AIM:Chronic exposure to elevated levels of free fatty acids (FFAs) in type 2 diabetes patients is toxic to pancreatic β-cells.Thioredoxin (Trx)-interacting protein (TXNIP), an endogenous Trx-inhibiting protein, is up-regulated by glucose and is a critical mediator of hyperglycemia-induced β-cell apoptosis in diabetes.However, the effects of FFAs on TXNIP are unknown.In this experiment we observed the effect of palmitate on TXNIP expression in cultured INS-1 islet cells and the pathways involved were analyzed meanwhile.METHODS:After the full basis of preliminary experiment of incubating INS-1 cells with palmitate at different concentrations for different time, INS-1 islet cells were cultured with 0.5 mmol/L palmitate for 24 h.TXNIP expression, cell apoptosis, and expression of transcription factors related to TXNIP transcriptional regulation were determined.RESULTS:Compared with control group, the expression of TXNIP at mRNA and protein levels in palmitate group was significantly up-regulated (P<0.01).Cleaved caspase-3/caspase-3 ratio was increased in palmitate group (P<0.05), and the apoptosis of the INS-1 cells was also significantly increased (P<0.01).Palmitate enhanced the phosphorylation of nuclear factor-κB (NF-κB) (P<0.01), and the NF-κB inhibitors, PDTC and SN50, both blocked the palmitate-induced up-regulation of TXNIP expression.CONCLUSION:Saturated fatty acid palmitate enhances the expression of TXNIP.The mechanism of palmitate-induced TXNIP expression may be associa-ted with the increase in NF-κB phosphorylation.

Objective: This study conducted a tobacco control intervention practice on vocational school students based on social cognitive theory, for exploring the practical and feasible tobacco control strategies among students, so as to reduce adolescents’ smoking behaviors. Methods: Cluster random sampling method was used to select students in four vocational schools in Shanghai, which were randomly divided into the intervention group (2 schools 1 003 students) and the control group (2 schools 1 096 students). The intervention was conducted on the intervention group based on the social cognitive theory and lasted for 6 months. The control group was blank. Descriptive and analytical statistical methods were used to evaluate the effect of intervention. Results: After the intervention, in the intervention group, the current smoking rate (2.77%) and the smoking intention in the next 1 year (8.50%) both decreased, the scores of the cognition of the harm of smoking as well as second hand smoking and the attitudes towards tobacco all increased(39.04%, 32.93%), the self-efficacy of refusing smoking increased (88.93%), the social pressure decreased(12.40%), the exposure rate of secondhand smoke in family decreased(35.45%), and the exposure to tobacco control message on media increased (36.68%). The difference was statistical significant compared to the control group (χ2=8.67，19.32，17.87，8.32，13.51，14.71，17.36，20.09，P<0.01). Conclusion The tobacco control model based on social cognitive theory could effectively improve adolescents’ self-efficacy, increase their tobacco-related knowledge, and significantly reduce their future smoking intention and behavior.

Objective:To analyze the changing trends in maternal mortality ratios (MMRs) and the main cause-specific MMRs in China from 2010 to 2020, evaluate the association between MMRs and pregnancy healthcare and predict the MMRs for the next five years.Methods:Data on MMRs, the main cause-specific MMRs, and maternal healthcare in China from 2010 to 2020 were collected from China Health Statistical Yearbook. Estimated annual percent changes (EAPCs) were used to analyze the trends in MMRs and the main cause-specific MMRs in China. Average growth rate was used to describe the trend of perinatal healthcare indicators, and spearman rank correlation was used to analyze the correlation between MMRs and perinatal healthcare indicators. GM (1,1) model was established to predict the MMRs for the following five years. Results:(1) From 2010 to 2020, the EAPCs were－5.16%,－6.24%, and－4.28%, respectively, indicating downward trends in MMRs in the whole nation, urban and rural areas ( t=－0.98,－12.42 and－8.96, all P<0.001). (2) From 2010 to 2020, the main cause-specific MMRs in China from obstetric hemorrhage, hypertension during pregnancy, amniotic fluid embolism, and liver disease were all in downward trends ( t=－12.42,－5.44,－3.98 and－3.63, all P<0.001). Except for the MMR from hypertension during pregnancy in urban areas (average growth rate =0.51%), all main cause-specific MMRs in both urban and rural areas decreased significantly, especially the MMRs from hepatopathy in urban and rural areas (average growth rate=－10.40% and－13.96%). (3) The nation wide MMR was negatively correlated with maternal system management rate ( r s=－0.80, P=0.003), prenatal examination rate ( r s=－0.97, P<0.001), postpartum visit rate ( r s=－0.82, P=0.002) and hospital delivery rate ( r s=－0.98, P<0.001). Negative correlations were also found between the MMR and hospital delivery rate in both urban ( r s=－0.82, P=0.002) and rural areas ( r s=－0.95, P<0.001). (4) The GM (1, 1) models for forecasting MMRs in the whole nation, urban and rural areas were established with an accuracy of level 1. The MMR was predicted to show a downward trend in the following five years. The MMRs in China were 15.86/100 000 in 2021 and 15.13/100 000 in 2022 through prediction, similar to the 16.1/100 000 and 15.7/100 000 as announced by the government. Conclusions:The overall MMR in China shows a downward trend, and it dropped faster in urban areas than the rural areas. In addition, it is predicted that the MMR will continue to decline in the following five years, but the gap between urban and rural areas will remain.

