Reactions of alkynes with C-S bond formation: recent developments.

Alkynes are important in organic synthesis. This review mainly focuses on recent advances (2013-2023) on alkynes with C-S bond formation, based on more than 30 types of sulfur reagents. The reactions of alkynes with various sulfur-containing compounds including RSSR (disulfides), RSH (thiols), S8 (elemental sulphur), alkynyl thioethers, RSCN, AgSCF3, K2S, Na2S, dithiane, RSCl, NFSI, RNCS, EtOCS2K, thiocarbamate, RSONH2, thiourea, sulfoxide, RSO2N3, CS2, RSO2NH2, RSO2NHNH2, RSO2Cl, RSO2Oar, RSO2SR', DABCO·(SO2)2, Na2S2O5, K2S2O5, RSO2H, RSO2Na and related compounds are discussed. Diverse mechanisms such as radical, electrophilic/nucleophilic addition, rearrangement, C-C bond cleavage, and CuAAC are discussed. The content is organized by substrates and reactivity patterns. We hope it will help in future research in this area.

PDGFRß modulates aerobic glycolysis in osteosarcoma HOS cells via the PI3K/AKT/mTOR/c-Myc pathway.

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRß is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRß on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson's correlation test, and PPI correlation analysis indicated positive regulation of PDGFRß on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRß could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRß was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRß mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRß provides a novel metabolic therapeutic target for osteosarcoma.

PDGF-BB/PDGFRß promotes epithelial-mesenchymal transition by affecting PI3K/AKT/mTOR-driven aerobic glycolysis in Wilms' tumor G401 cells.

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRß belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRß on WT G401 cells. Transwell assay and wound-healing assay were used to detect the effect of PDGFRß on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT-related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRß and aerobic glycolysis was studied by assessing the expression of glycolysis-related enzymes detected by qRT-PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit-glucose oxidase method separately. To investigate the mechanism of PDGFRß in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRß. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRß promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRß in G401 cells provides a new target for the treatment of WT.

Temperature and hand, foot and mouth disease in California: An exploratory analysis of emergency department visits by season, 2005-2013.

BACKGROUND: For the past decade, hand, foot and mouth disease (HFMD), caused by entero and coxsackie viruses, has been spreading in Asia, particularly among children, overloading healthcare settings and creating economic hardships for parents. Recent studies have found meteorological factors, such as temperature, are associated with HFMD in Asia. However, few studies have explored the relationship in the United States, although HFMD cases have steadily increased recently. As concerns of climate change grow, we explored the association between temperature and HFMD admissions to the Emergency Department (ED) in California. METHODS: Weekly counts of HFMD for 16 California climate zones were collected from 2005 to 2013. We calculated weekly temperature for each climate zone using an inverse distance-weighting method. For each climate zone stratified by season, we conducted a time-series using Poisson regression models. We adjusted models for weekly averaged relative humidity, average number of HFMD cases in previous weeks and long-term temporal trends. Climate zone estimates were combined to obtain an overall seasonal estimate. We attempted stratified analyses by region, race/ethnicity, and sex to identify sensitive subpopulations. RESULTS: Risk of ED visits for HFMD per 1 °F increase in mean temperature during the same week increased 2.00% (95% confidence intervals 1.15, 2.86%) and 2.35% (1.38, 3.33%) during the warm and cold seasons, respectively. The coastal region showed a higher, though not statistically different, association during the cold season [3.18% (1.99, 4.39)] than the warm season [1.64% (0.47, 2.82)]. CONCLUSIONS: Our findings indicated an association between temperature and ED visits for HFMD, with variation by season and region. Thus, the causative pathogen's ability to persist in the atmosphere may vary by season. Furthermore, the mild and wet winter in the coastal region of California may contribute to different results than studies in Asia. With the onset of climate change, HFMD cases will likely grow in California, warranting further investigation on this relationship, including new populations at-risk.

Association between coarse particulate matter and inflammatory and hemostatic markers in a cohort of midlife women.

