Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). METHODS: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. RESULTS: Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. CONCLUSIONS: Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies.

Identification of a 5-gene-risk score model for predicting luminal A-invasive lobular breast cancer survival.

Breast cancer is a devastating malignancy, among which the luminal A (LumA) breast cancer is the most common subtype. In the present study, we used a comprehensive bioinformatics approach in the hope of identifying novel prognostic biomarkers for LumA breast cancer patients. Transcriptomic profiling of 611 LumA breast cancer patients was downloaded from TCGA database. Differentially expressed genes (DEGs) between tumor samples and controls were first identified by differential expression analysis, before being used for the weighted gene co-expression network analysis. The subsequent univariate Cox regression and LASSO algorithm were used to uncover key prognostic genes for constructing multivariate Cox regression model. Patients were stratified into high-risk and low-risk groups according to the risk score, and subjected to multiple downstream analyses including survival analysis, gene set enrichment analysis (GSEA), inference on immune cell infiltration and analysis of mutation burden. Receiving operator curve analysis was also performed. A total of 7071 DEGs were first identified by edgeR package, pink module was found significantly associated with invasive lobular carcinoma (ILC). 105 prognostic genes and 9 predictors were identified, allowing the identification of a 5-key prognostic genes (LRRC77P, CA3, BAMBI, CABP1, ATP8A2) after intersection. These 5 genes, and the resulting Cox model, displayed good prognostic performance. Furthermore, distinct differences existed between two risk-score stratified groups at various levels. The identified 5-gene prognostic model will help deepen the understanding of the molecular and immunological mechanisms that affect the survival of LumA-ILC patients and guide and proper monitoring of these patients.

Quercetin radiosensitizes non-small cell lung cancer cells through the regulation of miR-16-5p/WEE1 axis.

BACKGROUND: Quercetin, a widely distributed bioflavonoid, plays a role in combating diverse human cancers including non-small cell lung cancer (NSCLC). However, the role of quercetin in reversing the radioresistance of NSCLC cells and its underlying mechanism are far from being elucidated. METHOD: Radiation-resistant NSCLC cell lines were established. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-16-5p and WEE1 G2 checkpoint kinase (WEE1) mRNA in radiation-resistant cells. After being treated with different concentrations of quercetin and different doses of X-ray, cell proliferation and apoptosis were monitored by CCK-8 assay, colony formation assay, and flow cytometry, respectively. Ultimately, the targeting relationship between miR-16-5p and WEE1 was verified via a dual fluorescent reporter gene assay. RESULTS: The expression of miR-16-5p was down-regulated in radiation-resistant cells, while the expression of WEE1 was up-regulated. Quercetin enhanced the radiosensitivity of NSCLC cells in a dose- and time-dependent manner. Furthermore, quercetin treatment increased the expression of miR-16-5p and decreased the expression of WEE1. The function of quercetin was reversed by miR-16-5p inhibitors or the transfection of WEE1 overexpressing plasmids. CONCLUSION: In conclusion, quercetin enhanced the radiosensitivity of NSCLC cells via modulating the expression of miR-16-5p and WEE1.

Naringenin inhibits osteoclastogenesis through modulation of helper T cells-secreted IL-4.

Naringenin (NAR) is a natural predominant flavanone and has a wide range of pharmacological activities. The aim of this study was to investigate the protective mechanisms of NAR on RANKL-induced osteoclastogenesis and osteoclast bone resorption. T cells were divided into four groups under different concentrations of NAR (0, 25, 50, 100 µM). CD4+ T cell subsets in different groups were evaluated by flow cytometry. TRAP staining, pit formation assays and F-actin ring immunofluorescent staining were performed. In addition, gene expression of osteoclast-specific markers was analyzed by qPCR and Western blot. Our results showed that compared with the control group, there were relatively fewer Th1 and Th17 cells and more Th2 cells and Treg cells in the NAR groups. Besides, the number of TRAP-positive multinucleated osteoclasts, the areas of bone resorption pits and the size and number of F-actin rings were notably decreased in the bone marrow macrophages (BMMs) treated with T-cell supernatant containing NAR. Moreover, NAR treatment dramatically reduced the expressions of cathepsin K, c-Fos, DC-STAMP, NFATc1, TRAP, and V-ATPase d2 at mRNA and protein levels. However, these effects were abolished by adding a neutralizing antibody against IL-4. In conclusion, NAR suppressed RANKL-induced osteoclastogenesis and osteoclast bone resorption by promoting the release of IL-4 from T cells.

