Current Status of Cognition and Clinical Practice of Refractory Cancer Pain in Shanghai: A Questionnaire Survey.

Purpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai. Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China. Results: A total of 238 responses participated in the survey. This survey reports physicians' understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors' knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff's understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training. Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.

Aberrant KAT2A accumulations render TRIM22-low melanoma sensitive to Notch1 inhibitors via epigenetic reprogramming.

BACKGROUND: Aberrant ubiquitin-proteasome system (UPS) triggers various disorders of biological events and contributes to progression of tumorigenesis. The tripartite motif containing 22 (TRIM22) was demonstrated to participate in the progression of multiple malignancies. Nevertheless, the role of TRIM22 in melanoma is still indefinite. This project aims to investigate the biological function of TRIM22 in melanoma and provide novel therapeutical targets. METHODS: Bioinformatic algorithms were used to investigate prognostic significance of TRIM22. The in vitro or in vivo assays were used to explore the functions of TRIM22 in melanoma. The Co-Immunoprecipitation (Co-IP) and in vivo ubiquitination assays were used to assess regulations of TRIM22 on lysine acetyltransferase 2 A (KAT2A). The Chromatin immunoprecipitation (ChIP) assays and luciferase reporter assay were utilized to explore epigenetic regulations of KAT2A on Notch1. RESULTS: Here, we utilized the bioinformatic methods to confirm that TRIM22 is decreased in melanoma than normal tissues. Patients with low TRIM22 levels had shorter survival months than those with high TRIM22 levels. Targeting TRIM22 favors melanoma cell migration, proliferation, and tumor development in vitro and in vivo. Mechanistically, TRIM22 interacts with KAT2A and promotes its degradation in a ubiquitination-dependent manner. Melanoma cells with TRIM22 deficiency depended on KAT2A to enhance malignant progression, including proliferation, migration, and in vivo growth. KEGG analysis determined the positive correlation between KAT2A and Notch signaling. Chromatin Immunoprecipitation (ChIP) assays implicated that KAT2A directly binds to the promoter region of Notch1 and mediates the enrichment of H3K9ac modification. KAT2A activates Notch1 transcriptional levels and sustains the stemness feature of melanoma cells. Nocth1 inhibitor (IMR-1) effectively suppresses the growth of TRIM22low melanoma in vitro and in vivo but fails to inhibit TRIM22high melanoma. CONCLUSION: Together, our study illustrates the mechanism by which the TRIM22-KAT2A-Notch1 axis promotes melanoma progression, and demonstrates that KAT2A/Nocth1 confers an epigenetic vulnerability in TRIM22low melanoma.

All-Trans Retinoic Acid Promotes M2 Macrophage Polarization in Vitro by Activating the p38MAPK/STAT6 Signaling Pathway.

BACKGROUND: M2-type macrophages are inflammation-suppressing cells that are differentiated after induction by cytokines such as IL-4 or IL-13, which play an important regulatory role in inflammation and influence the regression of inflammation-related diseases. All-trans retinoic acid (ATRA) has an important role in suppressing immune-mediated inflammatory responses but the effect and underlying mechanism of ATRA on the polarization of M2 macrophages remains unclear. METHODS: Macrophages were isolated from peritoneal wash fluid, and IL-4 (20 ng/mL) was used to construct a m2-type macrophage polarization model. The model was incubated with different concentrations of ATRA (15 µg/ml, 30 µg/ml, 45 µg/ml) for 24 h, and pretreated macrophages with p38MAPKα inhibitor SB202190 (20 µM). MTT, Trypan blue staining, Annexin V-PE/7-AAD staining, flow cytometry, real-time PCR and western blotting were used to investigate the effect and mechanism of ATRA on the polarization of M2 macrophages. RESULTS: Compared with the IL-4 group, the proportion of F4/80+CD206+ M2-type macrophages was significantly higher in the ATRA group (P < 0.01). mRNA and protein expression levels of Arg-1, IL-10 and TGF-ß1 were as significantly higher (P < 0.01) in the ATRA group as phosphorylation levels of STAT6 and p38MAPK (P < 0.01). After pretreatment with the addition of the inhibitor SB202190, M2-type macrophages proportion and their associated factors expression were significantly (P < 0.01) reduced, as compared with those in the ATRA group, but they were comparable (P > 0.05) with the IL-4 group. CONCLUSION: The combination of ATRA and IL-4 activated the p38MAPK/STAT6-signaling pathway to promote polarization of M2 macrophages.

