1.Yijingtang Reduces Ovarian Inflammatory Responses in Rat Model of Diminished Ovarian Reserve via TLR4/MyD88/NF-κB Signaling Pathway
Heng HU ; Jijun CHU ; Zhe LI ; Haijing CHU ; Jing YU ; Chengcheng LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):20-30
ObjectiveTo investigate the effect and mechanism of Yijingtang (YJT) in treating diminished ovarian reserve (DOR) in rats by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank, model, low- and high-dose (12.579 and 25.158 g·kg-1, respectively) YJT, and dehydroepiandrosterone (7.487 5 mg·kg-1) groups, with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension (5 mg·kg-1) by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days, and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH)] and inflammatory factors [tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-10 (IL-10)] were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction(Real-time PCR) was conducted to determine the mRNA levels of TLR4, MyD88, NF-κB profilin α (IκBα), NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence (IF) was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group, the model group showed disturbed estrous cycles, increased inflammatory infiltration in the ovarian tissue, decreases in ovarian index and proportion of presinusoidal follicles, and an increase in the proportion of atretic follicles (P<0.05, P<0.01). In addition, the model group showed elevated serum levels of FSH, LH, TNF-α, and IL-1β, up-regulated mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.01), lowered serum levels of AMH, E2, and IL-10, down-regulated mRNA level of IL-10 (P<0.01), and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group, dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle, reduced inflammatory infiltration in the ovarian tissue, increased the ovarian index (P<0.01), and changed the follicular composition ratio (P<0.01). Furthermore, the drugs lowered the serum levels of FSH, LH, TNF-α, and IL-1β, down-regulated the mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and the protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.05, P<0.01), raised the serum levels of AMH, E2, and IL-10, up-regulated the mRNA level of IL-10 (P<0.05, P<0.01), and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue, thereby improving the ovarian function in DOR rats.
2.Yijingtang Reduces Ovarian Inflammatory Responses in Rat Model of Diminished Ovarian Reserve via TLR4/MyD88/NF-κB Signaling Pathway
Heng HU ; Jijun CHU ; Zhe LI ; Haijing CHU ; Jing YU ; Chengcheng LIANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):20-30
ObjectiveTo investigate the effect and mechanism of Yijingtang (YJT) in treating diminished ovarian reserve (DOR) in rats by regulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. MethodsFifty female SD rats with normal estrous cycles were randomly allocated into blank, model, low- and high-dose (12.579 and 25.158 g·kg-1, respectively) YJT, and dehydroepiandrosterone (7.487 5 mg·kg-1) groups, with 10 rats in each group. The rats in other groups except the blank group were administrated with the tripterygium glycosides tablet suspension (5 mg·kg-1) by gavage for 14 days for the modeling of DOR. The rats in the drug treatment groups were administrated with corresponding drugs by gavage from day 15 for 30 consecutive days, and those in the blank and model groups received equal volumes of distilled water. The vaginal exfoliated cell smears were observed to assess the changes in the estrous cycle. The wet weight of bilateral ovaries was weighed for calculation of the ovarian index. Hematoxylin-eosin staining was performed to observe the histopathological changes in the ovaries and the proportions of follicles at various levels were calculated. The serum levels of sex hormones [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH)] and inflammatory factors [tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-10 (IL-10)] were determined by enzyme-linked immunosorbent assay. Real-time quantitative polymerase chain reaction(Real-time PCR) was conducted to determine the mRNA levels of TLR4, MyD88, NF-κB profilin α (IκBα), NF-κB and inflammatory factors in the ovarian tissue. Western blot was employed to measure the protein levels of factors related to the TLR4/MyD88/NF-κB signaling pathway in the ovarian tissue. Immunofluorescence (IF) was used to detect the nuclear translocation of NF-κB p65 in the ovarian tissue. ResultsCompared with the blank group, the model group showed disturbed estrous cycles, increased inflammatory infiltration in the ovarian tissue, decreases in ovarian index and proportion of presinusoidal follicles, and an increase in the proportion of atretic follicles (P<0.05, P<0.01). In addition, the model group showed elevated serum levels of FSH, LH, TNF-α, and IL-1β, up-regulated mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.01), lowered serum levels of AMH, E2, and IL-10, down-regulated mRNA level of IL-10 (P<0.01), and massive nuclear translocation of NF-κB p65 in the ovarian tissue. Compared with the model group, dehydroepiandrosterone and low and high doses of YJT restored the disturbed estrous cycle, reduced inflammatory infiltration in the ovarian tissue, increased the ovarian index (P<0.01), and changed the follicular composition ratio (P<0.01). Furthermore, the drugs lowered the serum levels of FSH, LH, TNF-α, and IL-1β, down-regulated the mRNA levels of TLR4, MyD88, IκBα, NF-κB, TNF-α, and IL-1β and the protein levels of TLR4, MyD88, p-IκBα, and p-NF-κB p65 (P<0.05, P<0.01), raised the serum levels of AMH, E2, and IL-10, up-regulated the mRNA level of IL-10 (P<0.05, P<0.01), and reduced the nuclear translocation of NF-κB p65 in the ovarian tissue. ConclusionYJT may inhibit the release and expression of inflammatory factors by regulating the TLR4/MyD88/NF-κB signaling pathway to attenuate the inflammatory responses in the ovarian tissue, thereby improving the ovarian function in DOR rats.
