LncRNA HOTAIR promotes proliferation, invasion and migration in NSCLC cells via the CCL22 signaling pathway.

Long noncoding RNA (LncRNA) is a new type of regulatory RNA. LncRNA HOX antisense intergenic RNA (HOTAIR), as an oncogene in non-small cell lung cancer (NSCLC), is one of the key determinants of tumor progression. However, its possible molecular mechanism and the immunomodulatory pathway involved in NSCLC are still unclear. This study aims to explore whether HOTAIR promotes proliferation, migration and invasion of the NSCLC cells by inhibiting the expression of C-C Motif Chemokine Ligand 22 (CCL22). We collected 30 clinical samples of cancer and adjacent normal tissues from the patients with NSCLC, using real-time quantitative polymerase chain reaction (RT-qPCR) to detect the LncRNA HOTAIR and CCL22 mRNA expression in tissues. Immunohistochemistry was used to detect the protein expression of CCL22 in cancer and adjacent normal tissues. Cell experiments were conducted to verify that LncRNA HOTAIR regulates the expression of CCL22 and participates in the progress of NSCLC. The antisense oligonucleotide (ASO) probe interfering with LncRNA HOTAIR and the interference fragment of CCL22 (si-CCL22) were constructed. A549 cells were co-transfected with ASO-HOTAIR and si-CCL22. We used RT-qPCR to detect the expression of LncRNA HOTAIR and CCL22 mRNA in the cells, enzyme-linked immunosorbent assay (ELISA) used to detect the CCL22 protein level in the cell supernatant. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was applied to detect cell proliferation, the Flow cytometry to detect cell apoptosis. Finally, the Transwell test was utilized to detect cell migration and invasion. In conclusion, this study suggests that HOTAIR may promote proliferation, migration and invasion of the NSCLC cells by inhibiting CCL22 expression, which may play a key role in NSCLC cell immunity.

Sex Difference in the Association Between Eating Away From Home and the Risk of High Serum Uric Acid in South China.

Background: The prevalence of high serum uric acid is increasingly rising in recent years, and diet behavior is perceived to be associated with it. This study aimed to explore the relationship between eating away from home (EAFH) and the risk of high serum uric acid in adults in South China. Methods: The data utilized in this study were from Guangdong Nutrition and Health Survey (NHS) 2015. Serum uric acid concentration was detected. EAFH in the past week was investigated. We defined EAFH as food consumption away from home. Dietary data were collected by 24-h recalls on 3 consecutive days. A generalized linear mixed-effects model was applied to compute the odds ratio (OR) and its corresponding 95% CI. Results: A total of 3,489 individuals were included in this study. A 1.27-fold OR (95% CI: 1.05-1.52, P = 0.012) of high serum uric acid was identified in adults with EAFH in comparison with those without EAFH. With respect to men, a 1.66-fold OR (95% CI: 1.3-2.1, P < 0.001) of high serum uric acid was observed. We also observed that men with EAFH had higher intakes of red meat, poultry, vegetable, carbohydrate, protein, fat, and total energy, while a lower grain intake than those without EAFH. However, there was a lack of significant association between EAFH and the odds ratio of high serum uric acid in women. Women with EAFH did not have higher consumptions of red meat, vegetable, fish, fat, and water than those without EAFH. Conclusions: This study found that EAFH was associated with an increased odds ratio of high serum uric acid in men, but not in women.

The relationship between ambient temperature and fasting plasma glucose, temperature-adjusted type 2 diabetes prevalence and control rate: a series of cross-sectional studies in Guangdong Province, China.

