure time models were constructed to investigate the association between duration of ADL disability and overall survival. Subgroup analyses by sex, age, and multimorbidites, as well as sensitive analyses were conducted. Results: During 81,868.7 person-years follow-up, 11,092 deaths were recorded. Overall, ADL disability was associated with lower overall survival compared to non-ADL disability. With duration of ADL disability extending, the overall survival strikingly dropped in the first 12 months, reaching its lowest point with adjusted time ratio (TR) at 0.66 (95%CI: 0.61−0.72, p

Abstract Background To develop a fully automatic framework for the diagnosis of cause for left ventricular hypertrophy (LVH) via cardiac cine images. Methods A total of 302 LVH patients with cine MRI images were recruited as the primary cohort. Another 53 LVH patients prospectively collected or from multi-centers were used as the external test dataset. Different models based on the cardiac regions (Model 1), segmented ventricle (Model 2) and ventricle mask (Model 3) were constructed. The diagnostic performance was accessed by the confusion matrix with respect to overall accuracy. The capability of the predictive models for binary classification of cardiac amyloidosis (CA), hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) were also evaluated. Additionally, the diagnostic performance of best Model was compared with that of 7 radiologists/cardiologists. Results Model 3 showed the best performance with an overall classification accuracy up to 77.4% in the external test datasets. On the subtasks for identifying CA, HCM or HHD only, Model 3 also achieved the best performance with AUCs yielding 0.895–0.980, 0.879–0.984 and 0.848–0.983 in the validation, internal test and external test datasets, respectively. The deep learning model showed non-inferior diagnostic capability to the cardiovascular imaging expert and outperformed other radiologists/cardiologists. Conclusion The combined model based on the mask of left ventricular segmented from multi-sequences cine MR images shows favorable and robust performance in diagnosing the cause of left ventricular hypertrophy, which could be served as a noninvasive tool and help clinical decision.

Abstract Background Whether healthy lifestyles mediate the association of socioeconomic status (SES) with mortality in older people is largely unknown. Methods A total of 22,093 older participants (age ≥ 65 years) from 5 waves (2002–2014) of Chinese Longitudinal Healthy Longevity Survey cohort were included for analysis. Mediation analysis of lifestyles on the association of SES with all-cause mortality was conducted. Results During a mean follow-up period of 4.92 ± 4.03 years, 15,721 (71.76%) deaths occurred. Compared with high SES, medium SES increased the risk of mortality by 13.5% (HR [total effect]: 1.135, 95% CI 1.067–1.205, p

Yunnan plays a pivotal role in transmitting electricity from west to east within China’s Southern Power Grid. During 7–13 January 2021, a large-scale continuous ice-covering event of ultra-high voltage (UHV) transmission lines occurred in the Qujing area of eastern Yunnan Province. Based on ERA5 reanalysis data and meteorological observation data of UHV transmission line icing in China’s Southern Power Grid, the synoptic causes of the icing are comprehensively analyzed from various perspectives, including weather situations, vertical stratification of temperature and humidity, local meteorological elements, and atmospheric circulation indices. The results indicate a strong East Asian trough and a blocking high directing northern airflow southward ahead of the ridge. Cold air enters the Qujing area and combines with warm and moist air from the subtropical high pressure of 50–110° E. As warm and cold air masses form a quasi-stationary front over the northern mountainous area of Qujing due to topographic uplift, the mechanism of “supercooling and warm rain” caused by the “warm–cold” temperature profile structure leads to freezing rain events. Large-scale circulation indices in the Siberian High, East Asian Trough, and 50–110° E Subtropical High regions provided clear precursor signals within 0–2 days before the icing events.

Objectives The application of artificial intelligence (AI) to the field of pathology has facilitated the development of digital pathology, hence, making AI-assisted diagnosis possible. Due to the variety of lung cancers and the subjectivity of manual evaluation, invasive non-mucinous lung adenocarcinoma (ADC) is difficult to diagnose. We aim to offer a deep learning solution that automatically classifies invasive non-mucinous lung ADC histological subtypes.Design For this investigation, 523 whole-slide images (WSIs) were obtained. We divided 376 of the WSIs at random for model training. According to WHO diagnostic criteria, six histological components of invasive non-mucinous lung ADC, comprising lepidic, papillary, acinar, solid, micropapillary and cribriform arrangements, were annotated at the pixel level and employed as the predicting target. We constructed the deep learning model using DeepLab v3, and used 27 WSIs for model validation and the remaining 120 WSIs for testing. The predictions were analysed by senior pathologists.Results The model could accurately predict the predominant subtype and the majority of minor subtypes and has achieved good performance. Except for acinar, the area under the curve of the model was larger than 0.8 for all the subtypes. Meanwhile, the model was able to generate pathological reports. The NDCG scores were greater than 75%. Through the analysis of feature maps and incidents of model misdiagnosis, we discovered that the deep learning model was consistent with the thought process of pathologists and revealed better performance in recognising minor lesions.Conclusions The findings of the deep learning model for predicting the major and minor subtypes of invasive non-mucinous lung ADC are favourable. Its appearance and sensitivity to tiny lesions can be of great assistance to pathologists.

