Evaluation of tumour heterogeneity by 18F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment.

BACKGROUND: Predictive biomarkers are needed to identify oestrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER + /HER2-) metastatic breast cancer (MBC) patients who would likely benefit from cyclin-dependent kinase 4 and 6 inhibitors combined with endocrine therapy. Therefore, we performed an exploratory study to evaluate the tumour heterogeneity parameters based on 16α-18F-fluoro-17ß-oestradiol (18F-FES)-PET imaging as a potential marker to predict progression-free survival (PFS) in MBC patients receiving palbociclib combined with endocrine therapy. METHODS: Fifty-six ER + MBC patients underwent 18F-FES-PET/CT before the initiation of palbociclib. 18F-FES uptake was quantified and expressed as the standardized uptake value (SUV). Interlesional heterogeneity was qualitatively identified according to the presence or absence of 18F-FES-negative lesions. Intralesional heterogeneity was measured by the SUV-based heterogeneity index (HI = SUVmax/SUVmean). Association with survival was evaluated using the Cox proportional hazards model. RESULTS: A total of 551 metastatic lesions were found in 56 patients: 507 lesions were identified as 18F-FES-positive, 38 lesions were distributed across 10 patients without 18F-FES uptake, and the remaining 6 were liver lesions. Forty-three patients obtained a clinical benefit, and 13 developed progressive disease (PD) within 24 weeks. Nine out of 10 patients with an 18F-FES-negative site developed PD, and the median PFS was only 2.4 months. Among 46 patients with only 18F-FES-positive lesions, only four patients had PD, and the median PFS was 23.6 months. There were statistically significant differences between the two groups (P < 0.001). For the subgroup of patients with only 18F-FES-positive lesions, low FES-HI patients experienced substantially longer PFS times than those with high FES-HI (26.5 months vs. 16.5 months, P = 0.004). CONCLUSIONS: 18F-FES-PET may provide a promising method for identifying and selecting candidate ER + /HER2- MBC patients who would most likely benefit from palbociclib combined with endocrine treatment and could serve as a predictive marker for treatment response. Trial registration NCT04992156, Date of registration: August 5, 2021 (retrospectively registered).

Electrolyte-Gated Graphene Field Effect Transistor-Based Ca2+ Detection Aided by Machine Learning.

Flexible electrolyte-gated graphene field effect transistors (Eg-GFETs) are widely developed as sensors because of fast response, versatility and low-cost. However, their sensitivities and responding ranges are often altered by different gate voltages. These bias-voltage-induced uncertainties are an obstacle in the development of Eg-GFETs. To shield from this risk, a machine-learning-algorithm-based LgGFETs' data analyzing method is studied in this work by using Ca2+ detection as a proof-of-concept. For the as-prepared Eg-GFET-Ca2+ sensors, their transfer and output features are first measured. Then, eight regression models are trained with the use of different machine learning algorithms, including linear regression, support vector machine, decision tree and random forest, etc. Then, the optimized model is obtained with the random-forest-method-treated transfer curves. Finally, the proposed method is applied to determine Ca2+ concentration in a calibration-free way, and it is found that the relation between the estimated and real Ca2+ concentrations is close-to y = x. Accordingly, we think the proposed method may not only provide an accurate result but also simplify the traditional calibration step in using Eg-GFET sensors.

Longitudinal impact of caregiver transition and family caregiving on psychiatric symptoms and psychosocial functioning among persons with schizophrenia in rural China.

This study examines the 21-year longitudinal impacts and predictive effects of family caregiver transition and the presence of family caregiving on the clinical status of persons with schizophrenia (PwSs) in a rural area of China. Using panel data derived from the Chengdu Mental Health Project (CMHP), 250 dyads of PwSs and their family caregivers were investigated in 1994 and 2015. The Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF) were utilized. The generalized linear model (GLM) approach was used. The results of this study showed that more severe symptoms in PwSs were found to be significantly predicted by older age and nonmarried status at baseline. Compared with "spousal caregiving in two waves," the PANSS score was significantly higher in the "transition into sibling caregiving" group. A higher degree of psychosocial functioning was found to be significantly predicted by marital status, shorter duration of illness, and better mental status. Compared with "spousal caregiving in two waves," the GAF score was significantly lower in the "transition into parental caregiving" group. The presence of family caregiving was not a significant predictor of the severity of symptoms or psychosocial functioning in the PwSs. In conclusion, this study shows the 21-year predictive effects of family caregiver transition on the mental status of PwSs but not the presence of family caregiving. Psychosocial interventions and specific guidance should be provided to family caregivers to enhance their quality of caregiving and improve the prognosis of PwSs during long periods of home care.

