1.Exploration of Mechanism of Huanglian Zhimutang in Treatment of Type 2 Diabetes Mellitus Based on PI3K/Akt Pathway
Lei WANG ; Yun PAN ; Lihua WAN ; Wenling TU ; Lingyong CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):168-177
ObjectiveBased on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance (IR) with type 2 diabetes mellitus (T2DM) were investigated. MethodsGoto-Kakizaki (GK) rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups: normal control group, model control group, metformin group (0.10 g·kg-1), and Huanglian Zhimutang group (3.60 g·kg-1), with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin (FINS) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin (HE) staining. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes (DEGs) in liver tissue from the normal control group, model control group, and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of insulin receptor substrate-1 (IRS-1), PI3K, Akt, and peroxisome proliferator-activated receptor gamma (PPARγ) in liver tissue, while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention, typical symptoms of T2DM rats such as polydipsia, polyphagia, and polyuria were significantly alleviated, along with reductions in fasting blood glucose levels and insulin resistance(P<0.01). Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC, TG, and LDL-C(P<0.01). ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α(P<0.05,P<0.01). Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue(P<0.05,P<0.01), thereby reducing inflammation, alleviating hepatic lipid accumulation, and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway, which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.
2.Exploration of Mechanism of Huanglian Zhimutang in Treatment of Type 2 Diabetes Mellitus Based on PI3K/Akt Pathway
Lei WANG ; Yun PAN ; Lihua WAN ; Wenling TU ; Lingyong CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):168-177
ObjectiveBased on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance (IR) with type 2 diabetes mellitus (T2DM) were investigated. MethodsGoto-Kakizaki (GK) rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups: normal control group, model control group, metformin group (0.10 g·kg-1), and Huanglian Zhimutang group (3.60 g·kg-1), with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin (FINS) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the homeostasis model assessment of insulin resistance (HOMA-IR) index was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin (HE) staining. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes (DEGs) in liver tissue from the normal control group, model control group, and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to assess the mRNA expression of insulin receptor substrate-1 (IRS-1), PI3K, Akt, and peroxisome proliferator-activated receptor gamma (PPARγ) in liver tissue, while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention, typical symptoms of T2DM rats such as polydipsia, polyphagia, and polyuria were significantly alleviated, along with reductions in fasting blood glucose levels and insulin resistance(P<0.01). Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC, TG, and LDL-C(P<0.01). ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α(P<0.05,P<0.01). Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue(P<0.05,P<0.01), thereby reducing inflammation, alleviating hepatic lipid accumulation, and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway, which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.
3.Near Infrared Spectral Analysis Based on Data Augmentation Strategy and Convolutional Neural Network
Yun ZHENG ; Si-Yu YANG ; Tao WANG ; Zhuo-Wen DENG ; Wei-Jie LAN ; Yong-Huan YUN ; Lei-Qing PAN
Chinese Journal of Analytical Chemistry 2024;52(9):1266-1276
Near infrared spectroscopy(NIRS)technology combined with chemometrics algorithms has been widely used in quantitative and qualitative analysis of food and medicine.However,traditional chemometrics methods,especially linear classification methods,often yield unsatisfactory results when addressing multi-class classification problems.Convolutional neural network(CNN)is adept at extracting deep-level features from data and suitable for handling non-linear relationships.The modeling performance of CNN depends on the size and diversity of sample,while the collection and preprocessing of NIRS sample data is often time-consuming and labor-intensive.This study proposed a NIRS qualitative analysis method based on data augmentation strategies and CNN.The data augmentation strategy included two steps.Firstly,applying Bootstrap resampling and generative adversarial network(GAN)methods to augment three NIRS datasets(Medicine,coffee and grape).Secondly,combining the original samples(Y)with the Bootstrap augmented samples(B)and GAN augmented samples(G)to obtain three augmented datasets(Y-B,Y-G and Y-B-G).Based on this,a CNN model structure suitable for these datasets was designed,consisting of 2 one-dimensional convolutional layers,1 max-pooling layer,and 1 fully connected layer.The results showed that compared to the optimal models of partial least squares discriminant analysis(PLS-DA),support vector machine(SVM),and back propagation neural network(BP),the CNN model based on Y-B dataset achieved average accuracy improvements of 3.998%,9.364%,and 4.689%for medicine(Binary classification);the CNN model based on the Y-B-G dataset achieved average accuracy improvements of 6.001%,2.004%,and 7.523%for coffee(7-class classification);and the CNN model based on the Y-B dataset achieved average accuracy improvements of 33.408%,51.994%,and 34.378%for grapes(20-class classification).It was evident that the models established based on data augmentation strategies and CNN demonstrated better classification accuracy and generalization performance with different datasets and classification categories.
