Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective: To investigate the prospective effects of the consumption of protein and animal foods before menarche on the age at menarche among Chinese girls. Methods: This paper was based on the data collected in the China Health and Nutrition Survey(CHNS) from 1997 to 2015. A total of 683 girls aged 6 and over who had completed information on age at menarche, height, weight, per capita annual household income, maternal education level and participated in at least one complete dietary survey within 1 to 4 years before menarche were included. Urban-rural stratified multivariable linear regression model was used to examine the effects of protein and animal foods intake before menarche on Chinese girls age at menarche in urban and rural areas. Results: After adjusted for total energy intake, body mass index standard deviation score and per capita annual household income, the consumption of meat before menarche was negatively associated with the age at menarche among rural Chinese girls(B=-0.003, P=0.00), but not among urban Chinese girls(B=0.002, P>0.05). Total protein, dairy, eggs and aquatic products intake before menarche were not associated with Chinese girls age at menarche in urban and rural areas(B=0.002, -0.001, 0.003, 0.000; 0.001, 0.001, -0.001, -0.003, P>0.05). Conclusion Higher intake of meat before menarche might lead to earlier menarche onset in rural Chinese girls. The consumption of total protein, dairy, eggs, and aquatic products before menarche did not affect the age at menarche in Chinese girls.

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95% CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95% CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.

Based on the data from China Health and Nutrition Survey (CHNS), 840 girls aged 6-15 years who had information about menarche and participated in dietary survey at least once within 1-5 years before onset of menarche between 1989 and 2015 were included in the study. The median age at baseline of the 840 participants was 10 (9, 11) years. The median age at menarche of the participants was 13 (12, 14) years. After adjusting for the age of birth, place of residence, body mass index Z-score, physical activity level and annual household income per capita, the average age of menarche was advanced by 0.036 (95% CI: -0.068, -0.004) years for every 10 g increase in daily fat intake before menarche. The average age at menarche was 0.008 (95% CI: -0.014, -0.001) years earlier for every 1% increase in the daily energy supply ratio of fat before menarche.

Objective: To investigate the impact of type 2 diabetes mellitus on progression and revascularization of coronary non-target lesions in patients with coronary heart disease. Methods: From January 2010 to September 2014, we retrospectively analyzed the clinical data of patients with coronary heart disease who underwent two consecutive coronary angiographies at Fuwai Hospital. At least one coronary non-target lesion was recorded at the first procedure in these patients. Patients were grouped according to the diagnose of type 2 diabetes mellitus. Demographic features, risk factors of coronary heart disease, laboratory results as well as characteristics of coronary non-target lesions were collected at baseline (first coronary angiography) and follow-up (second coronary angiography). Lesion progression was defined by quantitative coronary angiography analysis. Lesions revascularization was recorded. Multivariable Cox regression analysis was used to define the impacts of diabetes mellitus on progression and revascularization of non-target lesions. Subgroup analysis in diabetic and non-diabetic groups were further performed. Receiver operating characteristics curve was used to identify the predictive value of HbA1c. Results: A total of 1 255 patients were included, and 1 003(79.9%) were male, age was(58.0±9.7) years old. And 486 patients were diagnosed with type 2 diabetes mellitus. Follow-up time was (14.8±4.5) months. Compared with non-diabetic group, diabetic group were older with less male and had higher BMI index as well as higher prevalence of hypertension, dyslipidemia, prior myocardial infarction and prior percutaneous coronary intervention(all P<0.05). Diabetic patients also had higher level of white blood cells, erythrocyte sedimentation rate, C-reactive protein, endothelin and HbA1c at both baseline and follow-up compared with non-diabetic patients (all P<0.01). There was no significant difference on progression of non-target lesions (20.0%(97/486) vs. 18.5%(142/769), P=0.512), revascularization of non-target lesions (13.2%(64/486) vs. 15.9%(122/769), P=0.190) and non-target lesion related myocardial infarction(1.9%(9/486) vs. 1.3%(10/769), P=0.436) between diabetic and non-diabetic patients. Multivariable Cox regression analysis revealed that diabetes mellitus was not an independent predictor for progression and revascularization of non-target lesions (Both P>0.05). Subgroup analysis in diabetic patients showed that baseline HbA1c level(HR=1.160, 95%CI 1.009-1.333, P=0.037) was an independent predictor for non-target lesion progression. Cut-off value of HbA1c was 6.5% (Area Under Curve(AUC) 0.57, specificity 88.7%; sensitivity 24.2%, P=0.046) by receiver operating characteristics curve. Patients with HbA1c level above 6.5% had 2.8 times higher risk of lesion progression compared with patients with HbA1c level below 6.5% (HR=2.838, 95%CI 1.505-5.349, P=0.001). Compared with non-diabetic patients, diabetic patients with HbA1c below 6.5% also had lower risk of lesion progression (HR=0.469, 95%CI 0.252-0.872, P=0.012). ST-segment elevated myocardial infarction was an independent predictor for revascularization of non-target lesions in diabetic patients. Conclusion: Type 2 diabetes mellitus is not an independent predictor for progression and revascularization of coronary non-target lesions in patients with coronary heart disease. However, elevated HbA1c level is a risk factor for progression of non-target lesion in patients with type 2 diabetes mellitus.
Aged ; Coronary Angiography ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/complications* ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; Retrospective Studies ; Risk Factors ; Treatment Outcome

