1.Study on the effect and mechanism of Xinyang Tablet on myocardial ferroptosis in mice with chronic heart failure
Jinhua KANG ; Pengpeng LIANG ; Xiaoxiong ZHOU ; Ao LIU ; Zhongqi YANG ; Hongyan WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):516-528
Objective:
Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure.
Methods:
Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue.
Results:
Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05).
Conclusion
Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.
2.Equivalence of SYN008 versus omalizumab in patients with refractory chronic spontaneous urticaria: A multicenter, randomized, double-blind, parallel-group, active-controlled phase III study.
Jingyi LI ; Yunsheng LIANG ; Wenli FENG ; Liehua DENG ; Hong FANG ; Chao JI ; Youkun LIN ; Furen ZHANG ; Rushan XIA ; Chunlei ZHANG ; Shuping GUO ; Mao LIN ; Yanling LI ; Shoumin ZHANG ; Xiaojing KANG ; Liuqing CHEN ; Zhiqiang SONG ; Xu YAO ; Chengxin LI ; Xiuping HAN ; Guoxiang GUO ; Qing GUO ; Xinsuo DUAN ; Jie LI ; Juan SU ; Shanshan LI ; Qing SUN ; Juan TAO ; Yangfeng DING ; Danqi DENG ; Fuqiu LI ; Haiyun SUO ; Shunquan WU ; Jingbo QIU ; Hongmei LUO ; Linfeng LI ; Ruoyu LI
Chinese Medical Journal 2025;138(16):2040-2042
3.Isopsoralen accelerates tibia fracture healing by promoting bone formation in mice
Xi WU ; Zhongqi WANG ; Yuhai GAO ; Zhenlong WEI ; Xin BAI ; Keming CHEN
Journal of Army Medical University 2024;46(3):240-248
Objective To determine the effect of isopsoralen(ISO)on the healing of tibia fracture in mice and explore its underlying mechanism.Methods Fifty male C57BL/6 mice(2 month old,20±2 g)were randomly divided into model group and ISO treatment group,with 25 animals in each group.From the 3rd day after modeling,the mice from the ISO group were given an intragastric gavage of 40 mg/kg ISO,once per day for 28 consecutive days,while those of the model group was given same volume of normal saline in same way.On the 7th,14th,21st,and 28th day after gavage,the tibia on the surgical side was taken,and the fracture area was quantified by bone volume/total volume(BV/TV)after micro-CT scanning.The healing and shaping of the fracture end were observed through HE staining.ELISA was used to detect the serum contents of bone alkaline phosphatase(BALP)and procollagen type I N-terminal peptide(PINP)on the 14th day of gavage.Western blotting was employed to determine the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX,and VEGF in the tibial callus tissue in 7 and 14 d after gavage.Vascular perfusion was applied to observe the callus microvessels in 28 d to quantitatively analyze the vascular volume fraction and vessel diameter.Immunohistochemical staining was conducted to observe the expression of VEGF in the callus in 14 d after gavage.Results HE staining displayed that the ISO group had faster healing process than the model group.Micro-CT quantification results showed that the ISO group had higher BV/TV ratio in 7 d after gavage though no statistical difference,significantly higher ratio in 14 d(P<0.05),but obviously lower ratio in 21 and 28 d after gavage(both P<0.05)when compared with the model group.The serum contents of BALP and PINP were also remarkably higher in the ISO group than the model group(P<0.05).Western blotting results indicated that the expression levels of Collagen Ⅰ,Runx2,BMP2,OSX and VEGF in the ISO group were higher than those in the model group(P<0.05).The results of angiography revealed that the vascular volume fraction and vessel diameter were notably increased in the ISO group than the model group(both P<0.05).Immunohistochemical assay showed that the expression of VEGF was higher in the ISO group than the model group(P<0.05).Conclusion ISO can improve the activity of osteoblasts,increase the expression of osteogenesis-related proteins,and accelerate the angiogenesis to promote fracture healing.