En este estudio se analizan los efectos longitudinales a 21 años y los efectos pronósticos de la transición de los cuidadores familiares y la presencia de cuidado familiar en el estado clínico de las personas con esquizofrenia en un área rural de China. Utilizando datos de panel extraídos del Proyecto de salud mental de Chengdu (Chengdu Mental Health Project, CMHP), se investigaron 250 díadas de personas con esquizofrenia y sus cuidadores familiares en 1994 y 2015. Se utilizó la Escala de síndrome positivo y negativo (Positive and Negative Syndrome Scale, PANSS) y la Evaluación global del funcionamiento (Global Assessment of Functioning, GAF). También se utilizó el método de modelo lineal generalizado. Los resultados de este estudio demostraron que los síntomas más intensos en las personas con esquizofrenia fueron pronosticados principalmente por la edad avanzada y el estado de soltería en el momento basal. En comparación con el grupo de "cuidado de los cónyuges en dos intervalos", el puntaje de la PANSS fue considerablemente más alto en el grupo de "transición al cuidado de los hermanos". Se descubrió que principalmente el estado civil, la duración más corta de la enfermedad y un mejor estado mental pronosticaron un grado más alto de funcionamiento psicosocial. En comparación con el grupo de "cuidado de los cónyuges en dos intervalos", el puntaje de la GAF fue considerablemente más bajo en el grupo de "transición al cuidado de los padres". La presencia de cuidado familiar no fue un factor pronóstico importante de la intensidad de los síntomas ni del funcionamiento psicosocial en las personas con esquizofrenia. En resumen, en este estudio se muestran los efectos pronósticos a 21 años de la transición de los cuidadores familiares en el estado mental de las personas con esquizofrenia, pero no la presencia de cuidado familiar. Deben ofrecerse intervenciones psicosociales y orientación específica a los cuidadores familiares para mejorar su calidad de cuidado y mejorar el pronóstico de las personas con esquizofrenia durante los periodos prolongados de cuidado en el hogar.

Phase II trail of nab-paclitaxel in metastatic breast cancer patients with visceral metastases.

BACKGROUND: Visceral metastases account for 48-67% of metastatic breast cancer (MBC) patients and presage a worse overall survival. Previous study suggested potential effect of nab-paclitaxel on patients with visceral metastases subgroups. This phase II trial was conducted to explore the efficacy and safety of nab-paclitaxel in such a high-risk group of patients. METHODS: In this prospective, single-center, open-label, phase II study, MBC patients with visceral metastases (N = 80) received nab-paclitaxel (Abraxane, 125 mg/m2, D1, D8, D15 every 28 days). RESULTS: The median PFS was 5.1 months (95% CI: 4.2-6.0 months), with an ORR of 33.8% (95% CI 21.3-43.8%) and CBR of 66.2% (95% CI 56.3-75.0%). In univariate analysis, patients with premenopausal status had a trend of better treatment outcome. Multivariate analysis demonstrated non brain metastasis (adjusted HR 0.31, 95% CI 0.12-0.83, P = 0.019) and first line treatment (adjusted HR 0.37, 95% CI 0.17-0.81, P = 0.013) as independent predictors of longer PFS. The overall safety was acceptable with most common treatment-related, grade ≥ 3 toxicities of neutropenia (16.3%) and sensory neuropathy (3.7%). CONCLUSIONS: This phase II trial documented satisfactory efficacy and safety of nab-paclitaxel in MBC patients with visceral metastases, providing evidence for relative clinical practice. Patients in first line therapy had better treatment outcome. For patients with premenopausal status or brain metastasis, further alternatives (for example, combined chemotherapy or targeting therapy) might be required. This study also demonstrated the efficacy and safety of 125 mg/m2 nab-paclitaxel among Asian patients. TRIAL REGISTRATION: This research is registered under clinicaltrials.gov (NCT02687490, February 22, 2016).