BACKGROUND: Coronary atherosclerotic plaque could go through rapid progression and induce adverse cardiac events. This study aimed to evaluate the impacts of smoking status on clinical outcomes of coronary non-target lesions. METHODS: Consecutive patients with coronary heart disease who underwent two serial coronary angiographies were included. All coronary non-target lesions were recorded at first coronary angiography and analyzed using quantitative coronary angiography at both procedures. Patients were grouped into non-smokers, quitters, and smokers according to their smoking status. Clinical outcomes including rapid lesion progression, lesion re-vascularization, and myocardial infarction were recorded at second coronary angiography. Multivariable Cox regression analysis was used to investigate the association between smoking status and clinical outcomes. RESULTS: A total of 1255 patients and 1670 lesions were included. Smokers were younger and more likely to be male compared with non-smokers. Increase in percent diameter stenosis was significantly lower (2.7 [0.6, 7.1] % vs. 3.5 [0.9, 8.9]%) and 3.4 [1.1, 7.7]%, P = 0.020) in quitters than those in smokers and non-smokers. Quitters tended to have a decreased incidence of rapid lesions progression (15.8% [76/482] vs. 21.6% [74/342] and 20.6% [89/431], P = 0.062), lesion re-vascularization (13.1% [63/482] vs. 15.5% [53/432] and 15.5% [67/431], P = 0.448), lesion-related myocardial infarction (0.8% [4/482] vs. 2.6% [9/342] and 1.4% [6/431], P = 0.110) and all-cause myocardial infarction (1.9% [9/482] vs. 4.1% [14/342] and 2.3% [10/431], P = 0.128) compared with smokers and non-smokers. In multivariable analysis, smoking status was not an independent predictor for rapid lesion progression, lesion re-vascularization, and lesion-related myocardial infarction except that a higher risk of all-cause myocardial infarction was observed in smokers than non-smokers (hazards ratio: 3.00, 95% confidence interval: 1.04-8.62, P = 0.042). CONCLUSION Smoking cessation mitigates the increase in percent diameter stenosis of coronary non-target lesions, meanwhile, smokers are associated with increased risk for all-cause myocardial infarction compared with non-smokers.

OBJECTIVE: To analyze the effect of serum free light chain (sFLC) on renal function and prognosis in patients with newly diagnosed multiple myeloma (MM). METHODS: The clinical data of 70 newly diagnosed MM patients who received sFLC examination in Fujian Medical University Union Hospital were retrospectively analyzed from April 2012 to November 2016. Univariate analysis was used to analyze the risk factors that associated with renal impairment (RI) and prognosis. Logistic regression and Kaplan-Meier analyze were used to analyze the roles of sFLC in RI and the prognosis. RESULTS: Out of the 70 patients, 20 patients had RI at the initial diagnosis. Compared to normal renal function group, RI group had lower level of hemoglobin, elevated levels of serum uric acid, corrected calcium, serum creatinine, serum β2 microglobulin, and involved sFLC, higher proportion of patients with ISS stage III, involved sFLC≥500 mg/L, hemodialysis (all P＜0.05). Multivariate logistic regression analysis showed that serum uric acid≥430 μmol/L, ISS stage III and a involved sFLC≥500 mg/L were all the independent risk factors for RI in patients with newly diagnosed MM patients (all P＜0.05). Receiver operating characteristic (ROC) curves analysis showed that the involved sFLC was 705.0 mg/L, which was a best cut-off value area under curve (AUC) for prediting RI in patients with MM was 0.727 (P=0.003), sensitivity was 65.0% and specificity was 82.0%). After a median follow-up period of 31 (1-84) months, the median overall survival (OS) of patients with involved sFLC≥500mg/L and involved sFLC＜500 mg/L were 52.0 and 27.0 months, respectively, there was no statistically significant difference (P=0.137). There was also no statistically significant difference in median OS between the high sFLC ratio group (κ/λ＞32 or ＜0.03) and the low sFLC ratio group (0.03≤κ/λ≤32) (27 months vs 40 months, P=0.436). CONCLUSION The involved sFLC in the RI group is significantly higher than that in the normal renal function group in newly diagnosed MM patients. Serum uric acid≥430 μmol/L, ISS stage III and involved sFLC≥500 mg/L are the independent risk factors for RI. Monitoring sFLC in newly diagnosed MM patients is helpful to the prediction of RI, and the involved sFLC level or sFLC ratio may not affect the prognosis of newly diagnosed MM patients.
Humans ; Immunoglobulin Light Chains ; Multiple Myeloma ; Prognosis ; Retrospective Studies ; Uric Acid

Objective: To examine the association of pre-pregnancy body mass and weight gain during pregnancy with macrosomia. Methods: From January 2015 to December 2015, a total of 20 477 pregnant women were recruited by probabilistic proportional scale sampling with simple randomization in Sichuan, Yunnan and Guizhou Provinces. Basic information of pregnant women, weight gain during pregnancy and weight of newborn were collected. A multiple logistic regression model was used to assess the association between the pre-pregnancy body mass and gestational weight gain indicators with macrosomia. Results: 20 321 mother-infant were included in the final analysis. 20 321 pregnant women were (30.09±4.10) years old and delivered at (39.20±1.29) weeks, among which 12 341 (60.73%) cases were cesarean delivery. The birth weight of 20 321 infants were (3 292.26±431.67) grams, and 970 (4.77%) were macrosomia. The multiple logistic regression model showed that after adjusting for the age of women, compared to the normal weight group in the pre-pregnancy, the overweight and obesity group elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.69−2.35) and 4.05 (95%CI: 3.05−5.39), respectively. After adjusting for the age, the pre-pregnancy BMI, delivery weeks, delivery mode and infant′s gender, compared to the weight-gain appropriate group, higher weight gain rate in the mid-pregnancy and excessive total gestational weight gain elevated the risk of macrosomia, with OR (95%CI) about 1.99 (95%CI: 1.66−2.39) and 1.80 (95%CI: 1.55−2.08), respectively. Conclusion The overweight before pregnancy, obesity before pregnancy, the rate of weight gain in the second trimester and the high total weight gain during pregnancy could increase the risk of macrosomia.