1.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
2.Mechanism of Yizhi Qingxin Prescription in Regulating PKA/CaN Pathway to Improve Cognitive Function in Alzheimer's Disease Model Mice
Xiaochen GUO ; Jiangang LIU ; Dandan SHI ; Ziqi NING ; Yaoyao ZHANG ; Fang LIU ; Meixia LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):97-108
ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease (AD) through regulating mitochondrial Ca2+ homeostasis and kinetic balance based on the protein kinase A (PKA)/calcineurin (CaN) signaling pathway. MethodsSixty three-month-old amyloid precursor protein (APP)/presenilin 1 (PS1) double transgenic mice were randomly divided into a model group, a donepezil group(0.65 mg·kg-1), a low-dose Yizhi Qingxin prescription group (YQF-L,2.6 g·kg-1), a medium-dose Yizhi Qingxin prescription group (YQF-M,5.2 g·kg-1), and a high-dose Yizhi Qingxin prescription group (YQF-H,10.4 g·kg-1), with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily, with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition (NOR) and Morris water maze (MWM) tests. Hematoxylin-eosin (HE)/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy (TEM) was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester (Fluo-4 AM) Ca2+ probe was used to measure intracellular Ca2+ concentration in brain tissue. Western blot was used to determine the protein expression of PKA, CaN, sodium/calcium/lithium exchanger (NCLX), mitochondrial calcium uniporter (MCU), calmodulin (CaM), dynamin-related protein 1 (Drp1), and phosphorylated dynamin-related protein 1 (serine 637 site) [p-Drp1(S637)] in the hippocampus. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the expression of PKA, CaN, CaM, NCLX, MCU, and Drp1 mRNAs. ResultsCompared with those in the normal group, the recognition index (RI) of the model group decreased (P0.01), and the number of crossings through the original platform area, the duration of stay in the target quadrant, and the distance were reduced (P0.01). The protein expression of PKA, NCLX, and p-DRP1 (ser637) significantly decreased (P0.05), and the mRNA expression of PKA and NCLX significantly decreased (P0.05). The escape latency (EL) was prolonged (P0.05), and the intracellular Ca2+ level significantly increased (P0.01). The protein expression of CaN, CaM, MCU, and Drp1, as well as the mRNA expression of CaN, MCU, and Drp1, significantly increased (P0.05). After intervention with Donepezil and Yizhi Qingxin prescription, compared with that in the model group, the RI of the treatment group significantly increased (P0.05), and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased (P0.05). The protein expression of PKA, NCLX, and p-Drp1 (ser637) and the mRNA expression of PKA and NCLX significantly increased (P0.05). On the 4th and 5th days, the EL was shortened (P0.05), and the intracellular Ca2+ level decreased (P0.05). The protein expression of CaN, CaM, MCU, and Drp1 and the mRNA expression of CaN, MCU, and Drp1 significantly decreased (P0.05). ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway, upregulates the expression of PKA, NCLX, and p-Drp1 (ser637) proteins, reduces the expression of CaN, CaM, MCU, and Drp1 proteins, and regulates Ca2+ homeostasis and mitochondrial dynamic balance, thereby enhancing the spatial learning and memory abilities of AD mice.
3.Empirical study of input, output, outcome and impact of community-based rehabilitation stations
Xiayao CHEN ; Ying DONG ; Xue DONG ; Zhongxiang MI ; Jun CHENG ; Aimin ZHANG ; Didi LU ; Jun WANG ; Jude LIU ; Qianmo AN ; Hui GUO ; Xiaochen LIU ; Zefeng YU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):83-89
ObjectiveTo investigate the present situation of input, output, outcome and impact of all registered community-based rehabilitation stations in Inner Mongolia in China, and analyze how the input predict the output, outcome and impact. MethodsFrom March 1st to April 30th, 2025, a questionnaire survey was conducted on all registered community-based rehabilitation stations in Inner Mongolia, covering four dimensions: input, output, outcome and impact. A total of 1 365 questionnaires were distributed. The input included four items: laws and policies, human resources, equipment and facilities, and rehabilitation information management. The output included two items: technical paths and benefits/effectiveness. The outcome included three items: coverage rates, rehabilitation interventions and functional results. The impact included two items: health and sustainability. Each item contained several questions, all of which were described in a positive way. Each question was scored from one to five. A lower score indicated that the situation of the community-based rehabilitation station was more in line with the content described in the question. Regression analysis was performed using the total score of each item of input dimension as independent variables, and the total scores of the output, outcome and impact dimensions as dependent variables. ResultsA total of 1 262 valid questionnaires were collected. The mean values of input, output, outcome and impact of community-based rehabilitation stations were 1.827 to 1.904, with coefficient of variation of 45.892% to 49.239%. The regression analysis showed that, rehabilitation information management, human resources, and laws and policies significantly predicted the output dimension (R² = 0.910, P < 0.001). Meanwhile, all four items in the input dimension predicted both the outcome (R² = 0.850, P < 0.001) and impact dimensions (R² = 0.833, P < 0.001). ConclusionInput, output, outcome and impact of the community-based rehabilitation stations in Inner Mongolia were generally in line with the content of the questions, although some imbalances were observed. Additionally, the input of community-based rehabilitation stations could significantly predict their output, outcome and impact.