BACKGROUND: Exposure to particulate matter air pollution has been associated with cardiovascular disease (CVD) morbidity and mortality; however, most studies have focused on fine particulate matter (PM2.5) exposure and CVD. Coarse particulate matter (PM10-2.5) exposure has not been extensively studied, particularly for long-term exposure, and the biological mechanisms remain uncertain. METHODS: We examined the association between ambient concentrations of PM10-2.5 and inflammatory and hemostatic makers that have been linked to CVD. Annual questionnaire and clinical data were obtained from 1694 women (≥ 55 years old in 1999) enrolled in the longitudinal Study of Women's Health Across the Nation (SWAN) at six study sites from 1999 to 2004. Residential locations and the USEPA air monitoring network measurements were used to assign exposure to one-year PM10-2.5, as well as co-pollutants. Linear mixed-effects regression models were used to describe the association between PM10-2.5 exposure and markers, including demographic, health and other covariates. RESULTS: Each interquartile (4 µg/m3) increase in one-year PM10-2.5 exposure was associated with a 5.5% (95% confidence interval [CI]: 1.8, 9.4%) increase in levels of plasminogen activator inhibitor-1 (PAI-1) and 4.1% (95% CI: - 0.1, 8.6%) increase in high-sensitivity C-creative Protein (hs-CRP). Stratified analyses suggested that the association with PAI-1 was particularly strong in some subgroups, including women who were peri-menopausal, were less educated, had a body mass index lower than 25, and reported low alcohol consumption. The association between PM10-2.5 and PAI-1 remained unchanged with adjustment for PM2.5, ozone, nitrogen dioxide, and carbon monoxide. CONCLUSIONS: Long-term PM10-2.5 exposure may be associated with changes in coagulation independently from PM2.5, and thus, contribute to CVD risk in midlife women.

Wearable Sensor System to Monitor Physical Activity and the Physiological Effects of Heat Exposure.

Mobile health monitoring via non-invasive wearable sensors is poised to advance telehealth for older adults and other vulnerable populations. Extreme heat and other environmental conditions raise serious health challenges that warrant monitoring of real-time physiological data as people go about their normal activities. Mobile systems could be beneficial for many communities, including elite athletes, military special forces, and at-home geriatric monitoring. While some commercial monitors exist, they are bulky, require reconfiguration, and do not fit seamlessly as a simple wearable device. We designed, prototyped and tested an integrated sensor platform that records heart rate, oxygen saturation, physical activity levels, skin temperature, and galvanic skin response. The device uses a small microcontroller to integrate the measurements and store data directly on the device for up to 48+ h. continuously. The device was compared to clinical standards for calibration and performance benchmarking. We found that our system compared favorably with clinical measures, such as fingertip pulse oximetry and infrared thermometry, with high accuracy and correlation. Our novel platform would facilitate an individualized approach to care, particularly those whose access to healthcare facilities is limited. The platform also can be used as a research tool to study physiological responses to a variety of environmental conditions, such as extreme heat, and can be customized to incorporate new sensors to explore other lines of inquiry.

A Review of Coccidioidomycosis in California: Exploring the Intersection of Land Use, Population Movement, and Climate Change.

California has seen a surge in coccidioidomycosis (valley fever), a disease spread by the Coccidioides immitis fungus found in soil throughout the state, particularly in the San Joaquin Valley. We reviewed epidemiologic studies in which outbreak and sporadic cases of coccidioidomycosis were examined, and we considered the possible relationship of these cases to environmental conditions, particularly the state's increasing aridity, drought, and wildfire conditions. Most of the studies we reviewed pertained to cases occupationally acquired in construction, military, archeological, and correctional institutional settings where workers were exposed to dust in C. immitis-endemic areas. A few reviewed outbreaks in the general population related to dust exposure from natural disasters, including an earthquake-associated landslide and a dust storm that carried particles long distances from endemic areas. Although many of California's coccidioidomycosis outbreaks have been occupationally related, changing demographics and new, immunologically naïve populations in dry, endemic areas could expose the general population to C. immitis spores. Given the high rate of infection among workers who, for the most part, are healthy, the general population, including some elderly and immunocompromised individuals, could face additional risk. With climate-related events like drought and wildfires also increasing in endemic areas, research is needed to address the possible associations between these phenomena and coccidioidomycosis outbreaks.

Recent advances in the direct functionalization of quinoxalin-2(1H)-ones.

