Objective To explore the expression of miR-221/222 in non-small cell lung cancer (NSCLC) and its correlation with clinical pathological parameters. Methods The clinical pathological data and formalin fixed-paraffin embedded (FFPE) tissues of 55 NSCLC patients and 10 benign lesion patients who underwent surgery in the First Affiliated Hospital of Nanhua University from February 2012 to May 2014 were collected and followed. The relationship between miR-221/222 expression detected by real-time PCR and clinical pathological parameters and progression-free survival (PFS) were analyzed. The differential survival between the high expression group and the low expression group of miR-221/222 were compared. A Cox proportional hazard regression model was utilized to examine the prognostic factors of NSCLC. Results The expression level of miR-221/222 was significantly higher in tumor tissues than that in corresponding benign lesion tissues (Fold change=3.52, P=0.000;Fold change=2.01, P=0.000). There was a negative correlation between miR-221/222 expression and pathological grades (r=-0.732, P=0.000;r=-0.451, P=0.001). The relative expression of miR-221 showed a positive correlation with miR-222 (r=0.376, P=0.000). Patients with higher levels of miR-221/222 were closely associated with a shorter PFS (miR-221: 55.43 weeks vs. 81.29 weeks, P=0.028; miR-222: 45.00 weeks vs. 87.04 weeks, P=0.008). Finally, multivariate analysis demonstrated that miR-222 expression was independently associated with poor PFS (RR=2.808, P=0.033). Conclusions miR-221/222 is highly expressed in NSCLC tumor tissues with a positive correlation. A negative correlation is observed between the expression of miR-221/222 and tumor differentiation. The potential high expression of miR-221/222 is considered as tumor biomarkers for the prognosis of NSCLC patients.

Objective:To explore the correlation between fluoride intake and serum alkaline phosphatase (ALP) in pregnant women of different gestational periods in endemic fluorosis area.Methods:Pregnant women in Rencheng District, Jinxiang County, Jiaxiang County of Jining City and Yuncheng County of Heze City were selected in April 2020. According to the gestational weeks, pregnant women were divided into early pregnancy group (0 - 12 weeks), middle pregnancy group (13 - 27 weeks) and late pregnancy group (> 27 weeks). The levels of urinary fluoride, ALP, osteocalcin (BGP), C-terminal peptide of β-Ⅰ collagen (β-CTX) and N-terminal propeptide of type Ⅰ collagen (PINP) of pregnant women in each group were measured, and the correlation between urinary fluoride and ALP, BGP, β-CTX, and PINP in pregnant women of different gestational periods was analyzed.Results:A total of 372 pregnant women were selected, including 97 cases in early pregnancy group, 169 cases in middle pregnancy group and 106 cases in late pregnancy group. There was no significant difference in urinary fluoride level between the three groups [(1.20 ± 0.25), (1.23 ± 0.19), (1.24 ± 0.30) mg/L, P > 0.05]. There was significant difference in serum ALP among the three groups ( P < 0.05), among them, the ALP level in early pregnancy was significantly lower than those of middle pregnancy group and late pregnancy group ( P < 0.05), and the ALP level in middle pregnancy was significantly lower than that of late pregnancy group ( P < 0.05). There was no significant differences in serum β-CTX among the three groups ( P > 0.05). There were significant differences in serum BGP and PINP levels among the three groups ( P < 0.05). The serum BGP and PINP levels in late pregnancy group were significantly higher than those of early pregnancy group and middle pregnancy group ( P < 0.05), and there were no significant differences in serum BGP and PINP levels between early pregnancy group and middle pregnancy group ( P < 0.05). There was a significant positive correlation between urinary fluoride and ALP in early pregnancy group ( r = 0.364, P < 0.05), but no significant correlation between urinary fluoride and BGP, β-CTX and PINP ( r = 0.164, 0.117, 0.136, P > 0.05). There was a significant positive correlation between urinary fluoride level and ALP in middle pregnancy group ( r = 0.417, P < 0.05), but no significant correlation between urinary fluoride level and BGP, β-CTX and PINP ( r = 0.127, 0.108, 0.129, P > 0.05). There was no significant correlation between urinary fluoride level and ALP, BGP, β-CTX and PINP in late pregnancy group ( r = 0.179, 0.158, 0.184, 0.149, P > 0.05). Conclusions:The urinary fluoride level of pregnant women in endemic fluorosis area is relatively stable in gestational period. The urinary fluoride level affects the ALP secretion of pregnant women in early and middle pregnancy. It is still necessary to strengthen the measures of improving water quality and defluoridation to reduce the impact of excessive fluoride intake on pregnancy complications in endemic fluorosis area.

