LncRNA SEMA3B-AS1 suppresses the tumor-initiating characteristics of triple negative breast cancer via engaging in MLL4-mediated H3K4 trimethylation.

Long noncoding RNAs (lncRNAs) are crucial regulators of tumor-initiating cells (TICs) and hold particular importance in triple negative breast cancer (TNBC). Yet, the precise mechanisms by which TIC-associated lncRNAs influence TNBC remain unclear. Our research utilized The Cancer Genome Atlas Breast Cancer (BC) data set to identify prognostic lncRNAs. We then conducted extensive assays to explore their impact on the tumor-initiating phenotype of TNBC cells and the underlying mechanisms. Notably, we found that low expression of lncRNA SEMA3B-AS1 correlated with unfavorable survival in BC patients. SEMA3B-AS1 was also downregulated in TNBC and linked to advanced tumor stage. Functional experiments confirmed its role as a TIC-suppressing lncRNA, curtailing mammosphere formation, ALDH + TIC cell proportion, and impairing clonogenicity, migration, and invasion. Mechanistic insights unveiled SEMA3B-AS1's nuclear localization and interaction with MLL4 (mixed-lineage leukemia 4), triggering H3K4 methylation-associated transcript activation and thus elevating the expression of SEMA3B, a recognized tumor suppressor gene. Our findings emphasize SEMA3B-AS1's significance as a TNBC-suppressing lncRNA that modulates TIC behavior. This study advances our comprehension of lncRNA's role in TNBC progression, advocating for their potential as therapeutic targets in this aggressive BC subtype.

M7G-Related lncRNAs predict prognosis and regulate the immune microenvironment in lung squamous cell carcinoma.

BACKGROUND: N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely studied in cancer and have been found to be useful for assessing tumor progression. However, the role of m7G-related lncRNAs in lung squamous cell carcinoma (LUSC) remains unclear. Thus, it is crucial to identify m7G-associated lncRNAs with definitive prognostic value. This study aimed to investigate the prognostic value, correlation with tumor mutation burden, and impact on the tumor immune microenvironment of m7G-related lncRNAs in LUSC.  METHODS: LUSC transcriptome data and clinical data were downloaded from The Cancer Genome Atlas, and an m7G-related lncRNA-mRNA co-expression network was constructed using Pearson's correlation analysis. Cox regression analyses were used to determine a risk model for m7G-associated lncRNAs with prognostic value. The risk signature was verified using the Kaplan-Meier method, receiver operating characteristic curve analysis, and principal component analysis. A nomogram based on risk scores and clinical characteristics was then developed. Gene set enrichment analysis was used for functional annotation to analyze the risk signature. The association among the risk signature, tumor mutational burden, and tumor-infiltrating immune cells was then analyzed. RT-qPCR was used to investigate the expression of 6 m7G-related lncRNAs in LUSC cells. The cytological function of SRP14-AS1 was verified by wound-healing assay and transwell assay. RESULTS: A total of 293 m7G-related lncRNAs were identifed, 27 candidate m7G-related lncRNAs were signifcantly associated with overall survival (OS). Six of these lncRNAs (CYP4F26P, LINC02178, MIR22HG, SRP14-AS1, TMEM99, PTCSC2) were selected for establishment of the risk model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p < 0.001). Multivariate cox regression analysis indicated that the model could be an independent prognostic factor for LUSC (HR = 1.859; 95% CI 1.452-2.380, p < 0.001). The ROC curve analysis revealed that the AUCs for OS in the 3-, and 5-year were 0.682, 0.657, respectively. GSEA analysis revealed that the risk model was closely related to immune-related pathways. Compared with normal lung epithelial cells, four m7G-related lncRNAs were higher expressed in cancer cells and two were lower expressed, among which knockdown of SRP14-AS1 promoted the proliferation and migration of LUSC cells. CONCLUSION: A risk model based on six m7G-related lncRNAs with prognostic value may be a promising prognostic tool in LUSC and guide individualized patient treatment.