Identification of C4BPA as biomarker associated with immune infiltration and prognosis in breast cancer.

Background: C4BPA is a gene that encodes the C4BP protein α chain and is involved in the complement system. C4BPA is regarded as a new biomarker for cancer, especially for non-small cell lung cancer and ovarian cancer. However, its role in breast cancer (BC) has not yet been determined. Methods: In this research, we used a bioinformatics approach to assess the prognostic significance of C4BPA in BC. Utilizing a variety of databases and analysis tools, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), R, STRING, and the Kaplan-Meier plotter, we specifically assessed the connection between C4BPA and BC. Results: C4BPA expression was markedly decreased in BC tissues compared to its expression in normal breast tissues (P<0.05). Additionally, a receiver operating characteristic (ROC) curve revealed that C4BPA has a significant capacity for prognostication and diagnostics. Additionally, C4BPA expression was linked to some immune infiltrating cells' functionality, according to gene set enrichment analysis (GSEA) and immune infiltration analysis. Low C4BPA expression was additionally related to poor progression-free interval (PFI) and overall survival (OS), according to the Kaplan-Meier method. We also found that C4BPA expression was independently connected to PFI and OS through Cox regression analysis. Finally, prognostic analysis of the various subgroups of breast invasive carcinoma (BRCA/BIC) in TCGA showed that patients with low C4BPA expression might have worse PFI and OS in patients with Luminal A compared to other BC subtypes. Conclusions: In conclusion, these results revealed that C4BPA could potentially act as a diagnostic biomarker for BC patients indicating unfavorable prognoses and offers valuable knowledge for creating therapeutics and prognostic indicators.

Effect of Previous Cancer History on Survival of Patients with Different Subtypes of Breast Cancer.

Patients with a previous cancer history (PCA) are routinely excluded from most clinical trials, which may limit the accuracy and universality of clinical trials. We aimed to explore the association between PCA and survival of patients with different molecular subtypes of breast cancer. Patients diagnosed with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were included in this retrospective cohort study. The primary outcome was overall survival (OS), which was calculated from date of diagnosis to date of death or censor date during this period. The relationship between PCA and OS of patients with different molecular subtypes of breast cancer was analyzed by the Kaplan-Meier curves and multivariate Cox proportional-hazards model. A total of 35,640 primary breast cancer patients were included, and 2,038 (5.72%) patients had a PCA. Female genital system cancer (491 cases, 24.09%) was the largest proportion type of previous cancer, and HER2-positive (24,754 cases, 69.46%) breast cancer was the most common subtype. Patients with previous female genital/endocrine system cancer history and other cancers history were associated with a poorer OS in overall patients, and in patients with triple-negative and HER2-positive subtypes (P < 0.05). In patients with Luminal A and Luminal B subtypes, previous other cancers history was related to poor OS (P < 0.05), while female genital/endocrine system cancer history may not influence the OS (P > 0.05). Subgroup analyses presented that PCA was related to poor OS in patients aged 40-64 years and ≥65 years (P <0.05), while prognosis in patients aged 18-40 years may not be influenced by PCA (P > 0.05). The impact of PCA on the prognosis of breast cancer patients was related to molecular type, patient age, and type of PCA. In clinical trials of breast cancer, the exclusion criteria for PCA patients may be modified according to the above variables.

Global Trends in Research of Androgen Receptor Associated With Breast Cancer From 2011 to 2020: A Scientometric Analysis.

Recently, the androgen receptor has been found as a potential prognostic index and therapeutic target for breast cancer. To reveal the current research status and hotspots in this area, we analyzed the characteristics of related publications from 2011 to 2020. All related publications from 2011 to 2020 were retrieved from the Web of Science. Biblioshiny, VOSviewer, and CiteSpace V were applied to obtain the information on annual publications and citations, the highest yielding countries and authors, influential journals and articles, as well as hot keywords. In total, 2,118 documents, including 1,584 original articles and 534 reviews, were retrieved. Annual publication output was rich from 2014 to 2018, reaching the top in 2017. A systematic review written by Lehman et al. in 2011 was the most-cited document and reference. The United States was the leading country with the maximum number of publications, citations, and link strengths with other countries. The journal publishing the most was Oncotarget. Lehmann was the author who had the highest link strengths with other authors. The most highlighted keywords were "androgen receptor" (n = 1,209), "breast cancer" (n = 690), "expression" (n = 545), "breast cancer" (n = 410), "prostate cancer" (n = 290), and so on, revealing the trend from molecular mechanism level to therapeutic use level. The androgen receptor plays a significant role in the development of breast cancers, whereas its therapeutic value seems to be controversial and needs further study. With the help of a scientometric analysis in this field, researchers can clarify the current research status and hotspots worth fully exploring.

