1.Identification of Pharmacodynamic Material Basis of Ruyi Zhenbaowan by Multidimensional Correlation Model of "Pharmacodynamic-target-component-pharmacokinetic"
Mingzhu XU ; Huaiping LI ; Zhaochen MA ; Tao LI ; Yudong LIU ; Ziqing XIAO ; Chu ZHANG ; Kedian CHEN ; Weihua MA ; Feng HUANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):68-77
ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2, and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them, and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that, plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points, and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry(UPLC-Q-TRAP/MS), and drug concentration-time curves were plotted, then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network, a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes, such as estrogen receptor 1(ESR1), cyclic adenosine monophosphate(cAMP)-dependent protein kinase catalytic subunit alpha(PRKACA) and protein kinase B1 (Akt1), and 10 corresponding potential effect components, such as glycyrrhizic acid and betulinic acid, were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components, gallic acid, apigenin-7-O-glucuronide, glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid, with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic, this study analyzes the main effective materials of Ruyi Zhenbaowan, such as glycyrrhizic acid, gallic acid, apigenin-7-O-glucuronide and apigenin, which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.
2.Identification of in Vitro and in vivo Chemical Constituents of Ruyi Zhenbaowan Based on UHPLC-Q Exactive Orbitrap HRMS
Kedian CHEN ; Zhaochen MA ; Bingbing CAI ; Ying LIU ; Yudong LIU ; Tao LI ; Mingzhu XU ; Haiping WANG ; Na LIN ; Yanqiong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):78-84
ObjectiveTo identify the chemical constituents of Ruyi Zhenbaowan in vitro and in vivo. MethodThe chemical constituents of Ruyi Zhenbaowan were identified based on UHPLC-Q Exactive Orbitrap HRMS. A total of 12 male SD rats were randomized into two groups: control (pure water) and Ruyi Zhenbaowan (1.8 g·kg-1). The rats were administrated with the suspension of Ruyi Zhenbaowan or pure water by gavage. After 1.5 h, the plasma and cerebrospinal fluid were collected. Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 mm × 150 mm, 1.7 μm) with a mixture of 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phase. Gradient elution was carried out according to the procedure of 0~15 min,97%~80%A;15~30 min ,80%~60%A;30~40 min,60%~30%A;40~45 min,30%~5%A. The ion source was electrospray ionization, and scan range was m/z 100-1 500. The prototype components and the components in the plasma and cerebrospinal fluid were analyzed qualitatively by scanning in positive and negative ion modes and identified by comparison with the data in published literature and the information of standard substances. ResultA total of 126 chemical constituents were identified from the 80% methanol solution of Ruyi Zhenbaowan, and 14 and 7 prototype constituents were detected in the plasma and the cerebrospinal fluid, respectively. In addition, the fragmentation rules of apigenin, apigenin-7-O-glucuronide, galangin, liquiritin, piperine, glycyrrhizic acid, eugenol, gallic acid, and cholic acid were deduced. ConclusionThis study achieved rapid multicomponent characterization and identification of Ruyi Zhenbaowan in vitro and in vivo, providing theoretical support for exploring active substances and performing quality control.l.
3.Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China
Bing WU ; Yang LI ; Lanjing XU ; Zheng ZHANG ; Jinhui ZHOU ; Yuan WEI ; Chen CHEN ; Jun WANG ; Changzi WU ; Zheng LI ; Ziyu HU ; Fanye LONG ; Yudong WU ; Xuehua HU ; Kexin LI ; Fangyu LI ; Yufei LUO ; Yingchun LIU ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Epidemiology 2024;45(1):48-55
Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.
