1.Exercise preconditioning combined with bone marrow mesenchymal stem cell transplantation for myocardial infarction in rats
Zhikun WANG ; Shaoxuan BAI ; Wei ZHAO ; Chenyu WANG
Chinese Journal of Tissue Engineering Research 2025;29(1):65-73
BACKGROUND:Stem cell therapy has broad prospects in improving cardiac remodeling after myocardial infarction;however,alteration in the myocardial microenvironment affects the therapeutic efficacy of stem cells.Exercise preconditioning is similar to ischemic preconditioning and can have a protective effect on the myocardium.However,little attention has been paid to the effects and mechanisms of the combined effects of exercise preconditioning and stem cell transplantation. OBJECTIVE:To observe the effect of exercise preconditioning on bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction and to explore the mechanism of local inflammatory microenvironment. METHODS:Eighty female SD rats were randomly divided into sham operation group,model group,transplantation group,and combination group,with 20 rats in each group.The rat model of myocardial infarction was made by ligating the left anterior descending branch of coronary artery.The sham operation group was only threaded without ligature.The transplantation and combination groups were injected with bone marrow mesenchymal stem cells of male rats into the myocardium after modeling.In addition,the combination group also required 8 weeks of treadmill exercise(i.e.,exercise preconditioning)before modeling.Four weeks after stem cell transplantation,exercise performance was measured by incremental exercise exhaustion test;cardiac structure and function were measured by echocardiography;left ventricular hemodynamics was measured by pressure-volume catheterization,and myocardial histopathology was observed by in situ staining and myocardial collagen volume fraction was obtained.Quantitative reverse transcription polymerase chain reaction was used to detect left ventricular pro-inflammatory factor(interleukin-1β,interleukin-6,tumor necrosis factor-α),anti-inflammatory factor(interleukin-10),sex-determining region of Y chromosome,and fetal genes(atrial natriuretic peptide,brain natriuretic peptide,β-myosin heavy chain)mRNA expression level at 1,7 days and 4 weeks after stem cell transplantation. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:compared with sham operation group,exercise performance,and left ventricular ejection fraction were reduced(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were increased(P<0.05);the mRNA expression of fetal genes and pro-inflammatory factors were up-regulated(P<0.05),and the mRNA expression of interleukin-10 was down-regulated(P<0.05)in the model group.Compared with the model group,exercise performance and left ventricular ejection fraction were increased(P<0.05);myocardial infarction area,cardiomyocyte cross-sectional area,and collagen volume fraction were decreased(P<0.05);mRNA expression of fetal genes and pro-inflammatory factors was down-regulated(P<0.05),and that of interleukin-10 had no significant change(P>0.05)in the transplantation group.Compared with the transplantation group,all the above indicators in the combination group were further improved(P<0.05).(2)One day and 7 days after stem cell transplantation,compared with the transplantation group,the mRNA expression of sex-determining region of Y chromosome in the combination group increased(P<0.05).(3)Correlation analysis showed that interleukin-1β,interleukin-6(except on the 1st day after transplantation),and tumor necrosis factor-α were negatively correlated with the mRNA expression of sex-determining region of Y chromosome(P<0.05),while interleukin-10 was positively correlated with that of sex-determining region of Y chromosome(P<0.05).These findings suggest that exercise preconditioning can enhance the effect of bone marrow mesenchymal stem cell transplantation in rats with myocardial infarction,which is characterized by suppression of cardiac remodeling and further amelioration of cardiac function.The mechanism is related to the improvement of the myocardial inflammatory microenvironment to promote bone marrow mesenchymal stem cell retention and survival.
2.Herbal Textual Research on Houttuyniae Herba in Famous Classical Formulas
Dan ZHAO ; Changgui YANG ; Chuanzhi KANG ; Chenghong XIAO ; Zhikun WU ; Hongliang MA ; Jiwen WANG ; Xiufu WAN ; Sheng WANG ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):250-259
This article systematically analyzes the historical evolution of the name, medicinal parts, origin, harvesting, processing and other aspects of Houttuyniae Herba(HH) by referring to the medical books, prescription books and other documents of the past dynasties, combined with the research materials related to modern and contemporary times, in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature, HH was often referred to as "Ji" and "Jicai", the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties, and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent, all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas, mostly self-produced self-marketing. In ancient times, fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine, the fresh products uses the whole plant, while the dried products uses the aboveground parts, which are cleaned, selected and processed before use. Fresh products are harvested regardless of season, while dried products are harvested in both summer and autumn, with summer as the best. In ancient times, there were no specific requirements for the quality of HH, while in modern times, "intact stems and leaves with a strong fishy smell" are preferred. In addition, the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period, it was believed that its medicinal property was slightly warm, until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores, Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat, since Diannan Bencao recorded that it can be used for lung carbuncle, and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results, it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.
