[Biological characteristics of triple negative breast cancer with low expression of HER2].

Objective: To investigate the biological characteristics of triple negative breast cancer (TNBC) with low expression of HER2 (HER2-low). Methods: A total of 93 TNBC cases in Shanxi Cancer Hospital from 2017 to 2019 were collected and divided into HER2-negative and HER2-low groups according to HER2 expression status. The clinicopathological features and prognostic differences between the two groups were retrospectively analyzed and compared, and genetic detection of tumor tissues was performed to clarify somatic mutation status and differences between the two groups. Results: Ninety-three patients aged 26 to 86 years were enrolled, including 60 patients in the HER2-negative group and 33 patients in the HER2-low group. The distribution of HER2-low in luminal androgen receptor (LAR) subtype (14/23, 60.87%) and non-LAR subtype (19/70, 27.14%) was significantly different (P=0.005). There were no significant differences in age, pT stage, histological grade, infiltration mode, lymph node metastasis and survival analysis. The expression of HER2-low in the tumor was heterogeneous, including different proportions of weak, weak to moderate intensity, and incomplete to intact membrane staining. With the change of the proportion of HER2-positive cells, the different distribution of those cells in the total tumor cells was noted, including cluster, mosaic and scattered patterns. The concentration and quality of DNA extracted from 71 of the 93 samples met the requirements for making libraries, including 43 in the HER2-negative group and 28 in the HER2-low group. Genetic mutations were mainly missense mutations, single nucleotide mutations, and point mutations in which base C was replaced by base T. There was no significant difference in genes with mutation frequency>3 times between the two groups. CTNNB1 and FGFR3 genes were only mutated in HER2-low group; while ALK, CYP2D6 and FAT1 genes were only mutated in HER2-negative group. HER2-low group included 18 HER2 1+ cases and 10 HER2 2+ cases. Genes with mutation frequency>3 times between the two groups included PIK3CA, TP53, SLX4, ATM and BRCA1. The mutation frequency of PIK3CA in HER2 2+ was significantly higher than that in HER2 1+ group (P<0.05), and SLX4 gene was only mutated in HER2 1+ group. Conclusions: There are some differences of histological morphology and genetic variation between HER2-negative group and HER2-low group, and also differences in genetic variation between HER2 1+ and HER2 2+ in HER2-low group, which are helpful for more accurate stratification of TNBC and useful for finding the therapeutic target and precise treatment of HER2-low TNBC.

Genetic analysis of a Kaijiang duck conservation population through genome-wide scan.

1. The Kaijiang duck is a native Chinese breed known for its excellent egg laying performance, killing-out percentage (88.57%), and disease resistance. The assessment of population genetic structure is the basis for understanding the genetics of indigenous breeds and for their protection and management.2. In this study, whole-genome sequencing was performed on 60 Kaijiang ducks to identify genetic variations and investigate the population structure. Homozygosity (ROH) analysis was conducted to assess inbreeding levels in the population.3. The study revealed a moderate level of inbreeding, indicated by an average inbreeding coefficient of 0.1043. This may impact the overall genetic diversity.4. Genomic Regions of Interest identified included 168 genomic regions exhibiting high levels of autozygosity. These regions were associated with processes including muscle growth, pigmentation, neuromodulation, and growth and reproduction.5. The significance of these pathways indicated their potential role in shaping the desirable traits of the Kaijiang duck. These findings provide insights into the genetic basis of the Kaijiang duck's desirable traits and can inform future breeding and conservation efforts.

[Clinical value of the implication of extracorporeal carbon dioxide removal in patients with acute respiratory distress syndrome].

Extracorporeal carbon dioxide removal (ECCO2R) is a respiratory support technique based on extra-pulmonary gas exchange, which can effectively remove carbon dioxide generated in-vivo, reducing the requirements of respiratory support from mechanical ventilation. With improvements in extracorporeal life support technologies and increasing clinical experience, ECCO2R has potential value in clinical application with acute respiratory distress syndrome (ARDS). This review article discusses the principles of ECCO2R, its relevant indications for ARDS, clinical evidence, existing issues, and future directions, aiming to provide more references for the application in ARDS.

