Lumican is a member of the small leucine-rich proteoglycan family, which is involved in cell processes related to tumorigenesis and development, such as epithelial-mesenchymal transition, cell proliferation, migration, invasion and adhesion. The expression of Lumican in different tumors is positively or negatively correlated with tumor progression, and can be used as a reference for tumor prognosis and efficacy evaluation. Further study of the correlation and potential mechanism between Lumican and tumor therapy resistance can provide new ideas for predicting clinical therapeutic efficacy.

OBJECTIVE To investigate the cellular uptake and in vivo imaging of paclitaxel(PTX)-loaded polyethylene glycol(PEG)-modified rhein conjugate micelles. METHODS (P4/P2+PTX)/CRmP micelles were prepared by co-loading environment-responsive fluorescent probes P4/P2 and PTX into CRmP micelles. Using MCF-7 cells as cell models, the uptake of the micelles by MCF-7 cells was analyzed by laser confocal microscopy and flow cytometry. The H22 subcutaneous transplanted tumor mice were used as animal models, and the distribution of the micelles in vivo and in vitro were analyzed by in vivo imaging system. RESULTS (P4+PTX)/CRmP micelles in the intact form were internalized by MCF-7 cells and distributed in the cytoplasm. (P2+PTX)/CRmP micelles were more accumulated in the liver and tumor sites in vivo, and gradually accumulated at the tumor sites during the experimental time. CONCLUSION The intact micelles can be taken up by tumor cells, and have liver and tumor targeting properties in vivo.

Objective:To explore the effect of endoplasmic reticulum stressed (ER) on colorectal cancer (CRC) cell proliferation and invasion via ATG5-mediated autophagy pathway and the underlying mechanism.Methods:We performed bioinformatics analysis to identify the expression level of PERK, ATF6 and ATG5 in CRC tissues and adjacent tissues and the correlation between PERK and ATG5 expression in CRC tissues.The expression level of PERK in CRC cell lines was examined by qRT-PCR assay. Cell proliferation was quantified by CCK-8.The invasion of the cells was detected by Transwell.Western blot assay was performed to verify the levels of protein. The levels of autophagy were examined by electron microscopy.Results:PERK and ATF6 expression in CRC tissues was higher than that in the adjacent tissues and PERK expression was higher in CRC cells than intestinal mucosal cells. Expression level of PERK in CRC cell lines HCT116,SW480,HT29,LoVo and colonic mucosa cell lines FHC was 1.51±0.04,3.12±0.05,2.19±0.04,2.38±0.06 and 0.98±0.04 ( P<0.001) .The increased expression of PERK promoted CRC cell proliferation and invasion. PERK expression levels was positively associated with ATG5 expression levels ( r=0.52, P<0.001) and overexpression of PERK accelerated the protein expression of ATG5 (1.00±0.04,3.53±0.07, t=74.61, P<0.001) . ATG5 was highly expressed in CRC tissues. Overexpression of ATG5 could promote proliferation,invasion and accelerate autophagy of CRC cells (the number of autophagosomes in the blank control group,the negative control group and ATG5-Overexpression group was 4.33±1.53, 4.00±1.00, 9.67±2.52, and t=3.14,3.62, P=0.035,0.022, respectively) .ATG5 promoted colorectal cancer cell proliferation and invasion through autophagy pathway. Conclusion:ER stressed-CRC cells could promote CRC cell proliferation and invasion through ATG5-mediated autophagy pathway.

Objective To assess the influences of early implementation of patient-controlled epidural analgesia (PCEA) in labor on uterine myoelectrical activity and delivery outcomes. Methods A prospective study was conducted on 240 singleton cephalic primiparae with spontaneous labor at Guangzhou Women and Children's Medical Center from January 2015 to October 2018. Those women, who were ready to accept PCEA, were randomly assigned to early- or late-PCEA group based on cervical dilation of 0-3 cm or 3-6 cm at the time of commencing PCEA, while those who refused PCEA in labor were classified as non-PCEA group. Uterine electromyographic activity and visual analogue score (VAS)were recorded before and 1 h and 2 h after PCEA. Patient satisfaction with labor, duration of the first stage of labor, volume of postpartum bleeding within 2 h after delivery and neonatal Apgar score were compared between different groups using multivariate analysis of variance, repeated measures analysis of variance, LSD-t test or Chi-square test. Results The VAS values 1 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (2.08±1.34 and 2.00±1.28 vs 7.65±1.04, LSD-t were － 27.713 and － 27.663, P<0.001) and those before PCEA (7.65±0.91 and 7.62±0.86, LSD-t were －32.879 and －33.349, P<0.001). The VAS values 2 h after PCEA in the early- and late-PCEA group were both lower than that in the non-PCEA group (1.63±1.53 and 1.41±1.56 vs 7.66±0.87, LSD-t were －27.018 and －27.823, P<0.001) and those before PCEA (LSD-t were －31.379 and －32.718, P<0.001).The patient satisfaction rate with labor was higher in the early-PCEA group comparing to the late-PCEA group [80.0% (72/90) vs 61.1% (55/90), P<0.001], and the two figures above were both higher than that of the non-PCEA group [20.0% (12/60), both P<0.001]. There was no significant difference in the duration of the first stage of labor, the volume of postpartum blood loss 2 h after delivery, oxytocin usage rate, the rate of convertion to cesarean section, neonatal birth weight or Apgar score at 1 or 5 min among the three groups (all P>0.05). There was also no significant difference in uterine electromyographic parameters among the three groups before or 2 h after PCEA (all P>0.05). The number and duration of burst, power density spectrum peak frequency, root mean square and total power 1 h after PCEA in the early- and later-PCEA group were all lower than those in the non-PCEA group [4.80±2.49 and 5.54±3.04 vs 9.67±2.44; (34.41±1.21) and (36.94±1.18) vs (41.68±1.53) s; (0.36±0.08) and (0.36±0.07) vs (0.48±0.05) Hz ; (0.05±0.04) and (0.05±0.05) vs (0.07±0.05) mV; (4.33±0.51) and (5.36 ±0.59) vs (9.90±1.43) pV2; all P<0.05]. Conclusions The effect of PCEA on uterine myoelectrical activity has no association with the commencing time. While early PCEA could alleviate the labor pain as soon as possible, which enable us to improve the efficacy of labor analgesia, patient satisfaction and maternal and neonatal safety without increasing cesarean section rate.