4.Au/Three-dimensional Graphene Hydrogel Modified Graphene Electrochemical Transistor for Highly Sensitive Detection of Dopamine
Ru-Ling WANG ; Zhi-Wei CAI ; Jun-Zi PAN ; Ru-Nan TAN ; Yun-Bin HE ; Gang CHANG
Chinese Journal of Analytical Chemistry 2024;52(9):1307-1315,中插5-中插10
Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.
5.The impact of different contrast agent concentrations on excimer laser ablation:an in vitro study
Pan HE ; Yang SHI ; Hai-Wei CHEN ; Jun-Jie YANG ; Jun GUO ; Yun-Dai CHEN ; Qi WANG
Chinese Journal of Interventional Cardiology 2024;32(1):39-44
Objective To explore the impact of contrast agent concentration on the excimer laser's effect on plaque ablation.Methods Using a laser catheter with a diameter of 0.9 mm,we conducted plaque model ablation experiments employing a 308-nanometer xenon chloride excimer laser.During the excimer laser ablation process,five groups were formed based on the injected contrast agent concentrations:a saline group,25%concentration group,50%concentration group,75%concentration group,and 100%concentration group.Optical coherence tomography was utilized to assess the changes in plaque lumen area after excimer laser ablation,evaluating the impact of contrast agent concentration on the excimer laser's ablation efficacy.Simultaneously,a water manometer was used to measure the shockwave pressure generated by the excimer laser in liquids with different contrast agent concentrations,aiming to explore the correlation between the shockwave pressure of the excimer laser and its ablative effect.Results The ablation areas in the 75%concentration group and the 100%concentration group were similar(P>0.05),both exceeding those in the 50%concentration contrast agent group,25%concentration group,and saline group(all P<0.001).Specifically,the ablation area in the 50%concentration group was significantly larger than that in the 25%concentration group and saline group(both P<0.001),while the 25%concentration group was larger than the saline group(P<0.001).The influence of contrast agent concentration on the shockwave pressure of the excimer laser exhibited a similar trend.Additionally,there was a significant positive correlation between the shockwave pressure generated by the excimer laser and its ablation area(r=0.9987,P<0.001).Conclusions The intensity of excimer laser ablation on plaque tissue can be modulated by altering the contrast agent concentration.These findings offer guidance for the application of excimer laser in conjunction with contrast agent injection techniques in the treatment of coronary artery disease.
6.Simultaneous content determination of seventeen constituents in Yangxue Ruanjian Capsules by UPLC-MS/MS
Yong-Ming LIU ; Shu-Sen LIU ; Yi-Zhe XIONG ; Xiang WANG ; Yu-Yun WU ; Jin LIU ; Ling-Yun PAN ; Guo-Qing DU ; Hong-Sheng ZHAN
Chinese Traditional Patent Medicine 2024;46(2):353-358
AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.
