Gate-tunable bolometer based on strongly coupled graphene mechanical resonators.

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

Association between age at initial diagnosis and post-metastasis mortality among women with recurrent metastatic breast cancer in China.

BACKGROUND: Little is known about whether age at initial diagnosis influences the prognosis of recurrent metastatic breast cancer (rMBC). Here, we analyzed the association between age at initial diagnosis and rMBC mortality in China. METHODS: A total of 1636 women diagnosed with rMBC between 1989 and 2020 at West China Hospital, Sichuan University were included in this study. The age at initial diagnosis was categorized as young (≤ 40 years), middle-aged (41-64 years) and elderly (≥ 65 years). Post-metastasis mortality was the primary outcome and its associated factors were analyzed by Cox proportional hazards models. RESULTS: During a median follow-up of 5.2 years after initial diagnosis of breast cancer, 620 deaths were identified. Compared with middle-aged patients, elderly patients had a 70% increased risk of post-metastasis mortality (95%CI, 1.24-2.33) after adjusting for demographics, tumor characteristics and treatment modes. Similarly, elderly patients were associated with a 75% increased risk of post-metastasis mortality (95%CI, 1.19-2.59) compared with young patients. Subgroup analyses also showed similar trends. CONCLUSION: Our findings suggest that in breast cancer, elderly patients at initial diagnosis face a higher risk of post-metastasis mortality.

Knowledge Difference of Tumor Nutrition Risk Among Thoracic Cancer Patients, Their Family Members, Physicians, and Nurses.

To investigate the difference among patients, family members, physicians, and nurses in their ability to identify malnutrition risk in patients with thoracic cancer. The enrolled patients were evaluated by the NRS2002 nutritional risk scale. The patient-centered groups, including the patient, the primary caretaker, the physician, and the nurse, were given a questionnaire on their knowledge and understanding of nutrition therapy in cancer treatment. The incidence rate of nutritional risk in hospitalized patients with thoracic cancer was 13.8%. There were significant differences in the accuracy rate of nutritional risk assessment among the four groups (P < 0.001), in which the nurses' was 70.3%, 55.1% for the physician, 38.7% for family members, and 33.0% for patients, which was the poorest accuracy rate. No significant correlation was found between the accuracy of nutritional risk assessment and the education level and personal monthly income of each population (P > 0.05). Nearly all four groups considered it necessary to learn more about cancer nutrition therapy. For patients and their families, the main way to understand the knowledge of tumor nutrition was consultation with medical staff and information exchange between patients; for doctors, new media; and for nurses, classroom training. Nurses' assessment of nutritional risk in cancer patients achieved the highest accuracy, while the poorest accuracy originated from the patients.

Prognosis of limited-stage small cell lung cancer with comprehensive treatment including radical resection.

BACKGROUND: The NCCN (National Comprehensive Cancer Network) Clinical Practice Guidelines in Oncology (NCCN guidelines) recommend radical resection for T1-2N0M0 patients with limited-stage small cell lung cancer (LS-SCLC). However, only about 5% of patients with small cell cancer (SCLC) were initially diagnosed as T1-2N0M0. The purpose of our study was to analyze and compare the effects of the comprehensive treatment including radical surgery and concurrent chemoradiotherapy on the prognosis of patients with LS-SCLC. METHODS: We comprehensively reviewed the medical data of patients with SCLC diagnosed by pathology in our hospital from January 2011 to April 2018. The Ethics Committee of West China Hospital of Sichuan University approved the study. Finally, 50 patients with good follow-up and complete medical data were selected as the surgical group (S group). According to the clinical characteristics of the patients in the S group, 102 LS-SCLC patients who received concurrent chemoradiotherapy in the same period were included in the CCRT group (concurrent chemoradiotherapy group) as the control group. Then according to the orders of the adjuvant treatments, the patients in the S group were divided into the SA group (radical surgery + adjuvant chemotherapy + adjuvant radiotherapy group, 30 cases in total) and the NS group (neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy group, 20 cases in total) for subgroup analysis. The SPSS 23.0 software was used for statistical analysis, and the t test was used for group comparison; Kaplan-Meier was used for survival analysis. P < 0.05 demonstrates a statistically significant difference. RESULTS: The median progress-free survival (PFS) in the S group (73 months) was significantly better than that in the CCRT group (10.5 months, P < 0.0001), and the median overall survival (OS) in the S group (79 months) was also significantly better than that in the CCRT group (23 months, P < 0.0001). Subgroup analysis showed that there was no significant difference between the NS group and the SA group. CONCLUSIONS: For LS-SCLC patients, the comprehensive treatment including radical surgery (radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy/neoadjuvant chemotherapy + radical surgery + adjuvant chemotherapy ± adjuvant radiotherapy)may be superior to concurrent chemoradiotherapy.

