1.Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis.
Shuran FAN ; Ming QI ; Qi QI ; Qun MIAO ; Lijuan DENG ; Jinghua PAN ; Shenghui QIU ; Jiashuai HE ; Maohua HUANG ; Xiaobo LI ; Jie HUANG ; Jiapeng LIN ; Wenyu LYU ; Weiqing DENG ; Yingyin HE ; Xuesong LIU ; Lvfen GAO ; Dongmei ZHANG ; Wencai YE ; Minfeng CHEN
Acta Pharmaceutica Sinica B 2024;14(2):682-697
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
2.Construction of Knowledge Service and Clinical Application System of"Prevention of Disease"in Traditional Chinese Medicine Based on Big Data Convergence
Xiuying KUANG ; Qi YU ; Jinghua LI ; Guoxiang LI ; Xianhong LI ; Weimin ZHAO ; Fan YAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):236-241
Objective To explore the construction idea and application method of knowledge base and knowledge mining system for the prevention and treatment of diseases in traditional Chinese medicine.Methods Guided by the theory of traditional Chinese medicine(TCM),firstly,the knowledge system of TCM Prevention and treatment was sorted out,and the structure and relationship of TCM Prevention and treatment knowledge base were designed according to the classification method of TCM Prevention and treatment;Secondly,according to the needs of pre treatment research,the ancient and modern literature data sources and knowledge collection methods of TCM pre treatment database are proposed;Then,under the framework of the pre treatment classification system,the core knowledge is studied in the aspects of professional annotation,relationship extraction,knowledge audit,and a variety of data mining algorithms are introduced to analyze and mine the knowledge;Finally,the massive data obtained are combined with big data analysis and computer machine learning to realize intelligent information collection,disease analysis and diagnosis and treatment suggestions.Results Under the guidance of traditional Chinese medicine theory,the knowledge base of traditional Chinese medicine for prevention and treatment of diseases can digitize,digitize and intellectualize the basic knowledge and clinical knowledge of traditional Chinese medicine for prevention and treatment of diseases,and can objectively mine and analyze the data,providing a basis for the service and sharing of knowledge of traditional Chinese medicine for prevention and treatment of diseases.Conclusion The knowledge base of TCM Prevention and treatment is an important way for the digital storage of TCM Prevention and treatment knowledge,and provides literature knowledge support and objective evidence of data mining for TCM Prevention and treatment research.
3.Influencing factors of metabolic syndrome in community patients with schizophrenia
Yu FAN ; Shaoling ZHONG ; Liang ZHOU ; Jinghua SU ; Xiyuan CHEN ; Xiaomin HUANG
Sichuan Mental Health 2023;36(6):515-520
BackgroundPatients with schizophrenia are at high risk of suffering from metabolic syndrome. Most previous studies on the influencing factors of metabolic syndrome focused on the inpatients and limited ones on patients dwelling in community. ObjectiveTo explore the influencing factors at different risk levels of metabolic syndrome in community-dwelling patients with schizophrenia in Guangzhou, so as to provide references for future interventions on metabolic syndrome in this patient population. MethodsIn November 2021, 3 339 patients with schizophrenia who were registered in and administered by Guangzhou Mental Health Information System were included. All these patients had finished the physical examination in 2020, and whether they had metabolic syndrome was assessed basing on Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition). Patients were divided into high-risk group (n=423), critical group (n=1 524) and metabolic syndrome group (n=1 392) according to the Chinese expert consensus on the management of metabolic syndrome in patients with schizophrenia. Multiple logistic regression analysis were performed on the risk factors of metabolic syndrome in community-dwelling patients with schizophrenia. ResultsThe prevalence rate of metabolic