1.Yulin Hukun Decoction Ameliorates Diminished Ovarian Reserve via PI3K/Akt/mTOR-Mediated Autophagy
Ruixia WANG ; Huan CHENG ; Yaxing FAN ; Tingyun CAI ; Meifang LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):77-85
ObjectiveTo observe the effect of Yulin Hukun decoction on autophagy mediated by phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in the mouse model of cyclophosphamide-induced diminished ovarian reserve and explore the follicular development-improving mechanism of this decoction. MethodsSixty female ICR mice with normal estrous cycle were assigned into a blank group (n=10) and a modeling group (n=50). The model was established by intraperitoneal injection of cyclophosphamide (60 mg·kg-1) for 5 days. The successfully modeled mice were randomly grouped as follows: model, estradiol (0.26 mg·kg-1), and high-, medium-, and low-dose (56.42, 28.21, 14.105 g·kg-1, respectively) Yulin Hukun decoction, with 10 mice in each group. The blank group and the model group received normal saline (10 mL·kg-1). The intervention was performed once a day for 21 days. The general conditions, estrous cycle, body weight, and ovary index were observed and recorded for each group. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were measured by enzyme-linked immunosorbent assay. Histopathological changes in the ovarian tissue were observed by hematoxylin-eosin staining. Western blot was employed to determine the protein levels of PI3K, Akt, mTOR, autophagy-related protein 7 (Atg7), beclin1, microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ), ubiquitin-binding adaptor protein (p62), forkhead box protein O1 (FoxO1), and acetylated forkhead box protein O1 (Ac-FoxO1) in mouse ovaries. Real-time PCR was adopted to determine the mRNA levels of PI3K, Akt, mTOR, Atg7, beclin1, and LC3Ⅱ in the mouse ovarian tissue. ResultsCompared with the blank group, the model group had disturbed estrous cycle, decreased body weight (P<0.05), loose ovarian structure with increased atretic follicles, increased serum FSH level (P<0.05), and decreased AMH and estradiol levels (P<0.05). Compared with the model group, the treatment groups showed recovered estrous cycles and body weight. The estradiol group and high- and medium-dose Yulin Hukun decoction groups showed declined FSH level (P<0.05) and elevated AMH levels (P<0.05). In addition, the treatment groups showed downregulated protein levels of Atg7, LC3Ⅱ, beclin1, FoxO1, and Ac-FoxO1 (P<0.01), upregulated protein levels of PI3K, Akt, mTOR, and p62 (P<0.01) in the ovarian tissue, gradual repair of the ovarian structure, with more intact and numerous follicles of various stages. ConclusionYulin Hukun decoction can inhibit autophagy in ovarian granulosa cells by activating the PI3K/Akt/mTOR signaling pathway and inhibiting the expression of autophagy-related proteins and transcription factors, thereby improving follicular development and ovarian reserve.
2.Clinical value of abdominal adipose volume in predicting early tumor recurrence after resec-tion of hepatocellular carcinoma
Guojiao ZUO ; Mi PEI ; Zongqian WU ; Fengxi CHEN ; Jie CHENG ; Yiman LI ; Chen LIU ; Xingtian WANG ; Xuejuan KONG ; Lin CHEN ; Xiaoqin YIN ; Hongyun RAO ; Wei CHEN ; Ping CAI ; Xiaoming LI
Chinese Journal of Digestive Surgery 2024;23(1):140-146
Objective:To investigate the clinical value of abdominal adipose volume in predicting early tumor recurrence after resection of hepatocellular carcinoma (HCC).Methods:The retrospective case-control study was conducted. The clinicopathological data of 132 HCC patients with tumor diameter ≤5 cm who were admitted to The First Affiliated Hospital of Army Medical University from December 2017 to October 2019 were collected. There were 110 males and 22 females, aged (51±4)years. All patients underwent resection of HCC. Preoperative computer tomography scanning was performed and the visceral and subcutaneous fats of patients were quantified using the Mimics Research 21.0 software. Based on time to postoperative tumor recurrence patients were divided to two categories: early recurrence and non-early recurrence. Observation indicators: (1) consistency analy-sis; (2) analysis of factors influencing early tumor recurrence after resection of HCC and construction of prediction model. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribu-tion were represented as M( Q1,Q3) or M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Consistency analysis was conducted using the intragroup correlation coefficient (ICC) test. Multivariate analysis was performed using the binary Logistic regression model forward method. Independent risk factors influencing early tumor recurrence after resection of HCC were screened. The area under curve (AUC) of receiver operating characteristic (ROC) curve was applied to select the optimal cut-off value to classify high and low risks of recurrence. The Kaplan-Meier method was used to draw survival curve and calculate survival time. The Log-Rank test was used for survival analysis. Results:(1) Consistency analysis. The consistency ICC of abdominal fat parameters of visceral fat volume (VFV), subcutaneous fat volume, visceral fat area, and subcutaneous fat area measured by 2 radiologists were 0.84, 1.00, 0.86, and 0.94, respectively. (2) Analysis of factors influencing early tumor recurr-ence after resection of HCC and construction of prediction model. All 132 patients were followed up after surgery for 662(range, 292-1 111)days. During the follow-up, there were 52 patients with non-early recurrence and 80 patients with early recurrence. Results of multivariate analysis showed that VFV was an independent factor influencing early tumor recurrence after resection of HCC ( odds ratio=4.07, 95% confidence interval as 2.27-7.27, P<0.05). The AUC of ROC curve based on VFV was 0.78 (95% confidence interval as 0.70-0.85), and the sensitivity and specificity were 72.2 % and 77.4 %, respectively. The optimal cut-off value of VFV was 1.255 dm 3, and all 132 patients were divided into the high-risk early postoperative recurrence group of 69 cases with VFV >1.255 dm 3, and the low-risk early postoperative recurrence group of 63 cases with VFV ≤1.255 dm 3. The disease-free survival time of the high-risk early postoperative recurrence group and the low-risk early post-operative recurrence group were 414(193,702)days and 1 047(620,1 219)days, showing a significant difference between them ( χ2=31.17, P<0.05). Conclusions:VFV is an independent factor influen-cing early tumor recurrence of HCC after resection. As a quantitative indicator of abdominal fat, it can predict the prognosis of HCC patients.
