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Objective: Health psychology (HP) plays a critical role within a multidisciplinary, integrative oncology team. HP provides coping tools, helping patients engage in healthy lifestyle. HP in integrative oncology is not well established and criteria for referral has not been examined. This study examined characteristics of referral to HP. Methods: A retrospective chart review of 1827 patients seen for consultation in the IMC between January 1st, 2019 and January 13th, 2020 was conducted. Patient assessments included the Edmonton Symptom Assessment Scale, Measure Yourself Concerns and Well-being, and PROMIS-10. Chi-square tests were used to compare categorical variables, Mann-Whitney test for non-normally distributed continuous variables, and t-tests for normally distributed continuous variables comparing those referred and not referred to HP. Results: Referred patients were mostly female (85.4%), White (67.1%), married/partnered (67.7%), obese (42.1%), with breast cancer (52.2%). Compared to those not referred, patients referred to HP were significantly more likely to be female, younger, Black, and had a higher BMI (p ≤ .01). Referred patients reported worse fatigue, sleep, depression, anxiety, well-being, spiritual pain, financial distress, memory, and overall mental health, physical health, and global health (p ≤ .01). Most common concerns of referrals were diet/nutrition, overall health, and stress/anxiety. Compared to non-referred, HP referrals were more likely to prioritize depression, spirituality, and stress/anxiety as their concerns (p ≤ .01). Conclusions: Patient characteristics are well-suited treatment targets for HP, including addressing emotional distress, healthy lifestyle, and quality of life. Our findings can help cancer programs develop strategies to facilitate engagement with psychological counseling.

Weight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

Clonal haematopoiesis, which is highly prevalent in older individuals, arises from somatic mutations that endow a proliferative advantage to haematopoietic cells. Clonal haematopoiesis increases the risk of myocardial infarction and stroke independently of traditional risk factors1. Among the common genetic variants that give rise to clonal haematopoiesis, the JAK2V617F (JAK2VF) mutation, which increases JAK–STAT signalling, occurs at a younger age and imparts the strongest risk of premature coronary heart disease1,2. Here we show increased proliferation of macrophages and prominent formation of necrotic cores in atherosclerotic lesions in mice that express Jak2VF selectively in macrophages, and in chimeric mice that model clonal haematopoiesis. Deletion of the essential inflammasome components caspase 1 and 11, or of the pyroptosis executioner gasdermin D, reversed these adverse changes. Jak2VF lesions showed increased expression of AIM2, oxidative DNA damage and DNA replication stress, and Aim2 deficiency reduced atherosclerosis. Single-cell RNA sequencing analysis of Jak2VF lesions revealed a landscape that was enriched for inflammatory myeloid cells, which were suppressed by deletion of Gsdmd. Inhibition of the inflammasome product interleukin-1β reduced macrophage proliferation and necrotic formation while increasing the thickness of fibrous caps, indicating that it stabilized plaques. Our findings suggest that increased proliferation and glycolytic metabolism in Jak2VF macrophages lead to DNA replication stress and activation of the AIM2 inflammasome, thereby aggravating atherosclerosis. Precise application of therapies that target interleukin-1β or specific inflammasomes according to clonal haematopoiesis status could substantially reduce cardiovascular risk. Accelerated atherosclerosis in a mouse model of clonal haematopoiesis is prevented by genetic interruption of AIM2 inflammasome activation or by inhibition of interleukin-1β.

ObjectiveTo characterise the oral microbiome, gut microbiome and serum lipid profiles in patients with active COVID-19 and recovered patients; evaluate the potential of the microbiome as a non-invasive biomarker for COVID-19; and explore correlations between the microbiome and lipid profile.DesignWe collected and sequenced 392 tongue-coating samples, 172 faecal samples and 155 serum samples from Central China and East China. We characterised microbiome and lipid molecules, constructed microbial classifiers in discovery cohort and verified their diagnostic potential in 74 confirmed patients (CPs) from East China and 37 suspected patients (SPs) with IgG positivity.ResultsOral and faecal microbial diversity was significantly decreased in CPs versus healthy controls (HCs). Compared with HCs, butyric acid-producing bacteria were decreased and lipopolysaccharide-producing bacteria were increased in CPs in oral cavity. The classifiers based on 8 optimal oral microbial markers (7 faecal microbial markers) achieved good diagnostic efficiency in different cohorts. Importantly, diagnostic efficacy reached 87.24% in the cross-regional cohort. Moreover, the classifiers successfully diagnosed SPs with IgG antibody positivity as CPs, and diagnostic efficacy reached 92.11% (98.01% of faecal microbiome). Compared with CPs, 47 lipid molecules, including sphingomyelin (SM)(d40:4), SM(d38:5) and monoglyceride(33:5), were depleted, and 122 lipid molecules, including phosphatidylcholine(36:4p), phosphatidylethanolamine (PE)(16:0p/20:5) and diglyceride(20:1/18:2), were enriched in confirmed patients recovery.ConclusionThis study is the first to characterise the oral microbiome in COVID-19, and oral microbiomes and lipid alterations in recovered patients, to explore their correlations and to report the successful establishment and validation of a diagnostic model for COVID-19.

Background: T-LAK cell-Originated Protein Kinase (TOPK) belongs to the serine/threonine protein kinase family. It is highly expressed in RPMI7951 melanoma cells. Scutellarin (SCU) is an active ingredient extracted from Erigeron breviscapus (Vant.) Hand.–Mazz. Its main physiological functions are related to its anti-inflammatory and antitumour activities. Methods: The relationship between SCU and TOPK was assessed by molecular docking, an in vitro binding assay and an in vitro kinase assay. The effect of SCU on RPMI7951 cells was detected by MTS and soft agar assays. TOPK knockdown was induced by lentiviral infection. The TOPK downstream signalling pathway was detected by western blot and immunohistochemical analyses in vitro and in vivo. Results: SCU was found to directly bind with TOPK and inhibit TOPK activity in vitro. SCU inhibited the proliferation and colony formation of RPMI7951 cells in a dose-dependent manner. Silencing TOPK decreased the sensitivity of colon cancer cells to SCU. SCU inhibited the phosphorylation levels of Extracellular Regulated protein Kinases 1/2 (ERK1/2) and histone H3 in a time- and dose-dependent manner in RPMI7951 cells. In addition, SCU inhibited the growth of xenograft tumours of RPMI7951 cells and decreased the phosphorylation levels of extracellular regulated protein kinases 1/2 and histone H3 in vivo. Conclusion: The results showed that SCU exerts promising antitumour effects on human RPMI7951 cells by inhibiting the activity of TOPK.

Background: Morbidity of chronic kidney disease (CKD) is increased, with many complications and high mortality rates. The characteristics of oral microbiome in CKD patients have not been reported. This study aims to analyze the oral microbiome, and to demonstrate the potential of microbiome as noninvasive biomarkers for CKD patients. Methods: The study collected 253 oral samples from different regions of China (Central China and East China) prospectively and finally 235 samples completed Miseq sequencing, including 103 samples from CKD patients and 132 healthy controls (HCs). Results: Compared with HCs (n=88), the oral microbial diversity in CKD patients (n=44) was increased. Fourteen genera including Streptococcus, Actinomyces and Leptotrichia were enriched, while six genera including Prevotella and Haemophilus were decreased in CKD patients. Moreover, 49 predicted microbial gene functions including arginine metabolism and tryptophan metabolism increased, while 55 functions including Ribosome and DNA repair recombination proteins decreased. Furthermore, correlation analysis demonstrated that 38 operational taxonomic units (OTUs) were closely related to 5 clinical indicators of CKD. Notably, 7 optimal biomarkers were identified using random forest model, and the classifier model respectively reached an area under the curve (AUC) of 0.9917 and 0.8026 in the discovery and validation phase, achieving a cross-region validation. Conclusions: We first illustrated the characteristics of the oral microbiome of patients with CKD, identified the potential of oral microbial makers as noninvasive tools for the diagnosis of CKD and achieved cross-region validation.