LncRNA ELF3-AS1 Promotes Non-Small Cell Lung Cancer Cell Invasion and Migration by Downregulating miR-212.

LncRNA ELF3-AS1 has been characterized as an oncogenic lncRNA in bladder cancer and oral cancer, whereas its role in non-small cell lung cancer (NSCLC) is unknown. In this study, the authors observed that ELF3-AS1 was upregulated in NSCLC tissues in comparison with that in paired nontumor tissues collected from 68 NSCLC patients. High expression levels of ELF3-AS1 predicted the poor survival of NSCLC patients. Expression levels of miR-212 were inversely and significantly correlated with the expression levels of ELF3-AS1 across NSCLC tissue samples. In NSCLC cells, overexpression of ELF3-AS1 led to downregulated miR-212 and increased methylation of miR-212 gene. In addition, overexpression of ELF3-AS1 inhibited the role of miR-212 in suppressing cancer cell invasion and migration. Therefore, ELF3-AS1 is upregulated in NSCLC and promotes cancer cell invasion and migration by downregulating miR-212 through methylation.

Value of Traditional Chinese Medicine syndrome differentiation in predicting the survival time of patients with advanced cancer.

OBJECTIVE: To prospectively study the accuracy of the palliative prognostic index (PPI) survival prediction model combined with Traditional Chinese Medicine (TCM) syndrome differentiation. METHODS: The PPI survival prediction model was used to predict survival time. Patients' real survival time was recorded. The survival time was calculated using the Kaplan-Meier method, and the logrank method was used to test the difference. RESULTS: The average PPI survival prediction score of 227 patients was 5.83 (95% CI: 5.29-6.37). There was a significant difference in the real-life period between the different PPI groups (P < 0.05). PPI group I (predicted survival of > 6 weeks) showed the highest predictive sensitivity and PPI group II (predicted survival of 3-6 weeks) showed the highest predictive specificity. According to TCM syndrome differentiation, 82 cases (36% ) were diagnosed with liver and kidney Yin deficiency (type IV). The actual survival time of type IV patients was significantly shorter than that of other types of patients (mean: 21.85 vs 28.70, P = 0.007). In group I, the median survival time of type IV patients and other types was 25 and 34 d, respectively (P < 0.001). The sensitivity and specificity of PPI prediction were improved in group II by TCM syndrome differentiation. For patients in group III whose predicted survival time was < 3 weeks, the specificity of PPI survival prediction was higher in type IV patients. CONCLUSION: This study shows that the PPI predictive tool for survival rate has important value. TCM syndrome differentiation and typing has certain significance for further classification and survival prediction.

Mononuclear nickel(II) dithiolate complexes with chelating diphosphines: Insight into protonation and electrochemical proton reduction.