Identification and Validation of a Four-Gene Ferroptosis Signature for Predicting Overall Survival of Lung Squamous Cell Carcinoma.

Background: Lung squamous cell carcinoma (LUSC) represents 30% of all non-small cell lung carcinoma. Targeted therapy is not sufficient for LUSC patients because of the low frequency of targeted-effective mutation in LUSC whereas immunotherapy offers more options for patients with LUSC. We explored a ferroptosis-related prognostic signature that can potentially assess the prognosis and immunotherapy efficacy of LUSC patients. Methods: A total of 502 LUSC patients were downloaded from The Cancer Genome Atlas (TCGA). The external validation data were obtained from the Gene Expression Omnibus (GEO): GSE73403. Then, we identified the candidate genes and constructed the prognostic signature through the Cox survival regression analyses and least absolute shrinkage and selection operator (LASSO). Risk score plot, Kaplan-Meier curve, and ROC curve were used to assess the prognostic power and performance of the model. The CIBERSORT algorithm estimated the fraction of immune cell types. TIDE was utilized to predict the response to immunotherapy. IMvigor210 was used to explore the association between the risk scores and immunotherapy outcomes. A nomogram combined selected clinical characteristics, and the risk scores were constructed. Results: We screened 132 differentially expressed ferroptosis-related genes. According to KEGG and GO pathway analyses, these genes were mainly engaged in the positive regulation of cytokine production, cytokine metabolic process, and oxidoreductase activity. We then constructed a prognostic model via LASSO regression. The proportions of CD8+ T cells, CD4+ activated T cells, and follicular helper T cells were significantly different between low-risk and high-risk groups. TIDE algorithm indicated that low-risk LUSC patients might profit more from immune checkpoint inhibitors. The predictive value of the ferroptosis gene model in immunotherapy response was further confirmed in IMvigor210. Finally, we combined the clinical characteristics with a LASSO regression model to construct a nomogram that could be easily applied in clinical practice. Conclusion: We identified a prognostic model that provides an accurate and objective basis for guiding individualized treatment decisions for LUSC.

Addition of Capecitabine to Adjuvant Chemotherapy May be the Most Effective Strategy for Patients With Early-Stage Triple-Negative Breast Cancer: A Network Meta-Analysis of 9 Randomized Controlled Trials.

Background and Objective: Previous studies determined the therapeutic effects of capecitabine-based chemotherapy regimens on early-stage triple-negative breast cancer (TNBC). However, the optimal strategy of capecitabine-based chemotherapy remains uncertain. We conducted this network meta-analysis to address this issue. Methods: We systematically searched PubMed, Embase, and the Cochrane Registry of Controlled Trials (CENTRAL) to retrieve eligible studies published before September 2021. Two independent reviewers extracted information from eligible studies using a pre-designed data extraction sheet. The primary outcome included disease-free survival, and the second outcome showed overall survival and adverse events. Direct meta-analysis was performed using RevMan 5.4, and Bayesian network analysis was performed using R version 3.6.1 with the "gemtc" and "rjags" packages. Results: Nine studies involving 3661 TNBC patients met the selection criteria. The network meta-analysis suggested that the addition of capecitabine to adjuvant chemotherapy achieved a significantly longer disease-free (HR = 0.66, 95% CrI = 0.49 to 0.86) and overall survival time (HR = 0.60, 95% CrI = 0.43 to 0.83) than standard chemotherapy. All comparisons did not achieve statistical significance. The addition of capecitabine to adjuvant chemotherapy was the most effective treatment for improving disease-free (81.24%) and overall survival (78.46%) times, and the replacement of capecitabine to adjuvant chemotherapy was the safest regime. Conclusions: Based on available evidence, capecitabine-based chemotherapy benefits TNBC patients, and the addition of capecitabine with adjuvant chemotherapy was the most effective regime. In contrast, the replacement of capecitabine to adjuvant chemotherapy was the safest regime. More studies of high quality and large scale are needed to confirm our findings.

Follicular carcinoma of the thyroid with a single metastatic lesion in the lumbar spine: A case report.