syndrome in community-dwelling patients with schizophrenia was 41.69%. Univariate analysis showed that the results in gender (χ2=44.610), age (χ2=55.992), marriage status (χ2=30.755), illness course (χ2=25.913) and body mass index (χ2=829.265) were significantly different among the three groups (P<0.01). Kruskal-Wallis H test showed that the levels of waist circumference (H=920.331), systolic blood pressure (H=436.673), diastolic blood pressure (H=393.337), fasting blood glucose (H=807.304), triglyceride (H=1 134.125) and high-density lipoprotein cholesterol (H=593.615) among the three groups were significantly different (P<0.01). Logistic regression analysis showed that age ≥50 (OR=1.761, 95% CI: 1.087~2.853), overweight (OR=2.418, 95% CI: 1.862~3.140) and obesity (OR=57.903, 95% CI: 14.340~233.802) were risk factors contributing to high-risk patients becoming critical population (P<0.05 or 0.01). Female gender (OR=1.295, 95% CI: 1.034~1.622), aged 40~49 (OR=2.597, 95% CI: 1.582~4.263), age ≥50 (OR=4.392, 95% CI: 2.609~7.395), overweight (OR=7.844, 95% CI: 6.018~10.223) and obesity (OR=426.785, 95% CI: 105.724~1 722.839) were risk factors for high-risk patients developing into metabolic syndrome population (P<0.05 or 0.01). ConclusionThe prevalence rate of metabolic syndrome is higher in community-dwelling patients with schizophrenia. Female gender, older age, overweight and obesity would increase the risk of metabolic syndrome in schizophrenic patients. [Funded by Health Science and Technology Project in Guangzhou (number, 20221A010028)]
4.The change trend analysis of incidence of intracerebral hemorrhage in Tengzhou City,Shandong Province from 2013 to 2021
Xin WANG ; Jinghua FAN ; Yuluan XU ; Nana YAN ; Xianli SONG ; Wen HUANG ; Li CHENG ; Liyu ZHOU ; Hongyu ZHU ; Shujun YE ; Zongyi WU ; Fengping ZHAO ; Fuzhong SI
Chinese Journal of Neurology 2023;56(7):770-779
Objective:To analyze the changing trend of intracerebral hemorrhage (ICH) incidence among residents with different characteristics during 9 years of comprehensive hypertension prevention and control (hypertension prevention and control) in Tengzhou from 2013 to 2021.Methods:From January 1, 2013 to December 31, 2021, the new ICH cases collected by the Center for Disease Control and Prevention in Tengzhou City were analyzed to calculate the incidence of ICH, and the trend of its distribution was analyzed among residents with different ages, sexes, and between urban and rural areas. The registered population information came from Tengzhou Public Security Bureau. Age and sex standardized incidence was calculated based on the 7th National Population Census in 2020. The Cochran-Armitage test was used to analyze the time and age trends of the incidence.Results:The overall ICH crude and standardized incidence in Tengzhou City decreased from 97.30/100 000 to 52.13/100 000 ( Z=-9.93, P<0.001) and 119.30/100 000 to 50.69/100 000 ( Z=-15.40, P<0.001) from 2013 to 2021, and both elevated to form a single peak in 2020, with 22.58% ( χ 2=24.02, P<0.001) and 18.09% ( χ 2=17.08, P<0.001) higher than in 2019, respectively. The trends in male and female incidence over the same period were similar to the overall trends, and the incidence was higher in males than in females in all years. The incidence of ICH increased with age in all years. The difference of increase in male incidence rate in 2020 was statistically significant in three age groups ≥45 years compared with 2019 (36.29%, 23.57% and 16.18%, respectively, χ 2=6.73, 4.65, 4.00, P<0.001). The incidence of ICH decreased by 70.07% and 36.23% ( Z=18.44, 5.22, P<0.001) in urban and rural areas respectively from 2013 to 2021, whereas increased by 34.15% ( χ 2=10.88, P<0.01) and 22.08% ( χ 2=18.63, P<0.001) in 2020 compared with 2019 separately. Conclusions:The incidence of ICH in Tengzhou from 2013 to 2021 showed a significant downward trend, with the decrease in the incidence of ICH in women exceeding that in men. The decrease in the incidence of ICH in urban areas exceeded that in rural areas, and male morbidity seemingly had a younger trend.
