Breast cancer has emerged as the leading cause of cancer incidence and mortality among women globally,with approximately 70%of cases being estrogen receptor(ER)and/or progesterone receptor(PR)positive.The primary treatment for hormone receptor(HR)positive breast cancer is endocrine therapy;however,endocrine therapy resistance remains a critical area of ongoing research.Cyclin D1 is recognized as a biomarker for tumor phenotype and disease progression,and it has been established to correlate with the onset,progres-sion,and prognosis of breast cancer.Recently,studies have also reported the significant role of Cyclin D1 in endocrine resistance in breast cancer.This article provides an overview of the research progress on Cyclin D1 in breast cancer,with a particular emphasis on its relation-ship with endocrine therapy resistance,aiming to offer novel insights for the endocrine treatment of breast cancer.

Purpose To explore the relationship between the proportion of HER2 low expression and clinicopatho-logical characteristics of gastric adenocarcinoma patients.Methods Clinical data from 3 779 gastric adenocarcinoma patients who underwent radical resection were collected.HER2 expression was categorized using immunohistochemistry combined with FISH,and the clinicopathological characteristics and prognosis of HER2 low expression gastric adeno-carcinoma patients were analyzed.Results Among the 3 779 gastric adenocarcinoma cases,1 251 cases(33.10％)showed HER2 low expression.Compared with HER2 negative expression,HER2 low expression patients were more likely to be older males,present with well-differentiated Lauren's intestinal-type adenocarcinoma,and have less nerve invasion.Furthermore,compared to HER2 negative expression,they showed higher Ki67 proliferation index and more advanced clinical stage.Meanwhile,compared with patients with HER2 over expression,those with low HER2 expres-sion were more likely to be younger females,present with well-differentiated Lauren's diffuse-type adenocarcinoma,and have more nerve invasion.Furthermore,compared to HER2 over expression,they showed lower Ki67 proliferation index and more advanced clinical stage.There was no significant difference in prognosis between HER2 low expression,HER2 negative,and HER2 over expression groups.Conclusion HER2 low expression have a relatively large propor-tion in gastric adenocarcinoma patients,and HER2-targeted antibody-drug conjugates may provide an effective treatment option for these patients with HER2 low expression.

Objective:To screen differentially expressed circular RNAs(circRNA)associated with lymph node metastasis in cervical cancer and investigate their molecular mechanism and biological function.Methods:Cancer tissue samples were collected from 40 cervical cancer patients(20 with lymph node metastasis and 20 without lymph node metastasis).Three specimens were randomly selected from each group,and the circRNA expression profile was analyzed using high-throughput sequencing technology,and perform KEGG and GO enrichment analy-sis was performed on the differentially expressed circRNA derived mother genes.Real-time fluorescence quantita-tive PCR(qRT-PCR)technology was used to validate four significantly upregulated circRNAs with high differential multiples,and a ceRNA network was constructed for database prediction.The relationship between circRNA with the most significant differential expression and clinical pathological features was analyzed.Transfect circRNA small interfering RNA(siRNA)into cervical cancer cell lines.Cell lines were divided into circRNA knockdown group and negative control(si-NC)group.The proliferation of SiHa cells and HeLa cells in cervical cancer was detected by Cell Counting Kit-8(CCK-8).Results:①A total of 2039 differentially expressed circRNAs were detec-ted.The differentially expressed circRNA derived mother genes are mainly enriched in ubiquitin mediated protein hydrolysis,MAPK signaling pathway,endocytosis,apoptosis and other signaling pathways.②Four significantly up-regulated circRNAs with high differential multiples in the transfer group were selected,which are hsa_circ_0067492,hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718.qRT-PCR showed that hsa_circ_0004904,hsa_circ_0085465,and hsa_circ_0007718 were all highly expressed in cervical cancer tissues with lymph node metas-tasis(P<0.01).Hsa_circ_0004904 could interact with microRNAs(miRNAs)such as hsa-miR-3916.Hsa_circ_0085465 could interact with miRNAs such as hsa-miR-4659b-3p,and hsa_circ_0007718 could interact with miRNAs such as hsa-miR-127-5p.③The high and low expression groups of hsa_circ_0004904 showed statistically signigi-cant differences in lymph node metastasis and lymphovascular invasion status(P<0.05).Compared with the si-NC group,the proliferation ability of SiHa cells and HeLa cells was significantly reduced after transfection with hsa_circ_0004904 at 24,48,and 72 hours(P<0.05).Conclusions:Differentially expressed circRNAs were identi-fied in cervical cancer patients with lymph node metastasis.Silencing these circRNAs significantly inhibited the proliferation of cervical cancer cells,suggesting their potential involvement in the progression of lymph node me-tastasis.These circRNAs may serve as specific biomarkers for predicting lymph node metastasis.