Objective To further understand potential mechanism of miRNAs in bladder cancer .Mtehods Human microarray was used to analyze the expression of miRNAs in four pair human BC cancer tissues and adjacent normal tissues.Then RT-Qpcr was used to verified that the expression of two most up -regulated miRNAs and target genes for results of miRNA/Mrna microarray.Subsequently, it was deduced that miR-130b-3p could target at PTEN through a bioinformatics approach and dual-luciferase reporter assay.CCK8, EDU, flow cytometry, wound healing, Transwell and cytoskeleton assay were applied to prove that miR-130b could affect proliferation, apoptosis, migration and invasion of BC cells.The effects of PTEN regula-ted by miR-130b-3p on the key target protein expression of PI 3K/AKT and integrin β1/FAK signaling pathway were determined by Western blot.Resulst miR-130b-3p was significantly up-regulated and nega-tively correlated with PTEN expression in clinical bladder cancer specimens as compared with normal urothelial tissue.miR-130b-3p mimics could down-regulate PTEN expression, which leads to the activation of PI3K/AKT and integrinβ1/FAK signaling pathway related to cell proliferation , migration and invasion in bladder cancer EJ cells.When the cells were transfected with miR-130b-3p inhibitors, they could be sur- veyed with rearranging cytoskeleton.Conclusions miR-130b/PTEN may be used as a marker for bladder cancer.

OBJECTIVETo identify non-invasive biomarkers for diagnosis and/or prognosis of liver fibrosis in chronic hepatitis B (CHB).

METHODSPeripheral blood samples were obtained from 48 patients with CHB, including 24 with mild fibrosis (stage 1, S1) and 24 with severe fibrosis (stage 4, S4), and subjected to Ficoll density gradient centrifugation in order to obtain enriched samples of peripheral blood mononuclear cells (PBMCs).The PBMC proteomes of the two groups were assessed by first separating the total proteins by two-dimensional gel electrophoresis (2DE) and then identifying the differentially expressed proteins by liquid chromatography combined with tandem mass spectrometry (LCMS/MS).

RESULTSThe enriched PBMC samples from the S1 group and the S4 group had similar amounts of platelets [(19.268+/- 6.413) * 109/L and(19.480+/- 6.538) * 109/L, respectively); however, for both, the platelet amounts were 5 to 15-fold lower than that of the normal reference (100-300 *109/L). There was no significant difference found between the platelet amounts in the S1 patients and healthy controls (P=0.930). Twelve differentially expressed proteins were identified through 2DE-LC-MS/MS, including proteins such as moesin and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 that are involved in various biological processes like cell movement, cell adhesion, kinase signaling and transcription.

CONCLUSIONs The 12 proteins with differential expression in S1 and S4 patients with CHB and liver fibrosis may represent markers related to development and/or progression of liver fibrosis.

Biomarkers ; Disease Progression ; Electrophoresis, Gel, Two-Dimensional ; Hepatitis B, Chronic ; complications ; Humans ; Leukocytes, Mononuclear ; chemistry ; metabolism ; Liver Cirrhosis ; etiology ; metabolism ; pathology ; Mass Spectrometry ; Prognosis ; Proteome ; Proteomics ; Tandem Mass Spectrometry