3.Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma.
Zhikun LIU ; Yichao WU ; Abid Ali KHAN ; L U LUN ; Jianguo WANG ; Jun CHEN ; Ningyang JIA ; Shusen ZHENG ; Xiao XU
Journal of Zhejiang University. Science. B 2024;25(1):83-90
Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans
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Aged
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Sarcopenia/diagnostic imaging*
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Carcinoma, Hepatocellular/diagnostic imaging*
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Muscle, Skeletal/diagnostic imaging*
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Deep Learning
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Prognosis
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Radiomics
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Liver Neoplasms/diagnostic imaging*
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Retrospective Studies
4.Effect of locking plate combined with cortical screw internal fixation on ankle function and quality of life in patients with ankle fracture combined with inferior tibiofibular separation
Zhikun WEI ; Xudong WANG ; Jinjie YANG ; Pengyan NIU ; Fei SHAO ; Shaohai REN
Journal of Clinical Surgery 2024;32(1):71-74
Objective To investigate the effect of locking plate combined with cortical screw internal fixation on ankle function and quality of life in patients with ankle fracture with tibiofibular separation.Methods A total of 120 patients with ankle fracture and distal tibiofibular separation treated in our hospital from May 2020 to December 2021 were selected and divided into control group and observation group according to random number table method,with 60 patients/group.The control group was treated with cortical screw fixation alone,and the observation group was treated with locking plate combined with cortical screw internal fixation.Before surgery and 6 months after surgery,the recovery function of the two groups was compared.X-ray,operation duration,healing time,intraoperative blood loss,postoperative complications were compared,and the living ability of the two groups of patients was evaluated.Results Before treatment,there was no difference in joint function between the two groups(P>0.05).After treatment,the longest walking of the control group(15.89±0.85),foot alignment(15.06±0.71),pain response(29.03±4.48)and ground walking(15.65±0.59).The longest walking distance(16.19±0.87),foot alignment(15.29±0.76),pain response(31.24±4.55)and ground walking(15.96±0.68)in the observation group,which were higher than those in control group(P<0.05).Compared with the control group,the intraoperative blood loss and healing time in the observation group were lower(P<0.05).BI index of the two groups before treatment had no difference(P>0.05);After treatment,BI index of observation group was higher than that of control group(P<0.05).There was no difference in the total complication rate between the two groups(P>0.05).Conclusion Locking plate combined with cortical screw internal fixation has a good therapeutic effect on improving ankle function,reducing intraoperative blood loss,promoting healing and improving behavioral ability in the treatment of ankle fracture combined with hypotibiofibular syndesmosis injury.
5.Analysis of Specific Chromatogram of Classical Formula Qianghuo Shengshi Tang Reference Samples
Wenya GAO ; He XU ; Mingli LI ; Haiyu ZHAO ; Yanyan ZHOU ; Hongjie WANG ; Jian YANG ; Xiaolu WEI ; Zhikun FAN ; Nan SI ; Baolin BIAN
Chinese Journal of Modern Applied Pharmacy 2024;41(10):1350-1356
OBJECTIVE
To establish the specific chromatogram of Qianghuo Shengshi Tang(QHSS) reference sample, clarify the key quality attributes of QHSS, providing reference for the quality evaluation of QHSS reference sample.
METHODS
The SilGreen C18 column(4.6 mm×250 mm, 5 μm) was used. The mobile phase consisted acetonitrile and 0.2% formic acid aqueous solution. The detection wavelength was 328 nm. Established an HPLC characteristic spectrum analysis method for the reference sample of QHSS. A variety of chromatographic columns and different instruments were applied to investigate the adaptability of the system. HPLC-LTQ-Orbitrap MS was used to identify the specific peaks of the QHSS reference samples in positive ion mode.
RESULTS
There were 14 peaks in the specific chromatogram, which belonged to Notopterygii Rhizoma Et Radix, Angelicae Pubescentis Radix, Ligustici Rhizoma Et Radix, Chuanxiong Rhizome, Viticis Fructus, respectively. Ferulic acid(peak 3) was reference peak. A total of 22 compounds were identified by mass spectrometry, including coumarin and flavonoids.
CONCLUSION
The established specific chromatogram method of QHSS is simple, stable and reproducible. The material basis of QHSS reference sample is basically determined, providing a reference for the development and quality control of QHSS.
