1.Analysis of Potential Active Ingredients and Mechanism of Baihu Jia Renshentang in Treatment of Obesity Complicated with Type 2 Diabetes Mellitus
Danni TAN ; Qin XIANG ; Yunfeng YU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):1-10
ObjectiveTo investigate the potential active ingredients and targets of Baihu Jia Renshentang(BHJRST) for the treatment of obesity combined with type 2 diabetes mellitus(T2DM) by network pharmacology and in vivo experiments. MethodUltra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was used to analyze and identify the material basis of BHJRST. Subsequently, potential targets for the action of the active ingredients were queried in databases such as ChEMBL, Therapeutic Target Database(TTD), YaTCM, DisGeNET and Traditional Chinese Medicine on Immuno-Oncology(TCMIO), and the shared targets were identified by taking the intersection of these targets with disease targets. The shared targets were imported into the STRING database to construct a protein-protein interaction(PPI) network, the hub genes were identified by cytoHubba plug-in, and molecular docking was used to validate the binding energy of the hub genes to the bioactive ingredients in BHJRST. Meanwhile, the shared targets were imported into the DAVID platform for gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The predicted results were subsequently verified by animal experiments. Eighteen 8-week-old male skeletal muscle insulin-like growth factor-1 receptor dysfunction(MKR) mice were induced by a high-fat diet for 12 weeks in order to prepare a mouse model of obesity combined with T2DM. The mice were randomly divided into the model group, metformin group(0.2 g·kg-1) and BHJRST group(27 g·kg-1 in raw material), and another 6 male FVB mice of the same age as the normal group. The mice in each group were were given the corresponding drugs by gavage, and the normal and model groups were given the same amount of distilled water by gavage, 1 time/d for 6 consecutive weeks. At the end of administration, the body mass, Lee's index, fasting blood glucose(FBG), oral glucose tolerance test(OGTT) of mice in each group were examined, and the pathological morphology of the white adipose tissue of the epididymis was observed, and the expression of the mRNA of the hub genes in the white adipose tissue of the epididymis was detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR). ResultA total of 200 bioactive components of BHJRST were identified, of which 64 bioactive components were reverse-matched to 384 targets, and a total of 308 targets were associated with obesity combined with T2DM. Hub genes included mitogen-activated protein kinase 1(MAPK1), signal transducer and activator of transcription 3(STAT3), MAPK3, interleukin(IL)-2, Janus kinase 1(JAK1), nuclear transcription factor-κB p65(RELA), estrogen receptor 1(ESR1), transcription factor AP-1(JUN), MAPK14 and lymphocyte-specific protein tyrosine kinase(LCK). GO functional annotation showed that it was mainly enriched in cytoplasm, cell membrane and nucleus, and was closely related to important biological processes such as peptide serine phosphorylation, protein phosphorylation and inflammation. In KEGG enrichment analysis, metabolic pathway, lipid and atherosclerosis, phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) and MAPK signal pathways were significantly enriched. The molecular docking results showed that the hub genes had a stable binding relationship with 10 bioactive components, including quercetin, isoliquiritigenin, and morin, in BHJRST. The results of animal experiments showed that BHJRST could significantly reduce body mass, Lee's index and FBG levels(P<0.01) in mice with obesity combined with T2DM, improve the pathological changes of white adipose tissue, and down-regulate the the mRNA expression of the hub genes in white adipose tissue of the epididymis(P<0.01). ConclusionIn this study, 10 potentially active components such as quercetin, isoliquiritigenin, and morin in BHJRST are identified through network pharmacology and animal experiments, and it is possible to treat obesity combined with T2DM by regulating lipid and atherosclerosis, phosphatidylinositol PI3K/Akt and MAPK signal pathways, which provides important clues and theoretical basis for the study of its mechanism and clinical application.
2.Unsupervised clustering analysis based on multidimensional features reveals distinct clinical characteristics and associated factors of different phenotypes in patients with chronic rhinosinusitis with nasal polyp
Jingyu HUANG ; Yongge LUO ; Hao LYU ; Duo LIU ; Yunfei WANG ; Peiqiang LIU ; Lu TAN ; Rong XIANG ; Wei ZHANG ; Yu XU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):590-601
Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.
