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.Herbal Textual Research on Bletillae Rhizoma in Famous Classical Formulas
Dan ZHAO ; Tao ZHOU ; Chaolei LUO ; Dewei GAN ; Lingling LIU ; Chuanzhi KANG ; Zhikun WU ; Xu LI ; Yan FU ; Guoqiong CAO ; Yongping ZHANG ; Chenghong XIAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):77-88
In order to provide basic information for the utilization and development of famous classical formulas containing Bletillae Rhizoma, this article systematically analyzes the historical evolution of the name, origin, harvesting and processing of Bletillae Rhizoma by reviewing the ancient materia medica, prescription books, medical books and modern literature. The research results showed that Baiji(白及) was the main name, some scholars took Baiji(白芨) as its main name, and there were many other names such as Baiji(白给), Baigen(白根), Baiji(白苙). The mainstream source of Bletillae Rhizoma was the tubers of Bletilla striata, and drying, large, white, solid, root-free and skin removed completely were the good quality standards. With the promotion of wild to cultivated medicinal materials, there were certain differences between their traits, and the quality evaluation indexes should be adjusted accordingly. The origin of records in the past dynasties was widely distributed, with Guizhou and Sichuan having high production and good quality in modern times. The harvesting period is mostly in spring and autumn, and harvested in autumn was better. The processing and processing technology is relatively simple, and it was used fresh or powdered in past dynasties, while it is mainly sliced for raw use in modern times. Based on the results, it is suggested that the tubers of Bletilla striata of Orchidaceae should be used in the famous classical formulas, and it should be uniformly written as Baiji(白及). And if the original formula indicates the requirement of processing, it should be operated according to the requirement, if the requirement of processing is not indicated, it can be used in raw form as medicine.
4.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.
5.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.
6.Clinical value of peripheral blood circulating tumor cells in the diagnosis and treatment of prostate cancer
Yawei ZHAO ; Lei TANG ; Qianyue LI ; Wang MA ; Zhikun LI
Chinese Journal of Primary Medicine and Pharmacy 2022;29(5):683-687
Objective:To investigate the clinical value of peripheral blood circulating tumor cells (CTC) in the diagnosis and treatment of prostate cancer.Methods:Sixty-four patients with prostate cancer who received treatment in Xinjiang Production and Construction Corps Hospital, China between June 2018 and May 2020 were included in the cancer group. An additional 35 patients with benign prostatic lesions who concurrently received treatment in the same hospital were included in the benign disease group. Twenty male patients with non-prostate disease were included in the control group. Cell enrichment, separation, staining and identification together with Gleason score and pathological stage were subjected to one-way analysis of variance.Results:The percentage of patients with CTC count ≥ 3 in the cancer, benign disease and control groups was 73.43% (47/64), 17.14% (6/35) and 10.00% (2/20), respectively. The level of prostate-specific antigen in patients with CTC was significantly higher than that in patients without CTC ( t = 2.89, P < 0.05). There was significant difference in CTC count between different Gleason score groups ( F = 3.25, P < 0.05) and between different pathological stage groups ( F = 3.42, P < 0.05). Conclusion:Peripheral blood CTC measurement can be used as an auxiliary method for the differentiation of benign and malignant prostate diseases. CTC count in patients with prostate cancer is correlated with prostate-specific antigen level, Gleason score, and pathological stage. Therefore, peripheral blood CTC measurement plays an auxiliary role in predicting prognosis in patients with CTC. This study is innovative and scientific.
7.Generation of αGal-enhanced bifunctional tumor vaccine.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2022;12(7):3177-3186
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.
