1.Xinjia Congrong Tusizi Decoction Regulates Ferroptosis of Granulosa Cells in Rat Model of Premature Ovarian Insufficiency via p53/Nrf2 Signaling Pathway
Min LIU ; Wei SHI ; Jing YANG ; Keming WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):104-111
ObjectiveTo investigate the effects of Xinjia Congrong Tusizi decoction (XJCTD) on ovarian functions in the rat model of premature ovarian insufficiency (POI) and decipher the mechanism of regulating the tumor suppressor protein (p53)/nuclear factor E2-related factor 2 (Nrf2) pathway to attenuate granulosa cell ferroptosis. MethodForty-eight SPF-grade female SD rats were randomized into control, model, low-, medium-, and high-dose (1.1, 2.2, 4.4 g·kg-1) XJCTD, and Western medicine (coenzyme Q10, 0.002 7 g·kg-1) groups, with eight rats in each group. The rat model of POI was established by gavage of triptolide (TP), and after successful modeling, each group was administrated with the corresponding drugs by gavage for 14 d. The body weight and ovarian weight of each rat were weighed and the ovarian index was calculated. The morphology of the ovarian tissue was observed by hematoxylin-eosin staining, and the proportions of growing follicles and atretic follicles were calculated. The serum levels of anti-Müllerian hormone (AMM), estradiol (E2), and follicle-stimulating hormone (FSH) were measured by enzyme-linked immunosorbent assay (ELISA). The DCFH-DA fluorescent probe was used to measure the reactive oxygen species (ROS) content in granulosa cells. The content of cellular Ferrous ion (Fe2+), lipid peroxide (LPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) was detected by colorimetry. The expression of the tumor suppressor protein p53,Nrf2, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) was determined by immunohistochemistry and Western blot. ResultCompared with the control group, the model group showed decreased ovarian weight, body weight, and ovarian index (P<0.01), reduced ovarian tissue volume and proportion of growing follicles (P<0.01), increased proportion of atretic follicles (P<0.01), lowered AMH and E2 levels and elevated FSH level in the serum (P<0.01), and elevated levels of Fe2+, ROS, LPO, and MDA (P<0.01) and lowered levels of GSH and SOD in granulosa cells (P<0.01). Moreover, the modeling up-regulated the expression of p53 (P<0.01) and down-regulated the expression of Nrf2, SLC7A11, and GPX4 (P<0.05, P<0.01) in the ovarian tissue. Compared with the model group, XJCTD increased the body weight, ovarian weight, and ovarian index (P<0.01), alleviated the pathological changes in the ovarian tissue, increased the proportion of growing follicles (P<0.01), decreased the proportion of atretic follicles (P<0.01), and reduced the content of ROS in granulosa cells (P<0.05, P<0.01). In addition, medium- and high-dose XJCTD lowered the FSH level (P<0.01) and raised E2 and AMH levels (P<0.01) in the serum, reduced the Fe2+ content (P<0.05, P<0.01), and increased the SOD content (P<0.01) in granulosa cells. High-dose XJCTD reduced the LPO and MDA content (P<0.01) and increased the SOD content (P<0.01) in the granulosa cells, down-regulated the expression of p53 (P<0.05), and up-regulated the expression of Nrf2, SLC7A11, and GPX4 in the ovarian tissue (P<0.05, P<0.01). ConclusionXJCTD may protect the ovarian function in the rat model of POI by regulating the p53/Nrf2 signaling pathway to attenuate the ferroptosis of ovarian granulosa cells.
