1.Establishment of primary breast cancer cell line as new model for drug screening and basic research
Xian HAO ; Jianjun HUANG ; Wenxiu YANG ; Jinting LIU ; Junhong ZHANG ; Yubei LUO ; Qing LI ; Dahong WANG ; Yuwei GAO ; Fuyun TAN ; Li BO ; Yu ZHENG ; Rong WANG ; Jianglong FENG ; Jing LI ; Chunhua ZHAO ; Xiaowei DOU
China Oncology 2024;34(6):561-570
Background and purpose:In 2016 the National Cancer Institute(NCI)decided stopping to use NCI-60 cell lines for drug screening,suggesting that tumor cell lines were losing their value as a tool for drug discovery and basic research.The reason for NCI-60 cells'retirement'was that the preclinical studies based on traditional cellular and animal models did not obtain the corresponding expected efficacy in clinical trials.Since the major cancer behaviors,such as proliferation and metastasis,are fundamentally altered with long-term culture,the tumor cell lines are not representative of the characteristics of cancer in patients.Currently,scientists hope to create a new cancer model that are derived from fresh patient samples and tagged with details about their clinical past.Our purpose was to create patient-derived breast cancer primary cell lines as new cancer model for drug screening and basic research.Methods:Breast cancer tissues were collected in the Department of Breast Surgery,Affiliated Hospital of Guizhou Medical University.The collection of tumor tissue samples was approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University(approval number:2022 ethics No.313),and the collection and use of tumor tissues complied with the Declaration of Helsinki.The primary breast cancer cell lines were isolated from the patient's breast cancer tissues and cultured in BCMI medium.After the cells proliferated,the media were replaced with DEME medium.Cell line STR genotyping was done to determine cell-specific genetic markers and identification.Clone formation assay and transplantation assay were done to analyze the ability of breast cancer primary cell lines to form tumors.Results:We created 6 primary breast cancer cell lines.The 6 primary breast cancer cell lines from the patients were tagged with the definitively clinicopathological features,clinical diagnosis,therapeutic regimens,clinical effectiveness and prognostic outcomes.The STR genotyping assays identified the genetic markers and determined the identities of the 6 primary breast cancer cell lines.Clone formation assays and transplantation assay showed that the proliferative capacities of the patient-derived primary breast cancer cell lines were significantly greater compared with the conventional breast cancer cell lines.Conclusion:We created a panel of 6 patient-derived primary breast cancer cell lines as new cancer model for drug screening and basic research in breast cancer.
2.Diagnostic significance of serum chemokine CXCL-10 and Krebs von den lungen-6 level in patients with rheumatoid arthritis associated interstitial lung disease.
Rui YAN ; Dan KE ; Yan ZHANG ; Li LI ; Huanran SU ; Wei CHEN ; Mingxia SUN ; Xiaomin LIU ; Liang LUO
Journal of Peking University(Health Sciences) 2024;56(6):956-962
OBJECTIVE:
To detect the serum level of chemokine CXC motif chemokine 10 (CXCL-10) and Krebs von den lungen-6 (KL-6) in patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD), and to analyze their correlation with RA-ILD, as well as the significance in RA-ILD.
METHODS:
A total of 169 RA patients were enrolled in the study. According to imaging findings of with and without ILD in high-resolution computed tomography scans of chest, the subjects were divided into RA-ILD group and RA-non-ILD group. According to the inclusion and exclusion criteria, 80 patients in each of the two groups were finally selected. Two groups were matched according to the 1 ∶ 1 ratio using propensity score matching (PSM). The serum CXCL-10 and KL-6 levels were detected by enzyme-linked immunosorbent assay. The clinical features, laboratory data and medications between the two groups were compared after PSM and the correlation between serum levels and clinical parameters were analyzed. Binary Logistic regression was used to analyze the risk factors of ILD in the RA patients, and the predictive value of CXCL-10 and KL-6 in RA-ILD was evaluated.
RESULTS:
In this study, 49 patients with RA-ILD and 49 patients with RA-non-ILD were selected by PSM. The levels of CXCL-10 and KL-6 in the RA-ILD group [64.36 (34.01, 110.18) ng/L, 360.70 (236.35, 715.05) U/mL] were significantly higher than those in the RA-non-ILD group [29.80 (16.89, 40.55) ng/L, 210.69 (159.98, 255.50) U/mL] (all P < 0.001). The results of correlation analysis showed that the level of serum CXCL-10 was positively correlated with the Warrick score on chest CT (r=0.378, P=0.007) and negatively correlated with the percentage of forced vital capacity to the predicted value (FVC%, r=-0.338, P=0.018). And the level of KL-6 was positively correlated with rheumatoid factor (RF, r=0.296, P=0.039) and negatively correlated with FVC% (r=-0.436, P=0.002) and the percentage of diffusion capacity for carbon monoxide to the predicted value (DLCO%, r=-0.426, P=0.002). Both univariate and multivariate Logistic regression analysis showed that CXCL-10 and KL-6 were positively correlated with ILD, the values of OR were 1.035 and 1.023 in CXCL-10 and those were 1.004 and 1.005 in KL-6 respectively (P < 0.05). The ROC curves were plotted with CXCL-10 and KL-6. The area under the curve (AUC) was 0.770 and 0.752 respectively. The AUC of combined detection increased to 0.800.
