1.Analysis of Kidney Differential Metabolites and Hypoxia Adaptation Mechanism of Plateau Pikas Based on UHPLC-QE-MS
Yuxin HE ; Zhenzhong BAI ; Hua XUE ; Zixu GUO ; Xuefeng CAO
Laboratory Animal and Comparative Medicine 2025;45(1):3-12
Objective To explore the potential mechanisms of hypoxic adaptive metabolic changes in the kidneys of plateau pikas at different altitudes using non-targeted metabolomics analysis via ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbital trap-mass spectrometry (UHPLC-QE-MS). Methods 10 plateau pikas were captured at an altitude of 4 360 m in Xingxiuhai area, Maduo County, Guoluo Tibetan Autonomous Prefecture, Qinghai Province (MD group), and 10 plateau pikas were captured at an altitude of 2 900 m in Menyuan area, Haibei Tibetan Autonomous Prefecture, Qinghai Province (MY group). After anesthesia, serum samples were collected, and kidney samples were collected after euthanasia. General physiological and biochemical indicators were measured and metabolomics analysis was performed. Part of the serum samples was used for hematology analysis, another part for blood gas analysis, and the remaining part for biochemical indicator detection. Metabolites were extracted from the kidney tissue samples and then analyzed using UHPLC-QE-MS. Differential metabolites were analyzed using metabolomics principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), with screening criteria set as variable importance in projection (VIP)>1.5 and fold change (FC)>1.5, or VIP>1.5 and FC<1/1.5. Correlation analysis heatmaps, significance analysis volcano plots, signaling pathway recognition bubble charts, and rectangular graphs were used for the analysis of differential metabolites and related signaling pathways. Results The red blood cell count, glucose, urea nitrogen, uric acid, and homocysteine levels in the MD group plateau pikas were higher than those in the MY group, while hemoglobin, hematocrit, creatinine, and carbon dioxide combining power were lower than those in the MY group. This indicated a significant difference in the blood oxygen-carrying capacity of plateau pikas at different altitudes. The principal component pattern recognition analyses, and OPLS-DA permutation test showed that the kidney metabolites of the MD and MY groups of plateau pikas had distinct clustering distributions (R²Y=0.930, Q²=0.655). According to the screening criteria and database comparison, 46 differential metabolites were identified in the kidneys of plateau pikas at different altitudes. In the MD group of plateau pikas, the expression levels of bufadienolide, adenosine, adenine, diosgenin, berberine chloride, carnosol, and astaxanthin were significantly increased (VIP>1.5, P<0.05), while the levels of arachidonic acid, histamine, and coumarin were significantly decreased (VIP>1.5, P<0.05). The analysis of related signaling pathways showed that the biosynthetic pathways of valine, leucine, and isoleucine had the largest impact factors (P<0.05), while the biosynthetic pathways of pantothenate and coenzyme A showed the most significant enrichment (P<0.05). Conclusion The differential metabolites of amino acids, pantothenate, and coenzyme A pathways in the kidneys of plateau pikas at different altitudes may be involved in the metabolic mechanisms of plateau pikas' hypoxia adaptation in high-altitude environments.
2.A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.
Jianbing WU ; Duorui JI ; Weijie JIAO ; Jian JIA ; Jiayi ZHU ; Taijun HANG ; Xijing CHEN ; Yang DING ; Yuwen XU ; Xinglong CHANG ; Liang LI ; Qiu LIU ; Yumei CAO ; Yan ZHONG ; Xia SUN ; Qingming GUO ; Tuanjie WANG ; Zhenzhong WANG ; Ya LING ; Wei XIAO ; Zhangjian HUANG ; Yihua ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
3.Perioperative outcomes of single-lumen versus double-lumen endotracheal tubes in totally thoracoscopic cardiac surgery: A retrospective cohort study
Zhenzhong WANG ; Shuo XIAO ; Dou FANG ; Yuxin LI ; Jinfeng WEI ; Yingxian YE ; Jianjun ZHANG ; Xiaogang GUO ; Qingshi ZENG ; Huanlei HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(11):1606-1612
Objective To investigate the relationship between two-lung ventilation (TLV) with single-lumen endotracheal tube (SLT), one-lung ventilation (OLV) with double-lumen endotracheal tube (DLT) and postoperative pulmonary complications (PPCs) after total thoracoscopic cardiac surgery. Methods The clinical data of patients who underwent totally thoracoscopic cardiac surgeries in the Guangdong Provincial People’s Hospital from October 2019 to October 2021 were retrospectively analyzed. The patients were divided into 2 group according to the type of endotracheal tube, including a SLT group and a DLT group. Baseline data, surgical variables and PPCs were compared. The influencing factors of PPCs in the two groups were analyzed by binary logistic regression analysis. Results Finally 349 patients were enrolled, including 180 males and 169 females with an average age of (50.0±14.8) years. There were 219 patients in the SLT group and 130 patients in the DLT group. There was no statistical difference in baseline data, surgical variables or PPCs between the two groups (P>0.05). Binary logistic regression analysis showed that PPCs were related to body mass index in the SLT group (OR=0.778, 95%CI 0.637 to 0.951, P=0.014) and preoperative smoking history in the DLT group (OR=0.058, 95%CI 0.004 to 0.903, P=0.042). Conclusion For the patients who undergo totally thoracoscopic cardiac surgery, TLV with SLT and OLV with DLT show no significant association with PPCs. At the same time, PPCs are associated with body mass index in the SLT group, while associated with preoperative smoking history in the DLT group.