Flexed elbow, abducted shoulder, forearm supinated (FABS) reconstruction from three-dimensional elbow MRI: diagnostic performance assessment in biceps head anatomy and pathology.

AIM: To determine inter-reader analysis and diagnostic performance on digitally reconstructed virtual flexed, abducted, supinated (FABS) imaging from three-dimensional (3D) isotropic elbow magnetic resonance imaging (MRI). MATERIALS AND METHODS: Six musculoskeletal radiologists independently evaluated elbow MRI images with virtual FABS reconstructions, blinded to clinical findings and final diagnoses. Each radiologist recorded a binary result as to whether the tendon was intact and if both heads were visible, along with a categorical value to the type of tear and extent of retraction in centimetres where applicable. Kappa and interclass correlation (ICC) were reported with 95% confidence intervals. Areas under the receiver operating curve (AUC) were reported. RESULTS: FABS reconstructions were obtained successfully in all 48 cases. With respect to tendon intactness, visibility of both heads, and type of tear, the Kappa values were 0.66 (0.53-0.78), 0.24 (0.12-0.37), and 0.55 (0.43-0.66), respectively. For the extent of retraction, the ICC was 0.85 (0.79-0.91) when including the tendons with and without retraction and 0.78 (0.61-0.91) when only including tendons with retraction. For tear versus no tear, AUC values were 0.82 (0.74-0.89) to 0.96 (0.91-1.01). CONCLUSION: Digital reconstruction of FABS positioning is feasible and allows good assessment of individual tendon head tears and retraction with high diagnostic performance.

[Validation and comparison of diabetic retinopathy-based diagnostic models for diabetic nephropathy].

OBJECTIVE: To validate and compare the efficacy of two noninvasive diagnostic models for diabetic nephropathy (DN) based on diabetic retinopathy (DR). METHODS: A total of 565 patients with type 2 diabetes undergoing kidney biopsy in the Department of Nephrology, PLA General Hospital from January, 1993 to December, 2014 were studied. The patients were divided into DN group and non-diabetic nephropathy (NDRD) group according to renal pathological diagnosis. The data from the 22-year period were divided into 3 stages based on chronological order: early stage (from 1993 to 2003), middle stage (from 2004 to April, 2012), and late stage (from May, 2012 to December, 2014). The changes in clinical features and pathological diagnosis of the patients with renal biopsy over the 22 years were analyzed. The published DNT model and JDB model, both based on DR, were validated and compared for diagnostic effectiveness of DN, and the characteristics of the misdiagnosed cases were analyzed. RESULTS: The incidences of hypertension and DR and levels of glycosylated hemoglobin (HbA1c), creatinine and 24-h urinary protein were all significantly higher, while hemoglobin and triglyceride levels were lower in DN group than in NDRD group (P<0.05). The proportion of NDRD cases increased gradually over time, with IgA nephropathy and membranous nephropathy as the main pathological types. The AUC of JDB model was 0.946, similar to that of NDT model (0.925; P=0.198). The disease course of diabetes, hematuria and incidence of DR were important clinical features affecting the diagnostic accuracy of the models. CONCLUSION: The clinical features and pathological diagnosis of DR change over time. The non-invasive diagnostic models based on DR have good diagnostic efficacy for DN.

Combining the triglyceride-glucose index and glycated hemoglobin A1c to assess the risk of preeclampsia in women with normal glucose tolerance: a cross-sectional study.