BACKGROUND: The bone is the second most common site of thyroid cancer metastasis, after the lung. Treatment options for bone metastasis of thyroid cancer include surgery, radioiodine therapy (RAIT), external radiation therapy, thyroid-stimulating hormone (TSH) inhibition, bisphosphonates, and small-molecule targeted therapies. In most cases, thyroid carcinoma is found in the thyroid tissue; reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare. CASE SUMMARY: We report a case of bone metastasis as the only clinical manifestation of thyroid cancer. The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion. No abnormal nodules were found in the bilateral thyroid glands. However, imaging studies were consistent with a spinal tumor, and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin. We adopted a multidisciplinary collaboration and comprehensive treatment approach. The patient underwent lumbar spine surgery, total resection of the thyroid, postoperative TSH suppression therapy, and RAIT. There were no complications associated with the operation, and the patient had good postoperative recovery. She has experienced no recurrence. CONCLUSION: Follicular thyroid carcinoma is associated with early hematogenous metastasis, and the bone is a typical site of metastasis. Single bone metastasis is not a contraindication to medical procedures, and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

Development and validation of a novel endoplasmic reticulum stress-related lncRNA prognostic signature and candidate drugs in breast cancer.

Breast cancer (BC), the most common malignancy in women, has a high cancer-related mortality. Endoplasmic reticulum stress (ERS), a response to the accumulation of unfolded proteins, has emerging roles in tumorigenesis, including invasion, metastasis, immune escape, etc. However, few studies have focused on the correlation between ERS with long non-coding RNAs (lncRNAs) in BC. We attempted to construct an ERS-related lncRNA prognostic signature and study its value in BC from tumor mutational burden (TMB), tumor immune microenvironment (TIME), cluster, clinical treatment, and so on. In the present study, transcriptomic and clinical data of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. Correlation test, Cox regression analysis, least absolute shrinkage, and selection operator (LASSO) method were performed to determine an ERS-related lncRNA prognostic signature. Survival and predictive performance were analyzed according to Kaplan-Meier curves and receiver operating characteristic (ROC) curves, while nomograms and calibration curves were established. Then, an enrichment analysis was performed to study the functions and biological processes of ERS-related lncRNAs. TMB and TIME were also analyzed to assess the mutational status and immune status. Additionally, by using consensus cluster analysis, we compared differences among tumor subtypes. Drug sensitivity analysis and immunologic efficacy evaluations were performed together for further exploration. We identified a novel prognostic signature consisting of 9 ERS-related lncRNAs. High-risk patients had worse prognoses. The signature had a good predictive performance as an independent prognostic indicator and was significantly associated with clinicopathological characteristics. Enrichment analysis showed that metabolic pathways were enriched in high-risk patients, while immune pathways were more active in low-risk patients. Low-risk patients had lower TMB, higher immune scores, and stronger immune functions. Cluster analysis clarified that cluster 2 had the most active immune functions and was sensitive to more drugs, which may have the best clinical immunological efficacy. A clinical efficacy evaluation revealed that patients in the low-risk group may benefit more from chemotherapy, targeted therapy, and immunotherapy. The novel signature has significant clinical implications in prognosis prediction for BC. Our study clarifies that there is a potential connection between the ERS-related lncRNAs and BC, which may provide new treatment guidelines for BC.

Nomogram for predicting overall survival in Chinese triple-negative breast cancer patients after surgery.

BACKGROUND: There are few nomograms for the prognosis of Chinese patients with triple-negative breast cancer (TNBC). AIM: To construct and validate a nomogram for overall survival (OS) of Chinese TNBC patients after surgery. METHODS: This study used the data of SEER*stat 8.3.5 and selected Chinese patients with TNBC operated on between 2010 and 2015. Univariate and multivariate Cox proportional hazard regression models were used. The identified variables were integrated to form a predictive nomogram and risk stratification model; it was assessed with C-indexes and calibration curves. RESULTS: The median and maximal OS of the 336 patients was 39 and 83 mo, respectively. The multivariate analysis showed that age (P = 0.043), marital status (P = 0.040), tumor localization (P = 0.030), grade (P = 0.035), T classification (P = 0.012), and N classification (P = 0.002) were independent prognostic factors. The six variables were combined to construct a 1-, 3- and 5-year OS nomogram. The C-indexes of the nomogram to predict OS were 0.766 and compared to the seventh edition staging system, which was higher (0.766 vs 0.707, P < 0.001). In order to categorize patients into different prognostic groups, a risk stratification model was created. There was a significant difference between the Kaplan-Meier curves of the entire cohort and each disease stage according to the nomogram. CONCLUSION: The nomogram provided prognostic superiority over the traditional tumor, node and metastasis system. It could help clinicians make individual OS or risk predictions for Chinese TNBC patients after surgery.