Background We aimed to determine whether hypomagnesemia predicts osteoradionecrosis development in patients with squamous cell carcinoma of the oropharynx and oral cavity who received platinum-based concurrent chemoradiation with or without induction therapy. Methods We reviewed data from patients with head and neck cancers who had undergone chemoradiation with weekly cisplatin/carboplatin between January 1, 2010 and December 31, 2014 at our institution. Pathologic features, laboratory test results, disease stage, and social histories were recorded. The association between hypomagnesemia and osteoradionecrosis was analyzed controlling for known confounding factors. Results Hypomagnesemia during cancer treatment was associated with osteoradionecrosis development (HR = 2.72, P = .037) independent of total radiation dose (HR = 1.07, P = .260) and smoking history (HR = 2.05, P = .056) among the patients who received platinum-based induction chemotherapy followed by concurrent chemoradiation. Conclusions Hypomagnesemia was predictive of the development of osteoradionecrosis in patients with cancers of the oropharynx and oral cavity receiving platinum-based induction followed by concurrent chemoradiation.

BACKGROUND: Prior research has confirmed that persistent hypomagnesemia was predictive of shorter survival among patients with ovarian cancer who received carboplatin-based chemotherapy. In the current retrospective study, the authors examined the association between hypomagnesemia and survival in patients with head and neck cancer who received concurrent chemoradiation with weekly infusions of cisplatin and/or carboplatin. METHODS: Patients with head and neck cancers who had undergone chemoradiation with cisplatin and/or carboplatin between January 1, 2010, and December 31, 2014, were included. Patients were aged ≥18 years with pathology of squamous cell carcinoma of the larynx, oral cavity, or oropharynx who had received at least 30 fractions of radiotherapy with concurrent weekly cisplatin and/or carboplatin. Pathology features, laboratory results, Eastern Cooperative Oncology Group performance status, social histories, and survival were recorded. The association between hypomagnesemia and survival was analyzed controlling for known prognostic factors. RESULTS: The final cohort consisted of 439 patients with a median age of 59 years. A greater frequency of hypomagnesemia during the treatment course was found to be significantly associated with shorter survival (hazard ratio [HR], 1.13; P = .033) independent of age (HR, 1.65; P = .042), cancer site (nonoropharynx vs oropharynx: HR, 2.15 [P = .003]), Eastern Cooperative Oncology Group performance status (>1 vs ≤1: HR, 2.64 [P < .001]), and smoking history (smoker vs nonsmoker: HR, 1.88 [P = .012]). In addition, more severe hypomagnesemia was associated with shorter survival compared with the milder form. CONCLUSIONS: The frequency and severity of hypomagnesemia during treatment are prognostic of survival for patients with head and neck cancers who are receiving concurrent chemoradiation with cisplatin and/or carboplatin. A prospective study is needed to investigate the impact of the prevention of hypomagnesemia on survival in this patient population.

This pilot randomized controlled trial investigated massage therapy for symptomatic relief of chemotherapy-induced peripheral neuropathy (CIPN) to determine the ideal weekly frequency and number of weeks of providing massage. We evaluated the feasibility and initial efficacy of a Swedish massage protocol to treat lower extremity (LE) CIPN. Inclusion criteria: LE neuropathy attributed to oxaliplatin, paclitaxel, or docetaxel, with no other attributable causes; ≥ 6 months since last chemotherapy; self-reported neuropathy score ≥ 3, 0–10 scale; age ≥ 18. Participant randomization (2:2:1:1) to one of four groups: LE (2) or head/neck/shoulder (control; 1) massage 3 times (3X) a week for 4 weeks; LE (2) or control (1) massage 2X/week for 6 weeks. Completion rate and the Pain Quality Assessment Scale (PQAS) was measured at baseline and 10 weeks later. 71 patients participated: 77.5% women; 57.7% (breast cancer), and 42.3% (GI cancer); mean age 60.3 y/o (range: 40–77); average > 3 years since last chemotherapy. Massage was deemed feasible: mean completion rates (max = 12) were 8.9 (SD 4.2) for 3X/week and 9.8 (SD 4.0) for 2X/week with no statistically significant differences. There were no statistically significant treatment group interactions in PQAS scores at 10-weeks follow-up. There was a statistically significant treatment schedule main effect for PQAS subscales (p

Transcranial magnetic stimulation (TMS), a non-invasive technique to stimulate human brain, has been widely used in stroke treatment for its capability of regulating synaptic plasticity and promoting cortical functional reconstruction. As shown in previous studies, the high electric field (E-field) intensity around the lesion helps in the recovery of brain function, thus the spatial location and angle of coil truly matter for the significant correlation with therapeutic effect of TMS. But, the error caused by coil placement in current clinical setting is still non-negligible and a more precise coil positioning method needs to be proposed. In this study, two kinds of real brain stroke models of ischemic stroke and hemorrhagic stroke were established by inserting relative lesions into three human head models. A coil position optimization algorithm, based on the genetic algorithm (GA), was developed to search the spatial location and rotation angle of the coil in four 4 × 4 cm search domains around the lesion. It maximized the average intensity of the E-field in the voxel of interest (VOI). In this way, maximum 17.48% higher E-field intensity than that of clinical TMS stimulation was obtained. Besides, our method also shows the potential to avoid unnecessary exposure to the non-target regions. The proposed algorithm was verified to provide an optimal position after nine iterations and displayed good robustness for coil location optimization between different stroke models. To conclude, the optimized spatial location and rotation angle of the coil for TMS stroke treatment could be obtained through our algorithm, reducing the intensity and duration of human electromagnetic exposure and presenting a significant therapeutic potential of TMS for stroke.

This study used data from the China Health and Retirement Longitudinal Study to investigate the temporal relationship between blood lipids and sleep duration in Chinese middle-aged and older adults. We used medical examinations and questionnaire data of 5,016 Chinese middle-aged and older adults (age 45+) in 2011 and 2015. Cross-lagged path analysis was performed to examine the bidirectional relationships between blood lipids and sleep duration. Sleep duration and lipids data were analyzed as continuous variables. Temporal relationships between sleep duration and HDL-cholesterol, LDL-cholesterol, total cholesterol, and triglycerides were different. Sleep duration was negatively associated with HDL-cholesterol 4 year later (β1 = −0.171, P = 0.005), and HDL-cholesterol was negatively associated with sleep duration 4 year later (β2 = −0.006, P = 0.002). Longer sleep duration was associated lower levels of LDL-cholesterol (β1 = −0.275, P = 0.097) and total cholesterol (β1 = −0.329, P = 0.096) 4 year later. There was a positive correlation between triglycerides and sleep duration. The path coefficient from triglycerides to sleep duration 4 year later (β2 = 0.001, P = 0.018) was greater than that from sleep duration to triglycerides 4 year later (β1 = 0.109, P = 0.847), with P = 0.030 for the difference between β1 and β2. In stratified analysis, we found that the strength and direction of the relationships may be related to age and BMI. Effects of sleep duration on blood lipids were only observed among participants aged 25.

