1.A retrospective analysis of rescue events among 86 inpatients following radiotherapy for head and neck cancer
LIAO Yanling ; WU Jianlin ; LIANG Feixin
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):65-74
Objective:
To summarize the circumstances of rescue events in hospitalized patients after radiotherapy for head and neck cancer in order to provide a reference for clinical decision-making.
Methods:
This study was approved by the hospital's medical ethics committee. A retrospective analysis was conducted on the clinical data of 86 hospitalized patients admitted between 2015 and 2023 for oral and maxillofacial diseases following radiotherapy for head and neck cancer. Based on the occurrence of rescue events, patients were divided into a rescue group (n=20) and a non-rescue group (n=66). In addition, 20 healthy subjects matched for age and gender with the rescue group were included as a control group. First, baseline characteristics were compared between the rescue and non-rescue groups. Second, a descriptive analysis of the clinical characteristics and rescue events of the rescue group patients was performed. Third, differences in laboratory inflammatory and nutritional indicators, as well as tracheostomy status, were compared between the rescue and non-rescue groups. Fourth, Dolphin Imaging software was used to measure cone beam computed tomography images of the rescue group, non-rescue group, and control group. Upper airway parameters were measured, including the sagittal and coronal diameters of the nasopharyngeal, palatopharyngeal, glossopharyngeal, and laryngopharyngeal segments
Results:
① A comparison of baseline characteristics between the rescue and non-rescue groups showed no statistically significant differences in age, gender, or body mass index, but the proportion of patients with comorbid pulmonary diseases was higher in the rescue group (P<0.05). ② In the rescue group, the primary reasons for radiotherapy were nasopharyngeal carcinoma (65%) and tongue cancer (25%). The mean age was (54.75 ± 11.59) years, with a male-to-female ratio of 3:1. The main reasons for this admission included radio-osteomyelitis in the mandible (55%) and recurrence of oral and maxillofacial tumors or new primary tumors in the oral and maxillofacial region (40%). The primary reason for rescue during hospitalization was dyspnea (55%), followed by acute massive hemorrhage (15%) and cardiac arrest (15%). Rescue events occurred mostly postoperatively (65%), with a median time of occurrence at 5 days post-operatively; 30% occurred preoperatively, and 5% occurred intraoperatively. ③ Laboratory indicators and tracheostomy status: preoperative and postoperative neutrophil counts, as well as the proportion of patients undergoing tracheostomy, were higher in the rescue group compared to the non-rescue group, while postoperative albumin levels were lower (P<0.05). ④ Upper airway measurements: the coronal and sagittal diameters of the nasopharyngeal segment and the coronal diameter of the glossopharyngeal segment were smaller in both the rescue and non-rescue groups compared to the control group (P<0.001).
Conclusion
The data from this study indicate that hospitalized patients experiencing rescue events after radiotherapy for head and neck cancer often have comorbid pulmonary diseases or tumor recurrence/new primary tumors, and frequently present with dyspnea. They exhibit a higher inflammatory state, poorer nutritional status, a greater need for emergency airway intervention, and share a common anatomical basis for dyspnea--upper airway narrowing. Clinical attention should be fully given to high-risk patients with these characteristics.
2.Mechanism prediction and verification of Xihuang pill against diffuse large B-cell lymphoma
Ruyi HUANG ; Jinyu LI ; Wenqi LIN ; Xin JIANG ; Yanling CHEN ; Weikun HUANG ; Lin YANG
China Pharmacy 2026;37(2):161-167
OBJECTIVE To investigate the mechanism of Xihuang pill (XHP) against diffuse large B-cell lymphoma (DLBCL). METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP, GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics (MD) simulation were conducted to verify the interactions between core components and core targets, and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay, flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components (e.g., 17 beta-estradiol, quercetin) and ten core targets [e.g., tumor protein 53 (TP53), proto-oncogene tyrosine-protein kinase Src (SRC)] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis (P<0.05). Molecular docking, MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail:stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells; compared with control group, XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells, and significantly down- regulated the expressions of SRC protein, phosphorylated (p)-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells (P<0.05). CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.