Objective The present study was undertaken to examine the regulatory effect of endogeous sulfur dioxide (SO2) on interleukins in rats with acute lung injury (ALI) induced by sepsis.Methods Twenty Two male Sprague Dawley (SD) rats were randomly (random number) divided into sham group (Control group),sham + SO2 donor (Na2SO3/NaHSO3,0.54 mmol/kg:0.18 mmol/kg) group (SO2 group),sepsis induced ALI group (sepsis group) and sepsis induced ALI with sulfur dioxide pretreatment group (sepsis + SO2 group).Index of quantitative assessment of histological lung injury (IQA),wet/dry weight ratio (W/D) and the level of SO2 in plasma were measured.IL 6,IL 8,IL 10,MCP-1 and TNF-α were measured by ELISA.Results The IQA score and W/D ratio of lung tissues significantly increased in sepsis rats compared with control group (all P ＜ 0.01),but significantly decreased in sulfur dioxide pretreatment rats compared with in sepsis rats (all P ＜0.01).The level of SO2 in plasma decreased in sepsis rats (3.17 ± 3.44) μmol/L compared with control group (5.87 ± 1.96) μmol/L,but significantly increased in sulfur dioxide pretreatment rats (9.78 ± 3.26) μmol/L compared with in sepsis rats (P ＜0.01).The level of IL 6,IL 8,IL 10,MCP-1 and TNF-α significantly increased in sepsis rats [(87.08 ± 22.03) pg/mg,(79.82 ± 19.69) pg/mg,(66.38 ± 21.77) pg/mg,(157.58 ± 42.36) pg/mg and (65.04 ± 19.42) pg/mg,respectively] compared with control group [(47.41±9.64) pg/mg,(42.25±8.16) pg/mg,(31.96±4.63) pg/mg,(67.65±10.18) pg/mg and (33.83 ± 5.75) pg/mg] (all P ＜ 0.01).but the level of IL 6,IL 8,IL 10 significantly decreased in sulfur dioxide pretreatment rats [(66.01 ± 16.52) pg/mg,(61.52 ± 18.32) pg/mg and (45.61 ± 16.47) pg/mg,respectively] compared with sepsis group (all P ＜ 0.05).The level of MCP-1 significantly decreased in sulfur dioxide pretreatment rats (117.86 ± 34.20) pg/mgcompared with sepsis group (all P ＜0.01).The level of TNF-α decreased in sulfur dioxide pretreatment rats (61.49 ± 15.33 pg/mg) compared with sepsis group.Conclusions These results suggested that exogenous SO2 could inhibit the pulmonary tissue inflammatory response by inhibiting MCP-1 and TNF-α in rats with sepsis induced ALI.

OBJECTIVETo explore the mechanism of podophyllotoxin nanostructured lipid carriers (POD-NLC)-induced apoptosis of VK2/E6E7 cells mediated by endoplasmic reticulum stress (ERS).

METHODSVK2/E6E7 cells cultured in vitro were exposed to 0.125, 0.25, and 0.5 µg/ml POD-NLC or blank NLC for 24 h. The intracellular calcium concentration was measured by laser scanning confocal microscopy (LSCM), and the expression levels of GRP78, GRP94, and calpain2 mRNA and proteins in the cells were detected using RT-PCR and Western blotting.

RESULTSCompared with the control cells, the cells exposed to POD-NLC showed a concentration-dependent increase of intracellular calcium concentration (P<0.01), and the differences were statistically significant between different dose groups (P<0.05). RT-PCR and Western blotting showed that POD-NLC up-regulated GRP78, GRP94 and calpain2 mRNA and proteins expressions, which showed significant differences between blank-NLC and the control groups (P>0.05).

CONCLUSIONPOD-NLC induces apoptosis of VK2/E6E7 cells possibly by triggering the endoplasmic reticulum stress response.