3.Arthroscopic surgery for injuries to the popliteal tendon area of the lateral meniscus
Ming-Tao ZHANG ; Zhi-Tao YANG ; Tao LIU ; Bo-Rong ZHANG ; Xiao-Yi TAN ; Jin JIANG ; Li-Ping AN ; Xiang-Dong YUN
China Journal of Orthopaedics and Traumatology 2024;37(7):713-717
Objective To investigate the mid-term effect and complications of arthroscopic popliteal tendon suture in the treatment of lateral meniscus injury.Methods From January 2016 to December 2020,the data of 57 patients with lateral meniscus popliteal tendon injury treated by arthroscopic popliteal tendon suture fixation were retrospectively analyzed,includ-ing 35 males and 22 females,aged from 18 to 47 years old with an average of(32.9±7.9)years old.Knee function was evaluat-ed using the International Knee Documentation Committee(IKDC)and Lysholm scores both before the operation and at the fi-nal follow-up.Meniscus healing was evaluated according to the postoperative Barrett standard.Wound healing complications,such as vascular injury,nerve injury,and lower extremity venous thrombosis,were recorded.Results All 57 patients were fol-lowed up for 12 to 58 months with an average of(38.1±14.9)months.The incisions of the patients after the operation were all Grade A healing without infection,popliteal tendon injury,blood vessel injury,nerve injury and lower extremity venous throm-bosis.The IKDC score increased from(49.7±3.6)points preoperatively to(88.5±4.4)points in the final follow-up(P<0.05).The Lysholm score increased from(48.8±4.9)points preoperatively to(91.9±3.9)points at the final follow-up(P<0.05).At 3,6 months and 1 year after operation,according to Barrett's criteria,54 cases were clinically healed,the healing rate was 94.7%(54/57).Conclusion This study preliminarily confirmed that arthroscopic suture technique can result in clinical sta-bility through suture and fixation of the meniscus in the injured lateral popliteal tendon area.No adverse effects on knee joint function were found in the mid-term follow-up after the operation.
4.Different Characteristics of Psychological and Sleep Symptoms Across Social Media Addiction and Internet Gaming Disorder in Chinese Adolescents- A Network Analysis
Wanling ZHANG ; Liwen JIANG ; Minglan YU ; Rong MA ; Tingting WANG ; Xuemei LIANG ; Rongfang HE ; Chun XU ; Shasha HU ; Youguo TAN ; Kezhi LIU ; Bo XIANG
Psychiatry Investigation 2024;21(7):782-791
Objective:
Previous research has explored a variety of mental disorders associated with Internet Gaming Disoder (IGD) and Social Media Addiction (SMA). To date, few studies focused on the network characteristics and investigated mood and sleep symptoms across SMA and IGD of adolescence at a group-specific level. This study aims to identify different characteristics of IGD and SMA and further determine the group-specific psychopathology process among adolescents.
Methods:
We conducted a cross-sectional study to recruit a cohort of 7,246 adolescents who were scored passing the cutoff point of Internet Gaming Disorder Scale-Short Form and Bergen Social Media Addiction Scale, as grouped in IGD and SMA, or otherwise into the control group. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item, and Pittsburgh Sleep Quality Index were assessed for the current study, and all assessed items were investigated using network analysis.
Results:
Based on the analytical procedure, the participants were divided into three groups, the IGD group (n=789), SMA group (n=713) and control group (n=5,744). The edge weight bootstrapping analysis shows that different groups of networks reach certain accuracy, and the network structures of the three groups are statistically different (pcontrol-IGD=0.004, pcontrol-SMA<0.001, pIGD-SMA<0.001). The core symptom of SMA is “feeling down, depressed, or hopeless”, while IGD is “feeling tired or having little energy”.
Conclusion
Although IGD and SMA are both subtypes of internet addiction, the psychopathology processes of IGD and SMA are different. When dealing with IGD and SMA, different symptoms should be addressed.
