1.Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
Ping ZHANG ; Lijuan YANG ; Shenghui CHEN ; Wenliang YAO ; Yuliang ZHOU ; Ling MA ; Huiying WU ; Yanwen XU ; Ziyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):46-55
ObjectiveTo observe the effects of Yangjing Zhongyutang (YJZYT) on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling pathway in cyclophosphamide (CTX)-induced rats with diminished ovarian reserve (DOR), and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group (n=7) and a model group (n=35). Rats in the model group received a single intraperitoneal injection of CTX (90 mg·kg-1) to establish the DOR model. After modeling, estrous cycles were monitored for 7 consecutive days, and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling, rats were divided into groups for intervention: estradiol valerate group (0.09 mg·kg-1), and YJZYT high-, medium-, and low-dose groups (19.98, 9.99, 5.00 g·kg-1). The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state, body weight, and ovarian wet weight of rats were observed and recorded, and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). Hematoxylin-eosin (HE) staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species (ROS) expression levels. Colorimetric assays were employed to measure adenosine triphosphate (ATP) and malondialdehyde (MDA) content in ovarian tissues. Quantitative Real-time polymerase chain reaction (Real-time PCR) was used to detect mitochondrial DNA (mtDNA) copy number and the mRNA expression levels of key genes including SIRT1, PGC-1α, nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). Western blot was performed to detect the protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM. ResultsCompared with the blank group, rats in the model group exhibited disrupted estrous cycles, obviously reduced body weight, and decreased ovarian index (P<0.05). Ovarian histopathology revealed cortical thinning, loose structure, and a significant reduction in both primordial and growing follicles (P<0.01). Serum FSH and LH levels were significantly elevated (P<0.01), while E2 and AMH levels were obviously reduced (P<0.05, P<0.01). ATP content and mtDNA copy number decreased in ovarian tissue (P<0.01), ROS expression increased, MDA levels rose, while SOD and GSH-Px activities obviously decreased (P<0.05, P<0.01), mRNA and protein expression levels of SIRT1, PGC-1α, NRF1, and TFAM were obviously downregulated (P<0.05, P<0.01). After treatment, compared with the model group, body weight and ovarian index obviously recovered in rats administered various doses of YJZYT (P<0.05), serum E2 and AMH levels increased, while FSH and LH levels obviously decreased (P<0.05, P<0.01), ovarian tissue ATP content and mtDNA copy number were up-regulated, ROS and MDA levels decreased, and antioxidant enzymes SOD and GSH-Px activity obviously increased (P<0.05, P<0.01), Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group (P<0.05, P<0.01), HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups, with a obviously increase in the number of primordial and growing follicles (P<0.05, P<0.01). Granulosa cells were neatly arranged, indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway, promoting mitochondrial biogenesis, enhancing mitochondrial function, and alleviating oxidative stress damage.
2.Efficacy and Safety of Qihuang Acupuncture Theory Combined with Opioid Analgesics in the Treatment of Moderate to Severe Cancer Pain in Lung Cancer Patients:a Randomize-Controlled Trial
Yingqi WANG ; Ruifang YU ; Jinpeng HUANG ; Guiya LIAO ; Ziyan GAN ; Zhenhu CHEN ; Xiaobing YANG ; Chunzhi TANG
Journal of Traditional Chinese Medicine 2025;66(4):358-366
ObjectiveTo observe the analgesic efficacy and safety of Qihuang acupuncture theory combined with opioid analgesics in patients with moderate to severe cancer pain due to lung cancer. MethodsPatients with moderate to severe cancer pain from lung cancer were randomly divided into Qihuang acupuncture group and control group, with 33 cases in each group. The control group was treated with long-acting opioid analgesics at maintenance doses and supplementary analgesic medications as needed. In case of breakthrough pain, short-acting opioids were used for rescue. The Qihuang acupuncture group received Qihuang acupuncture treatment in addition to the treatment used in the control group, administered once every other day, with 3 sessions constituting one treatment course. The treatment duration for both groups was 5 days. The primary outcome was the change in pain intensity, measured using the numerical rating scale (NRS) before and after treatment, and the NRS change rate was calculated. Secondary endpoints included the daily NRS change