4.The Current Issues and Thoughts on the Empowerment of Famous Doctors' Experience Inheritance by Artificial Intelligence
Xiaochen JIANG ; Fudong LIU ; Chuanlong ZHANG ; Yi LI ; Qian SHEN ; Bo PANG
Journal of Traditional Chinese Medicine 2026;67(7):710-715
In the context of the modernization of traditional Chinese medicine (TCM), the inheritance of the experiences of famous doctors faces significant challenges due to its complex nonlinear characteristics and dynamic evolution. There are still issues in the current inheritance system, such as the homogenization of talent cultivation models, lack of standardized mentoring practices, and monotonous evaluation method, which hinder the systematic inheritance and innovative development of famous doctors' experiences. Based on a systematic review of the current state of artificial intelligence (AI)-assisted inheritance of famous doctors' experiences, this study explores innovative pathways for deep integration of modern information technologies with famous doctors' experiences from key dimensions, including data authenticity assurance, interdisciplinary collaboration mechanisms, and the establishment of dynamic inheritance standards. It proposes a paradigm shift in the inheritance of TCM famous doctors' experiences in the AI era, aiming to build a new TCM inheritance system of "digital intelligence empowerment and cross-disciplinary innovation", providing theoretical support and practical pathways for the inheritance of famous doctors' experiences in TCM.
5.Traditional Chinese Medicine Intervening Mitochondrial Dysfunction for Treatment of Diabetic Kidney Disease: A Review
Xiaochen WEN ; Ying WANG ; Ruoshi LIU ; Ziying LIU ; Xiaoyan MA ; Chengjun GONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):300-311
Diabetic kidney disease (DKD) is a microvascular complication of diabetes, with a complex pathogenesis, in which mitochondrial dysfunction is considered to be the core of DKD development. Taking mitochondria as a target to regulate mitochondrial energy metabolism, mitochondrial oxidative stress, mitophagy, and mitochondrial dynamic function represents a promising strategy for the DKD prevention and treatment, with good prospects in clinical application. Traditional Chinese medicine (TCM) has great potential to mediate mitochondrial dysfunction in the DKD prevention and treatment. This article deeply explores the intrinsic relationship between various forms of mitochondrial dysfunction and DKD, and summarizes the current research status of various Chinese herbal compounds and Chinese herbal formulas in targeting mitochondrial dysfunction for the DKD prevention and treatment. This article aims to provide new targets and strategies for the DKD prevention and treatment, and the research and development of TCM.
6.Effectiveness of carvedilol alone versus carvedilol combined with endoscopic variceal ligation in secondary prevention of gastroesophageal variceal bleeding in patients with liver cirrhosis
Xiaochen LIU ; Yifu XIA ; Chunqing ZHANG
Journal of Clinical Hepatology 2025;41(5):900-906
ObjectiveTo compare the therapeutic effects of carvedilol alone and carvedilol combined with endoscopic variceal ligation (EVL) in the prevention of re-bleeding from gastroesophageal varices, and to provide strategies for clinical treatment. MethodsWe retrospectively included 178 patients who had received carvedilol alone or carvedilol plus EVL to prevent gastroesophageal variceal re-hemorrhage from October 2010 to June 2023. They were divided into carvedilol alone group (47 cases) and carvedilol+EVL group (131 cases). Between-group comparisons were conducted using the paired t test for normally distributed continuous data, the Mann-Whitney U test for non-normally distributed continuous data, and the chi-square test for categorical data. A Cox proportional hazards model was employed for univariable and multi-variable analyses. The cumulative incidence rates of re-bleeding and mortality were estimated using the Kaplan-Meier method. The baseline characteristics of the two groups were matched through propensity score matching (PSM) to reduce selection bias and enhance the credibility of causal inference. ResultsThe re-bleeding rate of the carvedilol+EVL group was significantly lower than that of the carvedilol alone group (10-year cumulative incidence: 29.8% vs 36.2%, hazard ratio [HR]=0.505, 95% confidence interval [CI]: 0.292 — 0.847, P=0.015). There was no significant difference in liver-related mortality (10-year cumulative incidence: 21.3% vs 21.4%, HR=0.799, 95%CI: 0.406 — 1.578, P=0.518). The results were stable with PSM analysis. The Cox regression analysis revealed that creatinine was an independent risk factor affecting re-bleeding (HR=1.004, 95%CI: 1.001 — 1.008, P=0.011) and liver-related mortality (HR=1.004, 95%CI: 1.001 — 1.007, P=0.019). ConclusionCarvedilol combined with EVL is better than carvedilol alone in the prevention of gastroesophageal variceal re-bleeding.