4.Currentstatus and effect of"communication with intractable high-risk patients"in a tertiary hospital in Guangzhou
Zhongqi LIU ; Cheng QIU ; Zhonghua ZENG ; Ting WU ; Hongzhong HUANG ; Qiusheng LIU ; Dayue LIU
Modern Hospital 2024;24(5):726-728,732
This paper aims to focus on and implement strategies for preventing and resolving medical complaints and dis-putes at their emergence.The hospital promptly compiled a summary of the main problems and concerns reported from patients o-ver the past few years.It combined medical practices with the characteristics of admitted patients with severe diseases,complex treatment plans,and high risks.Since 2020,this hospital has been actively engaging with intractable high-risk patients and de-veloped a scheme that engaging clinical departments,medical management,and dispute management departments together to con-duct preoperative/pre-treatment communication.With a focus on patient management,this hospital upholds the concept of the pa-tient-centered humanistic philosophy in the process of doctor-patient communication to enhance the quality of communication.Consequently,the hospital has benefited from the communication scheme,achieving satisfactory effect in ensuring a solid medical safety and reducing the incidence of medical disputes.
5.Chinese Herbal Medicine Feiyanning Prescription Regulates EMT to Reverse Cisplatin Resistance in Non-small Cell Lung Cancer
Jinli XIA ; Yuejiao CAI ; Xinhong WU ; Zhongqi WANG ; Haibin DENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):43-51
ObjectiveTo observe the effect of Feiyanning prescription (FYN) on cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) and explore the underlying mechanism. MethodCell counting kit-8 (CCK-8) assay was used to detect the proliferation of A549 and A549/DDP (DDP-resistant) cells treated by DDP (0, 2.0, 4.0, 6.0, 8.0, 10.0 mg⋅L-1) and the proliferation of A549/DDP cells treated by FYN (0, 100, 200, 300, 400, 500, 600 mg⋅L-1). Based on immunofluorescence staining and Western blot (WB), the expression of epithelial mesenchymal transition (EMT)-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group, FYN group (200 mg⋅L-1), DDP group (6.0 mg⋅L-1), and combination group [FYN (200 mg⋅L-1) + DDP (6.0 mg⋅L-1)] and respectively treated with corresponding drugs. Then, invasion ability of each group was examined by transwell assay, and the expression of EMT-related proteins in each group by WB. Moreover, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group, respectively. ResultCompared with A549 group, A549/DDP group showed high resistance to DDP (P<0.01), low expression of E-cadherin, and high protein expression of Vimentin, N-cadherin, and Snail (P<0.05, P<0.01). As compared with the control group, FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner (P<0.01), and the FYN group, DDP group, and combination group demonstrated low invasion ability (P<0.01). In addition, the invasion ability in the combination group was particularly lower than that in the DDP group (P<0.01). The expression of E-cadherin protein was higher and the protein expression of N-cadherin, Vimentin, and Snail was lower in the in FYN group than in the control group (P<0.01). The protein expression of E-cadherin, N-cadherin, and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group (P<0.05,P<0.01). The protein expression of E-cadherin, N-cadherin, Vimentin, and Snail in the combination group decreased as compared with that in the control group (P<0.01). Compared with the DDP alone, the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin, Vimentin, and Snail (P<0.01). The protein and mRNA expression of lung resistance-related protein (LRP) and multidrug resistance 1 (MDR1) was lower and the protein and mRNA expression of topoisomerase Ⅱα (TOPO Ⅱα) was higher in the FYN group than in the control group (P<0.01). The protein and mRNA expression of LRP, MDR1, and TOPO Ⅱα was higher in the DDP group than in the control group (P<0.01). The expression of LRP protein and mRNA showed no significant variation, but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group (P<0.01). Compared with the DDP group, FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα (P<0.01). Compared with FYN, the combination elevated the protein and mRNA expression of LRP, MDR1, and TOPO Ⅱα (P<0.01). ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.
6.Management and outcomes of gastric leak after sleeve gastrectomy: results from the 2010-2020 national registry.
Mengyi LI ; Na ZENG ; Yang LIU ; Xitai SUN ; Wah YANG ; Yanjun LIU ; Zhongqi MAO ; Qiyuan YAO ; Xiangwen ZHAO ; Hui LIANG ; Wenhui LOU ; Chiye MA ; Jinghai SONG ; Jianlin WU ; Wei YANG ; Pin ZHANG ; Liyong ZHU ; Peirong TIAN ; Peng ZHANG ; Zhongtao ZHANG
Chinese Medical Journal 2023;136(16):1967-1976
BACKGROUND:
Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.