3.Research progress on the microecological strategies of root caries management
WU Lijing ; TAO Yiwei ; ZENG Bo ; CAI Yanling
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(3):244-251
Root caries is a prevalent chronic oral disease with an average global prevalence of 41.5%, characterized by high incidence, low rate of treatment, and high rate of retreatment. Root caries is primarily caused by core microbiome-induced dysbiosis and has multiple risk factors, including gingival recession, root surface exposure, and salivary dysfunction. The traditional preventive measures and treatments such as fluoride, mineralizing agents, and restorative materials, are unable to restore or maintain oral microecological homeostasis. Recent studies have demonstrated that probiotics, prebiotics, synbiotics, and antimicrobial peptides may prevent and treat root caries by reversing dysbiosis. In addition, these biotherapeutics can reduce acid production by acidiferous bacteria, promote alkali production (hydrogen peroxide and ammonia) by alkali-producing bacteria, inhibit biofilm formation, decrease extracellular polysaccharide production, and suppress microbial adhesion and aggregation. It is expected to play an important role in the prevention and control of root caries. This article aims to review oral probiotics (Streptococcus oligofermentans, Streptococcus oralis subsp. dentisani, and Streptococcus salivarius), prebiotics (arginine, nitrates, and synthetic compounds), synbiotics, and antimicrobial peptides (gallic acid-polyphemusin I and LH12) to provide evidence and guidance for root caries management through microecological modulation.
4.Effect of Zuogui Wan and Yougui Wan on Mitochondrial Biogenesis in BMSCs Through PGC-1α/PPARγ
Ying YANG ; Xiuzhi FENG ; Yiran CHEN ; Zhimin WANG ; Xian GUO ; Yanling REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):28-36
ObjectiveBased on the TCM theory of "Yang transforms materials to Qi while Yin constitutes material form", this paper explored the effects of Zuogui Wan and Yougui Wan on the molecular mechanism of mitochondrial biogenesis during the adipogenic differentiation process of rat bone marrow mesenchymal stem cells (BMSCs) by mediating peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and peroxisome proliferators-activated receptor γ (PPARγ), providing theoretical support for the prevention and treatment of postmenopausal osteoporosis (PMOP) using Zuogui Wan and Yougui Wan. MethodsBMSCs were divided into a blank group, Zuogui Wan (ZGW) group, Yougui Wan (YGW) group, and Progynova group. Cell identification was performed using flow cytometry. The growth curves of BMSCs were plotted using the methylthiazolyldiphenyl-tetrazolium bromide (MTT) method, and the effects of Zuogui Wan and Yougui Wan on the proliferation of BMSCs were detected. The Oil red O staining method was used to detect lipid droplet formation. The Western blot method was used to detect the expression of adipogenesis-related factors PPARγ, CCAAT/enharcer-binding protein (C/EBP)α, C/EBPβ, lipoprotein lipase (LPL) protein, brown adipose tissue-related (BAT) proteins PGC-1α, uncoupcing protein 1 (UCP1), PR domdin-containing protein 16 (PRDM16), mitochondrial biogenesis-related PGC-1α, nuclear respiratory factor 1 (Nrf1), nuclear factor E2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). The expression of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, LPL genes, and the copy number of cytochrome B (CytoB mtDNA) gene was detected using real-time polymerase chain reaction (Real-time PCR). Mitochondrial ultrastructure was detected using transmission electron microscopy. ResultsCompared with that in the blank group, the proliferation ability of BMSCs in each treatment group increased continuously as the intervention progressed, and lipid droplets significantly decreased after the drug intervention. The mRNA and protein expression levels of adipogenesis-related factors PPARγ, C/EBPα, C/EBPβ, and LPL were significantly downregulated (P<0.01), while those of the BAT-related factors PGC-1α, UCP1, PRDM16 were significantly upregulated (P<0.01). The number of mitochondria increased, accompanied by reduced swelling. The double membrane and cristae structure were clear, and the internal cristae rupture was reduced. The copy number of CytoB mtDNA in each treatment group was significantly increased (P<0.01). The protein expression levels of mitochondrial biogenesis-related PGC-1α, Nrf1, Nrf2, and TFAM in each treatment group were significantly increased (P<0.01). ConclusionBoth Zuogui Wan and Yougui Wan can prevent and treat PMOP by intervening in mitochondrial biogenesis in BMSCs through PGC-1α/PPARγ.
