The density of the inner cell mass is a new indicator of the quality of a human blastocyst: a valid supplement to the Gardner scoring system.

STUDY QUESTION: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst? SUMMARY ANSWER: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth. WHAT IS KNOWN ALREADY: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further. STUDY DESIGN, SIZE, DURATION: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM. MAIN RESULTS AND THE ROLE OF CHANCE: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone. LIMITATIONS, REASONS FOR CAUTION: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Multiple collapses of blastocysts after full blastocyst formation is an independent risk factor for aneuploidy - a study based on AI and manual validation.

BACKGROUND: The occurrence of blastocyst collapse may become an indicator of preimplantation embryo quality assessment. It has been reported that collapsing blastocysts can lead to higher rates of aneuploidy and poorer clinical outcomes, but more large-scale studies are needed to explore this relationship. This study explored the characteristics of blastocyst collapse identified and quantified by artificial intelligence and explored the associations between blastocyst collapse and embryo ploidy, morphological quality, and clinical outcomes. METHODS: This observational study included data from 3288 biopsied blastocysts in 1071 time-lapse preimplantation genetic testing cycles performed between January 2019 and February 2023 at a single academic fertility center. All transferred blastocysts are euploid blastocysts. The artificial intelligence recognized blastocyst collapse in time-lapse microscopy videos and then registered the collapsing times, and the start time, the recovery duration, the shrinkage percentage of each collapse. The effects of blastocyst collapse and embryo ploidy, pregnancy, live birth, miscarriage, and embryo quality were studied using available data from 1196 euploid embryos and 1300 aneuploid embryos. RESULTS: 5.6% of blastocysts collapsed at least once only before the full blastocyst formation (tB), 19.4% collapsed at least once only after tB, and 3.1% collapsed both before and after tB. Multiple collapses of blastocysts after tB (times ≥ 2) are associated with higher aneuploid rates (54.6%, P > 0.05; 70.5%, P < 0.001; 72.5%, P = 0.004; and 71.4%, P = 0.049 in blastocysts collapsed 1, 2, 3 or ≥ 4 times), which remained significant after adjustment for confounders (OR = 2.597, 95% CI 1.464-4.607, P = 0.001). Analysis of the aneuploid embryos showed a higher ratio of collapses and multiple collapses after tB in monosomies and embryos with subchromosomal deletion of segmental nature (P < 0.001). Blastocyst collapse was associated with delayed embryonic development and declined blastocyst quality. There is no significant difference in pregnancy and live birth rates between collapsing and non-collapsing blastocysts. CONCLUSIONS: Blastocyst collapse is common during blastocyst development. This study underlined that multiple blastocyst collapses after tB may be an independent risk factor for aneuploidy which should be taken into account by clinicians and embryologists when selecting blastocysts for transfer.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

Enhancing clinical utility: deep learning-based embryo scoring model for non-invasive aneuploidy prediction.

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.

Understanding community-dwelling older adults' preferences for home- and community-based services: A conjoint analysis.

BACKGROUND: Older adults' preference for home- and community-based service programs has been highlighted as an essential but usually ignored ingredient in current care models. Disentangling how preferences contribute to older adults' decision-making could facilitate finding optimal ways to deliver home- and community-based services in times of increasing scarcity. OBJECTIVE: To identify Chinese community-dwelling older adults' preference structure for home- and community-based services and thus to optimize service provision. METHODS: Conjoint analysis, a preference-based technique, was employed to study older adults' preferences. A stepwise qualitative approach was first adopted to identify the attributes and attribute levels of home- and community-based services. Scenarios were defined through an orthogonal fractional factorial design, and a cross-sectional survey was conducted through a face-to-face, anonymous questionnaire. Conjoint analysis was performed to determine preference weights representing the relative importance of the identified attributes, and cluster analysis was performed to identify clusters of participants with similar preference structures. All data analyses were performed using SAS v9.4 and SPSS 22.0. RESULTS: A total of 321 of 350 invited participants completed the questionnaire. Four attributes were identified and used to create the conjoint scenarios: care-giving attitude, price, technical care-giving skills, and the type of service provider. Care-giving attitude was the most valued attribute for older adults when making decisions (relative importance score = 48.28), followed by price (relative importance score = 21.618), technical care-giving skills (relative importance score = 19.518), and finally, the type of service provider (relative importance score = 10.585). Three preference phenotypes were identified by applying cluster analysis: "price-oriented", "comprehensively balanced", and "attitude-oriented". CONCLUSION: The present study underscored the importance of considering attributes valued by Chinese older adults in the design and delivery of home- and community-based services. The preference structure, including the utility score of the attribute levels, differs among older adults. The findings could inform future research and practice and suggest incorporating flexibility during the service delivery stage.

