Memory B cell repertoire from triple vaccinees against diverse SARS-CoV-2 variants.

Omicron (B.1.1.529), the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising concerns about the effectiveness of antibody therapies and vaccines1,2. Here we examined whether sera from individuals who received two or three doses of inactivated SARS-CoV-2 vaccine could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2 out of 60) and 95% (57 out of 60) for individuals who had received 2 and 3 doses of vaccine, respectively. For recipients of three vaccine doses, the geometric mean neutralization antibody titre for Omicron was 16.5-fold lower than for the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in triple vaccinees, half of which recognized the receptor-binding domain, and showed that a subset (24 out of 163) potently neutralized all SARS-CoV-2 variants of concern, including Omicron. Therapeutic treatments with representative broadly neutralizing monoclonal antibodies were highly protective against infection of mice with SARS-CoV-2 Beta (B.1.351) and Omicron. Atomic structures of the Omicron spike protein in complex with three classes of antibodies that were active against all five variants of concern defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to a class of antibodies that bind on the right shoulder of the receptor-binding domain by altering local conformation at the binding interface. Our results rationalize the use of three-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are rational targets for a universal sarbecovirus vaccine.

Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

Time-dependent analysis of erectile dysfunction in kidney transplant recipients: insights from four distinct time periods.

BACKGROUND AND INTENTION: Erectile dysfunction (ED) is an underappreciated clinical condition in men. This study aims to compare the dynamic changes in the distribution of ED among male kidney transplant recipients (mKTRs) in four epochs: end-stage renal disease period (ESRDp), early post-transplant period (EPTP), pre-COVID-19, and post-COVID-19. METHODS: General information was gathered through interviews, follow-ups, and medical records. The International Index of Erectile Function Questionnaire-5 was used to assess erectile function. The Mann-Whitney U test and chi-square test were used to analyze differences in ED strength. Univariate and logistic regression analyses were conducted to identify risk factors for ED. RESULTS: The database contains 230 mKTRs. In the ESRDp, 17.0% had normal erectile function, 53.5% had mild ED, 18.3% had moderate ED, and 11.3% had severe ED. In the EPTP, the distribution was 38.2% normal, 42.6% mild, 10.8% moderate, and 8.2% severe. In the pre-COVID-19 period, it was 34.3%, 47.3%, 10.4%, and 7.8%, and in the post-COVID-19 period, it was 23.0%, 45.6%, 21.3%, and 10.0%. Overall, erectile function improved after kidney transplant (KT). However, post-COVID-19, the proportion of erectile function significantly decreased compared to EPTP and pre-COVID-19 periods. Risk factors for post-pandemic ED included degree, Generalized Anxiexy Disorder-7, kidney donor type, postoperative time, hypertension and hemoglobin concentration. CONCLUSION: KT improves erectile function in mKTRs within 5 years, but post-SARS-CoV-2 viral infection, ED worsens due to altered risk factors. These findings inform future research for comprehensive ED prevention and management strategies in this population.

A nomogram and risk stratification system for predicting survival in T1-2N0-1 breast cancer patients with liver metastasis in females: a population-based study.

PURPOSE: Liver was one of the most common distant metastatic sites in breast cancer. Patients with distant metastasis were identified as American Joint Committee on Cancer (AJCC) stage IV indicating poor prognosis. However, few studies have predicted the survival in females with T1-2N0-1 breast cancer who developed liver metastasis. This study aimed to explore the clinical features of these patients and establish a nomogram to predict their overall survival. RESULTS: 1923 patients were randomly divided into training (n = 1154) and validation (n = 769) cohorts. Univariate and multivariate analysis showed that age, marital status, race, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), chemotherapy, surgery and bone metastasis, brain metastasis were considered the independent prognostic indicators. We developed a nomogram according to these ten parameters. The consistency index (c-index) was 0.72 (95% confidence interval CI 0.70-0.74) in the training cohort, 0.72 (95% CI 0.69-0.74) in the validation cohort. Calibration plots indicated that the nomogram-predicted survival was consistent with the recorded 1-, 3- and 5-year prognoses. Decision curve analysis curves in both the training and validation cohorts demonstrated that the nomogram showed better prediction than the AJCC TNM (8th) staging system. Kaplan Meier curve based on the risk stratification system showed that the low-risk group had a better prognosis than the high-risk group (P < 0.001). CONCLUSIONS: A predictive nomogram and risk stratification system were constructed to assess prognosis in T1-2N0-1 breast cancer patients with liver metastasis in females. The risk model established in this study had good predictive performance and could provide personalized clinical decision-making for future clinical work.

