1.Shexiang Tongxin dropping pills ameliorate myocardial ischemia-reperfusion injury progression via the S1PR2/RhoA/ROCK pathway
Ying Sun ; Boyang Jiao ; Yizhou Liu ; Ran Wang ; Qiong Deng ; David N Criddle ; Yulin Ouyang ; Wei Wang ; Xuegong Xu ; Chun Li
Journal of Traditional Chinese Medical Sciences 2025;2025(1):31-43
Objective:
To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD).
Methods:
A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model.
Results:
The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology.
Conclusion
STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
2.Pitavastatin-loaded procyanidins self-assembled nanoparticles alleviate advanced atherosclerosis via modulating macrophage efferocytosis and cholesterol efflux.
Yizhou WU ; Hongyan ZHOU ; Hao LIU ; Jiayao HU ; Yue SUN ; Wei YAN ; Chunyi TONG ; Ying KONG ; Bin LIU
Acta Pharmaceutica Sinica B 2025;15(6):3305-3320
Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE -/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.
3.Effects of Left Ventricular Assist and Aortic Graft Angle on Aortic Valve: A Hemodynamic Study
Yufeng SUN ; Yizhou KANG ; Zhenxia MU ; Suqin HUANG ; Bin GAO
Journal of Medical Biomechanics 2023;38(1):E129-E134
Objective To investigate the effect of left ventricular assist device (LVAD) and aortic graft angle on hemodynamics of aortic valve. Methods Three models of aorta and aortic valve with 45°, 60° and 90° anastomosis angles between LVAD and aorta were constructed, and an in vitro pulsating table was built for in vitro experiments. Using particle image velocimetry (PIV) system, three moments in the cardiac cycle ( T1 systolic peak, T rapid closure, T3 diastolic peak), were selected to study the hemodynamic state of aortic valve. Results Velocity vector, vorticity and viscous shear stress were used to evaluate the effect of LVAD anastomosis angle on hemodynamics of aortic valve. During the period of rapid valve closure, with the increase of graft angle, the blood flow velocity near the valve wall, the average vorticity and the maximum viscous shear stress all increased. Conclusions When the graft angle is lower, the impact velocity of blood on the valve is smaller, and the shear force on the valve decreases, so that the valve is in a better hemodynamic environment. This study provides references for the selection of anastomotic angles in clinical operations.
4.Clinical value of metagenomics next-generation sequencing in the diagnosis of urinary calculi with secondary infection
Zhongliang HONG ; Mingfa WAN ; Yizhou YE ; Zewei SUN ; Qian XU
Chinese Journal of Postgraduates of Medicine 2023;46(12):1144-1148
Objective:To explore the clinical value of metagenomics next-generation sequencing (mNGS) in the diagnosis of urinary calculi with secondary infection.Methods:From September 2021 to May 2022, a total of 110 urinary calculi patients from the First People′s Hospital of Zhejiang Province Tonglu County were collected retrospectively, the urine sample of the patients with bacterial meningitis was measured by urine bacterial culture and mNGS respectively. Taking urine bacterial culture as the "gold standard", the sensitivity, specificity, positive predictive value, negative predictive value, and Kappa consistency of mNGS in the diagnosing of urinary calculi with secondary infection were analyzed. Results:The positive of urine bacterial culture were 35 cases and negative were 75 cases; while positive and negative were 39 cases and 71 cases in the mNGS detection. Taking urinary bacterial culture as the "gold standard", the specificity, sensitivity, positive predictive value, negative predictive value and Kappa consistency coefficient of mNGS in the diagnosis of secondary infection of urinary calculi were 89.3%, 88.6%, 79.5%, 94.4% and 0.756 respectively. Compared with urine bacterial culture, the Kappa consistency coefficients of three common pathogens detected by the mNGS of macrogenomics, included escherichia coli, klebsiella pneumoniae and enterococcus faecalis were 0.703, 0.735 and 0.769, respectively. Conclusions:mNGS can improve the detection rate of pathogens of secondary infection of urinary calculi, and has a high consistency with the detection results of urinary bacterial culture.
