A phase IV study to evaluate the safety of fruquintinib in Chinese patients in real-world clinical practice.

INTRODUCTION: Fruquintinib is approved in China for patients with metastatic colorectal cancer (CRC) who progressed after 2 lines of chemotherapy. This postmarketing study was conducted to evaluate the safety of fruquintinib in the Chinese population, including previously treated patients with advanced CRC and other solid tumors. METHODS: Patients in the first cycle of fruquintinib or expected to start fruquintinib within a week were enrolled. Fruquintinib was administrated according to the label or per physicians' discretion. Patient characteristics and safety information were collected at baseline, 1 month, and 6 months after consent (or 30 days after the last dose). RESULTS: Overall, 3005 patients enrolled between April 24, 2019 and September 27, 2022. All enrolled patients received at least one dose of fruquintinib. Most patients had metastases at baseline. The median age was 60 years. More than half (64.0%) of the patients started fruquintinib at 5 mg, and the median treatment exposure was 2.7 months. Nearly one-third (32.5%) of patients with CRC received fruquintinib with concomitant antineoplastic agents. Treatment-emergent adverse events (TEAEs) leading to dose modification were reported in 626 (20.8%) patients, and 469 (15.6%) patients experienced TEAEs leading to treatment discontinuation. The most common grade ≥ 3 TEAEs were hypertension (6.6%), palmar-plantar erythrodysesthesia syndrome (2.2%), and platelet count decreased (1.0%). Combination therapy did not lead to excessive toxicities. CONCLUSIONS: The safety profile of fruquintinib in the real world was generally consistent with that in clinical studies, and the incidence of TEAEs was numerically lower than known VEGF/VEGFR inhibitor-related AEs. Fruquintinib exhibited manageable safety and tolerability in Chinese patients in the real-world setting.

Polyfluorinated Organic Diammonium Induced Lead Iodide Arrangement for Efficient Two-Step-Processed Perovskite Solar Cells.

The inefficient conversion of lead iodide to perovskite has become one of the major challenges in further improving the performance of perovskite solar cells fabricated by the two-step method. Herein, the discontinuous lead iodide layer realized by introduction of a polyfluorinated organic diammonium salt, octafluoro-([1,1'-biphenyl]-4,4'-diyl)-dimethanaminium (OFPP) iodide which does not form low-dimensional perovskites, can enable the satisfactory conversion of lead iodide into perovskite, leading to meliorated crystallinity and enlarged grains in the OFPP modulated perovskite (OFPP-PVK) film. Combined with the effective defect passivation, the OFPP-PVK films show enhanced charge mobility and suppressed charge recombination. Accordingly, the OFPP-based perovskite solar cells exhibit a champion efficiency of 24.76 % with better device stability. Moreover, a superior efficiency of 21.04 % was achieved in a large-area perovskite module (100 cm2). Our work provides a unique insight into the function of organic diammonium additive in boosting photovoltaic performance.

Downregulation of AC092894.1 promotes oxaliplatin resistance in colorectal cancer via the USP3/AR/RASGRP3 axis.

BACKGROUND: Oxaliplatin resistance is a complex process and has been one of the most disadvantageous factors and indeed a confrontation in the procedure of colorectal cancer. Recently, long non-coding RNAs (lncRNAs) have emerged as novel molecules for the treatment of chemoresistance, but the specific molecular mechanisms mediated by them are poorly understood. METHODS: The lncRNAs associated with oxaliplatin resistance were screened by microarray. lncRNA effects on oxaliplatin chemoresistance were then verified by gain- and loss-of-function experiments. Finally, the potential mechanism of AC092894.1 was explored by RNA pull-down, RIP, and Co-IP experiments. RESULTS: AC092894.1 representation has been demonstrated to be drastically downregulated throughout oxaliplatin-induced drug-resistant CRC cells. In vivo and in vitro experiments revealed that AC092894.1 functions to reverse chemoresistance. Studies on the mechanism suggested that AC092894.1 served as a scaffold molecule that mediated the de-ubiquitination of AR through USP3, thereby increasing the transcription of RASGRP3. Finally, sustained activation of the MAPK signaling pathway induced apoptosis in CRC cells. CONCLUSIONS: In conclusion, this study identified AC092894.1 as a suppressor of CRC chemoresistance and revealed the idea that targeting the AC092894.1/USP3/AR/RASGRP3 signaling axis is a novel option for the treatment of oxaliplatin resistance.