Objective·To screen a long non-coding RNA(lncRNA)signature and construct a competing endogenous RNA(ceRNA)network associated with the prognosis of pediatric sepsis based on the Gene Expression Omnibus(GEO)database,and explore their potential application value in the prognosis assessment of children with sepsis.Methods·Microarray data in GSE4607,GSE26440,GSE26378,and GSE9692 in the GEO database were used to compare the differences in lncRNA profiles between the survival and non-survival groups of children with septic shock.Then,multivariate linear regression,LASSO analysis,and receiver operating characteristic(ROC)curves were used to evaluate the capacity of the lncRNA signature for predicting the outcome of pediatric sepsis.The potential targeted microRNAs(miRNAs)and their downstream mRNAs,targeted by the screened lncRNAs,were used to construct a protein-protein interaction(PPI)network and perform pathway enrichment analysis.Results·Transcriptomic data from GSE4607,GSE26440,GSE26378 and GSE9692 revealed 55 differentially expressed lncRNAs associated with prognosis,and miR503 host gene(MIR503HG),TAPT1 antisense RNA 1(TAPT1-AS1),apoptosis-associated transcript in bladder cancer(AATBC),SBF2 antisense RNA 1(SBF2-AS1),MGC16275,and small nucleolar RNA host gene 15(SNHG15)were identified as a 6-lncRNA signature(lncSig6)associated with the prognosis of pediatric septic shock by LASSO regression analysis.The area under the ROC curve(AUC)of lncSig6 was 0.859(95％CI 0.722-0.996)and 0.854(95％CI 0.687-1.000)in internal and external validation,respectively.As lncRNA act as miRNA sponge,a lncRNA-miRNA-mRNA network based on 3 lncRNAs(MIR503HG,SNHG15,and SBF2-AS1)was constructed and involved in the regulation of signaling pathways,including forkhead box O(FoxO)signaling pathway,phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,cell senescence,insulin signaling pathway,hypoxia-inducible protein-1(HIF-1)signaling pathway and advanced glycation end products(AGEs)and receptor of AGEs(RAGE)signaling pathway.Conclusion·The lncSig6 can be used as an evaluation method to predict the prognosis of septic shock in children,and the constructed ceRNA molecular networks can provide an experimental basis for the study of signaling pathways.

Objective:To investigate the expression of Cullin associated NEDD8 dissociated protein 1 in colorectal cancer and its effect on the biological behavior of colorectal cancer.Method:A total of 70 pairs of colorectal cancer and paired normal tissue specimens were collected from Jun to Dec 2017 at the Department of Gastrointestinal Surgery at Peking University People's Hospital. Immunohistochemistry was used to detect the expression of Cullin associated NEDD8 dissociated protein 1 and analyze its relationship with clinical pathological indicators and prognosis. CCK8, colony formation assay, transwell assay, and wound healing assay were used to evaluate the effects of Cullin associated NEDD8 dissociated protein 1 on the proliferation, migration, and invasion ability of colon cancer cells.Result:Compared with normal tissues, Cullin associated NEDD8 dissociated protein 1 was highly expressed in colorectal cancer (Immunohistochemistry score: 3.685±1.257 vs. 2.000±0.851, Z=6.536, P<0.001). The expression level of Cullin associated NEDD8 dissociated protein 1 was significantly correlated with T stage ( χ2=5.67, P=0.017), N stage ( χ2=7.20, P=0.007), and pathology stage ( χ2=4.66, P=0.031). Patients with high expression of Cullin associated NEDD8 dissociated protein 1 had a worse prognosis than those with low expression ( χ2=4.80, P=0.037). Knocking down Cullin associated NEDD8 dissociated protein 1 significantly reduced the proliferation, colony formation, and invasive migration ability of DLD1 cells (all P<0.05). Conclusion:Cullin associated NEDD8 dissociated protein 1 is significantly overexpressed in colorectal cancer and has a promoting effect on the occurrence and development of colorectal cancer.