Cost-Effectiveness Analysis of Adjuvant Endocrine Therapy With Ovarian Suppression in Premenopausal Patients With Hormone Receptor-Positive Early Breast Cancer in China.

PURPOSE: Endocrine therapy combined with ovarian function suppression (OFS) is recommended in intermediate- or high-risk patients among premenopausal women with hormone receptor-positive early breast cancer. However, in China, the cost-effectiveness of this strategy compared with endocrine therapy alone is unclear. This study aimed to evaluate the long-term cost-effectiveness of tamoxifen (TAM), TAM+OFS, and exemestane plus OFS (EXE+OFS). METHODS: On the basis of prognostic data from the Suppression of Ovarian Function Trial (SOFT), cost data from the Hospital Information System of the West China Hospital of Sichuan University, and health utility values from the published literature, a Markov model was established. The incremental cost-effectiveness ratio (ICER) was used to compare the treatment strategies. RESULTS: In a 25-year simulation of adjuvant therapy in Chinese women with early breast cancer, the total costs of TAM, TAM+OFS, and EXE+OFS were $7821, $9318, and $9445, respectively. The quality-adjusted life-years (QALYs) were 11.615, 11.896, and 11.734 years, respectively. Compared with TAM, the ICERs of TAM+OFS and EXE+OFS were $5,327.4021/QALY and $13,647.0588/QALY, respectively. The ICERs of TAM+OFS and EXE+OFS were below the threshold of $32,517/QALY. The reliability and stability of the simulation results were verified using Monte Carlo simulation and sensitivity analysis. CONCLUSION: In the context of limited resources in China, TAM+OFS and EXE+OFS are cost-effective options compared with TAM.

Efficacy and safety of tucidinostat in patients with advanced hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: real-world insights.

Background: Tucidinostat, which is a subtype-selective histone deacetylase inhibitor, has been approved in China for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). However, existing evidence mainly stemmed from randomized controlled trials, and might have limitations in representing the complexities of clinical practice and diverse patient populations. Therefore, there is a need to explore the efficacy and optimal therapeutic modality for tucidinostat in real-world clinical settings. Methods: The objective of this real-world study was to analyze the clinical data of 47 patients with HR+/HER2- ABC who received tucidinostat treatment at West China Hospital, Sichuan University, between August 2020 and May 2023. The primary outcomes were progression-free survival (PFS) and clinical benefit rate [CBR; defined as partial response (PR) and stable disease (SD) for ≥6 months on clinical evaluation]. Results: A total of 47 patients were included, and the median follow-up time was 18.20 months. The median line of tucidinostat therapy was 3 (range, 1-9). In all, 52.17% patients were treated with tucidinostat plus fulvestrant, while 38.30% were treated with tucidinostat plus aromatase inhibitors. Notably, 10.64% of the patients with rapidly progressing visceral metastases received tucidinostat plus endocrine therapy as maintenance treatment after achieving disease control with chemotherapy. The median PFS was 4.43 months [95% confidence interval (CI), 2.77-10.53], and the median overall survival was 19.57 months (95% CI, 12.83-not reached). The 6-month CBR for the overall population was 41.86%. Patients undergoing maintenance therapy demonstrated a significantly longer PFS than did those who did not receive it as maintenance therapy (14.13 vs. 3.93 months; P=0.01). Univariate Cox regression analysis showed that use of tucidinostat in lines 1-2, use of tucidinostat plus fulvestrant, presence of one metastatic site, and lack of brain metastasis were favorable factors for PFS. Thrombocytopenia was the most frequently reported adverse event, with an incidence rate of 31.91% at all grades and 14.89% at grade ≥3. Four (8.51%) patients discontinued the treatment. Conclusions: For patients with HR+/HER2- ABC, tucidinostat combination therapy offers certain survival benefits with controllable safety. Furthermore, compared with non-maintenance therapy, maintenance therapy after chemotherapy may have promising efficacy.

Tuning the nonlinearity of graphene mechanical resonators by Joule heating.