BACKGROUND: There existed evidence that type 2 diabetes mellitus (T2DM) prevalence and control rate have seasonal variation. Our study aimed to examine the ambient temperature and fasting plasma glucose (FPG) association and estimate temperature-adjusted T2DM prevalence and control rate. METHODS: Four cross-sectional health surveys with 26,350 respondents were conducted in Guangdong Province from 2007 to 2015. Multistage cluster sampling was used to recruit study participants. The data of demographic characteristics, lifestyle factors, diet and use of hypoglycemic medicine, height, weight, FPG and meteorological information were collected. And an inverse distance-weighted method was employed to estimate daily temperature exposures at the individual' s residential district/county. Base on World Health Organization 2006 criteria, participants were divided into normal fasting glucose (NFG) participants (n = 23,877), known T2DM patients (n = 916) and newly detected T2DM patients (n = 1557). Generalized additive mixed model was employed to evaluate the nonlinear associations between temperature and FPG among different T2DM subgroups. The T2DM prevalence and control rate were estimated based on temperature-FPG association. RESULTS: The curves of temperature and FPG were downward parabola for total, NFG and known T2DM groups, while it was "U"-shaped for newly detected T2DM patients. When temperature decreased from 30 °C to 4 °C, the FPG significantly increased 0.24 (95%CI: 0.15, 0.33) mmol/L, 0.10 (95%CI: 0.06, 0.14) mmol/L and 1.34 (95%CI: 0.56, 2.12) mmol/L in total, NFG and known T2DM groups, respectively. Compared to 19 °C, newly detected T2DM patients' FPGs were increased 0.73 (95%CI: 0.13, 1.30) mmol/L at 4 °C and 0.53 (0.00, 1.07) mmol/L at 30 °C. The model-estimated temperature-adjusted T2DM prevalence had a down and up trend, with 9.7% at 5 °C, 8.9% at 20 °C and 9.4% at 30 °C, respectively. At 5, 10, 15, 20, 25 and 30 °C, the model-estimated temperature-adjusted T2DM control rates were 33.2, 35.4, 38.2, 43.6, 49.1 and 55.2%. CONCLUSION: Temperature was negatively associated with FPG for NFG and known T2DM subgroups, while their association was U-shape for newly detected T2DM patients. Hence, the temperature-adjusted T2DM prevalence show a dip/peak pattern and T2DM control rate display a rising trend when temperature increase. Our findings suggest temperature should be considered in T2DM clinic management and epidemiological survey.

Gemcitabine Plus Cisplatin Versus Fluorouracil Plus Cisplatin as First-Line Therapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: Final Overall Survival Analysis of GEM20110714 Phase III Study.

PURPOSE: GEM20110714 (ClinicalTrials.gov identifier: NCT01528618), the first randomized, phase III study of systemic chemotherapy in recurrent or metastatic nasopharyngeal carcinoma (NPC), reported significant progression-free survival improvement with gemcitabine plus cisplatin (GP) versus fluorouracil plus cisplatin (FP; hazard ratio, 0.55; 95% CI, 0.44 to 0.68; P < .001). Data from the final analysis of overall survival (OS) are presented here. METHODS: From February 2012 to October 2015, 362 patients were randomly assigned to receive either GP (gemcitabine 1 g/m2 once daily on days 1 and 8 and cisplatin 80 mg/m2 once daily on day 1; n = 181) or FP (fluorouracil 4 g/m2 in continuous intravenous infusion over 96 hours and cisplatin 80 mg/m2 once daily on day 1; n = 181) once every 21 days. The primary end point was progression-free survival, which has been previously reported; OS was a secondary end point. RESULTS: After a median follow-up time of 69.5 months with GP and 69.7 months with FP, 148 (81.8%) and 166 (91.7%) deaths occurred in the GP and FP arms, respectively. The estimated hazard ratio for OS was 0.72 (95% CI, 0.58 to 0.90; two-sided P = .004). The median OS was 22.1 months (95% CI, 19.2 to 25.0 months) with GP versus 18.6 months (95% CI, 15.4 to 21.7 months) with FP. The OS probabilities at 1, 3, and 5 years were 79.9% versus 71.8%, 31.0% versus 20.4%, and 19.2% versus 7.8%, respectively. Poststudy therapy was administered in 51.9% and 55.2% of patients in the GP and FP arms, respectively. CONCLUSION: Among patients with previously untreated advanced nasopharyngeal carcinoma, those who receive GP have longer OS than those receive FP. Gemcitabine plus cisplatin should be considered a preferred front-line option for these patients.

Effect of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Women: A Randomized Clinical Trial.

Importance: The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment. Objective: To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk. Design, Setting, and Participants: This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020. Interventions: Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1). Main Outcomes and Measures: The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points. Results: A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase. Conclusions and Relevance: The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption. Trial Registration: ClinicalTrials.gov Identifier: NCT03674294.

Pathologic complete response after neoadjuvant tislelizumab and chemotherapy for Pancoast tumor: A case report.