Acute lung injury（ALI）is a common，deadly complication of sepsis，involving multiple pathophysiological mechanisms.Research on prevention and treatment strategies for ALI has always been a key focus in critical-care medicine field.In recent years，the role of reactive oxygen species in ALI has received extensive attention.This review summarized the research on reactive oxygen species processes in sepsis-induced ALI，to provide new insights for ALI prevention and treatment.

Objective:To compare the differences in clinical characteristics among the patients at clinical high risk for bipolar disorder(CHR-BD),the patients with bipolar disorder(BD),and the healthy controls(HC)at low risk,and to provide the basis for the diognasis and treatment of CHR-BD.Methods:For the first time,the BD risk criteria and prospective structured assessment tools were jointly used in outpatients aged 16-30 years,and 43 CHR-BD patients were included to ensure the accuracy of the assessment.Meanwhile,33 BD patients and 32 HC subjects were also enrolled.The clinical symptoms,neurocognitive function,and global functional levels of the subjects in the three groups were evaluated using observer-rated and self-rated tools.The CHR-BD and BD groups were combined,and Logistic regression analysis was used to identify the independent influencing factors related to diagnostic status;Pearson or Spearman correlation analysis was used to analyze the correlations between the global functional levels and the symptoms or neurocognitive characteristics of the patients in CHR-BD and BD groups.Results:There were statistically significant differences in the scores of symptom and global functional level scales among HC,CHR-BD,and BD groups(P<0.05).Compared with HC group,the scores of mood symptoms(anxiety,depression,and mania/hypomania),psychotic symptoms,total affective temperament questionnaire scores,and some dimensions(cyclothymic,depressive,irritable,and anxious temperaments)in CHR-BD and BD groups were significantly increased(P<0.001),while the global functional levels were significantly decreased(P<0.001).Compared with BD group,the lowest global functional level score in the past year in CHR-BD group was significantly increased(P=0.022),while the current global functional level score was significantly decreased(P=0.005).No significant differences were observed in neurocognitive function scores among the three groups(P>0.05).The lowest global functional level score in the past year was an independent influencing factor for BD diagnosis[odds ratio(OR)=0.952,95%confidence interval(CI):0.917-0.988,P=0.010].In both CHR-BD and BD patients,the current global functional levels were negatively correlated with depressive(r=-0.417,P=0.005;r=-0.617,P<0.001)and anxiety symptoms(r=-0.360,P=0.018;r=-0.506,P=0.003).In BD patients,the current global functional level was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.360,P=0.039),psychotic symptoms(r=-0.502,P=0.003),and affective temperament scores(r=-0.479,P=0.005),while the lowest global functional level in the past year was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.391,P=0.024).Conclusion:CHR-BD patients share similar mood symptom characteristics with BD patients,and their global functional levels are negatively correlated with depressive and anxiety symptoms.BD patients exhibit worse lowest global functional levels in the past year,and their global functional levels are negatively correlated with manic/hypomanic symptoms.

Breast cancer has emerged as the leading cause of cancer incidence and mortality among women globally,with approximately 70%of cases being estrogen receptor(ER)and/or progesterone receptor(PR)positive.The primary treatment for hormone receptor(HR)positive breast cancer is endocrine therapy;however,endocrine therapy resistance remains a critical area of ongoing research.Cyclin D1 is recognized as a biomarker for tumor phenotype and disease progression,and it has been established to correlate with the onset,progres-sion,and prognosis of breast cancer.Recently,studies have also reported the significant role of Cyclin D1 in endocrine resistance in breast cancer.This article provides an overview of the research progress on Cyclin D1 in breast cancer,with a particular emphasis on its relation-ship with endocrine therapy resistance,aiming to offer novel insights for the endocrine treatment of breast cancer.