As an inherent property of the device itself, nonlinearity in micro-/nano- electromechanical resonators is difficult to eliminate, and it has shown a wide range of applications in basic research, sensing and other fields. While many application scenarios require tunability of the nonlinearity, inherent nonlinearity of a mechanical resonator is difficult to be changed. Here, we report the experimental observation of a Joule heating induced tuning effect on the nonlinearity of graphene mechanical resonators. We fabricated multiple graphene mechanical resonators and detected their resonant properties by an optical interference method. The mechanical vibration of the resonators will enter from the linear to the nonlinear intervals if we enhance the external driving power to a certain value. We found that at a fixed drive power, the nonlinearity of a mechanical resonator can be tuned by applying a dc bias current on the resonator itself. The tuning mechanism could be explained by the nonlinear amplitude-frequency dependence theory. Our results may provide a research platform for the study of mechanical nonlinearity by using atomic-thin layer materials.

Neoadjuvant pyrotinib plus trastuzumab and nab-paclitaxel for HER2-positive early or locally advanced breast cancer: an exploratory phase II trial.

BACKGROUND: The anti-tumor activity and acceptable tolerability of pyrotinib plus chemotherapy have been demonstrated in phase III trials in human epidermal growth factor receptor 2-positive metastatic breast cancer (BC). In this study, we assessed the efficacy and safety of neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel in women with human epidermal growth factor receptor 2-positive early or locally advanced BC. METHODS: In this single-arm exploratory phase II trial, patients with untreated human epidermal growth factor receptor 2-positive BC (stage IIA-IIIC) received pyrotinib 400 mg once daily, trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg once a week, and albumin-bound paclitaxel 125 mg/m2 once a week for four 21-day cycles before surgery. The primary endpoint of the study was total pathological complete response (pCR) rate, defined as no microscopic invasive tumor remnants in the breast and axillary lymph nodes. The secondary endpoints were investigator-assessed objective response rate (ORR) and adverse event profiles. RESULTS: Between May 17, 2019 and November 26, 2019, a total of 21 patients were enrolled. The total pCR rate was 57.1% (12/21), whereas 23.8% (5/21) and 19.0% (4/21) of patients had minimal and moderate residual disease (RD), respectively. The ORR reached 100% (21/21) at the end of the neoadjuvant therapy. Grade ≥3 treatment-related adverse events were observed in 42.9% (9/21) of patients, including decreased neutrophil count [7 (33.3%)], diarrhoea [6 (28.6%)], decreased white blood cell count [5 (23.8%)], and vomiting [2 (9.5%)]. Adverse event-related dose reduction and interruption of pyrotinib occurred in 6 (28.6%) and 11 (52.4%) patients, respectively. CONCLUSIONS: In women with human epidermal growth factor receptor 2-positive early or locally advanced BC, neoadjuvant pyrotinib plus trastuzumab and albumin-bound paclitaxel effectively promoted total pCR rate with an acceptable safety profile (ClinicalTrials.gov, NCT04152057).

A Retrospective Analysis of the Effect of Irinotecan-Based Regimens in Patients With Metastatic Breast Cancer Previously Treated With Anthracyclines and Taxanes.

BACKGROUND: At present, patients with metastatic breast cancer (MBC) have few treatment options after receiving anthracyclines and taxanes. Studies have shown that irinotecan has modest systemic activity in some patients previously treated with anthracyclines and taxanes. This study aimed to evaluate the efficacy of irinotecan-based chemotherapy for breast cancer patients in a metastatic setting. METHODS: We retrospectively collected the clinical information and survival data of 51 patients with MBC who received irinotecan at West China Hospital of Sichuan University. The primary endpoints were the progression free survival (PFS) and overall survival (OS), and the secondary endpoint was the objective response rate (ORR). To minimize potential confounding factors, we matched 51 patients who received third-line chemotherapy without irinotecan through propensity score matching (PSM) based on age, hormone receptor (HR), and human epidermal growth factor receptor 2 (HER2), compared their OS and PFS rates to those treated with irinotecan. RESULTS: From July 2012 to October 2020, 51 patients were treated with an irinotecan-containing regimen. The median number of previous treatment lines was 4, and a median of two previous chemotherapy cycles (ranging from 1-14 cycles) were given in a salvage line setting. The ORR was 15.7%, and the disease control rate (DCR) was 37.3%. For the irinotecan group, the median PFS was 3.2 months (95% CI 2.7-3.7), while the median OS was 33.1 months (95% CI 27.9-38.3). Univariate analysis results suggested that irinotecan could improve PFS in patients with visceral metastasis (P=0.031), which was 0.7 months longer than patients without visceral metastasis (3.5 months vs. 2.8 months). Compared to the patients who received third-line non-irinotecan chemotherapy, the irinotecan group showed a longer trend of PFS without statistical significance (3.2 months vs 2.1 months, P = 0.052). Similarly, the OS of the irinotecan group was longer than the third-line survival without irinotecan, but it was not statistically significant (33.1 months vs 18.0 months, P = 0.072). CONCLUSIONS: For MBC patients who were previously treated with anthracyclines and/or taxanes, an irinotecan-containing regimen achieved moderate objective response and showed a trend of survival benefit, which deserves further study.

