1.Changes in hepatic bile acid profile in a mouse model of metabolic-associated steatohepatitis induced by a high-fat, high-sugar, and high-cholesterol diet combined with carbon tetrachloride
Jingjing WANG ; Jinghua PENG ; Yu LIU ; Feipeng XU ; Wei LIU ; Hailin YANG ; Ping LIU
Journal of Clinical Hepatology 2025;41(4):661-669
ObjectiveTo compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis (MASH) induced by a high-fat, high-sugar, and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride (CCl4) and MASH cases in clinical practice, and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group, with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil, and those in the model group were given a high-fat, high-sugar, and high-cholesterol diet, high-sugar drinking water, and weekly injections of CCl4+olive oil. At the end of weeks 8, 12, and 16, 5 mice were selected from each group to collect samples. Behavioral assessments were performed, and body weight and liver wet weight were measured; liver pathology and lipid deposition were evaluated by HE staining, SAF scoring, oil Red O staining, the semi-quantitative analysis of stained area, the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and liver triglyceride (TG) content; Sirius Red staining was performed for liver tissue to assess liver fibrosis; ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile, including cholic acid (CA), glycocholic acid (GCA), chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), hyodeoxycholic acid (HDCA), and glycodeoxycholic acid (GDCA). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point, the model group had disheveled and dull fur, reduced activity, and relatively slow reactions at weeks 8, 12, and 16, as well as significant increases in liver wet weight (P<0.05), the serum level of ALT (P<0.05), the content of TG in the liver (P<0.05), and SAF score (P<0.05). As for the differentially expressed bile acids in liver tissue, compared with the control group at week 8, the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA, TUDCA, HDCA, and GDCA (all P<0.05); compared with the control group at week 12, the model group had significantly higher levels of CA, GCA, CDCA, and GCDCA and significantly lower levels of UDCA and HDCA (all P<0.05); compared with the control group at week 16, the model group had significantly higher levels of CA, GCA, CDCA, GCDCA, and TUDCA and significantly lower levels of UDCA, HDCA, and GDCA (all P<0.05). As for the differentially expressed bile acids in the bile acid pool of liver tissue, compared with the control group at week 8, the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA, TUDCA, GDCA, and HDCA (all P<0.05); compared with the control group at weeks 12 and 16, the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA, GDCA, and HDCA (all P<0.05). ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat, high-sugar, and high-cholesterol diet combined with CCl4, which are similar to the changes in bile acids in MASH cases in clinical practice, suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.
2.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
3.Effects of mindfulness-based stress reduction therapy on fear of the disease progression, sleep and quality of life in patients with acute ischemic stroke
Xiongpo LIN ; Yunxiao LIU ; Jinghua MA ; Jing ZHAO ; Zilan HAO
Chinese Journal of Practical Nursing 2024;40(3):167-173