Porous Graphene Oxide Decorated Ion Selective Electrode for Observing Across-Cytomembrane Ion Transport.

The technology for measuring cytomembrane ion transport is one of the necessities in modern biomedical research due to its significance in the cellular physiology, the requirements for the non-invasive and easy-to-operate devices have driven lots of efforts to explore the potential electrochemical sensors. Herein, we would like to evidence the exploitation of the porous graphene oxide (PGO) decorated ion selective electrode (ISE) as a detector to capture the signal of cytomembrane ion transport. The tumor cells (MDAMB231, A549 and HeLa) treated by iodide uptake operation, with and without the sodium-iodide-symporter (NIS) expression, are used as proofs of concept. It is found that under the same optimized experimental conditions, the changed output voltages of ISEs before and after the cells' immobilization are in close relation with the NIS related ion's across-membrane transportation, including I-, Na+ and Cl-. The explanation for the measured results is proposed by clarifying the function of the PGO scaffold interfacial micro-environment (IME), that is, in this spongy-like micro-space, the NIS related minor ionic fluctuations can be accumulated and amplified for ISE to probe. In conclusion, we believe the integration of the microporous graphene derivatives-based IME and ISE may pave a new way for observing the cytomembrane ionic activities.

Study of porphyrin-modified liquid exfoliated graphene field-effect transistors for evaluating DNA methylation degree.

The applications of graphene field-effect transistors (FETs) for monitoring DNA hybridization have been widely accepted; however, for evaluating DNA methylation degree, an emerging requirement of epigenetic research, no work has been found due to the difficulties in detecting 5-methylcytosine (5mC) sites along the genomic sequence as well as counting their amount (NmC). Herein, to achieve this, a strategy for exploiting a liquid exfoliated graphene (LEG)-based FET (LEG-FET) as a sensing platform was proposed. First, LEG-FETs were prepared and activated by tetra-4-aminophenyl-porphyrin (TAPP) for anchoring single-strand DNAs (ssDNAs). Second, the 5mC sites in ssDNA were recognized by the specifically absorbed 5mC antibody (5mCab) and transduced to the changed currents (ΔIDS) by LEG-FET according to the integration of the methylation-immuno sensing principle and FET's working mechanism. Briefly, more 5mCab molecules could be captured by more 5mC sites, resulting in larger ΔIDS. The TAPP effects on LEG-FET were analyzed by SEM, Raman, AFM, and XPS characterizations as well as electronic measurements. The validity of this LEG-FET sensing platform for evaluating DNA methylation degree was proven step by step; this included the examinations of the synthesized ssDNAs with the known NmC and real ssDNA samples, whose methylation degrees were pre-determined by the gold-standard method, which is based on tedious bisulphite sequence operations and expensive mass spectrometry technology. Moreover, theoretical explanations were also provided for the sensing mechanism in the proposed DNA methylation analytical components. In conclusion, the positive and linear relations of IDS changing ratio vs. NmC as well as the detection limit of one 5mC site indicate that TAPP-modified LEG-FET can provide an alternative analytical tool to realize fast and economical DNA methylation evaluation.

Treatment Status of Elderly Patients With Severe Mental Disorders in Rural China.

This study was performed to compare the treatment status between older (≥65 years) and younger adults (18-64 years) with severe mental illness (SMI) and explore factors associated with treatment status in rural China. Persons with SMI were identified in one mental health survey in 2015 in 6 townships of Xinjin County, Chengdu, China. Logistic regressions were conducted to explore factors associated with treatment status. Older adults with SMI, especially major depressive disorder, reported significantly lower rates of treatment than younger group. Older age, longer duration of illness, and poor mental status were risk factors for never-treated status in these patients. Never-treated status (46.3%) and poor treatment status in these older patients are serious issues. Different treatment statuses in these patients had various influencing factors. It is crucial to develop culture-specific, community-based mental health services to improve early identification, diagnosis, treatment, and recovery of older adults with SMI in rural China.