7.Effect of Xibining Formula (膝痹宁) on Knee Cartilage Tissue Damage and the cGAS-STING Signaling Pathway in Knee Osteoarthritis Model Mice
Houyu FU ; Xiaochen LI ; Zijian GONG ; Lishi JIE ; Jiangyu LIU ; Yingqi CHEN ; Peimin WANG
Journal of Traditional Chinese Medicine 2025;66(12):1257-1264
ObjectiveTo investigate the possible mechanism of action of Xibining Formula (膝痹宁) for cartilage damage in knee osteoarthritis (KOA) through the cyclic guanosine-adenosine monophosphate synthase (cGAS)- stimulator of interferon genes (STING) signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups (10 per group), sham operation group, KOA model group, low-dose Xibining Formula group, high-dose Xibining Formula group, and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus (DMM) method in all groups but the sham surgery group. Two weeks after surgery, the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/(kg·d) and 14.32 g/(kg·d) respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/(kg·d) of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan (DMXAA) at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/(kg·d) via gavage, once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were measured by ELISA; pathological changes in cartilage tissue were observed using hematoxylin-eosin (HE) staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system; the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 (MMP3), matrix metalloproteinase 13 (MMP13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS), type-Ⅱ collagen (CⅡ) and aggregated proteoglycan (Aggrecan), and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group, the KOA model group showed severe cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with the control group, serum level of IL-6, IL-1β, TNF-α in all the intervented groups decreased (P<0.01), while compared with high-dose Xibining Formula group, level of IL-6, IL-1β, and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased (P<0.01). Compared with the KOA model group, all the intervention groups exhibited alleviated cartilage pathological changes, signi-ficantly reduced Mankin scores, significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan, and significantly decreased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). Compared with high-dose Xibining Formula group, high-dose Xibining Formula + agonist group showed cartilage edge destruction, significantly increased Mankin scores, significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan, and increased protein and mRNA expression levels of cGAS, STING, MMP3, MMP13, and ADAMTS5 (P<0.01). ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway, decreasing matrix degradation-related proteins, and elevating matrix composition-related proteins.
8.Retrospective analysis of the application of the"triple"transformation treatment regimen in 52 cases advanced liver cancer
Jianfeng DUAN ; Xiaochen LIU ; Xirong ZHAO ; Changhu DUAN ; Fan YANG ; Qingjuan CHEN ; Lin WU ; Lifei ZHAO ; Qiao HE
Journal of Clinical Surgery 2025;33(4):420-423
Objective To retrospective analysis summarized the effectiveness and safety of the"triple"conversion therapy regimen combining immune,targeted and local therapy.Methods From February 2019 to June 2023,52 patients with advanced liver cancer from February 2019 to June 2023 in XI,an Jiao Tong university medicine college affiliated 3201 hospital were admitted and received conversion treatment regimens combining sintilimab with bevacizumab and combined with local treatment,analyzed the surgical resection rate and pathological complete response rate(pCR),complete response rate(CR),partial response rate(PR),progression of disease(PD),stable disease(SD),objective response rate(ORR)and disease control rate(DCR).To evaluated the effect of conversion therapy and adverse reactions.Results 21 cases had recived operative resection in the 52 patients with primary liver cancer receiving sintilimab and bevacizumab.The postoperative resection rate was 40.4%(21/52),pCR 42.9%(9/21).The other 31 cases have complete response 5.8%(3/52),PR 25.0%(13/52),PD 11.5%(6/52),SD 17.3%(9/52).The overall objective response rate(ORR)was71.2%(37/52),and the disease control rate(DCR)was 88.5%(46/52).Adverse reactions manifest as Grade 1-2 skin-related damage primarily affecting the epidermis.Conclusions For patients with potentially resectable primary liver cancer in middle and advanced stage,the"triple"conversion therapy with sintilimab combined with bevacizumab as systematic treatment and combined with local therapy can achieve good conversion treatment effect with controllable safety.