3.Research progress in the application of supercooling preservation technology in graft preservation
Heng ZHAO ; Jinteng FENG ; Bangrui YU ; Yixing LI ; Haotian BAI ; Haishui HUANG ; Guangjian ZHANG
Organ Transplantation 2025;16(3):394-403
Supercooling preservation technology, as a groundbreaking innovation in the field of organ preservation, significantly reduces the metabolic rate of cells and inhibits ice crystal formation by placing organs in a low-temperature environment near or below the freezing point. This technology extends the preservation time of organs and maintains their biological activity. Compared with the traditional low-temperature preservation at 4 °C, supercooling preservation effectively avoids cell damage and the accumulation of metabolic products, demonstrating significant advantages in the preservation of cells, tissues and organs. In recent years, important progress has been made in the optimization of cryoprotectants, the application of antifreeze proteins, the improvement of vitrification technology, and the development of nanotechnology-based rewarming techniques. These advancements provide new pathways to address the challenges of toxicity, ice crystal formation and uneven rewarming rates during supercooling preservation. This review summarizes the basic principles of supercooling preservation, the application of key technologies, and their practical effects in organ transplantation. It also analyzes the challenges of toxicity and rewarming efficiency, aiming to provide theoretical support and research directions for the future optimization of organ low-temperature preservation technology and its clinical application.
4.Synthetic MRI Combined With Clinicopathological Characteristics for Pretreatment Prediction of Chemoradiotherapy Response in Advanced Nasopharyngeal Carcinoma
Siyu CHEN ; Jiankun DAI ; Jing ZHAO ; Shuang HAN ; Xiaojun ZHANG ; Jun CHANG ; Donghui JIANG ; Heng ZHANG ; Peng WANG ; Shudong HU
Korean Journal of Radiology 2025;26(2):135-145
Objective:
To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC).
Materials and Methods:
Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test.
Results:
The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively.
Conclusion
SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.
5.Can flexible ureteroscopy using flexible and navigable suction ureteral access sheath (FANS-UAS) minimize postoperative double J stent placement?Results from a propensity score-matched analysis of 540 patients of the European Association of Urology Section of Endourology and global FANS collaborative study group
Daniele CASTELLANI ; Bhaskar Kumar SOMANI ; Khi Yung FONG ; Steffi Kar Kei YUEN ; Chin Tiong HENG ; Mohamed ELSHAZLY ; Karl TAN ; Thomas R. W. HERRMANN ; Olivier TRAXER ; Vineet GAUHAR
Investigative and Clinical Urology 2025;66(3):236-244
Purpose:
To evaluate whether using flexible and navigable suction ureteral access sheath can obviate insertion of double J stent and establish the safety of overnight ureteric catheter placement as alternative following flexible ureteroscopy for kidney stones.
Materials and Methods:
Five hundred forty adults were prospectively enrolled across 25 centers (from April 2023 to January 2024). Patients were divided into group 1 (overnight ureteric catheter), and group 2 (double J stent). Surgeons could choose either modality as per their discretion. One-to-one propensity score-matching for age, sex, pre-stenting, Hounsfield units, stone volume and location was performed. Thirty-day computed tomography scan was done to estimate stone-free status.