Pamiparib in patients with locally advanced or metastatic HER2-negative breast cancer with germline BRCA mutations: a phase II study.

PURPOSE: To evaluate the efficacy and safety of pamiparib in patients with locally advanced or metastatic human epidermal growth factor receptor 2-negative (HER2-) breast cancer, with deleterious or suspected deleterious germline BRCA1/2 mutations (gBRCA1/2 m). METHODS: In this open-label, phase II, multicenter study in China (NCT03575065), patients with triple-negative breast cancer (TNBC cohort) or hormone receptor-positive (HR+)/HER2- breast cancer (HR+/HER2- cohort) and ≤ 2 prior lines of chemotherapy received pamiparib 60 mg orally twice daily in 28-day, continuous cycles. The primary endpoint was objective response rate (ORR; RECIST v1.1) by independent review committee. RESULTS: In total, 88 patients were enrolled (TNBC cohort: 62; HR+/HER2- cohort: 26). Median age was 45.5 (range: 27-67) years, and 60 patients (68.2%) had received 1 or 2 prior lines of chemotherapy; 42 patients (47.7%) had previously received platinum chemotherapy. In the TNBC cohort, ORR was 38.2% (95% confidence interval [CI] 25.4-52.3) and median duration of response (DoR) was 7.0 months (95% CI 3.9-not estimable). In the HR+/HER2- cohort, ORR was 61.9% (95% CI 38.4-81.9) and median DoR was 7.5 months (95% CI 5.6-14.8). The most common treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and ≥ Grade 3 TEAEs were hematologic (including anemia, decreased neutrophil count, and decreased white blood cell count). Overall, 64.8% of patients had TEAEs leading to dose reduction and 2.3% had TEAEs leading to treatment discontinuation. CONCLUSION: Pamiparib showed encouraging efficacy and an acceptable safety profile in patients with locally advanced and metastatic HER2- breast cancer with gBRCA1/2 m. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03575065; July 2, 2018.

LncRNA TDRKH-AS1 promotes breast cancer progression via the miR-134-5p/CREB1 axis.

BACKGROUND: Breast cancer (BC) is a prevalent malignancy with complex etiology and varied clinical behavior. Long non-coding RNAs (lncRNAs) have emerged as key regulators in cancer progression, including BC. Among these, lncRNA TDRKH-AS1 has been implicated in several cancers, but its role in BC remains unclear. METHODS: We conducted a comprehensive investigation to elucidate the role of TDRKH-AS1 in BC. Clinical samples were collected from BC patients, and BC cell lines were cultured. Bioinformatics analysis using the starBase database was carried out to assess TDRKH-AS1 expression levels in BC tissue samples. Functional experiments, including knockdown, colony formation, CCK-8, Transwell, and wound-healing assays, were conducted to determine the role of TDRKH-AS1 in BC cell proliferation and invasion. Luciferase reporter and RIP assays were used to examine the interactions between TDRKH-AS1 and miR-134-5p. In addition, the downstream target gene of miR-134-5p, cAMP response element-binding protein 1 (CREB1), was identified and studied using various methods, including RT-qPCR, immunoprecipitation, and rescue experiments. In vivo experiments using mouse tumor xenograft models were conducted to examine the role of TDRKH-AS1 in BC tumorigenesis. RESULTS: TDRKH-AS1 was found to be significantly upregulated in BC tissues and cell lines. High TDRKH-AS1 expression correlated with advanced BC stages and worse patient outcomes. Knockdown of TDRKH-AS1 led to decreased BC cell proliferation and invasion. Mechanistically, TDRKH-AS1 acted as a sponge for miR-134-5p, thereby reducing the inhibitory effects of miR-134-5p on CREB1 expression. Overexpression of CREB1 partially rescued the effects of TDRKH-AS1 knockdown in BC cells. In vivo studies further confirmed the tumor-promoting role of TDRKH-AS1 in BC. CONCLUSIONS: Our study unveiled a novel regulatory axis involving TDRKH-AS1, miR-134-5p, and CREB1 in BC progression. TDRKH-AS1 functioned as an oncogenic lncRNA by promoting BC cell proliferation and invasion through modulation of the miR-134-5p/CREB1 axis. These findings highlighted TDRKH-AS1 as a potential diagnostic biomarker and therapeutic target for BC treatment.