The association between prothrombin time-international normalized ratio and long-term mortality in patients with coronary artery disease: a large cohort retrospective study with 44,662 patients.

BACKGROUND: The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. METHODS: We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 < PT-INR ≤ 1.01; Quartile3: 1.01 < PT-INR ≤ 1.06; Quartile4: PT-INR > 1.06). The main endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. RESULTS: During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 < PT-INR ≤ 1.01], aHR = 1.00, 95% CI 0.91-1.00, P = 0.99; Quartile 3 [1.01 < PT-INR ≤ 1.06], aHR = 1.10, 95% CI 1.01-1.20, P = 0.03; Quartile 4 [PT-INR > 1.06], aHR = 1.33, 95% CI 1.22-1.45, P < 0.05). CONCLUSIONS: Our study demonstrates high levels of PT-INR were associated with an increased risk of all-cause mortality.

Malnutrition in patients with coronary artery disease: Prevalence and mortality in a 46,485 Chinese cohort study.

BACKGROUND AND AIMS: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population. METHODS AND RESULTS: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention. CONCLUSIONS: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936.

Prevalence and mortality of transient acute kidney injury within 48 h, as new subtype, following coronary angiography: a cohort study.

BACKGROUND: The association of transient acute kidney injury (AKI) with mortality was controversial. Our study aims to investigate the prevalence and impact of transient AKI on mortality in patients following coronary angiography (CAG). METHODS: Our study retrospectively enrolled 3970 patients with pre-operative serum creatinine (Scr) and twice measurements within 48 h after procedure. Transient AKI defined as the diagnosis of AKI (Scr > 0.3 mg/dL or > 50% from the baseline level) on day 1 when Scr failed to meet the criteria for AKI on the day 2. Maintained AKI was defined as AKI not meeting the definition for transient AKI. The primary outcome was 1-year all-cause mortality. Multivariable logistic regression was used to assess the association between transient AKI and 1-year mortality. RESULTS: Among 3,970 participants, 861 (21.7%) occurred AKI, of whom 128 (14.9%) was transient AKI and 733 (85.1%) was maintained AKI. 312 (7.9%) patients died within 1-year after admission. After multivariable analysis, transient AKI was not associated with higher 1-year mortality [adjusted odds ratio (aOR), 1.37; CI 0.68-2.51] compared without AKI. Among AKI patients, transient AKI was associated with a 52% lower 1-year mortality compared with maintained AKI. Additionally, maintained AKI was significantly associated with higher 1-year mortality (aOR, 2.67; CI 2.05-3.47). CONCLUSIONS: Our data suggested that transient AKI within 48 h was a common subtype of AKI following CAG, without increasing mortality. More attention needs to be paid to the patients suffering from maintained AKI following CAG.

Association of Early and Late Contrast-Associated Acute Kidney Injury and Long-Term Mortality in Patients Undergoing Coronary Angiography.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. METHODS: We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24-72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan-Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. RESULTS: The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02-1.74, P=0.038) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65-1.31, P=0.633) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. CONCLUSIONS: Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.

Predictive value of creatine kinase MB for contrast-induced acute kidney injury among myocardial infarction patients.

BACKGROUND: Predictive value of creatine kinase MB (CK-MB) for contrast-induced acute kidney injury (CI-AKI) among myocardial infarction (MI) patients has rarely been reported. We aim to evaluate the predictive value of CK-MB for CI-AKI among MI patients. METHODS: Totally, 1131 MI patients were included from the REduction of rIsk for Contrast-Induced Nephropathy (REICIN) study. The peak CK-MB before coronary angiography (CAG) was chosen. The study population was divided into two groups by log-transformed CK-MB cut-off point. The association between CK-MB and CI-AKI was tested by multivariable logistic regression. CK-MB was integrated with Age, creatinine and ejection fraction (ACEF) score and Mehran risk score (MRS) to evaluate the additive value of CK-MB. The integrated models were validated internally by the bootstrap method and externally by the PREdictive Value of COntrast voluMe to creatinine Clearance Ratio (PRECOMIN) study data set. RESULTS: Overall, 62(5.48%) patients developed CI-AKI, patients with CK-MB point > 4.7 displayed a higher incidence of CI-AKI than those without (11.9% vs. 4.0%, p < 0.001). CK-MB point > 4.7 was independently associated with CI-AKI (adjusted OR: 3.40, 95% CI: 1.93-5.98, p < 0.001). The additions of CK-MB to ACEF score, Mehran score A and Mehran score B resulted in increases in C-statistics, which ranged from 0.680 to 0.733 (p = 0.046), 0.694 to 0.727 (p = 0.091), 0.704 to 0.734 (p = 0.102), respectively. Internal validation also showed increases in C-statistics, and external validation performed well in discrimination and calibration. CONCLUSIONS: Preprocedural peak CK-MB was a predictor of CI-AKI among MI patients.