This study simulated the wind energy density distribution in the Jiaodong Peninsula region using the Weather Research and Forecasting (WRF) Model. The impacts of different boundary-layer and near-surface parameterization schemes on the simulated wind speed and direction were investigated. The results indicate that the Yonsei University (YSU) scheme and the Quasi-Normal Scale Elimination (QNSE) scheme performed optimally for wind speed and wind direction. We also conducted a sensitivity test of the simulation results for atmospheric pressure, air temperature, and relative humidity. The statistical analysis showed that the YSU scheme performed optimally, while the MRF and BL schemes performed poorly. Following this, the wind energy distribution in the coastal hilly areas of the Jiaodong Peninsula was simulated using the YSU boundary-layer parameterization scheme. The modeled wind energy density in the mountainous and hilly areas of the Jiaodong Peninsula were higher than that in other regions. The wind energy density exhibits a seasonal variation, with the highest values in spring and early summer and the lowest in summer. In spring, the wind energy density over the Bohai Sea is higher than over the Yellow Sea, while the opposite trend is modeled in summer.

Abstract Background Recently, a new metabolic health (MH) definition was developed from NHANES-III. In the origin study, the definition may stratify mortality risks in people who are overweight or normal weight. We aimed to investigate the association between the new MH definition and all-cause mortality in a nonobese Chinese population. Methods The data were collected in 1992 and then again in 2007 from the same group of 1157 participants. The association between the new MH definition and all-cause mortality were analyzed by Cox regression models with overlap weighting according to propensity score (PS) as primary analysis. Results At baseline in 1992, 920 (79.5%) participants were categorized as MH, and 237 (20.5%) participants were categorized as metabolically unhealthy (MUH) based on this new definition. During a median follow-up of 15 years, all-cause mortality occurred in 17 (1.85%) participants in MH group and 13 (5.49%) in MUH group, respectively. In the crude sample, Kaplan–Meier analysis demonstrated a significantly higher all-cause mortality in MUH group when compared to MH group (log-rank p = 0.002), and MUH was significantly associated with increased all-cause mortality when compared to MH with HR at 3.04 (95% CI: 1.47–6.25, p = 0.003). However, Kaplan–Meier analysis with overlap weighting showed that the cumulative incidence of all-cause mortality was not significantly different between MH and MUH groups (adjusted p = 0.589). Furthermore, in the primary multivariable Cox analysis with overlap weighting, adjusted HR for all-cause mortality was 1.42 (95% CI: 0.49—4.17, p = 0.519) in MUH group in reference to MH group. Other additional PS analyses also showed the incidence of all-cause mortality was not significantly different between the two groups. Conclusion The new MH definition may be not appropriate for mortality risk stratification in non-obese Chinese people. Further investigations are needed.

Abstract Background The metabolic syndrome (Mets) is a multiplex risk factor for atherosclerotic cardiovascular diseases. The aims of the study were to assess the association of the Mets with TyG index and TyG-related parameters in an urban Chinese population. Methods The data were collected in 1992 and then again in 2007 from the same group of 590 individuals (363 males and 227 females) without Mets in 1992. The fasting lipid profile and blood glucose were measured. TyG index and related parameters were calculated, and Mets defined according to the harmonized criteria. The area under the curve (AUC) of receiver operating characteristic curves was used to evaluate TyG index and related parameters for their diagnostic ability to identify people with Mets. Odd ratios (OR) for Mets prediction were calculated using stepwise logistic regression analyses. Results The incidence of Mets was 18.64% over the 15-year follow-up period.During 15 years’ follow-up, TyG-waist to height ratio (TyG-WHtR) shows the largest AUC for Mets detection (0.686) followed by TyG-waist circumference (TyG-WC) (0.660), TyG-waist-to-hip ratio (TyG-WHpR) (0.564), and TyG index (0.556) in all participants. Gender analysis revealed that TyG-WHtR and TyG-WC have the largest AUC in both genders. TyG-WHtR significantly predicted Mets in all participants, with an unadjusted odds ratio of 5.63 (95% CI 3.23–9.83 P