Despite the initial success of some drugs and vaccines targeting COVID-19, understanding the mechanism underlying SARS-CoV-2 disease pathogenesis remains crucial for the development of further approaches to treatment. Some patients with severe Covid-19 experience a cytokine storm and display evidence of inflammasome activation leading to increased levels of IL-1β and IL-18; however, other reports have suggested reduced inflammatory responses to Sars-Cov-2. In this study we have examined the effects of the Sars-Cov-2 envelope (E) protein, a virulence factor in coronaviruses, on inflammasome activation and pulmonary inflammation. In cultured macrophages the E protein suppressed inflammasome priming and NLRP3 inflammasome activation. Similarly, in mice transfected with E protein and treated with poly(I:C) to simulate the effects of viral RNA, the E protein, in an NLRP3-dependent fashion, reduced expression of pro-IL-1β, levels of IL-1β and IL-18 in broncho-alveolar lavage fluid, and macrophage infiltration in the lung. To simulate the effects of more advanced infection, macrophages were treated with both LPS and poly(I:C). In this setting the E protein increased NLRP3 inflammasome activation in both murine and human macrophages. Thus, the Sars-Cov-2 E protein may initially suppress the host NLRP3 inflammasome response to viral RNA while potentially increasing NLRP3 inflammasome responses in the later stages of infection. Targeting the Sars-Cov-2 E protein especially in the early stages of infection may represent a novel approach to Covid-19 therapy.

We present a user-friendly and transferable genome-wide DNA G-quadruplex (G4) profiling method that identifies G4 structures from ordinary whole-genome resequencing data by seizing the slight fluctuation of sequencing quality. In the human genome, 736,689 G4 structures were identified, of which 45.9% of all predicted canonical G4-forming sequences were characterized. Over 89% of the detected canonical G4s were also identified by combining polymerase stop assays with next-generation sequencing. Testing using public datasets of 6 species demonstrated that the present method is widely applicable. The detection rates of predicted canonical quadruplexes ranged from 32% to 58%. Because single nucleotide variations (SNVs) influence the formation of G4 structures and have individual differences, the given method is available to identify and characterize G4s genome-wide for specific individuals., Current methods to identify G-quadruplex structures in DNA require specialized protocols and multiple rounds of sequencing. Here, the authors develop a method to detect G-quadruplex structures in DNA based on fluctuations in sequencing quality in a standard sequencing experiment.

Complicated vessels pervade almost all body tissues and influence the pathophysiology of the human body significantly. However, current fabrication strategies have limited success at multi-scale vascular biofabrication. This study reports a methodology to fabricate soft vascularized tissue at centimeter-scale using multi-material bioprinting by a customized multistage-temperature-control printer. The printed constructs could be perfused via the branched endothelialized vasculatures to support the well-formed 3D capillary networks, which would ensure cellular activities with sufficient nutrient supply and then mimic a mature and functional liver tissue in terms of synthesis of liver-specific proteins. Moreover, an inner and external pressure-bearing layer was printed to support the direct surgical anastomosis of the carotid artery to the jugular vein. In summary, we present a versatile platform to recapitulate the vasculature network, in which case sustaining the optimal cellularization in engineered tissues is achievable. This article is protected by copyright. All rights reserved.

Background:Skin photoaging, skin inflammation and skin cancer are related with excessive exposure to solar UV. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a member of the serine/threonine protein kinase, which regulates the signaling cascades of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal regulated kinase 1/2 (ERK1/2). PBK/TOPK plays a significant role in solar-UV-induced cutaneous basal cell carcinoma (BCC), and targeting PBK/TOPK can be supposed to treat and prevent cutaneous BCC.Methods:The pathological feature and the expression level of PBK/TOPK in cutaneous BCC tissues of human were studied in clinical samples. SUV-induced the phosphorylation of p38 MAPK and ERK1/2 were demonstrated ex vivo. Moreover, the interaction between Gossypetin and PBK/TOPK were detected by in vitro kinase assay and Microscale thermophoresis (MST) assay. Furthermore, the effect of Gossypetin to solar UV-induced the activity of PBK/TOPK were detected ex vivo and in vivo.Results:The clinical samples showed that the expression levels of PBK/TOPK, phosphor-p38 MAPK and phosphor- ERK1/2 were up-regulated in cutaneous BCC tissues of human. The expression of phosphor-p38 MAPK or phosphor-ERK1/2 increased in a dose and time dependent manner after solar UV treatment in HaCaT cells. MTT cytotoxicity assay results showed that Gossypetin has no effect on HaCaT cells. In vitro kinase assay and MST assay results showed that Gossypetin bound with PBK/TOPK and suppressed PBK/TOPK activity. Ex vivo results showed Gossypetin inhibited solar UV-induced phosphorylation of PBK/TOPK, p38 MAPK, ERK1/2 and H2AX by suppressing PBK/TOPK activity. In vivo test results indicated that Gossypetin suppressed solar UV-induced increase of PBK/TOPK, phosphor-p38 MAPK, phosphor-ERK1/2 and phosphor- H2AX in SKH-1 hairless mice.Conclusion:Our data demonstrated that Gossypetin can alleviate solar-UV-induced cutaneous BCC by blocking PBK/TOPK, and Gossypetin could be a remarkable agent for treating solar-UV induced cutaneous basal cell carcinoma.

The olfactomedin 4 (OLFM4) gene has been analyzed as a tumor‐suppressor gene and a putative biomarker in many cancers. In our study, we analyzed the relationship of OLFM4 expression with clinicopathological features and with CpG site methylation in the OLFM4 gene promoter region in human primary prostate adenocarcinoma. OLFM4 protein expression was significantly reduced in prostate cancer tissue compared to adjacent normal tissue and was further significantly reduced in more advanced cancers. Bioinformatic studies with clinical datasets revealed that primary prostate adenocarcinoma patients with reduced OLFM4 mRNA expression exhibited higher Gleason scores and higher preoperative serum prostate‐specific antigen levels, as well as lower recurrence‐free survival. Three of the eight CpG sites in the OLFM4 gene promoter region were hypermethylated in cancerous prostate cells compared to adjacent normal cells, and reduced methylation of eight CpG sites was associated with increased OLFM4 mRNA expression in RWPE1 and PC‐3 cells. Furthermore, knockdown of OLFM4 gene expression was associated with enhanced epithelial–mesenchymal transition (EMT)‐marker expression in RWPE immortalized normal prostate cells. In contrast, restoration of OLFM4 expression in PC‐3 and DU145 prostate cancer cells lacking OLFM4 significantly inhibited both EMT‐marker expression and tumor cell growth in in vitro and in vivo models, indicating that OLFM4 may play a tumor‐suppressor role in inhibiting the EMT program, as well as tumor initiation and growth, in prostate cells. Taken together, these findings suggest that OLFM4 plays an important tumor‐suppressor role in prostate cancer progression and might be useful as a novel candidate biomarker for prostate cancer., What's new? Altered expression of the OLFM4 gene appears to be involved in many cancers. In this study of prostate cancers, the authors found that OLFM4 can suppress tumor initiation, growth and progression. Downregulation of OLFM4 was associated with higher serum PSA levels, higher Gleason scores, and lower recurrence‐free survival in prostate cancer patients. These results indicate that OLFM4 may play an important tumor‐suppressor role in the progression of prostate cancer, and may provide a novel prognostic biomarker for prostate cancer treatment.