5.Minimally invasive treatment of unstable pelvic fractures with blunt head technique of Kirschner wire and 3D-printed external template technigue
Yizhou WAN ; Kaifang CHEN ; Sheng YAO ; Yulong WANG ; Lian ZENG ; Tingfang SUN ; Xiaodong GUO
Chinese Journal of Orthopaedic Trauma 2022;24(12):1024-1029
Objective:To explore the safety and efficacy of the minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire and 3D-printed external template technique.Methods:A retrospective study was conducted of the clinical data of 21 patients with unstable pelvic fracture who had undergone minimally invasive treatment at Department of Orthopaedics, Union Hospital from May 2016 to July 2018 using 3D-printed external templates and the blunt head technique of Kirschner wire. There were 7 males and 14 females with an age of 43.6 years (from 19 to 65 years). According to the Tile classification, there were 3 cases of B1, 7 ones of B2, 6 ones of C1 and 5 ones of C2. The intraoperative fluoroscopy, operation time, postoperative fracture reduction and functional recovery of the pelvis at the last follow-up were recorded.Results:The 21 patients were followed up for an average of 16.3 months (from 12 to 24 months). A total of 33 wires were inserted in the 21 patients, including 15 S 1 ones and 18 S 2 ones. The intraoperative fluoroscopy ranged from 13 to 27 times, averaging 21.8 times. The operation time ranged from 65 to 130 min, averaging 88.6 min. The anterior subcutaneous internal fixation was used to fix the anterior ring in 9 patients. No vascular injury occurred during the operation. By the Matta criteria, the postoperative fracture reduction was assessed as excellent in 14 cases, good in 5, and fair in 2, giving an excellent to good rate of 90.5% (19/21). By the Majeed scoring system, the pelvic function at the last follow-up was assessed as excellent in 10 cases, good in 8, and fair in 3, giving an excellent to good rate of 85.7% (18/21). Lateral femoral cutaneous nerve injury occurred in 2 patients but was recovered by the 3-month follow-up. No other complications were follwed up. Conclusion:The minimally invasive treatment of unstable pelvic fractures with the blunt head technique of Kirschner wire assissted by 3D-printed external templates is safe and effective, showing advatages of reduced fluoroscopic frequency and operation time.
6.Expression of SLAMF5 in rat liver transplantation and its relationship with rejection
Shipeng LI ; Xiaojie CHEN ; Jinming ZHANG ; Guangpeng ZHOU ; Yizhou JIANG ; Rili LI ; Haiming ZHANG ; Liying SUN ; Zhijun ZHU
Chinese Journal of Hepatobiliary Surgery 2022;28(9):689-694
Objective:To investigate the role of signal lymphocyte activating molecule family member 5 (SLAMF5) in liver transplantation rejection in SD rats.Methods:Forty-five male SD rats without special pathogens, weight 260-300 g, aged 10-12 weeks were included. Among them, forty male SD rats (20 donors and 20 recipients respectively) were established with reference to the " two cuff" method. 15 liver transplantation model rats were randomly divided into 1 week (LT-1W) group, 2 weeks (LT-2W) group and 3 weeks (LT-3W) group, with 5 rats in each group, and 5 normal rats were taken as the normal control group. The expressions of SLAMF5, CD4 and CD8 were detected by polymerase chain reaction (PCR), Western blot and immunohistochemistry. The correlations between SLAMF5 expression in the lymphocyte infiltration area and the rejection activity index was analyzed.Results:The levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin were significantly higher in LT-1W group, LT-2W group and LT-3W group than those in the normal control group (all P<0.05). PCR results showed that the relative expression of SLAMF5 mRNA were (5.44±1.11), (4.69±1.12), (2.18±0.68) respectively, which were increased in LT-1W group, LT-2W group and LT-3W group than those in normal control group (1.01±0.23), and the differences were statistically significant (all P<0.05). Immunohistochemical staining showed that SLAMF5 and CD4, CD8 positive T cells were mainly distributed in the portal area, hepatic lobule area and around the proliferative bile duct, and there was a certain overlap. Correlation analysis showed that there was a positive correlation between the expression of SLAMF5 in the lymphocyte infiltration area and the rejection activity index ( r=0.519, P=0.048). Conclusion:The expression of SLAMF5 is increased after liver transplantation in SD rats, and there is a correlation between SLAMF5 expression and liver transplantation rejection in rats.
