A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*

Objective:To explore the application of BOPPPS(Bridge-in,Objective,Pre-assessment,Participatory Learning,Post-assessment,Summary)combined with Direct Observation of Procedural Skills(DOPS)in anesthesiology teaching under the background of medical-educational collaboration.Methods:A total of 60 students majoring in anesthesiology were selected as the research objects.A total of 30 students in grade 2018 were enrolled in the control group and receired traditional teaching mode.A total of 30 students in grade 2019 were enrolled in the research group and received BOPPPS teaching mode.The assessment of the internship after graduation for both groups adopted the DOPS assessment mode.Two groups of students were subject to pre-enrollment assessment,including process evaluations,such as theoretical class attendance,classroom interaction,pre-test scores,post-test scores,and the final theoretical test score.A comprehensive evaluation of teachers'teaching effect was conducted.When the two groups were discharged from the department,in addition to the assessment of professional theoretical knowledge of anesthesia and the operation of conventional anesthesia skills,they also underwent nine DOPS assessments.Results:There was no statistical difference between the two groups in the attendance(P＞0.05).The classroom interaction,pre-test scores,post-test scores,final test scores and total test scores in the study group were higher than those in the control group(P＜0.05).In terms of comprehensive evaluation of teaching effect,there was no statistical difference between the two groups in the evaluation of teachers'teaching attitude(P＞0.05).However,the research group reported higher satisfaction in teaching skills,methods,student-teacher interaction,and classroom engagement(P＜0.05).Both the theoretical and practical scores in the research group were higher than those in the control group(P＜0.05).The DOPS assessment results showed that the research group was superior to the control group in terms of indication mastery,operation completion,teamwork and problem-solving ability,and comprehensive ability performance(P＜0.05).Conclusion:The application effect of BOPPPS combined with DOPS in anesthesiology teaching is better than the conventional teaching mode.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

Objective:To explore the application of BOPPPS(Bridge-in,Objective,Pre-assessment,Participatory Learning,Post-assessment,Summary)combined with Direct Observation of Procedural Skills(DOPS)in anesthesiology teaching under the background of medical-educational collaboration.Methods:A total of 60 students majoring in anesthesiology were selected as the research objects.A total of 30 students in grade 2018 were enrolled in the control group and receired traditional teaching mode.A total of 30 students in grade 2019 were enrolled in the research group and received BOPPPS teaching mode.The assessment of the internship after graduation for both groups adopted the DOPS assessment mode.Two groups of students were subject to pre-enrollment assessment,including process evaluations,such as theoretical class attendance,classroom interaction,pre-test scores,post-test scores,and the final theoretical test score.A comprehensive evaluation of teachers'teaching effect was conducted.When the two groups were discharged from the department,in addition to the assessment of professional theoretical knowledge of anesthesia and the operation of conventional anesthesia skills,they also underwent nine DOPS assessments.Results:There was no statistical difference between the two groups in the attendance(P＞0.05).The classroom interaction,pre-test scores,post-test scores,final test scores and total test scores in the study group were higher than those in the control group(P＜0.05).In terms of comprehensive evaluation of teaching effect,there was no statistical difference between the two groups in the evaluation of teachers'teaching attitude(P＞0.05).However,the research group reported higher satisfaction in teaching skills,methods,student-teacher interaction,and classroom engagement(P＜0.05).Both the theoretical and practical scores in the research group were higher than those in the control group(P＜0.05).The DOPS assessment results showed that the research group was superior to the control group in terms of indication mastery,operation completion,teamwork and problem-solving ability,and comprehensive ability performance(P＜0.05).Conclusion:The application effect of BOPPPS combined with DOPS in anesthesiology teaching is better than the conventional teaching mode.

AIM:The study aims to investigate the effects of Huayu-Qutan formula(HYQT)-medicated serum on oleic acid-induced lipid damage and endoplasmic reticulum stress(ERS)in HepG2 cells,and to explore the mecha-nism underlying the prevention and treatment of lipid metabolism disorders by HYQT.METHODS:The HepG2 cells were treated with various concentrations of oleic acid,and CCK8 assay,oil red O staining and ELISA were used to identify the optimal treatment concentration and time of oleic acid and HYQT-medicated serum.Moreover,the cells were divided into control,model,thapsigargin(Tg),and Tg+HYQT groups.Cellular lipid deposition was measured using oil red O staining,while triglyceride(TG)and free fatty acid(FFA)levels were assessed by ELISA.Transmission electron micros-copy was used to examine endoplasmic reticulum structures,and RT-qPCR and Wes fully automated protein quantification analysis system were used to measure the mRNA and protein expression of glucose-regulated protein 78(GRP78),sterol regulatory element binding protein 1c(SREBP1c),acetyl coenzyme A carboxylase(ACC1),fatty acid synthase(FAS)and stearoyl coenzyme A desaturase 1(SCD1)in different groups.RESULTS:Significant lipid deposition was induced in HepG2 cells after treatment with 1 000 μmol/L oleic acid,while treatment with serum containing 10%HYQT for 48 h was found to be optimal.Compared with control group,the cells in model group showed significant deposition of oil red O-stained lipid droplets in the cytoplasm,associated with endoplasmic reticulum expansion,ERS,and nuclear condensa-tion.The TG and FFA levels,and the mRNA and protein expression levels of GRP78,SREBP1c,ACC1,FAS and SCD1 were increased significantly(P<0.01).Compared with model group,the cells treated with HYQT-mediated serum showed marked decrease in the number of lipid droplets in the cytoplasm,with restored endoplasmic reticulum morphology.The TG and FFA levels were significantly reduced(P<0.01),and the mRNA and protein levels of factors related to ERS and de novo fatty acid synthesis were markedly decreased(P<0.01).Treatment with Tg,an ERS agonist,led to greater accu-mulation of cytoplasmic lipid droplets and increased endoplasmic reticulum expansion.Marked variations in the morpholo-gy and size of the endoplasmic reticulum were observed,with fusion and clustering of vacuoles.The TG and FFA levels,and the expression of ERS-and fatty acid synthesis-related factors were increased(P<0.01).Compared with Tg group,the cells treated with Tg+HYQT showed reduced number of cytoplasmic lipid droplets,attenuated endoplasmic reticulum dilation,and decreased number and volume of vacuoles,while the TG and FFA levels and the expression of ERS-and fatty acid synthesis-associated factors were significantly decreased(P<0.01).CONCLUSION:Serum containing HYQT alle-viates oleic acid-induced lipid damage in HepG2 cells by inhibiting ERS-induced de novo synthesis of fatty acids.

