Smart Solid-State Interphases Enable High-Safety and High-Energy Practical Lithium Batteries.

With the electrochemical performance of batteries approaching the bottleneck gradually, it is increasingly urgent to solve the safety issue. Herein, all-in-one strategy is ingeniously developed to design smart, safe, and simple (3S) practical pouch-type LiNi0.8Co0.1Mn0.1O2||Graphite@SiO (NCM811||Gr@SiO) cell, taking full advantage of liquid and solid-state electrolytes. Even under the harsh thermal abuse and high voltage condition (100 °C, 3-4.5 V), the pouch-type 3S NCM811||Gr@SiO cell can present superior capacity retention of 84.6% after 250 cycles (based pouch cell: 47.8% after 250 cycles). More surprisingly, the designed 3S NCM811||Gr@SiO cell can efficiently improve self-generated heat T1 by 45 °C, increase TR triggering temperature T2 by 40 °C, and decrease the TR highest T3 by 118 °C. These superior electrochemical and safety performances of practical 3S pouch-type cells are attributed to the robust and stable anion-induced electrode-electrolyte interphases and local solid-state electrolyte protection layer. All the fundamental findings break the conventional battery design guidelines and open up a new direction to develop practical high-performance batteries.

Immune checkpoint inhibitor plus chemotherapy as first-line treatment for non-small cell lung cancer with malignant pleural effusion: a retrospective multicenter study.

BACKGROUND: Immune checkpoint inhibitors (ICI) combined with chemotherapy are efficacious for treating advanced non-small cell lung cancer (NSCLC); however, the effectiveness of this approach in the malignant pleural effusion (MPE) population is unclear. This study evaluated ICI plus chemotherapy in NSCLC patients with MPE. METHODS: Patients from 3 centers in China with NSCLC and MPE who received ICI plus chemotherapy (ICI Plus Chemo) or chemotherapy alone (Chemo) between December 2014 and June 2023 were enrolled. Clinical outcomes and adverse events (AEs) were compared. RESULTS: Of 155 eligible patients, the median age was 61.0 years old. Males and never-smokers accounted for 73.5% and 39.4%, respectively. Fifty-seven and 98 patients received ICI Plus Chemo or Chemo, respectively. With a median study follow-up of 10.8 months, progression-free survival (PFS) was significantly longer with ICI Plus Chemo than with Chemo (median PFS: 7.4 versus 5.7 months; HR = 0.594 [95% CI: 0.403-0.874], P = 0.008). Median overall survival (OS) did not differ between groups (ICI Plus Chemo: 34.2 versus Chemo: 28.3 months; HR = 0.746 [95% CI: 0.420-1.325], P = 0.317). The most common grade 3 or worse AEs included decreased neutrophil count (3 [5.3%] patients in the ICI Plus Chemo group vs. 5 [5.1%] patients in the Chemo group) and decreased hemoglobin (3 [5.3%] versus 10 [10.2%]). CONCLUSIONS: In patients with untreated NSCLC with MPE, ICI plus chemotherapy resulted in significantly longer PFS than chemotherapy and had a manageable tolerability profile, but the effect on OS may be limited.

A deep-learning-based genomic status estimating framework for homologous recombination deficiency detection from low-pass whole genome sequencing.

Genome-wide sequencing allows for prediction of clinical treatment responses and outcomes by estimating genomic status. Here, we developed Genomic Status scan (GSscan), a long short-term memory (LSTM)-based deep-learning framework, which utilizes low-pass whole genome sequencing (WGS) data to capture genomic instability-related features. In this study, GSscan directly surveys homologous recombination deficiency (HRD) status independent of other existing biomarkers. In breast cancer, GSscan achieved an AUC of 0.980 in simulated low-pass WGS data, and obtained a higher HRD risk score in clinical BRCA-deficient breast cancer samples (p = 1.3 × 10-4, compared with BRCA-intact samples). In ovarian cancer, GSscan obtained higher HRD risk scores in BRCA-deficient samples in both simulated data and clinical samples (p = 2.3 × 10-5 and p = 0.039, respectively, compared with BRCA-intact samples). Moreover, HRD-positive patients predicted by GSscan showed longer progression-free intervals in TCGA datasets (p = 0.0011) treated with platinum-based adjuvant chemotherapy, outperforming existing low-pass WGS-based methods. Furthermore, GSscan can accurately predict HRD status using only 1 ng of input DNA and a minimum sequencing coverage of 0.02 × , providing a reliable, accessible, and cost-effective approach. In summary, GSscan effectively and accurately detected HRD status, and provide a broadly applicable framework for disease diagnosis and selecting appropriate disease treatment.