7.Factors influencing the outcomes of two-stage radical surgery for perianal fistulizing Crohn′s disease
Heng ZHANG ; Yizhou SUN ; Dan SU ; Wei WANG ; Jia KE ; Donglin REN
Chinese Journal of Inflammatory Bowel Diseases 2021;05(2):156-161
Objective:To explore the factors which influence the outcomes of two-stage radical surgery for the patients with perianal fistulizing Crohn′s disease (pfCD) .Methods:Clinical data of 31 pfCD patients who underwent two-stage radical surgery in the Sixth Affiliated Hospital of Sun Yat-sen University from March 2016 to June 2018 were analyzed retrospectively. All the patients got good drainage results comfirmed by MRI after the treatment of one-stage seton drainage and the following medical treatment. According to the outcome of two-stage radical surgery, the patients were divided into the healing group ( n = 23) and the failed group ( n = 8) . The clinical characteristics between the two groups were analyzed statistically. Wilcoxon rank sum test was used to analyze the difference in C-reactive protein (CRP) , erythrocyte sedimentation rate (ESR) , platelet (PLT) , body mass index (BMI) , hemoglobin (HB) and albumin (ALB) between before the one-stage seton drainage and before the two-stage radical surgery in each group. Results:The healing rate of pfCD after two-stage radical surgery was 74.2% (23/31) . The ratio of proctitis before the one-stage seton drainage (8.70% vs.50.00%, P = 0.026) , the ratio of multiple internal openings or multiple independent fistulas before the one-stage seton drainage (21.74% vs. 75.00%, P = 0.012) and the PLT before the two-stage radical surgery [240.0 (202.0, 277.0) × 10 9/L vs. 319.5 (247.3, 385.5) × 10 9/L, P = 0.04] in the healing group were significantly lower than those in the failed group. The variations of PLT [240.0 (202.0, 277.0) × 10 9/L vs. 300.9 (230.0, 413.0) × 10 9/L, P = 0.004], HB [136.0 (114.0, 144.0) g/L vs. 127.0 (107.0, 137.0) g/L, P = 0.004], ALB[43.10 (39.62, 47.41) g/L vs. 40.45 (36.58, 42.58) g/L, P = 0.011] and BMI [19.93 (17.99, 21.22) kg/m 2 vs. 18.22 (16.61, 19.38) kg/m 2, P<0.001] in the healing group before two-stage radical surgery showed better trends than those before one-stage seton drainage, while there was no significant variation trend of ESR and CRP between the two points in time (both P>0.05) . There were no sigificant differences in all indexes in the failed group between before one-stage seton drainage and before the two-stage radical surgery (all P>0.05) . Conclusions:Beside the initial proctitis and multiple internal openings or multiple independent fistulas, PLT level before the two-stage radical surgery for pfCD is also an influencing factor of surgical outcome. The situations of BMI, HB, ALB, and PLT before the two-stage radical surgery are better than those before the one-stage seton drainage may be used as the screening indications of the radical surgery.
8.Factors influencing the outcomes of two-stage radical surgery for perianal fistulizing Crohn′s disease
Heng ZHANG ; Yizhou SUN ; Dan SU ; Wei WANG ; Jia KE ; Donglin REN
Chinese Journal of Inflammatory Bowel Diseases 2021;05(2):156-161
Objective:To explore the factors which influence the outcomes of two-stage radical surgery for the patients with perianal fistulizing Crohn′s disease (pfCD) .Methods:Clinical data of 31 pfCD patients who underwent two-stage radical surgery in the Sixth Affiliated Hospital of Sun Yat-sen University from March 2016 to June 2018 were analyzed retrospectively. All the patients got good drainage results comfirmed by MRI after the treatment of one-stage seton drainage and the following medical treatment. According to the outcome of two-stage radical surgery, the patients were divided into the healing group ( n = 23) and the failed group ( n = 8) . The clinical characteristics between the two groups were analyzed statistically. Wilcoxon rank sum test was used to analyze the difference in C-reactive protein (CRP) , erythrocyte sedimentation rate (ESR) , platelet (PLT) , body mass index (BMI) , hemoglobin (HB) and albumin (ALB) between before the one-stage seton drainage and before the two-stage radical surgery in each group. Results:The healing rate of pfCD after two-stage radical surgery was 74.2% (23/31) . The ratio of proctitis before the one-stage seton drainage (8.70% vs.50.00%, P = 0.026) , the ratio of multiple internal openings or multiple independent fistulas before the one-stage seton drainage (21.74% vs. 75.00%, P = 0.012) and the PLT before the two-stage radical surgery [240.0 (202.0, 277.0) × 10 9/L vs. 319.5 (247.3, 385.5) × 10 9/L, P = 0.04] in the healing group were significantly lower than those in the failed group. The variations of PLT [240.0 (202.0, 277.0) × 10 9/L vs. 300.9 (230.0, 413.0) × 10 9/L, P = 0.004], HB [136.0 (114.0, 144.0) g/L vs. 127.0 (107.0, 137.0) g/L, P = 0.004], ALB[43.10 (39.62, 47.41) g/L vs. 40.45 (36.58, 42.58) g/L, P = 0.011] and BMI [19.93 (17.99, 21.22) kg/m 2 vs. 18.22 (16.61, 19.38) kg/m 2, P<0.001] in the healing group before two-stage radical surgery showed better trends than those before one-stage seton drainage, while there was no significant variation trend of ESR and CRP between the two points in time (both P>0.05) . There were no sigificant differences in all indexes in the failed group between before one-stage seton drainage and before the two-stage radical surgery (all P>0.05) . Conclusions:Beside the initial proctitis and multiple internal openings or multiple independent fistulas, PLT level before the two-stage radical surgery for pfCD is also an influencing factor of surgical outcome. The situations of BMI, HB, ALB, and PLT before the two-stage radical surgery are better than those before the one-stage seton drainage may be used as the screening indications of the radical surgery.