A Statistical Prediction Model for Survival After Kidney Transplantation from Deceased Donors.

BACKGROUND In an environment of limited kidney donation resources, patient recovery and survival after kidney transplantation (KT) are highly important. We used pre-operative data of kidney recipients to build a statistical model for predicting survivability after kidney transplantation. MATERIAL AND METHODS A dataset was constructed from a pool of patients who received a first KT in our hospital. For allogeneic transplantation, all donated kidneys were collected from deceased donors. Logistic regression analysis was used to change continuous variables into dichotomous ones through the creation of appropriate cut-off values. A regression model based on the least absolute shrinkage and selection operator (LASSO) algorithm was used for dimensionality reduction, feature selection, and survivability prediction. We used receiver operating characteristic (ROC) analysis, calibration, and decision curve analysis (DCA) to evaluate the performance and clinical impact of the proposed model. Finally, a 10-fold cross-validation scheme was implemented to verify the model robustness. RESULTS We identified 22 potential variables from which 30 features were selected as survivability predictors. The model established based on the LASSO regression algorithm had shown discrimination with an area under curve (AUC) value of 0.690 (95% confidence interval: 0.557-0.823) and good calibration result. DCA demonstrated clinical applicability of the prognostic model when the intervention progressed to the possibility threshold of 2%. An average AUC value of 0.691 was obtained on the validation data. CONCLUSIONS Our results suggest that the proposed model can predict the mortality risk for patients after kidney transplants and could help kidney specialists choose kidney recipients with better prognosis.

Photoredox-Catalyzed Dehydrogenative Csp3-Csp2 Cross-Coupling of Alkylarenes to Aldehydes in Flow.

Executing photoredox reactions in flow offers solutions to frequently encountered issues regarding reproducibility, reaction time, and scale-up. Here, we report the transfer of a photoredox-catalyzed benzylic coupling of alkylarenes to aldehydes to a flow chemistry setting leading to improvements in terms of higher concentration, shorter residence times, better yields, ease of catalyst preparation, and enhanced substrate scope. Its applicability has been demonstrated by a multi-gram-scale reaction using high-power light-emitting diodes (LEDs), late-stage functionalization of selected active pharmaceutical ingredients (APIs), and also a photocatalyst recycling method.

Fifteen-MiRNA-Based Signature Is a Reliable Prognosis-Predicting Tool for Prostate Cancer Patients.

Recurrence is a major problem for prostate cancer patients, thus, identifying prognosis-related markers to evaluate clinical outcomes is essential. Here, we established a fifteen-miRNA-based recurrence-free survival (RFS) predicting signature based on the miRNA expression profile extracted from The Cancer Genome Atlas (TCGA) database by the LASSO Cox regression analysis. The median risk score generated by the signature in both the TCGA training and the external Memorial Sloan-Kettering Cancer Center (MSKCC) validation cohorts was employed and the patients were subclassified into low- and high-risk subgroups. The Kaplan-Meier plot and log-rank analyses showed significant survival differences between low- and high-risk subgroups of patients (TCGA, log-rank P < 0.001 & MSKCC, log-rank P = 0.045). In addition, the receiver operating characteristic curves of both the training and external validation cohorts indicated the good performance of our model. After predicting the downstream genes of these miRNAs, the miRNA-mRNA network was visualized by Cytoscape software. In addition, pathway analyses found that the differences between two groups were mainly enriched on tumor progression and drug resistance-related pathways. Multivariate analyses revealed that the miRNA signature is an independent indicator of RFS prognosis for prostate cancer patients with or without clinicopathological features. In summary, our novel fifteen-miRNA-based prediction signature is a reliable method to evaluate the prognosis of prostate cancer patients.

Mitochondrial targeted doxorubicin derivatives delivered by ROS-responsive nanocarriers to breast tumor for overcoming of multidrug resistance.

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer: Screening of 16,501 unselected patients with breast cancer and 5890 controls by next-generation sequencing.

BACKGROUND: Partner and localizer BRCA2 (PALB2) is a breast cancer predisposition gene, but the clinical relevance of PALB2 germline mutations in Chinese patients with breast cancer remains unknown. This study attempted to investigate the full prevalence and spectrum of PALB2 germline mutations in China and the associations between PALB2 germline mutations and breast cancer risk. METHODS: A total of 21,216 unselected patients with breast cancer were enrolled from 10 provinces in China, and 5890 Chinese women without cancer were enrolled as healthy controls. PALB2 screening was based on next-generation sequencing. RESULTS: A total of 16,501 BRCA1/2-negative patients with breast cancer were analyzed. Deleterious PALB2 mutation carriers accounted for 0.97% (n = 160) in the breast cancer cohort and for 0.19% (n = 11) in the healthy control cohort. Forty-one novel PALB2 germline mutations were identified. A high frequency of PALB2 c.751C>T was detected, and it accounted for 10.63% of the PALB2 germline mutations detected (17 of 160). PALB2 mutations were significantly associated with increased breast cancer risk (odds ratio [OR], 5.23; 95% confidence interval [CI], 2.84-9.65; P < .0001), especially among women 30 years old or younger (OR, 10.09; 95% CI, 3.95-25.79; P < .0001). Clinical characteristics, including a family history, bigger tumor size, triple-negative breast cancer, positive lymph nodes, and bilateral breast cancer, were closely related to PALB2 mutations. CONCLUSIONS: This study revealed a comprehensive spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer in China. PALB2 germline mutations confer a moderately increased risk for breast cancer but profoundly increase breast cancer risk for those 30 years old or younger in the Chinese population.

A Practical Method for Continuous Production of sp3-Rich Compounds from (Hetero)Aryl Halides and Redox-Active Esters.

A practically useful coupling reaction between aromatic halides and redox-active esters was realized by nickel catalysis through the use of a packed zinc bed column in continuous flow. Multiple reuse of the column showed a negligible decrease in efficiency, affording high space/time yields. A wide range of substrates, including a number of heteroaryl halides and polyfunctional materials were coupled in generally good yields. Longer-time and larger-scale experiments further demonstrates the robustness of the system.

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China.

To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.

Using the capnogram to assess pulmonary perfusion during a lobectomy: case studies.

Capnography is an effective and non-invasive method for monitoring patients during general anesthesia and can reflect the changes in both the respiratory function as well as the circulatory function. In this paper, we present four cases of lobectomy in which we observed a "chair-like" waveform on performing capnography after the surgery. In all the cases, the appearance of this "chair-like" waveform led to the suspicion of a blockage in the pulmonary artery perfusion, which was then confirmed to be an obstruction in the pulmonary artery on further investigation. This suggests that during lobectomy, capnography can help confirm that the pulmonary circulation is unobstructed. We believe that it is very important to observe the changes of end-tidal carbon dioxide pressure and capnogram during one-lung ventilation, particularly in cases of pulmonary artery anastomosis.