Objective To investigate the changes of verbal fluency test(VFT) in patients with castration resistant prostate cancer(CRPC) after chemotherapy.Methods 61 patients with CRPC were recruited.Thirty-one of those patients voluntarily accepted chemotherapy as CT group.The other thirty patients who did not received chemotherapy served as control group.CT group underwent VFT assessments at 3 time points:pre-chemotherapy (T1),during-chemotherapy (T2) and post-chemotherapy (T3).Patients in the control group were also assessed at the same time.Results (1) In phonetic fluency tasks,the interaction of time and group (time×group) between the CT group and control group was insignificant in the aspects of word capacity,cluster size,mean cluster size and phonetic switches(P＞0.05).The effect of time between the CT group and control group was significant difference in word capacity,cluster size,mean cluster size and phonetic switches(P＜0.05),but the effect of group was not significant(P＞0.05).CT group and control group both produced more words at T2 and T3 compared with that at T1 (P＜0.05).CT group had a lower score in cluster size and average cluster size than that of the control group at T3 ((6.17 ± 2.71) vs (7.64 ± 2.36),(3.14±0.78)vs (4.28± 1.53),P＜0.05).(2)In semantic fluency tasks,the interaction of time and group (time×group) between the CT group and control group was insignificant in the aspects of word capacity,cluster size,mean cluster size and semantic switches(P＞0.05).The effect of time between the CT group and control group was significantly different in word capacity,cluster size and semantic switches(P＜0.05),but the effects of groups and the effect of time in mean cluster were not significantly different(P＞0.05).The control group produced more words at T2 and T3 than T1 (P＜0.05).The CT group had a smaller cluster size at T3 than T1 and T2,and it was aslo smaller than control Group(P＜0.05).CT group had smaller cluster size at T3 than T2 ((5.47± 1.28) vs (7.15± 1.49),P＜ 0.05).At T3,the semantic switches of the CT group were more than T1,but less than control Group((20.81 ±3.63) vs (19.36±4.84) vs (21.54±6.18),P＜ 0.05)).The semantic switches of CT group were less at T2 than T1 ((18.25±4.25) vs (19.36±4.84),(P＜0.05)).Conclusion Standard dose chemotherapy has no significant impairment on the verbal fluency of patients with CRPC.Chemotherapy does not induce the impairment of patients' phonetic fluency,but may have a negative influence on semantic fluency.

Objective To learn the biovars,antimicmbial susceptibility in Ureaplasma species isolated from respiratory tracts of infants hospitalized in tertiary children's hospital,and to provide evidences and clinical basis for the prevention and treatment of Ureaplasma infection in infants.Methods Ureaplasma species cultivation,identification and antibiotic susceptibility testing were performed using Mycoplasma IST2.The primers according to the conservative MB-Ag gene were designed to identify Ureaplasma biovars.Erythmmcin resistant genes (ermA,ermB and ermC) and active effiux transporter genes (mefA/E,msrA/B and mreA) were amplified using PCRs.Results A total of 78 Ureaplasma positive cases,of them,48 Ureaplasma strains were isolated from premature neonates.Biovar 1 was present in 51 (65.38％) strains,and biovar 2 was present in 27 (34.62％) strains.There were no significant differences among sex,premature infant,age,gestational age,birth weight,length of stay (P ＞ 0.05).The drug resistance rates to ciprofloxacin and ofloxacin were 80.77％,and to tetracycline was 1.28％.All strains were sensitive to doxycycline,josamycin and pristinomycin.The drug resistance rates to the macrolide antibiotics (erythromycin,azithromycinand and clarithromycin) were ＜ 12％.There was no statistically significant difference among the drug resistance rates of different biovars and these antibiotics (P ＞ 0.05).Only the methylated enzyme gene (ermB) and the active efilux pump gene (msrA/B) were detected,and the detection rate was 39.74％ and 12.82％ respectively.The ermB gene mainly exists in biovar 2,and the detection rate is 55.56％ (P ＜ 0.05).The msrA/B was balanced distributed between biovar 1 and 2 (P ＞ 0.05).A total of 78 Ureaplasma strains were isolated from 24 cases of neonatal septicemia,30 cases of congenital infection pneumonia,9 cases of retinopathy of prematurity,9 cases of neonatal intracranial hemorrhage,and 15 cases of bronchopulmonmT dysplasia.Conclusion Biovar 1 is more prevalent in Ureaplasma species isolated from infant respiratory tract,and higher detection rate of Ureaplasma is found in the preterm infants.All Ureaplasma strains have high drug resistance to both ciprofloxacin and ofloxacin,but low drug resistance to the macrolide antibiotics (erythromycin,azithromycin and clarithromyc),that could be used as a first choice for the treatment of Ureaplasma infection.Erythromycin resistance gene ermB,mainly exists in biovar 2.