Independent and joint effects of high-sensitivity c-reactive protein and hypoalbuminemia on long-term all-cause mortality among coronary artery disease: a prospective and multicenter cohort study.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients. METHODS: A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death. RESULTS: During a median follow-up of 2.9 (2.0-3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48-4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20-3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91-7.52). CONCLUSIONS: High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.

Platelet-to-hemoglobin ratio as a valuable predictor of long-term all-cause mortality in coronary artery disease patients with congestive heart failure.

BACKGROUND: The platelet-to-hemoglobin ratio (PHR) has emerged as a prognostic biomarker in coronary artery disease (CAD) patients after PCI but not clear in CAD complicated with congestive heart failure (CHF). Hence, we aimed to assess the association between PHR and long-term all-cause mortality among CAD patients with CHF. METHODS: Based on the registry at Guangdong Provincial People's Hospital in China, we analyzed data of 2599 hospitalized patients who underwent coronary angiography (CAG) and were diagnosed with CAD complicated by CHF from January 2007 to December 2018. Low PHR was defined as ˂ 1.69 (group 1) and high PHR as ≥ 1.69 (group 2). Prognosis analysis was performed using Kaplan-Meier method. To assess the association between PHR and long-term all-cause mortality, a Cox-regression model was fitted. RESULTS: During a median follow-up of 5.2 (3.1-7.8) years, a total of 985 (37.9%) patients died. On the Kaplan-Meier analysis, patients in high PHR group had a worse prognosis than those in low PHR group (log-rank, p = 0.0011). After adjustment for confounders, high PHR was correlated with an increased risk of long-term all-cause mortality in CAD patients complicated with CHF. (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.13-1.52, p < 0.0001). CONCLUSION: Elevated PHR is correlated with an increased risk of long-term all-cause mortality in CAD patients with CHF. These results indicate that PHR may be a useful prognostic biomarker for this population. Meanwhile, it is necessary to take effective preventive measures to regulate both hemoglobin levels and platelet counts in this population.

Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study.

BACKGROUND: Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the "cholesterol paradox". Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition. METHOD: A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C < 1.8 mmol/L, n = 4863; LDL-C ≥ 1.8 mmol/L, n = 36,366). The Kaplan-Meier method and Cox regression analyses were used to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition. RESULT: In this real-world cohort (mean age 62.9 years; 74.9% male), there were 5257 cases of all-cause death during a median follow-up of 5.20 years [interquartile range (IQR): 3.05-7.78 years]. Kaplan-Meier analysis showed that low LDL-C levels were associated with a worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that a low LDL-C level (< 1.8 mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96-1.24). After adjustment for nutritional status, the risk of all-cause mortality in patients with low LDL-C levels decreased (adjusted HR, 0.90; 95% CI, 0.83-0.98). In the final multivariate Cox model, a low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84-0.99). CONCLUSION: This study demonstrated that the cholesterol paradox existed in CAD patients but disappeared after accounting for the effects of malnutrition.

Association between baseline LDL-C and prognosis among patients with coronary artery disease and advanced kidney disease.