Inspired by the metal active sites of [FeFe]- and [NiFe]­hydrogenases, a series of mononuclear Ni(II) ethanedithiolate complexes [{(Ph2PCH2)2×}Ni(SCH2CH2S)] (X = NCH2C5H4N-p (2a), NCH2C6H5 (2b), NCH2CHMe2 (2c), and CH2 (2d)) with chelating diphosphines were readily synthesized through the room-temperature treatments of mononuclear Ni(II) dichlorides [{(Ph2PCH2)2×}NiCl2] (1a-1d) with ethanedithiol (HSCH2CH2SH) in the presence of triethylamine (Et3N) as acid-binding agent. All the as-prepared complexes 1a-1d and 2a-2d are fully characterized through elemental analysis, nuclear magnetic resonance (NMR) spectrum, and by X-ray crystallography for 1b, 2a-2d. To further explore proton-trapping behaviors of this type of mononuclear Ni(II) complexes for catalytic hydrogen (H2) evolution, the protonation and electrochemical proton reduction of 2a-2c with aminodiphosphines (labeled PCNCP = (Ph2PCH2)2NR) and reference analogue 2d with nitrogen-free diphosphine (dppp = (Ph2PCH2)2CH2) are studied and compared under trifluoroacetic acid (TFA) as a proton source. Interestingly, the treatments of 2a-2d with excess TFA resulted in the unexpected formation of dinuclear Ni(II)-Ni(II) dication complexes [{(Ph2PCH2)2×}2Ni2(µ-SCH2CH2S)](CF3CO2)2 (3a-3d) and mononuclear Ni(II) N-protonated complexes [{(Ph2PCH2)2N(H)R}Ni(SCH2CH2S)](CF3CO2) (4a-4c), which has been well supported by high-resolution electrospray ionization mass spectroscopy (HRESI-MS), NMR (31P, 1H) as well as fourier transform infrared spectroscopy (FT-IR) techniques, and especially by X-ray crystallography for 3d. Additionally, the electrochemical properties of 2a-2d are investigated in the absence and presence of strong acid (TFA) by using cyclic voltammetry (CV), showing that the complete protonation of 2a-2d gave rise to dinuclear Ni2S2 species 3a-3d for electrocatalytic proton reduction to H2.

MUC16 promotes EOC proliferation by regulating GLUT1 expression.

As a common malignancy in females with a higher incidence rate, epithelial ovarian cancer (EOC) is a heterogeneous disease with complexity and diversity in histology and therapeutic response. Although great progress has been made in diagnosis and therapeutic strategies, novel therapeutic strategies are required to improve survival. Although the promoting effect of mucin 16 (MUC16) on tumour progression has been reported, the potential mechanisms remain unclear. In our study, we reported that overexpression of MUC16 was significantly related to cell proliferation and disease progression in EOC. Results from clinical specimen analysis and cell experiment support this conclusion. Patients with a high MUC16 expression usually had a worse prognosis that those with a low expression. Cell proliferation ability was significantly decreased in EOC cell lines when the knockdown of MUC16. Further study shows that the function of MUC16 in cell proliferation is based on the regulation of glucose transporter 1 (GLUT1) expression. MUC16 can control glucose uptake by regulating GLUT1 in EOC cells, thereby promoting glycogen synthesis, so that tumour cells produce more energy for proliferation. This conclusion is based on two findings. First, the significant correlation between MUC16 and GLUT1 was verified by clinical specimen and TCGA data analysis. Then, alteration of MUC16 expression levels can affect the expression of GLUT1 and glucose uptake was also verified. Finally, this conclusion is further verified in vivo by tumour-bearing mice model. To summarize, our results suggest that MUC16 promotes EOC proliferation and disease progression by regulating GLUT1 expression.

Use of palliative chemotherapy near the end of life: a retrospective cohort study.

BACKGROUND: For patients with metastatic cancer, treatment with palliative chemotherapy can lead to more aggressive end-of-life (EOL) care. This retrospective study aimed to assess the time from the last chemotherapy treatment to death and investigate the variables associated with the delivery of palliative chemotherapy near the end of life. METHODS: Data from patients who died from metastatic cancer after receiving palliative chemotherapy from April 2007 to June 2019 at the Department of Integrated Therapy of Fudan University, Shanghai Cancer Center were analyzed. Statistical analysis was performed to evaluate variables including the patient's age, Charlson comorbidities, caregivers, and the type of cancer. RESULTS: A total of 605 patients were included in the analysis, of whom 335 (58.7%) were treated with palliative chemotherapy during their last year of life and 16.2% were treated in their last month of life. Treatment with palliative chemotherapy in the last month was independently associated with age (P<0.001). In the last year of life, treatment with palliative chemotherapy differed significantly according to caregivers and age (P<0.001). The interval between the last chemotherapy treatment and death was the shortest for patients whose caregivers were adult children or those aged ≤50 years. CONCLUSIONS: In this study, palliative chemotherapy was used to treat 58.7% of patients in their last year, and 16.2% of patients in their last month, which is in line with international recommendations. In the last month, palliative chemotherapy was independently associated with age (P<0.001), whereas patients were more likely to receive palliative chemotherapy in their last year if their caregivers were adult children or if they were aged ≤50 years. Significant variations in EOL treatment strategies were observed according to caregivers and patient age during the last year of life.

