1.Chemical constituents from the leaves of Cyclocarya paliurus and their α-glucosidase inhibitory activities
Yong YANG ; Ting-Si GUO ; Min XIE ; Li-Hong TAN ; Wen-Chu LI ; Hao ZHENG ; Fei-Bing HUANG ; Yu-Pei YANG ; Wei WANG ; Yu-Qing JIAN
Chinese Traditional Patent Medicine 2024;46(3):834-842
AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.
2.Effect of Baoyuan Decoction on Chronic Heart Failure Model Rats Based on PERK/ATF4 Signaling Pathway
Xiao-Yu GAO ; Feng JI ; Dan-Yang HAO ; Yong TAN ; Bai-Rong WANG ; Yi-Wen ZHENG ; Xue-Bin CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(7):1851-1857
Objective To observe the therapeutic effect and mechanism of Baoyuan Decoction for chronic heart failure model rat.Methods SD rats were randomly divided into blank group,model group,Baoyuan Decoction group,Captopril group,Baoyuan Decoction+CCT020312[protein kinase R-like endoplasmic reticulum kinase(PERK)activator]group,15 rats in each group.Except for the blank group,the rats in the other groups were induced by Adriamycin to construct a chronic heart failure model.After corresponding drug intervention,cardiac function indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),brain natriuretic peptide(BNP),cardiac troponin I(cTnI)],inflammation-related factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)],oxidative stress factors[malondialdehyde(MDA),superoxide dismutase(SOD)]were detected in each group.Changes in apoptosis-related indicators[B-cell lymphoma 2(Bcl-2),B-cell lymphoma 2-associated X protein(Bax),Caspase-3]and PERK/transcription activator 4(ATF4)signaling pathway-related proteins glucose-regulated protein 78(GRP78),PERK,ATF4,C/EBP homologous protein(CHOP)levels.Results Compared with the blank group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in the model group were significantly increased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly decreased(all P<0.05).Compared with the model group and Baoyuan Decoction+CCT020312 group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in Baoyuan Decoction group and Captopril group were significantly decreased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly increased(all P<0.05).Compared with the Captopril group,there was no significant change in the above indexes(except CHOP protein expression level)in the Baoyuan Decoction group(P>0.05).Conclusion Baoyuan Decoction can delay the progression of chronic heart failure rats,and its mechanism may be related to inhibiting the PERK/ATF4 signaling pathway to alleviate cardiomyocyte apoptosis,further reducing the degree of inflammatory response and oxidative stress,thereby promoting the repair of cardiac function and myocardial injury.
3.Establishment and verification of auditory brainstem implant vocoder model
Qinjie ZHANG ; Sui HUANG ; Haoyue TAN ; Xiang ZHOU ; Junyi WANG ; Yuzi LIU ; Wen WEN ; Jia GUO ; Hao WU ; Huan JIA
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(10):1279-1286
Objective·To develope an auditory brainstem implant(ABI)vocoder based on cochlear implant(CI)vocoder characteristics and ABI electrode array topology,and to verify its reliability.Methods·An"n-of-m"coding strategy CI/ABI vocoder was constructed based on MATLAB.Within each frame,only the envelopes of the n channels with the highest energy were selected.The interaction coefficient(IC)(range:1?3),channel numbers(range:5?22),and electrode array topology(CI/ABI)were adjustable parameters,allowing for the synthesis of simulated speech.Psychoacoustic evaluation was employed,recruiting normal hearing subjects to perform closed-set simulated phoneme perception.The phoneme recognition accuracy(20 vowel questions/condition,11 consonant questions/condition)was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli.In the closed-set CI-simulated speech recognition,the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature(P>0.05).The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature(vowel|d|=1.6%vs.20%,consonant|d|=8.4%vs.9.9%),thus determining the optimal interaction coefficient of this model as 2.Subsequently,when modifying the electrode array topology to ABI,it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group,consistent with the reported literature.The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference(P>0.05),also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on"n-of-m"coding strategy is established and the optimal IC is determined.The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments.It provides suitable technical means for validating ABI-specific coding strategies.
