Serum metabolomics reveals the effects of accompanying treatment on fatigue in patients with multiple myeloma.

PURPOSE: The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS: This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS: The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION: The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.

NORAD promotes multiple myeloma cell progression via BMP6/P-ERK1/2 axis.

Multiple myeloma (MM) is one of the most common tumors of the hematological system and remains incurable. Recent studies have shown that long noncoding RNA NORAD is a potential oncogene in a variety of tumors. However, the general biological role and clinical value of NORAD in MM remains unknown. In this study, we measured NORAD expression in bone marrow of 60 newly diagnosed MM, 30 post treatment MM and 17 healthy donors by real-time quantitative polymerase chain reaction (qPCR). The NORAD gene was knockdown by lentiviral transfection in MM cell lines, and the effects of NORAD on apoptosis, cell cycle and cell proliferation in MM cells were examined by flow cytometry, CCK8 assay, EDU assay and Western blot, and the differential genes after knockdown of NORAD were screened by mRNA sequencing, followed by in vivo experiments and immunohistochemical assays. We found that knockdown of NORAD promoted MM cell apoptosis, induced cell cycle G1 phase arrest, and inhibited MM cell apoptosis in in vivo and in vitro experiments. Mechanistically, NORAD plays these roles through the BMP6/P-ERK1/2 axis. We discuss a novel mechanism by which NORAD acts pro-tumorigenically in MM via the BMP6/P-ERK1/2 axis.

Serum Metabolomics Coupling With Clinical Laboratory Indicators Reveal Taxonomic Features of Leukemia.

Metabolic abnormality has been considered to be the seventh characteristic in cancer cells. The potential prospect of using serum biomarkers metabolites to differentiate ALL from AML remains unclear. The purpose of our study is to probe whether the differences in metabolomics are related to clinical laboratory-related indicators. We used LC-MS-based metabolomics analysis to study 50 peripheral blood samples of leukemia patients from a single center. Then Chi-square test and T test were used to analyze the clinical characteristics, laboratory indicators and cytokines of 50 patients with leukemia. Correlation analysis was used to explore the relationship between them and the differential metabolites of different types of leukemia. Our study shows that it is feasible to better identify serum metabolic differences in different types and states of leukemia by metabolomic analysis on existing clinical diagnostic techniques. The metabolism of choline and betaine may also be significantly related to the patient's blood lipid profile. The main enrichment pathways for distinguishing differential metabolites in different types of leukemia are amino acid metabolism and fatty acid metabolism. All these findings suggested that differential metabolites and lipid profiles might identify different types of leukemia based on existing clinical diagnostic techniques, and their rich metabolic pathways help us to better understand the physiological characteristics of leukemia.

Increased NRSF/REST in anterior cingulate cortex contributes to diabetes-related neuropathic pain.

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.

[Changes of serum anti-schistosome antibody levels in schistosomiasis japonica patients after treatment].

OBJECTIVE: To investigate the changes of serum anti-schistosome antibody titers in schistosomiasis japonica patients after treatment, in order to provide the evidence for formulating the schistosomiasis surveillance program in marshland and lake regions. METHODS: Upon prospective cohort study, the stool examination positive schistosomiasis patients and blood examination positive suspected patients (the titer was more than 1:80, including 1:80) were selected as the research objects in Jiangling County in 2014, and they received the 2-day praziquantel therapy. Half year, one year and two years after the treatment, their blood samples and fecal samples were collected for IHA anti-schistosome antibody detections and schistosome egg and miracidium detections. RESULTS: In 2014, the stool examination positives were 251, and the majority of them were over 41 years old, accounting for 93.23% (234/251) ; 581 cases of high antibody titers were detected by the IHA method, and the majority of them were over 41 years old, accounting for 89.16% (518/581) . Half year, one year and two years after the treatment, among the stool examination positives, the negative conversion rates of stool positives were 99.60% (250/251), 100% (239/239) and 100% (234/234) respectively and the negative conversion rates of antibody positives were 21.91% (55/251), 64.11% (156/239) and 76.89% (193/234) respectively. In the high antibody titer positives, the negative conversion rates were 38.04% (221/581), 64.11% (359/560), and 77.86% (429/551) respectively, Half year, one year and two years after the treatment. There were statistically significant differences among the antibody negative conversion rates by χ2 test (χ2 = 77.538, 183.412, 25.469 respectively, all P < 0.001) . The geometric mean values of antibody titers of different durations between 2 groups were analyzed by 2-independent-samples T test, and the geometric mean values of antibody titers between the 2 groups were different before the treatment (t = 23.576, P < 0.01), but the geometric mean values of antibody titers between the 2 groups were not different 6 months, 1 year and 2 years after the treatment (t = -0.046, 1.165, -0.132, P = 0.964, 0.245, 0.895 respectively). CONCLUSIONS: The levels of serum anti-schistosome antibody degrade slowly in schistosomiasis japonica patients after the treatment, and the results of IHA tests cannot distinguish the current schistosome infection from previous schistosome infection. Therefore, it is necessary to develop the specific diagnostic technology for schistosome infection in order to meet the need of monitoring.