METHODS:
To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks.
RESULTS:
A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor.
CONCLUSIONS
Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans
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Male
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Retrospective Studies
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Diabetes Mellitus, Type 2/complications*
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Obesity, Morbid
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Anastomotic Leak/epidemiology*
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Gastrectomy/methods*
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Reoperation/methods*
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Registries
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Laparoscopy/methods*
;
Treatment Outcome
7.Recent advancement in bariatric and metabolic surgery
Lee WEIJEI ; Xiaoguang QIN ; Tian ZHU ; Zhongqi MAO ; Xiaoqing ZHOU ; Erfan XIE ; Guoqiang WU ; Min ZHANG
Chinese Journal of Digestive Surgery 2023;22(8):958-964
Bariatric surgery is the most effective treatment for patients with severe obesity, which can significantly improve the metabolic disorders, especially type 2 diabetes mellitus. Bariatric and metabolic surgery is the latest and fastest-growing branch of surgery, with the types of procedure and other novel treatment modalities are still evolving and in progress. The authors summarize the recent advancement related to novel bariatric and metabolic surgery in the treat-ment of morbid obesity and type 2 diabetes mellitus in recent years through literature search, which can be divided into the following three parts: (1) novel surgical procedures and new guideline of indication. Sleeve gastrectomy and Roux-en-Y gastric bypass are the most performed bariatric surgery. Duodenal switch or the variant of one anastomosis duodenal ileostomy are also accredited procedures but been less performed. One anastomosis gastric bypass is the most recently accredited bariatric surgical procedures with better safety profile and weight loss efficacy than most of the procedures. For other novel procedures, bipartition procedure may be the next accredited proce-dure. A new worldwide guideline is recently launched and the indication for bariatric surgery is lowered BMI 27.5 kg/m 2 for Asian. (2) The effect and mechanism of bariatric surgery. Bariatric surgery can significantly reduce the incidence of cardiovascular disease and mortality in obese patients. The main beneficiary group is patients with diabetes mellitus. Along with the recent basic research and the success of new gut hormone related drugs, the mechanism of bariatric surgery can be mostly attributed to gut hormonal effect, however, gastric volume still play an important role. (3) Novel obesity treatment modalities. Endoscopic obesity treatment has a major progress in the success of endoscopic gastroplasty by endoscopic suturing designs. More noteworthy is the development of new intestinal hormone drug therapy, which can achieve a weight loss of 14% in one year by injec-ting once a week glucagon-like peptide-1 preparation, and then combining two or three intestinal hormone drugs can achieve a weight loss of 24% in one year, which is close to the effectiveness of bariatric surgery. Pharmacologic treatment of obesity is very promising and expected. With the increasing severity of obesity and diabetes mellitus in the world, in addition to the explosive develo-pment of bariatric and metabolic surgery in recent years, many new surgical methods and new treatments, especially new and effective intestinal hormone related therapeutic drugs, have been developed. The success of bariatric and metabolic surgery depends on a multidisciplinary team with rich clinical experience: precise preoperative planning and comprehensive postoperative manage-ment, as well as patient understanding and cooperation, in order to achieve the best results.
8.Manual reduction under general anesthesia and anterior cervical discectomy and fusion for treatment of cervical locked facet dislocation
Zhongqi LI ; Miao LI ; Yong CAO ; Chunyue DUAN ; Jianhuang WU ; Jianzhong HU ; Tianding WU
Chinese Journal of Orthopaedic Trauma 2022;24(7):577-582
Objective:To investigate the clinical efficacy of manual reduction under general anesthesia combined with anterior cervical discectomy and fusion (ACDF) in the treatment of lower cervical locked facet dislocation.Methods:Retrospectively analyzed were the data of 53 patients with traumatic single segment dislocation of lower cervical spine combined with single/bilateral facet articular lock who had been admitted to Department of Orthopaedic Spine Surgery, Xiangya Hospital, Central South University from January 2019 to December 2020. There were 36 males and 17 females, aged from 18 to 64 years (average, 45.5 years). All the patients were treated with ACDF under neuroelectrophysiological monitoring. Clinical efficacy was assessed by observing complications and comparing American Spinal Injury Association (ASIA) grading, Modified Japanese Orthopaedic Association (mJOA) scores, neck disability index (NDI) and visual analogue scale (VAS) before and after surgery.Results:All patients were followed up for 16 to 30 months (mean, 24 months). All incisions healed by primary intention with no infection after operation. There were 2 cases of delirium, 9 cases of abdominal distension, 4 cases of lower extremity venous thrombosis, and one case of central diabetes insipidus. Postoperative imaging data showed that all patients achieved sequential reduction of the cervical spine, intervertebral bony fusion, and no internal fixation loosening. The last follow-up showed that the overall improvement rate of ASIA grading of spinal cord function was 84.9% (45/53) compared with the preoperation and that the VAS score (2.0±0.5), mJOA score (13.1±3.1) and NDI index (16.6±5.9) were significantly improved compared with the preoperative values (7.5±1.5, 6.9±3.5, and 37.8±7.8) ( P< 0.05). Conclusion:On the premise of fully assessing the patient's injury status, manual reduction under general anesthesia combined with ACDF is a safe and effective treatment of single-level lower cervical fracture combined with facet dislocation.