Dopant-Free Polymer Hole Transport Materials for Highly Stable and Efficient CsPbI3 Perovskite Solar Cells.

All-inorganic perovskite CsPbI3 contains no volatile organic components and is a thermally stable photoactive material for wide-bandgap perovskite solar cells (PSCs); however, CsPbI3 readily undergoes undesirable phase transitions due to the hygroscopic nature of the ionic dopants used in commonly used hole transport materials. In the current study, the popular donor material PM6 in organic solar cells is used as a hole transport layer (HTL). The benzodithiophene-based backbone-conjugated polymer requires no dopant and leads to a higher power conversion efficiency (PCE) than 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-OMeTAD). Moreover, PM6 also shows priorities in hole mobility, hydrophobicity, cascade energy level alignment, and even defect passivation of perovskite films. With PM6 as the dopant-free HTL, the PSCs achieve a champion PCE of 18.27% with a competitive fill factor of 82.8%. Notably, the present PCE is based on the dopant-free HTL in CsPbI3 PSCs reported thus far. The PSCs with PM6 as the HTL retain over 90% of the initial PCE stored in a glovebox filled with N2 for 3000 h. In contrast, the PSCs with Spiro-OMeTAD as the HTL maintain ≈80% of the initial PCE under the same conditions.

Higher Levels of Tumour-Infiltrating Lymphocytes (TILs) are Associated with a Better Prognosis, While CDK5 Plays a Different Role Between Nonmetastatic and Metastatic Colonic Carcinoma.

OBJECTIVE: We investigated the prognostic value of cyclin-dependent kinase 5 (CDK5) in a true population-based cohort of patients with colon cancer. METHODS: 1. Immunohistochemical (IHC) staining was used to retrospectively analyse the expression of CDK5 in colon cancer tissue samples of 296 patients. The χ2 test, Kaplan-Meier method and Cox proportional regression model were used to analyse the difference between the patients with differential expression of CDK5 and with different stages (metastatic and nonmetastatic); 2. The number of tumour-infiltrating lymphocytes (TILs) in tumour sections was determined, and its relationship with prognosis was explored. RESULTS: 1. Among 296 patients stained for CDK5, 18 cases (6.09%) showed negative expression, 77 cases (26.01%) showed weak expression (+1), 124 cases (41.89%) showed medium positive expression (2+), and 77 cases (26.01%) showed strong positive expression (3+). The expression of CDK5 was neither related to mismatch repair nor TILs (p > .05). In non-metastatic patients, longer progression-free survival (PFS) and cancer-specific survival (CSS) were observed in patients with high CDK5 expression (2+ or 3+) than low CDK5 expression (- or 1+), while in metastatic disease, the opposite was true (p < .001). 2. TILs in 226 patients were detected in the study. Among them, 115 cases (50.88%) showed a low number of TILs (TILs-L), and 111 cases (49.12%) showed a high number of TILs (TILs-H). Patients with a TIL ratio greater than .2 had a significantly better CSS (p < .001) or PFS (p = .008) than patients with a lower TIL ratio. By multivariate analysis, TILs-H was a protective factor for CSS, however failed to reach a significant difference (hazard ratio: .59, 95% CI: .33∼1.06, p = .079), and so was the PFS (HR: .65, 95% CI: .29∼1.43, p = .279). CONCLUSION: High expression of CDK5 indicates a good prognosis in nonmetastatic colon cancer, while it is the opposite in metastatic colon cancer, and the expression of CDK5 is unrelated to TILs. Patients with TIL-H have a better prognosis, with a proper cut-off value of 20% for colon cancer.