Objective:To explore the effects of mindfulness-based decompression therapy on fear of disease progression, quality of life and sleep quality in patients with acute ischemic stroke, in order to provide intervention measures to alleviate fear of the disease progression degree and improve sleep and quality of life in patients with acute ischemic stroke.Methods:This study was a randomized controlled study. Using the convenience sampling method, 98 patients with acute ischemic stroke who attended the Department of Neurology at the Third Hospital of Hebei Medical University from November 2021 to September 2022 were selected for the study, and the study population was divided into experimental group ( n=49) and control group ( n=49) using the random number table method. The control group received conventional care, and the experimental group received mindfulness-based stress reduction therapy for 8 weeks in addition to conventional care. Compared the scores of the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Stroke-Specific Quality of Life Scale (SS-QOL), and Pittsburgh Sleep Quality Index (PSQI) between the two groups of patients before and after intervention using two independent sample t-tests, and further compared the score spread of each scale before and after intervention between the two groups of patients using Mann-Whitney U test. Results:In the experimental group, 4 cases fell off and 3 cases had imperfect questionnaire information, while in the control group, 2 cases fell off and 5 cases had imperfect questionnaire information. Finally, 42 cases were included in each group. The 23 males and 19 females in the control group aged (48.31 ± 7.61) years old, while 25 males and 17 females in the experimental group aged (50.19 ± 8.64) years old. There was no significant difference in FoP-Q-SF, SS-QOL and PSQI scores between the two groups before intervention (all P>0.05). After intervention, the scores of FoP-Q-SF and PSQI in the experimental group (35.79 ± 7.04, 7.19 ± 2.58) were lower than those in the control group (38.52 ± 4.02, 9.45 ± 2.28), while the SS-QOL score (200.36 ± 21.75) was higher than that in the control group (185.41 ± 15.90), the differences were statistically significant ( t=2.19, -4.26, 3.60, all P<0.05). After intervention, the scores of FoP-Q-SF and PSQI in the experimental group were lower than those before intervention (39.69 ± 4.15, 10.00 ± 2.85), while the SS-QOL score was higher than that before intervention (176.93 ± 23.54), the differences were statistically significant ( t=4.80, 10.45, -11.43, all P<0.05). The score spreads of FoP-Q-SF, SS-QOL, and PSQI in the experimental group before and after intervention were 1.00 (0.00, 9.25), 20.00 (12.75, 32.75), 3 (1, 4), which were higher than 1.00 (-1.25, 2.00), 5.50 (1.00, 10.25), 0 (-1, 2) in the control group, the differences were statistically significant ( Z=-2.30, -5.74, -5.53, all P<0.05). Conclusions:Mindfulness-based decompression therapy can effectively relieve the fear of disease progression and improve the quality of sleep and life in patients with acute ischemic stroke.
4.Establishment and application of drug use evaluation criteria of argatroban
Hengfen DAI ; Caiyun ZHENG ; Yunchun LIU ; Hong ZHANG ; Maobai LIU ; Jinghua ZHANG
Chinese Journal of Pharmacoepidemiology 2024;33(2):121-127
Objective To establish the argatroban drug use evaluation(DUE)criteria and provide reference for the rational use of argatroban in clinical practice.Methods Based on the domestic and foreign drug instructions of argatroban,referring to relevant guidelines and literature,the DUE standard rules were established by expert consultation.Using the established standard rules,the medical records of argatroban in the Fuzhou First Hospital Affiliated with Fujian Medical University from August 2020 to August 2022 were evaluated for the rationality of medication.Results A total of 368 medical records were included,the rational rate of drug use was 48.64%,and the irrational drug use was mainly without indications(46.19%)and inappropriate combination of drugs(4.35%).Conclusion The rational rate of argatroban clinical use in the hospital is not high,and the problems mainly include off-indication drug use and unreasonable combination drug use.Through the establishment and clinical application of DUE standard rules,the clinical use of argatroban can be further standardized and the ability of rational drug use can be improved.