rate, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score, the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) score, and the 24-hour equivalent hydrocodone sustained-release tablet dose. Laboratory tests, including routine blood, urine, stool, liver function, and kidney function, were performed before and after treatment. Adverse events were recorded throughout the trial. ResultsAll patients completed the trial, and both groups showed a decrease in average NRS scores and PS scores after treatment, with the Qihuang acupuncture group showing lower average NRS scores and PS scores than the control group (P<0.05 or P<0.01). After treatment, the NRS change rate in the Qihuang acupuncture group was (0.42±0.17), significantly higher than that in the control group (0.14±0.27, P<0.01). The daily NRS change rate during treatment was also higher in the Qihuang acupuncture group compared to the control group (P<0.01). The Qihuang acupuncture group showed an increase in overall health status and functional scores in the EORTC QLQ-C30, and a decrease in symptom scores for fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and financial difficulties. In contrast, overall health status and constipation scores in the control group increased, while scores of fatigue, nausea and vomiting, pain, and appetite loss decreased (P<0.05 or P<0.01). After treatment, the 24-hour equivalent hydrocodone sustained-release tablet dose did not show significant difference in the Qihuang acupuncture group (P>0.05), while the control group showed a significant increase in the 24-hour dose (P<0.01). No significant abnormalities were observed in laboratory tests before and after treatment in either group. During the study, the incidence of nausea and vomiting as well as constipation in the Qihuang acupuncture group was both 3.03% (1/33), while the incidence in the control group was 27.27% (9/33) and 36.36% (12/33), respectively, with the Qihuang acupuncture group showing significantly lower incidence (P<0.01). No serious adverse reactions were observed in either group. ConclusionQihuang acupuncture therapy combined with opioid analgesics is more effective than using opioids alone in relieving pain in patients with moderate to severe cancer pain due to lung cancer. It can improve the patients' physical condition and quality of life, reduce the dose of opioid analgesics, and has good safety.
3.CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.
Yong CHEN ; Xue YUAN ; Wei YAN ; Yurong ZOU ; Haoche WEI ; Yuhan WEI ; Minghai TANG ; Yulian CHEN ; Ziyan MA ; Tao YANG ; Kongjun LIU ; Baojian XIONG ; Xiuying HU ; Jianhong YANG ; Lijuan CHEN
Acta Pharmaceutica Sinica B 2025;15(7):3708-3724
Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.
4.A multicenter study on pioneering symptoms of gastrointestinal symptom cluster in 463 gastric cancer patients with chemotherapy
Chao XIA ; Peibei DUAN ; Liping YANG ; Chaonan FEI ; Ziyan ZHANG ; Yanling ZOU ; Yi LI ; Ling YANG
Journal of Clinical Medicine in Practice 2025;29(2):124-128,137
Objective To explore the pioneering symptoms of the gastrointestinal symptom cluster and their influencing factors in gastric cancer patients with chemotherapy.Methods Based on the hospital's management system for scientific research data,463 gastric cancer patients with chemothera-py were surveyed through multicenter collaboration by the corresponding module of the MD Anderson Symptom Inventory(MDASI),the Chinese Medicine Constitution Classification and Identification Standard,and the Chinese Medicine SyndromeIdentification Standard for Gastric Cancer.IBM SPSS Statistic 22.0 and IBM SPSS Modeler 18.0 were used for data analysis.Results The first occurrence of dry mouth in the gastrointestinal symptom cluster of gastric cancer patients with chemotherapy was(22.99±10.70)hours after chemotherapy.The support,confidence,and lift for the association be-tween dry mouth and decreased appetite were 62.2%,94.8%and 1.52,respectively;for dry mouth and nausea,the numerical values were 62.2%,89.6%and 1.44;for dry mouth and vomiting,the numerical values were 62.2%,79.5%and 1.28.The results of one-way ANOVA and multivariate linear regression analysis showed that alcohol consumption,syndrome of stomach heat injuring yin,and phlegm-dampness constitution were independent influencing factors for dry mouth in gastric cancer patients with chemotherapy(P<0.05).Conclusion Dry mouth,as a pioneering symptom of the gastroin-testinal symptom cluster,is of great significance in clinical assessment and management.Improved assessment of dry mouth can provide a basis for the construction of subsequent risk prediction model,the formulation of targeted interventions,and the enhancement of symptom management efficiency.