5.Research progress on chemical constituents and pharmacological activities of Blumea balsamifera
Dongsheng FAN ; Ling LI ; Keke WANG ; Yujie HU ; Jian HUANG ; Chanyuan ZHOU ; Jinghua RUAN ; Wenlong ZHANG
China Pharmacy 2022;33(10):1274-1280
Blumea balsamifera belonging to Blumea of Compositae family is a perennial herb or subshrub ,which is the only source of Traditional Chinese medicine Aipian and ethnic medicine essential oil of B. balsamifera . B. balsamifera contains volatile oil,flavonoids,sesquiterpenoids,phenylpropanoids,etc.,and shows antibacterial ,anti-inflammatory,analgesic,treating burns and scalds,neuroprotective and antioxidant effects ,etc. In this paper ,the chemical constituents and pharmacological activities are summarized by reviewing the domestic and foreign research literatures ,and it is expected to provide a reference for the in-depth research and development and utilization of B. balsamifera .
6.Modified Fired Glycyrrhizae Decoction as adjunct therapy on the hemodynamics and myocardial enzymes of the patients with coronary arrhythmia after bifurcation lesion surgery
Peng WANG ; Jinghua HAN ; Dongna FAN
International Journal of Traditional Chinese Medicine 2022;44(7):754-758
Objective:To explore the effects of modified Fired Glycyrrhizae Decoction on hemodynamics and levels of myocardial enzymes in coronary arrhythmia (CA) after bifurcation lesion (BCL) surgery.Methods:According to simple random method, 100 patients with CA after BCL surgery in the hospital who met the inclusion criteria were divided into two groups between May 2019 and May 2021, 50 in each group. The control group was treated with intravenous drip of amiodarone and routine treatment, while the observation group was treated with modified Fired Glycyrrhizae Decoction on basis of control group. Both groups were treated for 2 weeks. Before and after treatment, TCM syndromes were scored. The quality of life was assessed by World Health Organization Quality of Life Scale (WHOOLQ-100). The plasma or serum specific viscosity, fibrinogen and ESR were detected by non-invasive hemodynamic detector. The levels of cardiac troponin (cTnT), creatine kinase (CK) and brain natriuretic peptide (BNP) were detected by ELISA. The disappearance time of symptoms was observed. The adverse reactions were recorded. And the clinical responsive effect was evaluated.Results:The difference in total response rate between observation group and control group was not statistically significant [92.0% (46/50) vs. 90.0% (45/50); χ2=0.12, P=0.727]. After treatment, scores of fluster and shortness of breath, panic and irritability, and mental fatigue in the observation group were significantly lower than those in the control group ( t=7.38, 9.88, 4.87, P<0.01), and scores of physical function, independence and social relations were significantly higher than those in the control group ( t=8.69, 6.32, 5.76, P<0.01). After treatment, levels of plasma specific viscosity, fibrinogen and ESR in the observation group were significantly lower than those in the control group ( t=13.59, 8.30, 8.80, P<0.01). After treatment, levels of serum cTnT [(33.45±3.44) mg/L vs. ( 39.71±4.02) mg/L, t=8.37], CK [(70.49±7.32) U/L vs. (82.15±8.41) U/L, t=7.40] and BNP [(223.41±20.36) ng/L vs. (244.58±20.74) ng/L, t=5.15] in the observation group were significantly lower than those in the control group ( P<0.01). The disappearance time of palpitation, chest tightness and dizziness in the observation group was significantly earlier than those in the control group ( t=10.44, 11.91, 5.75, P<0.01). During treatment, differences in incidence of adverse reactions between observation group and control group was statistically significant [4.0% (2/50) vs. 32.0% (16/50); χ2=4.00, P=0.046]. Conclusion:The modified Fired Glycyrrhizae Decoction combined with routine western medicine can improve clinical symptoms, hemodynamics and levels of myocardial enzymes in CA patients after BCL surgery, and improve the clinical curative effect.