The direct C3-functionalization of quinoxalin-2(1H)-ones via C-H bond activation has recently attracted considerable attention, due to their diverse biological activities and chemical properties. This review will focus on the recent achievements, mainly including arylation, alkylation, acylation, alkoxycarbonylation, amination, amidation and phosphonation of quinoxalin-2(1H)-ones. Their mechanisms are also discussed.

Associations between ambient temperature and hepatobiliary and renal hospitalizations in California, 1999 to 2009.

BACKGROUND: High ambient temperature has been linked to a number of types of morbidity, such as cardiovascular disease and dehydration. Fewer studies have explored specifically the relationship between ambient temperature and liver, kidney, and urinary system morbidity despite known biological impacts of extreme high temperatures on those systems. OBJECTIVE: We assessed the relationship between temperature and hospitalizations related to selected renal system (urinary stones, urinary tract infections, septicemia, chronic kidney disease, and a composite of selected kidney diseases) and hepatobiliary (biliary tract disease, other liver diseases [e.g. cirrhosis], non-diabetic pancreatic disorders) ailments. METHODS: We compiled data on daily hospitalization counts for hepatobiliary and renal system diseases in California for 1999 through 2009, and matched it with meteorological data. Relationships between temperature and admissions during the warm season (May-October) were assessed at the climate zone-level cumulative over 14 days following exposure using distributed lag non-linear models, with adjustment for time trends and relative humidity, then combined using random-effects meta-regression to create statewide estimates. RESULTS: Higher mean temperatures in the warm season were associated with significant increases in renal admissions for urinary tract infection [% change per 10 °F: 7.3, 95% CI: 5.6, 9.1], septicemia [% increase: 2.9; 95% CI: 1.5, 4.3], urinary stones [% increase: 15.2; 95% CI: 10.3, 20.4], and composite kidney disease. Additionally, increased temperatures were linked to increased admissions for biliary tract disease, but lower risk of other liver diseases. Some differences in association by race/ethnicity and regional meteorology were observed. CONCLUSIONS: Exposure to higher temperatures was associated with increased risk of multiple renal system hospitalization types, with additional links to specific hepatobiliary morbidities observed.

Estimating the associations of apparent temperature and inflammatory, hemostatic, and lipid markers in a cohort of midlife women.

Associations between temperature and cardiovascular (CVD) mortality have been reported, but the underlying biological mechanisms remain uncertain. We explored the association between apparent temperature and serum biomarkers for CVD. Using linear mixed effects models, we examined the relationships between residence-proximate apparent temperature (same day and 1, 7, and 30 days prior) and several inflammatory, hemostatic, and lipid biomarkers for midlife women from 1999 through 2004. Our study population consisted of 2,306 women with mean age of 51 years (± 3 years) enrolled in Study of Women's Health Across the Nation (SWAN) in Chicago, Illinois; Detroit, Michigan; Los Angeles and Oakland, California; Newark, New Jersey; and Pittsburgh, Pennsylvania. Mean daily apparent temperature was calculated using temperature and relative humidity data provided by the National Climatic Data Center and the US Environmental Protection Agency, while daily data for fine particles, ozone, carbon monoxide, and nitrogen dioxide from the US Environmental Protection Agency Air Quality Data Mart were considered as confounders. All analyses were stratified by warm and cold seasons. More significant (p < 0.10) negative associations were found during the warm season for various lag times, including hs-CRP, fibrinogen, tissue plasminogen activator antigen (tPA-ag), tissue plasminogen activator antigen (PAI-1), Factor VIIc, high-density lipoprotein (HDL), and total cholesterol. During the cold season, significant negative associations for fibrinogen and HDL, but significant positive associations for tPA-ag, PAI-1, and triglycerides were observed for various lag times. With the exception of ozone, pollutants did not confound these associations. Apparent temperature was associated with several serum biomarkers of CVD risk in midlife women, shedding light on potential mechanisms.

Serum concentrations of perfluorinated compounds (PFC) among selected populations of children and adults in California.