6.Construction of a microvascular invasion risk scoring model for hepatocellular carcinoma based on preoperative data
Bijing DONG ; Li WANG ; Zhikun LIU
China Modern Doctor 2024;62(4):38-42
Objective Microvascular invasion(MVI)risk scoring model was established based on the preoperative data of hepatocellular carcinoma(HCC)patients.Methods The clinical data of 1153 HCC patients who underwent hepatectomy in Hangzhou First People's Hospital from January 2000 to December 2021 were retrospectively analyzed.Random sampling method was used to divide the samples into modeling group(n=864)and verification group(n=289)at a ratio of 3:1.The modeling group used Logistic regression analysis model to explore the independent risk factors of MVI and established a prediction model accordingly.Receiver operating characteristic(ROC)curve and correction curve were drawn to evaluate the predictive ability and performance of the risk model.Results The incidence of MVI was 24.1%(208/864)in modeling group.Multivariate Logistic regression analysis showed that alpha-fetoprotein(AFP)>160ng/ml and total tumor volume(TTV)>30cm3 were independent risk factors for MVI(P<0.05).The total score of risk scoring model was 6 points,0-1 was classified as low risk,2-3 was classified as medium risk,and 4-6 was classified as high risk.The model predicted that the area under the curve(AUC)of MVI was 0.714 in modeling group and 0.731 in verification group.The calibration diagram showed that the prediction model had good performance.Conclusion The MVI risk prediction model for HCC patients based on TTV and AFP is simple and easy to use,which is conducive to preoperative treatment decision-making and doctor-patient communication.
7.Clinical Efficacy and Transcriptomic Study on the Treatment of Coronary Heart Disease Angina of Qi Deficiency and Blood Sta-sis Type with Maitong Jun'an Decoction
Ziyang WANG ; Meizhi LIU ; Xiaozhen HU ; Miao ZHOU ; Jiahao WENG ; Zhikun LAI ; Yongning SUN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(4):419-428
OBJECTIVE To observe the clinical efficacy of Maitong Jun'an Decoction in treating coronary heart disease(CHD)angina of qi deficiency and blood stasis type,and preliminarily elucidate its possible mechanism of action through transcriptomics meth-ods.METHODS A total of 140 patients with CHD angina of qi deficiency and blood stasis type were included and randomly divided into a treatment group and a control group,with 70 cases in each group.During the treatment period,3 patients in the control group dropped out.The control group received basic Western medicine treatment for secondary prevention of CHD,while the treatment group received Maitong Jun'an Decoction in addition to the treatment in the control group.The treatment period for both groups was 8 weeks.Before and after treatment,the patients in both groups were evaluated for the TCM syndrome score,Canadian Cardiovascular Society(CCS)angina grading,Seattle angina questionnaire(SAQ)score,self-rating anxiety scale(SAS),self-rating depression scale(SDS)score,and adverse reactions.The peripheral blood of 9 patients before and after treatment was selected for transcriptomic sequencing based on the principle of gender,age,and disease duration matching.RESULTS After treatment,the TCM syndrome scores and total scores of the 2 groups were significantly reduced(P<0.01).The treatment group was better than the control group in improving chest pain,chest tightness,shortness of breath,fatigue and total score(P<0.05,P<0.01);the overall improvement rate of CCS angina grading in the treatment group was better than that in the control group(P<0.05);the SAQ,SAS and SDS scores of the 2 groups were significantly reduced before and after treatment(P<0.01),and the SAQ score of the treatment group was improved better than that of the control group(P<0.05,P<0.01).The transcriptomics results showed that there were 862 significantly different mR-NAs before and after treatment,including 509 up-regulated and 353 down-regulated.GO analysis showed that there were 666 biologi-cal processes in the differentially expressed mRNAs,mainly including viral gene expression,translation initiation,RNA catabolism,etc.There were 112 cell components,mainly including focal adhesion,ribosome subunit,nuclear spot,etc.There were 94 molecular functions,mainly including double-stranded RNA binding,cadherin binding,transcription co-regulatory factor activity,etc.KEGG analysis showed that the differentially expressed mRNAs enriched in 20 signaling pathways,mainly including glycerophospholipid me-tabolism pathway,AMPK signaling pathway,ribosome pathway,etc.CONCLUSION Maitong Jun'an Decoction can improve clini-cal symptoms in patients with CHD angina of qi deficiency and blood stasis type.Its mechanism of action is multi-target and multi pathway,mainly related to the regulation of glycerophospholipid metabolism pathway,AMPK signaling pathway,ribosome pathway.
