1.Mechanism of Modified Guishenwan in Regulating AMPK/Akt/Nrf2 Pathway to Improve Glucose and Lipid Metabolism and Oxidative Stress in Polycystic Ovary Syndrome Rats
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):1-8
ObjectiveBased on the adenosine 5'-monophosphate (AMP)-activated protein kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (AMPK/Akt/Nrf2) pathway, this study aims to explore the mechanism by which modified Guishenwan improves glucose and lipid metabolism and oxidative stress in polycystic ovary syndrome (PCOS) rats. MethodsA PCOS rat model was established by continuous oral administration of letrozole (1 mg·kg-1·d-1) for 21 days. Successfully modeled rats were randomly divided into a model group, a metformin group (0.25 g·kg-1), and low-, medium-, and high-dose modified Guishenwan groups (4.01, 8.02, and 16.04 g·kg-1·d-1), with 8 rats in each group. Ten normal rats were assigned to the normal group. The drug groups were given their respective doses, while the normal and model groups were given an equal volume of normal saline. Intervention lasted for 4 weeks. Testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by enzyme-linked immunosorbent assay (ELISA), and the LH/FSH ratio was calculated. Fasting blood glucose (FPG), fasting insulin (FINS), triglyceride (TG), and total cholesterol (TC) levels were measured using an automatic biochemical analyzer, and the insulin resistance index (HOMA-IR) and insulin sensitivity index (HOMA-ISI) were calculated. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted. Malondialdehyde (MDA), advanced glycation end products (AGEs), and superoxide dismutase (SOD) levels in serum and ovarian tissue were measured using a chemical fluorescence method. Hematoxylin-eosin (HE) staining was used to assess ovarian tissue pathology. Real-time quantitative fluorescent polymerase chain reaction (Real-time PCR) and Western blot were used to measure the expression of AMPK/Akt/Nrf2 pathway-related genes and proteins in ovarian tissue. ResultsCompared with the normal group, the model group exhibited significantly increased levels of T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly decreased (P<0.05, P<0.01). MDA and AGEs levels were significantly higher in both serum and ovarian tissue, and SOD levels were significantly reduced (P<0.05). AMPK, Akt, and Nrf2 mRNA and protein expression in ovarian tissue was also significantly reduced (P<0.05). The OGTT and ITT results showed significantly higher blood glucose levels at each time point (P<0.05, P<0.01), with impaired glucose and insulin tolerance. Ovarian follicles showed polycystic changes, reduced corpus luteum, and sparse granulosa cell layers. Compared with the model group, the metformin group and the high-dose modified Guishenwan group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05, P<0.01). In the high-dose modified Guishenwan group, MDA and AGEs levels in serum and ovarian tissue were significantly reduced, and SOD levels were significantly increased (P<0.05). The mRNA and protein expression of AMPK, Akt, and Nrf2 in ovarian tissue was significantly increased (P<0.05). OGTT and ITT results showed that blood glucose levels in rats decreased significantly at each time point (P<0.05, P<0.01). No obvious abnormalities were observed in ovarian tissue. Compared with the low-dose modified Guishenwan group, the high-dose group showed significant decreases in T, LH, LH/FSH, FPG, FINS, TG, TC, and HOMA-IR, while FSH, E2, and HOMA-ISI were significantly increased (P<0.05). OGTT and ITT results indicated that the high-dose modified Guishenwan group significantly improved glucose and insulin tolerance in rats. No significant abnormalities were observed in ovarian tissue. ConclusionModified Guishenwan effectively improves glucose and lipid metabolism abnormalities and inhibits oxidative stress in PCOS rats, potentially through regulation of the AMPK/Akt/Nrf2 pathway.
