Objective:To investigate the potential pro-apoptotic activity of arsenic trioxide (ATO) in human leukemia HL-60 cells,as well as the potential mechanism with focus on mitochondrial pathway.Methods:After treatment with different concentrations of ATO (1 μg/mL,5 μg/mL or 10 μg/mL) for 24 h,apoptotic cell death was detected by flow cytometry,oxidative stress was determined by measuring MDA and GSH levels,the expression of apoptotic factors was detected by western blot,and mitochondrial membrane potential (MMP) was determined by immunofluorescence staining.Results:ATO at the concentrations of 5 μg/mL or 10 μg/mL induces apoptotic cell death and increases oxidative stress in human leukemia HL-60 cells.ATO significantly increases the expression of pro-apoptotic factors (Bax and Caspase-3),whereas decreases the expression of anti-apoptotic factor Bcl-2.Compared with the control group,ATO treatment significantly decreases the MMP level in HL-60 ceils.Conclusions:Arsenic trioxide induces apoptotic cell death through mitochondrial pathway in human leukemia HL-60 cells.

Background and purpose:The effective rate of ifrst-line chemotherapy for advanced lung cancer is 30%-40%. The purpose of this study was to evaluate the efifcacy and adverse effects of pemetrexed combined with carboplatin or cisplatin in the treatment of patients with advanced non-squamous non-small cell lung cancer (NSCLC). Methods:One hundrend and twenty-one patients with advanced non-squamous NSCLC were enrolled in this study and all of these patients had been conifrmed with pathology or cytology. Among the 121 cases, 60 cases were male and 61 were female, the median age was 59 years, adnenocarcinoma in 113 patients and large cell carcinoma in 8 patients. Combination regimen: patients received pemetrexed 500 mg/m2 on day 1 and carboplatin 300 mg/m2 or cisplatin 70 mg/m2 on day 1 by intravenous infusion, administrated every 3 weeks for 2 to 6 cycles. All patients who received 2 or more cycles could be evaluated. Disease control rate (DCR) was the primary end point; secondary end points included progression-free survival (PFS), 1-year survival rate and safety.Results:There was 1 case with complete response (CR), 44 cases achieved partial response (PR), 50 had stable disease (SD) and 26 cases had progressive disease (PD) in the overall cases. ORR and DCR were 37.2% (45/121) and 78.5% (95/121), respectively. The median PFS time was 5.2 months and 1-year survival rate was 59.0%. In pemetrexed combined with carboplatin group, the ORR and DCRwere 38.3% (23/60) and 78.3% (47/60), respectively; The median PFS was 5.1 months (95%CI: 3.8-6.4 month) and 1-year survival rate was 55.2%. The patients treated with pemetrexed plus cisplatin, the ORR and DCR were 36.1% (22/61) and 78.7% (48/61), respectively. Median PFS was 6.2 months (95%CI: 4.3-8.1 month) and 1-year survival rate was 62.5%. There were no statistical differences between carboplatin/pemetrexed and cisplatin/pemetrexed for both ORR, DCR, PFS and 1-year survival rate (P>0.05). The major adverse effects were leukopenia, neutropenia, fatigue and gastrointestinal reaction.Conclusion:Pemetrexed plus platinum chemotherapy could be considered as the ifrst-line treatment option for advanced non-squamous NSCLC patients. Pemetrexed combined with carboplatin/ cisplatin regimen has efifcacy with mild toxicity and better tolerability.