OBJECTIVE: This study aimed to explore the relationship between the triglyceride-glucose (TyG) index, glycated hemoglobin A1c (HbA1c), and preeclampsia in pregnant women without gestational diabetes mellitus (GDM). PATIENTS AND METHODS: This retrospective study included pregnancies with normal oral glucose tolerance tests (OGTTs) from March 2018 to February 2019. During the second trimester, serum lipids, fasting plasma glucose (FPG), and HbA1c were measured, and OGTTs were performed. Participants were classified into four groups based on their TyG index and HbA1c levels. Logistic regression analysis was done to determine the odds ratios (ORs), and receiver operating characteristic (ROC) curve analysis was used to evaluate the ability of the TyG index and HbA1c to predict the risks of preeclampsia. RESULTS: Patients with preeclampsia exhibited higher TyG index and HbA1c levels (all p < 0.001). The incidence of preeclampsia increased with elevated TyG index and HbA1c levels individually. Furthermore, the highest incidence of preeclampsia was observed when both the TyG index and HbA1c levels were elevated. ROC curve analysis revealed that the combined TyG index and HbA1c displayed an area under the curve (AUC) of 0.689 in predicting the risk of preeclampsia. Even after adjusting for potential confounding factors, the risk of developing preeclampsia remained significantly higher. These associations were especially prominent in women aged ≥ 35 years or those with a normal BMI. CONCLUSIONS: The findings of this study indicate that increased TyG index and HbA1c levels are associated with a higher incidence and risk of preeclampsia in women with normal glucose tolerance during pregnancy. The TyG index and HbA1c levels may serve as potential markers for preeclampsia in individuals with normal OGTT results.

Genome-wide association analysis of neck ring traits in NongHua ma male ducks.

1. Male NongHua ma ducks have more colourful feathers than females, especially considering that the former have a distinctive neck ring that is different from that of females. This ring development might be influenced by sex selection, the environment, genetics and other elements.2. Genome-wide association analysis (GWAS) was used to locate candidate genes that affect the neck ring formation of male ducks to investigate the genetic basis of this phenomenon.3. In this study, the neck ring area and width of 180 male ducks were assessed at ages 80, 90, 100, 110 and 120 d. GWAS was used to identify associated genes. There were 0, 7, 14, 48 and 21 possible candidate genes annotated around the 0, 12, 25, 76 and 40 SNP loci n corresponding regions. A total of 13 candidate genes were identified around 21 SNP sites at the neck ring width of 120 d.4. These significant genes were annotated and GO and KEGG enrichment analyses were performed. All SNPs that exceeded the significance threshold were annotated and preliminarily screened as candidate genes affecting neck ring formation. From analysis of gene function and enriched KEGG pathways, genes such as THSD1, SLC6A4, DGAT2, PRKDC, B3GAT2, ROR1, GRK7, EXTL3, TXNDC12, COL4A2, PRKG1, ACTR3, were considered important candidate marker sites related to the neck ring. This provided a reference starting point for the genetic mechanism underlying duck feather colour.

[Anticoagulation status and adherence in patients with atrial fibrillation hospitalized for ACS and the impact on 1-year prognosis: a multicenter cohort study].

Objective: For patients with atrial fibrillation (AF) complicated with acute coronary syndrome (ACS), both anticoagulant and antiplatelet therapy should be applied, but the use of anticoagulation therapy is still poor in these patients in China. The purpose of this study was to explore the status and adherence of antithrombotic therapy in AF patients with ACS and the impact on 1 year clinical outcomes. Methods: Patients with AF hospitalized for ACS were retrospectively included from 6 tertiary hospitals in China between July 2015 and December 2020. According to the use of anticoagulant drugs at discharge, patients were divided into two groups: anticoagulant treatment group and non-anticoagulant treatment group. Logistic regression model was used to analyze the main factors influencing the use of anticoagulant drugs in patients with atrial fibrillation complicated with ACS. Major adverse cardiac events (MACEs) were defined as all-cause death, non-fatal myocardial infarction or coronary revascularization, and ischemic stroke and Bleeding Academic Research Consortium (BARC) 3 bleeding events were also collected at 1 year after discharge. After propensity score matching, Cox proportional hazards models and Kaplan-Meier analysis were used to evaluate the effect of anticoagulant treatment and non-anticoagulant treatment on 1-year prognosis. The patients were divided into different groups according to whether anticoagulation was performed at discharge and follow-up, and the sensitivity of the results was analyzed. Results: A total of 664 patients were enrolled, and 273 (41.1%) were treated with anticoagulant therapy, of whom 84 (30.8%) received triple antithrombotic therapy, 91 (33.3%) received double antithrombotic therapy (single antiplatelet combined with anticoagulant), and 98 (35.9%) received single anticoagulant therapy. Three hundred and ninety-one (58.9%) patients were treated with antiplatelet therapy, including 253 (64.7%) with dual antiplatelet therapy and 138 (35.3%) with single antiplatelet therapy. After 1∶1 propensity score matching between the anticoagulant group and the non-anticoagulant group, a total of 218 pairs were matched. Multivariate logistic regression analysis showed that history of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention were predictors of the absence of anticoagulant therapy, while history of ischemic stroke and persistent atrial fibrillation were predictors of anticoagulant therapy. At 1-year follow-up, 218 patients (79.9%) in the anticoagulant group continued to receive anticoagulant therapy, and 333 patients (85.2%) in the antiplatelet group continued to receive antiplatelet therapy. At 1-year follow-up, 36 MACEs events (13.2%) occurred in the anticoagulant group, and 81 MACEs events (20.7%) in the non-anticoagulant group. HR values and confidence intervals were calculated by Cox proportional risk model. Patients in the non-anticoagulant group faced a higher risk of MACEs (HR=1.802, 95%CI 1.112-2.921, P=0.017), and the risk of bleeding events was similar between the two group (HR=0.825,95%CI 0.397-1.715, P=0.607). Conclusions: History of diabetes, HAS-BLED score≥3, and percutaneous coronary intervention are independent factors for the absence of anticoagulant therapy in patients with AF complicated with ACS. The incidence of MACEs, death and myocardial infarction is lower in the anticoagulant group, and the incidence of bleeding events is similar between the two groups. The risk of bleeding and ischemia/thrombosis should be dynamically assessed during follow-up and antithrombotic regiments should be adjusted accordingly.

[Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia].

OBJECTIVE: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer. METHODS: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve. RESULTS: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration. CONCLUSION: It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Impact of rhG-CSF on Clinical Efficacy and Immune Cell Subsets after Initial Induction Chemotherapy in AML.

BACKGROUND: The impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in acute myeloid leukemia (AML) is still controversial. The purpose of this study is to explore the impact of rhG-CSF administration on clinical efficacy and immune cell subsets after initial induction chemotherapy in AML. METHODS: The clinical efficacy and immune cell subsets were compared in the newly diagnosed patients with AML according to whether rhG-CSF was used after initial induction chemotherapy. Next, rhG-CSF stimulation experi-ments on leukemia cell lines and primary leukemia blasts were performed in vitro. RESULTS: There was no statistical difference between control group and rhG-CSF therapy group in complete remission rate and relapse free survival. The duration of agranulocytosis was significantly shortened in rhG-CSF therapy group compared with control group. The percentage of circulating monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) were significantly increased after the administration of rhG-CSF. Furthermore, it was found that rhG-CSF did not promote the proliferation of leukemia cell lines and primary leukemia blasts, but increased the proportion of M-MDSCs and Tregs in vitro. CONCLUSIONS: Administration of rhG-CSF after initial induction therapy of AML does not affect the clinical remission and relapse rate, but reduces the duration of agranulocytosis and increases the proportion of M-MDSCs and Tregs.

Reference intervals of systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio during normal pregnancy in China.

OBJECTIVE: To observe the changes in systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) during normal pregnancy and establish appropriate reference intervals (RIs) for healthy pregnant women. PATIENTS AND METHODS: This retrospective study was conducted from March 2018 to February 2019. Blood samples were collected from healthy pregnant and nonpregnant women. The complete blood count (CBC) parameters were measured, and SII, NLR, LMR, and PLR were calculated. RIs were established using the 2.5th and 97.5th percentile of the distribution. Besides, the differences in CBC parameters between three pregnant trimesters and maternal ages were also compared to assess their influences on each indicator. RESULTS: SII and NLR in three pregnant trimesters increased in pregnant women, and the upper limit of SII and NLR in trimester 2 showed the highest value. On the contrary, LMR decreased in all three pregnant trimesters compared with nonpregnant women, and the values of LMR and PLR showed a gradual downward trend along with the trimesters. Besides, RIs of SII, NLR, LMR, and PLR during different trimesters in different age partitions showed that the values of SII, NLR, and PLR increased with age in a general trend, while LMR showed the opposite trend (p < 0.05). CONCLUSIONS: The SII, NLR, LMR, and PLR showed dynamic changes during pregnant trimesters. RIs of SII, NLR, LMR, and PLR for healthy pregnant women according to pregnant trimesters and maternal age were established and validated in this study, which will promote the standardization of clinical application.

