1.Traditional Chinese medicine regulates the gut microbiota-bile acids-FXR axis to intervene in the development of colorectal cancer
Ya-ni WANG ; Xiao-yu ZHANG ; Yu-ping LIU ; Xiao-ying QIN ; Jie-ge HUO ; Yan CHEN ; Huang-qin ZHANG
Acta Pharmaceutica Sinica 2024;59(11):3027-3041
The gut microbiota plays a crucial role in the development of colorectal cancer (CRC). The imbalanced gut microbiota causes damage to the body and disrupts bile acids metabolism, increases susceptibility to CRC, and affects the signaling of farnesol X receptor (FXR), thereby promoting CRC progression. Traditional Chinese medicine has unique advantages in the treatment of CRC due to its synergistic regulatory effects of multiple components, targets, and pathways. It can regulate gut microbiota, intervene in bile acids metabolism, and activate its receptor FXR to inhibit the occurrence and development of CRC. Based on this, this article discusses the main role of the gut microbiota-bile acids-FXR axis in the development of CRC, and reviews the anti CRC effects and mechanisms of traditional Chinese medicine intervention on gut microbiota-bile acids-FXR axis, in order to provide new ideas and methods for the prevention and treatment of CRC.
2.Preparation and Biodistribution of 131I-labeled Hepatoma Nucleic Acid Nanotrain
Xue LIN ; Jie-hua XU ; Ya-ni DUAN ; Yan-qiu ZHU ; Yuan-yuan CHU ; Ming-ming LIU ; Jie QIN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):416-422
ObjectiveTo construct 131Ⅰ-labeled hepatoma nucleic acid nanotrain and to explore its feasibility as a new nuclide carrier targeting hepatoma. MethodsThree short nucleic acid chains self-assembled to a long nucleic acid chain after being annealed, and 131Ⅰ-NT was obtained by radioiodine labeling using chloramine T method. The labeling efficiency and radiochemical purity of the nanoparticles were measured by paper chromatography. The stability of the labeled products in vitro at different temperatures and different storage solvents was detected. The specific uptake of nanoparticles by hepatocellular carcinoma cells was observed by laser confocal microscopy, and the radioactive uptake ratio of 131Ⅰ-NT combined with human hepatocellular carcinoma cell HepG2 and normal hepatocyte L02 was measured. The biodistribution of 131Ⅰ-NT was obtained through injecting 131Ⅰ-NT into HepG2 tumor-bearing mice via tail vein. ResultsThe labeling rate of 131Ⅰ-NT was (93.05±0.74) %, and the radiochemical purity post purification was (98.35±0.32) %. Its radiochemical purity in PBS and pure serum at 4℃ for 24 h was (92.77±0.04) % and (89.43±0.2) %, respectively. The radioactivity uptake rate of HepG2 cells was higher than that of L02 cells after 131Ⅰ-NT was incubated with two kinds of cells for 2 h significantly. After injection of 131Ⅰ-NT through tail vein, the radioactive uptake per gram of tumor tissue were (4.9±0.55)%ID/g, (10.12±0.32)%ID/g and (4.25±0.31)%ID/g at 30 min, 1 h and 2 h, respectively. The T/M ratio was 7.33±2.04, 36.54±12.72 and 44.93±7.90 respectively. ConclusionsThe 131Ⅰ-labeled long chain nucleic acid nanotrain was constructed successfully, which possesses relatively high stability in vitro , and high targeting ability to HepG2 cells in vitro and HepG2 tumor-bearing mouse model. Our study demonstrated that 131Ⅰ-NT may be a potential radionuclide carrier targeting human liver cancer, which provides a new idea for the targeted radionuclide diagnosis and treatment of hepatocellular carcinoma.
3.UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood.