A New World for Chemical Synthesis?

This perspective seeks to provide an overarching vision of the current state of chemical synthesis methodology using machinery as enabling tools. It highlights current capabilities and limitations in this highly digitallyconnected world and suggests areas where new opportunities may arise in the future by going well beyond our present levels of innovation and automation. There is a new need for improved downstream processing tools, advanced reactor design, computational predictive algorithms and integration of robotic systems to maximise the human resource to facilitate a new era in the assembly of our functional materials.

Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides.

First introduced into medicines in the 1930s, the sulfonamide functional group continues to be present in a wide range of contemporary pharmaceuticals and agrochemicals. Despite their popularity in the design of modern bioactive molecules, the underpinning methods for sulfonamide synthesis are essentially unchanged since their introduction, and rely on the use of starting materials with preinstalled sulfur-functionality. Herein we report a direct single-step synthesis of sulfonamides that combines two of the largest monomer sets available in discovery chemistry, (hetero)aryl boronic acids and amines, along with sulfur dioxide, using a Cu(II) catalyst, to deliver a broad range of sulfonamides. Sulfur dioxide is provided by the surrogate reagent DABSO. The reaction tolerates broad variation in both coupling partners, including aryl, heteroaryl and alkenyl boronic acids, as well as cyclic and acyclic alkyl secondary amines, and primary anilines. We validate the method by showing that a variety of drugs, and drug-fragments, can be incorporated into the process.

Photochemical Homologation for the Preparation of Aliphatic Aldehydes in Flow.

Cheap and readily available aqueous formaldehyde was used as a formylating reagent in a homologation reaction with nonstabilized diazo compounds, enabled by UV photolysis of bench-stable oxadiazolines in a flow photoreactor. Various aliphatic aldehydes were synthesized along with the corresponding derivatized alcohols and benzimidazoles. No transition-metal catalyst or additive was required to affect the reaction, which proceeded at room temperature in 80 min.

Germline mutations of PALB2 gene in a sequential series of Chinese patients with breast cancer.

BACKGROUND: PALB2 (Partner and Localizer of BRCA2) is recently recognized as a breast cancer predisposition gene. Germline loss-of-function mutations in PALB2 lead to increased breast cancer risk. Since the germline mutation frequency of PALB2 is much less than BRCA1/2, the distinct mutation spectrum of PALB2 is still obscure. To verify the utility of PALB2 genetic testing in Chinese population, we assessed the mutational frequency, spectrum, and predictors of the PALB2 gene in a sequential series of Chinese breast cancer patients from our Research DNA Bank. METHODS: We examined breast cancer samples (n = 2279) collected from 2000 through 2016 from Chinese patients who agreed to participate in research DNA banking. To identify the mutations, complete coding sequence and intron-exon boundaries of PALB2 were screened with Next-Generation Sequencing. Personal and family histories were synchronously collected for mutation identification. RESULTS: Among the 2279 breast cancer patients, 305 patients were familial breast cancer cases and the rest 1967 patients were sporadic breast cancer cases. PALB2 loss-of-function mutation carriers accounted for 1.31% (n = 4) and 0.56% (n = 11) in familial and sporadic breast cancer cohort separately. In total, 30 missenses, four nonsenses, three frameshifts, three splicings, and one inframe deletions of PALB2 were identified in this study. Among the deleterious mutations, PALB2 c.1744C>T, c.2748+1G>A, c.2749-1G>C, c.3114-1G>A were newly identified in sporadic breast cancer, and c.3271delC newly found in familial breast cancer. Based on in silico analysis, we found two potentially damaging missense variants with high frequency: c.1213C>G, c.3054G>C, and classified six new potentially damaging missense variants. CONCLUSIONS: Our data presented the germline mutation status of PALB2 in Chinese breast cancer patients, suggesting that loss-of-function germline mutations of PALB2 are important in both familial and sporadic breast cancer. Clinically, these data may be helpful in genetic counseling of breast cancer patients with PALB2 germline mutation.