Function of Tetra (4-Aminophenyl) Porphyrin in Altering the Electronic Performances of Reduced Graphene Oxide-Based Field Effect Transistor.

Porphyrin functionalized reduced graphene oxide (rGO) is attractive for multi-disciplinary research studies, and its improvements for an rGO-based field effect transistor (rGO-FET) were exploited to realize ultrasensitive biochemical and clinical assay. Although it was believed that the hybrids of porphyrin and rGO can make positive impacts on the rGO-FET's electronic performances, the understandings of its functions are still piecemeal. Herein, the reduced mixtures of tetra (4-aminophenyl) porphyrin (TAP), GO (TAP-rGO), and the FET channeled by them are examined to throw a light on the possible approaches through which TAP affects rGO's quality and its carrier mobilities. A TAP-caused game relationship is established by deliberating about the results of the intentionally altered experimental conditions, including TAP contents and the overmixing pretreatment. The p-type doping deduction for the right-shifted ambipolar transfer characteristic curves is evidenced by X-ray photoelectron spectroscopy (XPS). The problems posed by the TAP-induced FET features' improvement, regression, and deterioration are clarified by the integrated proofs from Raman fingerprints, the amide and carboxyl groups' changing trajectory found by C1s XPS core spectra, and the enlarged few-layer graphene morphology from atomic force microscope and transmission electron microscope. We hope that this effort will provide some constructive recommendations for producing low-cost graphene derivatives and promoting their applications in FET-like electronic components.

Different outcomes of never-treated and treated patients with schizophrenia: 14-year follow-up study in rural China.

BACKGROUND: The long-term outcome of never-treated patients with schizophrenia is unclear. AIMS: To compare the 14-year outcomes of never-treated and treated patients with schizophrenia and to establish predictors for never being treated. METHOD: All participants with schizophrenia (n = 510) in Xinjin, Chengdu, China were identified in an epidemiological investigation of 123 572 people and followed up from 1994 to 2008. RESULTS: The results showed that there were 30.6%, 25.0% and 20.4% of patients who received no antipsychotic medication in 1994, 2004 and 2008 respectively. Compared with treated patients, those who were never treated in 2008 were significantly older, had significantly fewer family members, had higher rates of homelessness, death from other causes, being unmarried, living alone, being without a caregiver and poor family attitudes. Partial and complete remission in treated patients (57.3%) was significantly higher than that in the never-treated group (29.8%). Predictors of being in the never-treated group in 2008 encompassed baseline never-treated status, being without a caregiver and poor mental health status in 1994. CONCLUSIONS: Many patients with schizophrenia still do not receive antipsychotic medication in rural areas of China. The 14-year follow-up showed that outcomes for the untreated group were worse. Community-based mental healthcare, health insurance and family intervention are crucial for earlier diagnosis, treatment and rehabilitation in the community.

Moringa oleifera Leaf Powder as New Source of Protein-Based Feedstuff Improves Growth Performance and Cecal Microbial Diversity of Broiler Chicken.

Currently, the lack of protein source feed has become a pressing issue. Moringa oleifera leaf powder (MOLP) has good potential for the development of protein-derived feeds due to its good protein quality and abundance, but little is known about its effects on broiler growth performance and cecal microbiota. In this study, the chickens were fed different rates of MOLP (1%, 3%, 5%, 7%, and 9%) instead of the rape seed cake, and the effects of different levels of MOLP on growth performance, carcass characteristics, and cecal microbiota of the broilers were evaluated at two different growth stages (day 28 and day 56). In terms of growth performance, the best results were obtained at the 3% MOLP level in the early stages (p < 0.05). In terms of carcass characteristics, in the early stage, the level of 5% MOLP had the best effect; in the later stage, 5% MOLP also had the best effect. In terms of cecal microbial changes, the alpha diversity analysis revealed that 5% MOLP enhanced the richness and diversity of broiler intestinal flora. At the phylum level, the addition of 5% MOLP adjusted the relative abundance of Firmicutes and Bacteroidetes to a level close to that of the A1 group on day 28, while 5% MOLP significantly reduced the relative abundance of Bacteroidetes (p < 0.05) compared to the A2 group on day 56, and the relative abundance of Firmicutes was still higher in the D2 group than in the A2 group (p < 0.05). At the genus level, MOLP addition consistently and significantly increased the relative abundance of Bacteroides (p < 0.05), except for 3% on day 28 and 1% on day 56. For Oscillospira, increasing MOLP levels in the pre- and post-period resulted in a significant decrease in the relative abundance of Oscillospira (p < 0.05). In conclusion, MOLP helps to enhance growth performance and carcass characteristics and improve the cecal microbial structure of broilers. The recommended rate of MOLP addition for broilers is 5% in both the early and late stages.