5.Enhancing doxorubicin’s anticancer impact in colorectal cancer by targeting the Akt/Gsk3β/mTOR-SREBP1 signaling axis with an HDAC inhibitor
Huaxin ZHAO ; Yanling WU ; Soo Mi KIM
The Korean Journal of Physiology and Pharmacology 2025;29(3):321-335
Colorectal cancer ranks third in global incidence and is the second leading cause of cancer-related mortality. Doxorubicin, an anthracycline chemotherapeutic drug, is integral to current cancer treatment protocols. However, toxicity and resistance to doxorubicin poses a significant challenge to effective therapy. Panobinostat has emerged as a critical agent in colorectal cancer treatment due to its potential to overcome doxorubicin resistance and enhance the efficacy of existing therapeutic protocols. This study aimed to evaluate the capability of panobinostat to surmount doxorubicin toxicity and resistance in colorectal cancer. Specifically, we assessed the efficacy of panobinostat in enhancing the therapeutic response to doxorubicin in colorectal cancer cells and explored the potential synergistic effects of their combined treatment. Our results demonstrate that the combination treatment significantly reduces cell viability and colony-forming ability in colorectal cancer cells compared to individual treatments. The combination induces significant apoptosis, as evidenced by increased levels of cleaved PARP and cleaved caspase-9, while also resulting in a greater reduction in p-Akt/p-GSK-3β/mTOR expression, along with substantial decreases in c-Myc and SREBP-1 levels, compared to monotherapies. Consistent with the in vitro experimental results, the combination treatment significantly inhibited tumor formation in colorectal cancer xenograft nude mice compared to the groups treated with either agent alone. In conclusion, our research suggests that the panobinostat effectively enhances the effect of doxorubicin and combination of two drugs significantly reduced colorectal cancer tumor growth by targeting the Akt/ GSK-3β/mTOR signaling pathway, indicating a synergistic therapeutic potential of these two drugs in colorectal cancer treatment.
6.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
7.Enhancing doxorubicin’s anticancer impact in colorectal cancer by targeting the Akt/Gsk3β/mTOR-SREBP1 signaling axis with an HDAC inhibitor
Huaxin ZHAO ; Yanling WU ; Soo Mi KIM
The Korean Journal of Physiology and Pharmacology 2025;29(3):321-335
Colorectal cancer ranks third in global incidence and is the second leading cause of cancer-related mortality. Doxorubicin, an anthracycline chemotherapeutic drug, is integral to current cancer treatment protocols. However, toxicity and resistance to doxorubicin poses a significant challenge to effective therapy. Panobinostat has emerged as a critical agent in colorectal cancer treatment due to its potential to overcome doxorubicin resistance and enhance the efficacy of existing therapeutic protocols. This study aimed to evaluate the capability of panobinostat to surmount doxorubicin toxicity and resistance in colorectal cancer. Specifically, we assessed the efficacy of panobinostat in enhancing the therapeutic response to doxorubicin in colorectal cancer cells and explored the potential synergistic effects of their combined treatment. Our results demonstrate that the combination treatment significantly reduces cell viability and colony-forming ability in colorectal cancer cells compared to individual treatments. The combination induces significant apoptosis, as evidenced by increased levels of cleaved PARP and cleaved caspase-9, while also resulting in a greater reduction in p-Akt/p-GSK-3β/mTOR expression, along with substantial decreases in c-Myc and SREBP-1 levels, compared to monotherapies. Consistent with the in vitro experimental results, the combination treatment significantly inhibited tumor formation in colorectal cancer xenograft nude mice compared to the groups treated with either agent alone. In conclusion, our research suggests that the panobinostat effectively enhances the effect of doxorubicin and combination of two drugs significantly reduced colorectal cancer tumor growth by targeting the Akt/ GSK-3β/mTOR signaling pathway, indicating a synergistic therapeutic potential of these two drugs in colorectal cancer treatment.