PURPOSE: The purpose of this study was to investigate the changes of tumor infiltrating lymphocytes (TILs) between core needle biopsy (CNB) and surgery removed sample (SRS) in early stage breast cancer patients and to identify the correlating factors and prognostic significance of TILs changes. MATERIALS AND METHODS: A retrospective study was carried out on 255 patients who received CNB and underwent surgical resection for invasive breast cancer. Stromal TILs levels of CNB and SRS were evaluated respectively. Tumors with ≥50% stromal TILs were defined as lymphocyte-predominant breast cancer (LPBC). Clinicopathological variables were analyzed to determine whether there were factors associated with TILs changes. Log-rank tests and Cox proportional hazards models were used to analyze the influences of TILs and TILs changes on survival. RESULTS: SRS-TILs (median, 10.0%) were significant higher than CNB-TILs (median, 5.0%; p<0.001). Younger age (<60 years, p=0.016) and long surgery time interval (STI, ≥4 days; p=0.003) were independent factors correlating with higher TILs changes. CNB-LPBC patients showed better breast cancer-free interval (BCFI, p=0.021) than CNB-non-LPBC (CNB-nLPBC) patients. Patients were categorized into four groups according to the LPBC change pattern from CNB to SRS: LPBC→LPBC, LPBC→nLPBC, nLPBC→LPBC, and nLPBC→nLPBC, with estimated 5-year BCFI 100%, 100%, 69.7%, and 86.0% (p=0.016). nLPBC→LPBC pattern was an independent prognostic factor of worse BCFI (hazard ratio, 2.19; 95% confidence interval, 1.06 to 4.53; p=0.035) compared with other patterns. CONCLUSION: TILs were significantly higher in SRS than in CNB. Higher TILs changes were associated with younger age and long STI. Changing from nLPBC to LPBC after CNB indicated a worse BCFI, which needs further validation.
Biopsy, Large-Core Needle ; Breast Neoplasms ; Breast ; Humans ; Lymphocytes, Tumor-Infiltrating ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Sexually Transmitted Diseases

Breast cancer is a heterogeneous disease. The formation and progression of tumor and the sensitivity to treatment differs from patient to patient. In addition to the widely used molecular subtype, novel markers are needed to better personalize the treatment of breast cancer. Tumor infiltrating lymphocyte (TIL) have been consistently documented in breast cancer lesions especially in triple negative and human epidermal growth factor receptor-2 positive breast cancer. Several clinical trials have revealed that TIL are associated with prognosis and can predict therapeutic efficacy of special therapy. TIL could be divided to different subtypes including CD8 + TIL, CD4 + TIL, cytotoxic T lymphocyte-associated antigen-4 + TIL, programmed death-1 + TIL. They play different roles in the process of anti-tumor immunity and can predict different prognosis. Screening out special TIL subtype which is well associated with prognosis and therapeutic efficacy and developing targeting immunotherapy can help to improve outcomes of breast cancer patients.
Breast Neoplasms ; diagnosis ; immunology ; Humans ; Lymphocytes, Tumor-Infiltrating ; classification ; cytology ; Prognosis

The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a "switch" type regulator. We identified through immunoprecipitation-mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Ovarian Neoplasms ; Phosphatidylinositol 3-Kinases ; Proteomics ; Repressor Proteins ; TOR Serine-Threonine Kinases ; Tacrolimus Binding Proteins

As a standard component in medical education in many countries, standardized patients have become professionals who provide valuable opportunities for training and evaluation of clinical skills among medical students and physicians. This paper reviewed the application of standardized patients in health care, discussed its advantages and disadvantages, and advocated continuation of in-depth research on standardized patients in China, and acceleration in the establishment of a formal system of standardized patients in medical education and health systems, so as to improve the quality of medical care.