2.Theoretical Research on the Detailed Classification of Traditional Chinese Medicine Visceral Syndrome Differentiation Based on Syndrome-Formula Correspondence
Liqiu YU ; Zhuien WANG ; Mengfan LI ; Chengye CHEN ; Jiayu ZHANG ; Yi YANG
Journal of Traditional Chinese Medicine 2025;66(14):1504-1507
The current classification methods for traditional Chinese medicine (TCM) visceral syndrome differentiation suffer from excessive generalization, which hinders their clinical application. Based on the analysis of the pattern of "one syndrome corresponding to multiple formulas", this paper focused on the principle of syndrome-formula correspondence, and proposed that formula-syndromes are the smallest units for refining visceral syndromes. By establishing the correspondence between formula-syndromes and visceral syndromes, this study aims to further clarify the refined categories of syndromes and their treatment patterns, providing a new perspective for the standardization and objectification of TCM syndromes.
3.Modified Guishenwan Alleviates Inflammation in Rat Model of Polycystic Ovary Syndrome by Inhibiting MAPK/NF-κB Pathway
Jiayu TIAN ; Wenyi QIN ; Juan YANG ; Xiaofeng RONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):86-94
ObjectiveTo explore the mechanism by which modified Guishenwan alleviates inflammation in the rat model of polycystic ovary syndrome (PCOS) by regulating the mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. MethodsAccording to the random number table method, 60 SPF female SD rats were randomized into a normal group (n=10) and a modeling group (n=50). The normal group received routine feeding, while the modeling group was administrated with letrozole (1 mg·kg-1·d-1) by gavage for 21 days for the modeling of PCOS. The successfully modeled rats were randomized into model, diane-35 (0.2 g·kg-1·d-1), high- (16.04 g·kg-1·d-1), medium- (8.02 g·kg-1·d-1), low- (4.01 g·kg-1·d-1) dose modified Guishenwan groups. The drug intervention groups were administrated with modified Guishenwan at corresponding doses by gavage, and the normal group and model group were given equal volumes of normal saline. All the groups were continuously treated for 28 days. After treatment, Gram staining of vaginal smears was employed to observe the estrous cycle in each group. Enzyme-linked immunosorbent assay was employed to determine the levels of follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), testosterone (T), and progesterone (PROG) in the plasma, as well as interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) in the plasma and ovarian tissue. The LH/FSH ratio was calculated. The morphological changes in the ovarian tissue were observed by hematoxylin-eosin (HE) staining. Western blot was employed to determine the protein levels of extracellular-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), p38 MAPK, NF-κB p65, IκBα, p-JNK, p-ERK, p-p38 MAPK, p-NF-κB p65, and p-IκBα in the ovarian tissue. Real-time quantitative polymerase chain reaction was used to determine the mRNA levels of ERK, JNK, p38 MAPK, NF-κB p65, and IκBα in the ovarian tissue. ResultsCompared with the normal group, the model group was in the estrus phase, with an increase in the number of ovarian vesicles and decreases in granulosa cells and corpus luteum formation (P<0.05), and lowered levels of FSH and E2 and elevated levels of LH, T, and LH/FSH in the plasma (P<0.05). Compared with the model group, high-, medium-, and low-dose modified Guishenwan recovered the estrous cycle, increased the generation of granulosa cells and corpus luteum, reduced the number of vesicles, elevated the levels of FSH and E2, and lowered the levels LH, T, and LH/FSH (P<0.05, P<0.01) in a dose-dependent manner. High-dose modified Guishenwan demonstrated the best therapeutic effect. Therefore, subsequent experiments for exploring the treatment mechanism were conducted in the normal group, model group, and high-dose modified Guishenwan group. The results showed that compared with the model group, high-dose modified Guishenwan lowered the levels of IL-1β, TNF-α, and IL-10 and elevated the level of IL-10 in the plasma and ovarian tissue (P<0.05, P<0.01), down-regulated the protein levels of p-ERK, p-JNK, p-p38 MAPK, p-NF-κB p65, and p-IκBα, while up-regulating the protein level of IκBα (P<0.01). At the same time, the mRNA levels of ERK, JNK, p38 MAPK, and NF-κB p65 in the high-dose modified Guishenwan group were down-regulated (P<0.05, P<0.01). ConclusionModified Guishenwan can improve the ovarian function in rat model of PCOS induced by letrozole and has anti-inflammatory effects, which may be related to inhibition of the MAPK/NF-κB pathway.