Perfluorinated compounds (PFCs) have been widely used in industrial applications and consumer products. Their persistent nature and potential health impacts are of concern. Given the high cost of collecting serum samples, this study is to understand whether we can quantify PFC serum concentrations using factors extracted from questionnaire responses and indirect measurements, and whether a single serum measurement can be used to classify an individual's exposure over a one-year period. The study population included three demographic groups: young children (2-8 years old) (N=67), parents of young children (<55 years old) (N=90), and older adults (>55 years old) (N=59). PFC serum concentrations, house dust concentrations, and questionnaires were collected. The geometric mean of perfluorooctane sulfonic acid (PFOS) was highest for the older adults. In contrast, the geometric mean of perfluorooctanoic acid (PFOA) was highest for children. Serum concentrations of the parent and the child from the same family were moderately correlated (Spearman correlation (r)=0.26-0.79, p<0.05), indicating common sources within a family. For adults, age, having occupational exposure or having used fire extinguisher, frequencies of consuming butter/margarine, pork, canned meat entrées, tuna and white fish, freshwater fish, and whether they ate microwave popcorn were significantly positively associated with serum concentrations of individual PFCs. For children, residential dust concentrations, frequency of wearing waterproof clothes, frequency of having canned fish, hotdogs, chicken nuggets, French fries, and chips, and whether they ate microwave popcorn were significant positive predictors of individual PFC serum concentrations. In addition, the serum concentrations collected in a subset of young children (N=20) and the parents (N=42) one year later were strongly correlated (r=0.68-0.98, p<0.001) with the levels measured at the first visits, but showed a decreasing trend. Children had moderate correlation (r=0.43) between serum and dust concentrations of PFOS, indicating indoor sources contribute to exposure. In conclusion, besides food intake, occupational exposure, consumer product use, and exposure to residential dust contribute to PFC exposure. The downward temporal trend of serum concentrations reflects the reduction of PFCs use in recent years while the year-to-year correlation indicates that a single serum measurement could be an estimate of exposure relative to the population for a one-year period in epidemiology studies.

Polybrominated diphenyl ether serum concentrations in a Californian population of children, their parents, and older adults: an exposure assessment study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in many household items. Given concerns over their potential adverse health effects, we identified predictors and evaluated temporal changes of PBDE serum concentrations. METHODS: PBDE serum concentrations were measured in young children (2-8 years old; N = 67), parents of young children (<55 years old; N = 90), and older adults (≥55 years old; N = 59) in California, with concurrent floor wipe samples collected in participants' homes in 2008-2009. We also measured serum concentrations one year later in a subset of children (N = 19) and parents (N = 42). RESULTS: PBDE serum concentrations in children were significantly higher than in adults. Floor wipe concentration is a significant predictor of serum BDE-47, 99, 100 and 154. Positive associations were observed between the intake frequency of canned meat and serum concentrations of BDE-47, 99 and 154, between canned meat entrees and BDE-154 and 209, as well as between tuna and white fish and BDE-153. The model with the floor wipe concentration and food intake frequencies explained up to 40% of the mean square prediction error of some congeners. Lower home values and renting (vs. owning) a home were associated with higher serum concentrations of BDE-47, 99 and 100. Serum concentrations measured one year apart were strongly correlated as expected (r = 0.70-0.97) with a slight decreasing trend. CONCLUSIONS: Floor wipe concentration, food intake frequency, and housing characteristics can explain 12-40% of the prediction error of PBDE serum concentrations. Decreasing temporal trends should be considered when characterizing long-term exposure.

Mitosis targeting in non-small lung cancer cells by inhibition of PAD4.

PAD4 expression and activity were significantly up-regulated in lung cancer tissues suggesting that PAD4 could be a possible target for lung cancer treatment. In this study we had demonstrated that PAD4 expression was higher in lung cancer patients whom with lymphnode metastasis and pleural invasion. Inhibiting PAD4 with a small molecular inhibitor could induce apoptosis and suppress growth in lung cancer cells. We used RNA-sequencing to further investigate transcriptional changes that induced by PAD4 inhibition, and results suggested its affected mostly on the cell cycle, mitotic cell cycle process, p53 signaling pathway. By using image flow cytometry analysis, we found that PAD4 inhibited by YW3-56 could accumulate cells in the G1/G0 phases and reducing the fraction of G2/M and S phase cells. Quantification of different phase of mitosis in cells treated with YW3-56 revealed an increasing trend of telophase and prophase cells. Taken together, our data indicated that PAD4 inhibitor could affect cell cycle and mitosis of lung cancer cells, and targeting PAD4 could be a promising strategy for discovery novel anti-NSCLC treatments.