Results:
After matching, 120 patients were included in each group. Group 1 had significantly shorter lasing, ureteroscopy, surgical time. Median day 1 loin pain score was similar (1 [1, 2] in both groups). Median postoperative stay was shorter in group 1 (0 days [0, 1] vs. 1 day [0, 2], p<0.001). One patient in group 2 required a blood transfusion. Incidence of fever was similar (5.0% vs. 0.8%).Loin/abdominal pain requiring medication occurred in one patient in group 2. Stent-related symptoms occurred in 2 patients in group 1. Three patients (2.5%) in group 1 and 2 patients (1.7%) in group 2 required readmission. Thirty-day stone-free status was higher in group 1 patients (79.2% vs. 56.7%).
Conclusions
In selected patients after thorough inspection to ensure no injury or residual fragments remain, placing an overnight ureteric catheter can be a safe alternative to a double J stent.
6.Synthetic MRI Combined With Clinicopathological Characteristics for Pretreatment Prediction of Chemoradiotherapy Response in Advanced Nasopharyngeal Carcinoma
Siyu CHEN ; Jiankun DAI ; Jing ZHAO ; Shuang HAN ; Xiaojun ZHANG ; Jun CHANG ; Donghui JIANG ; Heng ZHANG ; Peng WANG ; Shudong HU
Korean Journal of Radiology 2025;26(2):135-145
Objective:
To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC).
Materials and Methods:
Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test.
Results:
The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively.
Conclusion
SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.
7.Synthetic MRI Combined With Clinicopathological Characteristics for Pretreatment Prediction of Chemoradiotherapy Response in Advanced Nasopharyngeal Carcinoma
Siyu CHEN ; Jiankun DAI ; Jing ZHAO ; Shuang HAN ; Xiaojun ZHANG ; Jun CHANG ; Donghui JIANG ; Heng ZHANG ; Peng WANG ; Shudong HU
Korean Journal of Radiology 2025;26(2):135-145
Objective:
To explore the feasibility of synthetic magnetic resonance imaging (syMRI) combined with clinicopathological characteristics for the pre-treatment prediction of chemoradiotherapy (CRT) response in advanced nasopharyngeal carcinoma (ANPC).
Materials and Methods:
Patients with ANPC treated with CRT between September 2020 and June 2022 were retrospectively enrolled and categorized into response group (RG, n = 95) and non RGs (NRG, n = 32) based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The quantitative parameters from pre-treatment syMRI (longitudinal [T1] and transverse [T2] relaxation times and proton density [PD]), diffusion-weighted imaging (apparent diffusion coefficient [ADC]), and clinicopathological characteristics were compared between RG and NRG. Logistic regression analysis was applied to identify parameters independently associated with CRT response and to construct a multivariable model. The areas under the receiveroperating characteristic curve (AUC) for various diagnostic approaches were compared using the DeLong test.
Results:
The T1, T2, and PD values in the NRG were significantly lower than those in the RG (all P < 0.05), whereas no significant difference was observed in the ADC values between these two groups. Clinicopathological characteristics (Epstein–Barr virus [EBV]-DNA level, lymph node extranodal extension, clinical stage, and Ki-67 expression) exhibited significant differences between the two groups. Logistic regression analysis showed that T1, PD, EBV-DNA level, clinical stage, and Ki-67 expression had significant independent relationships with CRT response (all P < 0.05). The multivariable model incorporating these five variables yielded AUC, sensitivity, and specificity values of 0.974, 93.8% (30/32), and 91.6% (87/95), respectively.
Conclusion
SyMRI may be used for the pretreatment prediction of CRT response in ANPC. The multivariable model incorporating syMRI quantitative parameters and clinicopathological characteristics, which were independently associated with CRT response, may be a new tool for the pretreatment prediction of CRT response.
8.Identification of core genes of osteoarthritis by bioinformatics
Xuekun ZHU ; Heng LIU ; Hui FENG ; Yunlong GAO ; Lei WEN ; Xiaosong CAI ; Ben ZHAO ; Min ZHONG
Chinese Journal of Tissue Engineering Research 2025;29(3):637-644
BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.