BACKGROUND. Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. MATERIALS AND METHODS. We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high‐grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. RESULTS. The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). CONCLUSION. Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin‐containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. IMPLICATIONS FOR PRACTICE. Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum‐based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin‐containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.

BACKGROUND Sleep disturbance (SD) is highly prevalent in oncology and negatively affects quality of life and mortality. Evidence supports the use of integrative oncology (IO) practices to treat SD, but there is limited published data on the characteristics of SD and factors associated with SD in IO. We determined the prevalence, severity, and factors associated with SD among cancer patients seen in an ambulatory IO consultation. METHODS Patients with cancer referred for initial outpatient IO consultation in 2017 were eligible. Patient demographics, clinical characteristics, and patient-reported outcomes (Edmonton Symptom Assessment Scale (ESAS), Measure Yourself Concerns and Wellbeing (MYCaW), PROMIS-10) were retrospectively reviewed. RESULTS One thousand five hundred twenty patients were included in the analysis. The majority (70%) were women with breast cancer (42%). Nine hundred seventy-one (64%) patients reported significant SD with ESAS Sleep ≥ 4, yet only 11% expressed poor sleep as their primary or secondary concern for the IO consultation. The median SD (IQR) was 5 (3,7). ESAS scores for fatigue (adjusted OR 1.16; CI 1.07-1.26, p

Ensemble coding is the ability of the visual system to extract a summary statistic from a set of stimuli. For example, observers often spontaneously extract an average face identity from a set of faces. Ensemble coding is known to operate in the frame of a distributed/global attention model. Because both attention and holistic processing are modulated by emotion – where positive emotions broaden the scope of attention and facilitate global processing, whereas negative emotions narrow the scope of attention and promote local processing – the current research explored whether emotional states could affect visual averaging of multiple face identities. Participants completed an ensemble-coding task before and after their emotion was induced via film clips. In the ensemble-coding task, a set of four face identities was shown briefly, followed by a probe face. Participants judged whether the probe face was presented in the preceding set. Evidence for ensemble coding was indexed by responses that treated an average face of the preceding set as a member of that set. The results showed that the tendency to choose this average was modulated by emotional states. Visual averaging increased after seeing positive film clips, but decreased after seeing negative film clips. These results support Frederickson’s broaden-and-built theory, and extended its application to ensemble perception.

Small intestine adenocarcinoma is a rare intestinal malignancy with distinct clinical, pathological, and molecular characteristics. Recently, a fusion of the intestinal stem-cell marker olfactomedin 4 (OLFM4) and the proto-oncogene RET has been identified in a small intestine adenocarcinoma patient. Here we investigated the biological effects of OLFM4-RET fusion and whether it can initiate tumorigenesis in small intestine. OLFM4 expression was found to be frequently lost or reduced in human small intestine adenocarcinoma, and its downregulation correlated with high tumor grade and advanced tumor stage. Expression of OLFM4-RET fusion-induced cellular transformation in HEK293 cells and blocked RET-induced inhibition of colony growth in HuTu 80 small intestine adenocarcinoma cells. Further, expression of OLFM4-RET activated the RAS-RAF-MAPK and STAT3 cell signaling pathways in both HEK293 cells and HuTu 80 cells. OLFM4-RET expression in HEK293 cells upregulated multiple families of genes related to carcinogenesis, cancer progression, and metastasis. Targeted expression of OLFM4-RET in the small intestine led to the development of hyperplasia, adenoma, or adenocarcinoma in transgenic mice. Our study suggests that OLFM4-RET is an oncogenic driver of small intestine tumorigenesis. Therefore, the small intestine adenocarcinoma patients with OLFM4-RET fusion may benefit from treatment with RET kinase inhibitor.

In the present study, we explored the clinical and immunological characteristics of 575 uterine corpus endometrial carcinoma (UCEC) samples obtained from The Cancer Genome Atlas (TCGA) using the ESTIMATE and CIBERSORT algorithms. First, Kaplan–Meier and univariate Cox regression analyses indicated that the immune cell score was a prognostic factor for overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox regression analysis further revealed that the immune cell score was an independent prognostic factor for UCEC patients. Second, we investigated the correlation between the infiltration levels of 22 types of immune cells and the immune score. Survival analysis based on the 22 immune cell types showed that higher levels of regulatory T cell, activated NK cell, and follicular helper T-cell infiltration were associated with longer OS, while higher levels of CD8+ T cell and naive B-cell infiltration were associated with longer RFS. Next, we performed differential expression and prognosis analyses on 1534 immune-related genes and selected five from 14 candidate genes to construct a prognostic prediction model. The area under the receiver-operating characteristic (ROC) curve (AUC) for 3- and 5-year survival were 0.711 and 0.728, respectively. Further validation using a stage I–II subgroup showed similar results, presenting AUC values for 3- and five-year survival of 0.677 and 0.692, respectively. Taken together, the present study provides not only a deeper understanding of the relationship between UCEC and the immune landscape but also guidance for the future development of UCEC immunotherapy.

Based on the linkage of genotype and phenotype, display technology has been widely used to generate specific ligands for profiling, imaging, diagnosis and therapy applications. However, due to the lack of effective monoclonal manipulation and affinity evaluation methods, traditional display technology has to undergo tedious steps of selection, clone isolation, amplification, sequencing, synthesis and characterization to obtain the binding sequences. To directly acquire high-affinity clones, we propose a double monoclonal display approach (dm-Display) for peptide screening based on highly paralleled monoclonal manipulation in emulsion droplets. dm-Display can monoclonally link the genotype, phenotype and affinity to realize integrated monoclonal separation, amplification, recognition and staining in one droplet so that discrete high-affinity clones can be quickly extracted. Monoclonal manipulations highly-parallelly occur in millions of droplets so that molecular screening of a highly diverse phage library is achieved. We have screened specific peptide ligands against CD71 and GPC1, proving the feasibility and generality of dm-Display. As a highly efficient ligand screening platform, dm-Display will promote the further development of molecular screening.

Aberrant expression of long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) has been identified in many tumors, but its role in cutaneous malignant melanoma remains largely obscure. Our present study was intended to unveil the role and potential mechanism of ZFPM2-AS1 in cutaneous malignant melanoma. RT-qPCR was utilized to analyze ZFPM2-AS1 expression in cutaneous malignant melanoma cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry and transwell analyses were utilized to assess ZFPM2-AS1 function on cell proliferation, apoptosis and migration. Luciferase reporter, RNA immunoprecipitation (RIP) and RNA-pull down assays were applied to probe the regulatory mechanism of ZFPM2-AS1 in cutaneous malignant melanoma cells. Up-regulation of ZFPM2-AS1 was discovered in cutaneous malignant melanoma cells. ZFPM2-AS1 deletion restrained cell proliferation, migration and elevated cell apoptosis in cutaneous malignant melanoma. ZFPM2-AS1 regulated notch receptor 1 (NOTCH1) to activate the NOTCH pathway. ZFPM2-AS1 acted as a competing endogenous RNA (ceRNA) to affect NOTCH1 expression via sponging miR-650. Collectively, ZFPM2-AS1 exerted an oncogenic role in cutaneous malignant melanoma progression via targeting miR-650/NOTCH1 signaling. Our study might offer a novel sight for cutaneous malignant melanoma treatment. This article is protected by copyright. All rights reserved.

Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4’s physiological functions in these cells have not been elucidated. Using single-cell RNA sequencing analysis, we found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations in both the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the stem/progenitor-like cell population, shifts stem/progenitor-like cell division to favor symmetric division and differentiated into higher levels PSA expression cells in organoid assays compared with OLFM4-wild RWPE1 cells. Bulk-cell RNA sequencing analysis pinpointed that cMYC expression were enhanced in the OLFM4-knockout RWPE1 cells compared with OLFM4-wild cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate multiple biological processes, in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation.

Background: There is increasing interest in complementary approaches such as Tai Chi (TC) and Qi Gong (QG) in oncology settings. We explored the effects of TC/QG delivered in group classes at a comprehensive cancer center. Methods: Patients and caregivers who participated in TC or QG completed assessments before and after an in-person group class. Assessments included questions about expectancy/satisfaction and common cancer symptoms (Edmonton Symptom Assessment Scale [ESAS]). ESAS distress subscales analyzed included global (GDS), physical (PHS), and psychosocial (PSS). Results: Three hundred four participants (184 patients, 120 caregivers) were included in the analysis. At baseline, caregivers had a greater expectancy for change in energy level as a result of class participation compared with patients (22.9% vs 9.9%). No significant difference was observed between baseline patient and caregiver PSS. Clinically significant improvement in well-being was observed among patients in TC classes (1.0) and caregivers in QG classes (1.2). For fatigue, patients (1.4) and caregivers (1.0) participating in QG experienced clinically significant improvement. Both TC and QG classes were associated with clinically significant improvements (ESAS GDS decrease ≥3) in global distress for patients (TC = 4.52, SD= 7.6; QG = 6.05, SD = 7.9) and caregivers (TC = 3.73, SD = 6.3; QG = 4.02, SD = 7.8). Eighty-nine percent of participants responded that their expectations were met. Conclusions: Patients and caregivers participating in TC or QG group classes were satisfied overall and experienced significant improvement in global distress. Additional research is warranted to explore the integration of TC and QG in the delivery of supportive cancer care.

Background: Acupuncture intervention in actual practice is rarely reported and may be different from that applied in acupuncture research. Objectives: To review acupuncture practice in an integrative medicine clinic and characterize the association between targeted symptoms, traditional Chinese medicine (TCM) diagnosis, and acupoint selection. Methods: We reviewed outpatient acupuncture records from March 2016 to April 2018. Statistical analyses were applied to characterize referral symptoms and associated TCM diagnosis as well as acupoint selection. Results: The final analysis included 5393 acupuncture records (1264 patients). Twelve TCM diagnosis components were identified in the referral symptoms of pain, neuropathy, xerostomia, and hot flashes. Pain was associated with 78 different TCM diagnoses (combinations of TCM diagnosis components). Total of 217 different acupoints were used in the acupuncture treatments (1739) for neuropathy. The acupoint yintang was used in 73.8% of the visits for neuropathy, yet only in 26.5% ( P < .001) of the treatments when patients had a TCM diagnosis of qi deficiency, qi stagnation, and blood stagnation. Similarly, both consistencies and variations were seen in acupoint selection with each targeted symptom and its associated TCM diagnoses. Conclusions: TCM diagnosis was not homogeneous among acupuncture treatments for a single referral symptom. In contrast to most of the research on acupuncture for symptom control, there were considerable variations in acupoint selection among treatments for the same symptom in a clinical setting. Future research is needed to examine the clinical relevance of a fixed intervention structure in acupuncture research and the value of individualized acupuncture treatment.

Introduction: There is limited research regarding the benefits of mind-body practices such as meditation in hospitalized patients with an active diagnosis of any cancer type. Methods: We conducted a prospective, randomized, clinical trial (NCT03445572) comparing 2 meditative practices—Isha Kriya (IK) and meditative slow breathing (MSB)—versus wait-list controls in hospitalized cancer patients. Our aim was to determine the feasibility of meditation practice in cancer inpatients. Feasibility was defined as recruitment of more than 50% of the eligible patients approached and at least 60% of the patients having meditated at least 4 days by day 7. Acceptability was assessed on day 7 as a positive response on at least 2 questions on the modified Global Symptom Evaluation (GSE) scale. Results: Forty patients (39% of the eligible patients approached) consented to participate in the study and were randomly assigned to the MSB (n = 13), IK (n = 14), or wait-list (n = 13) groups. Of the 27 patients assigned to receive MSB and IK meditations, day 7 data were available for 18 patients. Fifteen of the 18 patients meditated at least once in the first 7 days, and most (12/15) responded positively on the GSE. Conclusion: Both IK and MSB meditations were acceptable among the hospitalized cancer patients. Feasibility for enrollment and practice was likely not achieved due to limited uninterrupted time for daily meditation, high levels of morbidity in some participants, and limited research staff support. Shorter term outcomes should be explored in future meditation studies involving hospitalized cancer patients.

Background: Actinic Keratosis (AK), is the most common precancerous skin lesion induced by the excessive Ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK. Objective: This study aimed at the development of a nature compound which can inhibit UVB-induced AK. Method: MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo. Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice. Conclusion: These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.

Background & Aims Nonalcoholic steatohepatitis (NASH) is an increasingly prevalent nonalcoholic fatty liver disease, characterized by inflammatory cell infiltration and hepatocellular damage. Mammalian target of rapamycin complex 1 (mTORC1) has been investigated extensively in the context of cancer, including hepatocellular carcinoma. However, the role of mTORC1 in NASH remains largely unknown. Methods mTORC1 activity in macrophages in human mild and severe NASH liver was compared. Mice with macrophage-specific deletion of the regulatory-associated protein of mTOR (Raptor) subunit and littermate controls were fed a high-fructose, palmitate, and cholesterol diet for 24 weeks or a methionine- and choline-deficient diet for 4 weeks to develop NASH. Results We report that in human beings bearing NASH, macrophage mTORC1 activity was lower in livers experiencing severe vs mild NASH liver. Moreover, macrophage mTORC1 disruption exacerbated the inflammatory response in 2 diet-induced NASH mouse models. Mechanistically, in response to apoptotic hepatocytes (AHs), macrophage polarization toward a M2 anti-inflammatory phenotype was inhibited in Raptor-deficient macrophages. During the digestion of AHs, macrophage mTORC1 was activated and coupled with dynamin-related protein 1 to facilitate the latter’s phosphorylation, leading to mitochondrial fission-mediated calcium release. Ionomycin or A23187, calcium ionophores, prevented Raptor deficiency–mediated failure of lysosome acidification and subsequent lipolysis. Blocking dynamin-related protein 1–dependent mitochondria fission impaired lysosome function, resulting in reduced production of anti-inflammatory factors such as interleukins 10 and 13. Conclusions Persistent mTORC1 deficiency in macrophages contributes to the progression of NASH by causing lysosome dysfunction and subsequently attenuating anti-inflammatory M2-like response in macrophages during clearance of AHs., Graphical abstract