7.The early diagnosis value of electrocardiographic characteristics in acute embolism in the pulmonary trunk and the main pulmonary arteries
Fan YANG ; Jinghua ZHANG ; Luosha ZHAO ; Fankai XIAO ; Tongwen SUN
Chinese Journal of Emergency Medicine 2017;26(7):790-794
Objective To investigate the abnormal characteristics of electrocardiogram and its early diagnostic value in acute pulmonary embolism (PE) of different positions.Methods A total of 147 hospitalized patients of acute PE diagnosed by the pulmonary artery CT angiography (CTA) were enrolled in this study and divided into the following two groups:pulmonary trunk or main pulmonary artery (MPA) embolism (group A) and lobar artery or remote branch embolism (group B).ECG,D-dimer,BNP,cTnT were collected and determined,the varieties of abnormal ECG were counted.Then,the relationships between the severities of the PEs at different positions and the corresponding ECG abnormalities as well as the degree of right ventricular hypertrophy (RVH) were analyzed.Results There were significant differences in dyspnea,syncope,in-hospital mortality and the level of cTnT,BNP between the two groups (P < 0.05).There were significant differences in the occurrence of SIQ Ⅲ T Ⅲ,right bundle branch block (RBBB),ST segment depression (STD) in leads Ⅲ and aVF,ST segment elevation (STE) in lead aVR,negative T waves (NTWs) in leads Ⅲ and aVF,STD in leads V1-V3/V6,and STE in leads V1-V3 in combination with STD in leads V4-V6 between the two groups (P < 0.05).The proportion of RVH diagnosed via ECG has significantly different between the two groups.The result of correlation analysis showed that the incidence of pulmonary trunk or MPA embolism was significantly related to the number of ECG abnormalities (r =0.782,t =-7.086,P < 0.05).Conclusions The number of abnormal ECGs increase and the RVH is more serious when PE occurring in pulmonary trunk as well as in the MPA,early recognition of electrocardiographic abnormalities is of greater value in the diagnosis of acute pulmonary trunk and MPA embolism.
8.Clinical research of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura
Jigang WANG ; Fan ZHOU ; Yanqin LIU ; Jinghua LIU ; Ying BAI ; Xianping XU ; Yuanli DONG ; Guanghan MENG ; Danjiang TONG
Chinese Journal of Postgraduates of Medicine 2016;(1):32-35
Objective To investigate the efficacy and safety of low-dose rituximab therapy and sequential maintenance for patients with refractory idiopathic thrombocytopenic purpura. Methods Thirty-three patients with refractory idiopathic thrombocytopenic purpura received intravenous rituximab at the dose of 100 mg once a week for 4 consecutive weeks. Complete blood cell count and serum concentrations of immunoglobulin (IgG,IgM and IgA) were monitored regularly. The numbers of CD3+ and CD19+ CD20+ lymphocyte cells were assayed by flow cytometry before and after therapy. Twenty-five patients with responses(complete response and response) were divided into maintained group (12 patients) and control group (13 patients) by random digits table method. The patients in maintained group were treated with rituximab 100 mg every 6 months. The efficacy of maintenance therapy was evaluated through long-term follow-up. Results The complete response(CR) rate, response (R) rate and no response(NR) rate were 48.48%(16/33), 27.27%(9/33) and 24.24% (8/33), respectively. As a result, total effective rate was 75.76% (25/33). There were no significant changes of peripheral blood white blood cell count,hemoglobin,serum immunoglobulin and CD3+lymphocyte counts before and after treatment (P>0.05). However, CD19+ CD20+ cells were almost depleted in patients treated with rituximab: (3.71±2.64)×106/L vs. (279.33±92.78)×106/L, P<0.01. Five patients suffered from allergic response, and 1 patient developed pneumonia and respiratory failure. The relapse rates of maintained group and control group were 1/12 and 4/13, respectively. Conclusions Treatment with low-dose rituximab may be an effective and safe approach in patients with idiopathic thrombocytopenic purpura. Relapse rates can be decreased through maintenance therapy with refractory low-dose rituximab. However, the optimal therapeutic schedule need further investigation.