A 60-year-old man was hospitalized because of numbness and weakness in the right upper limb. Magnetic resonance imaging revealed a large mass in the right upper lobe invading the right eighth cervical and first thoracic nerve root. Biopsy pathology confirmed primary lung adenocarcinoma with a clinical stage of cT4N0M0 IIIA, negative for anaplastic lymphoma kinase fusion gene and epidermal growth factor receptor mutations but positive for programmed death ligand 1 (3%). Neoadjuvant tislelizumab and chemotherapy were offered to this patient with Pancoast tumor, and tumor shrinkage of 71% was achieved. After the operation, surgical pathology indicated pathologic complete response (pCR). Circulating tumor cells testing was negative after the first adjuvant treatment. In this case, we provide real-world evidence of encouraging pCR with neoadjuvant tislelizumab and chemotherapy for a patient with Pancoast tumor.

Development of two continuous hemocyte cell sublines in the Asian corn borer Ostrinia furnacalis and the identification of molecular markers for hemocytes.

Granulocytes and plasmatocytes play important roles in clearing foreign objects in insects, but it is difficult to distinguish between them in immune reactions. Based on the hemocyte cell line SYSU-OfHe-C established at our lab, two cell sublines, SYSU-OfHe-C Granulocyte (Gr cells) and SYSU-OfHe-C Plasmatocyte (Pl cells), which possess the morphological characteristics of granulocytes and plasmatocytes, respectively, were established. Gr and Pl cells showed different behaviors in immune reactions, such as spreading, phagocytosis and encapsulation. Pl cells were easier to spread, but Gr cells tended to undergo aggregation, indicating that they may take different strategies to clear foreign objects. These results also suggested that granulocytes and plasmatocytes may express some different proteins. By comparing the gene expression in cells from the two sublines, 1662 differentially expressed genes were identified, and 13 out of 30 transmembrane proteins highly expressed in Pl cells (six) or Gr cells (seven) were further screened and confirmed by reverse-transcription polymerase chain reaction (PCR). Finally, three transmembrane genes specifically expressed in Pl cells and two transmembrane genes specifically expressed in Gr cells were screened out based on their expressions in immune reactions by quantitative PCR analysis. These genes may potentially be used as molecular markers to distinguish between granulocytes and plasmatocytes in Ostrinia furnacalis, and further to clarify the functions of immune hemocytes in cellular immune reaction such as encapsulation and so on.

Correction to: Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015-2017).

It was highlighted that in the original article [1] the data on categorical variables was wrongly arranged in Table 1 and there was an incorrect statement in the fourth paragraph of the Discussion section.

Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer.

BACKGROUND: Monosialotetrahexosylganglioside (GM1) is a neuroprotective glycosphingolipid that repairs nerves. Oxaliplatin-based chemotherapy is neurotoxic. This study assessed the efficacy of GM1 for preventing oxaliplatin-induced peripheral neurotoxicity (OIPN) in colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy. METHODS: In total, 196 patients with stage II/III CRC undergoing adjuvant chemotherapy with mFOLFOX6 were randomly assigned to intravenous GM1 or a placebo. The primary endpoint was the rate of grade 2 or worse cumulative neurotoxicity (NCI-CTCAE). The secondary endpoints were chronic cumulative neurotoxicity (EORTC QLQ-CIPN20), time to grade 2 neurotoxicity (NCI-CTCAE or the oxaliplatin-specific neuropathy scale), acute neurotoxicity (analog scale), rates of dose reduction or withdrawal due to OIPN, 3-year disease-free survival (DFS) and adverse events. RESULTS: There were no significant differences between the arms in the rate of NCI-CTCAE grade 2 or worse neurotoxicity (GM1: 33.7% vs placebo: 31.6%; P = .76) or neuropathy measured by the EORTC QLQ-CIPN20 or time to grade 2 neurotoxicity using NCI-CTCAE and the oxaliplatin-specific neuropathy scale. GM1 substantially decreased participant-reported acute neurotoxicity (sensitivity to cold items [P < .01], discomfort swallowing cold liquids [P < .01], throat discomfort [P < .01], muscle cramps [P < .01]). The rates of dose reduction or withdrawal were not significantly different between the arms (P = .08). The 3-year DFS rates were 85% and 83% in the GM1 and placebo arms, respectively (P = .19). There were no differences in toxicity between the arms. CONCLUSION: Patients receiving GM1 were less troubled by the symptoms of acute neuropathy. However, we do not support the use of GM1 to prevent cumulative neurotoxicity. (ClinicalTrials.gov number, NCT02251977).