2.Chinese expert consensus on surgical treatment of aortic valve disease in children
Hao ZHANG ; Keming YANG ; Xinxin CHEN ; Nianguo DONG ; Shoujun LI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1560-1566
The consensus was authored by National Society of Congenital Heart Diseases. After employing the Delphi process and incorporating literature reviews and expert discussions, seven recommendations were ultimately formulated. The consensus provides a detailed elaboration on the pathoanatomy, pathophysiology, clinical manifestations, diagnostic methods, and surgical treatment approaches for aortic valve diseases in children. It emphasizes that the treatment of aortic valve diseases in children should take into account the needs of growth and development, and recommends surgical strategies for different age groups and types of lesions, including valve plasty, Ross procedure, valve replacement, and balloon dilation. Specifically, aortic valve plasty is recommended for neonates and infants, while surgical options for older children are more diversified. The consensus only discusses isolated aortic valve disease and does not cover cases complicated with other heart malformations
3.Reamer-scraping and implant-pushing technique for transcrestal sinus floor elevation
Peizhao PENG ; Lan WANG ; Mingzhang XU ; Ziyang ZHENG ; Renshengjie ZHAO ; Keming XIAO ; Yang ZHOU ; Ke YU
West China Journal of Stomatology 2024;42(5):683-688
Transcrestal maxillary sinus floor elevation is an effective method to solve the problem of insufficient bone height in the posterior maxillary region.However,current methods,such as osteotome sinus floor elevation,cushioned grind-out technique,Smart Drill technique,etc.,require specialized surgical tool boxes.In this article,we introduce a new method of transcrestal maxillary sinus elevation that uses built-in reamers of various implant systems to scrap residu-al bone at the sinus floor and uses the implant to push the sinus membrane during implant placement.This technique is easy to operate and time saving and has a low rate of sinus membrane perforation.After a one-year follow-up observa-tion of 146 people and 175 implants,the endo-sinus bone gains were 5.00(4.70,5.30)mm and 2.10(1.40,2.70)mm in the group of 3 mm≤residual bone height(RBH)<5 mm and the group of 5 mm≤RBH<8 mm,respectively,which can meet the clinical requirements of implant stability.This technique is suitable in generalizing dental implantation.
4.Metabolomics-based screening of biomarkers for fenpropathrin-exposed rats
Qian YANG ; Tao WANG ; Fang GUO ; Yudie NING ; Keming YUN ; Zhiwen WEI
Chinese Journal of Forensic Medicine 2024;39(3):308-314
Objective Metabolomics was used to analyze the changes of metabolites in the plasma of Fenpropathrin-contaminated rats to find potential biomarkers for forensic identification of Fenpropathrin poisoning.Methods SD rats in the two experimental groups were given 20.5 mg/kg and 41 mg/kg doses of fenpropathrin respectively by gavage.The rats in the control group were given equivalent volume of normal saline.The angular vein blood of rats was collected 24 hours after gavage,and endogenous small molecule metabolites in plasma were investigated by ultra-performance liquid chromatography-time-of-flight mass spectrometry(UPLC-TOF-MS).The data was processed by SIMCA14.1.The differential metabolites in plasma of fenpropathrin-infected rats were screened out according to the Variable Importance in Projection(VIP)and p<0.05 in the OPLS-DA model.Finally,the pathways were analyzed.Results There were significant differences in plasma metabolite levels between the control group and the experimental group,and 17 biomarkers were selected to identify whether the rats had received fenpropathrin,which mainly affected purine metabolism,Alanine,aspartate and glutamate metabolism,arginine biosynthesis,biosynthesis of unsaturated fatty acids and pyrimidine metabolism.Conclusion Fenpropathrin can change the composition of metabolites in rats,and the differential markers screened can provide supportive forensic evidence for cases related to deltamethrin poisoning.
