OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Persistent and maladaptive drug-related memories represent a key component in drug addiction. Converging evidence from both preclinical and clinical studies has demonstrated the potential efficacy of the memory reconsolidation updating procedure (MRUP), a non-pharmacological strategy intertwining two distinct memory processes: reconsolidation and extinction-alternatively termed "the memory retrieval-extinction procedure". This procedure presents a promising approach to attenuate, if not erase, entrenched drug memories and prevent relapse. The present review delineates the applications, molecular underpinnings, and operational boundaries of MRUP in the context of various forms of substance dependence. Furthermore, we critically examine the methodological limitations of MRUP, postulating potential refinement to optimize its therapeutic efficacy. In addition, we also look at the potential integration of MRUP and neurostimulation treatments in the domain of substance addiction. Overall, existing studies underscore the significant potential of MRUP, suggesting that interventions predicated on it could herald a promising avenue to enhance clinical outcomes in substance addiction therapy.
Humans ; Substance-Related Disorders/psychology* ; Memory Consolidation/physiology* ; Animals ; Extinction, Psychological/physiology*

The high prevalence of childhood caries poses a considerable threat to children's overall health. Traditional Chinese medicine (TCM) concepts offers a distinctive and valuable perspective on caries prevention. This study explores TCM's conceptualization of dental caries in relation to the physiological characteristics of children and proposes targeted preventive strategies, including holistic care, dietary regulation, and lifestyle modification. In addition, the study highlights the role of traditional modalities, such as Chinese herbal medicine, acupuncture, moxibustion, and tuina, in caries prevention, while emphasizing the importance of supporting children's mental health. The integration of TCM with modern medical practices holds promise for advancing research into the prevention and treatment of caries. Furthermore, promoting the overall improvement of children's health.
Dental Caries/prevention & control* ; Humans ; Medicine, Chinese Traditional ; Child ; Acupuncture Therapy ; Moxibustion ; Life Style ; Drugs, Chinese Herbal/therapeutic use*

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.

Background::In vitro fertilization (IVF) has emerged as a transformative solution for infertility. However, achieving favorable live-birth outcomes remains challenging. Current clinical IVF practices in IVF involve the collection of heterogeneous embryo data through diverse methods, including static images and temporal videos. However, traditional embryo selection methods, primarily reliant on visual inspection of morphology, exhibit variability and are contingent on the experience of practitioners. Therefore, an automated system that can evaluate heterogeneous embryo data to predict the final outcomes of live births is highly desirable. Methods::We employed artificial intelligence (AI) for embryo morphological grading, blastocyst embryo selection, aneuploidy prediction, and final live-birth outcome prediction. We developed and validated the AI models using multitask learning for embryo morphological assessment, including pronucleus type on day 1 and the number of blastomeres, asymmetry, and fragmentation of blastomeres on day 3, using 19,201 embryo photographs from 8271 patients. A neural network was trained on embryo and clinical metadata to identify good-quality embryos for implantation on day 3 or day 5, and predict live-birth outcomes. Additionally, a 3D convolutional neural network was trained on 418 time-lapse videos of preimplantation genetic testing (PGT)-based ploidy outcomes for the prediction of aneuploidy and consequent live-birth outcomes.Results::These two approaches enabled us to automatically assess the implantation potential. By combining embryo and maternal metrics in an ensemble AI model, we evaluated live-birth outcomes in a prospective cohort that achieved higher accuracy than experienced embryologists (46.1% vs. 30.7% on day 3, 55.0% vs. 40.7% on day 5). Our results demonstrate the potential for AI-based selection of embryos based on characteristics beyond the observational abilities of human clinicians (area under the curve: 0.769, 95% confidence interval: 0.709–0.820). These findings could potentially provide a noninvasive, high-throughput, and low-cost screening tool to facilitate embryo selection and achieve better outcomes. Conclusions::Our study underscores the AI model’s ability to provide interpretable evidence for clinicians in assisted reproduction, highlighting its potential as a noninvasive, efficient, and cost-effective tool for improved embryo selection and enhanced IVF outcomes. The convergence of cutting-edge technology and reproductive medicine has opened new avenues for addressing infertility challenges and optimizing IVF success rates.