Wen-Long WANG ; An LI ; Lan-Ying CHEN ; Jia-Rong LI ; Ya-Ru CUI ; Ni ZHANG ; Ying-Ying LUO ; Rong-Hua LIU ; Can-Yue OUYANG ; Bei-Xin YUAN ; Ying ZHANG ; Peng-Hao-Bang LIU
China Journal of Chinese Materia Medica 2023;48(4):1043-1053
This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
Male
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Animals
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Rats
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Rats, Sprague-Dawley
;
Dalbergia
;
Myocardial Ischemia
;
Metabolomics
;
Heart
;
Heart Injuries
;
Creatine Kinase, MB Form
4.Recent progress in the treatment of intractable sialolithiasis.
Deng Gao LIU ; Dan Ni ZHENG ; Ya Ning ZHAO ; Ya Qiong ZHANG ; Xin YE ; Li Qi ZHANG ; Xiao Yan XIE ; Lei ZHANG ; Zu Yan ZHANG ; Guang Yan YU
Journal of Peking University(Health Sciences) 2023;55(1):8-12
Sialolithiasis occurs in approximately 0.45% to 1.20% of the general population. The typical clinical symptom manifests as a painful swelling of the affected glands after a meal or upon salivary stimulation, which extremely affects the life quality of the patients. With the development of sialendoscopy and lithotripsy, most sialoliths can be successfully removed with preservation of the gland. However, sialoliths in the deep hilar-parenchymal submandibular ducts and impacted parotid stones located in the proximal ducts continue to pose great challenges. Our research center for salivary gland diseases (in Peking University School and Hospital of Stomatology) has used sialendoscopy for 17 years and treated >2 000 patients with salivary gland calculi. The success rate was approximately 92% for submandibular gland calculi and 95% for parotid calculi. A variety of minimally invasive surgical techniques have been applied and developed, which add substantial improvements in the treatment of refractory sialolithiasis. Further, the radiographic positioning criteria and treatment strategy are proposed for these intractable stones. Most of the hilar-parenchymal submandibular stones are successfully removed by a transoral approach, including transoral duct slitting and intraductal basket grasping, while a small portion of superficial stones can be removed by a mini-incision in submandibular area. Impacted stones located in the distal third of parotid gland ducts are removed via "peri-ostium incision", which is applied to avoid a cicatricial stenosis from a direct ostium incision. Impacted parotid stones located in the middle and proximal third of the Stensen's duct are removed via a direct mini-incision or a peri-auricular flap. A direct transcutaneous mini-incision is commonly performed under local anesthesia with an imperceptible scar, and is indicated for most of impacted stones located in the middle third, hilum and intraglandular ducts. By contrast, a peri-auricular flap is performed under general anesthesia with relatively larger operational injury of the gland parenchyma, and should be best reserved for deeper intraglandular stones. Laser lithotripsy has been applied in the treatment of sialolithiasis in the past decade, and holmium ∶YAG laser is reported to have the best therapeutic effects. During the past 3 years, our research group has performed laser lithotripsy for a few cases with intractable salivary stones. From our experiences, withdrawal of the endoscopic tip 0.5-1.0 cm away from the extremity of the laser fiber, consistent saline irrigation, and careful monitoring of gland swelling are of vital importance for avoidance of injuries of the ductal wall and the vulnerable endoscope lens during lithotripsy. Larger calculi require multiple treatment procedures. The risk of ductal stenosis can be alleviated by endoscopic dilation. In summary, appropriate use of various endoscopy-assisted lithotomy helps preserve the gland function in most of the patients with refractory sialolithiasis. Further studies are needed in the following aspects: Transcervical removal of intraglandular submandibular stones, intraductal laser lithotripsy of impacted parotid stones and deep submandibular stones, evaluation of long-term postoperative function of the affected gland, et al.
Humans
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Salivary Gland Calculi/surgery*
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Constriction, Pathologic
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Endoscopy
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Salivary Ducts/surgery*
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Lithotripsy
;
Treatment Outcome
5.Value of Intraplaque Neovascularization on Contrast-Enhanced Ultrasonography in Predicting Ischemic Stroke Recurrence in Patients With Carotid Atherosclerotic Plaque
Zhe HUANG ; Xue-Qing CHENG ; Ya-Ni LIU ; Xiao-Jun BI ; You-Bin DENG
Korean Journal of Radiology 2023;24(4):338-348
Objective:
Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS).