Background: Hypoxia is an essential cause of fatigue and aging, and is associated with the occurrence and development of many diseases. Polygonatum kingianum (PK) is a deficiency-nourishing Chinese herbal medicine utilized as both medicine and food, and it has long been used to ameliorate human conditions associated with fatigue and aging over 2000 years in China. PK is an important genuine-medicinal-materials cultivated in Yunnan, China, and is used by the Bai, Wa, and Zhuang nationalities as a traditional medicine for enhancing immunity, anti-fatigue, and anti-aging, while the preventive effect of PK on hypoxia-induced injury and the underlying mechanism are indefinite. Aim of the study: The present study aimed to evaluate the anti-hypoxia efficacy and understand the corresponding mechanism of PK water extract. Materials and methods: The main active ingredients and targets of PK were predicted using network pharmacology, and the anti-hypoxia activities of Gracillin and Liquiritigenin were verified by in vitro experiments. The pharmacodynamic experiments were conducted to evaluate the major signal pathways of PK for detecting anti-hypoxia activity. Results: Fifty active ingredients and 371 potential targets were screened by network pharmacology, then, we confirmed that Gracillin and Liquiritigenin were the main active components of PK to exert anti-hypoxia effect in vitro. The pharmacodynamic experiments revealed that PK enhanced the extension rate of the survival time (ERST) and regulated the targets-related biochemical parameters of rats under hypoxia, showing significant anti-hypoxia effects on rats. Conclusion: The network pharmacology results suggested that PK exerts its anti-hypoxia effect through a multi-component and multi-target manner. Simultaneously, we also observed that Gracillin (saponins) and Liquiritigenin (flavonoids) are the main active components of PK to play a role in anti-hypoxia. The anti-hypoxia effect of PK could be associated with scavenging excess free radicals, maintaining the activities of antioxidant enzymes, and inhibiting oxidative stress due to lipid peroxidation. These findings provide insight into the Polygonatum kingianum as promising medicines or healthcare products for preventing and treating hypoxia.

Background Hypertrophic cardiomyopathy (HCM) and hypertension coexist fairly frequently in clinical practice. However, the evidence about the impact of hypertension on the prognosis of HCM is limited. The present study aims to investigate the impact of hypertension on the prognosis of HCM patients. Methods A total of 468 HCM patients were enrolled, and patients were divided into hypertension group (31.8%) and non-hypertension group (68.2%). The primary study endpoint was HCM-related death, consisting of heart failure (HF)-related death, stroke-related death and sudden cardiac death (SCD). Associations between hypertension and HCM-related death were analyzed by Cox regression models with the use of propensity score matching (PSM) as primary analysis. Results There were 55 HCM-related death during a median follow-up time of 4.6 years, and the mortality rate was 2.53 per 100 person years. Kaplan-Meier analysis based on the crude cohort or PSM cohort revealed no significant difference regarding the HCM-related death between the two groups. In the crude cohort, both univariable and multivariable Cox regression analysis indicated that hypertension was not significantly associated with HCM-related death with hazard ratios (HR) at 0.74 (95% CI [0.40–1.36], p value: 0.329) and 0.77 (95% CI [0.35–1.71], p value: 0.521), respectively. Similarly, no strong evidence for an association was observed between hypertension and HCM-related death in the PSM cohort with unadjusted HR at 0.90 (95% CI [0.34–2.41]; p value: 0.838) and adjusted HR at 0.77 (95% CI [0.35–1.71]; p value: 0.521), respectively. Other propensity score methods, including overlap weighting and inverse probability treatment weighting demonstrated similar results. Sensitivity analysis also indicated that the concomitant hypertension did not significantly increase the risk of HF-related death, stroke-related death or SCD in HCM patients. Conclusion HCM-related death did not significantly differ between hypertension and non-hypertension groups, suggesting a negative impact of hypertension on the clinical prognosis of HCM patients.

Abstract Background Optimal projection is essential for valve deployment during transcatheter aortic valve implantation (TAVI). The purpose of this study was to propose an approach to predict optimal projection in TAVI candidates with different aortic valve anatomies. Methods 331 patients undergoing self-expanding TAVI were included and the so-called non-coronary cusp (NCC)-parallel technique was utilized, which generated the predicted projection by connecting NCC commissures on the transverse plane on the pre-procedural computed tomography images. Results 37.8% of the study cohort were bicuspid aortic valve (BAV) patients. Around 80% of both NCC-parallel views and final views were in the right anterior oblique (RAO) and caudal (CAU) quadrant. There was less than 5° change required from the NCC-parallel view to the final implanted view in 79% of tricuspid aortic valve (TAV) patients but only in 27% (13/48) of type 0 BAV patients with coronary arteries originated from the different cusps. After excluding the above mentioned BAV patients, 62.3% (48/77) of BAV patients needed less than 5° change to achieve optimal projection and only in 8 patients, the angular change was larger than 10° in either left/right anterior oblique or cranial/caudal direction. Conclusions The NCC-parallel technique provides reliable prediction for optimal projection in self-expanding TAVI in all TAV and most BAV patients, with a vast majority of views in the RAO and CAU quadrant.