4.Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
Tingting YANG ; Jiayu YUAN ; Yuting PENG ; Jiale PANG ; Zhen QIU ; Shangxiu CHEN ; Yuhan HUANG ; Zhenzhou JIANG ; Yilin FAN ; Junjie LIU ; Tao WANG ; Xueyan ZHOU ; Sitong QIAN ; Jinfang SONG ; Yi XU ; Qian LU ; Xiaoxing YIN
Journal of Pharmaceutical Analysis 2024;14(1):52-68
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
5.Pathological types and clinical features of unilateral primary aldosteronism
Jiayu LI ; Yi YANG ; Linqiang MA ; Junlong LI ; Wenwen HE ; Ying SONG ; Jinbo HU ; Shumin YANG ; Qifu LI ; Qianna ZHEN
Chinese Journal of Endocrinology and Metabolism 2024;40(2):139-144
Objective:To investigate the distribution of pathological types of unilateral primary aldosteronism, and to explore the clinical characteristics and prognosis of patients with different pathological types.Methods:A total of 241 patients with unilateral primary aldosteronism who underwent adrenal surgery were included in this study. The clinical data and postoperative follow-up data were collected, and the postoperative tissue sections were stained with HE and aldosterone synthase. According to the staining results, pathological types of 241 patients were classified, and the clinical characteristics and surgical prognosis of patients with unilateral primary aldosteronism were compared.Results:According to the international histopathology consensus for unilateral primary aldosteronism, among 241 patients with unilateral primary aldosteronism, 223 were classical(92.5%), 17 were non-classical(7.1%), and 1 was aldosterone producing carcinoma(0.4%). Among classical cases, 189 were aldosterone producing adenoma and 34 were aldosterone producing nodule. In the non-classical cases, 8 cases were multiple aldosterone producing nodule and 9 cases were multiple aldosterone producing nodule. Compared with the classical group, the non-classical group had a longer duration of hypertension(9.0 vs 5.0 years, P=0.062) and a lower baseline plasma aldosterone concentration(273 vs 305 pg/mL, P=0.147), but the difference was not significant. There was no significant difference between the two groups in the proportion of patients who achieved a complete biochemical response after surgery(98% vs 92.3%, P=0.281), but the proportion of patients who achieved a complete clinical response was significantly lower in the non-classical group(23.1% vs 52.9%, P=0.046). Conclusion:The pathological types of unilateral primary aldosteronism are predominantly classical, with aldosterone-producing adenoma being the most common. There were no significant differences in the clinical characteristics and postoperative biochemical remission rates between classical and non-classical patients, but the clinical prognosis of the latter was inferior to the former.
6.Analysis of Color and Odor Changes of Different Processed Products of Paeoniae Radix Alba Based on HS-GC-MS and Electronic Sensory Techniques
Jiayu PENG ; Yuzhen HUANG ; Jiawen WEN ; Yuqing ZHENG ; Ming YANG ; Jinlian ZHANG ; Yufan CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):141-150
ObjectiveTo investigate the correlation between the color, odor and volatile components of Paeoniae Radix Alba(PRA) and its processed products, and to examine the effects of different processing methods on the odor and color formation of PRA. MethodThe odor and chromaticity information of PRA, honey chaff-fried PRA and honey bran-fried PRA were identified by electronic nose and colorimeter, and the volatile components in the different processed products of PRA were identified and relatively quantified by headspace gas chromatography-mass spectrometry(HS-GC-MS), and analyzed using principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), then the differential key flavor components among the three were screened according to the principles of variable importance in the projection(VIP) value>1 and relative odor activity value(ROAV)≥1. Pearson correlation analysis was used to investigate the association between the differential flavor components and the colorimetric values and electronic nose sensors, respectively. ResultAfter being fried with honey chaff and honey bran, the lightness value(L*) of PRA decreased, and red-green value(a*) and yellow-blue value(b*) increased significantly(P<0.05, P<0.01). The odor differences were mainly reflected in the S1, S2, S4, S5, S6, S8 and S11 sensors, and the results of PCA of the electronic nose indicated that the odor differences among PRA, honey chaff-fried PRA and honey bran-fried PRA were obvious, among which the overall odor intensity of honey bran-fried PRA was higher than that of honey chaff-fried PRA. A total of 47 volatile components were identified from PRA and its processed products, including 21 for PRA, 36 for honey chaff-fried PRA, and 37 for honey bran-fried PRA. Odor analysis revealed that 12, 24 and 22 volatile components may be the key flavor components in PRA, honey chaff-fried PRA and honey bran-fried PRA, respectively. Correlation analysis showed that the L* of the decoction pieces was negatively correlated with the content of the Maillard reaction products, the a* and b* were positively correlated with the content of the Maillard reaction products, the S1 and S8 sensors were negatively correlated with the content of the Maillard reaction products, and the S2, S4, S5, S6 and S11 sensors were positively correlated with the Maillard reaction products. ConclusionThe color of PRA is deepened after being stir-fried with honey chaff and honey bran, and 5-hydroxymethylfurfural, furfural and other components are generated at the same time, which is in line with the theory of burning aroma strengthens the spleen of stir-fried with honey chaff and honey bran. Honey bran-fried PRA has a stronger Maillard reaction than honey chaff-fried PRA, which makes honey bran-fried PRA with a burnt flavor and a dark yellow color, while honey chaff-fried PRA has a sweet flavor and a bright yellow color.