CRP inhibits the osteoblastic differentiation of OPCs via the up-regulation of primary cilia and repression of the Hedgehog signaling pathway.

Inflammation disrupts bone metabolism and leads to bone damage. C-reactive protein (CRP) is a typical inflammation marker. Although CRP measurement has been conducted for many decades, how osteoblastic differentiation influences molecular mechanisms remains largely unknown. The present study attempted to investigate the effects of CRP on primary cultured osteoblast precursor cells (OPCs) while elucidating the underlying molecular mechanisms. OPCs were isolated from suckling Sprague-Dawleyrats. Fewer OPCs were observed after recombinant C-reactive protein treatment. In a series of experiments, CRP inhibited OPC proliferation, osteoblastic differentiation, and the OPC gene expression of the hedgehog (Hh) signaling pathway. The inhibitory effect of CRP on OPC proliferation occurred via blockade of the G1-S transition of the cell cycle. In addition, the regulation effect of proto cilium on osteoblastic differentiation was analyzed using the bioinformatics p. This revealed the primary cilia activation of recombinant CRP effect on OPCs through in vitro experiments. A specific Sonic Hedgehog signaling agonist (SAG) rescued osteoblastic differentiation inhibited by recombinant CRP. Moreover, chloral hydrate, which removes primary cilia, inhibited the Suppressor of Fused (SUFU) formation and blocked Gli2 degradation. This counteracted osteogenesis inhibition caused by CRP. Therefore, these data depict that CRP can inhibit the proliferation and osteoblastic differentiation of OPCs. The underlying mechanism could be associated with primary cilia activation and Hh pathway repression.

Transition-metal-catalyzed additions of C-H bonds to C-X (X = N, O) multiple bonds via C-H bond activation.

Chemical transformations via catalytic C-H bond activation have been established as one of the most powerful tools in organic synthetic chemistry. Transition-metal-catalyzed addition reactions of C-H bonds to polar C-X (X = N, O) multiple bonds, such as aldehydes, ketones, imines, isocyanates, nitriles, isocyanides, carbon monoxide and carbon dioxide, have undergone a rapid development in recent years. In this review, recent advances in this active area have been highlighted and their mechanisms have been discussed.

Synthetic applications of arylboronic acid via an aryl radical transfer pathway.

The transition-metal-catalyzed functionalization of arylboronic acids is the most powerful tool for the formation of carbon-carbon and carbon-heteroatom bonds in modern organic synthesis. These transformations are generally considered to proceed via organometallic intermediates generated by transmetalation from the boronic acids. Interestingly, there is a novel recognition that arylboronic acids can serve as aryl radical precursors via oxidative carbon-boron bond cleavage in recent years. Manganese(III) acetate, Ag(I)/persulfate and iron(II or III)/persulfate catalytic systems have been shown to be effective for this transformation. In this review, recent advances in this new area are highlighted and their mechanisms are also discussed.

Temporal variation of residential pesticide use and comparison of two survey platforms: a longitudinal study among households with young children in Northern California.

BACKGROUND: Pesticide use patterns are essential inputs into human pesticide exposure models. Currently, data included for modeling purposes have mostly been collected in cross-sectional surveys. However, it is questionable whether responses to one-time surveys are representative of pesticide use over longer periods, which is needed for assessment of health impact. This study was designed to evaluate population-wide temporal variations and within-household variations in reported residential pesticide use patterns and to compare alternative pesticide data collection methods - web surveys versus telephone interviews. METHOD: A total of 481 households in Northern California provided up to 3 annual telephone interviews on residential pesticide use; 182 of these households provided up to 6 quarterly web surveys that covered the same topics for some of the same time periods. Information on frequency and areas of application were collected for outdoor and indoor sprays, indoor foggers, professional applications, and behind-the-neck treatments for pets. Population-wide temporal variation and within-household consistency were examined both within telephone surveys and within web surveys, and quantified using Generalized Estimating Equations and Mixed Effect Modeling. Reporting between the two methods, the telephone survey and the web survey, was also compared. RESULTS: Use prevalence of outdoor sprays across the population reported in both the annual telephone surveys and the quarterly web surveys decreased over time, as did behind-the-neck treatment of pets reported in the quarterly web survey. Similarly, frequencies of use of these products decreased in the quarterly web surveys. Indoor sprays showed no statistically significant population-wide temporal variation in either survey. Intraclass correlation coefficients indicated consistent use within a household for behind-the-neck treatment on pets and outdoor sprays but great variability for the use of indoor sprays. Indoor sprays were most consistently applied in the bathroom and kitchen. Outdoor sprays were consistently more often applied by male household members, while indoor sprays were not. The two survey approaches obtained fairly similar results on the prevalence of using pesticides, but found discrepancies in use frequencies. In addition, the number of products purchased was positively correlated with application frequency for outdoor sprays (R = 0.51, p = 0.0005) but not for indoor sprays. CONCLUSIONS: In this population, repeated surveys are necessary either to obtain a reliable estimate of the average household use of pesticides or to project potential temporal changes of pesticide use. Web surveys could collect comparable data to traditional telephone surveys for some information. However, researchers need to consider the internet acceptability among the target population and balance lower participant burden against the need for sufficiently accurate time-varying measurement, to improve subject retention in longitudinal surveys.