Efficacy and safety of pyrotinib in advanced lung adenocarcinoma with HER2 mutations: a multicenter, single-arm, phase II trial.

BACKGROUND: There is currently a lack of effective treatments for non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. We examined the efficacy and safety of, and potential resistance mechanism to, pyrotinib, a pan-HER inhibitor, in advanced NSCLC carrying HER2 mutations. METHODS: In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day. The primary endpoint was 6-month progression-free survival (PFS) rate, and secondary endpoints were objective response rate (ORR), PFS, overall survival (OS), disease control rate (DCR), and safety. The impact of different HER2 mutation types on sensitivity to pyrotinib and the potential of utilizing mutational profile derived from circulating tumor DNA (ctDNA) to predict disease progression were also explored. RESULTS: Seventy-eight patients were enrolled for efficacy and safety analysis. The 6-month PFS rate was 49.5% (95% confidence interval [CI], 39.2-60.8). Pyrotinib produced an ORR of 19.2% (95% CI, 11.2-30.0), with median PFS of 5.6 months (95% CI, 2.8-8.4), and median OS of 10.5 months (95% CI, 8.7-12.3). The median duration of response was 9.9 months (95% CI, 6.2-13.6). All treatment-related adverse events (TRAEs) were grade 1-3 (all, 91.0%; grade 3, 20.5%), and the most common TRAE was diarrhea (all, 85.9%; grade 3, 16.7%). Patients with exon 20 and non-exon 20 HER2 mutations had ORRs of 17.7% and 25.0%, respectively. Brain metastases at baseline and prior exposure to afatinib were not associated with ORR, PFS, or OS. Loss of HER2 mutations and appearance of amplification in HER2 and EGFR were detected upon disease progression. CONCLUSIONS: Pyrotinib exhibited promising efficacy and acceptable safety in NSCLC patients carrying exon 20 and non-exon 20 HER2 mutations and is worth further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR1800020262.

Development and validation of a radiomics-based nomogram for the preoperative prediction of microsatellite instability in colorectal cancer.

BACKGROUND: Preoperative prediction of microsatellite instability (MSI) status in colorectal cancer (CRC) patients is of great significance for clinicians to perform further treatment strategies and prognostic evaluation. Our aims were to develop and validate a non-invasive, cost-effective reproducible and individualized clinic-radiomics nomogram method for preoperative MSI status prediction based on contrast-enhanced CT (CECT)images. METHODS: A total of 76 MSI CRC patients and 200 microsatellite stability (MSS) CRC patients with pathologically confirmed (194 in the training set and 82 in the validation set) were identified and enrolled in our retrospective study. We included six significant clinical risk factors and four qualitative imaging data extracted from CECT images to build the clinics model. We applied the intra-and inter-class correlation coefficient (ICC), minimal-redundancy-maximal-relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) for feature reduction and selection. The selected independent prediction clinical risk factors, qualitative imaging data and radiomics features were performed to develop a predictive nomogram model for MSI status on the basis of multivariable logistic regression by tenfold cross-validation. The area under the receiver operating characteristic (ROC) curve (AUC), calibration plots and Hosmer-Lemeshow test were performed to assess the nomogram model. Finally, decision curve analysis (DCA) was performed to determine the clinical utility of the nomogram model by quantifying the net benefits of threshold probabilities. RESULTS: Twelve top-ranked radiomics features, three clinical risk factors (location, WBC and histological grade) and CT-reported IFS were finally selected to construct the radiomics, clinics and combined clinic-radiomics nomogram model. The clinic-radiomics nomogram model with the highest AUC value of 0.87 (95% CI, 0.81-0.93) and 0.90 (95% CI, 0.83-0.96), as well as good calibration and clinical utility observed using the calibration plots and DCA in the training and validation sets respectively, was regarded as the candidate model for identification of MSI status in CRC patients. CONCLUSION: The proposed clinic-radiomics nomogram model with a combination of clinical risk factors, qualitative imaging data and radiomics features can potentially be effective in the individualized preoperative prediction of MSI status in CRC patients and may help performing further treatment strategies.