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial.

BACKGROUND: The combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus famitinib (a receptor tyrosine kinase inhibitor) as a first-line treatment for advanced or metastatic NSCLC patients with a programmed death ligand-1 (PD-L1) tumor proportion score (TPS) of ≥1%, in an open-label, multicenter, phase 2 basket trial. METHODS: Eligible patients received camrelizumab (200 mg once every 3 weeks via intravenous infusion) plus oral famitinib at an initial dose of 20 mg once daily. The primary endpoint was the objective response rate (ORR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors V.1.1. Key secondary endpoints included disease control rate (DCR), duration of respons, progression-free survival (PFS), overall survival (OS), 12-month OS rate, and safety profile. RESULTS: Of the enrolled 41 patients, 21 (51.2%) had a PD-L1 TPS of 1-49%. As of the cut-off date on June 22, 2022, the combination regimen of camrelizumab and famitinib achieved an ORR of 53.7% (95% CI 37.4% to 69.3%) and a DCR of 92.7% (95% CI 80.1% to 98.5%). The median PFS was 16.6 months (95% CI 8.3 to not reached), and OS data were not yet mature, with an estimated 12-month OS rate of 76.8% (95% CI 60.0% to 87.3%). The most common treatment-related adverse events of grade 3 or higher included hypertension (22.0%), increased alanine aminotransferase (12.2%), decreased neutrophil count (9.8%), proteinuria (7.3%), decrease platelet count (7.3%), and hypokalemia (7.3%). One (2.4%) patient died from grade 5 hemoptysis, which was considered possibly related to the study treatment by the investigator. CONCLUSION: Camrelizumab plus famitinib demonstrated promising antitumor activity in advanced or metastatic NSCLC patients and had an acceptable safety profile. These findings suggest that this combination regimen could be an alternative therapeutic option and warrant further investigation. TRIAL REGISTRATION NUMBER: NCT04346381.

Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion.

BACKGROUND: Several studies have indicated that intrapleural infusion of bevacizumab is an effective treatment for non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE). However, the impact of bevacizumab administered through an indwelling pleural catheter (IPC) on the prognosis of these patients is unknown. METHODS: Consecutive advanced NSCLC patients with symptomatic MPE receiving an IPC alone or bevacizumab through an IPC were identified in a tertiary hospital. The patient characteristics and clinical outcomes were collected. RESULTS: A total of 149 patients were included, and the median age was 60.3 years. Males and nonsmokers accounted for 48.3% and 65.8%, respectively. A total of 69.8% (104/149) of patients harbored actionable mutations, including 92 EGFR-activating mutations, 11 ALK fusions, and 1 ROS1 fusion. A total of 81.9% (122/149) of patients received IPC alone, and 18.1% (27/149) received bevacizumab through an IPC. The incidence of spontaneous pleurodesis during the first 6 months was greater in the bevacizumab-treated group than in the IPC-treated group in the subgroup with actionable mutations (64.3% vs. 46.9%, P = 0.28). The median overall survival (OS) in patients with actionable mutations treated with bevacizumab through an IPC was 42.2 months, which was significantly longer than the 26.7 months in patients who received an IPC alone (P = 0.045). However, the median OS did not differ between the two arms in the subgroup without actionable mutations (10.8 vs. 41.0 months, P = 0.24). No significant difference between the bevacizumab through an IPC group and the IPC group was detected in the number of participants who had adverse events, either in patients with actionable mutations (14.3% vs. 8.4%; P = 0.42) or in patients without actionable mutations (16.7% vs. 12.8%; P = 1.00). CONCLUSIONS: Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.

Joint application of metagenomic next-generation sequencing and histopathological examination for the diagnosis of pulmonary infectious disease.

IMPORTANCE: The diagnosis of some pulmonary infectious diseases and their pathogens is very difficult. A more precise diagnosis of pulmonary infectious diseases can help clinicians use proper antibiotics as well as reduce the development of drug-resistant bacteria. In this study, we performed both mNGS and pathology on lung puncture biopsy tissue from patients and found that combined mNGS and histopathology testing was significantly more effective than histopathology testing alone in detecting infectious diseases and identifying infectious diseases. In addition, the combined approach improves the detection rate of pathogenic microorganisms in infectious diseases and can be used to guide precision clinical treatment.