Objective:To explore the value of three-dimensional automatic right ventricular quantitive analysis（3D Auto RVQ）technology in predicting the improvement of left ventricular ejection fraction（LVEF）in patients with heart failure with reduced ejection fraction（HFrEF）.Methods:A retrospective analysis was conducted on 89 HFrEF patients admitted to the Cardiology Department of Central China Fuwai Hospital of Zhengzhou University from April 2022 to June 2024. All patients received medication treatment and were further divided into heart failure with improved ejection fraction（HFimpEF）group and non HFimpEF group based on changes detected by echocardiography in LVEF after treatment. The clinical data，biological indicators，and medication treatment status of patients were collected，routine echocardiographic parameters and right ventricular strain parameters were measured，3D right ventricular ejection fraction（3D-RVEF），3D right ventricular stroke volume index（3D-RVSVI），3D right ventricular end-diastolic volume index（3D-RVEDVI），3D right ventricular end-systolic volume index（3D-RVESVI），3D tricuspid annular plane systolic excursion（3D-TAPSE），and 3D right ventricular fractional area change（3D-RVFAC）were measured using 3D Auto RVQ technology. The differences of the above parameters between the two groups were compared. The ROC curve was used to analyze the predictive efficiency of right ventricular parameters for HFimpEF，and the area under ROC curve（AUC）was calculated and compared. Logistic regression models were used to analyze the predictive value of right ventricular parameters for HFimpEF.Results:Compared with the non HFimpEF group，the HFimpEF group had a younger age，shorter heart failure course，a smaller proportion of males，New York Heart Association（NYHA）functional class ≥Ⅲ，and patients with concomitant coronary heart disease. The baseline LVEF，absolute value of two dimensional right ventricular global longitudinal strain（2D-RVGLS），3D-RVEF，3D-TAPSE，and 3D-RVSVI were higher in the HFimpEF group（all P<0.05）. ROC curve analysis showed that the AUC of 3D-RVEF for predicting HFimpEF was 0.858，and the predictive efficiency was higher than other right ventricular parameters. According to the Yoden index，the optimal cutoff value for predicting HFimpEF based on 3D-RVEF was 36.2%，with a corresponding sensitivity of 84.0% and specificity of 75.0%. After adjusting for clinical and other echocardiographic parameters，the logistic regression model showed that 3D-RVEF was an independent predictor of HFimpEF（ OR=1.435，95% CI=1.145-1.800， P<0.05）. Conclusions:The 3D-RVEF evaluated by 3D Auto RVQ technology has high predictive value for HFimpEF，which can provide a reference for clinical treatment，thereby improving the prognosis of HFrEF patients.

Qingzao Jiufeitang is a famous classical formula for treating lung injury caused by warm and dryness， included in the Catalogue of Ancient Famous Classical Formulas（The First Batch）. By systematically organizing ancient and modern literature on this formula， this study analyzed and verified the origin， medicinal composition， original plants and processing， dosage and decoction method， efficacy and application of this formula. According to the research， Qingzao Jiufeitang was first recorded in Yimen Falyu in the Qing dynasty， and its creation was mainly inspired by the Ming dynasty physician MIAO Xiyong's idea of the moisturizing drugs with sweet flavour and cold nature. Based on the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia） and the textual research results of modern scholars on traditional Chinese herbal medicines， the botanical sources and processing methods of the herbs in this formula are basically clarified. Among them， Mori Folium， Gypsum Fibrosum， Ginseng Radix et Rhizoma， Sesami Semen Nigrum， Asini Corii Colla， Ophiopogonis Radix and Eriobotryae Folium are consistent with the 2020 edition of the Chinese Pharmacopoeia. The primary source of Glycyrrhizae Radix et Rhizoma is the dried roots and rhizomes of Glycyrrhiza uralensis， family Leguminosae， while the primary source of Armeniacae Semen Amarum is the dried mature seeds of Prunus armeniaca， family Rosaceae. It is recommended to use Gypsum Ustum， stir-fried Sesami Semen Nigrum， stir-fried Armeniacae Semen Amarum， Asini Corii Colla bead， and honey-fried Eriobotryae Folium， and the rest of the raw products. According to the conversion of ancient and modern doses， the recommended dosages are 11.19 g for Mori Folium， 9.33 g for Gypsum Fibrosum， 3.73 g for Glycyrrhizae Radix et Rhizoma， 2.61 g for Ginseng Radix et Rhizoma， 3.73 g for Sesami Semen Nigrum， 4.48 g for Ophiopogonis Radix， 2.61 g for Armeniacae Semen Amarum， 3.73 g for Eriobotryae Folium. The decoction method is to add 300 mL of water， decoct it down to 180 mL， remove the residue， and then add 2.98 g of Asini Corii Colla into the decoction. Take it warm after meals， two to three times a day. Qingzao Jiufeitang has the effects of clearing dryness and moistening the lungs， nourishing Yin and invigorating Qi. In ancient times， it was mainly used to treat stagnation and depression of various Qi， as well as paralysis， asthma and vomiting. In modern clinical practice， it is mostly used to treat diseases in respiratory system， otolaryngology， skin system and digestive system caused by warm-dry impairing lung， deficiency of both Qi and Yin. The above research results can provide a reference for the later development of Qingzao Jiufeitang.