[Heritability and genetic correlation of body mass index and coronary heart disease in Chinese adult twins].

Objective: To examine the heritability of body mass index (BMI) and coronary heart disease (CHD), and to explore whether genetic factors can explain their correlation. Methods: Participants were from 11 provinces/municipalities reqistered in the Chinese National Twin Registry (CNTR) from 2010 to 2018. Participants data were collected from face-to-face questionnaire survey. Bivariate structure equation model was used to estimate the heritability and the genetic correlation of BMI and CHD. Results: A total of 20 340 pairs of same-sex twins aged ≥25 years were included in this study. After adjusting for age and gender, the heritability of BMI and CHD was 0.52 (95%CI: 0.49-0.55) and 0.76 (95%CI: 0.69-0.81), respectively. Further, a genetic correlation was identified between BMI and CHD (rA=0.10, 95%CI:0.02-0.17). Conclusion: In Chinese adult twin population, BMI and CHD are affected by genetic factors, and their correlation can be attributed to the common genetic basis.

Impact of angiogenic inhibition in the treatment of newly diagnosed and recurrent glioblastoma: a meta-analysis based on randomized controlled trials.

OBJECTIVE: Glioblastoma (GBM) is the most common and aggressive primary malignant tumor of the central nervous system in adults with high recurrence and mortality rates. Although radiotherapy and temozolomide have become the standard therapeutic regimen for GBM as adjuvant chemoradiotherapy after surgical resection, clinical outcomes remain suboptimal. In recent years, targeted antiangiogenic therapy has attracted considerable attention, but its therapeutic efficacy and safety are still controversial. MATERIALS AND METHODS: Randomized controlled trials (RCTs) of chemoradiotherapy with or without bevacizumab for the treatment of glioblastoma were collected by searching on the Pubmed, Embase, Cochrane, Ovid, Scopus, Web of Science, and Google Scholar databases from the date of database establishment to February 2022. Meta-analysis was performed using RevMan 5.3 software after two investigators independently screened the literature, extracted data, and assessed the risk bias of included studies. RESULTS: A total of 7 RCTs were included. The meta-analysis showed that bevacizumab in combination with chemoradiotherapy was superior to chemoradiotherapy alone in terms of progression-free survival (PFS), with a statistically significant difference. Interestingly, bevacizumab in combination with chemoradiotherapy improved PFS more significantly in recurrent glioblastoma than in newly diagnosed glioblastoma. However, for overall survival (OS), the combination of bevacizumab with chemoradiotherapy was similar to chemoradiotherapy alone, which was not significantly different. With regard to safety, the incidence of most adverse events was higher in the combination of bevacizumab and chemoradiotherapy than in chemoradiotherapy alone, especially in terms of hematologic adverse events. CONCLUSIONS: Current evidence suggests that angiogenesis inhibitor-containing chemoradiotherapy regimens are preferentially recommended for patients with recurrent glioblastoma to prolong their progression-free survival, provided that safety is acceptable, but this does not confer a significant benefit on overall patient survival.

[Gene-lifestyle interaction on coronary heart disease in adult twins of China].

Objective: To explore the gene-lifestyle interaction on coronary heart disease (CHD) in adult twins of China. Methods: Participants were selected from twin pairs registered in the Chinese National Twin Registry (CNTR). Univariate interaction model was used to estimate the interaction, via exploring the moderation effect of lifestyle on the genetic variance of CHD. Results: A total of 20 477 same-sex twin pairs aged ≥25 years were recruited, including 395 CHD cases, and 66 twin pairs both had CHD. After adjustment for age and sex, no moderation effects of lifestyles, including current smoking, current drinking, physical activity, intake of vegetable and fruit, on the genetic variance of CHD were found (P>0.05), suggesting no significant interactions. Conclusion: There was no evidence suggesting statistically significant gene-lifestyle interaction on CHD in adult twins of China.