The clinical features and prognosis of fungal pleural infection: A case series and literature review.

Fungal pleural infections are infrequent and insidious, for which there are neither large clinical studies nor targeted guidelines to provide standardized treatment options. We reported 4 cases of fungal pleural infection and reviewed the cases of fungal pleural infections in previous studies to provide a basis for the diagnosis and treatment of fungal pleural infections. There were 2 females and 2 males with a mean age of 58.5 years in our data. The average time from onset to diagnosis was 30.25 days. Risk factors most frequently included pulmonary diseases (n = 4) and malignancy (n = 1). Two patients underwent pleural biopsy through a thoracoscope, and no pathogens were detected. Pleural fluid culture was positive in 2 out of 3 cases. The diagnoses were "possible" (n = 1), "probable" (n = 1), and "proven" (n = 2). All patients received systemic antifungal therapy, and 3 received combined thoracic drainage. The outcomes were cured (n = 1), improved (n = 2) and lost to follow-up (n = 1). We reviewed 12 cases of fungal pleural infection in previous studies. The diagnosis was confirmed via culture in 7 cases and via biopsy in 8 cases. The pathogen was Aspergillus in 7 cases. After a combination of systemic antifungal (n = 12) and local treatment (n = 11), 10 patients improved and 2 patients died. Diagnosis of fungal pleural infection should incorporate risk factors, clinical presentation and fungal evidence, with pleural fluid culture being an important and feasible mean of confirming the diagnosis; and treatment should be based on systemic antifungal therapy supplemented by topical therapy.

Acupuncture for ventilator-dependent patients at a hospital-based respiratory care center: A randomized controlled trial.

Background: In intensive care units, mechanical ventilation is an important therapy to help patients with dyspnea. However, long-term ventilator dependence would consume huge medical resources and increase the risk of morbidity and mortality. The aim of the study was to examine the efficacy of the acupuncture combined with western medical care on ventilator parameters in ventilator-dependent patients. Methods: In this clinical trial, 80 ventilator-dependent patients aged 20 to 80 years old were randomly assigned to acupuncture group and control group in the respiratory care center (RCC) of Changhua Christian Hospital. Besides regular medical care and therapy, participants in the acupuncture group received acupuncture therapy at the same 17 acu-points for 20 minutes once a day, a total of 12 sessions. The ventilator parameters were recorded to evaluate the respiratory efficiency for all participants. The primary outcome was rapid shallow breathing index (RSBI), and secondary outcomes were respiratory rate (RR), tidal volume (TV) and ventilation per minute (MV). Results: Though there was no significant difference in the parameter between the acupuncture group and the control group, we found the trend of decreasing RSBI in the acupuncture group. In subgroup analyses, the mean of RSBI significantly decreased 16.02 (with the SD in 60.84) in acupuncture group, while it increased 17.84 (with the SD in 39.38) in control group (p=0.036) after 12 sessions. Conclusion: Acupuncture treatment can improve breathing ability of patients with respirator dependence in respiratory care center.

Superior clinical outcomes in patients with non-small cell lung cancer harboring multiple ALK fusions treated with tyrosine kinase inhibitors.

Background: Patients with non-small cell lung cancer (NSCLC) harboring anaplastic lymphoma kinase (ALK) fusions may benefit from ALK-tyrosine kinase inhibitors (ALK-TKIs). However, few studies have analyzed the clinical outcome in patients harboring multiple ALK fusions, including double or triple ALK fusions. Here, our study aimed to analyze the impact of harboring multiple ALK fusions on the efficacy of receiving ALK-TKIs in NSCLC patients. Methods: A total of 125 patients with ALK-rearranged NSCLC detected by targeted capture DNA-based next-generation sequencing (NGS) at West China Hospital were enrolled. The literature on patients harboring multiple ALK fusions was systematically reviewed. The clinical response to ALK-TKIs was evaluated according to ALK fusion patterns in 62 patients: 56 from our center and 6 from the literature. Results: Among the 125 patients, a single canonical echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion was detected in 65.6% (82/125), a single non-EML4-ALK fusion was detected in 13.6% (17/125), and multiple ALK fusions were detected in 20.8% (26/125). Among the 62 patients with ALK fusion treated with ALK-TKIs, the median progression-free survival (PFS) was significantly longer in patients with multiple ALK fusions than in those with a single ALK fusion (26.9 vs. 11.2 months, P=0.009), irrespective of brain metastasis, type of TKI drug, and treatment lines. The multiple ALK fusion group also tended to have a longer overall survival (OS) (P=0.26). Multivariate Cox regression analysis revealed that harboring multiple ALK fusions had the potential to be an independent predictor of better PFS for ALK-positive NSCLC [hazard ratio (HR) =0.490; 95% confidence interval (CI): 0.229-1.049]. Conclusions: Harboring multiple ALK fusions could serve as an independent predictive marker of better clinical outcome for patients with NSCLC and ALK rearrangement who have received ALK-TKIs treatment.