The microRNAs (miRNAs/miRs) involved in the carcinogenesis and progression of malignant melanoma (MM) remain unclear. In the present study, miR‑590‑5p was identified to be upregulated in MM cells compared with human melanocytes using a reverse transcription‑quantitative polymerase chain reaction to screen established oncogenic and tumor suppressor miRNAs. miR‑590‑5p was demonstrated to inhibit the cell proliferation and tumor growth of MM cells in vitro and in vivo by performing Cell Counting Kit‑8 and tumour xenograft assays, respectively. In addition, flowcytometry assays indicated that miR‑590‑5p induced cell apoptosis and cell cycle arrest at the G1 stage in MM cells. Finally, luciferase assays and western blot analysis results confirmed that the transcriptional regulator Yes‑associated protein 1 (YAP1) is upregulated and inversely associated with miR‑590‑5p expression in MM cells, and is the direct target and functional mediator of miR‑590‑5p in MM. Altogether these results reveal the functional and mechanistic link between miR‑590‑5p and YAP1 in the progression of MM. Therefore, miR‑590‑5p is a potential therapeutic target in MM.

Since the transferrin receptor (CD71 or TFRC) is known to be highly expressed in numerous cancers, CD71 has become an attractive target in cancer research. Acquiring specific molecular probes for CD71, such as small molecular ligands, aptamers, peptides, or antibodies, is of great importance for cancer cell recognition and capture. In this work, we chose CD71 as the target for phage display, and after four rounds of positive selection and one round of negative selection, the specific phage library was enriched. After verification and sequence analysis, six peptides were identified to be able to bind to CD71 with high specificity. The specific recognition of the CD71-positive cells was confirmed by flow cytometry and confocal microscopy. Competition experiments demonstrated that peptide Y1 and transferrin (TF) were bound to distinct sites on CD71, indicating that peptide Y1 could replace TF as a potential probe for cell imaging and drug delivery, thus avoiding competition by endogenous TF and side effects. Graphical abstract Six peptides were successfully isolated using in vitro biopanning against CD71 with high specificity and affinity. Peptides Y1 and Y2 would be powerful tools in biosensors and biomedicine due to their unique properties.

The present study was aimed to investigate the effect of benzothiazole on the invasive and metastasis potential of HeLa DH cervical cancer cells and the underlying mechanism. HeLa DH cervical cells were cultured with 5, 10, 15, 20, 25 and 30 μM concentrations of benzothiazole for 48 h. Benzothiazole treatment did not induce any cytotoxic effect on HeLa DH cells after 48 h of incubation. The results from wound healing assay revealed that migration potential of HeLa DH cells was reduced to 4% on treatment with 20 μM concentration of benzithiazole compared to 99% in the control cells. The invasion potential of HeLa DH cells was reduced to 13% on treatment with 20 μM concentration of benzithiazole. Inhibition of HeLa DH cell migration was also significantly (p < 0.002) higher in the benzithiazole treated cell cultures compared to the control cells. HeLa DH cervical cancer cells on treatment with various concentrations of benzithiazole for 48 h showed a significant (p < 0.05) increase in the expression of E-cadherin in a dose dependent manner. Among the various concentrations of benzithiazole used, western blot assay revealed that the increase in E-cadherin was maximum at 20 μM. Analysis of the levels of mRNA corresponding to E-cadherin by RT-qPCR showed significant increase in HeLa DH cervical cancer cells on treatment with 20 μM concentration of benzithiazole. Thus benzithiazole treatment suppresses the invasive and metastasis potential of HeLa DH cervical cells through upregulation of E-cadherin expression. Therefore, benzithiazole has a potential to be used for the treatment of cervical cancer.

Fifty-eight patients with cervical spondylosis (CS) were treated with patented technology of ozone laser combined therapy using puncture needle between August 2008 and February 2010. Visual Analogue Scale (VAS) score changes before and 6 months after surgery and MacNab score criteria 6 months after surgery were analyzed.CS normally occurs over the age of 50 and broadly presents as either myelopathy or radiculopathy. Complementary treatment strategies have long been envisaged as a possible alternative in alleviating neck pain associated with CS; however, it is still in moderate use due to lack of adequate and convincing evidence of its safety and efficacy. The current study was to define and understand the therapeutic effects and safety of a newly developed patented technology, ozone, and laser via puncture needle, in the treatment of CS.The VAS score of preoperative neck and shoulder pain was (6.57±1.34) scores, which decreased to 1.80±0.65 at 1-week postsurgery, and was completely alleviated by the end of 1 month (VAS score 0-2 after 1, 3, and 6 mo after surgery) (Kruskal-Wallis rank-sum test, H=1.680, P=0.000). VAS scores did not exhibit any significant rebound within 6 months after surgery (29 patients were excellent; 23 good; and 6 were fair, overall excellent, and good rate of 89.6%).Ozone and laser combined therapy via puncture needle for the treatment of CS is safe and effective.

Objective. The relationship between serum progesterone and the first trimester pregnancy outcome of threatened abortion is still controversial. Therefore, we aimed to further study the association between these two parameters. Methods. The present study is an observational retrospective cohort study. A total of 726 participants who had threatened abortion from a hospital in Guangdong, China, were included in this study from 17th August 2011 to 30th October 2018. The exposure variable and the outcome variable were serum progesterone measured at baseline and early pregnancy outcome, respectively. Covariates involved in this study included patients’ basic demographics, obstetric history, and clinical information. Results. A negative association and a saturation effect were detected between serum progesterone and the first trimester pregnancy outcome. When progesterone Conclusion. There was a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L. Our findings can better assist the clinician in understanding patients’ conditions and making medical decisions.

There is growing interest in the value of routine collection and monitoring of patient-reported outcomes as part of high-quality, patient-centered, oncology care. Integrative oncology, with its focus on providing symptom and lifestyle support for patients throughout the cancer care continuum, serves a diverse patient population with a complex, changing symptom burden. Monitoring of patient-reported outcomes can contribute significantly to the successful comprehensive evaluation and management of patients receiving integrative oncology care. Data collected as part of an integrative oncology evaluation can also support real-world clinical research efforts to help learn more about the effects of integrative oncology interventions on patient symptoms, quality of life, and treatment outcomes.

Background: Acupuncture is a recognized integrative modality for managing hot flashes. However, data regarding predictors for response to acupuncture in cancer patients experiencing hot flashes are limited. We explored associations between patient characteristics, including traditional Chinese medicine (TCM) diagnosis, and treatment response among cancer patients who received acupuncture for management of hot flashes. Methods: We reviewed acupuncture records of cancer outpatients with the primary reason for referral listed as hot flashes who were treated from March 2016 to April 2018. Treatment response was assessed using the hot flashes score within a modified Edmonton Symptom Assessment Scale (0-10 scale) administered immediately before and after each acupuncture treatment. Correlations between TCM diagnosis, individual patient characteristics, and treatment response were analyzed. Results: The final analysis included 558 acupuncture records (151 patients). The majority of patients were female (90%), and 66% had breast cancer. The median treatment response was a 25% reduction in the hot flashes score. The most frequent TCM diagnosis was qi stagnation (80%) followed by blood stagnation (57%). Older age ( P = .018), patient self-reported anxiety level ( P = .056), and presence of damp accumulation in TCM diagnosis ( P = .047) were correlated with greater hot flashes score reduction. Conclusions: TCM diagnosis and other patient characteristics were predictors of treatment response to acupuncture for hot flashes in cancer patients. Future research is needed to further explore predictors that could help tailor acupuncture treatments for these patients.