9.Effects of a simulated plateau environment on fracture healing in rats
Xin BAI ; Xuefeng HOU ; Xi WU ; Zhongqi WANG ; Gaoqian XIE ; Yuhai GAO ; Keming CHEN
Chinese Journal of Orthopaedic Trauma 2022;24(8):700-708
Objective:To study the effects of a simulated plateau environment on fracture healing in rats.Methods:A rat model of mid-femoral fracture was established by hacksaw truncation and intramedullary fixation with Kirschner wires in 60 male Wistar rats which were divide into 2 groups ( n=30) by the random number table method. The rats in the control group were raised in the animal experiment center of The 940 Hospital of Joint Logistic Support Force of Chinese PLA at an altitude of 1,400 m, while the rats in the plateau group were placed in an animal experimental cabin in a simulated plateau environment at a simulated altitude of 5,000 m. The body weight was weighed once a week and X-ray films were taken every 2 weeks. Blood samples were collected after 4 weeks for detection of biochemical indicators of bone metabolism. After 8 weeks, the femurs of the surgical side were taken for bone biomechanical detection and the bone mineral density of the healthy side was detected. After 4 and 8 weeks, the femurs of the surgical side were taken for in vitro Micro-CT scanning and angiography detection. After 1, 2, 4 and 8 weeks, the femurs of the surgical side were taken for bone histopathologic detection. Results:During the entire experiment, no rats in the control group died while the mortality rate of the rats in the plateau group was as high as 26.7% (8/30). In the plateau group, some organs were pathologically damaged in the rats, fracture union was delayed, and the callus differentiated and matured slowly with the chondrocytes still dominant at the 8th week. The bone mineral density and the maximum load of the femur in the plateau group were significantly lower than those in the control group ( P< 0.05). Angiography showed that the rats in the plateau group had microvascular proliferation which did not penetrate the fracture end at the 8th week. The bone formation indexes like osteocalcin, procollagen type Ⅰ N-terminal propeptide (PⅠNP), and osteoprotegerin of the rats in the plateau group were significantly lower than those in the control group at the 4th week ( P<0.05). The bone resorption indexes like tartrate resistant acid phosphatase 5b (TRACP-5b) and receptor activator for nuclear factor-κB ligand (RANKL) in the plateau group were significantly higher than those in the control group ( P<0.05). Conclusion:A simulated plateau environment at an altitude of 5,000 m may lead to delayed fracture healing in rats.
10.One anastomosis gastric bypass: recent global advancement
Lee WEIJEI ; Xiaoguang QIN ; Zhongqi MAO ; Xiaoqing ZHOU ; Erfan XIE ; Guoqiang WU ; Min ZHANG
Chinese Journal of Digestive Surgery 2022;21(11):1403-1408
Bariatric surgery is effective on obesity, which can significantly improve the metabolic diseases of obesity patients, especially the type 2 diabetes. However, the surgical proce-dures of bariatric and metabolic surgery are still evolving and in progress. One anastomosis gastric bypass (OAGB) is the latest bariatric surgery recognized by the international bariatric and metabolic surgery community. The authors review the relevant literatures at home and abroad, and introduce the development history, surgical skills, clinical efficacy, status quo and adaptability of OAGB.


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