1.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
2.Effects of Modified Gegen Qinlian Decoction (葛根芩连汤) on Intestinal Mucosal Barrier and Epithelial Mesenchymal Transition in Ulcerative Colitis Model Mice
Lihui FANG ; Jiaqi ZHANG ; Lanshuo HU ; Xintong WANG ; Shan LIU ; Yuedan WANG ; Jinke HUANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2024;65(24):2580-2588
ObjectiveTo investigate the possible mechanism of modified Gegen Qinlian Decoction (葛根芩连汤) in treatment of ulcerative colitis (UC) from the view of intestinal mucosal epithelial barrier damage and epithelial mesenchymal transition. MethodsSixty male C57BL/6J mice were divided into blank group, model group, western medicine control group, and low-, medium-, and high-dose modified Gegen Qinlian Decoction groups, with 10 mice in each group. Except for the blank group, 3% dextran sodium sulfate (DSS) was used to induce colitis model by free drinking for 7 days, and on the first day of modelling, 6, 12, and 24 g/(kg·d) of modified Gegen Qinlian Decoction were given to the low-, medium-, and high-dose groups respectively, 5-aminosalicylic acid (5-ASA) 100 mg/(kg·d) given by gavage to western medicine control group, and 10 ml/kg distilled water were given to blank and model group by gavage, once a day for 7 days. Body mass of mice was recorded and disease activity index (DAI) scores were performed daily. The mice were anesthetized after 24h of the last administration and the colon was taken to observe the length of colon, HE staining was applied to observe the damage of colonic mucosa and score pathological states, Masson staining to detect the deposition of colonic collagen fibers, immunofluorescence to observe the distribution of F-actin in colonic mucosal epithelium, and immunohistochemistry to detect the expression of tight junction protein ZO-1, Occludin, E-cadherin and Vimentin. ResultsCompared with the blank group at the same time, the percentage of body mass of mice in the model group on day 7 of modelling significantly reduced and the DAI score was significantly increased (P<0.01); compared with the model group at the same time, the body mass of mice in the western medicine control group and all of modified Gegen Qinlian Decoction groups decreased, and the DAI scores of mice in the western medicine control group and the high-dose modified Gegen Qinlian Decoction group decreased (P<0.05 or P<0.01); compared with the same time of mice in the low-dos Gegen Qinlian Decoction group, the body mass of mice in the high-dose Gegen Qinlian Decoction group and the western medicine control group significantly elevated (P<0.05). Compared with the blank group, the length of the colon of mice in the model group was significantly shortened, the pathological score and the percentage of collagen area were significantly increased, the average fluorescence intensity of F-actin was reduced, the protein levels of ZO-1, Occludin and E-cadherin in the colon tissue decreased, and the protein level of Vimentin elevated (P<0.01). Compared with the model group, the length of colon significantly increased, patholo-gical score, collagen area percentage decreased, ZO-1, Occludin, E-cadherin protein levels increased and Vimentin levels decreased in all medicated groups; the average fluorescence intensity of F-actin increased in the western medicine control group and the middle- and high-dose Gegen Qinlian Decoction groups (P<0.05 or P<0.01). Compared with the low-dose Gegen Qinlian Decoction group, the proportion of collagen fibre area in the middle-dose Gegen Qinlian Decoction group and the western medicine control group reduced; the mean fluorescence intensity of F-actin increased in the middle-dose Gegen Qinlian Decoction group; the protein levels of ZO-1 and E-cadherin increased in the western medicine control group, and the protein levels of ZO-1 increased in the high-dose Gegen Qinlian Decoction group (P<0.05). Compared with the medium-dose Gegen Qinlian Decoction group, the protein levels of ZO-1 elevated in the high-dose Gegen Qinlian Decoction group (P<0.05). Comapred with the high-dose Gegen Qinlian Decoction group, level of E-cadherin and Vimentin protein of the western medicine control group increased (P<0.05). ConclusionModified Gegen Qinlian Decoction was able to reduce colonic inflammation and mucosal barrier damage and inhibit the process of epithelial mesenchymal transition in mice models of ulcerative colitis, which may be one of its action mechanisms .