Virtual Screening of Nrf2 Dietary-Derived Agonists and Safety by a New Deep-Learning Model and Verified In Vitro and In Vivo.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an essential regulatory target of antioxidants, but the lack of Nrf2 active site information has hindered discovery of new Nrf2 agonists from food-derived compounds by large-scale virtual screening. Two deep-learning models were separately trained to screen for Nrf2-agonists and safety. The trained models screened potentially active chemicals from approximately 70,000 dietary compounds within 5 min. Of the 169 potential Nrf2 agonists identified via deep-learning screening, 137 had not been reported before. Six compounds selected from the new Nrf2 agonists significantly increased (p < 0.05) the activity of Nrf2 on carbon tetrachloride (CCl4)-intoxicated HepG2 cells (nicotiflorin (99.44 ± 18.5%), artemetin (97.91 ± 8.22%), daidzin (87.73 ± 3.77%), linonin (74.27 ± 5.73%), sinensetin (72.74 ± 10.41%), and tectoridin (77.78 ± 4.80%)), and their safety were demonstrated by an MTT assay. The safety and Nrf2 agonistic activity of nicotiflorin, artemetin, and daidzin were also reconfirm by a single-dose acute oral toxicity study and CCl4-intoxicated rat assay.

Regulation of cleavage embryo genes upon DRP1 inhibition in mouse embryonic stem cells.

Dynamic-related protein 1 (DRP1) is a key protein of mitochondrial fission. In this study, we found that inhibition of activity of DRP1 led to increased levels of cleavage embryo genes in mouse embryonic stem cells (mESCs), which might reflect a transient totipotency status derived from pluripotency. This result indicates that DRP1 inhibition in mESCs leads to a tendency to obtain a new expression profile similar to that of the 2C-like state. Meanwhile, we also noticed that the glycolysis/gluconeogenesis pathway and its related enzymes were significantly downregulated, and the key glycolytic enzymes were also downregulated in various 2C-like cells. Moreover, when DRP1 activity was inhibited from the late zygote when cleavage embryo genes started to express, development of early embryos was inhibited, and these cleavage embryo genes failed to be efficiently silenced at the late 2-cell (2C) stage. Taken together, our result shows that DRP1 plays an important role in silencing cleavage embryo genes for totipotency-to-pluripotency transition.

Application of the International Classification of Functioning, Disability and Health (ICF) in dementia research and practice: A scoping review.

OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) endorsed by the World Health Organization provides a conceptual framework for describing functioning and disability based on a biopsychosocial model. Although dementia is one of the leading causes of disability, yet little is known on the extent to how the ICF has been utilized in dementia research and practice. The study aimed to examine and map the current applications of the ICF with dementia from a body of earlier studies and to explore the potential use in person-centred dementia care. METHODS: The Arksey and O'Malley framework was used to guide the searching, selecting, and synthesizing process. The scoping review was reported following The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines. RESULTS: A total of 34 studies were included. The applications of ICF were classified into 4 themes: (1) in clinical practice and the education of health professionals (n = 20); (2) community support services and income support (n = 3); (3) population-based, census, or survey data (n = 10); (4) advocacy and empowerment purposes (n = 1). CONCLUSION: The ICF has made a major impact on dementia in clinical settings. Findings strongly support applying the ICF to person-centered dementia care. In the future, more empirical studies are needed to expand the scope of ICF use in dementia research and practice.

Artificial intelligence in elderly healthcare: A scoping review.