A Retrospective Analysis of the Effect of Anlotinib in Patients With Lung Cancer With or Without Previous Antiangiogenic Therapy.

OBJECTIVE: The purpose of this study was to initially investigate the effect of previous antiangiogenic therapy (bevacizumab and endostatin) on the efficacy of anlotinib in patients with advanced or metastatic lung cancer (LC). METHODS: We retrospectively collected the clinical data of patients with LC treated with anlotinib and divided them into group A (treated with anlotinib after the failure of previous antiangiogenic drugs and group B (no prior use of antiangiogenic drugs). We used propensity score matching (PSM) for confounding factors between the groups. Progression-free survival (PFS) and overall survival (OS) were also recorded. RESULTS: A total of 160 patients were included in the analysis. The median OS in groups A and group B was 11.8 months and 16.1 months (P=0.120), whereas the median PFS was 3.1 months and 4.7 months (P=0.009), respectively. Moreover, the objective response rate (ORR) of the two groups was 9.6% and 10.4% (P=0.874), and the disease control rate (DCR) was 71.1% and 80.5% (P=0.165).After PSM (n=46), baseline characteristics were comparable between groups A and B. Furthermore, the median OS of the two groups was 14.6 months and 16.2 months (P=0.320), whereas the median PFS was 3.5 months and 4.5 months (P=0.040), respectively. Moreover, the ORR of the two groups were 13.0% and 10.9% (P=0.748), and the DCR were 78.3% and 82.6% (P=0.599), respectively. CONCLUSIONS: Previous antiangiogenic treatments may affect the PFS of patients who receive anlotinib later, but it might not affect the patient's ORR and OS.

Overall survival benefit of continuing immune checkpoint inhibitors treatment post dissociated response in patients with advanced lung cancer.

PURPOSE: Dissociated response (DR, reduction at baseline or increase < 20% in target lesions compared with nadir in the presence of new lesions) was observed in 20-34% of patients treated with immune checkpoint inhibitors (ICIs). DRs were defined as progression disease (PD) per response evaluation criteria in solid tumors (RECIST v1.1), while evaluation criteria related to immunotherapy incorporated the new lesions into the total tumor burden or conducted further evaluation after 4-8 weeks rather than declaring PD immediately. The main objective of this study is to compare survival between people who continuing initial ICIs treatment and those who switched to other anticancer therapy at the time of DR. PATIENTS AND METHODS: 235 patients with advanced lung cancer (LC) treated with ICIs were evaluated. Propensity score matching (PSM) was used to minimize potential confounding factors. Post-DR OS, target lesion changes were evaluated. RESULTS: 52 patients had been estimated as DRs. After PSM, the continuing ICIs treatment Post-DR cohort still had a significantly longer median post-DR OS than discontinuing ICIs treatment Post-DR cohort, 10.63 months (95% CI 6.27-NA) versus 4.33 months (95% CI 1.77-NA), respectively (p = 0.016). CONCLUSION: Within the limitations of this single-center retrospective analysis, clinically stable patients who were judged by clinicians to be eligible for continuing ICIs treatment post-DR derived apparent OS benefit than discontinuing counterpart.

[Therapeutic Relevance of Human Microbiota and Lung Cancer].

The human microbiome is closely related to human health status. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways, associated with approximately 20% of malignancies. The incidence and mortality of lung cancer (LC) in men in China are the highest among all malignancies, which is a serious threat to human health. Emerging evidence has suggested that the human microbiota may be closely related to lung cancer at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. At the same time, the human microbiota affects the efficacy of lung cancer on chemoradiotherapy, gene therapy, immunotherapy and other treatments. Immunotherapy is a promising method for the treatment of malignancies such as lung cancer, but the efficacy of immune checkpoint inhibitors in patients is heterogeneous. Preclinical studies based on lung cancer cell lines suggest that the intestinal microbiota can modulate responses to anti--PD-1 therapy through interactions with the host immune system. But for lung cancer patients, whether the intestinal flora can still regulate immunotherapy remains controversial. In this mini-review, we summarize current research findings describing therapeutic relevance of human microbiota and lung cancer. A better knowledge of the interplay between the human microbiome and lung cancer may promote the development of innovative strategies for prevention and personalized treatment in lung cancer.