[Distribution features of wild feces in schistosomiasis endemic areas in Jiangling County, Hubei Province].

OBJECTIVE: To understand the spatial distribution characteristics of wild feces in schistosomiasis endemic areas of Jiangling County, Hubei Province and further explore the source of infection efficiently, so as to provide the evidence for the development of corresponding monitoring and response technology. METHODS: In 2011, the fresh wild feces were investigated every two months in the selected 15 villages by the severity of historical endemic in Jiangling County. The schistosome miracidium hatching method was used to test the schistosome infection of the wild feces. The descriptive analysis and spatial analysis were used for the description of the spatial distribution of the wild feces. RESULTS: Totally 701 wild feces samples were collected with the average density of 0.055 6/100 m2, and the positive rate of the wild feces was 11.70% (82/701). The results of the regression analysis showed a positive spatial correlation between the positive rate of wild feces and the rate of human infection, the area with infected Oncomelania hupensis and the number of fenced cattle, and the corrected R2 of the model was 0.58. CONCLUSIONS: The infection rate of wild feces is positively correlated with the rate of human infection, area with infected O. hupensis and number of fenced cattle in space in Jiangling County, so the prevention and control measures could be conducted according to the spatial distribution of the positive wild feces.

[Effect of two-level community-based health education pattern on schistosomiasis control].

OBJECTIVE: To implement a two-level community-based health education pattern of schistosomiasis in residents of endemic areas in marshland and lake regions, so as to explore the suitable pattern of health education under hypo-endemic situation. METHODS: Two schistosomiasis endemic villages in Jiangling County, Hubei Province were collected as study areas, and among which, one village was treated as an intervention group, where the two-level community-based health education pattern as well as regular control measures was implemented; the other village was a control group, where only regular control measures were implemented. The awareness rates on schistosomiasis control, the rates of correct behavior and the compliance rates of examination, treatment and chemotherapy of the two groups before and after the intervention were compared. RESULTS: According to the results of the baseline survey in 2014, the awareness rates of schistosomiasis control of the intervention and control groups were 84.00% and 77.45%, respectively, the correct rates of behavior of the two groups were 72.00% and 63.73%, respectively, and the compliance rates of the treatment were 80.36% and 82.28%, respectively, there were no statistically significant differences between all the above rates of the two groups (all P > 0.05). After the intervention of the two-level community-based health education, the correct rates of behavior, and the compliance rates of examination and chemotherapy of the two groups were 92.31% and 80.37%, 95.11% and 82.55%, 84.13% and 63.64%, respectively, and the differences between all the rates above of the two groups were statistically significant (all P < 0.05). When compared to those before intervention, the growing rates of the compliance rates of examination, treatment and chemotherapy of the intervention group were 20.97%, 15.33% and 23.29%, respectively, while those of control group were 14.27%, 4.17%, -3.77%, respectively, the growing rates of the intervention groups were higher than those of the control groups. CONCLUSIONS: Through the two-level community-based pattern of health education, the compliance rates of examination and treatment of the residents have improved, and therefore, the pattern is suitable for popularization and application in marshland and lake regions.