Background: This study investigates the predictive value of the systemic immune-inflammation index (SII), which was calculated as platelet × neutrophil/lymphocyte ratio, for all-cause mortality in patients with hypertrophic cardiomyopathy (HCM). Methods: A total of 360 HCM patients were enrolled. They were divided into three groups based on the tertiles of baseline SII. The association between SII and all-cause mortality was analyzed. Results: There were 53 HCM patients who died during a mean follow-up time of 4.8 years (min: 6 days and max: 10.8 years), and the mortality rate was 3.0 per 100 person years. The cumulative mortality rate was significantly different among the three tertiles of SII (P = 0.004), and the mortality rate in tertile 3 was much higher than that in the first two tertiles. In reference to tertile 1, the fully adjusted hazard ratios of all-cause mortality were 1.02 for the tertile 2 (95% confidence interval [CI]: 0.45–2.31, P = 0.966) and 2.31 for tertile 3 (95% CI: 1.10–4.87, P = 0.027). No significant interactions between SII and other variables were observed during subgroup analysis. The discriminative power was better for mid-term outcome than that for short-term or long-term outcomes. Sensitivity analyses including patients with normal platelet and white blood cell count have revealed similar results. Conclusion: SII was a significant risk factor for all-cause mortality in HCM patients. However, the discriminative power was poor to moderate. It could be used in combination with other risk factors in mortality risk stratification in HCM.

Neonicotinoid insecticides (NIs) have been widely detected in environmental media and human body with concentrations reaching hundreds of nanomolar to micromolar levels. However, the information about their human health toxicology and mechanism is deficient. Previous studies have implied that NIs might exert estrogenic disruption and promote breast cancer progression, but the molecular mechanism is unclear, especially the molecular initiating event. G protein-coupled estrogen receptor (GPER), as a candidate therapeutic target, plays vital roles in the development of breast cancer. This work aimed to reveal the potential mechanism through GPER pathway. Firstly, we screened the activities of seven most common NIs on GPER signal pathway by calcium mobilization assay. Clothianidin, acetamiprid (ACE), and dinotefuran activated GPER most potently and ACE displayed the highest agonistic activity with the lowest observed effective concentration (LOEC) of 1 μM. The molecular docking and dynamics simulation showed favored interaction trend between the NIs and GPER. The three NIs with GPER activity induced 4T1 breast cancer cells migration and ACE showed the highest potency with LOEC of 100 nM. ACE also induced 4T1 cells proliferation at high concentration of 50 μM and up-regulated GPER expression in a dose-dependent manner. We speculated that both the induction effects of ACE on 4T1 cells proliferation and migration might be owing to the activation and up-regulation of GPER. By using 4T1-Luc cells injected orthotopic tumor model, we found that ACE also promoted in-situ breast cancer growth and lung metastasis in normal mouse dependent on GPER. However, ACE only promoted in-situ breast cancer growth through GPER but not lung metastasis in ovariectomized mice, implying that the ACE-induced lung metastasis should be related to endogenous estrogen from ovary. Overall, we demonstrated that NIs promoted breast cancer progression via GPER pathway at human related exposure levels and their female health risks need urgent concerns.

Background: There is no information about the clinical significance of the albumin-bilirubin (ALBI) score in patients with hypertrophic cardiomyopathy (HCM). Objective: We retrospectively performed clinical evaluations in 462 patients with HCM to estimate whether the ALBI score could be a new tool to predict mortality in HCM. Methods and Results: During a median follow-up of 4.7 years, HCM-related death occurred in 52 (11.3%) patients. Overall, there was a significant positive association between ALBI score and HCM-related death (adjusted hazard ratio [HR]: 1.79 per one standard deviation [SD] increment, 95% confidence interval [CI]: 1.36–2.35). When the score was assessed as tertiles, the adjusted HRs of HCM-related death were 1.30 (95% CI: 0.42–3.99) for the tertile 2 and 4.43 (95% CI: 1.65–11.89) for the tertile 3, compared with the tertile 1. Stratified analysis and E-value analysis suggested the robustness of the above-mentioned results. Meanwhile, time-dependent ROC analysis showed ALBI score could discriminate HCM-related death at various time points (AUC ranges: 0.725–0.850). Furthermore, exploratory analysis indicated the dynamic changes of ALBI score also could predict HCM-related death. Finally, multiple linear regression analysis suggested some pathogenetic pathways associated with HCM-related adverse outcomes significantly correlated with ALBI score, and the pathways included inflammation, myocardial injury, nutritional status and some clinical characteristics, but not abnormal cardiac structure and function itself. Conclusions: Higher ALBI score is a strong independent predictor of HCM-related death in patients with HCM.

The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (·OH) scavenging and superoxide anion radical (·O2−) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.