4.Establishment and evaluation of the comorbidity animal model of knee osteoarthritis and hypertension with pattern of liver and kidney deficiency
Zhaochen MA ; Chu ZHANG ; Mingzhu XU ; Yudong LIU ; Weiheng CHEN ; Yanqiong ZHANG ; Na LIN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):652-661
Objective To establish the animal model of comorbidity of knee osteoarthritis(KOA)and hypertension with pattern of liver and kidney deficiency and evaluate its characteristics of comorbidity and pattern.Methods Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)were assigned to the WKY control group(control group),hypertension combined with KOA sham-operation group(sham-operation group),hypertension combined with KOA group(model group),hypertension combined with KOA and liver-kidney deficiency pattern group(LKD group).The animal model of KOA combined with hypertension was prepared by anterior cruciate ligament transection(ACLT)in spontaneously hypertensive rats.ACLT combined with intramuscular injection of hydrocortisone was performed to prepare an animal model of KOA with liver-kidney deficiency(LKD)pattern type,combined with hypertension.Then,the related indexes of LKD syndrome were detected in turn,including the contents of thyroid stimulating hormone(TSH),testosterone(T),corticosterone(CORT),adrenocorticotropic hormone(ACTH)in serum,and enzyme activities of alanine transaminase(ALT),aspartate transaminase(AST),and alkaline phosphatase(ALP)in serum,the mass ratio of liver,kidney,spleen,thymus to the brain,body weight,anal temperature,activity situation,and emotion.Systolic blood pressure,diastolic blood pressure,and other blood pressure-related indices were also detected.The levels of serum tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β),plantar mechanical pain sensitivity threshold,weight difference score of both hind limbs,hind limb joint swelling,and quadruped gait parameters were also measured.Furthermore,hematoxylin-eosin,safranine-fast green,and Masson staining were performed to observe pathological changes,cartilage degeneration,and bone destruction of the knee joint,and the microstructure parameters of the tibia were detected by Micro-CT imaging.Results Compared to the model group,the contents of serum TSH,ACTH,T,CORT and the mass ratio of the kidney,spleen,and thymus to the brain in the LKD group decreased(P<0.05).Compared to the control group,the systolic blood pressure and diastolic blood pressure of the other three groups increased significantly(P<0.05).Compared to the sham-operation group,serum TNF-α and IL-1β levels increased,plantar mechanical pain threshold decreased,weight difference score of both hind limbs and joint swelling of the affected limb increased(P<0.05),and gait parameters(e.g.,gait length and standing time of the affected limbs)became abnormal in the model and LKD groups.Simultaneously,the cartilage surface defect of the rat knee joint was severe,the arrangement of the surface chondrocytes was altered,the cartilage layer became thinner,the muscle fibers increased,and the cartilage ossification was severe.Furthermore,the relative volume,thickness,and number of trabeculae of the knee joint decreased significantly(P<0.05).Conclusion The rat model established in this study is consistent with the clinical characteristics of integrated traditional Chinese and Western medicine in patients with comorbidities of hypertension and KOA with liver and kidney deficiency pattern.This rat model can characterize the typical symptoms of liver and kidney deficiency pattern.It has typical pathological changes in knee cartilage and subchondral bone tissues and can maintain a stable range of high systolic and diastolic blood pressure.It also explore the scientific connotation of simultaneous treatment of different diseases in traditional Chinese medicine,revealing the therapeutic mechanism and developing new drugs.
5.Problems and countermeasures of industry-university-research cooperation in Liaoning Province
Yudong WU ; Ji WU ; Wei WU ; Xin LI ; Yu YI ; Yanming LIU ; Shuyin LI ; Yuting KANG ; Wenrui LU ; Weiyun CHEN ; Fu REN ; Kebin XU
Journal of Shenyang Medical College 2024;26(5):542-546
Industry-university-research cooperation is not only the core of technological innovation,but also an important way to enhance industrial competitiveness and achieve high-quality development.Industry-university-research cooperation in Liaoning Province has achieved significant results in promoting technological innovation and economic development,but there are still some problems and challenges.The main problems include insufficient depth of industry-university-research cooperation,scattered innovation resources,lack of long-term stable cooperation mechanisms,as well as talent loss and lack of high-quality innovative talents.Through systematically sorting out the existing models of industry-university-research cooperation,it proposes a series of targeted and operable countermeasures and suggestions.These measures and suggestions provide solid theoretical support for the healthy development of industry-university-research cooperation in Liaoning Province.
6.Research on legal regulations of deep integration of industry-university-research in Liaoning
Yudong WU ; Ji WU ; Wei WU ; Xin LI ; Yu YI ; Yanming LIU ; Shuyin LI ; Kebin XU ; Wenrui LU ; Fu REN ; Yuting KANG
Journal of Shenyang Medical College 2024;26(6):644-649
Objective:To study the situation of legal regulations for the integration of industry-university-research in Liaoning,improve the concept of legal regulation,optimize the legal regulation methods,so as to promote the deep integration of industry-university-research in Liaoning.Method:Problem-oriented approach was used,and the problems of the current legal regulations for the integration of industry-university-research in Liaoning were reviewed.Result:It was found that legal regulations for the deep integration of industry-university-research in Liaoning were not yet perfect,which was manifested in insufficient coverage of policies and regulations,relatively lagging update of regulations,and insufficient highlighting of local characteristics.Conclusion:In response to the above issues,it is proposed to use measures such as collaborative regulation,incentive regulation and moderate regulation to establish and improve the legal system of the integration of industry-university-research in Liaoning province.
7.Analysis of surgical situations and prognosis of pancreaticoduodenectomy in Jiangsu province (a report of 2 886 cases)
Zipeng LU ; Xin GAO ; Hao CHENG ; Ning WANG ; Kai ZHANG ; Jie YIN ; Lingdi YIN ; Youting LIN ; Xinrui ZHU ; Dongzhi WANG ; Hongqin MA ; Tongtai LIU ; Yongzi XU ; Daojun ZHU ; Yabin YU ; Yang YANG ; Fei LIU ; Chao PAN ; Jincao TANG ; Minjie HU ; Zhiyuan HUA ; Fuming XUAN ; Leizhou XIA ; Dong QIAN ; Yong WANG ; Susu WANG ; Wentao GAO ; Yudong QIU ; Dongming ZHU ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Digestive Surgery 2024;23(5):685-693
Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.