5.Effect of Baihu Jia Renshen Tang on PI3K/Akt Signaling Pathway in Liver of MKR Diabetic Mice
Yutong CHEN ; Rong YU ; Yuqin WU ; Qin XIANG ; Yan TAN ; Cong ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(5):114-121
ObjectiveTo explore the effects of Baihu Jia Renshen Tang (BHRS) on the related molecules on the phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt)signaling pathway in the liver of MKR diabetic model mice. MethodThirty 6-week-old MKR mice were selected and fed on a high-fat diet for four weeks,followed by intraperitoneal injection of streptozotocin(STZ)for the diabetes model establishment. The model was properly induced in the case of the fasting blood glucose (FBG) of ≥11.1 mmol·L-1. After modeling,the mice were randomly divided into a model group,a BHRS group (12.09 g·kg-1·d-1),and a metformin group (0.065 g·kg-1·d-1),with 10 mice in each group. Ten FVB mice were assigned to the control group. The mice in the groups with drug intervention were continuously administered correspondingly for 28 days. After administration,the mice were sacrificed,followed by the oral glucose tolerance test (OGTT) and FBG detection. Serum very low-density lipoprotein(VLDL)content was determined by semi-quantitative enzyme-linked immunosorbent assay (ELISA). Four indexes related to blood lipid were determined by the biochemistry analyzer. Liver tissues were subjected to pathological examination by hematoxylin-eosin(HE)staining. Western blot was used to detect the protein expression of PI3K,Akt,phosphorylated(p)-PI3K,p-Akt,forkhead box protein O1 (FoxO1),insulin receptor(InsR),and insulin receptor substrate-2(IRS-2) in liver tissues of mice. Real-time polymerase chain reaction(Real-time PCR) was used to detect the mRNA expression of PI3K,Akt,FoxO1,InsR,and IRS-2 in liver tissues of mice. ResultCompared with the control group,the model group showed poor general conditions,abnormal glucose tolerance (P<0.05),increased FBG (P<0.01),abnormal blood lipid metabolism,increased serum total cholesterol (TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and VLDL (P<0.05),decreased level of high-density lipoprotein cholesterol(HDL-C)(P<0.05),fatty degeneration and obvious pathological changes of liver cells,reduced protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),increased protein expression of FoxO1(P<0.05),decreased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and increased FoxO1 mRNA expression(P<0.05). Compared with the model group,the BHRS group showed improved general conditions and glucose and lipid metabolism (P<0.05),improved pathological state of liver cells,increased protein expression of PI3K,Akt,p-PI3K/PI3K,p-Akt/Akt,IRS-2,and InsR in liver tissues(P<0.05),decreased protein expression of FoxO1(P<0.05),increased mRNA expression of PI3K,Akt,IRS-2,and InsR in liver tissues (P<0.05),and reduced FoxO1 mRNA expression(P<0.05). ConclusionBHRS can effectively reduce blood glucose,regulate blood lipid metabolism,and improve the pathological state of the liver in MKR diabetic mice,and its mechanism of action may be related to the regulation of the activity of molecules on the PI3K/Akt signaling pathway.
6.Exploration of the relationship between the storage time of leukodepleted red blood cell and transfusion adverse reactions
Liu HE ; Jian LIU ; Gang WU ; En WANG ; Fayan YI ; Xingshun TAN ; Shiyu ZHU ; Rui YU ; Guanghui LU ; Yan LIU ; Mei ZHAI ; Qing XIANG ; Ping LIU ; Yanhua LIAO ; Zhizhen FU ; Maolin LI ; Rong HUANG
Chinese Journal of Blood Transfusion 2023;36(10):889-891
【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.
7.Clinical study of intercondylar fossa formation to prevent intercondylar fossa impingement after high tibia osteotomy.
Sheng MA ; Xiang-Dong TIAN ; Ye-Tong TAN ; Jian WANG ; Guang-Yu ZHU ; Rong-Tian WANG ; Zhi-Peng XUE ; Yuan-Yi HU ; Tian-Song DING ; Xiao-Min LI
China Journal of Orthopaedics and Traumatology 2023;36(10):943-948
OBJECTIVE:
To observe the clinical efficacy of intercondylar fossa plasty in preventing intercondylar fossa impingement syndrome after high tibial osteotomy.
METHODS:
From August 2018 to August 2020, 84 patients with inverted knee osteoarthritis were treated by arthroscopy combined with high tibial osteotomy, and were divided into two groups with 42 cases in each group according to different surgical methods. In the intercondylar fossa plasty group, there were 13 males and 29 females, age ranged from 52 to 67 years old with an average of(58.27±4.32) years old, and arthroscopic intercondylar fossa plasty was performed first, and then high tibial osteotomy. In the arthroscopic cleansing group, 16 males and 26 females, age ranged from 50 to 71 years old with an average of (59.02±5.14) years old, underwent arthroscopic cleansing and then high tibial osteotomy. Postoperative treatment was evaluated using visual analogue scale(VAS), hospital for special surgery (HSS) score for the knee, and the occurrence of intercondylar percussa impingement.
RESULTS:
All 84 patients were followed up, the duration ranged from 12 to 18 months with an average of (14.1±1.6) months. The VAS and HSS score of knee joint at 6, 12 and 18 months after surgery were significantly improved compared with preoperative period, and there was no significant difference between the two groups (P>0.05), but the incidence of intercondylar fossa index and intercondylar fossa impact between the two groups was significantly compared 18 months after surgery (P<0.05).
CONCLUSION
Intercondylar fossa plasty can effectively prevent the incidence of intercondylar fossa impact after high tibial osteotomy, and has a more significant effect on postoperative knee pain and function improvement.