7.Association between variability of triglyceride glucose index and risk of type 2 diabetes
Ying PAN ; Shuting LIU ; Xiaohua CHEN ; Min HUANG ; Yueqing HUANG ; Yun TANG ; Qianqian WANG ; Kaixin ZHOU ; Jian SHAO ; Shao ZHONG
Chinese Journal of General Practitioners 2024;23(11):1162-1167
Objective:To explore the association between the variability of triglyceride glucose index (TyG) and the risk of type 2 diabetes mellitus(T2DM).Methods:This study was a retrospective cohort study. A total of 22 929 community-dwelling elderly (aged≥60 years) who received annual health check-ups in Kunshan city of Suzhou Municipality during 2014 to 2021 were enrolled in the study. Fasting triglycerides and blood glucose were measured during annual physical check-ups and the TyG was calculated, the standard deviation of TyG measurements in three consecutive physical check-ups was used as the indicatior of TyG long-term variability. According to the quartile of TyG long-term variability, the study subjects were divided into four groups, namely Q 1 (0-0.14), Q 2 (>0.14-0.22), Q 3 (>0.22-0.33), Q 4 (>0.33-1.90). The outcome variable was the occurrence of T2DM. The relationship between TyG variability and T2DM incidence was analyzed by multivariate Cox regression. Results:In the study cohort 11 518 (50.2%) were females and the mean age was (67.42±5.35) years. By the end of follow-up, 2 934 cases of new T2DM were diagnosed, with an oveall incidence rate of 12.8%. After adjusting for multiple confounders and average TyG, long-term variability of TyG was significantly associated with T2DM risk ( HR=1.83, 95% CI: 1.51-2.20). The risk of T2DM in Q 4 group was significantly higher than that in Q 1 group ( HR=1.33, 95% CI: 1.19-1.47). Kaplan-Meier survival curve showed that long-term variability of TyG was significantly correlated with the cumulative risk of T2DM incidence ( P<0.001). Conclusions:TyG variability is an independent risk factor for T2DM, suggesting that attention should be paid not only to specific time-point TyG levels but also to TyG fluctuation for early identification of T2DM risk.
8.Anti-SARS-CoV-2 antibody levels in previously infected and re-infected populations in Henan Province, China
Yun SONG ; Shidong LU ; Bicong WU ; Haiyan WEI ; Wenhua WANG ; Yafei LI ; Xue LUO ; Jingjing PAN ; Hongxia MA ; Haifeng WANG ; Ying YE ; Wanshen GUO ; Xueyong HUANG
Chinese Journal of Microbiology and Immunology 2024;44(9):801-808
Objective:To analyze the reinfection rates in people previously infected with SARS-CoV-2 in Zhengzhou and Yuzhou cities (first infected with Delta/B.1.617.2 variant), and Anyang city (first infected with Omicron/BA.1.1 variant) in January 2022 and the population characteristics, and compare the differences in antibody levels among different populations.Methods:Serum samples were collected from 371 previously infected, 134 reinfected and 19 uninfected people for IgG antibody detection. Among them, serum samples from 45 previously infected, 44 reinfected and 19 uninfected people were tested with different novel coronavirus variants (early original strain, BA.5.2 variant, XBB.1.5 variant) for neutralizing antibody detection.Results:The rate of reinfection was 32.82% (85/259) in Zhengzhou and Yuzhou cities, and 19.92% (49/246) in Anyang city. The IgG antibody level in reinfected people was higher than that in previously infected and uninfected people ( P<0.05). The IgG antibody level in uninfected group was higher in people vaccinated within three months than in those vaccinated six months ago ( P<0.05). The IgG antibody level in the group receiving four doses of vaccine was higher than that in the group receiving three doses of vaccine ( P<0.05). The results of true virus neutralization antibody detection showed that in the Zhengzhou and Yuzhou cases, the level of neutralization antibody against the early original strain was higher than those against the BA.5.2 variant and the XBB.1.5 variant ( P<0.05), and the level of neutralizing antibody against BA.5.2 variant was higher than that against XBB.1.5 variant ( P<0.05). In Anyang city cases, the level of neutralizing antibody against the early original strain was higher than those against BA.5.2 variant and XBB.1.5 variant ( P<0.05); in the reinfected population, the level of neutralizing antibody against the early original strain was higher than that against the XBB.1.5 variant ( P<0.05). In addition, the levels of all neutralizing antibodies in both previously infected and reinfected people were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody in the infected population in Zhengzhou and Yuzhou cities was higher than that in the infected population in Anyang city and in uninfected population ( P<0.05). The levels of antibodies against BA.5.2 and anti-XBB.1.5 variants in infected people in Zhengzhou and Yuzhou cities were higher than those in uninfected people ( P<0.05). The level of neutralizing antibody against BA.5.2 variants in the previously infected population in Anyang city was higher than that in the uninfected population ( P<0.05), and the level of neutralizing antibody against XBB.1.5 variants in the infected population in Anyang city was higher than that in the uninfected population ( P<0.05). Conclusions:After infection with SARS-CoV-2, the neutralizing antibodies produced in the human body have a certain cross-protection effect on other variants, but the antibody level will gradually decrease over time. Protection from a previous early SARS-CoV-2 variants infection against the current main circulating Omicron variants (such as XBB variants) is low, and the immunity conferred by pervious infection or booster vaccination may not be able to provide sufficient protection against new variants.