Objective To understand the status quo of nutrition working ability in primary medical and health institutions of Chongqing City.Methods Three primary medical institutions were randomly extracted from each of 39 districts and counties of Chongqing City,and Primary Nutrition Service Capacity Survey Form and Nutrition Work Capacity Survey System were adopted to conduct the questionnaire survey.Then the sur-vey results were analyzed.Results A total of 117 primary medical institutions were surveyed,in which 86 in-stitutions(73.50％)undertook the nutritional work.The number of engaging the nutrition full-time work in the units was 0(0,0).Among the nutritional staff,the age in 164 persons was 30-＜40 years old,accounting for 48.38％,180 persons(53.10％)had the primary title,232 persons(68.44％)had the bachelor degree,287 persons(84.66％)had the medical related background,but only 2 persons had the nutritional related profes-sional background.There were 57(48.72％),75(64.10％),77(65.81％)primary medical institutions in carry-ing out the nutrition and health management of pregnant women,children aged 0-6 years old and elderly peo-ple,34 institutions(29.10％)in carrying out nutritional monitoring,and 17 institutions(14.50％)had the clinical nutrition work ability.Compared with the villages and towns,the proportion of urban area primary medical institutions in carrying out the blood routine items in children aged 0-6 years old,hemoglobin,blood routine and urine routine items in elderly people was higher,the number of published popular science works on nutrition was more,and the differences were statistically significant(P＜0.05).Conclusion The nutrition work system of primary medi-cal institutions in Chongqing City is temporarily imperfect,the specialized persons still lack and the nutritional health service level needs to be further strengthened.

OBJECTIVE To investigate the effect and mechanism of action of KRT8 small interfering RNA(si-KRT8)in exosomes derived from patient serum with hypopharyngeal carcinoma on chemosensitivity to 5-fluorouracil(5-FU)in human pharyngeal squamous cell carcinoma FaDu cell line.METHODS The cancerous tissues of hypopharyngeal cancer patients and The serum,cancerous tissues and paracancerous tissues of drug-resistant patients after treatment were collected.A 5-FU-resistant cell line of FaDu(FaDu/R)was constructed for subsequent experiments.Exosomes were isolated from patient serum by ultrafast gradient centrifugation,identified using transmission electron microscopy and Western blot(WB)techniques.si-KRT8 was encapsulated into exosomes(Exosome@si-KRT8)using electroporation technology and subsequently used to treat cells.Real-time fluorescence quantitative PCR(RT-qPCR)and WB were used to detect the expression levels of KRT8 in different tissues,exosomes after electroporation of si-KRT8,and FaDu cells,respectively.Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,migration invasion technique and WB were used to detect the effects of Exosome@si-KRT8 on viability,apoptosis,and epithelial-mesenchymal transition of FaDu/R cells.RESULTS The expression level of KRT8 in drug-resistant tissues of hypopharyngeal carcinoma and FaDu/R cells was elevated compared with that in paraneoplastic tissues,cancer tissues and normal FaDu cells(t=15.79,P＜0.01).Isolated patient serum exosomes showed a double membrane structure and expressed both CD63 and TSG101 proteins,and KRT8 expression in exosomes was decreased after electro-transfection with si-KRT8(t=6.70,P＜0.01).Exosome@si-KRT8 inhibited KRT8 protein expression levels in FaDu/R cells(t=123.50,P＜0.01).Compared with the 5-FU group and the 5-FU+Exosome group,Exosome@si-KRT8 was able to inhibit the viability of FaDu/R cells(t=17.07,P＜0.01),promote the level of apoptosis in FaDu/R cells,and inhibit the expression of drug-resistance-associated proteins in FaDu/R cells(P-gp:t=103.20,MDR1:t=238.60,P＜0.01),and Exosome@si-KRT8 was able to suppress the expression of metastasis of FaDu/R cells(t=42.30,t=122.00,P＜0.01)and promoted the expression of E-cadherin while inhibiting the expression level of N-cadherin(t=130.80,t=83.90,P＜0.01).CONCLUSION Serum-derived exosome encapsulation of si-KRT8 enhances chemosensitivity of hypopharyngeal carcinoma cells and its mechanism of action may be related to inhibition of epithelial-mesenchymal transition.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.