1.Effect of Yiqi Yangyin Jiedu Huayu prescription on intestinal metabolites in liver cirrhosis with minimal hepatic encephalopathy: A study based on metabolomics
Tingting JIANG ; Qun ZHANG ; Xianbo WANG ; Yuyong JIANG ; Xiaoli LIU ; Hao YU ; Zhiyun YANG
Journal of Clinical Hepatology 2025;41(3):469-477
ObjectiveTo investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on minimal hepatic encephalopathy in liver cirrhosis based on intestinal metabolomics. MethodsA total of 11 patients with liver cirrhosis who were hospitalized in Beijing Ditan Hospital, Capital Medical University, from March to May 2024, and were diagnosed with MHE based on psychometric hepatic encephalopathy score were enrolled as subjects, and 11 healthy family members of the patients were enrolled as control group. Fecal samples were collected for metabolomics analysis from the control group and the patients with MHE before and after treatment with Yiqi Yangyin Jiedu Huayu prescription, and a population cohort study was conducted to investigate the effect of Yiqi Yangyin Jiedu Huayu prescription on intestinal metabolism of patients with MHE. The Fisher’s exact test was used for categorical data between two groups; the independent samples t-test was used for comparison of normally distributed continuous data between two groups, the paired t-test was used for comparision before and after treatment within the same group, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsA total of 29 differentially expressed metabolites were detected between the MHE group and the control group, mainly amino acids, organic acids, organic amines, carbohydrates, fatty acids, and vitamins, and there were 12 upregulated metabolites and 17 downregulated metabolites in the MHE group, which were mainly enriched in the metabolic pathways of ornithine, branched-chain amino acid, and aromatic amino acid. After the treatment with Yiqi Yangyin Jiedu Huayu prescription, 80 differentially expressed metabolites were detected in the patients with MHE, mainly carbohydrates, organic acids, and amino acids, and there were 56 upregulated metabolites and 24 downregulated metabolites, which were mainly enriched in the metabolic pathways of ornithine, branched-chain amino acid, and aromatic amino acid. ConclusionYiqi Yangyin Jiedu Huayu prescription can exert a therapeutic effect on patients with MHE by regulating intestinal metabolism.
2.Research progress on animal models of combined radiation-wound injury
Ruolin HAO ; Guifang DOU ; Zhiyun MENG ; Tong YE ; Nanxi LI ; Xiaoxia ZHU ; Ruolan GU ; Zhuona WU ; Hui GAN
Chinese Journal of Radiological Health 2024;33(2):209-214
A combined radiation-wound injury refers to a radiation injury combined with a traumatic wound, with the characteristics of repeated ulceration and a long and difficult healing process, which is a focus in the field of research on difficult-to-heal wounds. To research combined radiation-wound injuries, the establishment of animal models is a key part, and appropriate animal models are a guarantee of reliable experimental results. This review summarizes the current research progress on various animal models of combined radiation-wound injuries in terms of radiation types, animal species, and injury types and location, aiming to provide a scientific basis for establishing standardized animal models, studying injury mechanisms, and evaluating prevention and treatment efficacy for combined radiation-wound injuries.
3.Construction of luminescent bacteriophage using CRISPR technology and its application in Escherichia coli indentification
Minwei LI ; Jing YAN ; Hangyi LI ; Zhiyun HAO ; Zhong NI ; Zhaoyang HU ; Xiaorong WANG ; Menghan XU ; Chi WANG ; Ruibing LI ; Chengbin WANG
Chinese Journal of Laboratory Medicine 2024;47(4):437-443
Objective:To construct a recombinant bioluminescent bacteriophage (HT7) targeting Escherichia coli, and evaluate its ability to identify Escherichia coli. Methods:Initially, pCRISPR-sg (1-10) and PFN-1000 plasmid strains were constructed by genetic engineering, and the most efficient small guild RNA (sgRNA) were screened by bilayer plate. By the gene editing technique, which comprised homologous recombination and clustered regularly interspaced short palin dromic repeats (CRISPR)-Cas system, the Nanoluc luciferase gene was integrated into the downstream non-coding region of 10A gene of T7 phage, to constructe the bioluminescent phage HT7 successfully. The difference of biological characteristics between HT7 phage and T7 phage was evaluated by plaque assay and liquid amplification assay. In addition, 51 strains of Escherichia coli, 20 strains of Klebsiella pneumoniae, 14 strains of Staphylococcus aureus, 6 strains of Enterococcus faecium, 5 strains of Enterococcus faecalis, 3 strains of Acinetobacter baumannii and 1 strain of Pseudomonas aeruginosa were collected and isolated to evaluate the limit of detection and specificity of HT7 phage. Results:Among the 10 CRISPR-targeted cleavage systems constructed, sgRNA8 exhibited the highest cleavage efficiency, with a cleavage rate of 0.18. After three rounds of recombination screening using the pCas9/pCRISPR/PFN-1000 triple-plasmid system, PCR validation yielded recombinant phage bands at 2 798 bp, indicating the successful construction of the HT7 phage. The recombinant phage showed significant differences in biological characteristics in terms of lysis efficiency ( P<0.001), one-step growth curve ( P=0.001), and infection multiplicity ( P=0.031). Both lysis burst time and log growth node were extended by 10 min, with the optimal infection multiplicity being 0.1. Clinical sample testing identified lysis of 6 strains of Escherichia coli within 4.5 h, while other strains remained unaffected, with detection of pathogenic bacteria below 10 CFU/ml. Conclusions:The developed pCas9/pCRISPR/PFN-1000 triple-plasmid editing system efficiently edits the bacteriophage genome. The constructed HT7 fluorescent bacteriophage enables the detection of Escherichia coli below 10 CFU/ml within 4.5 hours, demonstrating low detection limits and high detection specificity.