4.Innovation and Practice of Chinese Medicinal Materials Resource Chemistry Leading the Whole Industry Chain Recycling and Green Development of Chinese Medicinal Materials
Jin'ao DUAN ; Sheng GUO ; Shulan SU ; Lanping GUO ; Ming ZHAO ; Rui LIU ; Hui YAN ; Tuanjie WANG ; Zhenzhong WANG ; Wei XIAO ; Luqi HUANG
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(10):1114-1122
The concept,connotation and extension,goals and tasks of the discipline of Chinese medicinal materials resource chem-istry have been proposed and developed for 20 years.Looking back at the 20-year construction and development process,continuous exploration and innovative practice have been carried out around the scientific production and effective utilization of traditional Chinese medicinal materials.The theoretical connotation has been further enriched,the research mode has been further improved,and the tech-nical system has been further expanded.A series of research results have been formed and promoted for application,serving the high-quality development of the traditional Chinese medicinal materials industry,and contributing to the improvement of quality,efficiency,and green development of the entire industry chain of Chinese medicinal resources.However,with the rapid growth of Chinese medici-nal materials industry and the continuous expansion and extension of the industry chain,the waste and by-products generated in the production process of Chinese medicinal agriculture and industry are increasing day by day,causing resource waste and environmental pollution,which has become a new major problem facing the development of the industry.This article focuses on the establishment and case analysis of a model for the full industry chain recycling and low-carbon green development of Chinese medicinal materials,as well as the creation of an ecological industry demonstration park for the recycling of Chinese medicinal materials.It showcases the phased a-chievements made in recent years,aiming to provide demonstration and reference for the low-carbon and green transformation of the Chinese medicinal materials industry from a linear economy model to a circular economy model.It provides reference for improving the efficiency of Chinese medicinal materials utilization and creating new quality productivity,and helps promote low-carbon and green de-velopment in the field of Chinese medicinal materials industry.
5.Qualitative study on sustainability of intervention measures in the Shandong Provincial Department′s Joint Salt Reduction Project
Jingsong YANG ; Jing DONG ; Zhenzhong WANG ; Jia LI ; Xiaolei GUO ; Yihao ZHAO ; Xuejun YIN ; Ruitai SHAO
Chinese Journal of Preventive Medicine 2024;58(11):1697-1704
Objective:To employ qualitative research methods to evaluate the sustainability of the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) interventions and their influencing factors.Method:In September 2023, interviewees meeting the inclusion criteria were recruited through purposive sampling in Jinan, Shandong Province. A semi-structured interview guide was designed based on the CFIR and RE-AIM frameworks. Personal in-depth interviews and focus group discussions were conducted to gather insights on the feasibility, effectiveness, and sustainability of the project interventions from various stakeholders, including representatives from the government, food manufacturers, restaurants, academia, and residents.Results:A total of 15 individuals participated in in-depth interviews, involving six representatives from food manufacturers, four from restaurants, three from the government, and two from academia. There were four focus group discussions with 30 residents. The study found that at the individual resident level, health awareness and the availability of sodium reduction tools in the market could affect their salt reduction practices. For food manufacturers and restaurants, consumers′ preferences, technical challenges in reformulation, and government support were key factors determining the smooth progress of their salt reduction efforts. At the governmental level, multi-sectional coordination, chronic disease management demonstration areas, and the impact of the pandemic were the main factors influencing the implementation of sodium reduction interventions.Conclusion:Future endeavours should strengthen long-term management and optimise the complex influencing factors associated with intervention measures. This will be essential in sustaining and expanding the positive health outcomes achieved through the Shandong population sodium reduction strategy.