BACKGROUND: Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (< 1.8 mmol/L) and mortality is unknown among patients with CAD and advanced kidney disease (AKD). The current study aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients. METHODS: In this observational study, 803 CAD patients complicated with AKD (eGFR < 30 mL/min/1.73 m2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C < 1.8 mmol/L, n = 138; LDL-C ≥ 1.8 mmol/L, n = 665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality. RESULTS: Among 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan-Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (< 1.8 mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01-1.89). CONCLUSIONS: Our data demonstrated that among patients with CAD and AKD, a lower baseline LDL-C level (< 1.8 mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD.

Trends in incidence and long-term prognosis of acute kidney injury following coronary angiography in Chinese cohort with 11,943 patients from 2013 to 2017: an observational study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. METHODS: This retrospective cohort study was based on the registry at Guangdong Provincial People's Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. RESULTS: 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13-1.68; P-value < 0.01, P for trend < 0.01). The temporal trends of incidence among patients of different ages and genders yielded similar findings. During a standardized follow-up of 1 year, 178 (13.7 %) CA-AKI patients died in total, which showed no obvious decreased trend in this 5 five years from 21.1 to 16.5 (adjusted hazard ratio [aHR], 0.72; 95 %CI, 0.36-1.45; P-value = 0.35, P for trend = 0.24). CONCLUSIONS: Our Chinese cohort showed that the incidence of CA-AKI increased significantly, while CA-AKI associated mortality showed no obvious decreased trend in the last five years. Our findings support more active measures to prevent CA-AKI and improve the prognosis of CA-AKI patients.

Quantitative features and clinical significance of two subpopulations of AChR-specific CD4+ T cells in patients with myasthenia gravis.

Acetylcholine receptor (AChR)-specific CD4+ T cells play a driving role in myasthenia gravis (MG) by regulating the production of autoantibodies. However, the quantitative features of AChR-specific T cells and their clinical significance in MG are unclear. In this study, we adopted standard and cultured enzyme-linked immunosorbent spot (ELISPOT) assays to quantify subpopulations of AChR-specific CD4+ T cells in MG patients, and evaluate their correlation with clinical characteristics. The results showed that Th1- and Th17-AChR-specific CD4+ T cells were detectable by standard and cultured ELISPOT assay respectively, with higher levels observed in MG patients comparing with healthy controls. The number of Th17-AChR-specific CD4+ T cells was positively correlated with anti-AChR antibody titer and quantitative MG score and may have latent capacity to reflect responses to immunosuppressants. These results highlight the differences in quantitative features of AChR-specific CD4+ T cells and imply Th17-AChR-specific CD4+ T cells can serve as a biomarker in MG.

A comparison between two different definitions of contrast-associated acute kidney injury for long-term mortality in patients with diabetes undergoing coronary angiography: a prospective cohort study.

BACKGROUND: The definitions of contrast-associated acute kidney injury (CA-AKI) are diverse and have different predictive effects for prognosis, which are adverse for clinical practice. Few articles have discussed the relationship between these definitions and long-term prognosis in patients with diabetes. METHODS: A total of 1154 diabetic patients who were undergoing coronary angiography (CAG) were included in this study. Two definitions of CA-AKI were used: CA-AKIA was defined as an increase ≥ 0.3 mg/dl or > 50% in serum creatinine (SCr) from baseline within 72 h after CAG, and CA-AKIB was defined as an increase ≥ 0.5 mg/dl or > 25% in SCr from baseline within 72 h after CAG. We used Cox regression to evaluate the association of these two CA-AKI definitions with long-term mortality and calculate the population attributable risks (PARs) of different definitions for long-term prognosis. RESULTS: During the median follow-up period of 7.4 (6.2-8.2) years, the overall long-term mortality was 18.84%, and the long-term mortality in patients with CA-AKI according to both CA-AKIA and CA-AKIB criteria were 36.73% and 28.86%, respectively. We found that CA-AKIA (HR: 2.349, 95% CI 1.570-3.517, p = 0.001) and CA-AKIB (HR: 1.608, 95% CI 1.106-2.339, p = 0.013) were associated with long-term mortality. The PARs were the highest for CA-AKIA (31.14%), followed by CA-AKIB (14.93%). CONCLUSIONS: CA-AKI is a common complication in diabetic patients receiving CAG. The two CA-AKI definitions are significantly associated with a poor long-term prognosis, and CA-AKIA, with the highest PAR, needs more clinical attention.