Olfactomedin 4 (OLFM4) is an olfactomedin domain-containing glycoprotein. Multiple signaling pathways and factors, including NF-κB, Wnt, Notch, PU.1, retinoic acids, estrogen receptor, and miR-486, regulate its expression. OLFM4 interacts with several other proteins, such as gene associated with retinoic-interferon-induced mortality 19 (GRIM-19), cadherins, lectins, nucleotide oligomerization domain-1 (NOD1) and nucleotide oligomerization domain-2 (NOD2), and cathepsins C and D, known to regulate important cellular functions. Recent investigations using Olfm4-deficient mouse models have provided important clues about its in vivo biological functions. Olfm4 inhibited Helicobacter pylori-induced NF-κB pathway activity and inflammation and facilitated H. pylori colonization in the mouse stomach. Olfm4-deficient mice exhibited enhanced immunity against Escherichia coli and Staphylococcus aureus infection. Olfm4 deletion in a chronic granulomatous disease mouse model rescued them from S. aureus infection. Olfm4 deletion in mice treated with azoxymethane/dextran sodium sulfate led to robust intestinal inflammation and intestinal crypt hyperplasia. Olfm4 deletion in Apc Min/+ mice promoted intestinal polyp formation as well as adenocarcinoma development in the distal colon. Further, Olfm4-deficient mice spontaneously developed prostatic epithelial lesions as they age. OLFM4 expression is correlated with cancer differentiation, stage, metastasis, and prognosis in a variety of cancers, suggesting its potential clinical value as an early-stage cancer marker or a therapeutic target. Collectively, these data suggest that OLFM4 plays important roles in innate immunity against bacterial infection, gastrointestinal inflammation, and cancer. In this review, we have summarized OLFM4’s initial characterization, expression, regulation, protein interactions, and biological functions.

To screen potential biomarkers of benzo(a)pyrene (BaP)-induced lung cancer, the proteomic profiles of BaP-transformed 16HBE cell line T-16HBE-C1 cells serum-free culture supernatant and xenografted nude mice sera were compared with those of 16HBE group by utilizing label-free quantitative proteomic strategy. By employing nano-LC-MS/MS technology followed by MaxQuant and Perseus processing, 489 differentially expressed proteins were identified between T-16HBE-C1 and 16HBE cells serum-free culture supernatant, and 49 significantly up-regulated proteins were identified in T-16HBE-C1 xenografted nude mice sera. Three proteins neuropilin-2 (NRP2), clusterin (CLU) and A-kinase anchor protein 12 (AKAP12) were up-regulated in the serum-free culture supernatant of T-16HBE-C1 cells. These 3 human proteins were present in the sera of nude mice xenografted with T-16HBE-C1 cells, but were undetectable in mice xenografted with 16HBE cells. The proteomic results of NRP2 and AKAP12 were confirmed by Western blotting and enzyme-linked immunosorbent assays, respectively. Moreover, the serum NRP2 levels were significantly elevated at the 4th day after tumor cell implantation and showed good positive correlation with tumor growth characterized by tumor volume. In conclusion, serum NRP2, CLU and AKAP12 could be potential biomarkers of BaP-induced lung cancer. The proteomic results will gain deeper insights into the mechanisms of BaP-induced carcinogenesis.

Objective Thalamic glioma is a type of midline glioma with poor outcomes. In the present study, we investigated the clinical and molecular features of thalamic gliomas in Chinese patients. Methods The data from 26 patients with thalamic glioma who had undergone surgery at Shanghai Huashan Hospital from January 2011 to August 2015 were retrospectively analyzed. Various clinical and molecular factors were evaluated to explore their effects on prognosis. H3K27M mutation status and its association with relevant molecular factors were also investigated. Results The mean age of the patients was 38.88 years, and no significant difference was found in sex. The most common initial symptoms were headaches (38.46%; 10 of 26) and motor deficits (30.77%; 8 of 26). The H3K27M mutation was identified in 12 patients, and mutant thalamic glioma showed less frequent O-6-methylguanine DNA methyltransferase (MGMT) promoter methylation compared with the wild-type group (P = 0.015; χ 1 test). Multivariate analysis showed that the H3K27M mutation was an independent unfavorable prognostic factor for overall survival. MGMT promoter unmethylation and the TP53 mutation were identified as negative prognostic factors for progression-free survival. Conclusions Our results revealed the clinical and molecular characteristics of thalamic glioma in China. Our data have shown the absence of MGMT promoter methylation in H3K27M mutant thalamic glioma, validating it as a hallmark of H3K27M mutant gliomas. In addition, H3K27M mutation was identified as the sole unfavorable prognostic factor on overall survival. MGMT promoter unmethylation and TP53 mutation were identified as independent prognostic factors for progression-free survival.

Using dyadic data from 198 dating heterosexual couples (aged 18–31) in Mainland China, the current study tested the direct associations between perceptions of their parents’ harsh and controlling parenting and psychological aggression and indirect associations via shame proneness. Results demonstrated that for women, greater perceived harsh and controlling parenting was directly related to higher levels of psychological aggression and indirectly related through higher levels of shame proneness. For men, perceived harsh and controlling parenting was not related to either shame proneness or psychological aggression. These findings provide initial insights into how shame, traditionally a valued and celebrated emotion in Chinese culture, can be maladaptive by contributing to psychological aggression in young adult intimate relationships. Although these findings merit further testing, especially for men, this study provides evidence that shame is an important mechanism for psychological dating violence.

The mechanisms driving atherothrombotic risk in individuals with JAK2The goal of this study was to assess atherosclerosis and underlying mechanisms in hypercholesterolemic mice with hematopoietic Jak2Irradiated low-density lipoprotein receptor knockout ( LdlrHematopoietic Jak2

Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. Recent studies reported that lncRNA MIR22HG could play important roles in hepatocellular carcinoma and lung cancer progression. However, the expression and underlying mechanism of MIR22HG in endometrial cancer (EC) remain unclear. In the present study, qRT-PCR showed that MIR22HG expression was significantly downregulated in EC tissues. In vitro function assays showed that increased MIR22HG expression significantly inhibited EC cells proliferation, induced EC cells apoptosis, and arrested EC cells in G0/G1 phase. Furthermore, miR-141-3p was identified and confirmed to be the target of MIR22HG. Subsequently, DAPK1 was confirmed to be regulated by MIR22HG and miR-141-3p, and could play a positive role in inhibiting EC cells proliferation. Collectively, these data demonstrated that lncRNA MIR22HG could act as a tumor suppressor and inhibited EC cells proliferation through regulating miR-141-3p/DAPK1 axis, which provides a new therapeutic target for EC treatment.