ER status conversion and subsequent treatment: an assessment of negative ER expression detected by 18F-FES PET in metastatic breast cancer patients with ER-positive primary tumors.

Background: The 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) technique provides a convenient method to evaluate the overall estrogen receptor (ER) expression in metastatic breast cancer (MBC) patients. There are long debates on the characteristics and treatment strategy of patients with positive primary ER lesions but negative ER expression in metastatic disease. 18F-FES PET offers an opportunity to answer this question. Objectives: This study aimed to characterize the primary ER-positive patients with advanced-stage FES negativity and investigate the real-world treatment decisions made by physicians subsequently, and compare the efficacy between different regimens. Design: This observational cohort study was conducted at Fudan University Shanghai Cancer Center, enrolling breast cancer patients with ER-positive primary tumors who showed advanced-stage FES negativity. Methods: Descriptive statistics were used in clinicopathologic characteristics and compared with a chi-square test or t-test. In addition, progression-free survival (PFS) was estimated by the Kaplan-Meier method and compared by log-rank test. Results: 16.6% (52/314) of patients with an ER-positive primary tumor had negative ER expression assessed by 18F-FES for MBC prior to receiving first-line systemic therapy, among whom adjuvant endocrine therapy was prevalently utilized (86.5%, 45/52). The rate of FES negativity in the advanced stage was negatively correlated with levels of ER expression of primary tumors. Chemotherapy (83.3%, 40/48) was the most common treatment strategy afterward, among which capecitabine monotherapy (62.5%, 25/40) was a dominant alternative. PFS was significantly prolonged with capecitabine alone versus other chemotherapy (median PFS: 13.14 versus 6.21 months, p = 0.029). Conclusion: Negative conversion of ER in MBC detected by 18F-FES occurred frequently. Patients with lower ER expression in the primary lesion were more likely to have negative ER expression in the metastasis. In real-world clinical practice, most physicians primarily opted for chemotherapy, with capecitabine monotherapy being a commonly selected regimen. Trial registration: ClinicalTrials.gov identifier: NCT05797987.

Chemotherapy Shows a Better Efficacy Than Endocrine Therapy in Metastatic Breast Cancer Patients with a Heterogeneous Estrogen Receptor Expression Assessed by 18F-FES PET.

Background: The heterogeneity of estrogen receptor (ER) expression has long been a challenge for the diagnosis and treatment strategy of metastatic breast cancer (MBC). A novel convenient method of ER detection using 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) offers a chance to screen and analyze MBC patients with ER uncertainty. Methods: MBC patients who received 18F-FES PET/CT were screened and patients with both FES positive (FES+) and negative (FES-) lesions were enrolled in this study. Progression-free survival (PFS) was estimated using the Kaplan−Meier method and was compared using the log-rank test. Results: A total of 635 patients were screened and 75 of 635 (11.8%) patients showed ER uncertainty; 51 patients received further treatment and were enrolled in this study. Among them, 20 (39.2%) patients received chemotherapy (CT), 21 (41.2%) patients received endocrine-based therapy (ET), and 10 (19.6%) patients received combined therapy (CT + ET). CT showed a better progression-free survival (PFS) compared with ET (mPFS 7.1 vs. 4.6 months, HR 0.44, 95% CI 0.20−0.93, p = 0.03). CT + ET did not improve PFS compared with either CT or ET alone (mPFS 4.4 months, p > 0.2). All three treatment options were well tolerated. Conclusions: 18F-FES PET/CT could identify patients with ER heterogeneity. Patients with bone metastasis are more likely to have ER heterogeneity. Patients with ER heterogeneity showed better sensitivity to CT rather than ET. Combined therapy of CT + ET did not improve the treatment outcome.