5.Artery anatomy of localized renal cell carcinoma: an initial study based on 3D Slicer software
Ke GAO ; Ziyan WAN ; Ya ZHANG ; Hui ZHANG ; Xiaojie YANG ; Tie CHONG ; Delai FU
Journal of Modern Urology 2024;29(4):298-301
【Objective】 To analyze the position of the feeding artery entering the renal cell carcinoma (RCC) with 3D Slicer software, so as to explore the distribution pattern of the tumor artery and to provide an anatomical basis for the accurate surgical resection. 【Methods】 The clinical data of RCC patients who underwent partial nephrectomy in the Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University during Jan.2021 and Jun.2022 were collected.The preoperative renal artery CT angiography data were imported into 3D Slicer software in DICOM format to construct the relative positions of tumor-feeding artery from horizontal, sagittal and coronary planes.The number and distribution of tumor feeding arteries in each plane were analyzed. 【Results】 A total of 112 patients (59 male and 53 female) with single tumor were involved.RENAL score was 4-10.The tumor stages were T1a in 58 cases, T1b in 48 cases, and T2a in 6 cases.Among them, 38 cases (33.93%) had 1 tumor artery, 53 cases (47.32%) had 2 tumor arteries, and 21 cases (18.75%) had 3 tumor arteries.Of these 207 tumor arteries, 22 (10.63%) entered the tumor through the superficial part of the tumor bed, and 185 (89.37%) through the deep part. 【Conclusion】 In localized RCC, nearly 90% of the feeding arteries enter the tumor from deep part of the tumor bed, which provides an anatomical basis for accurate tumor resection and wound suture in partial nephrectomy.
6.Effects of warm acupuncture on post-stroke cognitive impairment based on the theory of intestinal flora
Yaping XIAO ; Xiujuan LI ; Yang WU ; Ziyan MIAO ; Xianglai NIU ; Yu ZHOU
International Journal of Traditional Chinese Medicine 2024;46(1):37-41
Objective:To observe the effects of warm acupuncture on post-stroke cognitive impairment (PSCI) based on the theory of intestinal flora.Methods:A randomized controlled trial was conducted. 60 patients with PSCI in the Department of Acupuncture and Neurology of the First Affiliated Hospital of Xinjiang Medical University from October 2020 to June 2022 were selected as the observation objects, and were divided into 2 groups by random number table, with 30 cases in each group. On the basis of cognitive rehabilitation training, the treatment group was given warm acupuncture treatment, and the control group was given routine acupuncture treatment. 2 groups were treated for 4 weeks as 1 course, and a total of 4 courses were treated. Montreal cognitive assessment (MoCA) was used to assess patients' cognitive function before and after treatment, and mini-mental state examination (MMSE) was used to assess patients' intelligence level. The numbers of bifidobacteria and lactic acid bacteria in fecal samples were calculated, and plasma gamma-aminobutyric acid (GABA) levels were detected by ELISA to evaluate the clinical efficacy.Results:During the study, 1 case was lost in each of the two groups, and finally 29 cases were included in the curative effect statistics. The total effective rate was 79.3% (23/29) in the treatment group and 65.5% (19/29) in the control group, with statistical significance ( χ2=43.39, P<0.05). After treatment, MoCA score [(24.23±1.36) vs. (21.26±1.30), t=3.12] and MMSE score [(25.35±1.24) vs. (21.52±1.22), t=3.25] in the treatment group were higher than those in the control group ( P<0.05); Bifidobacterium [(9.20±1.25) LgCFU/g vs. (7.23±1.21) LgCFU/g, t=2.98], Lactic acid bacteria [(8.24±1.12) LgCFU/g vs. (6.25±1.22) LgCFU/g, t=2.92], and the level of GABA [(283.80±83.54) mmol/L vs. (264.76±61.38) mmol/L, t=10.54] were higher than those in the control group ( P<0.05 or P<0.01). Conclusion:Warm acupuncture and moxibustion can effectively regulate the number of intestinal beneficial bacteria in PSCI patients, increase the level of GABA, promote brain tissue repair and improve cognitive function.
7.Interpretation of 2023 AHA Scientific Statement:Cancer Therapy Related Hypertension
Lizhu HAN ; Qinan YIN ; Yuan BIAN ; Ziyan LYU ; Xuefei HUANG ; Yang LEI ; Min CHEN
Herald of Medicine 2024;43(2):155-160
In January 2023,the American Heart Association(AHA)released A Scientific Statement:Cancer Therapy Related Hypertension,provided an overview of the mechanisms and clinical management of anticancer therapy related hypertension.Contemporary anticancer drugs are mostly at the expense of cardiovascular toxicities,one of the most common side effects is hypertension,especially vascular endothelial growth factor inhibitors,as well as tyrosine kinase inhibitors and proteasome inhibitors.Cancer therapy related hypertension is often dose limiting,and is usually reversible after interruption or discontinuation of treatment.The exact molecular mechanisms underlying hypertension are unclear,recent discoveries indicate an important role for decreased nitric oxide,increased endothelin-1,endothelial dysfunction,increased sympathetic outflow,and microvascular rarefaction.Based on the International Cardio Oncology Society(IC-OS),this article provides an interpretation of the diagnosis and management of hypertension related to cancer treatment.Insufficient evidence exists supporting an antihypertensive medication strategy specific to patients with anticancer therapy induced hypertension,therefore,antihypertensive management should follow current guidelines for the general population..Multidisciplinary cooperation is needed to optimize management to ensure the optimal therapeutic effect from cancer treatment while minimizing competing cardiovascular toxicities.