Male
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Female
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Humans
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Middle Aged
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Aged
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Tibia/surgery*
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Osteoarthritis, Knee/surgery*
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Knee Joint/surgery*
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Treatment Outcome
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Osteotomy/methods*
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Pain, Postoperative
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Retrospective Studies
8.Effect of Huangqi Guizhi Wuwutang on Diabetic Peripheral Neuropathy in MKR Mice via Regulating Endoplasmic Reticulum Stress
Fan XIAO ; Cong ZHOU ; Miao CAO ; Yan TAN ; Jinwei YANG ; Qin XIANG ; Xiu LIU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(16):1-8
ObjectiveTo investigate the mechanism of Huangqi Guizhi Wuwutang (HQGZWWT) in the treatment of diabetic peripheral neuropathy (DPN) in MKR mice via regulating endoplasmic reticulum (ER) stress. MethodThirty-two 8-week-old MKR mice (half were male and half were female) were fed with a high-fat diet for four weeks, and then 1% streptozotocin (STZ) was injected intraperitoneally for five days. After the blood glucose was stabilized, the mice were housed in the cage covered with ice bags for another one hour stimulation per day for four weeks. Mice with fasting blood glucose (FBG) value ≥11.1 mmol·L-1 were randomly divided into model group , Huangqi Guizhi Wuwutang in original dosage group (30 g·kg-1·d-1), Huangqi Guizhi Wuwutang in formula dosage group (6.25 g·kg-1·d-1), and positive drug group (mecobalamin tablets, 0.17 mg·kg-1·d-1). Another eight MKR mice of the same age were set as blank group and eight FVB mice were normal group. After four weeks of intragastric administration in each group, the change in FBG was tested, and hematoxylin and eosin (HE) staining and transmission electron microscope were used for observing the morphology of sciatic nerve tissue. In addition, the expression of c-Jun N-terminal kinase (JNK), phosphorylated c-Jun N-terminal kinase (p-JNK) and inositol requiring enzyme 1α (IRE1α) proteins was determined by immunohistochemical test and Western blot (WB). ResultCompared with the conditions in the normal group and blank group, the time of paw withdrawal, paw licking and tail flick in the model group was shortened (P<0.01), and the conduction velocity of sciatic nerve was decreased (P<0.01). Compared with the conditions in the model group, the behavioral and functional indicators were improved by HQGZWWT (P<0.05,P<0.01). The immunohistochemical test revealed the JNK expression was elevated in the model group compared with the conditions in the normal group and blank group (P<0.05), while that was lowered by HQGZWWT compared with the condition in the model group (P<0.05). However, there was no difference among the treatment groups. According to the WB, the expression of IRE1α and p-JNK in the model group was enhanced compared with the conditions in the normal group and blank group (P<0.05,P<0.01), while that was decreased by HQGZWWT compared with the condition in the model group (P<0.05,P<0.01). No difference was observed between the HQGZWWTO and HQGZWWTF groups. ConclusionHQGZWWT can improve the neurophysiological function and pathological damage of sciatic nerve, which may be related to its delaying the ER stress response of sciatic nerve.
10. Effects of mangiferin on obesity complicated with type 2 diabetes in MKR mice
Xu LIU ; Dan-Ni TAN ; Qin XIANG ; Li-Qing SU ; Rong YU ; Xiu LIU ; Rong YU
Chinese Pharmacological Bulletin 2022;38(11):1639-1646
Aim To investigate the mechanism of the effect of mangiferin on obesity complicated with type 2 diabetes mellitus in MKR transgenic mice. Methods MKR mice were randomly divided into model group,metformin group(0.11 g·kg-1),mangiferin low-dose group(25 mg·kg-1),mangiferin medium-dose group(50 mg·kg-1),and mangiferin high-dose group(100 mg·kg-1); FVB/N mice of the same age were used as control group. The mice were given intragastric administration for five weeks,the body weight and fasting glucose of mice were measured every week,the oral glucose tolerance(OGTT)was detected on 30th day of administration,and the insulin tolerance(ITT)was detected on 33rd day,and serum metabolic indexes were detected after administration. HE staining,oil-red O staining and Masson staining were used to observe the changes of liver morphology in mice. HE staining was used to observe the changes of fat morphology in mice. Western blot was used to detect the protein expression changes of TNF-α,IL-6,IL-1β in adipose tissues. Results High-dose mangiferin significantly reduced body weight,decreased fasting blood glucose,increased insulin content,and improved OGTT and ITT; it decreased serum triglyceride,alanine aminotransferase and aspartate aminotransferase levels; it also decreased the expression of serum IL-6 and TNF-α; it significantly reduced the expression of inflammatory factors in adipose tissues. Conclusions Mangiferin has therapeutic effects on obese MKR mice with type 2 diabetes,which is related to reducing the inflammatory response in adipose tissues.

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