Abstract Background This study was performed to investigate the clinical significance of combined evaluation of both coronary artery disease (CAD) and high-sensitivity cardiac troponin T (hs-cTnT) for prediction of major adverse cardiovascular events (MACEs) in patients with hypertrophic cardiomyopathy (HCM). Methods We performed clinical evaluations, including coronary artery imaging and hs-cTnT measurement, in 162 patients with HCM. Results The patients were followed up for a median period of 3.7 years (interquartile range 2.4–5.6 years; total of 632.3 person-years [PYs]), during which time MACEs occurred in 24 (14.8%) patients. The incidence of MACEs was 6.4 and 2.7 per 100 PYs for patients with CAD and normal coronary arteries, respectively; similarly, the incidence was 5.8 and 2.1 per 100 PYs in patients with an elevated hs-cTnT concentration (> 14.0 ng/L) and a normal hs-cTnT concentration, respectively. The multivariate analysis suggested that CAD and an elevated hs-cTnT concentration tended to be positively associated with MACEs. When the groups were allocated according to these two markers, the patients were divided into four groups, which further improved the predictive values. The incidence of MACEs was 10.4 per 100 PYs in the CAD and elevated hs-cTnT group, which was much higher than the incidence in all other groups (range, 2.0–3.5 per 100 PYs). With the normal coronary arteries and normal hs-cTnT group serving as a reference, the adjusted hazard ratio was 5.0 (95% confidence interval 1.0–23.8; P = 0.046) for the CAD and elevated hs-cTnT group. In addition, the subgroup analysis showed similar findings among the patients without severe CAD. Conclusions In patients with HCM, combined evaluation of both CAD and hs-cTnT might facilitate more reliable prediction of MACEs than evaluation of a single marker. These may serve as clinically useful markers to guide risk management.

ObjectiveBecause of rapid economic growth and followed urban expansion in China, many people drinking natural water had to change their water sources to tap water. We aimed to test the unknown association that whether continued use of natural water for drinking is different from switching to tap water in all-cause mortality risks in elderly people.MethodsIn total, based on Chinese Longitudinal Healthy Longevity Survey, 26,688 elderly participants drinking natural water from childhood to young-old were included in the final analyses. Associations between whether changing drinking water sources or not and all-cause mortality risk were then estimated by Cox regression models with the use of multiple propensity score methods, and the primary analysis used propensity score matching, with other propensity score methods confirming the robustness of the results.ResultsBaseline characteristics were fairly well balanced by the three post-randomization methods. During a median follow-up period of 3.00 (IQR: 1.52, 5.73) years, 21,379 deaths were recorded. The primary analysis showed people using natural water unchangeably was associated with a lower risk of all-cause mortality than those switching to tap water in later life (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001). Other propensity score methods, as well as Cox regression analysis without using propensity score methods, showed similar results.ConclusionsAmong elderly people depending on natural water for drinking from their childhood to young-old in China, continued use of natural water was associated with a lower all-cause mortality risk than conversion to tap water later. Further studies in different countries and populations are needed to verify our conclusions.

ObjectiveWe sought to conduct a systematic review and meta-analysis of clinical adverse events in patients undergoing transcatheter aortic valve replacement (TAVR) with bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) anatomy and the efficacy of balloon-expandable (BE) vs. self-expanding (SE) valves in the BAV population. Comparisons aforementioned will be made stratified into early- and new-generation devices. Differences of prosthetic geometry on CT between patients with BAV and TAV were presented. In addition, BAV morphological presentations in included studies were summarized.MethodObservational studies and a randomized controlled trial of patients with BAV undergoing TAVR were included according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.ResultsA total of 43 studies were included in the final analysis. In patients undergoing TAVR, type 1 BAV was the most common phenotype and type 2 BAV accounted for the least. Significant higher risks of conversion to surgical aortic valve replacement (SAVR), the need of a second valve, a moderate or severe paravalvular leakage (PVL), device failure, acute kidney injury (AKI), and stroke were observed in patients with BAV than in patients with TAV during hospitalization. BAV had a higher risk of new permanent pacemaker implantation (PPI) both at hospitalization and a 30-day follow-up. Risk of 1-year mortality was significantly lower in patients with BAV than that with TAV [odds ratio (OR) = 0.85, 95% CI 0.75–0.97, p = 0.01]. BE transcatheter heart valves (THVs) had higher risks of annular rupture but a lower risk of the need of a second valve and a new PPI than SE THVs. Moreover, BE THV was less expanded and more elliptical in BAV than in TAV. In general, the rates of clinical adverse events were lower in new-generation THVs than in early-generation THVs in both BAV and TAV.ConclusionsDespite higher risks of conversion to SAVR, the need of a second valve, moderate or severe PVL, device failure, AKI, stroke, and new PPI, TAVR seems to be a viable option for selected patients with severe bicuspid aortic stenosis (AS), which demonstrated a potential benefit of 1-year survival, especially among lower surgical risk population using new-generation devices. Larger randomized studies are needed to guide patient selection and verified the durable performance of THVs in the BAV population.