8.Deciphering the placental abnormalities associated with somatic cell nuclear transfer at single-nucleus resolution.
Liyuan JIANG ; Xin WANG ; Leyun WANG ; Sinan MA ; Yali DING ; Chao LIU ; Siqi WANG ; Xuan SHAO ; Ying ZHANG ; Zhikun LI ; Wei LI ; Guihai FENG ; Qi ZHOU
Protein & Cell 2023;14(12):924-928
9.Abiraterone combined with prednisone in the treatment of high-risk high-tumor load metastatic castration-resistant prostate cancer: a case report and literature review
Yawei ZHAO ; Lei TANG ; Wang MA ; Zhikun LI ; Yi XIE ; Qianyue LI
Journal of Modern Urology 2023;28(3):192-196
【Objective】 To observe the efficacy of abiraterone (AA) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). 【Methods】 The clinical data of a newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) patient with high risk and high tumor load were analyzed. After operation and endocrine therapy, the disease evolution was observed. Relevant literature was reviewed. 【Results】 After laparoscopic radical prostatectomy, 6-month bicalutamide and androgen deprivation therapy (ADT), the total prostate specific antigen (tPSA) was reduced to the lowest of 0.51 ng/mL, and then increased month by month. After domestic abiraterone (trade name: Qingkeshu) in the 8th month was administered for 4 months, tPSA continued to increase to 12.39 ng/mL. The case was then diagnosed as mCRPC. The treatment was adjusted again in the 11th mouth and the patient received AA (trade name: Zeke) combined with prednisone and ADT, and tPSA decreased to 0.17 ng/mL 2 months later. After 14 months of treatment, tPSA remained at about 0.12 ng/mL. Systemic ECT examination indicated that the range of bone metastases decreased and some areas of nuclide concentration turned shallow without obvious adverse reactions. 【Conclusion】 AA combined with prednisone and ADT can produce rapid decline in PSA and a good response in mCRPC patients. It can also significantly slow the progression of bone metastasis and relieve pain symptoms without obvious adverse reactions. Long-term efficacy needs further observation.
10.Analysis of influential factors for blood concentrations and adverse drug reaction in the treatment of lymphoma with high-dose methotrexate
Jiajun YE ; Zeyu LI ; Hanbiao WU ; Jia WANG ; Yanhui GE ; Zhikun QIU
China Pharmacy 2023;34(5):587-590
OBJECTIVE To discuss the factors affecting the blood concentration of high-dose methotrexate (HD-MTX) and the occurrence of adverse drug reactions (ADR) when treating lymphoma with HD-MTX. METHODS From July 2020 to November 2021, the information of HD-MTX patients who had been monitored for HD-MTX blood drug concentration in the First Affiliated Hospital of Guangdong Pharmaceutical University was collected by retrospective analysis, such as medical record number, age, sex, height, body mass, chemotherapy plan, dosage; test indexes such as alanine transaminase, aspartate transaminase, total bilirubin, creatinine clearance (CrCl), albumin (ALB) and other indexes were also collected before and after administration. The blood concentrations (c6 h, c24 h, c48 h) of HD-MTX were recorded, drug information of proton pump inhibitors (PPIs) was extracted and used, and ADR occurring within 48 h after administration were all evaluated. Single factor analysis, multiple linear regression and χ2 test were used to analyze the influential factors. RESULTS A total of 133 patients were included in this paper. The results of the single factor analysis of HD-MTX blood drug concentration showed that age, CrCl had an effect on c 6 h (P<0.05); age, CrCl and ALB had an effect on c24 h (P<0.05); age, body mass index (BMI), CrCl, combined use of PPIs and ALB had an effect on c48 h (P<0.05). The results of multiple linear regression analysis showed that age and CrCl had no effect on c 6 h (P>0.05), age was the main influential factor of c 24 h (P<0.05), and CrCl and combined use of PPIs were the main influential factors of c48 h (P<0.05); the coefficient of variance expansion was between 1 and 3.5, indicating that the analysis results were acceptable. The overall incidence of adverse reactions was 51.13%, of which the blood and lymphatic system reactions were the most common. The results of the influential factors of ADR showed that age, BMI, liver function and CrCl had effect on the incidence of ADR (P<0.05). CONCLUSIONS During the process of HD-MTX in the treatment of lymphoma, the patient’s age, CrCl and combined use of PPIs should be considered, and the patient’s blood concentration should be monitored; at the same time, the age of patients, BMI, liver function and CrCl have an impact on the incidence of ADR.


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