Nickel nanoparticles exert cytotoxic effects on trophoblast HTR-8/SVneo cells possibly via Nrf2/MAPK/caspase 3 pathway.

Nickel nanoparticles are widely used in the industry and may affect the reproductive system. The potential molecular mechanism of exposing the first-trimester trophoblast cell line (HTR-8/SVneo) to nickel nanoparticles remains unclear. Hence, the aim of this study was to investigate the in vitro cytotoxicity of Ni NPs on HTR-8/SVneo cells. HTR-8/SVneo cells were subjected to various concentrations (0, 2.5, 5, 7.5, 10, and 12.5 µg/cm2) of Ni NPs. The toxicity of the Ni NPs was evaluated in HTR-8/SVneo cells by measuring cell viability. The underlying mechanism of nickel nanoparticles toxicity to HTR-8/SVneo cells was determined by measuring the content of intracellular reactive oxygen species, mitochondrial membrane potential, and the rate of cell apoptosis and cell cycle, by measuring adenosine triphosphate levels, intracellular lipid peroxidation malondialdehyde, total superoxide dismutase, and CuZn/Mn-SOD activities, and by determining proteins related to Nrf2, MAPK, and Cytochrome c. Our results showed that the nickel nanoparticles treatment reduced the viability of HTR-8/SVneo cells, while it increased their oxidative stress and lowered their mitochondrial respiratory capacity. Additionally, the nickel nanoparticles treatment induced cell S-phase arrest and apoptosis. These molecular events may be linked to the oxidative stress-Nrf2 pathway/MAPK/Caspase 3 cascade. Thus, nickel nanoparticles exert cytotoxic effects on HTR-8/SVneo cells, which could affect the function of the placenta in human.

Estrogen receptor-negative/progesterone receptor-positive and her-2-negative breast cancer might no longer be classified as hormone receptor-positive breast cancer.

BACKGROUND: The single progesterone receptor (PR)-positive phenotype (estrogen receptor (ER)-/PR + , sPR positive) is an infrequent and independent biological entity. However, the prognosis of patients with sPR-positive and her-2-negative phenotype is still controversial, and it is not always easy to decide treatment strategies for them. METHODS: Patients during 2010-2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was used to evaluate cancer-specific survival (CSS). The propensity score matching (PSM) method was used to balance differences of characteristics in groups. The Life-Table method was used to calculate 5-year CSS rates and the annual hazard rate of death (HRD). RESULTS: A total of 97,527 patients were included, and only 745 (0.76%) patients were sPR-positive phenotype. The majority of sPR-positive breast cancer were basal-like subtype. Survival analysis showed that the sPR-positive breast cancer had similar prognosis comparing to double hormonal receptor-negative (ER-/PR-, dHoR-negative) breast cancer, and had the highest HRD during the initial 1-2 years of follow-up, then maintained the HRD of almost zero during the late years of follow-up. CONCLUSIONS: The patients with sPR-positive and her-2-negative breast cancer, similar to dHoR-negative breast cancer, had a worse survival, and could benefit from chemotherapy significantly. However, the escalating endocrine therapy was not recommended for sPR-positive patients. The patients with sPR positive should be excluded from future clinical trials concerning endocrine therapy.

Resection of primary lesion with chemotherapy improves the survival of patients with metastatic colorectal neuroendocrine carcinoma.