5.Risk factors for recurrent left ventricular outflow tract obstruction after surgical repair for subaortic stenosis
Jie DONG ; Shun LIU ; Shuo DONG ; Mengxuan ZOU ; Chuhao DU ; Yangxue SUN ; Haitao XU ; Jiashu SUN ; Qiang WANG ; Shoujun LI ; Keming YANG ; Jun YAN
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(10):599-604
Objective:To investigate the prognosis and risk factors for children diagnosed with all types of subaortic stenosis(SAS) who developed recurrent left ventricular outflow tract obstruction after surgical treatment.Methods:The study retrospectively included patients aged 0-18 years old who underwent open heart SAS surgery at Fuwai Hospital from 2016-2019. Children with hypertrophic obstructive cardiomyopathy were excluded. Detailed operative notes, medical records and ultrasound information, and follow-ups were extracted. Recurrent SAS was defined as left ventricular outflow tract gradient 30 mmHg(1 mmHg=0.133 kPa) 1 month after SAS surgical treatment.Results:A total of 137 children were included in this study. The medium age of children at the time of SAS surgery was 4.6 years old(3 months-17.8 years old). After a median follow-up of 4.36 years(3.2-5.7 years), a total of 30 patients developed recurrent LVOTO, with a recurrence rate of 21.9%, and 7(5.1%) underwent a second surgery. Compared to the non-recurrent group, children in the recurrent group were younger at the time of surgery( P=0.0443), had a smaller body surface area( P=0.0485), and a longer length of stay( P=0.0380). In Cox analysis, when only considering preoperative variables, the independent risk factor for LVOTO recurrence were a peak left ventricular outflow tract gradient higher than 50 mmHg( HR=5.25, P=0.001), a BSA less than 0.9( HR=2.5, P=0.023), and a length of SAS 5 mm( HR=2.29, P=0.050). When both preoperative and intraoperative variables were considered, preoperative peak left ventricular outflow tract gradient 50 mmHg( HR=4.91, P=0.002) and peeling from the aortic valve( HR=3.23, P=0.010) were independent risk factors for postoperative recurrence. Conclusion:Recurrent LVOTO after SAS surgical repair is common, and regular postoperative follow-up is crucial to evaluate whether a secondary intervention is required. Regular postoperative follow-up is needed for children at high risk.
6.Mechanism of Chaihu Shugansan in Treatment of Functional Dyspepsia in Rats Based on Mitophagy and Pink1/Parkin Signaling Pathway
Xiangxiang WANG ; Yujiao WANG ; Li LI ; Qingling JIA ; Kailin JIANG ; Keming YANG ; Jianghong LING
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):45-51
ObjectiveTo investigate the mechanism of Chaihu Shugansan in the treatment of functional dyspepsia in rats based on mitophagy and PTEN-induced kinase 1 (Pink1)/E3 ubiquitin ligase (Parkin). signaling pathway. MethodAccording to the principle of random grouping, 40 SD rats were assigned into a normal group, a model group, a Chaihu Shugansan group, and a positive drug (domperidone) group, with 10 rats in each group. The rats in other groups except the normal group received tail-clamping stimulation to replicate the model of functional dyspepsia. After each time of stimulation, the rats in the normal, model, Chaihu Shugansan, and positive drug groups were administrated with normal saline, normal saline, Chaihu Shugansan (4.8 g·kg-1), and an aqueous solution of domperidone (4.5 mg·kg-1), respectively. After 28 days of modeling, the gastric emptying rate and the small intestine propulsion rate of the rats in each group were measured and the tissue samples were collected. Hematoxylin-eosin (HE) staining was employed for observation of damage in gastric antrum tissue, and transmission electron microscopy (TEM) for ultrastructural observation of gastric interstitial cells of Cajal (ICCs). Immunofluorescence co-localization was adopted to observe the expression of cytochrome c oxidase (COX Ⅳ) and Parkin. Western blot was employed to determine the expression levels of microtubule-associated protein 1, light chain 3 (LC3), and the mitophagy-associated proteins prohibitin2 (PHB2), Pink1, Parkin, and ubiquitin-specific protease 30 (USP30). ResultCompared with the normal group, the modeling decreased the gastric emptying rate and the small intestine propulsion rate (P<0.05). Compared with the model group, Chaihu Shugansan increased the gastric emptying rate and the small intestine propulsion rate (P<0.05). The results of TEM showed that Chaihu Shugansan reduced the swelling degree of mitochondria in gastric antrum tissue. Compared with the normal group, the modeling increased the fluorescence intensity of Parkin in mitochondria (P<0.01), while such increase can be alleviated by Chaihu Shugansan (P<0.01). Western blotting results showed that compared with the normal group, the modeling up-regulated the protein levels of LC3, Pink1, Parkin, and PHB2 (P<0.05, P<0.01) and down-regulated the protein level of USP30 (P<0.01). Compared with the model group, Chaihu Shugansan down-regulated the protein levels of LC3, Pink1, Parkin, and PHB2 (P<0.05, P<0.01) and up-regulated the protein level of USP30 (P<0.01). ConclusionChaihu Shugansan may treat functional dyspepsia by blocking the Pink1/Parkin signaling pathway to inhibit excessive mitochondrial autophagy in ICCs.
7.Effects of Chaihu Shugan Powder (柴胡疏肝散) on Duodenal Mucosal Barrier and Intestinal Flora in Functional Dyspepsia Model Rats
Keming YANG ; Yuebo JIA ; Yeertai YELIYA ; Xuejiao LIU ; Xiangxiang WANG ; Kailin JIANG ; Jianghong LING
Journal of Traditional Chinese Medicine 2023;64(23):2443-2453
ObjectiveTo study the possible mechanism of Chaihu Shugan Powder (柴胡疏肝散, CSP) in the treatment of functional dyspepsia (FD). MethodsTwenty-four SD rats were randomly divided into a normal group, a model group, a CSP group and a probiotic group, with six rats in each group.The tail-clamping provocation method was used in all groups except for the normal group to replicate the FD rat model. Simultaneously, the normal group and the model group were given 10 ml/(kg·d) of saline by gavage, while the CSP group and the probiotic group were given 9.6 g/(kg·d) of CSP aqueous decoction and 0.945 g/(kg·d) of probiotic aqueous solution by gavage, respectively, twice daily for four weeks. After four weeks, the gastric emptying and small intestinal propulsion rates were detected in each group of rats. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in the gastric sinusoids and duodenum of the rats. The changes in the intestinal flora were analyzed by 16s rDNA high-throughput gene sequencing, and the expressions of the duodenal zona occludin 1 (ZO-1) and Occludin were detected by immunohistochemistry and western blotting. Pearson correlation analysis was performed on intestinal flora and ZO-1 and Occludin protein expression. ResultsThe gastric antrum tissue structure was clear in all groups, and the gland structure was regular, with smooth gastric tissue mucosa and no pathological changes such as erosion and ulcer. Compared to those in the normal group, the intestinal villi in the duodenal tissue in the model group were significantly reduced or atrophied, and the goblet cells were arranged in disorder, with eosinophilic infiltration; the gastric emptying rate and small intestinal propulsion rate, as well as ZO-1 and Occludin protein expression in duodenal tissue significantly decreased (P<0.01). Compared to those in the model group, the duodenal tissue structure was clear, and the length intestinal villi was longer, with goblet cells neatly arranged in the CSP group and the probiotic group; no obvious eosinophil infiltration was found, and the gastric emptying rate and small intestinal propulsion rate as well as ZO-1 and Occludin protein expression significantly increased in the CSP group; a small amount of eosinophil infiltration was found, and the gastric emptying rate and Occludin protein expression significantly increased in the probiotic group (P<0.05 or P<0.01). Beta diversity analysis of intestinal flora showed that the overall structure of intestinal flora in the model group changed significantly compared to that in the normal group (P<0.01). The overall structure of the intestinal flora in the CSP group and the probiotic group was closer to the normal group than the model group. Species composition analysis showed that the relative abundance of the Firmicutes decreased, while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae increased, and the Bacteroidetes/Firmicutes value increased in the model group than those in the normal group (P<0.05 or P<0.01). Compared to those in the model group, the relative abundance of the Firmicutes increased, while the relative abundance of the Bacteroidetes and norank_f_Muribaculaceae, as well as the Bacteroidetes/Firmicutes value decreased in the CSP group and the probiotic group (P<0.05 or P<0.01). There was no statistically significant difference in each indicator between the probiotic group and the CSP group (P>0.05). Pearson correlation analysis showed that at the phylum level, Firmicutes was positively correlated with ZO-1 (r=0.610, P=0.016) and Occludin (r=0.694, P=0.004) protein expression. Bacteroidetes was negatively correlated with ZO-1 (r=
8.Effect of peripheral cannulation for cardiopulmonary bypass in patients with congenital heart disease undergoing reoperation: A retrospective cohort study
Chun ZHOU ; Qiang HU ; Gang LIU ; Song LOU ; Luyu BIAN ; Shujie YAN ; Yuan TENG ; Sizhe GAO ; Keming YANG ; Bingyang JI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(04):546-550
Objective To evaluate the safety and efficacy of peripheral cannulation for cardiopulmonary bypass (CPB) in patients with reoperation of congenital heart disease. Methods The perioperative data of patients with congenital heart disease who underwent reoperation in Fuwai Hospital from 2019 to 2020 were retrospectively collected. They were divided into two groups according to the cannulation methods: a central group and a peripheral group. The prognosis of the patients was analyzed. Results A total of 80 patients were collected, including 43 patients in the central group, and 37 pateints in the peripheral group. In the central group, the median age was 18 (14, 32) years, and 21 patients were male. The median age of the peripheral group was 16 (10, 27 ) years, and 18 patients were male. The CPB time in the peripheral group was 201 (164, 230) min, which was longer than that in the central group [143 (97, 188 ) min, P<0.001]. The lactate after CPB in the peripheral group was statistically higher than that in the central group [2 (1, 2 ) mmol/L vs. 1 (1, 1) mmol/L, P=0.002]. The dosage of albumin use during CPB in the peripheral group was statistically higher than that in the central group [10 (0, 20) g vs. 0 (0, 0) g, P=0.004]. There was no statistical difference in the postoperative dosage of red blood cells use [0 (0, 2) U vs. 0 (0, 0) U, P=0.117], mechanical ventilation time [14 (11, 19) h vs. 13 (10, 15) h, P=0.296], ICU stay time [43 (23, 80) h vs. 40 (20, 67) h, P=0.237] or postoperative hospital stay time [10 (7, 12) d vs. 8 (7, 10) d, P=778] between the two groups. Conclusion It’s safe and efficient to establish CPB through peripheral cannulation in patients with complex congenital heart disease undergoing reoperation.
9.The long-term durability of valved homograft conduit in right ventricular outflow tract reconstruction after Ross surgery and non-Ross surgery
Yaojun DUN ; Dong ZHAO ; Zhongdong HUA ; Jun YAN ; Shoujun LI ; Keming YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(06):884-889
Objective To compare the long-term durability of valved homograft conduit (VHC) in patients with Ross and non-Ross right ventricular outflow tract (RVOT) reconstruction. Methods Patients who underwent RVOT reconstruction using VHC in Fuwai Hospital from January 2008 to October 2020 were retrospectively included. Patients who received Ross RVOT reconstruction were allocated to a Ross group and patients who received non-Ross RVOT reconstruction were allocated to a non-Ross group. The survival and reintervention-free rates of the two groups were evaluated with the Kaplan-Meier survival curve and log-rank test. The propensity score matching analysis was performed on the patients who completed ultrasound follow-up in the two groups, and the VHC dysfunction-free rate was compared between the two groups. Results A total of 243 patients were enrolled, including 142 males and 101 females, with a median age of 6 years (4 months to 56 years). There were 77 patients in the ROSS group and 166 patients (168 operations) in the non-ROSS group. The cardiopulmonary bypass time in the Ross group was shorter than that in the non-Ross group (175.4±45.6 min vs. 200.1±83.5 min, P=0.003). Five patients in the non-Ross group died early after the operation. The follow-up was available in 231 patients (93.1%), with the average follow-up time of 61.7±44.4 months. During the follow-up, 5 patients in the non-Ross group died. The 12-year survival rate was 100.0% in the Ross group and 