Objective:By exploring the source of children's total fluoride intake and the relationship between children's total fluoride intake and dental fluorosis prevalence, to calculate the benchmark dose (BMD) of children's total fluoride intake and its 95% confidence lower limit (BMDL), and to provide the basis for revision of "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).Methods:The villages that had water improvement for 5 years and more in 6 provinces of Jiangsu, Shandong, Hebei, Anhui, Henan and Shaanxi were selected as survey sites in April 2014. The water fluoride content of these villages was 0.3 - 3.0 mg/L, tap water samples from the centralized water supply were collected, and fluoride content was detected by ion selective electrode method. Children aged 8 to 12 years were selected, children's dental fluorosis was checked by Dean's method. Children's dietary and drinking water volume were surveyed by duplicate portion study (measurement for 3 d), and dietary fluoride content was detected according to the "Method for Determination of Fluorine in Foods". The mean and standard deviation of drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were measured. According to the dose-response relationship between children's total fluoride intake and the detection rate of dental fluorosis, BMD and BMDL were calculated, and the reference dose (RfD) was calculated based on BMDL.Results:The mean of water fluoride of all 29 villages was 1.26 mg/L (from 0.41 to 2.85 mg/L). Totally 3 043 children aged 8 to 12 years were checked, and the detection rate of dental fluorosis was 30.2% (919/3 034). The lowest detection rate of dental fluorosis was 2.0% (2/100) and the highest was 71.4% (30/42) in the 29 villages. The children's dietary and drinking water volume of 769 person-time aged 8 to 12 years were surveyed, the children's daily drinking water fluoride intake, dietary fluoride intake, and total fluoride intake were (0.83 ± 0.66), (1.13 ± 0.61) and (1.96 ± 0.89) mg/d, respectively. The BMD of children's daily total fluoride intake was 2.43 mg, the BMDL was 2.21 mg, and the RfD was 2.21 mg.Conclusion:The BMD of 8 to 12 years old children's daily total fluoride intake is the same as the allowable limit (2.4 mg) of the national standard "Total Fluoride Intake for Inhabitants" (WS/T 87-2016).

OBJECTIVELuteolin, a flavone, has considerable neuroprotective effects by its anti-oxidative mechanism. However, it is still unclear whether luteolin can protect neurons against oxygen-glucose deprivation/reperfusion (OGD/R) induced injury.

METHODAfter 2 hours oxygen-glucose deprivation and 24 hours reperfusion treatment in primary cultured hippocampal neurons, the neuron viability, survival rate and apoptosis rate were evaluated by MTT assay, lactate dehydrogenase (LDH) leakage assay and Hoechst staining, respectively. The activity of Na+/K+ -ATPase was examined in cultured neurons or in the hippocampus of SD rats treated by 10 minutes global cerebral ischemia and followed 24 hours reperfusion.

RESULTTreatment by OGD/R markedly reduced neuronal viability, increased LDH leakage rate and increased apoptosis rate. Application of luteolin (10-100 micromol x L(-1)) during OGD inhibited OGD/R induced neuron injury and apoptosis in a dose-dependent manner. Compared to the control group or OGP/R-treated neurons, the activity of Na+/K+ -ATPase was significantly suppressed in global ischemia/reperfusion group or OGD/R-treated neurons. Application of luteolin during ischemia or OGD preserved the Na+/K+ -ATPase activity. Furthermore, inhibition of Na+/K+ -ATPase with ouabain attenuated the protective effect afforded by luteolin.

CONCLUSIONThe data provide the evidence that luteolin has neuroprotective effect against OGD/R induced injury and the protective effect may be associated with its ability to improve Na+/K+ -ATPase activity after OGD/R.

Animals ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Cell Hypoxia ; Glucose ; metabolism ; Luteolin ; pharmacology ; Neurons ; drug effects ; enzymology ; metabolism ; pathology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; metabolism ; pathology ; prevention & control ; Sodium-Potassium-Exchanging ATPase ; metabolism