8.Examining core symptoms and influencing factors of patients with gastric cancer undergoing chemotherapy:the role of Traditional Chinese Medicine constitutional traits
Yanling ZOU ; Yi LI ; Ziyan ZHANG ; Xun LI ; Lihua YANG ; Xiaoqing WANG ; Juan GAO ; Huiyun GUAN ; Peibei DUAN
Chinese Journal of Nursing 2024;59(18):2238-2243
Objective To investigate the incidence and severity of symptoms in patients with gastric cancer who received chemotherapy,we constructed a symptom network to explore core symptoms and bridge symptoms.Furthermore,the study explores the association between core symptoms and Traditional Chinese Medicine(TCM)constitutions.Methods Patients with gastric cancer who received chemotherapy in the medical oncology and surgical oncology department from March to August 2023 were selected for the study using a convenience sampling method.The MD Anderson Symptom Inventory Gastrointestinal Cancer was used for evaluating gastrointestinal symptoms and their severity among patients receiving chemotherapy for gastric cancer,as well as assessing the classification of TCM constitution among patients.The symptom network model was constructed using the R programming language,and the central index was analyzed to determine the core symptoms and bridge symptoms.Binary logistic regression analysis was employed to assess the association between different physical conditions and the occurrence of core symptoms.Results A total of 346 electronic questionnaires were collected,with 340 valid ones,and the effective recovery rate was 98.3%.The 3 most prevalent and severe symptoms among the 340 patients with gastric cancer were fatigue(85.59%),lack of appetite(82.35%),and taste alteration(81.18%).The centrality index results indicated that grief exhibited the highest intensity,medium,and compactness centrality values(rs=8.23,rb=2.00,rc=0.03),making it the core symptom of this condition.Sleep disorders,lack of appetite,drowsiness,and taste alteration were identified as bridging symptoms with bridge intensities of 0.74,0.76,0.99,and 0.94 respectively.The results of Spearman correlation analysis showed that there was a positive correlation between sadness and qi-deficiency constitution,phlegm-dampness constitution(P<0.05).The phlegm-dampness constitution was positively correlated with the taste alterations(P<0.05).Conclusion In patients with gastric cancer,fatigue emerges as the most prominent symptom,while sadness assumes the core symptom.Additionally,sleep disorder,lack of appetite,drowsiness,and taste alteration are bridge symptoms.According to the principles of TCM constitution,qi-deficiency and phlegm-dampness are constitutions associated with a higher risk of experiencing sadness,and phlegm-dampness is a constitution associated with a higher risk of taste changes.Nurses can integrate core symptoms and TCM constitutions characteristics to optimize the strategies for symptom intervention.
9.Experience in building a cooperative research system for rare diseases: a European perspective
Ziyan YUAN ; Yi QIN ; Huan YIN ; Ran ZHANG ; Xiaoyao WEI ; Yuan YANG ; Dongping GAO
Chinese Journal of Medical Science Research Management 2024;37(5):409-417
Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.
10.Comparative study on the registration management systems of innovative medical devices in China and the United States
Qianqian ZHAO ; Keyu CHEN ; Ziyan MENG ; Runping MA ; Qiufan SUN ; Lewen FU ; Zekun LIU ; Longping YANG ; Qing LI
Chinese Journal of Medical Science Research Management 2024;37(5):434-440
Objective:This article analyzed the current situation, similarities and differences and main problems of the registration and management systems of innovative medical devices in China and the United States.Methods:This article summarized the requirements and policies for the registration management of innovative medical devices in China and the United States, as well as the development and differences of the registration of innovative medical devices in China and the United States, and the main problems in the registration management of innovative medical devices in China.Results:At present, the development level of medical device industry in China and the United States was different, facing different development problems, and there were differences in the access standards and management methods of innovative medical devices. The registration management system established for innovative medical devices in China was gradually improving, and to a certain extent, it had promoted the enthusiasm of innovative product research and development and registration applications, but there were also problems such as unclear innovation evaluation scales, insufficient early intervention of review resources, and insufficient utilization of post-marketing data.Conclusions:Drawing on the beneficial experience of breakthrough device registration management in the United States, we will improve the registration management system for innovative products and shorten the review and approval cycle by clarifying the identification criteria for innovative medical devices, promoting the placement of review resources in the R&D stage, and further strengthening the use of post-marketing data and regulatory scientific research.

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