Background The impact of noncancerous factors on the morbidity and mortality of glioblastoma multiforme (GBM) has not been well studied. Using a large surgical cohort, we examined the association between multiple clinical characteristics and postoperative morbidities and survival in patients with GBM. Materials and Methods The study included 404 consecutive GBM patients who underwent initial tumor resection at MD Anderson Cancer Center between January 1, 2010, and December 31, 2014. Data about clinical characteristics, treatments, and postoperative complications were collected. The associations between clinical parameters and postoperative complications and survival were analyzed. Results Charlson Comorbidity Index was positively related to a higher incidence of postoperative total (odds ratio [OR] = 1.20; p = .002) and neurological (OR = 1.18; p = .011) complications. Preoperative systolic blood pressure (SBp) over 140 mmHg was associated with a higher incidence of postoperative intracranial hemorrhage (OR = 4.42; p = .039) and longer hospital stay (OR = 2.48; p = .015). Greater postoperative fluctuation of SBp (OR = 1.14; p = .025) and blood glucose (mmol/L; OR = 1.48; p = .023) were related to a higher incidence of neurological complications, whereas higher postoperative blood glucose (OR = 0.64; p Conclusion Short-term SBp and blood glucose levels and fluctuations are associated with postoperative complications in GBM patients. Their long-term optimization may impact survival of these patients. Future clinical trials are needed to confirm the benefit of optimizing medical comorbidities on GBM patients' outcomes. Implications for Practice Glioblastoma multiforme (GBM) is one of the most feared cancer diagnoses because of its limited survival and treatment. This study revealed significant associations of noncancerous factors on the morbidity and mortality of GBM. The complexity of medical comorbidities, as well as short-term postoperative levels and fluctuations of blood pressure and blood glucose, was associated with postoperative complications, but not overall survival. However, long-term levels of these common clinical parameters were significantly associated with survival. Optimization of medical conditions may be critical for reducing the morbidity and mortality of GBM patients. Future clinical trials are needed to validate the observed associations in an independent cohort.

Integrative Oncology (IO) consultations offer cancer patients counseling regarding complementary integrative medicine (CIM). We explored the CIM interests and symptom burden of AYA cancer patients presenting for an IO consultation. Patients referred for an IO physician consultation at an academic medical center from September 1, 2009 to December 31, 2013 completed an assessment on presentation: MYCaW, ESAS (10 symptoms, 0–10, 10 worst possible), CIM use survey, and SF-12 QOL survey. We compared findings of AYA patients (ages 15–39) with a control sample of adult patients (age ≥ 40). Of the total 2474 consecutive patients, 286 (12%) were AYA, 73.1% female, with the most common diagnosis of breast cancer (30%). Areas of greatest interest for both AYA and adult patients included developing a holistic approach, herbals, and diet, with no significant difference between groups. Comparing groups, AYA patients had significantly higher anxiety (3.4 vs 3.1, p = 0.042). AYA physical health was significantly higher (37.5 vs 35, p = 0.001), with no significant between group differences in mental health. AYA patients were more likely to have participated in yoga (22 vs 11%, p = 0.001) and pilates (9.2 vs 4.5%, p = 0.04), with no significant difference regarding overall CIM use. Differences persisted after correcting for stage. AYA patients make up a small number of overall referrals to an IO consultation, presenting with a low to moderate symptom burden. Physical CIM interventions such as yoga and pilates are of greater interest to the AYA population, suggesting the importance of making such interventions available in cancer programs serving this population.

Accurate electrophysiological diagnosis relies on high precision and well calibrated instruments. A method to simulate the human electrophysiological activity is proposed and a simulation system is developed, as a calibration tool for electrophysiological inspectors. The system performance is tested by calibrating the amplitude and the latency of a commercial visual electrophysiological instrument. Several typical simulating signals are tested. The minimum amplitude of the simulating signal can be lower than 1 μV. Measurement errors and uncertainties are calculated. The traceability of the measurement results to metrological standards is also demonstrated. It is proved by experimental results that the system can generate simulating signals with different waveforms and variable parameters and it can be used to simulate the human visual electrophysiological activities. With simple modifications to the simulation system, it can also be used to calibrate other electrophysiological inspectors.

Objectives: The study was conducted to simultaneously investigate the mediating effects of parental control and adolescents' self-control on the relationship between adolescents' negative emotions and emotional eating, and to determine pathways with the greatest effect among these variables. Methods: Negative emotions, emotional eating, parental control, and self-control were investigated in 594 high school students (average age = 16.70, SD = 1.09) in Changsha City, China. Results: High levels of negative emotions and parental control and low levels of self-control were strongly related to high levels of emotional eating in adolescents. In addition to the direct relationship between negative emotions and emotional eating, there was a mediating effect observed through low self-control and high parental control. The mediational effect of parental control was non-significant in adolescent boys. Furthermore, negative emotions related to emotional eating through the effect of parental control on adolescents' self-control. The degree to which both mediators explained the relationship between negative emotions and emotional eating ranged from 52.6% to 66.8%, and self-control had a stronger mediational effect than did parental control. Conclusion: The results indicate that both self-control and parental control should be considered in designing preventative measures against emotional eating in adolescents. Adolescent self-control training could also assist in preventing emotional eating.

ObjectivesThe aim of this study was to explore health professionals’ perception of risk factors related to child maltreatment in China.DesignQualitative research.SettingThe study was conducted in November and December 2014 in Hunan, Zhejiang, Shaanxi and Guangdong provinces in China.ParticipantsFive urban communities and five rural communities were randomly selected in each province, and interviews were conducted in maternal and child health hospitals, children’s hospitals, community health service centres and township hospitals in the selected areas. Doctors, nurses and administrators involved in child healthcare services were selected for in-depth-interview.ResultsA total of 102 health professionals were approached but 95 completed the interview. From their perspective, risk factors causing child maltreatment were categorised into four domains: (1) cultural factors, including parents’ absolute authority over their children and son preference; (2) social factors, including a fast-paced and stressful lifestyle, children left behind by migrant worker parents and lack of quality child care and education; (3) family factors, including economic status, family structure, parents’ inability to provide parental care, experience of maltreatment and parents’ illnesses; (4) children’s factors, including gender, temper, disabilities and poor awareness of self-protection.ConclusionsThe results indicate that health professionals in China are aware of certain risk factors for child maltreatment; however, some views are outdated and wrong. Based on the perception of health professionals, targeted training courses are needed to enable them to correctly identify and deal with suspected cases of child maltreatment.

The accurate estimation of patient’s exposure to the radiofrequency (RF) electromagnetic field of magnetic resonance imaging (MRI) significantly depends on a precise individual anatomical model. In the study, we investigated the applicability of an efficient whole-body individual modelling method for the assessment of MRI RF exposure. The individual modelling method included a deformable human model and tissue simplification techniques. Besides its remarkable efficiency, this approach utilized only a low specific absorption rate (SAR) sequence or even no MRI scan to generate the whole-body individual model. Therefore, it substantially reduced the risk of RF exposure. The dosimetric difference of the individual modelling method was evaluated using the manually segmented human models. In addition, stochastic dosimetry using a surrogate model by polynomial chaos presented SAR variability due to body misalignment and tilt in the coil, which were frequently occurred in the practical scan. In conclusion, the dosimetric equivalence of the individual models was validated by both deterministic and stochastic dosimetry. The proposed individual modelling method allowed the physicians to quantify the patient-specific SAR while the statistical results enabled them to comprehensively weigh over the exposure risk and get the benefit of imaging enhancement by using the high-intensity scanners or the high-SAR sequences.