5.Clinical Study on Zhuanyaotang Granules for the Treatment of Degenerative Lumbar Spinal Stenosis
Daiyuan LIU ; Chunyu GAO ; Luguang LI ; Kexin YANG ; Wu SUN ; Jie LUO ; Minshan FENG ; Jianguo LI ; Lei LI ; Peng FENG ; Minrui FU ; Haibao WEN ; Jinghua GAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(1):159-163
Objective To observe the clinical efficacy of Zhuanyaotang Granules for the treatment of degenerative lumbar spinal stenosis(DLSS).Methods Using a randomized double blind controlled design,104 DLSS patients were divided into an experimental group and a control group using a random number table method,with 52 patients in each group.The treatment group took oral Zhuanyaotang Granules,methylcobalamin tablets and celecoxib capsule simulants.The control group used Zhuanyaotang Granules simulants,methylcobalamin tablets and celecoxib capsules.The course of treatment was 3 weeks for both groups.The follow-ups were conducted at 1 month and 3 months after treatment.The intermittent claudication distance,visual analogue scale(VAS)score and JOA efficacy rating criteria for low back pain score were observed in both groups before treatment,1,2,3 weeks of treatment and 1 month after treatment and 3 months after treatment.Adverse reactions during treatment were recorded.Results There were 5 cases of detachment and 2 cases of exclusion in the experimental group,and 5 cases of detachment and 1 case of exclusion in the control group.Compared with before treatment,there were statistically significant differences in intermittent claudication distance,VAS score,and JOA score between the two groups of patients at various time points during treatment and follow-up(P<0.05);there was no statistically significant difference in intermittent claudication distance,VAS score,and JOA score between the experimental group and the control group before treatment and 1 and 2 weeks of treatment(P>0.05);compared with the two groups at 3 weeks of treatment and 1 and 3 months after treatment,the intermittent claudication distance and JOA score in the experimental group were lower than those in the control group(P<0.05);There was no significant difference in VAS score between the two groups and the control group after 3 weeks of treatment(P>0.05).There were 2 adverse reactions(4.4%)in the experimental group and 5 adverse reactions(10.8%)in the control group,without statistical significance(P>0.05).Conclusion Zhuanyaotang Granules can effectively relieve pain and improve lumbar function in patients with DLSS,which is more effective and safer than oral celecoxib capsules and methylcobalamin tablets.
6.Application of color doppler flow imaging in the diagnosis of ocular toxocariasis in children
Wei CHEN ; Wenli YANG ; Jinghua LIU ; Dongjun LI ; Ziyang WANG ; Qi ZHAO ; Yifeng LI ; Rui CUI ; Lin SHEN ; Qian LIU
Chinese Journal of Ocular Fundus Diseases 2024;40(1):39-43
Objective:To summarize the characteristics of color doppler flow imaging (CDFI) of ocular toxocariasis (OT) in children.Methods:A retrospective clinical study. From July 2014 to June 2020, 61 OT patients with 61 eyes diagnosed through clinical and laboratory testing in the Department of Ophthalmology of Beijing Tongren Hospital of Capital Medical University were included in the study. There were 45 males with 45 eyes and 16 females with 16 eye (male: female=2.81:1). Age were (6.93±2.50) years. The right eye and left eye were 29 and 32 eyes, respectively. Both eyes of the patient underwent two-dimensional ultrasound and CDFI examination. Two dimensional ultrasound was used to estimate the axial length (AL) of the affected eyes and healthy eyes on the opposite side. Among them, 52 cases were measured for AL using optical biometry and/or A-mode ultrasound. Vitreoretinal surgery was performed within one week after ultrasound examination. Two-dimensional ultrasound was used to observe the morphology of vitreous opacity, its connection to the eyeball wall, and whether posterior vitreous detachment and retinal detachment have occurred. CDFI examination was used to observe the presence of blood flow signals on the pathological membrane. The detection rates of different forms of vitreous opacity and traction retinal detachment were calculated. The location of proliferative lesions in the eye was analyzed. Paired t-test was performed to compare the AL of the affected eye and the healthy eye on the opposite side. Perform Kappa consistency test on the location of proliferative lesions was used during CDFI examination and vitreoretinal surgery. Results:All affected eyes have varying degrees of vitreous opacity. Among them, 23 eyes (37.7%, 23/61) showed typical "Christmas tree" like turbidity; 27 eyes (44.3%, 27/61) had clustered and striped echoes; 9 eyes (14.8%, 9/61) had weak punctate and strip echoes. Two eyes (3.3%, 2/61) showed a large amount of dense punctate and strip-shaped echoes. There were 50 eyes (82.0%, 50/61) with traction retinal detachment, of which 46 eyes (92.0%, 46/50) had visible blood flow signals on the detached retina, and the remaining 4 eyes (8.0%, 4/50) had no blood flow signals. During CDFI and surgery, there were 5 (8.2%, 5/61) and 4 (6.6%, 4/61) eyes with visible proliferative lesions in the periphery, respectively; 18 (29.5%, 18/61) and 14 (23.0%, 14/61) eyes were distributed in the posterior pole, respectively; there were 38 (62.3%, 38/61) and 43 (70.5%, 43/61) eyes with both peripheral and posterior polar regions, respectively. The consistency between CDFI and surgery in detecting the location of proliferative lesions was good ( κ=0.832, 95% confidence interval 0.691-0.973, P<0.001). The two-dimensional ultrasound measurement results showed that the AL of the affected eye was shorter than that of the contralateral healthy eye in 46 cases (75.4%, 46/61). Among the 52 patients who underwent AL biometry, the AL of the affected eye was shorter than that of the contralateral healthy eye by (0.63±0.68) mm, and the difference was statistically significant ( t=-6.738, P<0.05). Conclusions:CDFI can clearly display various intraocular lesions (vitreous opacity and traction retinal detachment) and eyeball sizes in children with OT. Vitreous opacity is often manifested as "Christmas tree" like, clustered, strip-shaped.