Materials and Methods:
This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15–27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS.
Results:
During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975–97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025–3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810–9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS.
Conclusion
Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.
6. Dichloroacetate and vitamin C synergistically suppress proliferation, migration and invasion of glioma U87 and U251 cells
Xiao-Yu ZHANG ; Jian LIU ; Liang-Zhao CHU ; Ni-Ya LONG ; Liang-Zhao CHU ; Jian LIU
Chinese Pharmacological Bulletin 2023;39(2):275-286
Aim To investigate the effects of dichloroacetate(DCA)combined with vitamin C(VC)on the malignant behavior of glioma U87 and U251 cells, and to explore the potential mechanism. Methods U87 and U251 cells were treated with different concentrations of DCA alone or in combination with 5 mmol·L-1 VC. The proliferation rate of each group was detected by CCK-8 method and the cooperative index was calculated. U87 and U251 cells were treated with DMSO, 15 mmol·L-1 DCA, 5 mmol·L-1 VC and their combination. The changes of clonal formation, reactive oxygen species content, apoptosis, cell cycle, migration and invasion were detected via in vitro experiments, while the proliferation of U251 cells in vivo in each group was detected by subcutaneous tumor-forming model. Western blot was used to detect the expression levels and degradation rates of BCL2A1 and CDC25A in each group of cells after network pharmacological analysis of DCA and VC targets and their value in glioma, and the expression levels of CDK4, CDK6, cytochrome C, caspase-7 and cleaved-caspase-7 were detected. Results The combined index of 15 mmol·L-1 DCA and 5 mmol·L-1 VC was the highest. Compared with the control and single drug groups, the clonal formation, migration and invasion ability of cells in combination group in vitro significantly decreased, the proliferation rate in vivo also decreased, and the content of reactive oxygen species, apoptosis rate and G1 phase arrest rate significantly increased. BCL2A1 and CDC25A proteins were important targets of DCA and VC in glioma. Compared with the control and single-drug groups, the expression levels of BCL2A1, CDC25A, CDK4, and CDK6 in the combination group were significantly reduced, and the expression levels of cytochrome C and cleaved-caspase-7 markedly increased, and the protein degradation rates of BCL2A1 and CDC25A significantly increased in the combination group. Conclusions VC can cooperate with DCA to promote the degradation of BCL2A1 and CDC25A, and inhibit the malignant behavior of glioma cells.
7.Different frequency of acupoint thread-embedding for overweight/obesity of spleen deficiency and dampness retention: a randomized controlled trial.
Jing-Xue YUAN ; Jin-Hong LIU ; Jin-Xia NI ; Zi-Niu ZHANG ; Ding-Hao WANG ; Lun-Xue QING ; Ya-Nan HE
Chinese Acupuncture & Moxibustion 2023;43(11):1229-1234
OBJECTIVES:
To compare the effect of different frequency of acupoint thread-embedding on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention.
METHODS:
A total of 126 subjects with overweight/obesity of spleen deficiency and dampness retention were randomized into a 2-week group(63 cases, 13 cases dropped out)and a 3-week group(63 cases, 11 cases dropped out, 1 case was eliminated). The two groups were treated with acupoint thread-embedding once every 2 weeks and once every 3 weeks respectively, Zhongwan(CV 12), Shuifen(CV 9), Qihai(CV 6), Guanyuan(CV 4) and bilateral Zhangmen(LR 13), Tianshu(ST 25), Liangmen(ST 21), Daheng(SP 15), Fujie(SP 14), Pishu(BL 20), Yinlingquan(SP 9)were selected. Four times were required in the two groups. Before and after treatment, follow-up after 2 months of treatment completion, the body mass index(BMI), body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, fat percentage(F%), skin fold thickness were observed in the two groups.