Heterogeneity derived from 18 F-FDG PET/CT predicts immunotherapy outcome for metastatic triple-negative breast cancer patients.

BACKGROUND: Recently, immunotherapy has been used to treat metastatic triple-negative breast cancer (mTNBC). Basic research has indicated a relation between tumor heterogeneity and the immune response. Tumor heterogeneity derived from 18 F-FDG PET/CT is a potential predictor of chemotherapy results; however, few studies have focused on immunotherapy. This study aims to develop a convenient and efficient measurement of tumor heterogeneity for the prediction of immunotherapy in mTNBC patients. METHODS: We enrolled mTNBC patients who received immunotherapy (PD-1/PD-L1 antibody) plus chemotherapy as first-line treatment and underwent 18 F-FDG PET/CT scans before treatment. We defined a novel index representing tumor heterogeneity calculated from the standard uptake value (SUV) as IATH and IETH. Optimal cutoffs were determined using time-dependent receiver operator characteristics (ROC) analysis. RESULTS: A total of 32 patients were enrolled and analyzed in this trial. A significantly longer median PFS was observed in the low SUVmax group than in the high SUVmax group (9.4 vs. 5.8 months, HR = 0.3, 95% CI 0.1-0.9, p = 0.025). The median PFS of low-IATH patients was significantly longer than that of high-IATH patients (HR = 0.3, 95% CI 0.1-0.8, p = 0.022). Similarly, patients with low IETH had significantly longer PFS than patients with high IETH (9.4 vs. 4.9 months, HR = 0.3, 95% CI 0.1-0.7, p = 0.01). Multivariate analysis demonstrated IETH as an independent predictor of PFS. CONCLUSIONS: This study proposed a novel method to assess intratumor and intertumor heterogeneity among metastatic breast cancer patients and determined that baseline IETH derived from 18 F-FDG PET/CT could represent a simple and promising predictor for first-line immunotherapy among mTNBC patients.

Predictors of family caregiving burden of persons with schizophrenia with and without transition of primary caregivers from 1994 to 2015 in rural China.

BACKGROUND: Little is known about how sociodemographic and clinical factors affect the caregiving burden of persons with schizophrenia (PwSs) with transition in primary caregivers. AIMS: This study aimed to examine the predictive effects of sociodemographic and clinical factors on the caregiving burden of PwSs with and without caregiver transition from 1994 to 2015 in rural China. METHOD: Using panel data, 206 dyads of PwSs and their primary caregivers were investigated in both 1994 and 2015. The generalised linear model approach was used to examine the predictive effects of sociodemographic factors, severity of symptoms and changes in social functioning on the caregiving burden with and without caregiver transition. RESULTS: The percentages of families with and without caregiver transition were 38.8% and 61.2%, respectively. Among families without caregiver transition, a heavier burden was significantly related to a larger family size and more severe symptoms in PwSs. Deteriorated functioning of 'social activities outside the household' and improved functioning of 'activity in the household' were protective factors against a heavy caregiving burden. Among families with caregiver transition, younger age, improved marital functioning, deteriorated self-care functioning, and better functioning of 'social interest or concern' were significant risk factors for caregiving burden. CONCLUSIONS: The effects of sociodemographic and clinical correlates on the caregiving burden were different among families with and without caregiver transition. It is crucial to explore the caregiver arrangement of PwSs and the risk factors for burden over time, which will facilitate culture-specific family interventions, community-based mental health services and recovery.

Risk factors for poor work functioning of persons with schizophrenia in rural China.