4.Feasibility study of three-dimensional nnU-Net deep learning network for automatic segmentation of colorectal cancer based on abdominal CT images
Kaiyi ZHENG ; Hao WU ; Wenjing YUAN ; Ziqi JIA ; Xiangliang TAN ; Xiaohui DUAN ; Zhibo WEN ; Xian LIU ; Weicui CHEN
Chinese Journal of Radiology 2024;58(8):829-835
Objective:To investigate the feasibility of a three-dimensional no new U-Net (3D nnU-Net) deep learning (DL) network for the automatic segmentation of colorectal cancer (CRC) based on abdominal CT images.Methods:This was a cross-sectional study. From January 2018 to May 2023, a total of 2180 primary CRC patients, confirmed by pathology at the Guangdong Provincial Hospital of Traditional Chinese Medicine (center 1, n=777), Nanfang Hospital, Southern Medical University (center 2, n=732), and Sun Yat-sen Memorial Hospital (center 3, n=671), were enrolled in this retrospective study. The baseline abdominal CT examination of each patient was conducted using CT equipment from 7 different models across 4 vendors, at the 3 centers, encompassing both the arterial phase (AP) and venous phase (VP). Two radiologists manually delineated the volume of interest to circumscribe the entire tumors in dual-enhanced phase CT images. The CT data of CRC patients from center 1 and center 3 were merged and divided into a training set ( n=1 159) and a validation set ( n=289) using a weighted random method with a ratio of 4∶1. The patients from center 2 were used as an independent external test set ( n=732). The 3D nnU-Net segmentation model was trained and tested. Using manually annotated label data as the benchmark, segmentation performance of the model was evaluated based on different phases and tumor locations. The segmentation coverage rate (SCR), Dice similarity coefficient (DSC), recall (REC), precision (PRE), F1-score, and 95% Hausdorff distance (HD 95) were calculated. The mean manual segmentation time and the mean automatic time were compared using independent samples t-test. Results:In the independent external test set, the performance of the 3D nnU-Net model based on the AP CT images was superior to that based on the VP CT images. On the AP images, the SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.865, 0.714, 0.716, 0.736, 0.714, and 27.228, respectively; on the VP images, they were 0.834, 0.679, 0.710, 0.675, 0.679, and 29.358, respectively. The model achieved the best performance on right-sided colon cancer, with SCR, DSC, REC, PRE, F1-score, and HD95 on the AP CT images at 0.901, 0.775, 0.780, 0.787, 0.775, and 21.793, respectively. Next were left-sided colon cancer and rectal cancer, while the segmentation performance for transverse colon cancer was the worst (SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.731, 0.631, 0.641, 0.630, 0.631 and 38.721, respectively). The automatic segmentation time on a single phase was (1.0±0.3) min, while the manual segmentation time was (17.5±6.0) min ( t=128.24, P<0.001). Conclusions:After training and validating on a dataset from multiple centers with various CT scanner vendors, the 3D nnU-Net DL model demonstrates the capability to automatically segment CRC based on abdominal CT images, while also showcasing commendable robustness and generalization ability.
5.Chaihu Longgu Mulitang in Treatment of Coronary Heart Disease Complicated with Anxiety and Depression: A Review
Bo NING ; Xishu TAN ; Hongwei HE ; Hao WEN ; Teng GE ; Yongqing WU ; Hubin YU ; Lanshuan FENG ; Shilin LI ; Jiongdong XIE ; Mingjun ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(18):218-228
Coronary heart disease (CHD) with atherosclerosis is a common chronic disease worldwide, and anxiety and depression are potential and crucial risk factors for adverse prognosis in CHD. Chaihu Longgu Mulitang (CLMT), first mentioned in the Shang Han Lun (《伤寒论》), is a classic prescription for treating Shaoyang diseases combined with disturbance of the mind and spirit, with the effects of harmonizing Shaoyang and calming the mind. Current research on mechanisms has shown that CLMT can play a role in CHD complicated with anxiety and depression through multiple pathways, including regulating related signaling pathways, inhibiting the expression of inflammatory factors, improving oxidative stress damage, modulating neurotransmitter levels, suppressing the hypothalamic-pituitary-adrenal axis, promoting mobilization of mesenchymal stem cells from the bone marrow, and inhibiting platelet activation. Clinical studies have demonstrated that CLMT significantly improves symptoms such as angina and insomnia caused by CHD complicated with anxiety and depression, effectively reduces negative emotions, improves traditional Chinese medicine (TCM) syndrome scores, and decreases levels of inflammatory factors. Furthermore, it has fewer adverse reactions and higher safety than conventional western medicine treatments. This article provides a review of the mechanisms and clinical studies of CLMT in the treatment of CHD complicated with anxiety and depression based on a comprehensive analysis of literature from the China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, PubMed, and other databases in the past 15 years, in order to provide references for further research on the use of CLMT in the management of CHD complicated with anxiety and depression.
