[Effects of occupational nickel exposure on glycemic parameters in workers].

Objective: To explore the effect of occupational nickel exposure on blood glucose related indicators of workers. Methods: In March 2019, five electroplating enterprises and one plastic hardware enterprise were selected by cluster sampling method. 159 nickel plating workers were selected as the contact group, and 66 administrative personnel of the same enterprise were selected as the control group. The serum nickel concentration, fasting blood glucose (FPG) , fasting insulin (FIns) and glycosylated hemoglobin (HbA1c) were measured in the contact group and the control group. The differences of blood glucose related indexes between the two groups were compared, and the risk factors of abnormal blood glucose indexes were analyzed. Results: Compared with the control group, the blood nickel concentration and detection rate of nickel in the contact group were higher, the levels of FIns were lower, and the proportion of HbA1c was higher in the contact group (P<0.05) . Stratified analysis showed that compared with the control group, the blood glucose index of men in the contact group changed significantly (P<0.05) ; logistic regression analysis showed that male was an independent influencing factor for decreased FIns (OR=8.264, P<0.05) . Conclusion: Long term exposure to nickel can affect the blood glucose related indexes such as fins and HbA1c.

[Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer].

Objective: To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods: A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ(2) test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level. Result: A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ(2)=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ(2)=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions: Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.

Enhanced antitumor efficacy of resveratrol-loaded nanocapsules in colon cancer cells: physicochemical and biological characterization.

OBJECTIVE: The aim of present work was to prepare resveratrol-loaded lipid-core-nanocapsule (RSV-LNC) and to characterize its ability to target the colon cancer cells. MATERIALS AND METHODS: The lipid-core nanocapsule was prepared by precipitation method. The nanoparticle was prepared and evaluated regarding physical, chemical and biological parameters. RESULTS: The average size of optimized nanocapsule was ~159 nm with a uniform size distribution index of 0.15 (PDI). The RSV-LNC showed a controlled and sustained release pattern with maximum release up to ~70% by the end of 48h study period. LNC showed an excellent cellular uptake potential. LNC showed a typical endocytosis-mediated cellular internalization process and located in the cell cytoplasm. DISCUSSION: Importantly, RSV encapsulated in a nanocapsule showed a superior anticancer effect in HT29 cancer cells than compared to that of free RSV. Consistently, RSV-LNC showed a remarkable ~36% of cell apoptosis indicating its superior anticancer effect. CONCLUSIONS: Based on the in vitro studies, RSV encapsulated in a nanocapsule showed promising potential to increase the therapeutic efficacy in colon cancer cells; however, further studies on animal models are warranted to confirm the improved effects of RSV nanoformulations.

Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.

Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol-treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol.