1.Mechanism of Shenmai Injection to Improve Cisplatin Resistance in NSCLC Based on Endoplasmic Reticulum Stress Through PERK/ATF4/CHOP Signaling Pathway
Shengnan GUO ; Hao CAO ; Dan WANG ; Wenjun LIU ; Jianguang WANG ; Jialu LYU ; Chun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):70-78
ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer (NSCLC) based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase (PERK)/activated transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line (A549/cisplatin) were randomly divided into four groups: Blank control group (0.9% sodium chloride), cisplatin group (5 µg·g-1cisplatin), Shenmai injection group (5.2 mg·g-1 Shenmai injection), and combination therapy group (5.2 mg·g-1 Shenmai injection +5 µg·g-1cisplatin). The drug intervention lasted for 4 weeks, and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin (HE) staining was performed to observe tumor tissue pathology. Transmission electron microscopy (TEM) was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK, ATF4, and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein (BIP), PERK, phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, B-cell lymphoma -2 (Bcl-2), and Bcl-2 Associated X protein (Bax). A549/cis cells were divided into blank group: Blank control group (normal culture medium), cisplatin group (23.3 µmol·L-1 cisplatin), Shenmai Injection group (20 g·L-1 Shenmai injection), and combination therapy group (20 g·L-1 Shenmai injection+23.3 µmol·L-1 cisplatin). Cell counting kit-8 (CCK-8) method was used to detect cell viability, TEM was used to observe the morphology of endoplasmic reticulum, and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group, the combination therapy group showed increased body weight (P<0.05), decreased tumor volume (P<0.05), and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK, ATF4, and CHOP increased (P<0.05). Western blot revealed elevated protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, and Bax (P<0.05), while Bcl-2 expression decreased (P<0.05). As shown in the in vitro experiment, compared with the cisplatin group, the combination therapy group exhibited a reduced cell survival rate (P<0.05). TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP and Bax (P<0.05), with decreased Bcl-2 expression (P<0.05). ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC, which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.
2.Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression.
Liu YANG ; Wenjun LI ; Yingfen CHEN ; Ru YA ; Shengying QIAN ; Li LIU ; Yawen HAO ; Qiuhong ZAI ; Peng XIAO ; Seonghwan HWANG ; Yong HE
Acta Pharmaceutica Sinica B 2025;15(8):4096-4114
Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.
3.Isodons A-H, seco-abietane and abietane-type diterpenoids from Isodon lophanthoides: isolation, structural elucidation, and anti-cholestatic activity.
Huiling ZHOU ; Mingzhu HAN ; Miaomiao NAN ; Yingrong LENG ; Weiming HUANG ; Shengtao YE ; Lingyi KONG ; Wenjun XU ; Hao ZHANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1133-1142
Eight new diterpenoids, Isodons A-H (1-8), comprising seco-abietane and abietane-type structures, together with 13 known analogues (9-21), were isolated from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara. The compounds (+)-3/(-)-3, (+)-4/(-)-4, and (+)-5/(-)-5 were identified as three enantiomeric pairs. The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), 1D & 2D nuclear magnetic resonance (NMR) spectroscopy, electronic circular dichroism (ECD) calculations, and X-ray diffraction crystallography. A cholesterol 7α-hydroxylase (Cyp7a1) luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1, (+)-4, 6, 7, 12-14, and 16. Additionally, compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor (FXR)-associated signaling pathways in vitro and in vivo. These findings suggest potential applications for I. Lophanthoides in pharmaceutical development.
Abietanes/pharmacology*
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Molecular Structure
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Animals
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Isodon/chemistry*
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Humans
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Diterpenes/pharmacology*
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Plant Extracts/chemistry*
4.Clinical Efficacy of Shuxin Jieyu Decoction in Treating Coronary Heart Disease with Angina Pectoris Complicated by Anxiety Disorder
Jiayu CHEN ; Daimei NI ; Xiang REN ; Tianruo PAN ; Hao ZHANG ; Wenjun XIAO ; Ji ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(10):2407-2413
Objective To observe the clinical efficacy of Shuxin Jieyu Decoction(composed of Chuangxiong Rhizoma,Angelicae Sinensis Radix,Bupleuri Radix,Paeoniae Radix Alba,Paeoniae Radix Rubra,Curcumae Radix,Ziziphi Spinosae Semen,Glycyrrhizae Radix et Rhizoma Praeparata cum Melle,Platycladi Semen,Polygoni Multiflori Caulis,Polygalae Radix,Toosendan Fructus,Corydalis Rhizoma,and Albiziae Cortex)in treating coronary heart disease(CHD)with angina pectoris complicated by anxiety disorder in patients with qi stagnation and blood stasis syndrome.Methods Sixty patients diagnosed with qi stagnation and blood stasis syndrome type of CHD with angina pectoris and anxiety disorder were enrolled from the outpatient and inpatient departments of Taihe Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Chinese Medicine between January 2024 and January 2025.Patients were randomly divided into an observation group(n=30)and a control group(n=30)using a random number table method.The control group received conventional CHD treatment and anxiolytic therapy(Flupentixol and Melitracen Tablets),while the observation group additionally received Shuxin Jieyu Decoction.Both groups were treated for 4 weeks.Changes in traditional Chinese medicine(TCM)syndrome scores and Hamilton Anxiety Rating Scale(HAMA)scores were evaluated before and after treatment.The therapeutic effects of angina pectoris,nitroglycerin reduction/cessation rates,and total adverse event rates were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate in the observation group was 93.33%(28/30),compared to 73.33%(22/30)in the control group.The intergroup comparison(by Fisher's precision probability test)showed that the observation group's efficacy was significantly superior to that of the control group(P<0.05).(2)After treatment,both groups showed significant reductions in TCM syndrome scores(P<0.05)for symptoms including chest tightness and pain,costal distension,anxiety,palpitations,excessive sighing,irritability,and insomnia.The observation group's reduction was significantly greater than that of the control group(P<0.05).(3)After 4 weeks,the total reduction/discontinuation rate of nitroglycerin was 90.00%(27/30)in the observation group versus 66.67%(20/30)in the control group.The intergroup comparison(by Fisher's precision probability test)showed that the observation group's reduction rate was significantly higher than that of the control group(P<0.05,Fisher's precision probability test).(4)After treatment,both groups exhibited reduced Hamilton Anxiety Rating Scale(HAMA)scores(P<0.05),with the observation group showing a significantly greater improvement(P<0.05).(5)The total incidence of adverse reactions was 20.00%(6/30)in the observation group and 23.33%(7/30)in the control group,with no statistically significant difference between groups(P>0.05).Conclusion The combination of Shuxin Jieyu Decoction with conventional western medicine treatment demonstrates superior clinical efficacy compared to conventional western medicine alone in patients with qi stagnation and blood stasis syndrome type of CHD with angina pectoris and anxiety disorder.It effectively alleviates angina symptoms and anxiety disorder,reduces nitroglycerin usage,without increasing adverse effects.
5.Construction of microfluidic organ-on-a-chip and its application in simulating subchondral bone remodeling
Fuming SHEN ; Lingni LIAO ; Wenjun WANG ; Jilong LI ; Hao ZHANG ; Yan HU ; Ke XU ; Jiacan SU
Chinese Journal of Trauma 2024;40(2):179-189
Objective:To construct a microfluidic organ-on-a-chip and evaluate its capability in simulating subchondral bone remodeling during the progression of osteoarthritis.Methods:The chip′s main body was designed based on the microfluidic technology and cell co-culture technique. MC3T3-E1 cells were cultured adherently within the cell seeding micro-chamber, with the culture medium perfused at a flow rate of 0.5 ml/min at the bottom of the micro-chamber. Evaluation metrics were as follows: (1) Assessment of the microfluidic organ-on-a-chip: The growth culture medium was perfused and simulation experiments were conducted to test the concentration differences and equilibrium times of the fluid inside and at the bottom of the cell seeding micro-chamber at various time points; live-dead staining was performed to observe the biocompatibility of cells cultured continuously for 3 days and 7 days at a set flow rate, which was divided into 3-day and 7-day groups. (2) Osteogenic potential of the microfluidic organ-on-a-chip: The osteogenic induction medium was perfused, and ALP staining and PCR were performed to compare the number of the black alkaline phosphatase (ALP)-positive cells and the expression levels of osteogenesis-related marker genes including osteoblast-specific transcription factor 2 (RUNX2), type I collagen (COL1A1), bone morphogenetic protein-2 (BMP-2), and osteocalcin (OCN) under static, 3-day and 7-day perfusion conditions, which was divided into static non-induced, static-induced and perfusion-induced groups. (3) Characterization of morphology and size, and biocompatibility of extracellular vesicles (EVs) of three osteoblast subtypes: Three different subtypes of osteoblasts were obtained [endothelial-type osteoblasts (EnOB)-EVs, stromal-type osteoblasts (StOB)-EVs and mineralizing-type osteoblasts (MinOB)-EVs]. Their morphology and size were obtained through transmission electron microscopy and particle size analysis. Growth medium containing EVs of three different cell subtypes was perfused, and cell proliferation/apoptosis assay was performed to compare the biocompatibility of the addition of different EVs concentrations (1, 1.25, 2.5, and 5 μg/ml) for 24 hours, which was categorized into the EnOB-EVs group, StOB-EVs group and MinOB-EVs group. (4) Osteogenic effect of EVs from three subtypes of osteoblasts: Osteogenic induction media containing EVs from three different osteoblast subtypes were perfused for 3 days, and ALP staining and PCR were performed to compare the number of black ALP-positive cells and the expression levels of osteogenesis-related marker genes including RUNX2, COL1A1, BMP-2, and OCN, which was divided into non-EVs group, EnOB-EVs group, StOB-EVs group and MinOB-EVs group.Results:(1) Evaluation of the microfluidic organ-on-a-chip: Simulation results showed that the concentration in the top layer of the upper chamber reached more than 95% of that in the lower chamber and that the concentration in the bottom layer was about 96.5% of that in the lower chamber after 12 hours of continuous perfusion, reaching an equilibrium state of the concentration difference between the upper and lower chambers. The results of live-dead staining showed that the chip was biocompatible at a flow rate of 0.5 ml/min, and the cell survival rate at 3 and 7 days of perfusion was (99.48±0.12)% and (97.07±1.05)% ( P<0.01). (2) ALP staining results showed that at 3 days, the perfusion-induced group showed the highest number of black ALP-positive cells, followed by the static-induced group, and the least in the static non-induced group. At 7 days, the static-induced group had the highest number of black ALP-positive cells, followed by the perfusion-induced group, and the least in the static non-induced group. PCR results indicated that at 3 days, the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.12, 1.00±0.01, and 1.00±0.02 respectively in the static non-induced group; 1.80±0.04, 4.05±0.37, 9.80±1.94, and 4.38±0.89 respectively in the static-induced group, and 2.45±0.23, 5.48±0.42, 91.50±4.56, and 10.82±4.96 respectively in the perfusion-induced group ( P<0.01). At 7 days, the expression levels of RUNX2 was 1.00±0.01 in the static non-induced group, 1.46±0.46 in the static-induced group, and 1.11±0.08 in the perfusion-induced group ( P>0.05); the expression levels of COL1A1, BMP-2, and OCN were 1.00±0.03, 1.00±0.13, and 1.00±0.09 respectively in the static non-induced group, 9.38±0.25, 14.27±4.35, and 84.01±4.02 respectviely in the static-induced group, and 2.39±0.08, 133.64±8.87, and 86.64±8.36 respectively in the perfusion-induced group ( P<0.01). When comparing the static non-induced, static-induced, and perfusion-induced groups at both 3 and 7 days, the perfusion-induced group demonstrated the strongest osteogenic capability. (3) Characterization of morphology and size and biocompatibility of EVs from three osteoblast subtypes: Under the transmission electron microscope, EVs from EnOB-EVs, StOB-EVs, and MinOB-EVs all exhibited a typical saucer-shaped morphology. The particle sizes of EnOB-EVs, StOB-EVs, and MinOB-EVs were (91.3±14.7)nm, (106.0±16.0)nm, and (68.1±10.7)nm, respectively. Cell proliferation/apoptosis assay results indicated that the optimal administration concentration of EnOB-EVs, StOB-EVs, and MinOB-EVs was all 1.25 μg/mL. (4) Validation of osteogenic effect of the microfluidic organ-on-a-chip on three types of EVs: ALP staining results showed that the non-EVs group had the fewest black ALP-positive cells, followed by the EnOB-EVs group, then the StOB-EVs group, and the MinOB-EVs group had the most. PCR results showed that the expression levels of RUNX2, COL1A1, BMP-2, and OCN were 1.00±0.01, 1.00±0.03, 1.00±0.02, and 1.00±0.02 respectively in the non-EVs group, 1.95±0.11, 6.78±2.04, 7.99±0.57, and 6.93±3.83 repectively in the EnOB-EVs group, 0.79±0.12, 5.68±1.53, 12.59±3.15, and 25.59±0.95 respectively in the StOB-EVs group, and 0.68±0.10, 4.36±0.69, 18.75±3.21, and 34.74±3.98 repectively in the MinOB-EVs group ( P<0.01). Compared with the non-EVs group, EnOB-EVs group, StOB-EVs group, and MinOB-EVs group, the MinOB-EVs group showed the most significant osteogenic effect. Conclusions:The microfluidic organ-on-a-chip constructed using microfluidic technology and cell co-culture techniques is capable of maintaining the normal growth of MC3T3-E1 cells, enhancing their proliferation and osteogenic induction differentiation. EVs released by osteoblasts at different stages possess osteogenic effects and can accelerate the bone sclerosis in the remodeling of subchondral bone during the progression of osteoarthritis.