Baicalein suppresses vasculogenic mimicry through inhibiting RhoA/ROCK expression in lung cancer A549 cell line.

Vasculogenic mimicry (VM) refers to a new tubular network of the blood supply system with abundant extracellular matrix. VM is similar to capillaries but does not involve endothelial cells. As a traditional herbal medicine commonly used in China, baicalein possesses anti-inflammatory and lipoxygenase activities. However, the effects of baicalein on the process of VM formation in non-small cell lung cancer (NSCLC) and the underlying mechanisms have remained poorly understood. In this study, baicalein was found to inhibit the viability and motility of A549 cells and induced the breakage of the cytoskeletal actin filament network. In addition, baicalein significantly decreased the formation of VM and downregulated the expressions of VM-associated factors, such as VE-cadherin, EphA2, MMP14, MMP2, MMP9, PI3K and LAMC2, similar to the effects of ROCK inhibitors. Indeed, baicalein inhibited RhoA/ROCK expression in vitro and in vivo, suggesting the underlying mechanisms of reduced VM formation. Collectively, baicalein suppressed the formation of VM in NSCLC by targeting the RhoA/ROCK signaling pathway, indicating that baicalein might serve as an emerging drug for NSCLC.

Long Noncoding RNA SNHG10 Sponges miR-543 to Upregulate Tumor Suppressive SIRT1 in Nonsmall Cell Lung Cancer.

Background: Long noncoding RNA SNHG10 has been reported to promote the development of liver cancer. While by analyzing The Cancer Genome Atlas (TCGA) dataset we observed the downregulation of SNHG10 in non-small cell lung cancer (NSCLC). This study aimed to investigate the roles of SNHG10 in NSCLC. Materials and Methods: This study included 60 pairs of NSCLC and nontumor tissue samples collected from 60 NSCLC patients (males and females, 39-66 years, 50.9 ± 5.5 years). Gene expression was detected by quantitative polymerase chain reaction and western blot. Overexpression experiments were used to analyze gene interactions. Effects of cell transfections on cell proliferation were analyzed by performing CCK-8 cell proliferation assays. Results: We confirmed the downregulation of SNHG10 in NSCLC. In addition, low expression level of SNHG10 predicted the poor survival of NSCLC patients. SNHG10 can directly interact with miR-543, while overexpression of miR-543 failed to downregulate SNHG10. However, SNHG10 overexpression led to upregulation of sirtuin 1 (SIRT1), a downstream target of miR-543. Cell proliferation assay showed that SNHG10 and SIRT1 overexpression led to the decreased proliferation rate of NSCLC cells. In contrast, miR-543 over-expression played an opposite role and reduced the effects of SNHG10 and SIRT1 overexpression. Conclusions: In conclusion, SNHG10 sponges miR-543 to upregulate tumor suppressive SIRT1 in NSCLC to suppress cell proliferation.

Referral Characteristics of Palliative Care Service in Patients With Advanced Non-Small Cell Lung Cancer in a Tertiary Cancer Center.