Population attributable risk estimates of risk factors for contrast-induced acute kidney injury following coronary angiography: a cohort study.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common complication with poor outcomes following coronary angiography (CAG) or percutaneous coronary intervention (PCI). However, no study has explored the population attributable risks (PARs) of the CI-AKI risk factors. Therefore, we aimed to identify the independent risk factors of CI-AKI and estimate their PARs. METHODS: We analyzed 3450 consecutive patients undergoing CAG/PCI from a prospective cohort in Guangdong Provincial People's Hospital. CI-AKI was defined as a serum creatinine elevation ≥50% or 0.3 mg/dL from baseline within the first 48 to 72 h after the procedure. Independent risk factors for CI-AKI were evaluated through stepwise approach and multivariable logistic regression analysis, and those that are potentially modifiable were of interest. PARs of independent risk factors were calculated with their odds ratios and prevalence among our cohort. RESULTS: The overall incidence of CI-AKI was 7.19% (n = 248), which was associated with increased long-term mortality. Independent risk factors for CI-AKI included heart failure (HF) symptoms, hypoalbuminemia, high contrast volume, hypotension, hypertension, chronic kidney disease stages, acute myocardial infarction and age > 75 years. Among the four risk factors of interest, the PAR of HF symptoms was the highest (38.06%), followed by hypoalbuminemia (17.69%), high contrast volume (12.91%) and hypotension (4.21%). CONCLUSIONS: These modifiable risk factors (e.g., HF symptoms, hypoalbuminemia) could be important and cost-effective targets for prevention and treatment strategies to reduce the risk of CI-AKI. Intervention studies targeting these risk factors are needed.

Hospital and healthcare insurance system record-based epidemiological study of myasthenia gravis in southern and northern China.

OBJECTIVE: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations. METHODS: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017. RESULTS: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance. CONCLUSIONS: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.

Imbalance of the two main circulating dendritic cell subsets in patients with myasthenia gravis.

Although it is well documented that circulating dendritic cells (DCs) have specialized features during many kinds of physiological and pathological conditions, there are few reports about the features of DCs in the peripheral blood of myasthenia gravis (MG) patients. We investigated the quantitative and component features of DCs and their implications in MG. Peripheral blood samples from different kinds of MG patients were collected and their clinical characteristics were recorded. Using flow cytometry, we distinguished circulating DC subsets [plasmacytoid DCs (pDCs) and myeloid DCs (mDCs)] and enumerated their densities in peripheral blood. Absolute numbers of circulating pDCs were significantly decreased in naïve MG patients compared with healthy controls, resulting in a markedly lower ratio of the pDC to mDC percentage in total circulating DCs (pDCs/mDCs), suggesting an imbalance in the proportions of the two main circulating DC subsets. The clinical status of MG patients was improved after drug treatment, together with increased pDCs/mDCs. In a longitudinal follow-up, we observed that circulating mDCs were significantly reduced after 1 month of therapy with a corticosteroid and immunosuppressant, resulting in recovery of pDCs/mDCs. Although the exact meaning of the proportion change in circulating DC subsets is unknown, pDCs/mDCs might reflect the balance between the autoimmune response and immune tolerance of a patient. Moreover, changes in pDCs/mDCs during treatment might be a promising marker to predict the efficacy of a specific drug used for MG patients.