Objective: To explore the differences in the gut microbiota of primary school students with different levels of sugar sweetened beverage intake, so as to provide scientific evidence for better identification of health risks in children and the development of targeted health policies. Methods: In June 2022, a total of 192 healthy primary school students from Chengdu were selected using a stratified cluster random sampling method. The sugar sweetened beverage intake was assessed through a dietary frequency questionnaire. Based on the median daily sugar sweetened beverage intake, primary school students were categorized into a low intake group ( n =96) and a high intake group ( n =96). The gut microbiota in fresh fecal samples from the two groups of primary school students was analyzed using 16S rRNA high throughput sequencing, and the diversity and community structure differences in the gut microbiota were compared. Results: Children in the low intake group had a sugar sweetened beverage intake of (21.3±1.6) mL/d, while the high intake group had an intake of (269.6±37.3) mL/d. Diversity analysis results showed that there were no statistically significant differences between the low intake and the high intake group in terms of α diversity metrics: Observed_otus index [298.50 (259.75, 342.25), 305.50 (244.25, 367.75)], Goods_coverage index [1.00 (1.00, 1.00), 1.00 (1.00, 1.00)], Chao index [304.18 (260.75, 348.78), 305.88 (245.68, 370.88)], Shannon index [5.88 (5.29, 6.45), 5.71 (4.89, 6.28)] and Simpson index [0.95 (0.91, 0.97), 0.94 (0.88, 0.97)] ( Z =-0.64, -0.76, -0.54, -1.76, -1.67, P >0.05). Furthermore, no statistically significant difference was observed in β diversity between the two groups ( R 2=0.006, P >0.05). At the genus level, the abundance of Blautia [0.033 (0.018, 0.055)] and Fusicatenibacter [0.009 (0.005, 0.015)] were higher in the low intake group compared to the high intake group [0.024 (0.013, 0.041),0.006 (0.003, 0.011)]and differences were statistically significant ( Z =-2.52, -2.81, P <0.05). LEfSe analysis highlighted intergroup differences primarily in Blautia, Fusicatenibacter and Sarcina( LDA= 3.56,3.12,3.53, P <0.05). Conclusions There is no significant difference in the diversity and overall structure of the gut microbiota in primary school students with different levels of sugar sweetened beverage intake. However, there are species variations at the genus level. The information can serve as a scientific basis for identifying health risks in primary school students and formulating targeted health strategies.

Objective To understand the implementation effects of control measures and the dynamic prevalence of drinking water-borne endemic fluorosis in Shandong Province.Methods From 2013 to 2017 in Shandong Province drinking water-borne endemic fluorosis areas,in accordance with the method of simple random sampling,10 monitored counties were selected,10 water fluorine decreasing projects were investigated of its running effect,and water fluoride was detected.In each monitored county,3 villages in the diseased areas were selected as fixed monitored villages.If the monitored village had changed its water,the operation of the project would be investigated.If the monitored village had not changed the water,one water sample would be collected according to 5 directions of east,west,south,north and middle to determine the water fluorine.All children aged from 8 to 12 in the village were also examined for dental fluorosis.X-ray fluorosis and urinary fluorosis in adults aged over 25 were detected in 2013 and 2017.Results From 2013 to 2017,in monitored counties,the normal operation rate of improved-water defluoridation projects was 99.19％ (368/371),the qualified rate of water fluoride content was 66.85％ (248/371).In 128 improved water projects,the normal operation rate was 100.00％ (128/128),the qualified rate of water fluoride content was 67.19％ (86/128).The average detection rate of dental fluorosis and community fluorosis index (CFI) in children aged 8-12 were 33.92％ (2 608/7 689) and 0.68 in all monitored counties from 2013 to 2017.The detection rate presented a declining trend year by year (x2 =152.47 P ＜ 0.01).The average detection rate and CFI in the villages with normal operation projects and qualified fluoride content were 26.10％ (1 311/5 023) and 0.47.The detection rate presented a declining trend year by year (x2 =207.67 P ＜ 0.01).The detection rate and CFI in the villages with water improvement projects under abnormal operation or excessive fluoride were 48.65％ (1 297/2 666) and 0.90.The detection rate of dental fluorosis in the villages with normal operation projects and qualified fluoride content was lower than the rate of the villages with water improvement projects under abnormal operation or excessive fluoride (x2 =193.98,P ＜ 0.01).In 2013 and 2017,X-ray detection rates of skeletal fluorosis in adults aged over 25 were 8.04％ (119/1 481) and 6.04％ (81/1 342),respectively.The adult urinary fluoride geometric mean values (1.24,1.49 mg/L) were lower than the normal limit of 1.6 mg/L both in qualified villages of water ffuoride content and exceeding-standard villages in 2017.Conclusions In Shandong Province,the effective water improvement has acquired some effects in control of drinking water-borne endemic fluorosis.But the water fluoride content of improved water defluoridation projects exceeds the national standard seriously and fluorosis has not been effectively controlled.