Development and validation of the CAIL prognostic score in non-small cell lung cancer patients with malignant pleural effusion.

BACKGROUND: Patients with malignant pleural effusion (MPE) typically have poor prognoses, and predicting survival is challenging. The present study aimed to identify prognostic factors of overall survival (OS) in non-small cell lung cancer (NSCLC) patients with MPE in the time of immunotherapy and targeted therapy. METHODS: Data of 344 consecutive NSCLC patients with MPE on clinical, radiological, and molecular characteristics and treatment options were collected. The risk factors in the training cohort were assessed using univariate and multivariate proportional hazards analyses. A clinical prognostic score was established and validated. RESULTS: According to the results of the multivariable survival analysis, the Eastern Cooperative Oncology Group (ECOG) performance score (PS), antiangiogenic therapy, immunotherapy, and lactic dehydrogenase (LDH) in pleural fluid (CAIL) prognostic score was developed (n = 275) and subsequently validated (n = 69). Patients who underwent risk stratification into low-, moderate-, and high-risk groups had median OS of 46.1, 23.1, and 9.6 months, respectively (P < 0.0001). The area under the curve (AUC) analysis showed the CAIL score to be superior at predicting survival compared with the LENT score at 6 (0.84 vs. 0.77, P < 0.01), 12 (0.87 vs. 0.82, P < 0.01), and 36 months (0.80 vs. 0.77, P < 0.01). CONCLUSIONS: For NSCLC patients with MPE, the validated CAIL prognostic score integrates clinical characteristics and therapeutic modalities to predict survival.

[Peripheral Blood Laboratory Test Results Combined with TCF1+CD8+ T Lymphocytes 
Ratio to Predict the Response and Prognosis of Immunotherapy to 
Advanced Lung Cancer].

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy lacks viable biomarkers for response and prognosis prediction. This study aimed to investigate the correlation of peripheral blood laboratory test results combined with lymphocyte subset ratios to the response and prognosis of immunotherapy in advanced lung cancer. METHODS: Advanced lung cancer patients admitted to West China Hospital, Sichuan University from May 2021 to July 2023 were prospectively enrolled in this study. Clinical data and peripheral blood were collected before and after treatment and lymphocyte subset ratios were analyzed by flow cytometry. Logistic regression was used to identify factors correlated to ICIs treatment efficacy. Cox modeling was applied to explore the prognostic factors. RESULTS: Logistic regression showed that the baseline level of transcription factor T cell factor 1 (TCF1)+CD8+ T cell ratio and peripheral white blood cell (WBC) count, lymphocyte percentage, cytokeratin 19 fragment (CYFRA21-1) after 1 cycle of ICIs treatment were the potential predictors for ICIs response (P<0.05). Cox regression analysis showed that the baseline level of TCF1+CD8+ T cell ratio (P=0.020) and peripheral WBC count after 1 cycle of ICIs treatment (P<0.001) were prognostic factors. CONCLUSIONS: Patients with high baseline TCF1+CD8+ T cell ratio combined with low WBC counts and low CYFRA21-1 level after 1 cycle of ICIs treatment are more likely to benefit from ICIs therapy.

Tislelizumab plus chemotherapy for patients with EGFR-mutated non-squamous non-small cell lung cancer who progressed on EGFR tyrosine kinase inhibitor therapy.