9.The supra-pectineal quadrilateral surface buttress plate for the treatment of complex acetabular fractures
Kaifang CHEN ; Sheng YAO ; Yizhou WAN ; Lian ZENG ; Fengzhao ZHU ; Zekang XIONG ; Liang YANG ; Jinge ZHOU ; Tingfang SUN ; Xiaodong GUO
Chinese Journal of Orthopaedics 2020;40(5):294-301
Objective:To introduce a novel anatomical supra-pectineal quadrilateral surface buttress plate, and explore its advantages, disadvantages and clinical efficacy in the treatment of complex acetabular fractures.Methods:Data of eighteen cases of acetabular fractures treated in our department from March 2017 to March 2019were retrospectively analyzed. There were 15 males and 3 females with an average age of 49.6 years (range, 27-62 years). According to the Letournel-Judet’s classification, there were 3 cases of anterior column fractures (involving quadrilateral surface), 2 cases of "T" shaped, 8 of cases anterior column and posterior hemi-transverse (ACPHT) and 5 cases of double columns fractures. The time from injury to operation was 5-14 days (mean, 7 days). Before operation, all patients were taken pelvic anterior-posterior X-ray and CT scan. All patients were adopted supra-ilioinguinal approach and fixed by supra-pectineal quadrilateral surface buttress plate. Surgical time, intraoperative blood loss and postoperative complications were collected. After operations all patients were taken pelvic X-ray in anterior-posterior and Judet position, as well as CT scan. The radiographic quality of reduction was evaluated by Matta criteria and hip functions were evaluated by Matta Modified Merle d’Aubigné-Postel scoring system.Results:The average surgical time was 130 min (range, 100-200 min). The average blood loss was 560 ml (range, 400-900 ml). An additional shaping was unnecessary in 18 patients who were implanted with the anatomical supra-pectineal quadrilateral surface buttress plate and all patients were operated successfully. All patients were followed up for an average time of 9 months (range, 6-15 months). The quality of fracture reduction was evaluated according to Matta standard, of which there were 11 cases excellent, 4 cases good, and 3 cases poor, with an excellent rate of 83.3% (15/18). At the latest follow-up, the function of the hip joint was evaluated according to the Matta Modified Merle d’Aubigné-Postel scoring system for a mean of 15.8 scores (range, 12-18 scores), of which there were 10 cases excellent, 6 cases good, 2 cases fair, with an excellent rate of 88.9% (16/18). All patients recovered well, and there were 2 cases of lateral femoral cutaneous nerve injury postoperative who had recovered one month later. There was no other postoperative complications.Conclusion:The anterior and posterior column and quadrilateral surface could be stabilized simultaneously by the anatomical supra-pectineal quadrilateral surface buttress plate without intraoperative shaping. Moreover, it is more likely to obtain a satisfactory clinical outcome by using this special plate with lower complications and rigid fixation. Therefore, it is a kind of internal fixation method worthy of promotion in the treatment of complex acetabular fractures.
10.Multi-center, prospective, open self-controlled, randomly crossed trial on the treatment with the conception aid kit in male infertility
Ruhui TIAN ; Zhen YE ; Tonghang GUO ; Hongfang SUN ; Yu WU ; Lina ZHOU ; Xiaoning JI ; Dongli CHEN ; Su SONG ; Xiaoke SUN ; Yizhou WANG ; Yunjing XUE ; Hui ZHOU ; Bin HU ; Hongbing LUAN ; Chengliang XIONG ; Zheng LI
Chinese Journal of Reproduction and Contraception 2020;40(9):734-740
Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.


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