Objective:To investigate the protective role of extracellular signal-regulated kinase (ERK) signaling pathway in the process that vasonatrin peptide (VNP) reduces hepatic ischemia-reperfusion injury in rats.Methods:Twenty SD rats, weighting 200-250 g, were randomly divided into four groups and each group has five rats. The four groups were sham operation group (S group), ischemia-reperfusion group (I/R group), VNP group (V group) and PD98059+ VNP group (P+ V group). In the rat model of hepatic warm ischemia and reperfusion, the hepatic artery and portal vein of the left lobe and middle lobe of the liver were clamped with arterial clamp for 45 min followed by reperfusion for 120 min. In the V group, VNP (50 μg/kg) was injected 10 minutes before ischemia. In the P+ V group, PD98059 (2 mg/kg) was injected 20 min before VNP injection followed by VNP administration and I/R treatment. The serum levels of alanine amino transaminase (ALT), aspartate amino transferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and the superoxide dismutase (SOD) in liver tissue homogenate and malondialdehyde (MDA) were measured. The histopathology of liver tissue was observed. The contents of p-ERK1/2 were detected by Western blot.Results:Compared with S group, in I/R group and P+ V group the serum levels of ALT [(489.65±11.22), (333.05±24.77) vs. (33.78±4.88) U/L], AST [(651.43±14.99), (503.18±21.48) vs. (154.84±12.32) U/L], TNF-α [(12.83±1.09), (9.64±0.57) vs. (2.11±0.11) ng/L], IL-1β [(7.19±0.62), (5.12±0.22) vs. (1.10±0.49) ng/L], MDA [(8.00±0.88), (5.60±1.01) vs. (2.76±1.29) μmol/mg] increased, while SOD [(54.89±10.60), (68.85±8.33) vs. (126.10±15.63) nmol/mg]decreased (all P<0.05). The histopathology of liver tissue revealed that liver structure damaged more seriously in I/R group and P+ V group. Western blot analysis showed that p-ERK1/2 decreased significantly in I/R group and P+ V group. Compared with I/R group, ALT, AST, MDA, TNF-α and IL-1β decreased significantly and SOD increased significantly in V group (all P<0.05). The histopathology of liver tissue revealed that liver structure was damaged slightly, and p-ERK1/2 increased significantly in V group compared with I/R group ( P<0.05). Conclusion:VNP can significantly reduce hepatic ischemia-reperfusion injury through activation of p-ERK1/2 signaling pathway and inhibition of hepatocyte inflammatory response.

Objective:To evaluate the clinical efficacy and failure patterns of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) on the basis of modern chemoradiotherapy and diagnostic techniques.Methods:In this retrospective study, clinical data of 201 LS-SCLC patients treated with chemotherapy (EP/CE regimens, ≥4 cycles) and intensity-modulated radiotherapy (IMRT) in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2014 were reviewed. All patients were primarily managed with concurrent or sequential chemoradiotherapy and achieved complete response (CR) or partial response (PR). Ninety percent of patients were revaluated for brain metastasis (BM) by MRI and 10% by CT scan. Long-term survival and failure patterns were compared between the PCI ( n=91) and non-PCI groups ( n=110). Results:The median follow-up time was 77.3 months (95% CI 73.0-81.5 months). The median overall survival (OS), 2-and 5-year OS rates were 58.5 months, 72.5% and 47.7% in the PCI group, and 34.5 months, 61.7% and 35.8% in the non-PCI group ( P=0.075). The median progression-free survival (PFS), 2-and 5-year PFS rate were 22.0 months, 48.0% and 43.4% in the PCI group, significantly higher than 13.9 months, 34.4% and 26.7% in the non-PCI group ( P=0.002). The 2- and 5-year cumulative incidence of BM were 6.6% and 12.2% in the PCI group, and 30.0% , 31.0% in the non-PCI group ( P=0.001). The median time and rate of BM as an isolated first site of relapse were 11.9 months and 4.4% in the PCI group, and 8.7 months and 25.5% in the non-PCI group ( P<0.001). Multivariate analysis showed that response after chemoradiotherapy ( P<0.001) and PCI ( P=0.033) were the independent prognostic factors for PFS. Stratified analysis demonstrated that PCI significantly improved the 5-year PFS in patients who achieved CR (72.7% vs. 48.0%, P=0.013), while it did not improve the 5-year PFS in patients who obtained PR (26.1% vs. 20.2%, P=0.213). Conclusion:In the new era of standard chemoradiotherapy and more accurate diagnostic methods for BM, PCI was associated with improved PFS and lower incidence of BM in LS-SCLC patients.

