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.Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome.
Hong-Hong ZHANG ; Qi LIU ; Hai-Jing ZHAO ; Ya-Ni YU ; Liu-Yang TIAN ; Ying-Yue ZHANG ; Zi-Hao FU ; Li ZHENG ; Yue ZHU ; Yu-Han MA ; Shuang LI ; Yang-Yang MA ; Yu-Qi LIU
Journal of Geriatric Cardiology 2023;20(5):330-340
		                        		
		                        			BACKGROUND:
		                        			The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients.
		                        		
		                        			METHODS:
		                        			A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared.
		                        		
		                        			RESULTS:
		                        			During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar.
		                        		
		                        			CONCLUSIONS
		                        			The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.
		                        		
		                        		
		                        		
		                        	
4.Burned-out testicular germ cell tumors: a clinicopathological analysis of three cases.
Ya Ping NI ; Zhi Han ZHANG ; Xiao Yan CHEN ; Jiang Shu LIU ; Xiao Qun YANG
Chinese Journal of Pathology 2023;52(4):347-352
		                        		
		                        			
		                        			Objective: To investigate the clinicopathological features and possible mechanisms of burned-out testicular germ cell tumors. Methods: The clinical and imaging data, histology and immunophenotypic characteristics of three cases of burned-out testicular germ cell tumors diagnosed at the Ruijin Hospital, Medical College of the Shanghai Jiaotong University, from 2016 to 2020 were retrospectively analyzed. The relevant literature was reviewed. Results: The mean age of the three patients was 32 years. Case 1 had an elevated preoperative alpha-fetoprotein level (810.18 μg/L) and underwent "radical pancreaticoduodenectomy and retroperitoneal lesion resection" for a retroperitoneal mass. Postoperative pathology showed embryonal carcinoma, which needed to exclude gonadal metastasis. Color Doppler ultrasound showed a solid mass of the right testis, with hypoechoic lesion and scattered calcification in some areas. Case 2 was a "right supraclavicular lymph node biopsy specimen." Chest X-ray showed multiple metastases in both lungs. The biopsy showed metastatic embryonic carcinoma and bilateral testicular color Doppler ultrasound revealed abnormal calcifications in the right testicle. Case 3 showed a cystic mass of the right testis with calcification and solid areas. All 3 patients underwent radical right orchiectomy. Grossly, borders of the testicular scar areas were well defined. Cross sectioning of the tumors showed a gray-brown cut surface and single focus or multiple foci of the tumor. The tumor maximum diameter was 0.6-1.5 cm. Microscopically, lymphocytes, plasma cells infiltration, tubular hyalinization, clustered vascular hyperplasia and hemosiderin laden macrophages were found in the scar. Atrophic and sclerotic seminiferous tubules, proliferation of clustered Leydig cells and small or coarse granular calcifications in seminiferous tubules were present around the scar. Seminoma and germ cell neoplasia in situ were seen in case 1, germ cell neoplasia in situ was seen in case 2 and germ cells with atypical hyperplasia were seen in case 3. Immunohistochemistry showed that embryonic carcinoma expressed SALL4, CKpan(AE1/AE3) and CD30, seminoma and germ cell tumor in situ expressed OCT3/4, SALL4 and CD117, and spermatogenic cells with atypical hyperplasia expressed CD99 and SALL4. The Ki-67 positive index was about 20%, while OCT3/4 and CD117 were both negative. Conclusions: Burned-out testicular germ cell tumors are rare. The possibility of gonad testicular metastasis should be considered first for extragonadal germ cell tumor. If fibrous scar is found in testis, it must be determined whether it is a burned-out testicular germ cell tumor. The burned-out mechanisms may be related to the microenvironment of tumor immune-mediated and local ischemic injury.
		                        		
		                        		
		                        		
		                        			Male
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		                        			Humans
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		                        			Adult
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		                        			Seminoma/secondary*
		                        			;
		                        		
		                        			Cicatrix/pathology*
		                        			;
		                        		
		                        			Hyperplasia
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			China
		                        			;
		                        		
		                        			Testicular Neoplasms/pathology*
		                        			;
		                        		
		                        			Neoplasms, Germ Cell and Embryonal/surgery*
		                        			;
		                        		
		                        			Calcinosis
		                        			;
		                        		
		                        			Carcinoma
		                        			;
		                        		
		                        			Tumor Microenvironment
		                        			
		                        		
		                        	
6.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. 
		                        		
		                        		
		                        		
		                        	
7.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
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		                        			Dalbergia
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		                        			Myocardial Ischemia
		                        			;
		                        		
		                        			Metabolomics
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		                        			Heart
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		                        			Heart Injuries
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		                        			Creatine Kinase, MB Form
		                        			
		                        		
		                        	
8.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
		                        			;
		                        		
		                        			Salivary Gland Calculi/surgery*
		                        			;
		                        		
		                        			Constriction, Pathologic
		                        			;
		                        		
		                        			Endoscopy
		                        			;
		                        		
		                        			Salivary Ducts/surgery*
		                        			;
		                        		
		                        			Lithotripsy
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
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
		                        			;
		                        		
		                        			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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