The Role of Peptidyl Arginine Deiminase IV(PADI4) in Cancers.

BACKGROUND: Peptidyl arginine deiminase IV (PADI4, also called PAD4), a Ca2+-dependent posttranslational modification enzyme, catalyzes the conversion of arginine residues to non-coded citrulline residues. Dysregulation of PADI4 is involved in a variety of diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Alzheimer's disease (AD) and many kinds of malignant tumors. OBJECTIVE: The roles of PADI4 in different tumors and the underlying molecular mechanisms are presented in this article. RESULTS: PADI4-mediated citrullination is associated with either transcriptional activation or repression in different contexts. Abnormal expression of PADI4 exists in a variety of malignant tumors and affects tumor progression and metastasis. Epithelial-to-mesenchymal transition (EMT), apoptosis, and neutrophil extracellular traps (NETs) may be the underlying molecular mechanisms. CONCLUSION: PADI4 plays crucial role in the occurrence, development, and metastasis of tumors, and PADI4 may be an effective biomarker for cancer prognosis and a potential target for cancer treatment.

Prognostic value of miR-219-5p in relation to mortality in patients with small cell lung cancer: a retrospective, observational cohort study in China.

OBJECTIVES: Small cell lung cancer (SCLC) is a lethal human malignancy, and previous studies support the contribution of microRNA to cancer progression. The prognostic value of miR-219-5p in patients with SCLC remains unclear. This study aimed to evaluate the predictive value of miR-219-5p with respect to mortality in patients with SCLC and to incorporate miR-219-5p level into a prediction model and nomogram for mortality. DESIGN: Retrospective observational cohort study. SETTING AND PARTICIPANTS: Our main cohort included data from 133 patients with SCLC between 1 March 2010 and 1 June 2015 from the Suzhou Xiangcheng People's Hospital. Data from 86 patients with non-SCLC at Sichuan Cancer Hospital and the First Affiliated Hospital of Soochow University were used for external validation. OUTCOME MEASURES: Tissue samples were taken during admission and stored, and miR-219-5p levels were measured at a later date. A Cox proportional hazard model was used for survival analyses and for analysing risk factors to create a nomogram for mortality prediction. The accuracy of the model was evaluated by C-index and calibration curve. RESULTS: Mortality in patients with a high level of miR-219-5p (≥1.50) (n=67) was 74.6%, while mortality in the low-level group (n=66) was 100.0%. Based on univariate analysis, we included significant factors (p<0.05) in a multivariate regression model: patients with high level of miR-219-5p (HR 0.39, 95% CI 0.26-0.59, p<0.001), immunotherapy (HR 0.44, 95% CI 0.23-0.84, p<0.001) and prognostic nutritional index score >47.9 (HR=0.45, 95% CI 0.24-0.83, p=0.01) remained statistically significant factors for improved overall survival. The nomogram had good accuracy in estimating the risk, with a bootstrap-corrected C-index of 0.691. External validation indicated an area under the curve of 0.749 (0.709-0.788). CONCLUSIONS: The miR-219-5p level was associated with a reduced risk of mortality in patients with SCLC. A nomogram incorporating MiR-219-5p level and clinical factors demonstrated good accuracy in estimating the risk of overall mortality. Prospective validation of the prognostic nomogram is needed.