[Prevalence of malnutrition status in children and adolescents in Guangdong Province, 2002-2012].

OBJECTIVE: To investigate the prevalence and change of growth retardation, weight loss and malnutrition among children and adolescents aged 6-17 years in Guangdong Province in 2002-2012. METHODS: A total of 7264 children and adolescents(3804 boys and 3460 girls) aged 6-17 years were selected in thirteen monitoring points of Guangdong for nutritional survey in 2002, and a total of 2319 children and adolescents(1158 boys and 1161 girls) aged 6-17 years were selected in nine counties/districts of Guangdong for nutritional survey during 2009-2012 through multistage random cluster sampling. The body height and weight of all the children and adolescents were measured. RESULTS: The prevalence of growth retardation, weight loss and malnutrition decreased from 10. 0% to 1. 6%, 18. 1% to 8. 0%, and 24. 7% to 9. 3%among children and adolescents in Guangdong from 2002 to 2009-2012. The result of2009-2012 survey indicated the average prevalence of growth retardation were higher in boys(1. 9%) than in girls(1. 1%), and the average prevalence of weight loss and malnutrition was higher in girls(10. 4% and 11. 3%) than in boys(6. 0% and 7. 7%). And the average prevalence of growth retardation, weight loss and malnutrition were all higher in those living in rural area(2. 5%, 12. 4% and 14. 5%) than in city area(0. 8%, 4. 4% and 5. 1%). CONCLUSION: Compared with 2002, the prevalence of growth retardation, weight loss and malnutrition in children and adolescents aged 6-17 in Guangdong Province all decreased significantly. The prevalence was still high in girls and those living in rural, and children aged 6-17, thus more attention should be paid to them.

Association between dietary acid load and the risk of hypertension among adults from South China: result from nutrition and health survey (2015-2017).

BACKGROUND: Higher dietary acid load (DAL) was considered to be associated with an elevated risk of hypertension, while related data from mainland China remains scarce and incomplete. We aim to evaluate the association between DAL and the risk of hypertension among adults from South China. METHODS: We conducted a nutrition and health survey in Guangdong Province located in southern China from 2015 to 2017. A four-stage probability sampling method was utilized to select representative samples of citizens aged ≥18 years old. DAL was assessed by potential renal acid load (PRAL) and net endogenous acid production (NEAP). Participants were divided to 4 groups (Q1-Q4) according to the quartile points of PRAL or NEAP distributions. Generalized linear mixed effects models were applied to evaluate the association between DAL and the risk of hypertension. RESULTS: A total of 3501 individuals were eligible for this study and 45.9% was male participants. Hypertension rate was 30.7%. A higher PRAL was associated with higher prevalence rate of hypertension among the male (P-trend = 0.03). OR for Q2 was 1.34 (95%CI, 0.94-1.91), Q3 was 1.53 (95%CI = 1.08, 2.16) and Q4 was 1.51 (95%CI, 1.08-2.16) among the male. However, as for total participants, the female, the participants with ≤55 years or participants with > 55 years, the associations were lack of significance. With respect to association between NEAP and hypertension, non-significant results were identified. CONCLUSIONS: The current study indicated male hypertension was associated with higher PRAL, while given to this study was cross-sectional design, further studies are warranted to verify the association.

Elevated hypertension risk associated with higher dietary acid load: A systematic review and meta-analysis.

BACKGROUND & AIMS: The association between dietary acid load and hypertension risk is inconclusive. We conducted a systematic review and meta-analysis to summarize effect of dietary acid load on blood pressure. METHODS: A comprehensively search was performed in electronic databases including EMBASE, PubMed, Web of Science and Chinese National Knowledge Infrastructure. Summary ORs and their corresponding 95% CIs were computed assuming a randomized model or fixed model. RESULTS: Ten publications comprising 4 cohort and 6 cross-sectional studies were eligible for meta-analysis. There were 8 studies about potential renal acid load (PRAL) and 4 about net endogenous acid production (NEAP). Essential hypertension was statistically associated with higher PRAL (OR = 1.14, 95% CI = 1.02-1.17). Our findings also demonstrated a positive impact of higher PRAL on elevating both diastolic pressure (WMD = 0.96, 95% CI = 0.67-1.26) and systolic pressure (WMD = 1.57, 95% CI = 1.12-2.03). A 35% increased risk of hypertension associated with higher NEAP was identified (OR = 1.35, 95% CI = 1.03-1.78). CONCLUSIONS: The current study suggests that dietary acid load might be potential risk factor of hypertension.