Objective To conduct Rh blood group serological testing and third-generation sequencing(TGS)on 22 RhD variant voluntary blood donors in Chongqing and explore the phenotypic distribution and genotyping of RhD variants in Chongqing.Methods From January to August 2023,individuals who participated in blood donation in our blood center were selected as the study objects.RhD variant phenotype identification was performed using routine serological methods.Once the RhD variants were identified,tests on different antigenic epitopes of RhD were conducted using a D-screen assay kit.Furthermore,after the genomic DNA from 22 RhD variant blood samples was extracted,imbraided primers design and multi-segment amplification and splicing were used to sequence the full-length RHD gene for TGS.The RHD gene sequence was analyzed using SnapGene software.Results Among the 22 RhD variants,8 were DVI type 3(36.36%),with the main mutation of RHD-CE(3-6)-D hybrid allele.Six cases(27.27%)showed partial weak D15 type,with the main mutation of c.845G>A.There were 6 cases of Asia type Del(27.27%),with the main mutation of c.1227G>A.One case was weak D17 type with a mutation of c.340C>T and 1 case speculated to be partial D(c.491A>T,p.Asp164Val,missense mutation).Conclusion The most common RhD variant phenotype among blood donors in Chongqing is DVI type 3,and the full-length haplotype sequence of RHD variant alleles can be obtained by Pacific Bioscience single-molecule real-time sequencing(SMRT).

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Objective:To explore the clinical efficacy and safety analysis of a novel laser localization technology assisted percutaneous puncture of trigeminal nerve microsphere capsule compression surgery for the treatment of primary trigeminal neuralgia.Methods:A retrospective selection was conducted on 63 patients with primary trigeminal neuralgia who underwent percutaneous puncture of the trigeminal nerve microsphere capsule compression surgery at the First Hospital of Hunan University of Chinese Medicine from January 2020 to December 2021. According to different surgical methods, they were divided into a new laser localization assisted puncture group (observation group) of 32 cases and a traditional barehanded localization puncture group (control group) of 31 cases. An analysis was conducted on the surgical time, puncture time, puncture frequency, intraoperative exposure to radiation, number of cases of poor balloon formation, and clinical efficacy within 6 months after surgery for two groups of patients. The prognosis of the patients was followed up at 6 months after surgery.Results:The surgical time, puncture time, puncture frequency, and intraoperative exposure of the observation group were all less than those of the control group, and the differences were statistically significant (all P<0.05). There was no statistically significant difference ( P>0.05) in the number of cases of poor balloon angioplasty between the observation group and the control group, as well as the pain score grading of the Barlow Neurological Institute (BNI) on the first day after surgery. Within 6 months after surgery, there was no statistically significant difference in the incidence of facial numbness, diplopia, masseter weakness, perilabial herpes, and recurrent pain between the two groups of patients (all P>0.05). Conclusions:Laser positioning technology can assist in precise puncture of the foramen ovale and accurate placement of balloons based on surgical experience, which helps to improve surgical safety, reduce postoperative complications and intraoperative radiation dose, and achieve satisfactory short-term follow-up results.

Coronary heart disease is a physical and mental disease that is often combined with mental disorders such as depression,anxiety,sleep disorders,and stress,affecting the patient's prognosis.This review introduces the common mental disorders of patients with coronary heart disease,the types,characteristics and application status of digital and intelligent intervention technology,and analyzes the challenges of digital and intelligent intervention technology in the development of mental disorders in coronary heart disease,with a view to providing new information technology-driven nursing practice ideas and directions.

OBJECTIVES: To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4). METHODS: One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types. RESULTS: In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations. CONCLUSIONS ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.
Child ; Humans ; Infant, Newborn ; Acyl-CoA Dehydrogenase/genetics* ; Genotype ; Phenotype ; Carnitine/metabolism* ; Mutation