7.Historical Evolution and Modern Clinical Application of Wuhutang
Zhiping LIU ; Kun SU ; Na LI ; Jianying BAI ; Rong WANG ; Jinghua MA
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):200-207
Wuhutang is the 51st Chinese medicine prescription of Han ethnic group on in the catalogue of ancient classical prescriptions (the second batch) ,which originated from Renzhai' Straight Diections Prescriptions (《仁斋直指方》) by YANG Shiying in the Song dynasty,it is composed of 5 medicines, including Ephedrae Herba,Armeniacae Semen Amarum, Glycyrrhizae Radix et Rhizoma, tea and Gypsum Fibrosum. It treats shortness of breath and phlegm. Following the principle of textual research on the key information of ancient classical famous prescriptions, the author collected and recorded the ancient books of traditional Chinese medicine of Wuhutang with the method of Bibliometrics, and screened out 53 valid data, involving 41 ancient books. Based on the historical evolution, drug composition, main treatment of disease and syndrome, drug dosage, method of preparation and usage, drug origin and processing, the author conducted a dig and a systematic study of Wuhutang. The results show that:in the later generations, besides inheriting the original prescription, the composition of medicine was added or subtracted, and the frequency of addition of Mori Cortex was the most;in the treatment of disease and syndrome, most of them inherited the original prescription mainly treating asthma syndrome, also see in the treatment of asthma, cough and other lung disease, in the drug dosage and method of use , it is suggested to inherit the original prescription, the dosage of each medicine is: Ephedrae Herba 2.89 g, Armeniacae Semen Amarum 4.13 g, Glycyrrhizae Radix et Rhizoma 1.65 g, tea 3.30 g, Gypsum Fibrosum 6.20 g, decoction, take warm clothes before eating;on the source of medcine,ephedra is made from the dried herbaceous stems of Ephedra sinica (Ephedraceae),bitter almond is made from the dried and mature seeds of Prunus armeniaca (Rosaceae),Licorice is made from the dried roots and rhizomes of Glycyrrhiza uralensis(Legumes), tea is made from the buds leaves of Camellia sinensis(Camellia),plaster is made from Gypsum Fibrosum of sulfate mineral gypsum family. At the same time, we collected and sorted the modern clinical application literature of Wuhutang, and obtained 73 effective literatures, all of which are for the treatment of respiratory system diseases, especially for children's pneumonia and asthma, and mostly belong to"phlegm-heat obstructing the lung syndrome". Through the analysis and study of ancient books and modern applied literature, the historical evolution and prescription evolution of Wuhutang are clarified, and its key information is determined, in order to provide more accurate reference for the research and development of the classic Wuhutang and the rational addition and subtraction of the application.