9.Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture (version 2024)
Yun HAN ; Feifei JIA ; Qing LU ; Xingling XIAO ; Hua LIN ; Ying YING ; Junqin DING ; Min GUI ; Xiaojing SU ; Yaping CHEN ; Ping ZHANG ; Yun XU ; Tianwen HUANG ; Jiali CHEN ; Yi WANG ; Luo FAN ; Fanghui DONG ; Wenjuan ZHOU ; Wanxia LUO ; Xiaoyan XU ; Chunhua DENG ; Xiaohua CHEN ; Yuliu ZHENG ; Dekun YI ; Lin ZHANG ; Hanli PAN ; Jie CHEN ; Kaipeng ZHUANG ; Yang ZHOU ; Sui WENJIE ; Ning NING ; Songmei WU ; Jinli GUO ; Sanlian HU ; Lunlan LI ; Xiangyan KONG ; Hui YU ; Yifei ZHU ; Xifen YU ; Chen CHEN ; Shuixia LI ; Yuan GAO ; Xiuting LI ; Leling FENG
Chinese Journal of Trauma 2024;40(9):769-780
Hip fracture in the elderly is characterized by high incidence, high disability rate, and high mortality and has been recognized as a public health issue threatening their health. Surgery is the preferred choice for the treatment of elderly patients with hip fracture. However, lower extremity deep venous thrombosis (DVT) has an extremely high incidence rate during the perioperative period, and may significantly increase the risk of patients′ death once it progresses to pulmonary embolism. In response to this issue, the clinical guidelines and expert consensuses all emphasize active application of comprehensive preventive measures, including basic prevention, physical prevention, and pharmacological prevention. In this prevention system, basic prevention is the basis of physical and pharmacological prevention. However,there is a lack of unified and definite recommendations for basic preventive measures in clinical practice. To this end, the Orthopedic Nursing Professional Committee of the Chinese Nursing Association and Nursing Department of the Orthopedic Branch of the China International Exchange and Promotive Association for Medical and Health Care organized relevant nursing experts to formulate Expert consensus on perioperative basic prevention for lower extremity deep venous thrombosis in elderly patients with hip fracture ( version 2024) . A total of 10 recommendations were proposed, aiming to standardize the basic preventive measures for lower extremity DVT in elderly patients with hip fractures during the perioperative period and promote their subsequent rehabilitation.
10.Different methods in predicting mortality of pediatric intensive care units sepsis in Southwest China
Rong LIU ; Zhicai YU ; Changxue XIAO ; Shufang XIAO ; Juan HE ; Yan SHI ; Yuanyuan HUA ; Jimin ZHOU ; Guoying ZHANG ; Tao WANG ; Jianyu JIANG ; Daoxue XIONG ; Yan CHEN ; Hongbo XU ; Hong YUN ; Hui SUN ; Tingting PAN ; Rui WANG ; Shuangmei ZHU ; Dong HUANG ; Yujiang LIU ; Yuhang HU ; Xinrui REN ; Mingfang SHI ; Sizun SONG ; Jumei LUO ; Juan LIU ; Juan ZHANG ; Feng XU
Chinese Journal of Pediatrics 2024;62(3):204-210
Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

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