CONCLUSION
Serum levels of CXCL-10 and KL-6 are significantly elevated in patients with RA-ILD and correlated with the severity of ILD. The combined estimate of them helps to improve the effectiveness of diagnosis.
Humans
;
Lung Diseases, Interstitial/etiology*
;
Arthritis, Rheumatoid/complications*
;
Chemokine CXCL10/blood*
;
Mucin-1/blood*
;
Female
;
Male
;
Tomography, X-Ray Computed
;
Risk Factors
;
Middle Aged
3.Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease.
Fang Ning YOU ; Liang LUO ; Xiang Jun LIU ; Xue Wu ZHANG ; Chun LI
Journal of Peking University(Health Sciences) 2023;55(6):1045-1052
OBJECTIVE:
To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).
METHODS:
This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.
RESULTS:
There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.
CONCLUSION
Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.
Pregnancy
;
Infant, Newborn
;
Female
;
Humans
;
Pregnancy Outcome
;
Retrospective Studies
;
Abortion, Spontaneous/etiology*
;
Undifferentiated Connective Tissue Diseases
;
Pre-Eclampsia/epidemiology*
;
Lupus Erythematosus, Systemic
;
Risk Factors
;
Leukopenia
;
Pregnancy Complications/epidemiology*
;
Disease Progression
;
Connective Tissue Diseases/epidemiology*
4.The relationship between socioeconomic status and childhood overweight/obesity is linked through paternal obesity and dietary intake: a cross-sectional study in Chongqing, China.
Jingyu CHEN ; Shunqing LUO ; Xiaohua LIANG ; Yetao LUO ; Rina LI
Environmental Health and Preventive Medicine 2021;26(1):56-56
BACKGROUND:
The prevalence of obesity and overweight in childhood has increased dramatically over the past decades globally. Thus, the risk factors of overweight and obesity in children and adolescents must be studied.
OBJECTIVES:
This study aimed to reveal the prevalence of childhood obesity and examine the relationship between socioeconomic status (SES) and z-body mass index (z-BMI) via parental obesity and dietary intake using path analysis.
METHODS:
Stratified cluster sampling was used to select 17,007 participants aged 6-12 years on two avenues per region in urban, suburban, and rural areas. Path analysis was conducted to examine the mediators between SES and z-BMI.
RESULTS:
The prevalence rates of overweight and obesity were 13.36% and 8.60%, respectively, and were positively correlated with the father's education level, family income, a birth weight > 3000g, a parental obesity history, vegetable intake and red meat intake (all P < 0.05). Four mediators (paternal obesity history, red meat intake, vegetable intake, and nutritional supplements) were observed, and the four path analyses were significant (all P < 0.05). The adjusted total effects on z-BMI were significant for income (β
CONCLUSIONS
The prevalence of overweight/obesity in children was notable, and the relationship between SES and z-BMI was mediated by paternal obesity history and dietary intake.
Child
;
China/epidemiology*
;
Cross-Sectional Studies
;
Eating/psychology*
;
Fathers/statistics & numerical data*
;
Female
;
Humans
;
Male
;
Obesity/psychology*
;
Pediatric Obesity/etiology*
;
Social Class
5. Meta-analysis of duct-to-mucosa and invagination of pancreaticoduodenectomy
Chuanyou WU ; Tao LUO ; Jianping GONG ; Shengwei LI
International Journal of Surgery 2020;47(1):23-27,f3-f4
Objective:
To systematically evaluate the surgical effect in duct-to-mucosa and invagination groups of pancreaticojejunostomy after pancreaticoduodenectomy.
Methods:
The Cochrane Library, PubMed, EMbase and CBM data bases were searched to identify randomized controlled trials that compared the postoperative pancreatic fistula, mortality, incidence of complications, delayed gastric emptying, postoperative haemorrhage, infection, reoperate rate, postoperative hospital stay of duct-to-mucosa and invagination for pancreaticcoduodenectomy. Meta-analysis was performed using the software RevMan 5.3.
Results:
Nine trials with 1 163 patients comparing the duct-to-mucosa group with invagination group were included, the duct-to-mucosa group with 579 patients and the invagination group with 584 patients. The meta-analysis revealed that, compared the duct-to-mucosa group with the invagination group, the rate of postoperative pancreatic fistula was not significantly reduced (

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