3.Circular RNAs Involved in The Development of Nasopharyngeal Carcinoma
Si-Cheng ZUO ; Dan WANG ; Yong-Zhen MO ; Yu-Hang LIU ; Jiao-Di CAI ; Can GUO ; Fang XIONG ; Guo-Qun CHEN
Progress in Biochemistry and Biophysics 2024;51(4):809-821
Circular RNAs (circRNAs) are a kind of non-coding RNA (ncRNA) with covalent closed-loop structure. They have attracted more and more attention because of their high stability, evolutionary conservatism, and tissue expression specificity. It has shown that circRNAs are involved in the development of a variety of diseases including malignant tumors recently. Nasopharyngeal carcinoma (NPC) is a malignant tumor that occurs in the nasopharynx and has a unique ethnic and geographical distribution in South China and Southeast Asia. Epstein-Barr virus (EBV) infection is closely related to the development of NPC. Radiotherapy and chemotherapy are the mainstays of treatment for NPC. But tumor recurrence or distant metastasis is the leading cause of death in patients with NPC. Several studies have shown that circRNAs, as gene expression regulators, play an important role in NPC and affect the progression of NPC. This review mainly summarized the research status of abnormally expressed circRNAs in NPC and EBV-encoded circRNAs. We also discussed the possibility of circRNAs as a therapeutic target, diagnostic and prognostic marker for NPC.
4.Molecular mechanism of ABO bood group variation
Hang LEI ; Xuefeng WANG ; Xiaowen CHENG ; Hui ZHANG ; Xiaohong CAI
Chinese Journal of Blood Transfusion 2024;37(4):385-391
【Objective】 To study the relationship between ABO subtype, para-Bombay blood group and genotype, so as to explore the possible molecular mechanism of these two blood groups, and provide accurate genetic detection targets and theoretical basis for the accurate identification of ABO blood group. 【Methods】 First, the serology of 24 200 patients with blood type identification in the Ruijin Hospital from February to December in 2022 were analyzed, as well as 10 ambiguous ABO samples from other hospitals(3 were suspected ABO subtype and 7 were suspected para-Bombay blood group). Then ABO subtypes and para-Bombay blood groups were directly sequenced or post-clonal sequencing was performed to analyze ABO, FUT1 and FUT2 gene sequences. 【Results】 Among the 24 200 patients underwent blood type identification, 7 cases of ABO subtypes were detected. Among the 10 ambiguous samples sent by other hospitals, 2 of ABO subtypes, 1 of normal type A, and 7 of para-Bombay blood type were detected. In total, we identified blood types as follows: 1) 9 ABO subtypes: A
5.Zhuangtongyin Modulates Ferroptosis via the Nrf2-SCL7A11/xCT-Gpx4 Pathway to Im-prove Cerebral Ischemia-reperfusion Injury
Chengyi WANG ; Yuefang CAI ; Zhenqiu NING ; Minzhen DENG ; Jingbo SUN ; Kim Sookja CHUNG ; Yan LI ; Xiao CHENG
Journal of Sun Yat-sen University(Medical Sciences) 2024;45(4):539-548
[Objective]To investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion(MCAO)model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism.[Methods]C57BL/6J mice were randomly divided into Sham operation group(Sham),model group(MCAO),low-dose Zhuangtongyin group(ZTY-L),high-dose Zhuangtongyin group(ZTY-H),with 5 mice in each group.The MCAO group was modelled by silica gel embolization,the middle cerebral artery of mice was embolized for 1h,then the silica gel was pulled out and reperfusion was performed after 72 h;and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted.The neural function of mice was evaluated by Zea-Longa method.TTC staining was used to evaluate the volume of cerebral infarction.The level of brain injury was evaluated by HE staining and Nissl staining.Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain.The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR,and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain.The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR.The expressions of Nrf2,SCL7A11/xCT,Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence.[Results]Zhuangtongyin improved the nerve function of mice after MCAO(P<0.05)and the cerebral infarction volume of mice(P<0.05)and alleviate the pathological injury of cerebral cortex cells after MCAO operation.Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO.Additionally,Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA(P<0.001),a transporter associated with cellular iron ion uptake,in the brains of post-MCAO mice.Furthermore,Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE(P<0.001)and suppressed ACSL4 mRNA expression in brain tissue post-MCAO(P<0.001).Besides,Zhuangtongyin downregulated the expression of PTGS2 mRNA(P<0.001),in the brains of post-MCAO mice.Zhuangtongyin increased the expression of nrf2 into the nucleus(P<0.001),and increased the expression of xCT and Gpx4 in neurons after MCAO(P<0.001).[Conclusion]Zhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice,alleviate the pathological damage of cerebral cortex cells,and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway.Therefore,it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.