8.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
9.Combination of CT/MRI LI-RADS With Second-Line Contrast-Enhanced Ultrasound Using Sulfur Hexafluoride or Perfluorobutane for Diagnosing Hepatocellular Carcinoma in High-Risk Patients
Yu LI ; Sheng LI ; Qing LI ; Kai LI ; Jing HAN ; Siyue MAO ; Xiaohong XU ; Zhongzhen SU ; Yanling ZUO ; Shousong XIE ; Hong WEN ; Xuebin ZOU ; Jingxian SHEN ; Lingling LI ; Jianhua ZHOU
Korean Journal of Radiology 2025;26(4):346-359
Objective:
The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).
Materials and Methods:
This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/ MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.
Results:
In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%–79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%–87%], 84% [95% CI: 79%–89%], 88% [95% CI: 83%–92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%–97%).
Conclusion
The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.
10.Mechanism of Modified Erxian Decoction Regulating Perimenopausal Syndrome via SIRT1/Kisspeptin/GnRH Signaling Pathway
Ruiyu HUANG ; Fang LEI ; Wuchaonan LIU ; Jingjing YANG ; Qianru ZENG ; Shengping LUO ; Yanling CHEN ; Mengge ZHANG ; Fanshun SHEN ; Yihui DENG ; Dingxiang LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):51-62
ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal (HPG) axis by modified Erxian decoction in rats with perimenopausal syndrome (PMS) and to further analyze the expression of proteins related to the silent information regulator 1 (SIRT1)/hypothalamic kisspeptin (Kisspeptin)/gonadotropin-releasing hormone (GnRH) signaling pathway in the arcuate nucleus region (ARC) of the hypothalamus, so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method, with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling, including a sham operation group, a model group, an estradiol valerate group (0.09 mg∙kg-1∙d-1), high-, medium-, and low-dose modified Erxian decoction groups (7.614, 3.807,1.903 5 g∙kg-1∙d-1), with 8 rats in each group. The estradiol valerate group and the high-, medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days, and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin-releasing hormone (GnRH). Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to determine the expression levels of SIRT1, Kisspeptin, kisspeptin receptor (GPR54), and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor (GnRH-R) in pituitary. ResultsCompared with the sham operation group, rats in the model group had a significantly increased body weight (P0.01), reduced wet weight and index of uterus (P0.01), endometrial thinning or atrophy, glandular atrophy, and a decreasing number of glands. Additionally, serum levels of E2 and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased (P0.01). Serum levels of FSH, LH, and GnRH, the expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus, and GnRH-R in pituitary significantly increased (P0.01). Compared with the model group, the estradiol valerate group and the high-, medium-dose modified Erxian decoction groups had significantly reduced body weight, serum levels of FSH, LH, and GnRH, and expression of Kisspeptin, GPR54, and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary (P0.05, P0.01) and significantly increased wet weight and index of uterus, serum level of E2, and expression of SIRT1 in the ARC region of the hypothalamus (P0.05, P0.01). In addition, they showed thickened endometrium, increased number of endometrial glands, and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets, and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus, the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway, the regulation of the expression of GnRH-R in the pituitary, the restoration of secretion balance of gonadotropins, and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.


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