The human body burden of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in residents' human milk from Guangdong Province, China.

Human milk samples were collected from 179 mothers in 2017 and 2018 in six counties of Guangdong province, China. Concentrations of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs) were determined to evaluate the human body burden of dioxin-like compounds on the general population of South China. Samples were analyzed using high-resolution gas chromatography/high-resolution mass spectrometry in six pools, according to the subjects' resident county. The mean ∑PCDD/Fs and ∑DL-PCBs concentrations in human milk samples were 323.10 pg g-1 lipid and 2166.58 pg g-1 lipid, respectively, and the corresponding WHO toxicity equivalent (TEQ) values calculated with Toxic Equivalent Factors (TEFs) established by the WHO in 2005 (TEFWHO 2005) were 6.96 and 2.13 pg g-1 lipid. The concentrations of samples collected in Guangzhou, the capital city of Guangdong Province, were higher than those taken in the other five investigation regions. The levels of PCDD/Fs and DL-PCBs in human milk and the estimated daily intake doses of breast-fed infants were still high when compared with some non-exposure areas in mainland China. TEQ levels of PCDD/Fs and DL-PCBs in the present study have been compared to data obtained from a reported national study conducted in 2011. The mean TEQ (calculated with TEFWHO 2005) of ∑(DL-PCBs + PCDD/Fs) (8.4-9.0 pg g-1 lipid in 2011 vs. 9.09 pg g-1 lipid in 2018) seemed to be relatively stable during the period 2011-2018. These findings and continuing the surveillance of PCDD/Fs and DL-PCBs in human milk will be helpful in furthering our understanding of human exposure to dioxin-like compounds in the general population.

Gut microbiota partially mediates the effects of fine particulate matter on type 2 diabetes: Evidence from a population-based epidemiological study.

BACKGROUND: Experimental studies have indicated that alterations in the gut microbiota might play a role in the pathway of diabetes induction resulting from particulate matter pollution with aerodynamic diameters < 2.5 µm (PM2.5). However, few human studies have examined such experimental findings. Here, we examine the mediating effects of gut microbial dysbiosis on the associations between PM2.5 and particulate matter pollution with aerodynamic diameters < 1 µm (PM1) on diabetes using the Guangdong Gut Microbiome Project (GGMP) dataset. METHODS: A multistage cluster sampling method was employed to recruit adult participants from communities in Guangdong. Each participant was interviewed using a questionnaire, fasting blood and stool samples were collected, and the exposure to air pollutants was assessed using a spatiotemporal land-use regression model. The mediation analysis was conducted to estimate the associations among air pollutants, gut microbiota diversity and diabetes. RESULTS: Both PM2.5 and PM1 were positively associated with the risks of impaired fasting glucose (IFG) or type 2 diabetes and negatively associated with alpha diversity indices of the gut microbiota. The mediation analyses indicated that the associations of PM2.5 and PM1 with the risk of type 2 diabetes were partially mediated by the decrease in gut microbiota diversity. Moreover, we found that 79 (PM2.5 on IFG), 84 (PM2.5 on type 2 diabetes), 83 (PM1 on IFG) and 89 (PM1 on type 2 diabetes) bacterial taxa could partially mediate the associations of PM2.5 and PM1 with IFG and type 2 diabetes, respectively. The relative abundance of most Firmicutes, Proteobacteria and Verrucomicrobia bacteria were negatively associated with particulate matter (PM) concentrations and the risks of diabetes. CONCLUSIONS: Long-term exposure to PM may increase the risk of diabetes, and alterations in the gut microbiota partially explained these associations.

Benefit-risk assessment of commonly consumed fish species from South China Sea based on methyl mercury and DHA.