93.2% in the non-Ross group (log-rank, P=0.026). In addition, 1 patient in the Ross group and 7 patients in the non-Ross group received VHC reintervention. There was no significant difference in the reintervention-free rate between the two groups (log-rank, P=0.096). Among the 73 patients in the Ross group and 147 patients in non-Ross group who were followed up by ultrasound after discharge, 45 patients (20.5%) developed VHC dysfunction. Before matching, the long-term durability of VHC in the Ross group was better than that in non-Ross group (10-year VHC dysfunction-free rate: 66.6% vs. 37.1%, log-rank, P=0.025). After the propensity score matching, 64 patients included in each group, and there was no statistical difference in the long-term durability of VHC between the two groups (10-year VHC dysfunction-free rate: 76.3% vs. 43.0%, log-rank, P=0.065). In the subgroup analysis, the 10-year VHC dysfunction-free rate in the Ross group was higher than that in the non-Ross group (71.0% vs. 20.0%, log-rank, P=0.032) among patients aged<6 years at surgery. However, there was no significant difference in the 10-year VHC dysfunction-free rate between the two groups (53.7% vs. 56.7%, log-rank, P=0.218) among patients aged ≥6 years at surgery. Conclusion After the propensity score matching analysis, the long-term durability of VHC has no significant difference between the Ross group and non-Ross group. The long-term durability of VHC after Ross surgery is superior to that of non-Ross surgery in patients aged<6 years at surgery.
10.Application status of right ventricular outflow tract reconstruction with valved homograft conduits: 13 years’ clinical analysis of a single center
Yaojun DUN ; Dong ZHAO ; Zhongdong HUA ; Jun YAN ; Shoujun LI ; Keming YANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):1019-1024
Objective To evaluate the clinical outcome of valved homograft conduits (VHC) used for right ventricular outflow tract (RVOT) reconstruction in Fuwai Hospital in recent 13 years, and explore the factors influencing the long-term durability of VHC. Methods Clinical data of patients using VHC for RVOT reconstruction in Fuwai Hospital from November 2007 to October 2020 were retrospectively analyzed. The Kaplan-Meier survival curve was used to evaluate survival, VHC reintervention and VHC dysfunction. Cox proportional risk regression model was used to analyze the risk factors for VHC dysfunction. Results Finally 251 patients were enrolled, including 145 males and 106 females. The median age at surgery was 6.0 (0.3-67.0) years. Early death occurred in 5 (2.0%) patients. The follow-up was available for 239 (95.2%) patients, with the follow-up time of 0.3-160.0 (61.3±45.4) months. Five patients died during the follow-up, and the 1-year, 6-year, and 13-year survival rates were 96.6%, 95.5% and 95.5%, respectively. Eight patients received VHC reintervention during the follow-up, and freedom rates from VHC reintervention were 100.0%, 97.1% and 82.4% at 1 year, 6 years and 13 years, respectively. A total of 226 patients were followed up by echocardiography after discharge, with the follow-up time of 0.2-138.0 (48.5±40.5) months. During the follow-up, 46 (20.4%) patients developed VHC dysfunction, and freedom rates from VHC dysfunction at 1 year, 5 years, and 10 years were 92.6%, 79.6% and 59.3%, respectively. Univariate Cox regression analysis showed that age<6 years and VHC diameter<19 mm were risk factors for VHC dysfunction (P=0.029, 0.026), but multivariate regression analysis only indicated that age<6 years was an independent risk factor for VHC dysfunction (P=0.034). Conclusion The early and late outcomes of VHC used for RVOT reconstruction are satisfactory, and the long-term durability of VHC is also optimal. In addition, age<6 years is an independent risk factor for VHC dysfunction.

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