Neutrophil extracellular trap-associated risk index for predicting outcomes and response to Wnt signaling inhibitors in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a type of breast cancer with poor prognosis, which is prone to distant metastasis and therapy resistance. The presence of neutrophil extracellular traps (NETs) contributes to the progression of breast cancer and is an efficient predictor of TNBC. We obtained the bulk and single-cell RNA sequencing data from public databases. Firstly, we identified five NET-related genes and constructed NET-related subgroups. Then, we constructed a risk index with three pivotal genes based on the differentially expressed genes between subgroups. Patients in the high-risk group had worse prognosis, clinicopathological features, and therapy response than low-risk group. Functional enrichment analysis revealed that the low-risk group was enriched in Wnt signaling pathway, and surprisingly, the drug sensitivity prediction showed that Wnt signaling pathway inhibitors had higher drug sensitivity in the low-risk group. Finally, verification experiments in vitro based on MDA-MB-231 and BT-549 cells showed that tumor cells with low-risk scores had less migration, invasion, and proliferative abilities and high drug sensitivity to Wnt signaling pathway inhibitors. In this study, multi-omics analysis revealed that genes associated with NETs may influence the occurrence, progression, and treatment of TNBC. Moreover, the bioinformatics analysis and cell experiments demonstrated that the risk index could predict the population of TNBC likely to benefit from treatment with Wnt signaling pathway inhibitors.

Long-term efficacy and safety of leflunomide combined with low-dose prednisone in treatment of myasthenia gravis: a retrospective study.

BACKGROUND: Leflunomide and low-dose prednisone (0.25 mg/kg/day) (LEF + Pred) rapidly improved the clinical symptoms of myasthenia gravis (MG) patients. Here, we aimed to analyze the long-term efficacy and safety of LEF + Pred in MG patients. METHODS: This retrospective cohort study enrolled MG patients treated with LEF + Pred in our center between 2012 and 2020. We reviewed all the MG patients continuously treated with LEF + Pred for more than 1 year. MG activities of daily living (MG-ADL) profile score and quantitative MG scale (QMG) score in each clinical follow-up visits were collected for the efficacy analysis. The laboratory testing results of MG patients, the relevant chief complain and physical examination results in each follow-up visits were collected for the safety evaluation. RESULTS: In total, 103 patients were examined. Effective treatment was achieved in 58.3% of patients after 1 month and in 88.4% after 12 months. Overall, 63 patients (61.2%) exhibited only minimal manifestations after 12 months of treatment. The average MG-ADL score decreased from 6.0 to 1.0, while the average QMG score decreased from 10.0 to 4.0. The decrease in MG-ADL and QMG scores of patients with generalized MG was more pronounced than those of the ocular MG patients. Patients with MG who had a thymectomy had a smaller decrease in MG-ADL and QMG scores than those who did not have a thymectomy. Sixteen adverse effects associated with LEF + Pred were observed; none was severe. CONCLUSIONS: Long-term LEF + Pred therapy could considerably improve clinical symptoms in MG patients while being well tolerated with just few side effects.

Effect of Missed Post-Procedure Creatinine Measurement on Sub-Acute Kidney Injury Following Coronary Angiography.

Serum creatinine (SCr) levels are essential for the diagnosis of kidney disease after coronary angiography (CAG). However, the influence of missed post-procedure SCr measurement in this situation is unclear. The present study included 14,127 patients undergoing CAG as part of the Cardiorenal ImprovemeNt registry II. Patients were divided into two groups according to whether a post-procedure SCr was measured within 3 days. The primary endpoint was acute kidney disease (AKD). Logistic regression was used to evaluate the relationship between post-procedure SCr and AKD. Of the 14,127 patients (61.6 ± 9.8 years, 34.2% females), 55.4% (n = 7822) did not have a post-procedure SCr measurement. The incidence of AKD was higher in the missed post-procedure SCr group (15.7 vs 11.9%; median follow-up 6.54 years). Multivariate logistic regression showed that missed post-procedure SCr measurement was associated with significantly higher risk of AKD (adjusted odds ratio [aOR]: 1.26, 95% CI: 1.10-1.45, P < .001). The results were more significant in patients with normal renal function at baseline (aOR: 1.36, 95% CI: 1.16-1.60, P < .001). In our study, over half of the patients undergoing CAG missed their post-procedure SCr measurement. The missed post-procedure SCr group had a significantly higher risk of developing AKD compared with those with a post-procedure SCr measurement.