1.Effects of peripheral blood-derived exosomes intervened by Naozhenning on injury of neuron induced by microglia
Li GAO ; Le ZHAO ; Liya WU ; Weiyi ZHANG ; Nan LI ; Nannan WEI ; Yonghui WANG
China Pharmacy 2025;36(19):2393-2398
OBJECTIVE To study the effects of peripheral blood-derived exosomes (Exo) intervened by Naozhenning (NZN) on injury of neuron cells HT22 induced by microglia BV-2 cells. METHODS Wistar rats were selected to prepare peripheral blood- derived Exo intervened by NZN (66.83 g/kg), referred to as NZN-Exo; peripheral blood-derived Exo intervened by normal saline and piracetam (PLXT, 1.62 g/kg) were prepared using the same method, denoted as KB-Exo and PLXT-Exo respectively, and all Exo were subsequently identified. Meanwhile, BV-2 cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) to prepare LPS- stimulated supernatant, and non-LPS-stimulated supernatant was prepared following the same protocol. HT22 cells were divided into four groups: KB-Exo group (treated with non-LPS-stimulated supernatant+KB-Exo), model group (treated with LPS-stimulated supernatant+KB-Exo), PLXT-Exo group (treated with LPS-stimulated supernatant+PLXT-Exo), and NZN-Exo group (treated with LPS-stimulated supernatant+NZN-Exo), with the concentration of the corresponding Exo in all groups being 50 μg/mL. After 24 hours of culture, the proliferation of HT22 cells was detected by the CCK-8 assay and EdU assay; the apoptosis of HT22 cells was detected; the microstructure of HT22 cells was observed; the contents of interleukin-1β (IL-1β), IL-10, nuclear factor-κB (NF- κB), and tumor necrosis factor-α (TNF-α) in HT22 cells were measured, as well as the expression levels of TNF-α, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Caspase-1, B-cell lymphoma-2( Bcl-2), and Bcl-2-associated X protein (Bax). RESULTS KB-Exo, PLXT-Exo and NZN-Exo were successfully prepared, and all Exo exhibited typical cup-shaped contours and membrane-enclosed characteristics. Compared with KB-Exo group, model group showed significantly decreased cell proliferation rates (detected by CCK-8 and EdU), intracellular IL-10 levels, and Bcl-2 protein expression levels (P<0.05); while the cell apoptosis rate, intracellular levels of IL-1β, TNF-α, and NF-κB, as well as the expression levels of NLRP3, TNF-α, Caspase-1, and Bax proteins were significantly increased (P<0.05). Additionally, in the model group, the cells showed volume swelling, incomplete cell membrane, nucleolar rupture, significant swelling and deformation of mitochondria, and severe vacuolization. Compared with model group, the above quantitative indicators in the PLXT-Exo group and NZN-Exo group were significantly reversed (P<0.05), with large and round cell nuclei, intact nuclear membranes, and reduced mitochondrial vacuolization. CONCLUSIONS Peripheral blood-derived Exo intervened by naozhenning can alleviate the injury of neuronal cells HT22 by inhibiting inflammatory responses and cell apoptosis.
2.The Development and Application of Chatbots in Healthcare: From Traditional Methods to Large Language Models
Zixing WANG ; Le QI ; Xiaodan LIAN ; Ziheng ZHOU ; Aiwei MENG ; Xintong WU ; Xiaoyuan GAO ; Yujie YANG ; Yiyang LIU ; Wei ZHAO ; Xiaolin DIAO
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1170-1178
With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.
3.Study on the modeling method of general model of Yaobitong capsule intermediates quality analysis based on near infrared spectroscopy
Le-ting SI ; Xin ZHANG ; Yong-chao ZHANG ; Jiang-yan ZHANG ; Jun WANG ; Yong CHEN ; Xue-song LIU ; Yong-jiang WU
Acta Pharmaceutica Sinica 2025;60(2):471-478
The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.