3.Effect analysis of humanistic care training for pediatric nurses based on KCS model
Yaojia HU ; Lihui ZHU ; Xin LIU ; Xiang DING ; Yuyuan XIONG
Chinese Journal of Medical Education Research 2023;22(1):157-160
Objective:To explore the effect of knowledge-clinical-sharing (KCS) model in humanistic care training of pediatric nurses.Methods:A total of 182 specialist nurses who were trained in Hunan Children's Hospital from June 2019 to December 2019 were selected as the research objects. Among them, 102 specialist nurses from June 2019 to August 2019 were selected as the control group, and 80 specialist nurses from September 2019 to December 2019 were selected as the intervention group. The Jefferson empathy scale was used to compare the effect of humanistic training before and after the implementation. SPSS 22.0 statistical software was used, measurement data were test by F-test and t-test, and the counting data were analyzed by Chi-square test. Results:After the implementation of humanistic care training based on KCS model, the empathy ability score of the intervention group was higher than that of the control group [(80.23±5.33) vs. (78.14±4.37)], and the difference was statistically significant ( P < 0.01). There was no significant difference between neonatal and pediatric specialist nurses before and after the training. Conclusion:The phased humanistic training based on KCS model can improve the empathy ability of pediatric nurses and enhance their confidence in the clinical implementation of humanistic care. However, the humanistic training mode of pediatric nurses should be improved according to the hospital's own situation, so as to adapt to the development of nursing industry.
4.Mechanism of Therapeutic Methods of Activating Blood, Resolving Phlegm, and Removing Toxins in Liver Cancer Based on Immune Microenvironment
Lihui YANG ; Kaiwen HU ; Jingxiao WANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(14):172-178
Primary liver cancer is one of the common tumors in China, which seriously endangers human health. With the advancement in medical science and technology, some achievements have been made in the clinical treatment of liver cancer, but there is an urgent need to find a safe and effective solution for patients with advanced liver cancer. As a unique therapy in China, traditional Chinese medicine (TCM) has the characteristics of multiple targets and multiple pathways and plays a certain role in the treatment of malignancies. The present study aimed to clarify the mechanism of action of "dispelling pathogens" in the treatment of liver cancer through literature research. In TCM etiology and pathogenesis, deficient healthy Qi and exuberance of pathogenic Qi, such as phlegm, blood stasis, and toxins, lead to the development of liver cancer. The treatment should follow the principles of reinforcing healthy Qi and eliminating pathogens. It has been generally believed that tumor cell is the "pathogenic factor" and the immune function serves as the "healthy Qi". In the treatment of malignancies and the regulation of the immune function of patients, it is often advocated to reinforce healthy Qi to eliminate the accumulation. With the continuous updating of knowledge on tumors and tumor microenvironment, it is also recognized that there are "healthy Qi" and "pathogenic Qi" in the immune microenvironment of tumors. For example, the immune cells and immune factors that inhibit tumor growth can be classified as "healthy Qi" with TCM attributes, while those promoting tumor growth can be classified as "pathogenic Qi". Additionally, as proved by clinical data and experimental research, the elimination methods represented by "activating blood, resolving phlegm, and removing toxins" in the treatment of liver cancer can combat tumor cells and also regulate the "healthy Qi" and "pathogenic Qi" in the immune microenvironment of liver cancer to achieve the balance of Yin and Yang. Based on this, the present study reviewed from the TCM theory and the mechanisms of western medicine to provide theoretical support for the TCM treatment of malignancies by elimination methods and some ideas for TCM in tumor resistance.
5.A strategy for population pharmaceutical quality assessment based on quality by design
Zhao YU ; Hu CHANGQIN ; Yao SHANGCHEN ; Yin LIHUI ; Ling XIAOMEI
Journal of Pharmaceutical Analysis 2021;11(5):588-595
From a regulatory perspective,drug quality consistency evaluation must concern different processes used for the same drug.In this study,an assessment strategy based on quality by design(QbD)was developed for population pharmaceutical quality evaluation.A descriptive analysis method based on QbD concept was first established to characterize the process by critical evaluation attributes(CEAs).Then quantitative analysis method based on an improved statistical process control(SPC)method was established to investigate the process indicators(PIs)in the process population,such as mean distri-bution,batch-to-batch difference and abnormal quality probability.After that rules for risk assessment were established based on the SPC limitations and parameters.Both the SPC parameters of the CEAs and the risk of PIs were visualized according to the interaction test results to obtain a better understanding of the population pharmaceutical quality.Finally,an assessment strategy was built and applied to generic drug consistency assessment,process risk assessment and quality trend tracking.The strategy demon-strated in this study could help reveal quality consistency from the perspective of process control and process risk,and further show the recent development status of domestic pharmaceutical production processes.In addition,a process risk assessment and population quality trend tracking provide data-based information for approval.Not only can this information serve as a further basis for decision-making by the regulatory authority regarding early warnings,but it can also reduce some avoidable adverse reactions.With continuous addition of data,dynamic population pharmaceutical quality is meaningful for emergencies and decision-making regarding drug regulation.