BACKGROUND: The long-term work performance of persons with schizophrenia in the community is unclear. This study examined the status of long-term work functioning and the predictors of poor work status among patients with schizophrenia in a Chinese rural area. METHODS: A 10-year follow-up investigation (1994-2004) of a cohort (n = 510) of persons with schizophrenia was conducted in Xinjin County, Chengdu, China. RESULTS: Compared with baseline data, work functioning of patients with schizophrenia deteriorated after 10 years. The rates of not working increased significantly from 12.0% in 1994 to 23.0% in 2004. Bivariate analyses showed that the poor work functioning in 2004 was significantly associated with male gender, older age, older age of first onset, higher level of education, longer duration of illness, lower family economic status, lack of caregivers, poor work status in 1994, living in shabby or unstable house, marked symptoms, and higher score on the Social Disability Screening Schedule (SDSS). In multiple logistic regression analyses, higher score of SDSS and poor work status in 1994 were identified as unique predictors of poor work status in 2004. CONCLUSION: The status of work functioning of persons with schizophrenia decreased over the course of the illness. The risk factors for poor work functioning and specific socio-cultural environment should be considered in planning community mental health services and rehabilitation for these patients.

Possibility of Combining Carbon Dots and Liquid Exfoliated Graphene as a Carbon-Based Light Addressable Potentiometric Sensor.

A light addressable potentiometric sensor (LAPS) is a versatile sensing platform for bioassay. However, the lack of carbon-based LAPS (C-LAPS) is a bottleneck for its sustainable development in a carbon electronic era. Herein, a study of C-LAPS based on the combinations of carbon dots (CDs) and liquid exfoliated graphene (LEG) is presented. Devices of C-LAPS are first fabricated by self-assembling the hydrothermally synthesized CDs and the cosolvent ultrasonic delaminated LEG on poly(diallyldimethylammonium chloride) (PDDA)-modified indium tin oxide (ITO) glasses. According to the stacking orders of CDs and LEG, C-LAPS are named as CDs/LEG@PDDA/ITO and LEG/CDs@PDDA/ITO. Then, their electronic and photoelectronic features are measured and compared with the pure CD- and pure LEG-decorated ITO electrodes. Furthermore, working mechanisms are proposed by means of the classical theories of energy band bending and built-in electric field at the heterojunction of CDs and LEG. The resemblances of CDs/LEG@PDDA/ITO-based C-LAPS with Si-based LAPS (Si-LAPS) are confirmed from the points of view of production and separation of the photogenerated carriers, the formation of photocurrent, and the distinction with LEG/CDs@PDDA/ITO. Finally, its feasibility for biological application is justified by using the immune reaction of 5-methylcytosine (5mC) and its antibody (anti-5mC) as a proof of concept. The improved linear responses are evidenced by the comparisons with Si-LAPS' results. Conclusively, the proposed C-LAPS is believed to be a candidate for traditional semiconductor-based LAPS, with the merit of solution-processable. Meanwhile, the theoretical deductions about C-LAPS' principle can also pave the way for developing similar carbon-based sensors.

Change of poverty and outcome of persons with severe mental illness in rural China, 1994-2015.

BACKGROUND: It is unknown whether and how poverty influences the long-term outcome of persons with severe mental illness (SMI). AIMS: To explore the change of poverty status in persons with SMI from 1994 to 2015 and examine the impact of poverty status on patients' outcome in rural China. METHOD: Two mental health surveys using identical methods and International Classification of Disease (ICD-10) were conducted in 1994 and 2015 in the same six townships of Xinjin County, Chengdu, China. RESULTS: The annual net income per person was 19.8% and 100.2% higher for the general population than for persons with SMI in 1994 and 2015 respectively. Compared with 1994 (48.2%), persons with SMI in 2015 had significantly higher rates of poor family economic status (

Real-world effectiveness of eribulin in heavily pretreated patients with metastatic breast cancer in China: a multicenter retrospective study.