Global research trends on anti-PD-1/anti-PD-L1 immunotherapy for triple-negative breast cancer: A scientometric analysis.

In recent years, anti-PD-1/anti-PD-L1 has been considered to be a valuable therapeutic target and prognostic indicator for triple-negative breast cancer. We analyzed all publications published in the field from their inception until the present day in order to determine the current research status and hotspots. All related publications were searched on the Web of Science. Our research used R-studio (bibliometrix package), VOSviewer, and CiteSpace to analyze and obtain annual publications and citation information, articles, highest publication countries and affiliations, influential journals and authors, keyword analysis, and keyword bursts. In total, 851 documents were retrieved including 628 articles and 223 review articles. The output of publications increased year by year from 2013 to 2021. However, the average article citation times reached the top in 2014 but generally showed a downward trend from 2014 to 2021. It was an article written by Schmid et al. in 2018 that received the most citations. With regard to publications, citations, and link strength, among the top countries was the United States. Cancers was the most published journal. Schmid and Loi ranked top in total citations and h-index. Schmid has the largest M-index and Loi has the most publication. The keywords that received the most attention were "Immunotherapy", "PD-L1", "Triple-negative breast cancer", "Tumor-infiltrating lymphocytes", and "Expression". According to the report, this current research focuses on immunotherapy for triple-negative breast cancer and the expression of PD-L1 and tumor-infiltrating lymphocytes (TILs). Pembrolizumab and Atezolizumab plus chemotherapy have completed the Phase 3 clinical trial. However, the biomarkers were limited in predicting the treatment prognosis. Through the scientometric analysis, we can understand the current research status and potential research points in this filed and provide research direction for researchers.

Regression of intervertebral disc calcification combined with ossification of the posterior longitudinal ligament: A case report.

BACKGROUND: Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment. CASE SUMMARY: Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment. CONCLUSION: IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

Prognostic and Immune-Infiltrate Significance of miR-222-3p and Its Target Genes in Thyroid Cancer.

Thyroid cancer (THCA) is a common endocrine malignancy. With increasing incidence and low mortality, balancing the therapeutic approach is an inevitable issue. This study aimed to confirm the role of miR-222-3p and its target genes in THCA survival and immune infiltration. From different expression analyses based on the GEO and TCGA databases, we predicted and subsequently identified the key target genes of miR-222-3p. We then explored the expression, enrichment, pairwise correlation, protein expression, survival analysis, principal component analysis, and immune significance of the critical genes using bioinformatics analysis. The present study demonstrated that NEGR1, NTNG1, XPNPEP2, NTNG2, CD109, OPCML, and PRND are critical genes. The miR-222-3p was highly expressed, probably leading to low NEGR1 and high PRND expression in THCA tissues. Low NEGR1 expression indicated favorable prognosis in THCA patients, and high PRND expression indicated poor prognosis. Seven critical genes were significantly related to gender, age, race, tumor stage, and lymph node metastasis. In addition, the seven-gene biomarker exhibited a certain diagnostic value. Finally, CD109 expression was closely correlated with immune cells, especially B cells and CD4+ T cells. The miR-222-3p and its critical target genes could be promising biomarkers for the prognosis of THCA and may emerge as key regulators of immune infiltration in THCA.

The Global, Regional, and National Burden and Trends of Breast Cancer From 1990 to 2019: Results From the Global Burden of Disease Study 2019.

BACKGROUND: The burden of breast cancer has been increasing globally. The epidemiology burden and trends need to be updated. This study aimed to update the burden and trends of breast cancer incidences, deaths, and disability-adjusted life-years (DALYs) from 1990 to 2019, using the Global Burden of Disease 2019 study. METHODS: The data of incidences, deaths, DALYs, and age-standardized rates were extracted. Estimated annual percentage changes were used to quantify the trends of age-standardized rates. Besides, the population attributable fractions of the risk factors of breast cancer were also estimated. RESULTS: Globally, the incidences of breast cancer increased to 2,002,354 in 2019. High social-development index (SDI) quintiles had the highest incidence cases with a declining trend in age-standardized incidence rate. In 2019, the global deaths and DALYs of breast cancer increased to 700,660 and 20,625,313, respectively. From 1990 to 2019, the age-standardized mortality rates and age-standardized DALY rates declined globally, especially in high and high-middle SDI quintiles. Besides, the trends varied from different regions and countries. The proportion of the patients in the 70+ years age group increased globally. Deaths of breast cancer attributable to high fasting plasma glucose and high body mass index increased globally, and high fasting plasma glucose was the greatest contributor to the global breast cancer deaths. CONCLUSION: The burden of breast cancer in higher SDI quintiles had gone down while the burden was still on the rise in lower SDI quintiles. It is necessary to appeal to the public to decrease the exposure of the risk factors.