Background The lymphocyte-to-monocyte ratio (LMR) has been proposed as a novel prognostic factor in malignancies and cardiovascular diseases. Our study aimed to ascertain whether LMR is a useful biomarker in discriminating the hypertrophic cardiomyopathy (HCM) patients at higher risk of all-cause mortality. Methods This retrospective study consisted of 354 adult HCM patients. Cox’s proportional hazards regression models were used to analyze the association between LMR and all-cause mortality. Smooth curve fitting was conducted to explore the linear relationship between LMR and all-cause mortality. Results During the follow-up, 44 patients reached the study endpoint. The all-cause mortality rate was 7.3 per 100 person-years in the first tertile and decreased across the three tertiles of LMR. With the first tertile as reference, adjusted hazard ratios (HR) for all-cause mortality were 0.43 for the second tertile (95% CI [0.20–0.91], p = 0.027) and 0.39 for the third tertile (95% CI [0.17–0.90], p = 0.028), respectively. Smooth curve fitting exhibited a nonlinear relationship between LMR values and all-cause mortality. For LMR < 6.5, per SD increase resulted in a significantly decreased risk of all-cause mortality by 62% (HR: 0.38, 95% CI [0.21–0.68]). For LMR ≥ 6.5, the all-cause mortality risk did not progressively increase. Stratified and subgroup analyses revealed similar results to the main analyses,andE-value analysis suggested robustness to unmeasured confounding. Conclusions The study demonstrated that LMR was an independent predictor of all-cause mortality in HCM patients, and LMR may be useful for identifying HCM patients at high mortality risk.

Objective: To validate the modified R-CHA2DS2VASc score as a predictor of thromboembolism in HCM patients. Methods: A total of 446 HCM patients were enrolled in our study, thirty-one (6.95%) patients experienced thromboembolic events during the follow-up time of 1786.7 person-years. The association between R-CHA2DS2VASc score and risk of thromboembolism was assessed by Cox’s proportional hazard analysis. The discriminatory power of R-CHA2DS2VASc score for thromboembolism prediction was assessed by Harrell’s C-statistic and validated internally by bootstrapping methods. Calibration plot was plotted by observed versus expected probabilities of thromboembolism. Results: The R-CHA2DS2VASc score was well calibrated with 0.84 thromboembolic events per 100 person-years in the predefined low risk (R-CHA2DS2VASc score ≤2) group, 1.84 in the low to moderate risk (R-CHA2DS2VASc score 3-4) group, 4.67 in the moderate to high risk (R-CHA2DS2VASc score 5-7) group, and 17.54 in the high risk (R-CHA2DS2VASc score ≥8) group. Hazard ratios for thromboembolism were 2.88 (95%CI: 1.06-7.82, P=0.038) for low to moderate versus low risk group, 5.30 (95%CI: 2.14-13.12, P=0.0003) for moderate to high versus low risk group, and 16.57 5.30 (95%CI: 4.96-55.33, P

Abstract Background Panax notoginseng is a medicinally important Chinese herb with a long history of cultivation and clinical application. The planting area is mainly distributed in Wenshan Prefecture, where the quality and safety of P. notoginseng have been threatened by high concentration of arsenic (As) from the soil. The roles of phosphate (Pi) transporters involved in Pi acquisition and arsenate (AsV) tolerance were still unclear in this species. Results In this study, two open reading frames (ORFs) of PnPht1;1 and PnPht1;2 separated from P. notoginseng were cloned based on RNA-seq, which encoded 527 and 541 amino acids, respectively. The results of relative expression levels showed that both genes responded to the Pi deficiency or As exposure, and were highly upregulated. Heterologous expression in Saccharomyces cerevisiae MB192 revealed that PnPht1;1 and PnPht1;2 performed optimally in complementing the yeast Pi-transport defect, particularly in PnPht1;2. Cells expressing PnPht1;2 had a stronger AsV tolerance than PnPht1;1-expressing cells, and accumulated less As in cells under a high-Pi concentration. Combining with the result of plasma membrane localization, these data confirmed that transporters PnPht1;1 and PnPht1;2 were putative high-affinity H+/H2PO4 − symporters, mediating the uptake of Pi and AsV. Conclusion PnPht1;1 and PnPht1;2 encoded functional plasma membrane-localized transporter proteins that mediated a putative high-affinity Pi/H+ symport activity. Expression of PnPht1;1 or PnPht1;2 in mutant strains could enhance the uptake of Pi and AsV, that is probably responsible for the As accumulation in the roots of P. notoginseng.

Background. No study has examined the effect of low serum uric acid (SUA) concentrations on mortality in hypertrophic cardiomyopathy (HCM) patients. The aim of the present study was to assess the relations between both low and high SUA concentrations and the risk of mortality across the full range of SUA concentrations in a retrospective cohort of HCM patients. Methods. A total of 454 HCM patients were enrolled in the study, and SUA concentrations were measured at baseline. The primary and secondary endpoints were all-cause mortality and HCM-related mortality, respectively. The associations between SUA concentrations and endpoints were analysed. Results. During a median follow-up of 3.8 years, there were 80 (17.6%) all-cause mortality events, and 52 of them (11.5%) were ascribed to HCM-related mortality. Patients with SUA concentrations of 250–350 µmol/L had the lowest all-cause mortality rate (11.8%) and HCM-related mortality rate (5.0%). Both low and high SUA concentrations were associated with increased all-cause and HCM-related mortality. Adjusted HRs were 2.52 (95% CI 1.13–5.61, p = 0.024) and 4.86 (95% CI 1.74–13.58, p = 0.003) for all-cause mortality and HCM-related mortality in the lowest SUA group (