BACKGROUND: Eribulin is a nontaxane microtubule inhibitor approved in China for patients with advanced breast cancer who show progression after ⩾2 lines of chemotherapy. The aim of this study was to determine the efficacy and safety profile of eribulin and explore potential predictive factors for the efficacy of eribulin among Chinese women with metastatic breast cancer (MBC) in real-world practice. PATIENTS AND METHODS: A total of 272 consecutive MBC patients who were treated with eribulin between November 2019 and October 2020 in 9 institutions nationwide were included in this study. Eribulin was administered intravenously at a dose of 1.4 mg/m2 on days 1 and 8 of a 21-day cycle. Efficacy outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Adverse events (AEs) were graded according to The National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0. RESULTS: Eribulin showed a median PFS of 4.1 months (95% confidence interval [CI] 3.6-4.6); however, the OS data were immature. The ORR was 17.6% and the CBR was 24.6%. A total of 51.8% of patients received eribulin monotherapy, while 48.2% of patients were treated with eribulin plus targeted therapy or other chemotherapy. The number of metastatic sites, duration of previous taxane treatment for MBC, and combination with bevacizumab were significant in Cox multivariate analysis (p = 0.023, p = 0.048, and p = 0.046, respectively) and were significantly associated with PFS of eribulin. The most common AEs with eribulin treatment were hematological toxicities, including neutropenia, leukopenia, and anemia. CONCLUSION: Eribulin was effective with a manageable toxicity profile in clinical practice. Furthermore, when prescribed in combination with other agents, eribulin did not increase the toxic effects of each agent. Eribulin monotherapy or plus other agents is an alternative for the heavily pretreated patients with MBC.

Mortality and suicide in schizophrenia: 21-year follow-up in rural China.

BACKGROUND: Little is known about the trend and predictors of 21-year mortality and suicide patterns in persons with schizophrenia. AIMS: To explore the trend and predictors of 21-year mortality and suicide in persons with schizophrenia in rural China. METHOD: This longitudinal follow-up study included 510 persons with schizophrenia who were identified in a mental health survey of individuals (≥15 years old) in 1994 in six townships of Xinjin County, Chengdu, China, and followed up in three waves until 2015. Kaplan-Meier survival analysis and Cox hazard regressions were conducted. RESULTS: Of the 510 participants, 196 died (38.4% mortality) between 1994 and 2015; 13.8% of the deaths (n = 27) were due to suicide. Life expectancy was lower for men than for women (50.6 v. 58.5 years). Males consistently showed higher rates of mortality and suicide than females. Older participants had higher mortality (hazard ratio HR = 1.03, 95% CI 1.01-1.05) but lower suicide rates (HR = 0.95, 95% CI 0.93-0.98) than their younger counterparts. Poor family attitudes were associated with all-cause mortality and death due to other causes; no previous hospital admission and a history of suicide attempts independently predicted death by suicide. CONCLUSIONS: Our findings suggest there is a high mortality and suicide rate in persons with schizophrenia in rural China, with different predictive factors for mortality and suicide. It is important to develop culture-specific, demographically tailored and community-based mental healthcare and to strengthen family intervention to improve the long-term outcome of persons with schizophrenia.

Differences in mortality and suicidal behaviour between treated and never-treated people with schizophrenia in rural China.

BACKGROUND: Many people with schizophrenia remain untreated in the community. Long-term mortality and suicidal behaviour among never-treated individuals with schizophrenia in the community are unknown. AIMS: To explore 10-year mortality and suicidal behaviour among never-treated individuals with schizophrenia. METHOD: We used data from a 10-year prospective follow-up study (1994-2004) among people with schizophrenia in Xinjin County, Chengdu, China. RESULTS: The mortality rate for never-treated individuals with schizophrenia was 2761 per 100 000 person-years during follow-up. There were no significant differences of rates of suicide and all-cause mortality between never-treated and treated individuals. The standardised mortality ratio (SMR) for never-treated people was 10.4 (95% CI 7.2-15.2) and for treated individuals 6.5 (95% CI 5.2-8.5). Compared with treated people, never-treated individuals were more likely to be older, poorer, have a longer duration of illness, marked symptoms and fewer family members. CONCLUSIONS: The never-treated individuals have similar mortality to and a higher proportion of marked symptoms than treated people, which may reflect the poor outcome of the individuals without treatment. The higher rates of mortality, homelessness and never being treated among people with schizophrenia in low- and middle-income nations might challenge presumed wisdom about schizophrenia outcomes in these countries.