BACKGROUND: The American Society of Clinical Oncology recently recommends patients with metastatic non-small cell lung cancer (NSCLC) should be offered palliative care services earlier. We sought to investigate the timing of palliative care referral of Chinese patients with NSCLC in our center. METHOD: Retrospective medical data including demographic characteristics and referral information were collected for analysis. Overall survival (OS) was calculated as the time since cancer diagnosis till patient's death. The time interval from palliative care (PC) referral to a patient's death (PC-D) was calculated. The PC-D/OS ratio was calculated to illustrate the comparison of the duration of PC in the overall length of disease. RESULTS: The mean age of 155 patients with advanced NSCLC was 62.83 years. Before referral to PC, 128 patients received anticancer treatment including surgeon (46.5%). Sixty-three (40.6%) patients died in palliative care unit. The median OS of 144 patients with end cutoff was 19 months (mean = 31.49, 95% confidence interval [CI] = 25.86-37.12). The median PC-D was 41 days (mean = 73.84, 95% CI = 60.37-87.40). The mean interval of PC-D/OS of 144 patients with definitely death time was 0.22 (SD: 0.27, 95% CI: 0.17-0.26). The median interval was 0.089. More than half of patients (n = 75, 51.8%) underwent PC less than 1% time (PC-D/OS < 0.1) of their whole disease course. Patients who were indigenous to Shanghai (P = .013) and who had brain metastasis (P = .072) had the potential longer PC-D/OS ratio. A high proportion of patients reported loss of appetite (92.8%) and fatigue (91.4%) at the initial of referral to PC. CONCLUSION: This retrospective study, in a population of patients with advanced NSCLC, gave detailed information about PC services in a tertiary cancer center.

Nomogram-based parameters to predict overall survival in a real-world advanced cancer population undergoing palliative care.

BACKGROUND: Although palliative care has been accepted throughout the cancer trajectory, accurate survival prediction for advanced cancer patients is still a challenge. The aim of this study is to identify pre-palliative care predictors and develop a prognostic nomogram for overall survival (OS) in mixed advanced cancer patients. METHODS: A total of 378 consecutive advanced cancer patients were retrospectively recruited from July 2013 to October 2015 in one palliative care unit in China. Twenty-three clinical and laboratory characters were collected for analysis. Prognostic factors were identified to construct a nomogram in a training cohort (n = 247) and validated in a testing cohort (n = 131) from the setting. RESULTS: The median survival time was 48.0 (95% CI: 38.1-57.9) days for the training cohort and 52.0 (95% CI: 34.6-69.3) days for the validation cohort. Among pre-palliative care factors, sex, age, tumor stage, Karnofsky performance status, neutrophil count, hemoglobin, lactate dehydrogenase, albumin, uric acid, and cystatin-C were identified as independent prognostic factors for OS. Based on the 10 factors, an easily obtained nomogram predicting 90-day probability of mortality was developed. The predictive nomogram had good discrimination and calibration, with a high C-index of 0.76 (95% CI: 0.73-0.80) in the development set. The strong discriminative ability was externally conformed in the validation cohort with a C-index of 0.75. CONCLUSIONS: A validated prognostic nomogram has been developed to quantify the risk of mortality for advanced cancer patients undergoing palliative care. This tool may be useful in optimizing therapeutic approaches and preparing for clinical courses individually.

C-Reactive Protein/Albumin Ratio Is an Independent Prognostic Predictor of Survival in Advanced Cancer Patients Receiving Palliative Care.

Background: The C-reactive protein/albumin (CRP/Alb) ratio has been reported as a prognostic factor of survival for patients with a variety of cancers. However, its prognostic impact for advanced cancer patients receiving palliative care remains presently unknown. Objective: The present study assessed the prognostic value of the CRP/Alb ratio, and compared this with that of the Glasgow Prognostic Score (GPS) and Palliative Prognostic Index (PPI) in a cohort of advanced cancer patients receiving palliative therapy. Methods: The medical records of 262 eligible patients who died of advanced cancer from February 1, 2013 to December 30, 2017 in the palliative care unit of the Fudan University Shanghai Cancer Center were retrospectively reviewed for the analysis. Results: The present results revealed that a CRP/Alb ratio ≥1.31 (hazard ratio [HR], 2.33 [1.78-3.05], p < 0.001) can predict poor prognosis through univariate analysis. In addition, the multivariate analysis revealed that CRP/Alb (HR, 2.09 [1.54-2.84], p < 0.001), GPS (HR, 1.81 [1.07-3.07], p < 0.001), and PPI (HR, 3.35 [2.25-4.99], p < 0.001) were all independent prognosis factors. To compare the discriminatory performance of the CRP/Alb ratio with that of other established prognostic indexes in palliative care settings, the c-statistics, integrated discriminatory improvement index, net reclassification index, and receiver operating characteristic curves were generated, and it was demonstrated that the CRP/Alb ratio (c-statistics, 0.64 [0.61-0.68]) was able to discriminate advanced cancer patients with different survivals, with analogous discriminatory ability as GPS (c-statistics, 0.63 [0.59-0.66]) and PPI (c-statistics, 0.64 [0.60-0.68]). Notably, the combination of multiple prognostic indexes exerted higher discriminatory ability, compared with any single predictive index (c-statistics, 0.69 [0.66-0.73], p < 0.001). Conclusions: The present study suggests that the CRP/Alb ratio is a promising prognostic factor in predicting cancer patient survival in palliative care settings. Incorporating both objective parameters and the subjective index may improve the prediction accuracy of prognosis.