RESULTS:
After treatment and in follow-up, the BMI, body weight, waist circumference, hip circumference, waist-to-hip ratio, obesity degree, F%, skin fold thickness in the two groups were decreased compared with those before treatment (P<0.001, P<0.01), the changes of BMI, body weight, obesity degree, F%, skin fold thickness in the 2-week group were larger than those in the 3-week group(P<0.05, P<0.01, P<0.001).
CONCLUSIONS
The effect of acupoint thread-embedding once every 2 weeks on weight loss in subjects with overweight/obesity of spleen deficiency and dampness retention is superior to that once every 3 weeks.
Humans
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Acupuncture Points
;
Overweight/therapy*
;
Spleen
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Obesity/therapy*
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Body Weight
;
Acupuncture Therapy
;
Weight Loss
8.Chemical constituents from stems and leaves of Cratoxylum cochinchinense and their inhibitory effects on proliferation of synoviocytes in vitro.
Yong ZHANG ; Ni-Fei SHI ; Zhen XIE ; Yi-Meng ZHAO ; Cai-Huan LIANG ; Ya-Yuan DENG ; Ran WANG ; Yan-Ping LIU ; Yan-Hui FU
China Journal of Chinese Materia Medica 2023;48(18):5014-5023
The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3β-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) μmol·L~(-1).
Synoviocytes
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Clusiaceae/chemistry*
;
Xanthones/analysis*
;
Plant Leaves/chemistry*
;
Cell Proliferation
;
Arthritis
9.Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer.
Mao-Yan TANG ; Dan-Ni DING ; Ya-Ya XIE ; Fang SHEN ; Jia LI ; Fang-Yuan LIU ; Feng-Juan HAN
China Journal of Chinese Materia Medica 2023;48(24):6572-6581
Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.
Humans
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Female
;
Medicine, Chinese Traditional
;
Vascular Endothelial Growth Factor A/metabolism*
;
Endothelial Cells/metabolism*
;
Angiogenesis
;
Angiogenesis Inhibitors/therapeutic use*
;
Ovarian Neoplasms/genetics*
;
Neovascularization, Pathologic/genetics*
10.Association between sleep duration and depressive symptoms inthe elderly
Deqiang XIAN ; Zhisong NI ; Jinfeng LAI ; Xiaoying MA ; Ya LIU
Sichuan Mental Health 2023;36(5):453-459
BackgroundDepression presents a significant risk to the physical and mental health of the elderly. The relationship between sleep and depressive symptoms has become a major research focus. However, previous research findings on this relationship have yielded inconsistent conclusions. ObjectiveTo explore the relationship between sleep duration and depressive symptoms in the elderly, in order to provide insights into the prevention of depressive symptoms and delaying their progression in the elderly. MethodsData analysis involved 8 210 adults aged 60 years or older, utilizing data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) survey. Participants were categorized into two groups those with depressive symptoms and those without- based on the Center for Epidemiologic Studies Depression-10 Scale (CESD-10) criteria. Logistic regression and restricted cubic spline models were used to analyze the association between sleep duration and depressive symptoms. ResultsThe 318 people with depressive symptoms were detected among the 8 210 elderly participants, with an average sleep duration of (6.14±2.05) hours per night. Restricted cubic spline models showed a non-linear association between sleep duration and depressive symptoms (χ2=412.670,P<0.01). After adjusting for confounding factors, compared to the elderly with a sleep duration 7~7.9 hours, the risk of depressive symptoms in the elderly was 2.971 times higher (95% CI: 2.560~3.449, P<0.01) in those with a sleep duration <6 hours, 1.372 times higher (95% CI: 1.161~1.621, P<0.01) in those with 6~6.9 hours, and 1 185 times higher (95% CI: 1.009~1.393, P<0.05) in those with ≥8 hours. Subgroup analysis showed no correlation between sleep duration ≥8 hours and the risk of depressive symptoms across genders and the 60~69 age group (P>0.05). ConclusionThere was an approximately nonlinear association between sleep duration and depressive symptoms, with differences by gender and age.[Funded by Sichuan Applied Psychology Research Center, Chengdu Medical College (number, CSXL-22226)]

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