The ageing population has led to a surge in the adoption of artificial intelligence (AI) technologies in elderly healthcare worldwide. However, in the advancement of AI technologies, there is currently a lack of clarity about the types and roles of AI technologies in elderly healthcare. This scoping review aimed to provide a comprehensive overview of AI technologies in elderly healthcare by exploring the types of AI technologies employed, and identifying their roles in elderly healthcare based on existing studies. A total of 10 databases were searched for this review, from January 1 2000 to July 31 2022. Based on the inclusion criteria, 105 studies were included. The AI devices utilized in elderly healthcare were summarised as robots, exoskeleton devices, intelligent homes, AI-enabled health smart applications and wearables, voice-activated devices, and virtual reality. Five roles of AI technologies were identified: rehabilitation therapists, emotional supporters, social facilitators, supervisors, and cognitive promoters. Results showed that the impact of AI technologies on elderly healthcare is promising and that AI technologies are capable of satisfying the unmet care needs of older adults and demonstrating great potential in its further development in this area. More well-designed randomised controlled trials are needed in the future to validate the roles of AI technologies in elderly healthcare.

Are Early Embryo Cleavage Kinetics Affected by Energy Substrates in Different Culture Media?

OBJECTIVE: This study aimed to investigate the influence of different culture media on early embryonic cleavage kinetics using time-lapse analysis and to determine the possible relationships between energy substrates in culture media and the cleavage kinetics. METHODS: A total of 10 021 embryos from 1310 couples were cultured in time-lapse incubators. Embryos cultured in Vitrolife media were allocated to group I, and those in COOK media to group II. Embryo cleavage time points up to the 8-cell stage (t2-t8) were observed after pronuclei fading. RESULTS: The baseline demographic features, in vitro fertilization indications, ovarian stimulation protocol, oocyte-cumulus complexes, fertilization rate, together with pregnancy and perinatal outcomes were similar (P>0.05) between groups I and II. According to the time-lapse analysis, all embryos in group I showed significantly faster cleavage speed than those in group II (P<0.05). Furthermore, there was better synchrony in division (s3) and a longer length of the third cell cycle duration (cc3) in group II. Interestingly, implanted embryos in group II showed faster cleavage speed than those in group I, especially at t4 and t7. The glucose contents and multiple major amino acids were similar between the two groups. Lactic and pyruvic acid contents were generally higher in group I than those in group II. CONCLUSION: Because different commercial culture media may influence cleavage kinetics of embryos, it is essential for embryologists to take culture media into consideration in selecting a potential embryo when using a time-lapse system before implantation.

Cytoplasmic strings between ICM and mTE are a positive predictor of clinical pregnancy and live birth outcomes: A time-lapse study.

Background: Elective single blastocyst transfer (eSBT) is considered to reduce the incidence of multiple pregnancy compared to double embryo transfer. Blastocyst selection is the key to achieving pregnancy. In the past, morphological assessment was the main criterion used to select blastocyst. Some important morphological parameters are considered to be clinically valuable, such as cytoplasmic strings traversing from the inner cell mass (ICM) and mural trophectoderm (mTE). Methods: In this study, 1,267 elective frozen-thawed eSBT cycles cultured in a time-lapse culture system from January 2018 to May 2019 were included. Blastocysts were grouped into "present" and "absent" according to the appearance of cytoplasmic strings between ICM and mTE cells. The "present" group was further categorized according to the quantity of cytoplasmic strings between the ICM and mTE cells. Results: A time-lapse analysis indicated that cytoplasmic strings between ICM and mTE were more visible among good quality blastocysts. Furthermore, blastocysts with cytoplasmic strings showed higher clinical pregnancy and live birth rates (P = 0.011 and 0.003), while no significant differences were observed in abortion rate and birth weight (P = 0.466 and 0.556). Conclusions: In conclusion, although the results of previous studies about cytoplasmic strings have been controversial, the present time-lapse analysis provides evidence for the first time that cytoplasmic strings between ICM and mTE cells are a positive predictor of clinical pregnancy and live birth outcomes in elective frozen-thawed single blastocyst transfer cycles.