6.Construction of evaluation index system for health literacy of parents of children with Kawasaki disease
Qian TANG ; Qingqing SONG ; Lihui ZHU ; Yaojia HU ; Juan HUANG
Chinese Journal of Modern Nursing 2021;27(28):3828-3833
Objective:To construct an evaluation index system for health literacy of parents of children with Kawasaki disease, so as to provide a basis for accurately determining health literacy of parents of children with Kawasaki disease.Methods:A research team was established in September 2020. With the three dimensions of 66 Items of Chinese Citizens' Health Literacy as the basic framework, based on literature analysis and semi-structured interviews with 10 parents of children with Kawasaki disease were conducted, the primary evaluation indicators of health literacy of parents of children with Kawasaki disease was constructed. From October to December 2020, questionnaires were sent to 15 experts through email or Wechat for three rounds of Delphi expert consultation. And the evaluation indicators of health literacy of parents of children with Kawasaki disease were determined according to authority coefficient and Kendall's coordination coefficient. Results:The recovery rates of the three rounds of expert consultation questionnaires were all 100.00%, and the expert authority coefficients were 0.907, 0.913 and 0.920, respectively. In the third round of expert consultation, the Kendall's coordination coefficient of the coordination degree of general indexes, the first-level indexes and the second-level indexes were 0.376, 0.328 and 0.319 respectively (all P<0.01) . The final health literacy evaluation index system for parents of children with Kawasaki disease consisted of 3 first-level indicators and 34 second-level indicators. Conclusions:The established health literacy evaluation index system for parents of children with Kawasaki disease is scientific and reliable, which can provide an effective tool for nursing staff to accurately assess the health literacy of parents of children with Kawasaki disease.
7.Application progress of family-centered hospice care service model in pediatrics
Na ZHANG ; Qian TANG ; Lihui ZHU ; Dan LUO ; Muhua CHEN ; Yaojia HU
Chinese Journal of Modern Nursing 2021;27(35):4882-4887
According to the state's relevant policies on the development of hospice care, hospice care has become a social concern, and it is currently one of the key areas of medical development in China. This article elaborates on the current status and necessity of the development of children's hospice care, summarizes the application effects of family-centered child hospice care in the quality of life of children, the degree of grief of family members and the relationship between doctors and patients, and puts forward corresponding suggestions. This article aims at speeding up the standardized construction of the family-centered hospice care model in our country, and promote the development of children's hospice care in our country.
8.Bibliometric analysis of oral motor intervention in premature infants in China from 2010 to 2020
Qian TANG ; Na ZHANG ; Yaojia HU ; Lihui ZHU
Chinese Journal of Modern Nursing 2021;27(21):2832-2836
Objective:To explore the research and development trends of oral motor intervention in premature infants in China, so as to provide an effective reference for further development of oral motor intervention in premature infants.Methods:Chinese literature on oral motor intervention in premature infants included in the China National Knowledge Infrastructure (CNKI) , WanFang, VIP and China Biology Medicine database were searched by computer from January 2010 to October 2020. Quantitative analysis was carried out using Medical Literature King, Excel 2019 and SPSS 25.0.Results:The number of documents that met the requirements was 303, and the number of documents was on the rise. A total of 224 documents were published from 2013 to 2019, accounting for 73.93% of the total number of documents. Guangdong Province had the largest number of published documents, with 53 articles (17.49%) , followed by Jiangsu with 29 articles (9.57%) . The document fund support rate was 16.17% (49/303) , and the co-author rate was 64.03% (194/303) , and the author's collaboration was 1.96 (595/303) . Among the document types, the number of case-control studies was the largest, with 249 (82.18%) , and the second was review literature, with 32 (10.56%) . The contents of the document research were mainly feeding and growth and development, with 182 articles (60.07%) and 34 articles (11.22%) respectively. The evaluation indicators used were mainly oral feeding time, body weight, hospital stay and milk sucking volume.Conclusions:The overall number of the document is on the rise, and the research efforts continue to increase, but the quality of the document, fund support rate, and evidence-based strength still need to be improved, and the research content needs to be further expanded.