6.Qualitative study on sustainability of intervention measures in the Shandong Provincial Department′s Joint Salt Reduction Project
Jingsong YANG ; Jing DONG ; Zhenzhong WANG ; Jia LI ; Xiaolei GUO ; Yihao ZHAO ; Xuejun YIN ; Ruitai SHAO
Chinese Journal of Preventive Medicine 2024;58(11):1697-1704
Objective:To employ qualitative research methods to evaluate the sustainability of the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) interventions and their influencing factors.Method:In September 2023, interviewees meeting the inclusion criteria were recruited through purposive sampling in Jinan, Shandong Province. A semi-structured interview guide was designed based on the CFIR and RE-AIM frameworks. Personal in-depth interviews and focus group discussions were conducted to gather insights on the feasibility, effectiveness, and sustainability of the project interventions from various stakeholders, including representatives from the government, food manufacturers, restaurants, academia, and residents.Results:A total of 15 individuals participated in in-depth interviews, involving six representatives from food manufacturers, four from restaurants, three from the government, and two from academia. There were four focus group discussions with 30 residents. The study found that at the individual resident level, health awareness and the availability of sodium reduction tools in the market could affect their salt reduction practices. For food manufacturers and restaurants, consumers′ preferences, technical challenges in reformulation, and government support were key factors determining the smooth progress of their salt reduction efforts. At the governmental level, multi-sectional coordination, chronic disease management demonstration areas, and the impact of the pandemic were the main factors influencing the implementation of sodium reduction interventions.Conclusion:Future endeavours should strengthen long-term management and optimise the complex influencing factors associated with intervention measures. This will be essential in sustaining and expanding the positive health outcomes achieved through the Shandong population sodium reduction strategy.
7.Eearly outcomes of totally thoracoscopic minimally invasive aortic valve and double valve replacement
Zhenzhong WANG ; Yanchen YANG ; Huanlei HUANG ; Lishan ZHONG ; Chengnan TIAN ; Zerui CHEN ; Biaochuan HE ; Xin ZANG ; Junfei ZHAO ; Huiming GUO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(05):710-717
Objective To summarize the early outcomes of totally thoracoscopic minimally invasive aortic valve replacement (AVR) and double valve replacement (DVR). Methods The clinical data of patients who underwent totally thoracoscopic minimally invasive AVR or DVR in Guangdong Provincial People’s Hospital from April 2020 to January 2021 were retrospectively analyzed. The patients were divided into an AVR group and a DVR group according to the surgical method, and the clinical data of the two groups were compared. Results Finally 22 patients were enrolled, including 14 males and 8 females with an average age of 50.0±11.2 years at operation. Eight patients were degenerative disease, 8 were rheumatic heart disease combined with valvular disease, and 6 were bicuspid aortic valve. Out of the 22 patients, 16 underwent AVR alone, and 6 underwent DVR. All patients completed the operation successfully, and there was no death. Perivalvular leakage during surgery occurred in 2 patients. The average cardiopulmonary bypass time was 187.0±39.9 minutes, and aortic cross-clamping time was 117.0 (99.0, 158.0) minutes. Duration of mechanical ventilation and intensive care unit stay was 9.5 (4.8, 18.3) hours and 41.0 (34.0, 64.0) hours, respectively. The volume of chest drainage at the first 24 hours after surgery was 214.0±124.6 mL, and the postoperative hospital stay was 5.5 (4.0, 8.3) days. The cardiopulmonary bypass time and aortic cross-clamping time in the DVR group were longer than those in the AVR group, and the volume of chest drainage at 24 hours after surgery was more than that in the AVR group, with a statistical difference (P<0.05). Echocardiography before hospital discharge showed paravalvular leakage in 1 patient. There was no death during follow-up of 5.9±3.0 months. Conclusion The early outcome of totally thoracoscopic minimally invasive AVR and DVR is satisfactory, and the approach of surgery is worth exploring.