Quantitative assessment of the relative contributions of climate change and human activities to NPP changes in the Southwest Karst area of China.

Net primary production (NPP) is an essential component of the terrestrial carbon cycle and an essential factor of ecological processes. In global change research, it was the core content to study the driving forces of NPP change. In this paper, we focused on the Southwest Karst area of China and analyzed the response mechanisms of NPP to topography, land-use types, climatic change, and human activities. Our results showed that (1) changes in elevation and slope lead to significant differences in the spatial distribution of NPP. With the increase of elevation and slope, NPP first increased and then decreased, their critical values were 2000 m and 15°, respectively. (2) NPP varied significantly among different land-use types. The average NPP of the forest was the highest, and the average NPP of cultivated land increased fastest. (3) Temperature and precipitation had the most substantial influence on NPP, both of them promoted the increase of NPP, and the effect of temperature was more obvious in the Southwest Karst area. (4) Ecological engineering significantly promoted the change of NPP, while animal husbandry significantly inhibited the change of NPP. (5) There were significant spatial differences in the driving effects and corresponding contributions of climatic change and human activities; both of them promoted the increase of NPP in the Southwest Karst area of China. Under climatic change and human activities, NPP increased by 1.24 gC·m-2·year-1 and 2.29 gC·m-2·year-1, respectively. The contributions rates of climatic change and human activities separately accounted for 35% and 65%. The contribution of human activities on NPP was much higher than that of climatic change in the Southwest Karst area, and the results suggested that we should focus on the role of human activities on NPP change.

Using deep learning to predict the outcome of live birth from more than 10,000 embryo data.

BACKGROUND: Recently, the combination of deep learning and time-lapse imaging provides an objective, standard and scientific solution for embryo selection. However, the reported studies were based on blastocyst formation or clinical pregnancy as the end point. To the best of our knowledge, there is no predictive model that uses the outcome of live birth as the predictive end point. Can a deep learning model predict the probability of live birth from time-lapse system? METHODS: This study retrospectively analyzed the time-lapse data and live birth outcomes of embryos samples from January 2018 to November 2019. We used the SGD optimizer with an initial learning rate of 0.025 and cosine learning rate reduction strategy. The network is randomly initialized and trained for 200 epochs from scratch. The model is quantitively evaluated over a hold-out test and a 5-fold cross-validation by the average area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: The deep learning model was able to predict live birth outcomes from time-lapse images with an AUC of 0.968 in 5-fold stratified cross-validation. CONCLUSIONS: This research reported a deep learning model that predicts the live birth outcome of a single blastocyst transfer. This efficient model for predicting the outcome of live births can automatically analyze the time-lapse images of the patient's embryos without the need for manual embryo annotation and evaluation, and then give a live birth prediction score for each embryo, and sort the embryos by the predicted value.

Global analysis of the COVID-19 research landscape and scientific impact.

OBJECTIVES: To consider a 1-year time window of the coronavirus disease 2019 (COVID-19) crisis to integrate qualitative and quantitative data and provide an in-depth analysis of all COVID-19 publications from geographical, epidemiological and chronological perspectives. METHODS: Publications on COVID-19 from December 1, 2019, to December 31, 2020 without document type limitations were extracted from the Web of Science database. Microsoft Excel 2016, GraphPad Prism 9, VOSviewer 1.6.15 and IBM SPSS 21.0 were used to analyze the global epidemiological publication landscape and its correlations, research hotspots around the world and the top 5 countries in terms of publications. RESULTS: A total of 51,317 documents were analyzed in the present study. The publication trend could be divided into an increasing output stage and an explosive output stage. There were positive correlations between monthly publications, confirmed cases and deaths. Research hotspots from the whole year, from individual quarters, and from the top 5 countries with the most publications were further identified. CONCLUSIONS: The correlation analysis of publications indicated that confirmed cases and deaths were forces driving the scientific output, reflecting the growing trend to some extent. Moreover, the hotspot analysis provided valuable information for scientists, funders, policy and decision-makers to determine what areas should be their focus when faced with public health emergencies in the future.