The prevalence of diabetes is increasing rapidly and becoming a major public health issue worldwide. We aimed to develop a novel nomogram model for long-term diabetic risk prediction in a Chinese population. A prospective cohort study was performed on 687 nondiabetic individuals who underwent routine physical examination in 1992 and 2007. Using the least absolute shrinkage and selection operator model to optimize feature selection. Multiple Cox regression analysis was performed, and a simple nomogram was constructed. The area under receiver operating characteristic curve (AUC) and calibration plot were conducted to assess the predictive accuracy of the model. The model was subjected to bootstrap internal validation. Of the 687 participants without diabetes at baseline, 74 developed diabetes during the follow-up time. This simple nomogram model was constructed by family history of diabetes, height, waist circumference, triglycerides, fasting plasma glucose and white blood cell count. The AUCs were 0.812 (95% CI: 0.729–0.895) and 0.794 (95% CI: 0.734–0.854) for 10-year and 15-year diabetic risk. The bootstrap corrected c-index was 0.771 (95% CI: 0.721–0.821). The calibration plot also achieved good agreement between observational and actual diabetic incidence. The stratification into different risk groups by optimal cut-off value of 12.8 allowed significant distinction between cumulative diabetic incidence curves in the whole cohort and several subgroups. We established and internally validated a novel nomogram which can provide individual diabetic risk prediction for Chinese population and this practical screening model may help clinicians to identify individuals at high risk of diabetes.

In the present paper, the effect of mechanical ball milling time on the fretting wear of GCr15 steel balls at different displacement amplitudes is investigated. TiC powder coating was fabricated on the surface of GCr15 steel balls using various process times, and the fretting wear tests were conducted on an AISI 52100 steel disk with the applied force of 80 N. Additionally, various displacement amplitudes (10 μm, 20 μm, and 60 μm) were selected. Specimen attributes and wear scars were characterized using an inverted metallographic microscope, a microhardness tester, an X-ray diffractometry analyzer, a white light interferometer, and a scanning electron microscope. The results showed that thick and continuous coatings could be obtained at the milling time of 18 h. The specimens processed for a longer milling time demonstrated better fretting wear resistance, which we attribute to higher microhardness of the surface layer. The coefficient of friction and wear volume of specimens at each different displacement amplitude significantly decreased with increasing milling time. As the displacement amplitude increased, the three fretting states were: partial slip coordinated by elastic deformation; partial slip state coordinated by plastic deformation; and gross slip condition. Our observations indicate that mechanical ball milling could be an efficient approach to improve the fretting wear resistance of GCr15 steel balls.

Objective: Polygonatum kingianum is a traditional Chinese medicine commonly used to treat diabetes and hyperlipidemia. Polysaccharides from Polygonatum kingianum could regulate glucose and lipid metabolism in high-fat diet (HFD) rats. Methods: The gel permeation chromatography (GPC), liquid chromatography (HPLC) and chemical analysis were used to determine the molecular weight, monosaccharide composition, protein, polysaccharide and uronic acid content of the polysaccharide from Polygonatum kingianum, respectively. Total (PS) and high molecular weight (PSF) polysaccharides (> 100 KDa) were isolated and treated HFD rats for a 14-week period. TC, TG contents in blood samples were measured every two weeks, and HDL-C, LDL-C was measured at 12 and 14 weeks evaluating of blood lipids regulation activity of polysaccharide. The stool samples were used for 16S rDNA V4 highly variable region measurement method to regulate the role of polysaccharide in the intestinal microflora. The content of short chain fatty acid (SCFAs) in faeces was determined by gas chromatography (GC) to investigate the effect of polysaccharides on the content of SCFAs in the intestinal tract of rats. The expression of tight junction protein ZO-1 and occludin of intestinal tissue, and detection of the key protein expression in the LPS-TLR4/NFκB signaling pathway were detected by Western blot technique. Results: We found that PS and PSF improved both diabetic symptoms and lipid metabolism. PS and PSF also modulated the gut microbiota composition, abundance and diversity of HFD rats, increased the relative abundance of short chain fatty acid (SCFA) producing bacteria and increased SCFA production, reduced intestinal permeability, relieved gastrointestinal inflammation, and improved lipid metabolism. Conclusion: Polygonatum kingianum polysaccharides regulated the abundance and diversity of the intestinal microbial community through increasing the relative abundance of SCFA-producing bacteria. This promotes recovery of the intestinal permeability barrier, inhibits LPS entry into the circulation, alleviates inflammation, and prevents glucose and lipid metabolic disorders.