Even though a growing number of reports indicated favorable health effects with fish consumption, kinds of hazardous substances in fish were detected in fish and to be exceeded advisory limitation. Benefit-risk assessment of commonly consumed fish is urgently needed. We conducted fish consumption survey and fish sampling in the coast of South China Sea to assess benefit-risk effect of commonly consumed fish species. For local residents, weekly methyl mercury (MeHg) exposures from commonly consumed fish species ranged from 0.12 to 2.11 µg/kg bw. Apart from Muraenesox cinereus and Acanthopagrus latus, the rest of 92% (23/25) fish species were at low risk of MeHg exposure. Daily docosahexaenoic acid intakes via consuming specific fish were between 42.18 and 1687.04 mg/day. A total of 72% (18/25) fish species could provide 200 mg/day of DNA for local residents. Benefit-risk assessment assuming intelligence quotient (IQ) score model showed net IQ point gains between 1.53 and 5.65 points with consuming various fish species, indicative of large distinction of health benefit from various fish species. This study suggests commonly consumed fish species from China South Sea could bring much more positive effect than negative effect. Species-specific fish should be considered when providing recommendations of fish consumption. Muraenesox cinereus and Acanthopagrus latus should be minded with risk of MeHg exposure in taking large amounts.

Successful treatment of metastatic extramammary Paget's disease with pemetrexed monotherapy systemically and 5-fluorouracil topically.

Advanced extramammary Paget's disease does not have a standardized treatment guideline as its incidence is low and has been rarely reported in literature. Here we describe a case of metastatic extramammary Paget's disease successfully treated with topical 5-fluorouracil (5-FU) and systemic pemetrexed. The therapy was safe without any appreciable adverse effects like diarrhea, rash, neutropenia or fatigue; maintaining remission for more than 6 months. Thus, we propose 5-FU and pemetrexed as the first-line therapy for advanced extramammary Paget's disease, especially for aged patients with unresectable skin lesions.

Dose-Dense Rituximab-CHOP versus Standard Rituximab-CHOP in Newly Diagnosed Chinese Patients with Diffuse Large B-Cell Lymphoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP- 14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.

[Expression of secreted frizzled-related protein 4 in DNA mismatch repair-deficient and mismatch repair-proficient colorectal cancers].

OBJECTIVE: To investigate the expressions of secreted frizzled-related protein 4 (SFRP4) in stage Ⅱ DNA mismatch repair-deficient (dMMR) and mismatch repair- proficient (pMMR) colorectal cancers and explore their clinical significance. METHODS: We collected fresh stage Ⅱ colon cancer tissues with different MMR status detected by immunohistochemistry (IHC). The differentially expressed mRNAs between dMMR and pMMR tumors were identified by Affymetrix Human oeLncRNA gene chip, and the expression of SFRP4 in these cancer tissues and in colorectal cancer cell lines were detected using Western blotting and real- time quantitative PCR. The apoptosis rates of HCT116 cells with and without siRNA- mediated transient SFRP4 knockdown were determined using flow cytometry. We further investigated the expression pattern of Ki-67 and its correlation with SFRP4 expression. RESULTS: Compared with pMMR colon cancer tissues or cells, both dMMR colon cancer tissues (P=0.014) and cells (P=0.0079) showed significantly increased expression of SFRP4, which was in negative correlation with Ki-67 (P=0.041). In HCT116 cells, transient SFRP4 knockdown resulted in decreased cell apoptosis, including both early apoptosis (P=0.003) and late apoptosis (P=0.024). CONCLUSIONS: Up-regulation of SFRP4 in dMMR stage Ⅱ colon cancer promotes apoptosis and inhibits proliferation of the cancer cells, and may improve the prognosis of dMMR colon cancer.

Health Risk Assessment for Local Residents from the South China Sea Based on Mercury Concentrations in Marine Fish.

The offshore area of the South China Sea is an important fishing ground in China. We used a food frequency questionnaire to determine marine fish consumption by local residents, and we detected mercury concentrations in commonly consumed marine fish species. In total, 127.9 g/day of the marine fish consumed was identified in 178 local residents. THg and MeHg concentrations in 209 samples of 22 fish species ranged from 11.3 to 215.0 µg/kg wt and 2.0 to 160.0 µg/kg wt, respectively. The mean MeHg exposure from marine fish to local residents was 0.099 µg/kg bw, accounting for 43.0% of the provisional tolerated weekly intake (PTWI) (1.6 µg/kg bw/week), suggesting a low health risk. However, a potentially high health risk (202.2% of PTWI) was identified in those with 97.5% MeHg exposure.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study.

BACKGROUND: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. METHODS: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. RESULTS: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. CONCLUSIONS: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.