Objective To grasp the current situation of drinking water-borne endemic fluorosis in Shandong Province,and provide a scientific basis for formulating preventive strategies.Methods In 2016,according to the "National Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis" and "Shandong Provincial Surveillance Scheme of Drinking Water-Borne Endemic Fluorosis",10 counties (cities,districts) were selected in Shandong Province,3-5 villages were selected in each county (city,district),to investigate the operation of water improvement and fluorine reduction project and the water fluorine,and 1 tap water sample in each village was collected to detect water fluorine.At the same time,dental fluorosis examination was performed on all children aged 8-12 years old and fluorosis X-ray examination was performed on adults aged ≥25 years old.Water fluorine was detected by ion selective electrode method;the water fluorine was determined according to "Standards for Drinking Water Quality" (GB 5749-2006);criteria for diagnosis,grading and epidemic intensity of dental fluorosis were based on "Diagnosis of Dental Fluorosis" (WS/T 208-2011);the diagnostic and grading criteria for skeletal fluorosis were based on the "Diagnostic Criteria for Endemic Skeletal Fluorosis" (WS 192-2008).Results All the 32 villages in 10 counties (cities,districts) changed water,water improvement and fluorine reduction project ran normally,24 villages had qualified water fluorine (≤ 1.20 mg/L),and 8 villages had water fluorine exceeding the standard.The detection rate of dental fluorosis in children was 25.75％ (419/1 627),and the difference between 10 counties (cities,districts) was statistically significant (x2 =288.55,P ＜ 0.01);the dental fluorosis index was 0.48,and the defect rate was 2.77％ (45/1 627).The detection rate of skeletal fluorosis in adults was 4.72％ (72/1 525),and the difference between 10 counties (cities,districts) was statistically significant (x2 =18.83,P ＜ 0.01).Conclusions The problem of water fluorine exceeding the standard in water improvement and fluorine reduction project in Shandong Province is still serious.The condition of fluorosis has not been fully controlled,and the prevention and treatment measures need to be further strengthened.

【Objective】 To investigate whether 17β-estradiol (βE2) can activate the NF-E2-related factor 2(Nrf2) pathway to resist the downregulation of retinal function induced by light damage. 【Methods】 Two weeks after female SD rats were castrated, they were divided into the following six groups: control group (control), light-damage group (LD), saline group, saline light-damage group (saline-LD), βE2 group, and βE2 light-damage group (βE2-LD). Rats in the light-damage were exposed to 8000-lux fluorescence for 12 h after 18 h of dark adaptation. Then electroretinogram (ERG), immunofluorescence, Real-time PCR and immunohistochemical detection were performed after one day of dark recovery. 【Results】 The results of ERG showed that ERG was lower in LD group than in control group (P<0.05). After light damage, ROS was increased and the mRNA expressions of antioxidant genes, such as Sod1, Sod2, Cat, Glrx1, Glrx2, Txn1, and Txn2 were decreased (all P<0.05). After βE2 administration, compared with those in saline-LD, ROS level was decreased, the levels of Nrf2 protein and antioxidant genes were increased, and ERG was recovered to a certain extent in βE2-LD (P<0.05). 【Conclusion】 βE2 can restore the function of rat retina, and its mechanism might be related to the upregulation of Nrf2 and antioxidant genes.

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R² = 0.033; P = 0.018), followed by acute kidney injury (AKI; R² = 0.032; P = 0.011) and plasma MIP-1β level (R² = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.
Acute Kidney Injury/complications* ; Bacteria/classification* ; Chemokine CCL4/blood* ; Community-Acquired Infections/microbiology* ; Humans ; Lung ; Microbiota/genetics* ; Pneumonia, Bacterial/diagnosis* ; Prognosis ; RNA, Ribosomal, 16S/genetics*