8.Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021
Ni CHEN ; He JIANG ; Huanhuan CHEN ; Qiuying ZHU ; Xiuling WU ; Jianjun LI ; Nengxiu LIANG ; Qin MENG ; Xuanhua LIU ; Jinghua HUANG ; Wenxuan HOU ; Zhaoquan WANG ; Guanghua LAN
Chinese Journal of Epidemiology 2024;45(4):529-535
Objective:To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021.Methods:The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis.Results:A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M ( Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m 2 and baseline CD4 +T lymphocyte (CD4) counts <200 cells/μl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m 2 and baseline CD4 counts ≥200 cells/μl were more likely to have complete immune reconstitution. Conclusions:In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.
9.Study on medication law of treatment for chronic atrophic gastritis based on data mining methods
Yunhao DIAO ; Ping LIU ; Ting CHEN ; Jinghua LI ; Ping WANG ; Xudong TANG
International Journal of Traditional Chinese Medicine 2024;46(10):1349-1355
Objective:To explore the medication law for treating chronic atrophic gastritis (CAG) through data mining methods.Methods:Literature on experiences in treating CAG was retrieved from CNKI, Wanfang data, and VIP from the establishment of the databases to December 31, 2023. The information on syndromes, treatment methods, and prescriptions was extracted for frequency statistics, clustering analysis, complex networks analysis were performed.Results:A total of 313 articles were included in the study, involving 581 experienced prescriptions, involving 5 kinds of TCM disease names, with "epigastric pain" as the most, followed by "fullness"; high-frequency syndromes included spleen-stomach qi deficiency syndrome, stomach collateral stasis syndrome, stomach yin deficiency syndrome, spleen-stomach damp-heat syndrome, liver-stomach qi stagnation syndrome; the main treatment methods used were promoting blood circulation and removing blood stasis, invigorating spleen and replenishing qi, regulating qi and harmonizing stomach, soothing liver and regulating qi, etc. The number of prescription drugs was mainly in 10-15 kinds of Chinese materia medica; a total of 321 kinds of Chinese materia medica were shared, and the top five Chinese medicines ranked by frequency were Atractylodis Macrocephalae Rhizoma, Poria, Paeoniae Radix Alba, Citri Reticulatae Pericarpium, Coptidis Rhizoma. The medicinal properties were mainly warm and neutral, and the tastes were mostly bitter, sweet and pungent. The meridians were mainly spleen, stomach, lung and liver meridians. The clustering analysis of high-frequency medication was mainly divided into 6 categories. The association rule analysis of Chinese materia medica and the complex network of Chinese materia medica showed the core compatibility and prescription of 5 high-frequency syndromes, respectively, showing the combination of Xiangsha Liujun Decoction, Chaihu Shugan Powder, Banxia Xiexin Decoction, Shashen Maidong Decoction and other classical prescriptions for syndrome differentiation and treatment combined with the experience of improving gastric mucosal lesions.Conclusion:Tonifying qi, removing blood stasis and detoxifying are the feature methods to treat CAG, embodying a "point surface combination" medication strategy that combines holistic diagnosis and syndrome differentiation and treatment with improvement of local mucosal lesions.
10.Genetic and molecular mechanism changes of adrenocortical carcinoma
Basic & Clinical Medicine 2024;44(6):748-752
Adreno-cortical carcinoma(ACC)is an uncommon tumor,some of them may produce excessive steroid hormone.The prognosis of ACC is quite poor and current treatment options are relatively limited,especially for pa-tients whose tumor is metastatic and difficult to remove by surgical operation.This makes the management of ACC challenging.Existing studies have shown that the mechanisms of ACC are complex.The molecular changes happen in adrenocortical development and homeostasis may explain the occurrence of ACC.This review focuses on recent studies and summarizes the genetic and molecular mechanism changes that potentially associated with ACC in the development process of the adrenal cortex and multi-omics studies,including genomic changes,epigenetic changes,differences in non-coding RNA,immune microenvironment and features found through multi-omics analy-sis.This information may support screening of therapeutic targets of ACC in future.

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