4.Therapeutic effect of Xiayuxue decoction on a mouse model of nonalcoholic fatty liver disease induced by high-fat diet and its mechanism
Linqi HOU ; Zhiyi WANG ; Xin ZHAO ; Jie ZHANG ; Wenting MA ; Xuling LIU ; Wei ZHANG ; Le TAO ; Cheng LIU ; Liu WU
Journal of Clinical Hepatology 2024;40(4):712-719
ObjectiveTo investigate the mechanism of action of Xiayuxue decoction in inhibiting nonalcoholic fatty liver disease (NAFLD) induced by high-fat diet in mice by regulating nucleotide binding oligomerization domain like receptor containing pyrin domain protein 6 (NLRP6). MethodsA total of 15 male C57BL/6 mice were randomly divided into low-fat diet (LFD) group, high-fat diet (HFD) group, and Xiayuxue decoction-HFD group (XYXD group), with 5 mice in each group. Liver function parameters (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and blood lipid metabolic indicators (triglycerides [TG] and total cholesterol [TC]) were measured; HE staining and oil red O staining were performed for liver tissue to observe histomorpholoty and lipid droplet deposition; quantitative real-time PCR was used to measure the expression levels of inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], interleukin-18 [IL-18], and NLRP6) in liver tissue; Western blot was used to measure the protein expression levels of NLRP6, nuclear factor-kappa B (NF-κB), and NF-κB p65; immunohistochemistry was used to measure the expression of NLRP6 and CD68. Mouse Raw264.7 cells were treated with palmitic acid (PA), lipopolysaccharide, and serum containing Xiayuxue decoction to observe inflammation. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the LFD group, the HFD group had significant increases in the serum levels of ALT, AST, TC, and TG (all P<0.05). Liver histopathological examination showed that the HFD group had marked hepatic steatosis and a signficant increase in NAS score (P<0.05), and quantitative real-time PCR showed significant increases in the inflammatory factors such as IL1β and IL-18 and a significant reduction in the expression of NLRP6 (all P<0.05). Immunohistochemistry showed that the expression of NLRP6 showed a similar trend as that of the macrophage marker CD68. Western blot showed that after the downregulation of NLRP6 expression, there was a significant increase in phosphorylated NF-κB p65 (P<0.05). Compared with the HFD group, Xiayuxue decoction effectively improved liver inflammation, upregulated the expression of NLRP6, and downregulated phosphorylated NF-κB p65 in HFD mice (all P<0.05). After Raw264.7 cells were treated with PA, NLRP6 was downregulated to promote the progression of inflammation (P<0.05), and treatment with Xiayuxue decoction could upregulate NLRP6 and inhibit inflammation NF-κB (P<0.05). ConclusionXiayuxue decoction can effectively improve hepatic steatosis and liver inflammation in a mouse model of NAFLD, possibly by regulating NLRP6/NF-κB to alleviate macrophage activation.
5.Research progress of natural product evodiamine-based antitumor drug design strategies
Zhe-wei XIA ; Yu-hang SUN ; Tian-le HUANG ; Hua SUN ; Yu-ping CHEN ; Chun-quan SHENG ; Shan-chao WU
Acta Pharmaceutica Sinica 2024;59(3):532-542
Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.
6.Mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in multiple cerebral concussion rats
Li GAO ; Le ZHAO ; Nannan WEI ; Liya WU ; Tiantian WANG ; Weiyi ZHANG ; Yonghui WANG
China Pharmacy 2024;35(9):1050-1056
OBJECTIVE To explore the mechanism of Naozhenning granules in regulating mitochondrial energy metabolism in hippocampal tissue of multiple cerebral concussion (MCC) model rats. METHODS SPF grade Wistar rats were used to prepare MCC models using the “free fall impact method”. The successfully modeled rats were divided into model group, piracetam group, and Naozhenning granule low-dose, medium-dose and high-dose groups, and a normal group was also set up, with 8 rats in each group. Rats in each treatment group orally administered corresponding drugs at doses of 0.324 g/kg for the piracetam group and 2.25, 4.5 and 9 g/kg for the Naozhenning granule low-dose, medium-dose and high-dose groups; the normal group and model group were given equal volumes of normal saline; once a day, for 14 consecutive days. The motor exploration ability, learning and memory ability of rats were tested; the adenosine triphosphate (ATP) content in the hippocampal tissue of rat was detected; the changes in the mitochondrial structure of hippocampal tissue was observed; the fluorescence intensity of mitochondrial dynamin- related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fusion 1 (Mfn1), and optic atrophy protein 1 (Opa1) were detected in the hippocampal tissue of rat; the protein expression levels of peroxisome proliferator activated receptor gamma coactivator-1α(PGC-1α), nuclear respiratory factor-1(NRF-1),mitochondrial transcription factor A(TFAM), Wnt-3a,β-catenin in hippocampal tissue of rat were detected. RESULTS Compared with the normal group, the total exercise distance, number of central grid entries, number of upright positions, new object recognition index, mitochondrial ATP content, fluorescence intensity of Mfn1 and Opa1, the protein expression levels of PGC-1α、NRF-1、TFAM、Wnt-3a、 β-catenin in the model group were significantly reduced (P<0.01), while the rest time and fluorescence intensity of Drp1 and Fis1 in hippocampal tissue were significantly increased (P<0.01). The results of transmission electron microscopy showed that the mitochondria in the hippocampal tissue were significantly swollen, with a large number of broken and reduced cristae, and some mitochondria had myeloid changes in the membrane. Compared with the model group, the levels/contents of the above indicators in rats of each administration group showed varying degrees of reversal, and most of the differences were statistically significant (P<0.05 or P<0.01); the degree of mitochondrial swelling in the hippocampal tissue was reduced, with a small amount of broken and reduced cristae, fuzzy fractures appeared in local areas of the rough endoplasmic reticulum. CONCLUSIONS Naozhenning granules can improve the motor exploration, learning and memory abilities of MCC model rats, repair neuronal damage, and exert neuroprotective effects. Its mechanism may be related to activating Wnt/β-catenin signaling pathway,maintaining the balance of mitochondrial division and fusion,and promoting mitochondrial biosynthesis.
7.Construction and Interpretation of Clinical Comprehensive Evaluation Index System for Chinese Patent Medicine Based on EVIDEM Framework
Zeqi DAI ; Chengyang JING ; Xue WU ; Le ZHANG ; Xing LIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):134-143
ObjectiveTo establish the clinical comprehensive evaluation index system for Chinese patent medicine(CPM) based on Evidence and Value:Impact on DEcisionMaking(EVIDEM) framework, so as to promote the scientific, systematic and standardized implementation of clinical comprehensive evaluation of CPM. MethodThe clinical comprehensive evaluation index system was determined through literature review, semi-structured interview and Delphi method, and the weights of each index were clarified by analytic hierarchy process(AHP). ResultThe recovery rates of both rounds of expert consultation were 100%, and the authority coefficient of experts was 0.90 and 0.905, respectively. Kendall's coordination coefficients(W) of the second- and third-level indicators in the first-round consultation were 0.320 and 0.283(P<0.001), and in the second round were 0.411 and 0.351, respectively(P<0.001). The finally constructed clinical comprehensive evaluation index system for CPM included 6 first-level indicators, 13 second-level indicators and 28 third-level indicators. Among the first-level indicators, the weights of effectiveness, safety, economy, innovation, suitability and accessibility were 37.34%, 32.68%, 11.85%, 5.87%, 5.79% and 6.47%, respectively. ConclusionThis study has constructed a universal clinical comprehensive evaluation index system for CPM, and the domain and criteria are introduced and interpreted in detail, which can provide reference and information for carrying out the clinical comprehensive evaluation of CPM, but it needs to be refined and improved in combination with the clinical practice of CPM for specialized diseases.
8.Mechanism of Electroacupuncture in Functional Dyspepsia Rats Based on Hypothalamic-Pituitary-Adrenal Axis
Wei LE ; Hanling YAO ; Gege YANG ; Yisen WU ; Paidi XU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):259-267
Objective We aimed to explore the therapeutic mechanism of electroacupuncture at Yintang(EX-HN3),Neiguan(PC6)and Zusanli(ST36)on the Hypothalamic-Pituitary-Adrenal axis(HPA)of functional dyspepsia(FD)rats.Methods Forty SD rats were randomly divided into blank group,model group and EA group.The FD model was replicated by tail clamping,irregular diet,and filling the stomach with ice of Saline Solution.After modeling,the EA group received acupuncture treatment for 1 time day,30 minutes time,for 14 days.Recording the general state of the rat.Detection of locomotion and catatonia in rats by open field test.HE staining to observe the morphology and inflammation of gastric mucosa in rats.PCR detection of mRNA expression of 5-hydroxytryptamine3 receptor and corticotropin-releasing hormone in rat hypothalamus.Detection of corticotropin-releasing hormone receptor-2 and NOD-like receptor protein 6 inflammasome protein expression in rat duodenum by Western blotting.Alcian blue staining was used to detect the expression of rat duodenum goblet cells.Results Compared with the blank group,the general state,distance,speed,duodenum CRHR2 and NLRP6 proteins in the model group were significantly decreased(P<0.05),the hypothalamic 5-HT3R and CRH mRNA were significantly increased(P<0.05).Compared with the model group,the general state,distance,speed,expression of CRHR2,NLRP6 protein and goblet cells in the duodenum of rats in the EA group were significantly increased(P<0.05),the 5-HT3R and CRH mRNA in the hypothalamus were significantly decreased(P<0.05).In the model group,the connective tissue of the gastric mucosa was loosely arranged,the submucosa had mild edema,and there were some lymphocytes.The connective tissue of the gastric mucosa of the rats in the blank group and the electroacupuncture group was closely arranged,and there was no obvious proliferation of interstitial cells and no inflammatory cells.Conclusion EA can increase the expression of CRHR2,NLRP6 protein and goblet cells in the duodenum,and inhibit the expression of 5-HT3R and CRH in the hypothalamus.EA can improve gastrointestinal motility and locomotion,relieve anxiety,repair the mucosal barrier of the defective intestine,and restore the function of the Hypothalamic-Pituitary-Adrenal axis.