RNA-Sequence Analysis Reveals Differentially Expressed Genes (DEGs) in Patients Exhibiting Different Risks of Tumor Metastasis.

BACKGROUND Breast cancer is one of the most common malignancies in women. In a previous study, we found that for two patients who had a high risk of lymphatic metastasis, lymphatic metastasis did not occur; whereas, for two patients who had a low risk of lymphatic metastasis, lymphatic metastasis did occur. MATERIAL AND METHODS We analyzed the differential gene expressions of these four patients by RNA-sequence. The data (HRNM_T versus HRNM_N, LRYM_T versus LRYM_N, and HRNM_T versus LRYM_T) was then processed using differentially expressed genes (DEGs) analysis, functional analysis for DEGs, and PPI network construct. RESULTS For HRNM_T versus HRNM_N, there were 224 DEGs. There were 504 DEGs for LRYM_T versus LRYM_N, and 88 DEGs for LRYM_T versus LRYM_N. For HRNM_T versus HRNM_N, DEGs were up-regulated mainly in the cell cycle, the IL-17 signaling pathway, and the progesterone-mediated oocyte maturation; DEGs were down-regulated mainly in the IL-17 signaling pathway. For LRYM_T versus LRYM_N, DEGs were up-regulated mainly in protein digestion and absorption, and cytokine-cytokine receptor interaction; DEGs were down-regulated mainly in ECM-receptor interaction. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in the PPAR signaling pathway; DEGs were downregulated mainly in the adipocytokine signaling pathway. The DEGs were screened to construct PPI networks. CONCLUSIONS The GO and KEGG functional enrichments of HRNM_T versus HRNM_N, and LRYM_T versus LRYM_N were consistent with earlier studies. For HRNM_T versus LRYM_T, DEGs were up-regulated mainly in PPAR signaling; DEGs were down-regulated mainly in the adipocytokine pathway.

Retrospective and comparative analysis of (99m)Tc-Sestamibi breast specific gamma imaging versus mammography, ultrasound, and magnetic resonance imaging for the detection of breast cancer in Chinese women.

BACKGROUND: Diagnosing breast cancer during the early stage may be helpful for decreasing cancer-related mortality. In Western developed countries, mammographies have been the gold standard for breast cancer detection. However, Chinese women usually have denser and smaller-sized breasts compared to Caucasian women, which decreases the diagnostic accuracy of mammography. However, breast specific gamma imaging, a type of molecular functional breast imaging, has been used for the accurate diagnosis of breast cancer and is not influenced by breast density. Our objective was to analyze the breast specific gamma imaging (BSGI) diagnostic value for Chinese women. METHODS: During a 2-year period, 357 women were diagnosed and treated at our oncology department and received BSGI in addition to mammography (MMG), ultrasound (US) and magnetic resonance imaging (MRI) for diagnostic assessment. We investigated the sensitivity and specificity of each method of detection and compared the biological profiles of the four imaging methods. RESULTS: A total of 357 women received a final surgical pathology diagnosis, with 168 malignant diseases (58.5 %) and 119 benign diseases (41.5 %). Of these, 166 underwent the four imaging tests preoperatively. The sensitivity of BSGI was 80.35 and 82.14 % by US, 75.6 % by MMG, and 94.06 % by MRI. Furthermore, the breast cancer diagnosis specificity of BSGI was high (83.19 % vs. 77.31 % vs. 66.39 % vs. 67.69 %, respectively). The BSGI diagnostic sensitivity for mammographic breast density in women was superior to mammography and more sensitive for non-luminal A subtypes (luminal A vs. non-luminal A, 68.63 % vs. 88.30 %). CONCLUSIONS: BSGI may help improve the ability to diagnose early stage breast cancer for Chinese women, particularly for ductal carcinoma in situ (DCIS), mammographic breast density and non-luminal A breast cancer.