OBJECTIVE: To evaluate the effect of resection of primary lesion and chemotherapy on survival of patients with metastatic colorectal neuroendocrine carcinoma (CRNEC). METHODS: Clinical data of 393 patients with metastatic CRNECs between January 2010 and December 2016 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, including 171 patients who received resection of primary lesion and 221 patients who did not undergo surgery. With the propensity score matching method 172 non-operated patients were selected as controls. Kaplan-Meier method and Log-rank test were used to evaluate the survival differences, while the prognostic factors were analyzed by Cox proportional-hazards model. Metastatic CRNEC patients from January 2001 to December 2021 in Affiliated Jinhua Hospital, Zhejiang University School of Medicine were selected for validation. RESULTS: Compared with non-operated patients, patients who received resection had longer cause-specific survival ( P<0.05). Patients with resected positive lymph nodes>8 had a poorer prognosis compared to those with resected positive lymph nodes≤8 ( P<0.05). Multivariate analysis showed that gender, location of primary lesion and treatments were independent risk factors for cause-specific survival in patients with metastatic CRNEC (all P<0.05). For metastatic CRNEC patients with resection of primary lesion, rectal neuroendocrine carcinoma, positive resected lymph nodes≤8 and resection of primary lesion combined with chemotherapy were associated with better cause-specific survival (all P<0.05). CONCLUSIONS: Patients with metastatic CRNEC may benefit from resection of primary lesion, and resection of primary lesion combined with chemotherapy might be the better strategy for metastatic CRNECs. The number of positive lymph nodes resected is correlated with the prognosis of patients.

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells.

BACKGROUND: Despite of the frequently reported Dnmt3a abormality in classical myeloproliferative neoplasms (cMPNs) patients, few research explores how the Dnmt3a is regulated by Jak2V617F mutation. In this study, we have investigated how the Dnmt3a is regulated by Jak2V617F mutation and its effects on downstream signaling pathways in cMPNs. METHODS: Specimens of Jak2V617F positive cMPN patients and normal controls were collected. Murine BaF3 cell line was used to construct cell models. Dual-Glo luciferase assays and chromatin immunoprecipitation (ChIP)-qPCR were performed to detect the impact of Stat5a on transcription activity of Dnmt3a. Soft agar colony formation assay and cell counting assay were performed to detect cell proliferation. BrdU staining and flow cytometry were used to investigate cell cycle distribution. Western blotting and quantitative reverse-transcription PCR (qPCR) were performed to detect the expression levels of genes. RESULTS: Firstly, the results of western blotting and qPCR revealed that compared with the control samples, Dnmt3a is downregulated in Jak2V617F positive samples. Then we explored the mechanism behind it and found that Dnmt3a is a downstream target of Stat5a, the transcription and translation of Dnmt3a is suppressed by the binding of aberrantly activated Stat5a with Dnmt3a promoter in Jak2V617F positive samples. We further revealed the region approximately 800 bp upstream of the first exon of the Dnmt3a promoter, which includes a gamma-activated sequence (GAS) motif of Stat5a, is the specific site that Stat5a binds to. Soft agar colony formation assay, cell counting assay, and BrdU staining and flow cytometry assay found that Dnmt3a in Jak2V617F-BaF3 cells significantly affected the cell proliferation capacity and cell cycle distribution by suppressing Cdkn1a via miR-17-5p/Cdkn1a axis and mediated G0/G1 arrest. CONCLUSIONS: Transcription and translation of Dnmt3a is downregulated by the binding of Stat5a with Dnmt3a promoter in Jak2V617F cells. The GAS motif at promoter of Dnmt3a is the exact site where the Stat5a binds to. Dnmt3a conducted G0/G1 arrest through regulating miR-17-5p/Cdkn1a axis. The axis of Stat5a/Dnmt3a/miR-17-5p/Cdkn1a potentially provides a treatment target for cMPNs.

Poorer prognosis for neuroendocrine carcinoma than signet ring cell cancer of the colon and rectum (CRC-NEC): a propensity score matching analysis of patients from the Surveillance, Epidemiology, and End Results (SEER) database.