9.Efficacy of nucleos(t)ide analogues combined with peginterferon α-2b on antiviral therapy in children with chronic hepatitis B
Wenting CHEN ; Shilian LI ; Xiaochen MA ; Fang CHEN ; Lijian RAN ; Yi WU ; Yan GUO ; Yan ZHU ; Qing MAO ; Huimin LIU
Chinese Journal of Experimental and Clinical Virology 2025;39(4):411-418
Objective:To analyze the efficacy of combination of peginterferon α-2b(Peg-IFN α-2b)with nucleos(t)ide analogues(NAs)on antiviral therapy in children with chronic hepatitis B(CHB)and to provide an optimized clinical treatment strategies for CHB children.Methods:A retrospective analysis was conducted on 30 CHB children treated in The First Affiliated Hospital of the Army Medical University(Southwest Hospital)from January 2022 to January 2025 with treatment duration at least 48 weeks. The enrolled children were aged between 2 and 17 years and divided into the NAs combined with Peg-IFN α-2b(NPI)group(n=13)and NAs group(n=17)by their therapy regimens. The characteristics of baseline,week 12,week 24,week 48 and week 96 were compared between groups,as well as the differences in response to biochemical,immune and viral indicators at each observation point. Logistic regression analysis and receiver operating characteristic(ROC)curve analysis were performed to identify factors influencing the HBsAg seroclearance. Results:At baseline of treatment,the proportion of HBeAg positivity in the NPI group and the NAs group was high(76.9% vs 86.6%, χ2=0.679, P=0.628),and the alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in the NPI group were significantly lower than those in the NAs group( P<0.001). At 24 weeks,the decrease in HBsAg in the NPI group was also significantly higher than that in the NAs group( Z=-3.161, P=0.002). Finally,the cumulative seroclearance rate of HBsAg at 96 weeks in the NPI group was significantly higher than that in the NAs group(46.15% vs 5.88%, χ2=0.679, P=0.025). Mulitivariate Logistic regression analysis showed that treatment regimen and gender were risk factors affecting the outcome of HBsAg( P<0.05). ROC curve analysis showed that the increase in ALT at 12 weeks compared with baseline(AUC=0.857,Cutoff value=3.615 IU/L),the decrease in ALT at 24 weeks(AUC=0.870,Cutoff value=47.85 IU/L),and the decrease in HBsAg at 12 weeks and especially at 24 weeks(AUC=0.885,Cutoff value=0.97log IU/ml)were effective predictors of HBsAg prognosis at 96 weeks. Conclusion:In CHB children,antiviral regimen Peg-IFN α-2b combined with NAs was more effective than NAs alone in improving the HBsAg seroclearance rate of CHB,and the effects in female were better than in male. The decline of HBsAg and the fluctuation of ALT in the early treatment period are valid predictors of HBsAg clearance.
10.Artificial intelligence-based sequential ultrasound-MRI strategy for ovarian masses:dual evaluation of diagnostic accuracy and healthcare costs
Jingjing YU ; Ruixia DAI ; Xiaomin LIU ; Peijun HU ; Xiaochen WANG ; Sihui HU ; Shanshan ZHANG ; Wenqian WANG ; Yu TIAN ; Jiale QIN
Chinese Journal of Ultrasonography 2025;34(9):759-765
Objective:To develop an artificial intelligence(AI)-based sequential ultrasound-magnetic resonance imaging(US-MRI)diagnostic strategy to optimize the imaging workflow for ovarian masses.Methods:A total of 1 120 patients with pathologically confirmed ovarian masses who underwent both preoperative pelvic ultrasound and MRI between January 2021 and December 2023 at Women's Hospital,Zhejiang University School of Medicine were retrospectively included. Patients were randomly divided into the training( n=672)and internal test set( n=448)at a ratio of 6∶4. An external test set( n=128)was established at the Forth Affiliated Hospital of School of Medicine. Deep learning was used for automated segmentation of MRI lesions,followed by radiomic feature extraction and machine learning classification to construct both a US-MRI multimodal model and sequential US-MRI strategy. Diagnostic performance and potential healthcare cost-saving effects were evaluated across strategies. Results:In the internal test set( n=448),the AI-based sequential US-MRI strategy achieved a F1 score of 0.863 and a diagnostic accuracy of 82.14%,with no significant difference compared to the US-MRI multi-modal model( P>0.05). The sequential strategy identified 82 cases(18.30%,82/448)of patients as low-risk true negatives during initial ultrasound screening,suggesting a potential to reduce the need for MRI examinations in future clinical practice. In the external test set( n=128),the strategy achieved an F1 score of 0.800 and a confirmed diagnosis rate of 85.94%,with a theoretical reduction of 26.56%(34 cases)in MRI utilization while maintaining a diagnostic accuracy rate higher than that of the multi-modal model(82.18%). Conclusions:The AI-based US-MRI sequential diagnostic strategy demonstrates favorable diagnostic accuracy while offering the potential to optimize MRI utilization. This approach may enhance the efficiency of imaging resource allocation and reduce healthcare burden in the management of ovarian masses.

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