7.Exploration on the mechanism of Jianpi Qingchang Decoction in the treatment of ulcerative colitis with network pharmacology, bioinformatics, molecular docking and experimental verification
Manting LIU ; Yanping DU ; Dongqiang LUO ; Qingyi YANG ; Jiayu WU ; Qiaoming FAN ; Huilian CAI ; Chuhong LIANG ; Yan LI ; Junwen OU
International Journal of Traditional Chinese Medicine 2024;46(7):889-897
Objective:To explore the mechanism of Jianpi Qingchang Decoction in the treatment of UC by integrating network pharmacology, bioinformatics, molecular docking and experimental verification.Methods:The effective components and targets of Jianpi Qingchang Decoction were obtained from TCMSP database, and UC data sets GSE16879, GSE48958 and GSE75214 were obtained from GEO database, and differentially expressed genes were screened; intersection targets were obtained through Venn diagram, and GO function and KEGG pathway enrichment analysis was performed. An intersection target PPI network was constructed using STRING database and topology analysis was performed; hub genes were screened through lasso regression and the expression consistency of core targets in the dataset was verified through logistic regression. A UC mouse model was established and hub genes were validated.Results:A total of 213 drug targets of Jianpi Qingchang Decoction were obtained, and 499 common intersection targets of GSE16879, GSE48958 and GSE75214 were obtained by differential gene expression analysis. Thirty intersection targets of Jianpi Qingchang Decoction and UC were obtained, mainly acting on IL-17 signaling pathway, TNF signaling pathway, AGE-RAGE signaling pathway in diabetic complications, etc. PPI network topology analysis obtained 7 common intersection targets, including PTGS2, IL-1B, IL-6, MMP9, CXCL8, CCL2 and MMP2. IL-6 and MMP2 were selected as hub genes by lasso regression. Logistics regression analysis showed that IL-6 and MMP2 were risk factors for the disease. Compared with the model group, the expressions of IL-6 and MMP2 mRNA and protein in the colon tissue of the TCM group decreased ( P<0.05), and the morphology of colon tissue was improved compared with the model group. Conclusion:IL-6 and MMP2 are risk factors for UC, the therapeutic effect of Jianpi Qingchang Decoction is to mediate Il-17 signal pathway, TNF signal pathway and AGE-RAGE signal pathway in diabetic complications through the targets of IL-6, and MMP2, thereby treating UC.