8.The value of high frequency ultrasound in the diagnosis of internal mammary lymph node metastasis in breast cancer
Xiaohui JI ; Kexin SHI ; Qianying ZHAO ; Mengying WEI ; Zhikun LIU
Chinese Journal of Ultrasonography 2021;30(1):58-63
Objective:To investigate the ultrasonographic characteristics and risk factors of breast cancer internal mammary lymph node (IMLN) metastasis.Methods:A retrospective analysis of 296 first diagnosed breast cancer patients in the Fourth Hospital of Hebei Medical University from March 2010 to May 2020. IMLN was divided into metastatic group (236 cases) and non-metastatic group (60 cases) based on pathology. Chi-square test and independent sample t test were used to analyze the ultrasound characteristics of IMLN metastasis and factors related to metastasis. ROC curve analysis of IMLNs were plotted to obtain the diagnostic thresholds and their sensitivity and specificity.Univariate and multivariate Logistic analysis was used to analyze the risk factors of IMLN metastasis. Results:①The appearances of IMLN in ultrasound were normal type, thickened-cortex type, unclear hilus structure type and thickened-nodular soft tissue type. ②In the two groups, the differences in IMLN long diameter, thickness diameter, number, and lymphatic hilum structure type were statistically significant (all P<0.05), and there were no significant differences in IMLN long diameter/thickness diameter and IMLN blood supply (all P>0.05). ③The long diameter threshold of IMLN for diagnosis of metastasis was 10.5 mm, the are under the ROC curve(AUC) was 0.825, with sensitivity of 58.5% and specificity 93.3%; thickness and diameter threshold was 4.5 mm, AUC was 0.790, with sensitivity 66.9% and specificity 75.0%. The sensitivity and specificity of the diagnosis of long-diameter combined structure type were 56.3% and 93.3%, respectively; the sensitivity and specificity of the diagnosis of thick-diameter combined structure type were 64.8% and 81.7%, respectively. The cortical thickness threshold was 1.9 mm, and the diagnostic sensitivity and specificity were 91.9% and 86.7%, respectively. ④The risk factors of IMLN metastasis inculded univariate analysis showed tumor length, tumor volume, axillary lymph node long diameter, axillary lymph node metastasis, and clavicle lymph node metastasis. There was a statistically significant difference in the pathology of the lower lymph nodes between the two groups ( P<0.05). Multivariate analysis showed that the long diameter of the tumor and the metastasis of the axillary lymph nodes were independent risk factors of IMLN metastasis. Conclusions:The metastatic IMLN mostly manifest as no lymphatic hilum structure or cortical thickening (≥1.9 mm), and multiple IMLN can help diagnose metastasis.Ultrasound can better assess breast cancer IMLN metastasis, and the diagnostic efficiency of IMLN long-diameter combines structure type is higher.Independent risk factors for IMLN metastasis include tumor size and axillary lymph node metastasis.
9.Efficacy of prophylactic irradiation of internal mammary lymph nodes in breast cancer: a Meta-analysis
Sicong JIA ; Zhikun LIU ; Jun ZHANG ; Chenguang ZHAO ; Longyu ZHU ; Jie KONG ; Huina HAN ; Yuguang SHANG ; Dongxing SHEN ; Xuejuan DUAN
Chinese Journal of Radiation Oncology 2021;30(9):903-909
Objective:To evaluate the effect of prophylactic irradiation of internal mammary lymph nodes in patients with breast cancer in this Meta-analysis.Methods:CNKI, Wanfang Medical network, CBM, PubMed, EMBASE and Web of Science were searched by computer. The controlled clinical studies comparing whether or not internal mammary lymph node irradiation as an intervention were included and the quality of the included literature was evaluated according to Newcastle-Ottawa Scale (NOS). RevMan 5.3 software and Stata 14 software were used for Meta-analysis.Results:A total of 11 original articles were included, and 13 181 patients were included for Meta-analysis. There was no statistically significant difference in the overall survival (OS) between patients with and without internal mammary lymph node irradiation ( P=0.490). The subgroup analysis using the date of treatment and the degree of risk in the enrolled population as criteria showed that 5-year OS was significantly increased after internal mammary area irradiation in high-risk stage Ⅱ-Ⅲ patients (N+ , T 3-T 4 stage) with the date of treatment of after 2000( P=0.003, 0.006). Compared with patients without internal mammary area irradiation, internal mammary irradiation significantly increased the 5-year disease-free survival (DFS)( P<0.001). Conclusion:Under the modern radiotherapy technology, internal mammary lymph node irradiation improves the DFS of patients, and may bring OS benefits to high-risk stage Ⅱ-Ⅲ breast cancer patients (N+ , T 3-T 4 stage).
10.scDPN for High-throughput Single-cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence
Wu LIANG ; Jiang MIAOMIAO ; Wang YUZHOU ; Zhou BIAOFENG ; Sun YUNFAN ; Zhou KAIQIAN ; Xie JIARUI ; Zhong YU ; Zhao ZHIKUN ; Dean MICHAEL ; Hou YONG ; Liu SHIPING
Genomics, Proteomics & Bioinformatics 2021;19(3):346-357
Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution. Unfortunately, classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification. We developed a single-cell DNA library preparation method without preamplification in nanolitre scale (scDPN) to address these issues. The method achieved a throughput of up to 1800 cells per run for copy number variation (CNV) detection. Also, our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification (MDA) method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation. We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepato-cellular carcinoma (HCC). We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome. Furthermore, we observed that a minor clone of the primary tumor containing additional alterations in chro-mosomes 1q, 10q, and 14q developed into the dominant clone in the recurrent tumor, indicating clonal selection during recurrence in HCC. Overall, this approach provides a comprehensive and scalable solution to understand genome hetero-geneity and evolution.


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