PURPOSE: Colorectal neuroendocrine carcinomas (CRC-NECs) are rare, comprising < 1% of colorectal cancers. This study aimed to assess the incidence, clinicopathologic characteristics, prognostic factors, and treatment outcomes of CRC-NEC. METHODS: We analysed the Surveillance, Epidemiology, and End Results (SEER) database to identify patients from 20 to 74 years old diagnosed with CRC-NEC or common CRC (non-NEC) during 2004-2013. Log-rank testing was conducted to assess survival differences. A competing-risks regression model was used to adjust for covariate effects in the propensity score-matched (PSM) cohort, and adjusted hazard ratios (HRs) were calculated for the raw and PSM cohorts. RESULTS: We identified 67,484 patients (344 CRC-NEC and 67,140 non-NEC). Lymph node metastasis (LNM) was more common in CRC-NEC (75.29%, n = 259) than in non-NEC (51.53%, n = 34,600) (P < 0.001); 56.40% (n = 194) of CRC-NECs were located on the right side, while 18.31% (n = 63) were located on the left side, with a statistically significant difference in distribution (P < 0.001) compared to that in non-NEC CRC. Multivariate analysis indicated that a left-side location was an independent adverse prognostic factor for CRC-NEC (P = 0.043). CRC-NEC had the poorest cancer-specific survival (median CSS, 9.0 months) among assessed cancers, even poorer than that of signet ring cell cancer (median CSS, 24.0 months). However, both radical operation (P = 0.007) and chemotherapy (P = 0.008) were beneficial for CSS. CONCLUSION: NEC is a rare and extremely aggressive tumour with a poor prognosis. Right-side NEC has a better prognosis than left-side NEC. Early diagnosis, radical surgery, and chemotherapy are imperative for improving survival.

Prevalence, risk factors, and clinical correlations of underweight in Chinese newly diagnosed and drug-naïve patients with Parkinson's disease.

OBJECTIVE: Studies have shown that patients with Parkinson's disease (PD) will experience weight loss during the progression of the illness, which suggests an increased rate of underweight. However, few studies have addressed underweight in early de novo population. This study aimed to examine the prevalence, risk factors, and clinical correlations of underweight in Chinese newly diagnosed and drug-naïve patients with PD. METHODS: A total of 245 inpatients with newly diagnosed PD and 213 age-, sex-, and education-matched healthy controls were enrolled in Ningbo. BMI, demographics, supine and upright blood pressure, Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) together with fasting blood glucose, low-density lipoprotein, total cholesterol, uric acid (UA), and homocysteine were collected in all subjects. Hoehn and Yahr (HY) rating and Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were also measured in patients. RESULTS: Overall, 35 (14.3%) patients were underweight and 14 (6.6%) controls were underweight. Binary regression analyses showed that low MoCA (p = 0.035), ΔSBP and ΔDBP values (both p < 0.001) were risk factors for underweight. Furthermore, correlation analysis indicated that BMI was associated with HY grade, UPDRS motor, HAMA, HAMD, MoCA, ΔSBP, ΔDBP, and UA values, stepwise multiple regression revealed significant correlations between BMI and ΔSBP (p < 0.001), ΔDBP (p = 0.001), MoCA (p = 0.002), UPDRS motor (p = 0.005), and HAMD scores (p = 0.014). CONCLUSIONS: Our study showed that the prevalence of underweight was significantly higher in Chinese newly diagnosed and drug-naïve patients with PD than in the healthy population, and several clinical variables were risk factors for underweight.