4.Risk factors for gastrointestinal bleeding after type A aortic dissection surgery: A retrospective cohort study
Hao CHENG ; Bailing LI ; Yangfeng TANG ; Lin HAN ; Zhiyun XU ; Wei ZHOU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):531-537
Objective To investigate the risk factors for postoperative gastrointestinal bleeding (GIB) in patients with type A aortic dissection, and further discuss its prevention and treatment. Methods The clinical data of patients with type A aortic dissection admitted to the Department of Cardiovascular Surgery of the First Affiliated Hospital of Naval Medical University from 2017 to 2021 were retrospectively analyzed. Patients were divided into a GIB group and a non-GIB group based on the presence of GIB after surgery. The variables with statistical differences between two groups in univariate analysis were included into a multivariate logistic regression model to analyze the risk factors for postoperative GIB in patients with type A aortic dissection. Results There were 18 patients in the GIB group including 12 males and 6 females, aged 60.11±10.63 years, while 511 patients in the non-GIB group including 384 males and 127 females, aged 49.81±12.88 years. In the univariate analysis, there were statistical differences in age, preoperative percutaneous arterial oxygen saturation (SpO2)<95%, intraoperative circulatory arrest time, postoperative low cardiac output syndrome, ventilator withdrawal time>72 hours, postoperative FiO2≥50%, continuous renal replacement therapy (CRRT) rate, extracorporeal membrane oxygenation (ECMO) rate, infection rate, length of hospital stay and ICU stay, and in-hospital mortality (all P<0.05). In the multivariate logistic regression analysis, preoperative SpO2<95% (OR=10.845, 95%CI 2.038-57.703), ventilator withdrawal time>72 hours (OR=0.004, 95%CI 0.001-0.016), CRRT (OR=6.822, 95%CI 1.778-26.171) were risk factors for postoperative GIB in patients (P≤0.005). In the intra-group analysis of GIB, non-occlusive mesenteric ischemia (NOMI) accounted for 38.9% (7/18) and was the main disease type for postoperative GIB in patients with type A aortic dissection. Conclusion In addition to patients with entrapment involving the superior mesenteric artery who are prone to postoperative GIB, preoperative SpO2<95%, ventilator withdrawal time>72 hours, and CRRT are independent risk factors for postoperative GIB in patients with type A aortic dissection. NOMI is a major disease category for GIB, and timely diagnosis and aggressive treatment are effective ways to reduce mortality. Awareness of its risk factors and treatment are also ways to reduce its incidence.
5.UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer.
Shuye LIN ; Hanli XU ; Lin QIN ; Mengdi PANG ; Ziyu WANG ; Meng GU ; Lishu ZHANG ; Cong ZHAO ; Xuefeng HAO ; Zhiyun ZHANG ; Weimin DING ; Jianke REN ; Jiaqiang HUANG
Acta Pharmaceutica Sinica B 2023;13(5):2086-2106
As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.