8.Preparation instructions of the Technical operation specification for TCM health care services (non-medical) foot bath (2024 edition)
Lingyun ZHANG ; Changhe YU ; Changxin LIU ; Luping LIU ; Yixuan GAO ; Jiayu LIU ; Yuhan WANG ; Mengmeng ZHANG ; Yang ZHANG ; Xiyou WANG
International Journal of Traditional Chinese Medicine 2024;46(10):1258-1263
Foot bath technique is booming in daily health care services. In order to develop a more standardized and complete technical operation process, the working group recorded the whole process of document formulation while writing the Technical Operation Specification for TCM Health Care Services (Non-Medical) Foot Bath (2024 edition). Work profile (including task background, task source, drafting unit, participant grouping and responsibilities), main technical content (including the basis and principles of preparation, key technical content of technical specifications), main preparation process (formation of working groups, registration and plan writing, selection and determination of clinical issues, literature research, drafting of the first draft, consensus on the main content of technical specifications, soliciting opinions, testing applications and external review), the relationship of current mandatory national standards or policies and regulations, the treatment process and basis of major differences, publicity and implementation and post-effect evaluation, the proposal to abolish the current relevant guidelines and the corresponding annexes were under detailed and in-depth description, which can assist the relevant practitioners of non-medical institutions to better understand and apply this technical specification.
9.Cost Analysis of Artificial Intelligence Assisted Diagnosis Technology Based on CCTA Imaging
Jiayu ZHAO ; Liwei SHI ; Nan LUO ; Zhenghan YANG ; Yongjun LIU ; Yue XIAO
Chinese Health Economics 2024;43(11):35-40
Objective:To carry out a study on the cost analysis of the clinical use of Artificial Intelligence-assisted Diagnosis Technology for Coronary CT Angiography(CCTA-AI)to explore the cost differences and cost effects of Coronary CT Angiography(CCTA)examinations before and after the introduction of Artificial Intelligence(AI),and analyze the impact of the application of AI technology on the high-quality development of public hospitals.Methods:The operation cost method was used to measure the changes in the cost and efficiency of CCTA examinations before and after the application of AI technology in five sample hospitals in Beijing,and diagnostic accuracy was used as the effect value to calculate the cost effect of CCTA-AI diagnosis versus CCTA-manual diagnosis,and to analyze the main factors affecting the unit cost.Results:The average cost of examination in 5 sample hospitals after the application of AI-assisted diagnosis system was 1 074.90 yuan,and 1 266.61 yuan before the application,with a large difference between institutions.The cost-effectiveness analysis based on diagnostic accuracy showed that the AI group had an absolute advantage over the manual group,with a cost of 1 074 900 yuan for the AI group and an effectiveness of 855.05 persons,and a cost of 1 266 610 yuan for the physician group,with an effectiveness of 815.07 persons for the high-year-end physician group,and an effectiveness of 793.40 persons for the low-year-end physician group;0.46 man-hours could be saved for each patient examined;the unit cost of CCTA examination was affected by a number of factors,among which"the number of annual examinations"and"the number of CT units involved in CCTA examination"had the greatest influence on the unit cost of CCTA examination.Conclusion:The application of AI-assisted diagnostic technology can promote the improvement of quality and efficiency in public hospitals in a certain extent,and help optimize the overall distribution of medical resources at the system level.In the future,the cost analysis of AI technology should be further strengthened to comprehensively assess its actual contribution to the healthcare system.
10.One case of myelosuppression caused by pamiparib in combination with temozolomide in the treatment of small cell lung cancer
Yuchen YANG ; Yuting ZHAO ; Shiqi LI ; Jiayu GONG ; Riguga SU ; Yanyan SUN ; Zhihui CAI
Chinese Journal of Pharmacoepidemiology 2024;33(7):824-829
A 50-year-old male patient diagnosed with extensive stage small cell lung cancer was treated with pamiparib in combination with temozolomide.Five days later,the patient developed fever with fatigue.After 10 days,the patient stopped taking the drug due to worsening symptoms and was diagnosed with chemotherapy-induced myelosuppression(grade 4).The clinicist evaluated the patient's condition and assessed the association of adverse reactions using the Naranjo's evaluation scale,and concluded that myelosuppression may be induced by the combination of pamiparib and temozolomide.After symptomatic treatment,the patient's myelosuppression recovered completely.This article discusses the correlation between myelosuppression and the combination of the two drugs,provides treatment measures for this situation,briefly describes the risk factors of myelosuppression,treatment and prevention,and guides medical personnel to adjust the treatment plan in time according to different individuals in the process of using similar programs,and strengthens the monitoring and education of adverse drug reactions,so as to provide references for safe drug use.

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