8.Clinical application of abdominal belts in difficult colonoscopy
Guangqiu YU ; Jianwei ZHU ; Lin SUN ; Yudong XU ; Wen TANG ; Weixia ZHOU
Chinese Journal of Digestive Endoscopy 2024;41(6):487-491
To evaluate the effects of abdominal belts in colonoscopy for patients with low body mass index (BMI) (BMI<18.5 kg/m2) or a history of abdominal surgery, a prospective, randomized, single-blind study was conducted on colonoscopy outpatients. Patients with low BMI or a history of abdominal surgery who underwent colonoscopy at the Second Affiliated Hospital of Soochow University from January 2018 to January 2022 were enrolled. The patients were divided into the abdominal belts group and non-abdominal belts group according to whether they used abdominal belts. Differences between the two groups were compared in terms of cecal intubation time, length of colonoscope intubation into the cecum, patient repositioning, abdominal pressure, and degree of abdominal distension. A total of 296 patients (98 low BMI patients and 198 patients with a history of abdominal surgery) were enrolled, 148 in each group. The results showed that cecal intubation time (4.35±1.85 min VS 7.99±3.86 min, t=35.624, P<0.001) and length of colonoscope intubation into the cecum (72.03±10.35 cm VS 86.42±17.71 cm, t=38.442, P<0.001) were lower in the abdominal belts group, compared with those of the non-abdominal belts group. The percentage of patients requiring repositioning [18.9% (28/148) VS 71.6% (106/148), χ2=82.959, P<0.001] and abdominal pressure [6.1% (9/148) VS 52.7% (78/148), χ2=77.504, P<0.001] in the abdominal belts group were significantly lower than those in the non-abdominal belts group. There were significant differences in the degree of abdominal distension during and after colonoscopy ( P<0.001). In conclusion, the use of abdominal belts significantly improves the efficiency and effects of colonoscope intubation in difficult colonoscopy patients with low BMI and a history of abdominal surgery.
9.Evaluation and influencing factor analysis of the detection effect of hepatitis B virus surface antigen and treponema pallidum using rapid screening immunochromatography technology
Haiying SUN ; Enyong FAN ; Yudong JIAO ; Shouguang XU ; Chuming SHEN
Chinese Journal of Blood Transfusion 2023;36(10):931-934
【Objective】 To evaluate the effectiveness of rapid initial screening using HBsAg and syphilis reagents of immunochromatography technology before blood donation, and explore the influencing factors. 【Methods】 The pre-donation screening of HBsAg and anti-TP and post-donation blood test results of blood donors in Yangzhou region from January 2020 to June 2023 were retrospectively analyzed. The HBsAg and anti-TP reactive samples by ELISA from January to June 2023 were, retested using colloidal gold immunochromatographic reagents, and the results were compared and analyzed. 【Results】 A total of 200 414 blood donors were screened, among which 781 were HBsAg and anti-TP positive, accounting for 0.39%. A total of 191 717 blood donors successfully donated blood, and 986 were HBsAg and anti-TP positive by ELISA, accounting for 0.51%. 62 HBsAg and 61 anti-TP reactive samples were retested using the initial screening reagent, with 24 HBsAg reactive samples and 26 anti-TP reactive samples, accounting for 38.71% and 42.62% respectively. 14 HBsAg and 6 anti-TP gray area samples were retested, but no reactivity was found.The reactivity rates of 9 samples with HBsAg detection S/CO values greater than 25.0 and 10 samples with anti-TP detection S/CO values greater than 15.0 were all 100%.There was a negative correlation between the reaction intensity (S/CO value) of reactive samples and interpretation time of initial screening reaction. 【Conclusion】 The rapid primary screening of hepatitis B and syphilis with immunochromatography technology among blood donors can effectively improve the quality of blood and the qualification rate of blood after collection. Through targeted training of primary screening staff, the quality of primary screening can be further improved, the rate of missed detection can be reduced, and costs can be saved, thus reducing the risk of transfusion transmitted infection and ensuring the health of blood donors.
10.Make a way in the wilderness, climb the highest mountain
Chinese Journal of Microsurgery 2023;46(2):121-125
In March 1973, the Department of Hand Surgery and Oral Surgery of Huashan Hospital Affiliated to Shanghai First Medical College (now Huashan Hospital Affiliated to Fudan University) jointly carried out the first case of free flap transfer in China. In the past 50 years, Chinese colleagues have been constantly exploring and innovating in the field of microsurgery, and have made great progress, always leading the world. On the occasion of the 50th anniversary celebration, it would like to pay tribute to the predecessors who made contributions to Chinese microsurgery, and also encourage the colleagues in microsurgery to take Professor Yang Dongyue as an example, forge ahead, scale brave heights, and make new contributions to the healthcare of mankind.

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