9.Clinicopathological features and differential diagnosis of metanephric adenoma:a re-port of sixteen cases
Chenguang XI ; Yu FAN ; Xinyu YANG ; Libo LIU ; Jinghua WANG ; Shuai HU ; Yanyan LI ; Qun HE
Journal of Peking University(Health Sciences) 2016;48(4):598-602
Objective:To study the clinicopathological features and differential diagnosis of metaneph-ric adenoma (MA).Methods:The clinicopathological data of 16 cases with MA diagnosed and treated in Peking University First Hospital from 2004 to 2016 were retrospectively analyzed,and the clinical characteristics,pathologic parameters,differential diagnosis,treatment options and prognosis of MA were analyzed with literature review.Results:The patients included 10 females and 6 males.The age of pa-tients ranged from 14 to 83 years (mean =33.7 years).The partial nephrectomy was carried out for most patients.All cases were located in renal codex with 3 growing into the renal sinus.Histologically,the tumor was composed of tubules,papillary or glomeruloid structures and psammoma bodies were focally seen.Immunohistochemical study showed that all the cases expressed vimentin,and 94% cases ex-pressed CD57,63% WT1,75% AE1 /AE3,19% cytokeratin 7 (CK7 )and 13%α-methylacyl-CoA racemase (AMACR),and negative expressions for MA included CD10,neuron-specific enolase (NSE) and CD56.Follow-up information from 1 to 125 months was available in all the patients;and none of the patients showed any evidence of recurrence and metastasis.Conclusion:The benign tumor characteris-tics of MA are not obvious for preoperative imaging diagnosis,and the diagnosis of MA should be based on the unique pathological features.Positive immunostain of CD57 is a useful indicator for MA diagnosis and differential diagnosis.The partial nephrectomy surgical treatment can achieve good clinical cure with good prognosis.
10.T-cell immune tolerance of HLA haploidentical donor induced by CTLA4Ig-modified bone marrow stromal cells
Jigang WANG ; Fan ZHOU ; Yanqin LIU ; Ying BAI ; Jinghua LIU ; Haiting ZHANG ; Minyan LI
Chinese Journal of Tissue Engineering Research 2015;(1):12-17
BACKGROUND:CTLA-4Ig as a tolerance-induction agent is a potential strategy in graft-versus-host disease prevention. OBJECTIVE:To investigate the efficacy of CTLA4Ig-gene-modified bone marrow stromal cels mediated by adenovirus to induce T-cel tolerance of haploidentical donors. METHODS: The bone marrow stromal cels isolated culture from the bone marrow of HLA haploidentical donors were transfected by recombinant adenovirus encoding CTLA4IgcDNA (AdCTLA4Ig) at a multiplicity of infection=50 for 72 hours. The expression rate and the location of CTLA4Ig in the transfected cels were detected by fluorescence microscope after immunofluorescence staining. CTLA4Ig-modified bone marrow stromal cels (2×104, 4×104and 8×104) were respectively co-cultured with 105 T cels from the peripheral blood of HLA haploidentical donors and 105 peripheral blood mononuclear cels from recipients. The proliferative inhibition rate was determined by MTT assay, and the level of interleukin-2 in the supernatant was detected by ELISA. The bone marrow mononuclear cels (1×105/wel) were co-cultured with CTLA4Ig-modified bone marrow stromal cel layers constructed in 6-wel plates. The number of bone marrow mononuclear cels and colony-forming unit-granulocyte macrophages were calculated after 5-day culture. RESULTS AND CONCLUSION: The expression rate of CTLA4Ig at the multiplicity of infection=50 was as high as 85%, and the immunofluorescence signals of CTLA4Ig were distributed unevenly in the cytoplasm. The inhibition rates of 2×104, 4×104, and 8×104 CTLA4Ig-modified bone marrow stromal cels on proliferation of T cels were higher than that of untransfected cels. The levels of interluekin-2 in the corresponding cel groups were significantly lower than that in the untransfected cels (P < 0.05). At 5 days of culture, there was no significant difference in the number of bone marrow mononuclear cels and colony-forming unit-granulocyte macrophages between the transfected and untransfected cel groups (P > 0.05). These findings indicate that CTLA4Ig-modified bone marrow stromal cels mediated by adenovirus can induce immune tolerance of T-lymphocyte from HLA haploidentical donors in vitro.

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