Neonatal Outcomes of Embryos Cultured in a Time-Lapse Incubation System: an Analysis of More Than 15,000 Fresh Transfer Cycles.

In the past 5 years, the time-lapse culture system (TLS) has gradually been applied to the field of assisted reproduction. However, there are few reports on the comparison between this system and the conventional culture system (CS) on the outcome of newborns. As a new model in embryo culture, we should pay attention to its neonatal outcomes. We examined 15,252 fresh transfer cycles processed between January 2016 and December 2019. After propensity score matching, embryos in two groups, TLS and CS, had similar rates of miscarriages, ectopic pregnancy, and live delivery (P > 0.05). Embryos in the TLS group achieved higher clinical pregnancy and implantation rates (P < 0.05). Of the perinatal and neonatal outcomes, singletons and twins were analyzed separately. No significant differences were observed in gestational age, preterm deliveries, birth weight, and sex ratio (P > 0.05). Incidences of malformations of babies delivered from CS and TLS groups were also similar between the two groups. Embryos cultured in a TLS are as safe as CS with regard to neonatal outcomes, including congenital malformations.

Observer-based event-triggered type-2 fuzzy control for uncertain steer-by-wire systems.

This paper addresses the tracking control problem for the uncertain steer-by-wire (SbW) system with the controller area network (CAN) communication and unavailable variables. First, an adaptive interval type-2 fuzzy logic system (IT2 FLS) and sliding mode observer are constructed to estimate the uncertain nonlinearity and unavailable variables of SbW control systems. Further, an event-triggered sliding mode control (ET-SMC) is presented to achieve the transient steering performance of SbW systems while saving CAN communication resources. Much importantly, the dynamic gain and nested technologies are incorporated in this scheme to deal with estimation error and the chattering phenomenon of the sliding mode control system. It is shown that the practical fixed-time stability of the closed-loop system can be guaranteed without the initial condition of tracking errors. Finally, simulations and vehicle experiments are presented to verify the designed scheme.

Measuring self-efficacy in defecation: Validation and utilization of a Chinese version of the self-efficacy for functional constipation questionnaire (SEFCQ) in a pediatric population.

BACKGROUND: Self-efficacy in defecation plays an important role on behavioral therapy for functional constipation (FC). There is an unmet need for valid child self-report measures of task-specific self-efficacy for pediatric FC. Our aim was to cross-culturally validate the Self-Efficacy for Functional Constipation Questionnaire (SEFCQ) and to explore the salient factor(s) of self-efficacy in defecation that correlate with anxiety and constipation symptom severity among Chinese children. METHODS: The SEFCQ was adapted to Chinese version following the Rome Foundation guidelines for the translation of questionnaires. Two hundred and three children with FC were involved in psychometric testing. Confirmatory factor analysis was conducted to determine the structure of the SEFCQ. Construct validity was evaluated by testing the relationship between the SEFCQ and both anxiety and the Patient Assessment of Constipation Symptoms (PAC-SYM). Test-retest reliability, internal consistency, and interfactor correlation were used to evaluate reliability. Hierarchical multiple regression was used to identify salient self-efficacy for FC that correlates with anxiety and constipation symptom severity. KEY RESULTS: Confirmatory factor analysis supports the two-factor structure of the SEFCQ. Adequate test-retest reliability (r = 0.973, p<0.001) and internal consistency (Cronbach's α = 0.871) were obtained. Both self-efficacy factors were significantly associated with anxiety (r = -0.227 to -0.350, p<0.001) and PAC-SYM (r = -0.495 to -0.602, p<0.001), with emotional self-efficacy being the most salient factor for predicting the symptom severity of constipation after controlling for sex, age, quality of parents' marriage, and family history. CONCLUSION AND INFERENCES: The SEFCQ showed satisfactory psychometric properties. Low self-efficacy in defecation correlates with anxiety and may contribute to poor adherence to behavior change, which exacerbates the symptoms of constipation. Further study is needed to apply social cognitive intervention to increase children's self-efficacy in defecation and assess its effect on treatment outcomes.

Evaluation of the hepatoprotective effect of Yigan mingmu oral liquid against acute alcohol-induced liver injury in rats.