6.Prevalence and risk factors of hyperuricemia among workers in an electronics factory in Wuhan
Jiajie SUN ; Chao XIA ; Yuqin SHI ; Pengli CAI ; Hao ZHANG ; Jinxin CHENG ; Ruixue ZHAO ; Ling ZHANG ; Wenjun YIN ; Jingrong LIU
Journal of Public Health and Preventive Medicine 2024;35(3):90-94
Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ2=46.077,P<0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m2 (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.
7.Predictors of a forgotten joint after medial open wedge high tibial osteotomy
Yiwei HUANG ; Bo PENG ; Chen ZHANG ; Hao GE ; Jiahao LI ; Yijin LI ; Jinlun CHEN ; Wenjun FENG ; Yirong ZENG
Chinese Journal of Tissue Engineering Research 2024;28(24):3903-3909
BACKGROUND:Medial open wedge high tibial osteotomy is an effective procedure for preserving the knee joint in patients with medial compartmental osteoarthritis.Previous studies have demonstrated that the forgotten joint score provides a lower ceiling effect and consistency of medial open wedge high tibial osteotomy outcomes compared to traditional assessment tools. OBJECTIVE:To identify predictive factors associated with the occurrence of a forgotten joint after medial open wedge high tibial osteotomy. METHODS:117 patients with medial open wedge high tibial osteotomy who were treated at First Affiliated Hospital of Guangzhou University of Chinese Medicine were selected,including 35 males and 82 females,with an average age of 61 years.They were followed up for at least 2 years.Patients were divided into a forgotten joint group(n=28)and a non-forgotten joint group(n=89)by evaluating whether they achieved forgotten joint after surgery.Univariate and multivariate logistic regression analyses were performed with preoperative patient characteristics and surgery-related factors as potential predictors. RESULTS AND CONCLUSION:(1)There were significant differences in the proximal medial tibial angle between the two groups before surgery(P<0.05).There were significant differences in the forgotten joint score,Knee Injury and Osteoarthritis Outcome Score,knee society knee score,function score,and patients joint perception between the two groups after surgery(P<0.05).There was a significant difference between the hip-knee-ankle angle and the medial proximal tibial angle after operation(P<0.05).(2)Univariate Logistic regression analysis showed that the medial proximal tibial angle had a significant influence on the forgotten joint before operation[OR=0.755,95%CI(0.635-0.897),P<0.001].There were significant effects on the forgotten joint of hip-knee-ankle angle and medial proximal tibial angle[OR=1.546,95%CI(1.242-1.924),P<0.001;OR=0.815,95%CI(0.713-0.931),P=0.003].(3)Multivariate logistic regression analysis showed that preoperative K-L grade 1 was a favorable factor for obtaining forgotten joints.Preoperative medial proximal tibial angle and postoperative hip-knee-ankle angle were independent predictors of forgetting joints,and they had a curvilinear relationship with the probability of achieving forgetting joints.When preoperative medial proximal tibial angle increased by 1°,the probability of achieving a forgotten joint decreased by 27.7%[OR=0.723,95%CI(0.593-0.882),P<0.001].Conversely,when postoperative hip-knee-ankle angle increased by 1°,the probability of achieving a forgotten joint increased by 46.4%[OR=1.464,95%CI(1.153-1.860),P=0.002].(4)The results showed that patients with preoperative knee osteoarthritis K-L grade 1,small medial proximal tibial angle(<85.5°),and large postoperative hip-knee-ankle angle(>176.0°)were predictors of forgotten joint.
8.Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve
Jun LI ; Chunsheng WANG ; Zheng ZUO ; Hao LAI ; Lili DONG ; Kai ZHU ; Junyu ZHAI ; Yongxin SUN ; Wenjun DING ; Tao HONG
Chinese Journal of Surgery 2024;62(11):1024-1031
Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.
9.Glycyrrhizic acid alleviates cisplatin-induced ototoxicity by inhibiting in-flammation of cochlear in C57BL/6J mice
Yuqian ZHANG ; Wenjun JIANG ; Hao LÜ ; Zixuan SHENG ; Ziyun HUANG ; Wenmin CHAI ; Jing XIAO ; Yang LI ; Li LI ; Xiansi ZENG
Chinese Journal of Pathophysiology 2024;40(2):291-300
AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P<0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P<0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P<0.01),which was improved by GL treatment(P<0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P<0.01),which was restored in CDDP+GL group(P<0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P<0.01),which was restored in CDDP+GL group(P<0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.
10.Therapeutic results of three-dimensional aortic valve anatomic repair for regurgitant bicuspid aortic valve
Jun LI ; Chunsheng WANG ; Zheng ZUO ; Hao LAI ; Lili DONG ; Kai ZHU ; Junyu ZHAI ; Yongxin SUN ; Wenjun DING ; Tao HONG
Chinese Journal of Surgery 2024;62(11):1024-1031
Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.


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