miR-503 expression is downregulated in cervical cancer and suppresses tumor growth by targeting AKT2.

Previous studies have reported that microRNAs function as key regulators in tumor development and progression. This study aims to investigate the functional effects of miR-503 expression in cervical cancer (CC) progression. We detected the expression of miR-503 in CC tissues and cell lines using quantitative real-time polymerase chain reaction. Synthesized miR-503 mimics or inhibitors were used to upregulate or downregulate the expression of miR-503 in HeLa or SiHa cells. Cell Counting Kit-8 and colony formation assay were used to detect the ability of cell proliferation. Furthermore, luciferase assay and Western blot were applied to confirm the target of miR-503 in CC cells. Here, we demonstrated that miR-503 expression was significantly downregulated in CC tissues, compared with adjacent normal tissues. miR-503 expression was significantly associated with tumor size and International Federation of Gynecology and Obstetrics stage. Furthermore, increasing miR-503 expression in CC cells dramatically inhibited cell proliferation, colony formation ability of CC. However, reducing miR-503 had reverse effects on these malignant behaviors. Moreover, we demonstrated that miR-503 inhibited cell proliferation by targeting AKT2 3'-untranslated region and affected its expression. Overexpression of AKT2 rescued the effects induced by miR-503 on cell proliferation. Therefore, our results indicated that miR-503 may serve as a tumor suppressor in CC and provide a potential value for CC treatment.

MiR-1204 promotes ovarian squamous cell carcinoma growth by increasing glucose uptake.

MiR-1204 has been recently identified as an oncogenic miRNA in breast cancer. Our study aims to investigate the role of miR-1204 in ovarian squamous cell carcinoma. Expression of miR-1204 and glucose transporter 1 in ovarian biopsies and plasma of both OC patients and healthy controls was detected by qRT-PCR. Correlations between patients' clinicopathological data were analyzed by Chi-square test. MiR-1204 overexpression OC cell lines were established. Expression of GLUT-1 protein was detected by western blot. Glucose uptake was measured by glucose uptake assay. Cell proliferation was detected by CCK-8 assay. We found that miR-1204 expression was significantly correlated with tumor size. Expression levels of miR-1204 and GLUT-1 were significantly high in OC patients. Expression levels of miR-1204 were positively correlated with expression levels of GLUT-1 in OC patients. MiR-1204 overexpression significantly promoted GLUT-1 expression, glucose uptake and cell proliferation. MiR-1204 may promote ovarian squamous cell carcinoma growth by increasing glucose uptake.

A surface magnetic imprinted polymers as artificial receptors for selective and efficient capturing of new neuronal nitric oxide synthase-post synaptic density protein-95 uncouplers.