8.The value of right atrial myocardial fibrosis in evaluating the prognosis of isolated tricuspid valve surgery after left heart valve surgery
Yanchen YANG ; Lishan ZHONG ; Zhenzhong WANG ; Liang YANG ; Yingjie KE ; Haijiang GUO ; Biaochuan HE ; Kan ZHOU ; Junfei ZHAO ; Huanlei HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(07):1008-1013
Objective To investigate the predictive value of right atrial myocardial fibrosis in the prognosis of isolated tricuspid regurgitation surgery after left heart valve surgery. Methods The patients who underwent tricuspid valvuloplasty by the same operator in Guangdong Provincial People's Hospital from April 2016 to August 2021 due to long-term isolated severe tricuspid regurgitation after left heart valve surgery were included in the study. According to the degree of right atrial myocardial fibrosis, the patients were divided into three groups: a mild group, a moderate group, and a severe group. The clinical data of these patients were compared and analyzed. Results A total of 75 patients were enrolled, including 16 males and 59 females with an average age of 57.0±8.4 years. There were 30 patients in the mild group, 29 patients in the moderate group and 16 patients in the severe group. In terms of the preoperative data, there were statistical differences in cardiac function grade, right atrial diameter, tricuspid incompetence area among the three groups (P<0.05). In terms of the postoperative data, there were statistical differences among the three groups in the cardiopulmonary bypass time, mechanical ventilation time, ICU monitoring time, complication rate and mortality (P<0.05). Further pairwise comparison showed that, compared with the mild group, the severe group had longer mechanical ventilation time (P=0.024), longer ICU monitoring time (P=0.003) and higher incidence of postoperative complications (P=0.024), while the moderate group had no statistical difference in all aspects (P>0.05); compared with the moderate group, the severe group had longer ICU monitoring time (P=0.021) and higher incidence of complications (P=0.006). Conclusion The early outcome of tricuspid valvuloplasty in patients with isolated tricuspid regurgitation after left heart valve surgery with severe right atrial myocardial fibrosis is worse than that in the patients with mild and moderate fibrosis, suggesting that the degree of myocardial fibrosis in the right atrium can be a predictor of the effect of tricuspid regurgitation surgery and a judgement indicator of the surgery timing.
9.NOGEA: A Network-oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning
Guo ZIHU ; Fu YINGXUE ; Huang CHAO ; Zheng CHUNLI ; Wu ZIYIN ; Chen XUETONG ; Gao SHUO ; Ma YAOHUA ; Shahen MOHAMED ; Li YAN ; Tu PENGFEI ; Zhu JINGBO ; Wang ZHENZHONG ; Xiao WEI ; Wang YONGHUA
Genomics, Proteomics & Bioinformatics 2021;19(4):549-564
Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and re-positioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.
10.Perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery for pelvic fractures: a prospective randomized control trial
Jinhui WANG ; Yufeng GE ; Xianfeng GUO ; Li TAO ; Xiaohua LIU ; Qiang LI ; Yuzhang WANG ; Minghui YANG ; Shiwen ZHU ; Zhenzhong WANG ; Lin JIN ; Zhiyong HOU ; Jian JIA ; Liancheng WANG ; Bin YU ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2021;23(10):850-855
Objective:To evaluate the efficacy and safety of perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery (ERAS) for pelvic fractures.Methods:A prospective randomized control trial was conducted to include 114 emergency patients who had been admitted to Department of Orthopaedic Trauma, Beijing Jishuitan Hospital for surgical treatment of pelvic fractures from June 2019 to December 2020. Of them, 57 were assigned into an intervention group according to a random digits table. They were 42 males and 15 females, aged from 18 to 77 years and subjected to management of pelvic fractures with tentative perioperative ERAS approaches which were adjusted at different stages. The other random 57 patients were assigned into a control group. They were 40 males and 17 females, aged from 17 to 70 years and subjected to management of pelvic fractures with conventional rehabilitation approaches which included postoperative in-hospital consultation and guidance by rehabilitation physicians. The 2 groups were compared in terms of Majeed pelvis scores and Barthel indexes at postoperative 2, 6, 12 and 24 weeks, and visual analogue scale (VAS) pain scores and SF36 scores at postoperative 12 and 24 weeks.Results:A total of 105 patients (55 in the intervention group and 50 in the control group) were completely followed up for 151 to 254 d (mean, 177 d). The 2 groups were comparable due to no significant difference between them in the preoperative general data ( P>0.05). The Majeed scores (44±13, 67±16, 86±14 and 98±7) and Barthel indexes (57±13, 79±16, 95±8 and 100±2) at postoperative 2, 6, 12 and 24 weeks in the intervention group were significantly higher than those in the control group [(35±16, 51±16, 73±14 and 91±12) and (45±19, 67±18, 86±12 and 98±4)] (all P<0.05). At postoperative 12 and 24 weeks, the SF-36 scores (129±15 and 141±6) in the intervention group were significantly higher than those in the control group (114±15 and 131±12) ( P<0.05). There was no significant difference in the pain degree between the 2 groups ( P>0.05). Conclusion:In management of pelvic fractures, compared with conventional perioperative rehabilitation approaches, the perioperative ERAS rehabilitation approaches may improve early functional outcomes and thus help the patients restore their activities of daily living earlier.

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