9.Effect of Slicing Angle and Initial Water Content on Water Migration and Effective Ingredient Content in Drying Process of Salviae Miltiorrhizae Radix et Rhizoma
Guohong YANG ; Bingqian ZHOU ; Heng LU ; Xiao WANG ; Lanping GUO ; Wei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):208-216
ObjectiveTo explore the effects of angle and original moisture content on the moisture distribution, migration and contents of effective components in the drying process of sliced Salviae Miltiorrhizae Radix et Rhizoma(SMRR). MethodsSet the slicing angles of SMRR at 30°, 45°, and 90°. Cut the fresh samples, 1/3 dehydrated samples, and 2/3 dehydrated samples, dry them in an oven at 40 ℃ and take samples at the set time points. Low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were used to analyze the changes in transverse relaxation time(T2) of SMRR samples in 9 treatment groups at specific times, as well as the distribution and migration of water in the samples. The contents of tanshinone ⅡA, tanshinone Ⅰ, cryptotanshinone, and salvianolic acid B in samples from 9 different treatment groups were determined by high performance liquid chromatography(HPLC), and the best processing technology of SMRR was screened by combining with One-way ANOVA, Duncan multiple comparison and principal component analysis(PCA). ResultsThe moisture content of dry basis of SMRR in each treatment group decreased with the extension of drying time. The drying rate of fresh cut group decreased slowly at first, while the drying rate of water loss group showed a trend of increasing at first and then decreasing. The internal water of SMRR could be divided into three states, including bound water, non flowing water and free water. During the drying process, the water migration law showed that the free water of fresh cut group disappeared after drying for 12 h, the content of bound water gradually decreased, and the overall fluidity deteriorated. In the water loss group, part of the free water was transformed into more cohesive and non flowing water after drying for 3 h, and the three kinds of water basically disappeared after drying for 12 h. The MRI results showed that the entire dehydration process slowly moved from the outer side to the center, and the internal water eventually dissipated. In terms of the contents of active ingredients, the order of the effect of slicing angle on the total content of active ingredients in SMRR was 30°>45°>90°. The content of tanshinones was ranked as 1/3 dehydrated group>2/3 dehydrated group>fresh cut group, and the content of salvianolic acid B was ranked as 1/3 dehydrated group>fresh cut group>2/3 dehydrated group. Combined with the results of PCA and comprehensive scoring results, the overall level of effective component content in SMRR was the highest when cut at 30° after 1/3 of water loss. ConclusionAfter comprehensive evaluation, SMRR can be sliced at 30° after 1/3 of water loss. It is not only easy to cut, but also the surface and cross-sectional colors remain basically unchanged after drying, which is similar to the color under traditional processing, and the effective ingredients are preserved the highest. This study can provide a basis for the optimization of processing technology of SMRR.
10.Mechanism and Combination Therapy of Berberine in Treatment of Nonalcoholic Fatty liver Disease:A Review
Xiaojie WANG ; Heng ZHANG ; Sutong LIU ; Lihui ZHANG ; Wenxia ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):269-281
Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in the world. Because of its complex pathogenesis, high clinical prevalence and large population, it poses a great threat and challenge to public health in the world. Therefore, active intervention measures are needed. Currently, western medicine is effective in reducing weight, reducing liver fat content, improving glucose-lipid metabolism and insulin resistance. However, for patients with NAFLD-related fibrosis and cirrhosis, there is still a lack of sufficient histological evidence to support its benefits, and randomized controlled trials are still needed to clarify. Lifestyle intervention is an important cornerstone for the treatment of NAFLD, but there are many problems such as poor implementation and low compliance of patients, and the clinical efficacy is not ideal. Traditional Chinese medicine(TCM) has the significant advantages of multiple pathways and multiple targets. Berberine, the active ingredient of TCM, can interfere with the production of NAFLD from multiple pathways, including increasing energy consumption, weight loss, improving glucose-lipid metabolism, improving insulin resistance, anti-inflammatory, anti-oxidation, regulating intestinal flora, restoring bile acid homeostasis, anti-fibrosis and so on, which can play a positive role in the treatment of NAFLD. At the same time, it was found that the combination of BBR with Chinese and western medicines had significant advantages in promoting drug absorption, improving oral bioavailability, increasing the highest biological distribution in the liver, enhancing the overall therapeutic effect of NAFLD, and reducing adverse drug reactions, which could provide reference for clinical medication.

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