6.Experimental observation on a new chimney shaped mechanical valve completely implanted above mitral annulus in animals
Hao TANG ; Yongchao YU ; Xufeng WEI ; Guokun WANG ; Dejun GONG ; Zhiyun XU
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(11):673-678
Objective:To fundamentally solve the problems of valve dysfunction caused by limited size of artificial valve, high requirements for implantation technology, destruction of subvalvular structure and proliferation of fibrous endothelial tissue. We have developed a prosthetic valve with zero left ventricular occupancy. The valve frame is appropriately higher than the existing products, slightly chimney shaped, fully accommodates the movement of the valve leaves in the valve frame, and completely supraannular surgical implantation. This study uses this valve for preclinical animal test.Methods:Seven sheep underwent the replacement of the artificial valve under the direct vision of cardiopulmonary bypass. Warfarin was used for anticoagulation for 6 months 24 hours after operation. The blood biochemistry, anticoagulation and cardiac color Doppler ultrasound were detected after operation. The sheep were killed 180 days later for autopsy to observe whether the artificial valve caused thromboembolism. The efficacy and safety of valve were observed.Results:Two of the seven sheep died within 24 hours after operation, and five survived for a long time. Later, they were killed at 180 days. The mechanical properties of the artificial valve were good, and there was no thromboembolism around the artificial valve and important organs. The tissue layer of suture ring has been completely organized and endothelial cells, and the thickness of tissue layer is about 0.6-1.0 mm. The mitral valve of experimental animals can be opened and closed freely, with smooth surface and no abnormal echo. The follow-up of color Doppler ultrasound showed that the left ventricular ejection fraction was normal (0.60-0.70) before and 6 months after operation. The results of cross valve pressure difference and blood flow velocity of artificial valve were good (vmean was far lower than 5 mmHg(1 mmHg=0.133 kPa) and pmean was lower than 1 m/s) , suggesting that the hemodynamic performance of artificial valve was good. Left ventricular retrograde angiography showed that the artificial valve was completely located in the left atrium with good position and normal opening and closing. There was no obvious perivalvular leakage and other abnormalities. Within 7 days of blood test, the indexes of surgical stress were more abnormal than those before operation. At 12 and 24 weeks, there were no obvious abnormalities in blood routine test, liver and kidney function and other blood test indexes of animals in each group.Conclusion:The new chimney shaped mechanical valve implanted completely above the mitral annulus has good wear resistance, histocompatibility, antithrombotic and hemodynamic performance.
7.Clinical analysis of redo aortic root replacement after cardiac surgery
Jie LU ; Qing XUE ; Yangfeng TANG ; Zhigang SONG ; Hao TANG ; Fanglin LU ; Lin HAN ; Zhiyun XU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(01):99-103
Objective To analyze the etiologies, operation techniques and outcomes of redo aortic root replacement after cardiac surgery. Methods Between December 2013 and December 2019, 30 patients who had at least one previous cardiac operation received aortic root replacement in our hospital, including 20 males and 10 females with an average age of 50.4±12.7 years. The mean time interval between this operation and the previous one was 8.0±8.5 years. The principal indication for surgery was aortic sinus dilatation and ascending aortic aneurysm in 14 patients (47%), acute aortic dissection in 5 patients (17%), pseudoaneurysm in 3 patients (10%), prosthetic valve endocarditis in 4 patients (13%), prosthetic leakage in 4 patients (13%). Bentall procedure was used in all 30 patients, with concomitant mitral valve plasticity or replacement in 5 patients, tricuspid valve plasticity in 6 patients, coronary artery bypass grafting in 3 patients, and total aortic arch replacement and elephant trunk procedure in 2 patients. Results The mean cardiopulmonary bypass time was 96-296 (161.3±43.0) min, and the mean aortic occlusion time was 48-117 (85.7±20.4) min. There were 5 in-hospital deaths with an overall in-hospital mortality of 17%. The causes of deaths were low cardiac output syndrome in 2 patients and septic shock in 3 patients. The follow-up time was 3-75 (33.5±21.1) months. Three patients died during the follow-up, 1 patient died of septic shock and 2 died of cerebral hemorrhage. Conclusion Redo aortic root replacement is difficult to deal with, and the risk is high. Preoperative evaluation is required, appropriate surgical approach, adequate myocardial protection, and a complete surgical plan are essential to ensure the success of the operation.
8.Research progress on the nursing and health management model for patients with non-alcoholic fatty liver disease
Meilian XIE ; Zhiyun ZHANG ; Haixia ZHANG ; Jing WEN ; Ying HAO
Chinese Journal of Modern Nursing 2020;26(26):3576-3581
In recent years, with the improvement of living standards, lifestyle changes, and the advancement of medical examination methods, the detection rate of non-alcoholic fatty liver disease (NAFLD) has increased year by year, and it has become one of the important chronic liver diseases that seriously threaten human health worldwide. By far, there has been no ideal and effective treatment for NAFLD. Successful lifestyle intervention is unanimously recognized by experts at home and abroad as the most effective way to change the outcome of the disease. Although many scholars at home and abroad have explored different aspects of diet and exercise for patients with NAFLD in the past two decades, there are still no effective strategies or programs that can be used for reference. Therefore, this study organizes and summarizes relevant articles in recent years, and aims to provide a reference and basis for the future prevention and control of fatty liver and health management in China.