BACKGROUND: Treatment options are limited for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after treatment failure with EGFR tyrosine kinase inhibitors (TKIs). This multicenter open-label, phase II study aims to evaluate the efficacy and safety of tislelizumab plus chemotherapy (cohort 1, TIS+chemo) or tislelizumab plus chemotherapy and bevacizumab (cohort 2, TIS+chemo+ beva) in EGFR-mutated non-squamous NSCLC patients who progressed on EGFR TKI therapies. Here, the primary analysis of the TIS+chemo cohort is reported. METHODS: In the TIS+chemo cohort, patients with EGFR-sensitizing mutations with prior EGFR TKI failure received tislelizumab plus carboplatin and nab-paclitaxel as induction treatment, followed by maintenance with tislelizumab plus pemetrexed. The primary endpoint was 1-year progression-free survival (PFS) rate. The planned sample size was 66 with a historical control of 7%, an expected value of 20%, a one-sided α of 0.05, and a power of 85%. RESULTS: Between July 11, 2020 and December 13, 2021, 69 patients were enrolled. As of June 30, 2022, the median follow-up was 8.2 months. Among the 62 patients in the efficacy analysis set, estimated 1-year PFS rate was 23.8% (90% CI 13.1% to 36.2%), and its lower bound of 90% CI was higher than the historical control of chemotherapy (7%), which met the primary endpoint. The median PFS was 7.6 (95% CI 6.4 to 9.8) months. Median overall survival (OS) was not reached (95% CI 14.0 to not estimable), with a 1-year OS rate of 74.5% (95% CI 56.5% to 86.0%). The objective response rate and disease control rate were 56.5% (95% CI 43.3% to 69.0%) and 87.1% (95% CI 76.1% to 94.3%), respectively. Patients who had progressed on first-generation/second-generation and third-generation EGFR-TKIs at baseline had shorter PFS than those who progressed on first-generation/second-generation EGFR-TKIs (median 7.5 vs 9.8 months, p=0.031). Patients with positive ctDNA had shorter PFS (median 7.4 vs 12.3 months, p=0.031) than those with negative ctDNA. No grade 5 treatment-emergent adverse events (TEAEs) were observed. Grades 3-4 TEAEs occurred in 40.6% (28/69) of patients. Grades 3-4 immune-related AEs occurred in 5 (7.2%) patients. CONCLUSION: The study met the primary endpoint for the TIS+chemo cohort. Tislelizumab plus chemotherapy is effective with an acceptable safety profile for EGFR-mutated non-squamous NSCLC after EGFR TKI failure.

Evaluation of Male Breast Cancer and the Application of Sentinel Lymph Node Biopsy: A Multicenter Retrospective Study.

Sentinel lymph node biopsy (SLNB) is currently used as a routine treatment for patients with breast cancer. However, it may not be applicable for patients with male breast cancer (MBC), because they have notably different clinicopathological features from those occurring in females. There is a lack of evidence of SLNB application and safe exemption from axillary lymph node dissection (ALND) in patients with MBC. This study aimed to evaluate the application of SLNB to provide information for the standardized treatment of patients with MBC. The MBC patient records from 4 institutions ranging from January 2001 to November 2020 were retrospectively reviewed. There were 220 patients with MBC with a median age of 60 (range 24-88) years and an average tumor size of 2.3 cm (range 0.5 cm-6.5 cm). Sixty-six percent of patients underwent SLNB, and 39% of them showed positive results. A total of 157 patients underwent ALND, while only half of them had positive nodes, causing unnecessary complications. For patients in the clinical early stage, we found that the SLNB showed a noninferiority to the ALND treatment in DFS (P = .18) and OS (P = .055). In conclusion, there are certain obstacles to the broad application of SLNB due to the lower proportion of patients with clinically negative lymph nodes. However, it is undeniable that SLNB can safely and effectively exempt patients with MBC at early stage with clinically negative nodes from ALND to reduce subsequent complications. It is still an ideal criterion for the axillary staging of patients with MBC.

Single nucleotide polymorphisms associated with female breast cancer susceptibility in Chinese population.