(E)-N,N-dimethyl-4-oxo-4-(4-(pyridin-4-yl)phenyl)but-2-enamide hydrochloride (IMB-YH-4py5-2H) is a novel Protein Kinase B (PknB) inhibitor with potent activity against Mycobacterium tuberculosis strains. In the present study, a sensitive and specific liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated to determine IMB-YH-4py5-2H in rat plasma. Sample pretreatment was achieved by liquid-liquid extraction with ethyl acetate, and separation was performed on an XTerra MS C18 column (2.1×50 mm, 3.5 μm) with gradient elution (methanol and 0.1% formic acid) at a flow rate of 0.3 mL/min. Detection was performed in multiple reaction monitoring (MRM) mode. Linear calibration curves were obtained over a concentration range of 1-100 ng/mL. The intra-day and inter-day precisions were lower than 8.46%, and the accuracies ranged from -8.71% to 12.36% at all quality control levels. The extraction recoveries were approximately 70%, and the matrix effects were negligible. All quality control samples were stable under different storage conditions. The validated method was successfully applied to a preclinical pharmacokinetic study in Sprague-Dawley rats. IMB-YH-4py5-2H demonstrated improved pharmacokinetic properties (higher exposure level) compared with its leading compound. IMB-YH-4py5-2H was also distributed throughout the lung pronouncedly, especially inside alveolar macrophages, indicating its effectiveness against lower respiratory infections.

Polygonatum kingianum Collett & Hemsl is one of the famous traditional Chinese herbs with satisfactory therapeutic effects on invigorating Qi, nourishing Yin and moistening lungs, in which steroidal saponins are one class of important active substances. The main purpose is to determine the optimal extraction technology of steroidal saponins and evaluate the quality of P. kingianum planted in five different areas. The optimal ultrasonic-assisted extraction (UAE) technology was established by using single-factor experiments and the response surface methodology (RSM), and the determination method of high-performance liquid chromatography (HPLC) for dioscin and diosgenin, two primary types of acid-hydrolyzed steroidal saponins, was constructed with good linear range and precision. The results showed that UAE was an efficient extraction method for steroidal saponins, and the extraction yield was significantly affected by the liquid-solid ratio. The optimal extraction technology was generated following a liquid-solid ratio of 10:1 (mL/g), an ethanol concentration of 85% (v/v), an extraction time of 75 min, an extraction temperature of 50 °C and three extractions, of which these parameters were in line with the predicted values calculated by RSM. Considering only dioscin and diosgenin, the quality of P. kingianum planted at five sample plots presented non-significant difference. However, the content of diosgenin in Pingbian Prefecture (PB) was higher than that of the other four areas with a value of 0.46 mg/g. Taken together, the optimal UAE technology for P. kingianum steroidal saponins was determined via RSM. The quality evaluation revealed that there was a non-significant difference among P. kingianum planted in different areas based on the contents of the sum of dioscin and diosgenin. This work has important reference value for the exploitation and utilization of P. kingianum.

For the controllability of the transmission power of DC transmission channels, the optimal power distribution (OPD) of AC-DC parallel transmission channels is an effective measure for improving the economic operation of an AC-DC interconnected power grid. A dynamic optimal power flow model for day-ahead OPD of AC-DC parallel transmission channels is established in this paper. The power flow equation constraints of an AC-DC interconnected power grid and the constraints of the discrete regulation requirement of the transmission power of DC channels are considered, which make the OPD model of the AC-DC parallel transmission channels a mixed-integer nonlinear non-convex programming (MINNP) model. Through a cone relaxation transformation and a big M method equivalent transformation, the non-convex terms in the objective function and constraints are executed with the convex relaxation, and the MINNP model is transformed into a mixed-integer second-order cone programming model that can be solved reliably and efficiently using the mature optimization solver GUROBI. Taking an actual large-scale AC-DC interconnected power grid as an example, the results show that the OPD scheme of the AC-DC parallel transmission channels obtained by the proposed algorithm can effectively improve the economical operation of an AC-DC interconnected power grid.

Due to the unbalanced three-phase loads, the single-phase distributed photovoltaic (PV) integration, the long feeders, and the heavy loads in a three-phase four-wire low voltage distribution network (LVDN), the voltage unbalance factor (VUF), the network loss and the voltage deviation are relatively high. Considering the uncertain fluctuation of the PV output and the load power, a robust optimal allocation of decentralized reactive power compensation (RPC) devices model for a three-phase four-wire LVDN is proposed. In this model, the uncertain variables are described as box uncertain sets, the three-phase simultaneous switching capacity and single-phase independent switching capacity of the RPC devices are taken as decision variables, and the objective is to minimize the total power loss of the LVDN under the extreme scenarios of uncertain variables. The bi-level optimization method is used to transform the robust optimization model with uncertain variables into bi-level deterministic optimization models, which could be solved alternately. The nonlinear programming solver IPOPT in the mature commercial software GAMS is adopted to solve the upper and lower deterministic optimization models to obtain a robust optimal allocation scheme of decentralized RPC devices. Finally, the simulation results for an actual LVDN show that the obtained decentralized RPC scheme can ensure that the voltage deviation and the VUF of each bus satisfied the secure operation requirement no matter how the PV output and load power changed within their own uncertain sets, and the network loss could be effectively reduced.