p.L105Vfs mutation in a family with thymic neuroendocrine tumor combined with MEN1: a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant disorder arising from mutations of the MEN1 tumor suppressor gene on chromosome 11q13; MEN1 is characterized by the development of neuroendocrine tumors, including those of the parathyroid, gastrointestinal endocrine tissue and anterior pituitary. Additionally, thymic neuroendocrine tumors in MEN1 are also rarely reported. CASE PRESENTATION: This case report observed a family that presented with MEN1 p.L105Vfs mutation, and two of the family members had been diagnosed with thymic neuroendocrine tumor combined with MEN1. To the best of our knowledge, this is the first time such a mutation in the MEN1 gene has been reported. The proband presented with thymic neuroendocrine tumor, parathyroid adenoma and rectum adenocarcinoma. The son of the proband presented with thymic neuroendocrine tumor, gastrinoma, hypophysoma and parathyroid adenoma. Genetic testing revealed the frameshift mutation p.L105Vfs, leading to the identification of one carrier in the pedigree (the patient's younger sister). The proband then underwent parathyroidectomy at the age of 26 years (in 1980) for a parathyroid adenoma. Subsequently, the patient underwent thymectomy, radiotherapy and chemotherapy. The patient is now 64 years old, still alive and still undergoing Lanreotide therapy. CONCLUSION: Thymic neuroendocrine MEN1 is rare, but it accounts for almost 20% of MEN1-associated mortality. Consequently, we should focus on regular clinical screening of the thymus in MEN1 patients.

Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer.

BACKGROUND: The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized. METHODS: Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model. RESULTS: There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model. CONCLUSIONS: OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society.

Signet ring cell carcinoma of resectable metastatic colorectal cancer has rare surgical value.

BACKGROUND AND OBJECTIVES: Signet ring cell carcinoma (SRCC) is a uniquely separated subgroup in metastatic colorectal cancer (mCRC). The aims are to investigate the value of resection in patients with resectable metastatic signet ring cell colorectal cancer. METHODS: Patients with mCRC who underwent resection in Surveillance, Epidemiology, and End Results database during 1998-2010 were retrospectively analyzed. Kaplan-Meier and COX models were used to analyze the differences in the survival. Logistic regression models were used to evaluate the relationship between SRCC and other clinicopathological factors. RESULTS: Among the 3,568 patients, 94 (2.63%) patients had SRCC. The median survival time of patients with SRCC and non-SRCC were 17 and 29 months, respectively (P < 0.001). Multivariate analysis indicated that SRCC was an independent prognostic factor for poor overall survival. Logistic regression model based on variables identified by univariate analysis indicated that younger age (≤50 years old) (P = 0.005), female (P < 0.001), location in colon (P = 0.012), and N positive status (P = 0.003) were independent variables correlated with the SRCC subgroup. SRCC had a dramatically higher invalid surgical outcome rate than non-SRCC (P = 0.001). CONCLUSION: SRCC patients might benefit little from the resection of primary and metastatic lesions with a high rate of undergoing invalid operations. J. Surg. Oncol. 2016;114:1004-1008. © 2016 Wiley Periodicals, Inc.

Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.

Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue.

[Benefit of network education to college students' knowledge about sexual and reproductive health in Ningbo city].

OBJECTIVE: To investigate how network education can improve college students' knowledge on sexual and reproductive health in Ningbo city. METHODS: From December 2012 to June 2013, we conducted a questionnaire investigation among college students in Ningbo city about the effects of network education on their knowledge about sexual psychology, sexual physiology, sexual ethics, and reproductive health. RESULTS: A total of 7 362 college students accomplished the investigation, of whom 2 483 (42.1% males and 57.9% females) received network education, while the other 4 879 (24.1% males and 75.9% females) did not. Approximately 47.1% of the male and 28.0% of the female students acquired sexual and reproductive knowledge via network education. Reproductive health-related network education significantly enriched the students' knowledge about the reproductive system and sex, pubertal development, sexual physiology, conception and embryonic development, methods of contraception, sexual psychology, sexually transmitted diseases and their prevention, pregnancy care and eugenics, and environment- and occupation-related reproductive health (P < 0.01). It also remarkably improved their cognitive attitude towards reproductive health knowledge (P < 0.01). Those who received reproductive health-related network education showed a significantly higher rate of masturbation (P < 0.01) but markedly later time of the first masturbation (P < 0.01) than those who did not. CONCLUSION: Network education can enhance the effect of reproductive health education among college students and improve their sexual experience and health.