6.Optimization of energy window of yttrium-90 bremsstrahlung SPECT imaging:In vitro experimental study
Wendi CHENG ; Yongzhao XIANG ; Haitao WANG ; Weiming WU ; Jingjing YANG ; Huawei CAI ; Zhen ZHAO
Chinese Journal of Interventional Imaging and Therapy 2024;21(3):175-178
Objective To observe the influence of different energy windows of the medium-energy general-purpose(MEGP)collimator on image quality,so as to optimize the energy window of yttrium-90(90Y)bremsstrahlung SPECT imaging.Methods 90Y bremsstrahlung spectrum was acquired,and the sensitivity,percentage of the source counts in useful field of view(S/FOV%)and signal-to-background ratio(S/B)of 90Y bremsstrahlung SPECT imaging at MEGP under different energy windows were compared.Results The energy spectrum of 90Y bremsstrahlung was a continuous curve,with the peak of 76.2 keV with MEGP collimator.The images obtained with MEGP collimator were clear,and no significant differences of S/FOV%nor S/B was found between 10%and 20%window width groups(both P>0.05),but the sensitivities of the latter was higher than the former(P<0.05).The sensitivity of 70-90 keV images was relatively high,while the S/FOV%and S/B had decreased.The S/FOV%and S/B of images ranging from 40-60 keV were high,but the sensitivity was low.Images acquired with 100 keV±20%showed fairly high sensitivity,S/FOV%and S/B,which was 69.73%,0.62 and 1.64,respectively.Conclusion When performing 90Y bremsstrahlung SPECT with MEGP collimator,the image quality at 20%window width was better than at 10%window width,and 100 keV±20%showed fairly high sensitivity and not significantly decreased S/FOV%and S/B.
7.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
8.Design, synthesis and antidepressant activity of novel genipin derivatives
Hong-yan CHENG ; Dan-hui WANG ; Wen-jie ZHAO ; Tian-cheng WANG ; Wen-xue XU ; Cai-yun ZHANG ; Ya-nan ZHAO ; Yan-chun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2564-2573
The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT1A) receptor,
9.Application value of a multi-dimensional digital monitoring platform for perioperative period in gastric cancer patients
Jiayu LI ; Zhiwei JIANG ; Gang WANG ; Huafeng PAN ; Miaomiao GE ; Haifeng WANG ; Pengyan XU ; Yuling CAI ; Nan HAIOU ; Cheng ZHANG
Chinese Journal of Digestive Surgery 2024;23(4):601-608
Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.
10.Rigid-body inverse dynamics modelling and analysis of 6RSS parallel bio-inspired masticatory robot
Chen CHENG ; Xiao-Jing YUAN ; Neng-Jun YANG ; Gen-Liang HOU ; Fan-Qi ZENG ; You-Cai WANG ; Wei-Peng LUO ; Guan ZHAO
Chinese Medical Equipment Journal 2024;45(3):16-22
Objective To carry out rigid-body inverse dynamics modelling and analysis of a self-designed 6RSS parallel bio-inspired masticatory robot.Methods Firstly,the functions of kinematic variables including translational/rotational velocities and accelerations were derived for rigid-body inverse dynamics modelling.Secondly,the rigid-body inverse dynamics model was established with the Newton-Euler's law.Finally,the chewing motion trajectories of the oral health volunteers were tracked and numerical calculations were carried out in the case where the robot was subjected to a chewing reaction force.Results Numerical calculations showed that the driving torque and the constraint force of the robot peaked when the chewing reaction force was at its maximum.Conclusion The external force has a large impact on the inverse dynamics of the robot,and theoretical references are provided for the motion control and optimal design of the robot.[Chinese Medical Equipment Journal,2024,45(3):16-22]

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