Objective To evaluate the value of perioperative multimodal stratified analgesia guided by PPRS-CYMZ 2.0. Methods One hundred and sixteen patients of both sexes, aged 16-85 yr, of A-merican Society of Anesthesiologists physical statusⅠ-Ⅲ, scheduled for elective surgery in our hospital in August 2016, were included in this study and assigned into empirical analgesia group(group E, n=79) and stratified analgesia group(group S, n=73). The risk of postoperative pain was estimated by an expe-rienced associate chief anesthesiologist based on his clinical experience, and the perioperative analgesic protocol was determined in group E. The risk of postoperative pain was assessed using the perioperative pain risk scale PPRS-CYMZ 2.0 by another experienced associate chief anesthesiologist, the risk was stratified according to the scores, and the corresponding stratified analgesic protocol was determined in group S. Vis-ual analog scale scores and parents′satisfaction with analgesia were recorded on postoperative day 30. The requirement for preventive analgesia, total pressing times of patient-controlled analgesia(PCA)pump in 0-6 h, 6-24 h and 24-72 h periods, PCA background infusion dose and consumption of rescue analgesics were recorded. The development of adverse events during postoperative hospital stay and postoperative re-covery were also recorded. Analgesia-related parameters of medical economics were calculated. Results There was no significant difference in postoperative pain risk stratification between group E and group S(P>0.05), and the majority of patients were at moderate risk. Compared with group E, no significant change was found in visual analog scale scores on postoperative day 30, PCA background infusion dose or incidence of postoperative adverse effects(P>0.05), the requirement for preventive analgesia and satisfaction scores were significantly increased in high risk patients, the consumption of rescue analgesics was decreased in moderate risk patients(P<0.05), no significant change was found in the total pressing times of PCA pump in each time period in low risk patients(P>0.05), the total pressing times of PCA pump was significantly decreased, and the direct analgesic cost per patient and total analgesic cost were decreased in moderate and high risk patients, and the first ambulation time and length of postoperative hospital stay were shortened in high risk patients in group S(P<0.05). Conclusion PPRS-CYMZ 2.0 can achieve perioperative multi-modal stratified analgesia and individualized treatment.

Objective To compare the clinical efficacy and toxicity between nedaplatin-and cisplatin-based regimens in patients with unresectable locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemoradiotherapy.Methods From January,2015 to December,2016,patients with unresectable locally advanced NSCLC receiving concurrent chemoradiotherapy were included in this study.Patients received thoracic radiotherapy (RT) combined with nedaplatin-based concurrent chemotherapy were enrolled in the nedaplatin group (n=38).Those treated with thoracic RT combined with cisplatin-based chemotherapy were allocated into the cisplatin group (n=84).The chemotherapy regime consisted of platinumin combination with paclitaxel or etoposide.Platinum combined with pemetrexed was adopted in patients with adenocarcinoma.Overall,the median age was 58 years old.Most of the patients were male (86.1％),77.0％ of them had a history of smoking and 63.9％ of the patients were pathologically diagnosed with squamous cell carcinoma.Besides,59.0％ of the patients had Ⅲ B NSCLC.Results In the nedaplatin and cisplatin groups,the overall response rate (ORR) was 79％ and 86％,and the disease control rate was 94％ and 94％.The median follow-up time was 20 months.In the nedaplatin group,the 1-and 2-year PFS was 49％ and 23％,and 67％ and 39％ in the cisplatin group (P=0.160).In the nedaplatin group,the 1-and 2-year OS was 91％ and 72％,and 89％ and 68％ in the cisplatin group (P=0.552).Nine patients (24％) had ≥grade 3 adverse events in the nedaplatin group and 25 patients (30％) in the cisplatin group (P=0.488).No statistical significance was found in radiation-induced esophagitis,bone marrow suppression and gastrointestinal toxicity between two groups.One patient in the nedaplatin group presented with grade 3 radiation-induced pneumonitis and 2 patients died of radiation-induced pneumonitis in the cisplatin group.Conclusions Thoracic radiotherapy combined with nedaplatin-based chemotherapy is a promising option for patients with unresectable locally NSCLC.Compared with the cisplatin-based chemotherapy,nedaplatin-based regime yields equivalent clinical efficacy and less adverse events,especially suitable for the elderly patients with poor tolerance.