OBJECTIVESTo study the factors influencing the non-sentinel lymph node(NSLN) status and to assess performance of Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram in predicting sentinel lymph node(SLN) metastases in a SLN positive Chinese breast cancer population.

METHODSData were collected from breast cancer patients who were diagnosed with pathological positive sentinel lymph node and received further axillary lymph node dissection(ALND) in Shanghai Ruijin Hospital from January 2011 to August 2014. MSKCC nomogram was used to calculate each patient's NSLN metastasis risk score. The receiver operator characteristic curve (ROC curve) and the area under the ROC curve (AUC) was used to assess the predictive accuracy of the model.

RESULTSAmong the 1 147 patients who received sentinel biopsy, 150 SLN positive patients who received ALND were enrolled in this study. By univariate analysis, multifocal breast cancer (χ(2)=5.887, P=0.015), SLN+ /SLN ratio (χ(2)=6.683, P=0.010) and abnormal axillary lymph node displayed by ultrasound (χ(2)=7.736, P=0.005) were the influencing factors of NSLN metastases. By multivariate analysis, multifocal breast cancer (OR=7.25, 95% CI: 1.73 to 30.43, P=0.007), SLN+ /SLN ratio ≥ 0.5 (OR=2.564, 95% CI: 1.22 to 5.39, P=0.013) and abnormal axillary lymph node displayed by ultrasound (OR=2.471, 95% CI: 1.18 to 5.19, P=0.017) were the independent influencing factors of NSLN metastases. The AUC of MSKCC nomogram in this population was 0.677.

CONCLUSIONSFor breast cancer patients with positive sentinel lymph node, multifocality, SLN+ /SLN ratio and axillary lymphadenopathy displayed by ultrasound is related to NSLN metastasis. MSKCC has low accuracy in predicting NSLN status of this population.

Area Under Curve ; Axilla ; Breast Neoplasms ; China ; Humans ; Lymph Node Excision ; Lymph Nodes ; Lymphatic Metastasis ; Multivariate Analysis ; Nomograms ; ROC Curve ; Risk Factors ; Sentinel Lymph Node Biopsy

Objective:To investigate the predictive value of serum D-dimer combined with myocardial injury markers on admission for early identification of high-risk patients with acute myocarditis.Methods:Patients hospitalized for acute myocarditis in China-Japan Friendship Hospital were retrospectively enrolled from 2010 to 2021. Patients were divided into the high D-dimer level group and low D-dimer level group according to the median value of D-dimer measured by immunoturbidimetry within 24 h of admission. In-hospital adverse events were defined as death, cardiogenic shock, malignant ventricular arrhythmia and new-onset heart failure. Multivariate logistic analysis was used to explore the independent predictors of in-hospital adverse events, and receiver operating characteristic curve was used to evaluate the predictive value.Results:A total of 106 patients were analyzed, including 52 high level D-dimer patients and 54 low level D-dimer patients, with an average age of (36±16) years, and 62.3% were male. Compared with the low D-dimer level group, patients in the high D-dimer level group had lower mean systolic blood pressure [(114±21) mmHg vs. (121±14) mmHg] and diastolic blood pressure [(71±13) mmHg vs. (76±10) mmHg], higher heart rate [(97±26) beats/min vs. (79±15) beats/min], higher C-reactive protein levels [6.82 (1.61, 20.05) mg/dL vs. 1.30 (0.13, 8.93) mg/dL] and creatinine levels [86.95 (67.63, 117.83) μmol/L vs. 68.80 (60.18, 81.93) μmol/L] on admission. The proportion of patients having QRS interval >120 ms on electrocardiogram was higher in high D-dimer level group (25.0% vs. 7.4%). There was no significant difference in patients with positive myocardial injury biomarkers between the two groups. The incidence of in-hospital adverse events was higher in the high D-dimer level group (67.3% vs. 22.2%, P<0.001). Multivariate logistic analysis showed that serum D-dimer levels and elevated myocardial injury markers on admission were independently associated with in-hospital adverse events. The area under the curve (AUC) of elevated serum D-dimer level on admission for predicting in-hospital adverse events was 0.781 (95% CI: 0.690-0.873), the sensitivity was 74.5%, and the specificity was 71.2%. When combined with positive cardiac biomarkers, the AUC was 0.831 (95% CI: 0.752-0.910) with a sensitivity of 80.9% and a specificity of 78.0%. Conclusions:Elevated D-dimer level on admission can predict the risk of in-hospital adverse events in patients with acute myocarditis. The combination of cardiac injury biomarkers can improve the predictive value.

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.