In this work, surface magnetic molecularly imprinted polymers (SMMIPs) were synthesized and used as artificial receptors in the dispersive magnetic solid phase extraction (DMSPE) for capturing potential neuronal nitric oxide synthase-post synaptic density protein-95 (nNOS-PSD-95) uncouplers, which is known as neuroprotection against stroke. Factors that affected selective separation and adsorption of the artificial receptors, such as the amount of template, the types of functional monomer and porogen solvents, and the molar ratio of template/functional monomer/cross-linker were optimized. The artificial receptors were also characterized using fourier transformed infrared, scanning electron microscope, thermal gravimetric analysis and physical property measurement systems. Multiple interactions between template and SMMIPs led to larger binding capacities, faster binding kinetics, quicker separation abilities and more efficient selectivity than the surface magnetic nonimprinted polymers (SMNIPs). The SMMIPs were successfully applied to capture potential nNOS-PSD-95 uncouplers from complex samples, and eight compounds were seized and confirmed rapidly when combined with HPLC and MS. The detection of the new nNOS-PSD-95 uncouplers ranged from 0.001 to 1.500 mg/mL with correlation coefficients of 0.9990-0.9995. The LOD and LOQ were 0.10-0.68 µg/mL and 0.47-2.11 µg/mL, respectively. The neuroprotective effect and co-immunoprecipitation test in vitro revealed that Emodin-1-O-ß-d-glucoside, Rhaponticin, Gnetol and 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-d-glucoside have neuroprotective and uncoupling activities, and that they may be the new uncouplers of nNOS-PSD-95.

Palliative Chemotherapy Near the End of Life in Oncology Patients.

BACKGROUND: Although palliative chemotherapy during end-of-life (EOL) care is used to relieve symptoms in patients with metastatic cancer, chemotherapy may lead to more aggressive EOL care. We evaluated the use of and variables associated with chemotherapy at EOL. METHODS: This study included data from patients who died from advanced cancer and underwent palliative chemotherapy between April 2007 and May 2017 at the Department of Palliative Care of Fudan University, Shanghai Cancer Center. Data were collected from hospital medical records. Univariate and multivariate analyses were conducted to identify the variables that independently predicted the use of palliative chemotherapy. RESULTS: Among the 542 patients in the study, 85 (15.7%) underwent palliative chemotherapy during the last month and 28 (5.2%) underwent it during the last 2 weeks of life. Age <59 years (odds ratio [OR] = 1.82, 95% confidence interval [CI]: 1.51-2.61), performance status <3 (OR = 3.73, 95% CI: 1.46-4.67), and cardiopulmonary resuscitation (OR = 3.88, 95% CI: 3.01-5.34) were independently associated with the use of chemotherapy. The use of palliative chemotherapy during the last year of life differed significantly by patient age ( P < .001). CONCLUSION: The observed chemotherapy rates of 15.7% during the last month of life and 5.2% during the last 2 weeks of life are in line with international recommendations. This study showed that palliative chemotherapy is associated with more aggressive EOL care and indicates that younger patients and those with lower performance status are more likely to receive palliative chemotherapy. Significant variations in EOL treatment strategies among different age groups during the last year of life were also identified.

Analysis of the effect of laparoscopy and hysteroscopy on ovarian function, immune function and quality of sexual life of patients with hysteromyoma at different ages.

This study aims to comparatively analyze the impact of laparoscopic myomectomy (LM) and transcervical resection of myoma (TCRM) on ovarian function, immune function and quality of sexual life of patients with hysteromyoma. Two hundred and forty patients with hysteromyoma admitted into the Second Affiliated Hospital of Zhengzhou University from June 2014 to June 2016 were divided into laparoscopic myomectomy group (LM group, n=120) and transcervical resection of myoma group (TCRM group, n=120) according to random figure table. The difference between the two surgical methods were compared among hysteromyoma patients of different age in the following aspects: perioperative indicators, ovarian function, immune function and quality of sexual life before treatment and after operation. 1) there was no significant difference in age structure between LM and TCRM group (P>0.05). 2) There were no significant differences in the amount of bleeding, operative time, analgesics usage rate between the groups (P>0.05), but the anal exhaust time, postoperative ambulation time, hospitalization time and hospitalization costs in TCRM group were significantly less than that in LM group, the difference was statistically significant (P<0.01). 3) Before treatment and in the 3rd, and 6th month after operation, there was no significant difference on follicle stimulating hormone (FSH), luteinizing hormone (LH) or estradiol (E2) level between the two groups (P>0.05); but in the 3rd month after operation, the level of E2 decreased remarkably, with FSH and LH level increased significantly compared with the 6th month after operation and before treatment (P<0.05). 4) Compared with the preoperative status, there was no significant decrease in humoral immunity (IgG, IgA, IgM) and cellular immune function (CD4+, CD8+) in TCRM group at the 3rd and 6th month after operation (P>0.05). While at the 3rd month after operation, the levels of CD4+, CD8+ were decreased significantly in comparison to those at the 6th month after operation (P<0.05), but the levels of IgG, IgA and IgM were not decreased significantly (P>0.05). 5) There was no significant difference in the quality of sexual life between the two groups before operation or at the 3rd and 6th month after operation (P>0.05). In recent years, endoscopic treatment has become the main treatment evolution of hysteromyoma, patients of all ages are paying attention to the preservation of the uterus. This study showed that TCRM is approaching through the natural cavity, which has the features of less damage to body, faster recovery and lower cost of hospitalization than LM. The two surgical methods have no obvious influence on ovarian function, immune function and quality of sexual life.