9.Research progress of the relationship between high fat diet-Induced gastrointestinal microbiota and gastro-intestinal cancer
The Journal of Practical Medicine 2024;40(1):123-128
In healthy individuals,there is a favourable balance between commensal and potentially patho-genic bacteria.When the balance is broken,the host might suffer from gastrointestinal cancer.Studies have shown that high-fat diet can alter the composition of gastrointestinal microbiota,gastrointestinal microbiota may promote gastrointestinal cancer by affecting metabolites of gastrointestinal microbiota,leading to loss of gastrointestinal barrier function,suppressing anti-tumor immunity,etc.In this work,we will summary the current knowledge on relations and possible mechanisms of high-fat diet-associated gastrointestinal microbiota and gastrointestinal cancer.To provide new ideas for the treatment of gastrointestinal cancer.
10.Factors influencing the height development of children and adolescents in Chengguan District of Lhasa of Xizang Autonomous Region, China
Xiaolong WU ; Xiaoyong YUAN ; Yunyi LE ; Lihui YANG
Chinese Journal of Primary Medicine and Pharmacy 2024;31(3):386-391
Objective:To analyze the factors that influence the height development of children and adolescents aged 3 to 16 years in Chengguan District of Lhasa of Xizang Autonomous Region, China.Methods:During the period from August 2021 to June 2022, a convenient sampling method was used to select 100 children and adolescents aged 3-16 years residing in Chengguan District of Lhasa of Xizang Autonomous Region, China. The subjects' physical measurement indicators, Tanner stage, height development questionnaire, wrist bone age, sex hormones, and nutritional biochemical indicators were carefully collected. The factors that influence height development were analyzed using univariate and multivariate logistic regression analyses. Furthermore, the receiver operating characteristic (ROC) curves were constructed to visualize the effects of these influential factors.Results:The study involved a total of 100 children and adolescents, with 51 (51.0%) participants in the tall stature group and 49 (49.0%) participants in the low stature group. Significant differences were observed between the two groups in terms of height difference relative to the national average, body weight, waist circumference, luteinizing hormone level, the percentage of individuals with an abnormal luteinizing hormone level, follicle stimulating hormone level, and bone age [ χ2 ( t) = 13.6, 2.65, 2.47, -2.58, 10.9, -2.95, 11.8, all P < 0.05]. A univariate logistic regression analysis revealed that body mass, waist circumference, the percentage of individuals with an abnormal luteinizing hormone level, follicle stimulating hormone level, and bone age are factors that possibly affect height development ( OR = 1.05, 1.05, 4.56, 1.18, 2.99, all P < 0.05). Furthermore, a multivariate logistic regression analysis revealed waist circumference, the percentage of individuals with an abnormal luteinizing hormone level, and bone age as independent factors influencing height development ( OR = 1.10, 7.01, 3.14, all P < 0.05). The receiver operating characteristic (ROC) curve analysis showed that the values of the area under the curve were 0.65, 0.65, 0.67, and 0.75 respectively for waist circumference, the percentage of individuals with an abnormal luteinizing hormone level, bone age, and their combination (all P < 0.05). Conclusion:Waist circumference, the percentage of individuals with an abnormal luteinizing hormone level, and bone age appear to be critical factors influencing the height development of children and adolescents In Chengguan District of Lhasa of Xizang Autonomous Region, China.

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