9.Phosphorylcholine coating enhances biocompatibility of expanded polytetrafluoroethylene used in polymeric prosthetic heart valves
Ben ZHANG ; Dejun GONG ; Xiwu ZHANG ; Tongyi XU ; Lin HAN ; Hao TANG ; Fanglin LU ; Zhiyun XU
Chinese Journal of Tissue Engineering Research 2014;(34):5509-5514
BACKGROUND:Our preliminary study found that the monocusp valves made of ultramicropore expanded
polytetrafluoroethylene (ePTFE) revealed no significant thrombus, calcification, or degradation 20 weeks after implanted into the descending aorta and the left pulmonary artery in sheep, which verified the good property of ePTFE. However, the surface of ePTFE in the left pulmonary artery was covered with obvious neointima.
OBJECTIVE: To assess the biocompatibility of phosphorylcholine-coated ePTFE.
METHODS:ePTFE surface was modified by phosphorylcholine derivative. Then the changes of surface shape, tensile stress at yield and elasticity modulus, water contact angle, and protein absorption capacity of ePTFE after surface modification were observed. (1) Hemolytic test: the leaching solution of phosphorylcholine-coated ePTFE, leaching solution of uncoated ePTFE, normal saline, and distiled water were added to the diluted human blood, respectively. (2) Platelet count test: the phosphorylcholine-coated ePTFE, uncoated ePTFE, high density
polyethylene, and Zymosan A were added to the whole blood samples from healthy volunteers, respectively.
(3) Platelet activation test: the phosphorylcholine-coated ePTFE, uncoated ePTFE, γ-Globulins, and Zymosan A
were added to the whole blood samples from healthy volunteers, respectively.
RESULTS AND CONCLUSION: The mean micropore diameter of ePTFE was significantly decreased after
phosphorylcholine coating (P < 0.001). The hydrophilicity and the ability of suppressing protein adsorption were
significantly strengthened after phosphorylcholine coating (P < 0.001). Phosphorylcholine coating did not influence
ePTFE in biomechanical properties and hemolytic test. The platelet count test and platelet activation test demonstrated that phosphorylcholine coating significantly improved anti-thrombus function of ePTFE. So, phosphorylcholine coating can enhance anti-thrombus function, suppress protein adsorption, and improve biocompatibility of ePTFE.
10.Clinical effects of levodopa benserazide combine with dl-3-butylphthalide capsules on limbs function of patients after stroke
Yuqiang MA ; Fengxue WANG ; Yucui GAO ; Zhiyun TONG ; Jianxin ZHANG ; Like HAO
Clinical Medicine of China 2014;(7):683-685
Objective To investigate the effects of levodopa benserazide hydrochloride combine with dl-3-butyl phthalide capsule on patient's limbs function after stroke. Methods Ninety patients with stroke were randomly divided into rehabilitation group,treatment group and control group,and 30 cases for each group. Patients in rehabilitation group were treated with exercise therapy,in treatment group were given exercise therapy and levodopa Benserazide and Dl-3-butylphthalide capsules,and in control group were given placebo treatment. Adult hemiplegic motor function score(FMA)and motor function assessment scale(MAS)were used to assess the motor function and lower extremity function before treatment and 8 weeks after treatment. Results Before treatment,FMA and MAS in rehabilitation group,treatment group and control group were(22. 6 ± 3. 6), (23. 1 ± 2. 5)and(20. 3 ± 2. 9),and(1. 6 ± 0. 6),(2. 1 ± 0. 5),(1. 7 ± 0. 9),respectively. There was no significant differences between the two groups( F = 1. 64,P > 0. 05;F = 1. 66,P > 0. 05). After 8 weeks of treatment,FMA and MAS in rehabilitation group and treatment group were(60. 6 ± 3. 5),(14. 6 ± 1. 1),and (75. 7 ± 4. 5),(17. 7 ± 4. 5),significant improved more than that before treatment(t = 1. 738,1,716,1. 732 respectively;P < 0. 05). Meanwhile,patients in the treatment group improved more than that in rehabilitation group(P < 0. 05),and they were superior to patients in control group((31. 0 ± 3. 6),(5. 5 ± 1. 1);P < 0. 05). Conclusion Benserazide combined with dl-3- butyl phthalide capsule can further improve the limbs function.

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