7.Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
Si-Nai LI ; Zi-Hao LIU ; Ming-Xue ZHOU ; Wei-Hong LIU ; Xiao-Lei LAI ; Ping LI ; Lei ZHANG ; Ju-Ju SHANG ; Sheng-Lei QIU ; Yan LOU ; Yu-Pei TAN ; Wen-Long XING ; Hong-Xu LIU
Chinese journal of integrative medicine 2023;29(12):1099-1110
OBJECTIVE:
To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:
A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:
DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION
DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice
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Animals
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Tumor Suppressor Protein p53/metabolism*
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Endothelial Cells/metabolism*
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Exosomes/metabolism*
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bcl-2-Associated X Protein/metabolism*
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Myocardium/metabolism*
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Myocardial Infarction/drug therapy*
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Apoptosis
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MicroRNAs/metabolism*
8. Glucose and serum deprivation under hypoxia treatment inducing oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells through inhibition of Nrf2 signaling pathway
Qiu-Min XIE ; Yan-Ting SUN ; Hui-Wen LIU ; Qin YI ; Bin TAN ; Jing ZHU ; Hao XU ; Jie TIAN
Acta Anatomica Sinica 2023;54(3):305-312
Objective To investigate the effects of glucose and serum deprivation under hypoxia(GSDH)treatment on oxidative stress and apoptosis in rat bone marrow mesenchymal stem cells (BMSCs), so to provide an experimental support for improving the therapeutic efficacy of BMSCs. Methods The cell injury model was established by hypoxia (1% O
9.A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city.
Ying Yin LIU ; Zhi Xing LI ; Zi Jina TAN ; Wen FANG ; Hao Min TAN ; Di FU ; Zhong Guo HUANG ; Jia Wei LIU ; Tao LIU ; Guan Hao HE ; Sui ZHU ; Wen Jun MA
Chinese Journal of Preventive Medicine 2022;56(10):1423-1428
Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.
Humans
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Air Pollution/adverse effects*
;
Temperature
;
Outpatients
;
Cities
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Eczema/epidemiology*
;
China/epidemiology*
;
Air Pollutants/analysis*
10.The Association of Obstructive Sleep Apnea With Breast Cancer Incidence and Mortality: A Systematic Review and Meta-analysis
Dominic Wei TING YAP ; Nicole Kye WEN TAN ; Benjamin Kye JYN TAN ; Yao Hao TEO ; Veronique Kiak MIEN TAN ; Anna SEE ; Song Tar TOH
Journal of Breast Cancer 2022;25(3):149-163
Purpose:
Emerging evidence from animal models suggests that intermittent hypoxia due to obstructive sleep apnea (OSA) is a risk factor for breast cancer. Despite their biological plausibility, human epidemiological studies have reported conflicting results. Therefore, we conducted a meta-analysis to delineate this relationship.
Methods:
We searched the PubMed, Embase, Scopus, and Cochrane Library databases for eligible studies from inception until June 6, 2021. Two reviewers selected randomized trials or observational studies reporting the association between OSA and breast cancer incidence compared with those without OSA. Two reviewers extracted relevant data and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and Newcastle-Ottawa Scale (NOS). We pooled the maximally covariate-adjusted hazard ratios (HRs) using a random-effects inverse varianceweighted meta-analysis and performed pre-specified subgroup analyses.
Results:
We included six studies out of 1,707 records, comprising a combined cohort of 5,165,200 patients. All studies used the International Classification of Diseases codes to classify OSA and breast cancer. OSA patients had a 36% increased breast cancer risk (HR, 1.36; 95% confidence interval [CI], 1.03–1.80; N = 6, I 2 = 96%) compared to those without OSA. Most studies adjusted for confounders, such as age, sex, obesity, diabetes mellitus, alcohol use, and hypertension. Subgroup analyses for studies with (1) multivariate adjustment and (2) at least five years of follow-up yielded HRs of 1.35 (95% CI, 0.98–1.87; N = 5, I 2 = 96%) and 1.57 (95% CI, 1.14–2.18; N = 4; I 2 = 90%), respectively. One Mendelian randomization study suggested a causal relationship, with a two-fold increase in the odds of breast cancer in patients with OSA.
Conclusion
This meta-analysis suggested that OSA is a risk factor for breast cancer. Future studies should explore the dose-response relationship between OSA and breast cancer, and whether treatment may mitigate breast cancer risk or progression.

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