Neutrophil count and percentage: potential independent prognostic indicators for advanced cancer patients in a palliative care setting.

The purpose of this study was to evaluate the count and percentage of neutrophils as prognostic indicators in advanced cancer patients undergoing palliative care. 378 consecutive patients receiving treatment at the palliative care unit of Fudan University Shanghai Cancer Center between July 2013 and October 2015 were reviewed. In 106 of these patients, the data were extended during the follow-up. The cut-off values selected for the neutrophil count and percentage were 8.0×109/L and 85%, respectively. Both a high pretreatment neutrophil count (HR = 1.828, 95% CI: 1.409∼2.371, P<0.001) and a high pretreatment neutrophil percentage (HR = 1.475, 95% CI: 1.106∼1.967, P=0.008) were independent prognostic factors for decreased overall survival. Furthermore, in the follow-up cohort of readmitted patients (n = 106), patients with a newly increased neutrophil count or percentage were respectively, 1.837 (95% CI: 1.096∼3.079) and 3.268 (95% CI: 1.848∼5.778) times more likely to have a poor prognosis compared with patients with low neutrophil conditions (P=0.021, P<0.001). In conclusions, both high pretreatment or newly increased count and percentage of neutrophils were confirmed as independent prognostic factors for adverse outcomes. These parameters may be used as stratification factors in identifying advanced cancer patients with poor prognosis in palliative care settings.

Lymphocyte count or percentage: which can better predict the prognosis of advanced cancer patients following palliative care?

BACKGROUND: The lymphocytes played an important role in the natural history of cancer. The aim of this study was to explore the prognostic value of lymphocyte count and percentage for survival in advanced cancer patients receiving palliative care. METHODS: A retrospective review of clinicopathological data from 378 consecutive advanced cancer patients and 106 extended follow-up patients treated with palliative care was conducted. Kaplan-Meier curves and multivariate cox regression analyses were used to evaluate the relationships of peripheral lymphocyte count (LC) and lymphocyte to white blood cell ratio (LWR) with overall survival (OS). RESULTS: The median values for pretreatment LC and LWR were 1.1 (IQR, 0.8 ~ 1.5 × 109/L) and 0.138 (IQR, 0.086 ~ 0.208). The median survival times across LWR quartiles were 19, 47, 79, and 101 days (P < 0.001). Multivariate analysis indicated that patients in the highest quartiles of LC and LWR had an HR of 1.082 (95% CI 0.777 ~ 1.506, P = 0.642) and 0.466 (95% CI 0.328 ~ 0.661, P < 0.001), respectively, compared with patients in the lowest quartiles. Furthermore, only the dynamic changes of LWR were confirmed as an independent prognostic factor for overall survival during the follow-up (HR = 0.396, 95% CI 0.243 ~ 0.668; P = 0.001), as were primary tumor site and ECOG. No effect was observed for the dynamic changes of LC. CONCLUSIONS: Our findings demonstrate that measurement of the dynamic changes of LWR prior to treatment and during follow-up may represent a simple and new powerful prognostic factor for patients with advanced cancer, unlike measurement of LC. As a bedside marker of immune status, the prognostic role of LWR should be further evaluated in prospective studies.