Individualized treatment of breast cancer with chronic renal failure: A case report and review of literature.

BACKGROUND: Studies have shown that patients with chronic renal failure (CRF) are more likely to suffer from breast cancer and other malignant tumors. To our knowledge, CRF can reduce drug excretion, thereby increase drug exposure and lead to increased toxicity, which will limit drug treatment and lead to tumor progression. Currently, there are few successful reports on the combination of docetaxel, trastuzumab, and pertuzumab (THP) as a neoadjuvant treatment regimen for breast cancer patients with CRF. CASE SUMMARY: We report a breast cancer (cT2N2M0, Her-2+/HR-) patient with CRF. It was a clinical stage IIIA tumor on the left breast. The patient had suffered from uremia for 2 years, and her heart function was normal. Based on the pathological type, molecular type, and clinical stage of breast cancer, and the patient's renal function, the clinician analyzed the pharmacological and pharmacokinetic characteristics of the antitumor drugs after consulting the relevant literature, and prescribed the neoadjuvant regimen of THP (docetaxel 80 mg/m², trastuzumab 8 mg/kg for the first dose, and 6 mg/kg for the maintenance dose with pertuzumab 840 mg for the first dose and 420 mg for the maintenance dose), once every 3 wk, for a total of 6 courses. The neoadjuvant treatment had a good effect, and the patient then underwent surgery which was uneventful. CONCLUSION: CRF is not a contraindication for systemic treatment and surgery of breast cancer. The THP regimen without dose adjustment may be a safe and effective neoadjuvant treatment for HER-2 positive breast cancer patients with CRF.

Prognostic and predictive value of HURP in non­small cell lung cancer.

Previous studies have revealed that HURP (also known as DLGAP5 or KIAA0008) is overexpressed in many types of human cancers, such as hepatocellular carcinoma, squamous cell bladder cancer, and transitional cell carcinoma, indicating that HURP is a putative oncoprotein that promotes carcinogenesis through various molecular mechanisms. However, the role of HURP in the pathogenesis of non­small cell lung cancer (NSCLC) has not been reported. In the present study, we investigated the prognostic value of HURP among NSCLC patients through the GEO database. The online tool of KM­plotter was used to identify the correlation of HURP expression and the survival of NSCLC patients. We found the HURP expression at the mRNA level was correlated with the clinicopathologic characteristics and prognosis of NSCLC patients. HURP was highly expressed in aggressive NSCLC cells, and its higher expression was associated with shorter survival. Further cytological experiments revealed that the silencing of HURP caused cell cycle arrest and inhibited the proliferation of NSCLC cells. Transwell assay showed that HURP shRNA inhibited cell migration and invasion in vitro. The bioinformatic analysis suggests that HURP promotes carcinogenesis in multiple manners. Taken together, we revealed the prognostic value of HURP in NSCLC patients and HURP may be a potential therapeutic target for NSCLC.

One visualization simulation operation system for distal femoral fracture.

A computer-aided 3-dimensional (3D) visualization operation simulation system based on computer-aided design (CAD) Unigraphics NX and Mimics software was established to provide orthopedic surgeons with an actual and reliable system in treating of distal femoral fracture.According to the preoperative CT data, 3D reconstruction of the distal femoral fracture could be achieved by the Mimics software. Then, the CAD Unigraphics NX software was used to measure the model function of all the related surgical instruments, including less invasive stabilization system (LISS) and retrograde intramedullary nail fixation.The function of CAD Unigraphics NX and Mimics software was successful in assisting in the treatment of distal femoral fracture with LISS and retrograde intramedullary nail fixation. The operation procedure was actual, visualized, and lifelike. Moreover, the operation effect could be estimated before surgery.The virtual surgery system may improve the reliability and safety of the operative care of distal femoral fracture.