BACKGROUND: Yigan mingmu oral liquid (YGMM) is a herbal medicine based on a famous Chinese herbal formula that has been used for sore eyes for more than 400 years. Eye health is closely associated with the liver based on TCM. This study aimed to investigate the hepatoprotective effect of YGMM against acute liver injury induced by alcohol in rats. METHODS: Experimental rats were administered with silymarin and YGMM through the gastric gavage during the entire experiment. Starting from the 11th day, the rats were administered orally with 14 ml/kg Red Star Erguotou Liquor, a popular brand, at 4 h after the dose of silymarin (100 mg/kg) and YGMM (1, 2.5 and 5 ml/kg in low, middle and high dosage group, respectively) once a day for 4 weeks except for the rats in the normal group. Biochemical parameters, including ALT, AST, TB, TG, T-SOD, GSH, and MDA were detected to evaluate the protective effect of YGMM. Pathological changes were observed through histopathological examination. RESULTS: Treatment with YGMM exhibited a significant protective effect by reversing the biochemical parameters (ALT, AST, TB, TG, and GSH) and histopathological changes. Histopathological examination by Oil Red O Staining Solution showed that lipid droplets were significantly reduced in the silymarin and YGMM groups (p < 0.001) when compared to alcohol group. CONCLUSIONS: YGMM exhibits a significant hepatoprotective activity against acute liver injury induced by alcohol in rats.

Active Constituent in the Ethyl Acetate Extract Fraction of Terminalia bellirica Fruit Exhibits Antioxidation, Antifibrosis, and Proapoptosis Capabilities In Vitro.

Terminalia bellirica (Gaertn.) Roxb. fruit (TBF) is a widely planted traditional medicinal herb in Tibet. We aimed to determine the most active substance-enriched extract by comparing the in vitro antioxidant activities of different extract fractions of TBF that were subsequently extracted by petroleum ether, chloroform, ethyl acetate, and n-butanol after initial extraction by 95% ethanol. The main compounds of the ethyl acetate extract fraction (EF) were analyzed via HPLC-MS. Gallic acid (GA) was obtained from EF to determine in vitro antifibrotic activity based on the traditional usage of TBF. After HSC-T6 cells were incubated with GA, extracellular secreted levels of fibrosis-associated cytokines, such as collagen I, collagen III, TGF-ß1, and hydroxyproline, were estimated by ELISA. Gene and protein expressions of PDGFR, CTGF, NF-κB, MMP-2, TIMP-1, TIMP-2, α-SMA, and the Bcl-2/Bax family were determined by quantitative PCR and western blot. The proapoptotic effect of GA was further investigated by annexin V-PI and TUNEL staining. These results indicate that EF has prominent in vitro antioxidant activity among four extract fractions, and its main component, GA, manifests antifibrosis activity and its potential mechanism of action includes inhibition of cytokine secretion and collagen synthesis, as well as proapoptosis of HSCs.

The in silico and in vivo evaluation of puerarin against Alzheimer's disease.

The root of Pueraria lobata has been utilized as a food source for thousands of years in China. Puerarin is the major bioactive and the most abundant secondary metabolite obtained from the root of P. lobata. The potential therapeutic effect of puerarin against Alzheimer's disease was screened by in silico methods and confirmed by the amyloid ß-peptide-induced Alzheimer's disease (AD) rat model. The in silico study displayed that puerarin had the potential to penetrate across the blood-brain barrier and had high stability in molecular docking and dynamics simulation with acetylcholinesterase (AChE), cyclooxygenase-2 (COX-2) and caspase-3 (C3), which play a central role in the development of AD. The in vivo results showed that puerarin could restrain the AChE activity, restore the activities of antioxidant defense substances toward normal levels, and decrease the expression of inflammatory factors and apoptosis genes in the brain, especially down-regulating the expressions of COX-2 and C3. The histopathological examination of brain sections and behavioral testing also verified the biochemical observations, which further validates the in silico study. These results not only suggest that puerarin, as a potential compound, could relieve AD, but also broaden the applications of puerarin.