Breast cancer is a complex disease influenced by both external and internal factors, among which genetic factors play a critical role. Single-nucleotide polymorphisms (SNPs) are major contributors to the heritability of breast cancer, and their frequencies vary across ethnic groups. In this study, we aimed to investigate the association between 34 SNPs identified in previous genome-wide association studies (GWAS) and overall breast cancer risk, as well as breast cancer subtypes, in the Chinese female population. To accomplish this, we conducted an extensive association analysis using the high-throughput Sequenom MassARRAY® platform in a case-control study comprising 1848 breast cancer patients and 709 healthy controls. Our analysis, which utilized the SNPassoc package in R based on chi-squared (χ2) test and genetic model analysis, identified significant associations between breast cancer risk and SNP rs12493607 (TGFBR2, risk allele C, OR = 1.28 [1.11-1.47], P = 0.0005), as well as a less conservatively significant association with rs4784227 (CASC16, risk allele T, OR = 1.24 [1.08-1.42], P = 0.0017) and rs2046210 (ESR1, risk allele A, OR = 1.50 [1.16-1.95], P = 0.0016). Furthermore, our stratified analyses revealed that rs12493607 was significantly associated with invasive carcinoma, estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, HER2-negative, and young (aged younger than 45) breast cancer. SNP rs4784227 and rs3803662 (CASC16) were associated with invasive carcinoma and ER-positive breast cancer, while rs2046210 was linked to ductal carcinoma in situ, ER-negative, PR-negative, HER2-positive, and elder (aged more than 45) breast cancers. SNPs rs10484919 (ESR1) and rs1038304 (CCDC170) showed links to HER2-positive breast cancer, and rs616488 (PEX14) with premenopausal breast cancer. In summary, our study shed light on the relationship between SNPs and breast cancer susceptibility within a vast Chinese cohort, supporting the development of polygenetic risk scores for the Chinese population. These findings provide valuable insights into the genetic basis of breast cancer and have important implications for risk prediction, early detection, and personalized treatment of this disease.

A novel non-invasive exhaled breath biopsy for the diagnosis and screening of breast cancer.

BACKGROUND: Early detection is critical for improving the survival of breast cancer (BC) patients. Exhaled breath testing as a non-invasive technique might help to improve BC detection. However, the breath test accuracy for BC diagnosis is unclear. METHODS: This multi-center cohort study consecutively recruited 5047 women from four areas of China who underwent BC screening. Breath samples were collected through standardized breath collection procedures. Volatile organic compound (VOC) markers were identified from a high-throughput breathomics analysis by the high-pressure photon ionization-time-of-flight mass spectrometry (HPPI-TOFMS). Diagnostic models were constructed using the random forest algorithm in the discovery cohort and tested in three external validation cohorts. RESULTS: A total of 465 (9.21%) participants were identified with BC. Ten optimal VOC markers were identified to distinguish the breath samples of BC patients from those of non-cancer women. A diagnostic model (BreathBC) consisting of 10 optimal VOC markers showed an area under the curve (AUC) of 0.87 in external validation cohorts. BreathBC-Plus, which combined 10 VOC markers with risk factors, achieved better performance (AUC = 0.94 in the external validation cohorts), superior to that of mammography and ultrasound. Overall, the BreathBC-Plus detection rates were 96.97% for ductal carcinoma in situ, 85.06%, 90.00%, 88.24%, and 100% for stages I, II, III, and IV BC, respectively, with a specificity of 87.70% in the external validation cohorts. CONCLUSIONS: This is the largest study on breath tests to date. Considering the easy-to-perform procedure and high accuracy, these findings exemplify the potential applicability of breath tests in BC screening.

Clinical outcomes of stage-IV non-small-cell lung cancer in young patients and the impact of tumor markers.

INTRODUCTION: Non-Small Cell Lung Cancer (NSCLC) diagnosed at a younger age have patterns of care, responses to treatment, and outcomes not entirely clear. A particular feature includes more advanced stages at diagnosis. Our objective was to characterize these young patients with advanced disease and evaluate the impact of targeted therapies. METHODS: Analyzing our cohort of 18,252 newly diagnosed NSCLC patients, we defined Young-age versus Norm-age based on the age distribution at the time of diagnosis. Stage-IV patients were investigated on their clinical information and outcomes; deaths were considered lung cancer-related. Primary outcome was overall survival (OS). Multivariate Cox models were built to evaluate independent prognostic factors in comparative age groups. RESULTS: We found 4,267 patients with stage-IV NSCLC (359 Young-age; 3,908 Norm-age). Young patients had predominance of females (52.6% vs. 43.3%, P = 0.001), never-smokers (43.2% vs. 14.8%, P < 0.001), and adenocarcinoma (73.5% vs. 62.5%, P < 0.001). Mean OS was 21.1 months in the Young and 15.1 months in Norm, respectively (P < 0.001). Young patients were more often treated with surgery (6.7% vs. 5.0%), chemotherapy (53.2% vs. 44.1%), and targeted therapy (10.6% vs. 5.7%). Molecular studies were assessed in patients when the mutation tests became clinically available (93 Young, 875 Norm) and revealed a critical role of targeted therapy in the improved survival of both age groups. DISCUSSION: Young patients with stage-IV NSCLC have a specific profile and benefit more when treated with surgery and targeted therapy. Molecular testing is critical in this population, where improved survival was identified. A more aggressive approach to this population needs to be considered.