9.Analysis of clinical characteristics and related influencing factors of patients with early-onset gout
Lihui CHEN ; Si CHEN ; Fengjing LIU ; Zhumeng HU ; Ying HAN ; Mian WU ; Yiwen MA ; Junxi LU ; Haibing CHEN
Chinese Journal of Endocrinology and Metabolism 2020;36(9):767-772
Objective:To investigate the clinical features and influencing factors of early-onset gout.Methods:Male patients with gout admitted to Department of Endocrinology and Metabolism were recruited from 2015 to 2018. Patients with gout onset before age 30 were defined as the " early-onset" group, and those with onset at 30~60 years were defined as the "late-onset" group. Clinical characteristics were compared between two groups. Factors associated with early-onset gout were analyzed.Results:A total of 1 243 male patients were enrolled in this study; 480 individuals were in the early-onset, and 763 in the late-onset groups. Compared with the late-onset group, patients with early-onset gout had higher consumption rates of sugar-sweetened beverage(28.0% vs 15.0%, P=0.001), a higher homeostasis model assessment for insulin resistance level(3.78±2.93 vs 3.10±2.39, P<0.01), and larger proportions of family histories of diabetes(30.8% vs 20.4%, P<0.01)and hypertension(51.2% vs 42.6%, P=0.003). Logistic regression analysis showed that factors associated with early-onset gout were drinking sugar-sweetened beverage( P=0.012), family history of diabetes( P=0.037). Conclusion:Early-onset gout was associated with a family history of diabetes. Patients with family histories of diabetes are more likely to have early-onset gout, which may be associated with a common genetic basis.
10.Analysis of Clinical Characteristics and Driver Genes in 405 Patients with Lung Cancer Complicated with Tuberculosis.
Ying HU ; Xinjie YANG ; Lihui NIE ; Dan ZHAO ; Jun AN ; Baolan LI
Chinese Journal of Lung Cancer 2020;23(5):337-342
BACKGROUND:
New treatment methods such as targeted therapy and immune checkpoint inhibitors have been applied to lung cancer patients. It is necessary to further understand the patients with lung cancer combined with pulmonary tuberculosis with the development of lung cancer research. The purpose of this study was to analyze the clinical characteristics of lung cancer patients with pulmonary tuberculosis, the status of driver genes, and their relationships.
METHODS:
A retrospective analysis was performed on 405 patients with lung cancer and pulmonary tuberculosis hospitalized in our hospital from January 2014 to December 2019. The relationship between clinical characteristics and driver genes status was analyzed.
RESULTS:
Among the 405 patients with lung cancer combined with pulmonary tuberculosis, 77.3% were male and 85.3% were patients with a history of smoking. The pathological type was mainly lung adenocarcinoma. When there were cavities in chest computed tomography (CT) , squamous cell carcinoma was the main type. 214 patients underwent driver genes testing. The epidermal growth factor receptor (EGFR) gene mutation rate was 35.9%, of which 41.8% were exon 19 deletion mutations and 50.9% were exon 21 L858R mutations. When there were cavities in the chest CT, the EGFR mutation rate was significantly reduced (16.1%). The positive rate of anaplastic lymphoma kinase (ALK) fusion gene detection was 2.5%, the mutation rate of c-ros oncogene 1 receptor kinase (ROS1) gene was 1.9%, the mutation rate of V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene was 1.1%, and the mutation rate of Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene was 10.1%. The genetic mutation rate of female patients with lung cancer and pulmonary tuberculosis was 50.0%, and that of men was 27.9%.
CONCLUSIONS
Patients with lung cancer and pulmonary tuberculosis are predominantly male with smoking history. Adenocarcinoma is the most common pathological type. The positive rate of gene mutation was not significantly different from that of simple lung cancer, but when there were cavities in the chest image, the genetic mutation rate was significantly reduced.

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