NRS2002 score as a prognostic factor in solid tumors treated with immune checkpoint inhibitor therapy: a real-world evidence analysis.

To observe the antitumour efficacy of programmed death 1 (PD-1) inhibitors in the real world and explore the relationship between NRS2002 score or other clinical characteristics and immunotherapy efficacy, we retrospectively analyzed 341 tumor patients who received immune checkpoint inhibitor (ICI) treatment at one center. A total of 341 solid tumor patients treated with ICIs from June 2018 to December 2021 were retrospectively included in this study. Patient characteristics, ICI responses, and survival status were documented, and the relationships between clinical factors and survival were analyzed. Among all patients, the median progression-free survival (PFS) was 5.8 months, and the median overall survival (OS) was 12.5 months. The Performance Status (PS), NRS2002 score, The Naples Prognostic Score (NPS), Lymphocyte and C-reactive protein ratio (LCR), line of therapy, and nutritional support were significantly related to PFS or OS according to univariate analysis. The median PFS and OS were significantly better in the group without nutritional risk (NRS2002 0-2) than those with nutritional risk (NRS2002 ≥ 3) (PFS: HR = 1.82, 95% CI 1.30-2.54, p value < .001; OS: HR = 2.49, 95% CI 1.73-3.59, p value < .001). Cox regression analysis revealed that the NRS2002 score was an independent prognostic factor for both PFS and OS. The objective response rate (ORR) in the group at nutritional risk was lower than that in the group without nutritional risk (8.33% and 19.71%, respectively, p value = .037). Patients at nutritional risk according to the NRS2002 score at initial treatment had a poorer prognosis than those without nutritional risk. The NRS2002 could be used as a preliminary index to predict the efficacy of immune checkpoint inhibitor therapy.

Green spaces exposure and the risk of common psychiatric disorders: A meta-analysis.

Objective: To explore the effects of green spaces exposure on common psychiatric disorders. Methods: PubMed, Embase, Web of Science and MEDLINE were screened and articles published prior to November 15, 2023 were included. Analyses were performed on common psychiatric disorders, categorized into depression, anxiety, dementia, schizophrenia, and attention deficit hyperactivity disorder (ADHD). And the subgroup analyses were conducted for depression, anxiety, dementia, and schizophrenia. Results: In total, 2,0064 studies were retrieved, 59 of which were included in our study; 37 for depression, 14 for anxiety, 8 for dementia, 7 for schizophrenia and 5 for ADHD. Green spaces were found to benefit the moderation of psychiatric disorders (OR = 0.91, 95% CI: 0.89 to 0.92). Green spaces positively influence depression (OR = 0.89, 95% CI: 0.86 to 0.93), regardless of the cross-sectional or cohort studies. Green spaces can also help mitigate the risk of anxiety (OR = 0.94, 95%CI:0.92 to 0.96). As an important index for measuring green spaces, a higher normalized difference vegetation index (NDVI) level related to a lower level of depression (OR = 0.95, 95%CI:0.91 to 0.98) and anxiety (OR = 0.95, 95%:0.92 to 0.98). The protection was also found in dementia (OR = 0.95, 95% CI: 0.93 to 0.96), schizophrenia (OR = 0.74, 95% CI: 0.67 to 0.82), and ADHD (OR = 0.89, 95% CI: 0.86 to 0.92) results. Conclusion: Green spaces decrease the risk of psychiatric disorders, including depression, anxiety, dementia, schizophrenia, and ADHD. Further studies on green spaces and psychiatric disorders are needed, and more green spaces should be considered in city planning.