Apoptosis ; Calcium ; metabolism ; Calpain ; metabolism ; Cell Line ; Endoplasmic Reticulum Stress ; HSP70 Heat-Shock Proteins ; metabolism ; Heat-Shock Proteins ; metabolism ; Humans ; Membrane Proteins ; metabolism ; Nanostructures ; chemistry ; Podophyllotoxin ; chemistry ; RNA, Messenger

Objective To explore the mechanism of podophyllotoxin nanostructured lipid carriers (POD-NLC)-induced apoptosis of VK2/E6E7 cells mediated by endoplasmic reticulum stress (ERS). Methods VK2/E6E7 cells cultured in vitro were exposed to 0.125, 0.25, and 0.5 μg/ml POD-NLC or blank NLC for 24 h. The intracellular calcium concentration was measured by laser scanning confocal microscopy (LSCM), and the expression levels of GRP78, GRP94, and calpain2 mRNA and proteins in the cells were detected using RT-PCR and Western blotting. Results Compared with the control cells, the cells exposed to POD-NLC showed a concentration-dependent increase of intracellular calcium concentration (P<0.01), and the differences were statistically significant between different dose groups (P<0.05). RT-PCR and Western blotting showed that POD-NLC up-regulated GRP78, GRP94 and calpain2 mRNA and proteins expressions, whish showed significant differences between blank-NLC and the control groups (P>0.05). Conclusion POD-NLC induces apoptosis of VK2/E6E7 cells possibly by triggering the endoplasmic reticulum stress response.

Objective To explore the mechanism of podophyllotoxin nanostructured lipid carriers (POD-NLC)-induced apoptosis of VK2/E6E7 cells mediated by endoplasmic reticulum stress (ERS). Methods VK2/E6E7 cells cultured in vitro were exposed to 0.125, 0.25, and 0.5 μg/ml POD-NLC or blank NLC for 24 h. The intracellular calcium concentration was measured by laser scanning confocal microscopy (LSCM), and the expression levels of GRP78, GRP94, and calpain2 mRNA and proteins in the cells were detected using RT-PCR and Western blotting. Results Compared with the control cells, the cells exposed to POD-NLC showed a concentration-dependent increase of intracellular calcium concentration (P<0.01), and the differences were statistically significant between different dose groups (P<0.05). RT-PCR and Western blotting showed that POD-NLC up-regulated GRP78, GRP94 and calpain2 mRNA and proteins expressions, whish showed significant differences between blank-NLC and the control groups (P>0.05). Conclusion POD-NLC induces apoptosis of VK2/E6E7 cells possibly by triggering the endoplasmic reticulum stress response.

Objective To explore the effects of proton pump inhibitors (PPIs) therapy on esophageal acid exposure of patients with gastroesophageal reflux disease(GERD),and the correlation of anxiety and depression with recurrence of acid-related symptoms after discontinuation of PPIs.Methods From February 2010 to June 2011,28 patients with GERD diagnosed by ambulatory 24 h esophageal pH monitoring admitted to Beijing Jishuitan Hospital were treated with esomeprazole 20 mg 2 times/d for 8 weeks (male 16,female 12).Symptoms after drug discontinuation were monitored.Ambulatory 24 h esophageal pH monitoring was performed on patients,whose symptom recurred within 8 weeks after treatment.BMI,Self-rating Anxiety Scale(SAS),and Self-rating Depression Scale (SDS) were detected.Results Among the 28 patients with GERD,15 (53.6％) recurred symptoms after withdraw of PPIs.Compared with the asymptomatic group after withdraw of PPIs,the pretreatment duration of pH 4 (supine),24 h total acid reflux time,number of time periods with acid reflux ＞5 minutes,the maximal acid reflux time and 24 h total number of acid reflux in the symptomatic recurrence group were statistically significantly increased ( 11.7％vs 4.5％,138.8 minutes vs 62.1 minutes,6.0 vs 2.0,27.0 minutes vs 12.4 minutes,74.0 times vs43.0times,respectively,all P values ＜ 0.05 ).There were no significant differences in BMI,SAS and SDS between the two groups.Conclusions The basic level of esophageal acid exposure of patients with GERD before PPIs therapy may influence the esophageal acid exposure after PPIs therapy and then may affect the recurrence of symptoms.Although anxiety and depression is common in patients with GERD,it is not found that the recurrence of acid-related symptoms after the discontinuation of PPIs therapy is related to the anxiety and depression.

ObjectiveTo probe into the influence of the zero price margin for drugs on the revenue-expenditure structure at primary healthcare organizations.MethodsOne of the pilot districts experimenting with this system in Ningbo city was earmarked as the research object.Within this district,the data of their revenue,expenditure and surplus were collected from 20 primary healthcare organizations prior to and after the zero price margin for drugs was in place for classification analysis.ResultsThe percentage of service revenue among the total revenue has dropped from 68.34％ before the system was in place to 65.44％ after,reducing 4.24％.The percentage of drug revenue has dropped from 71.68％ before to 63.57％ after,reducing 11.31％.The percentage of service surplus has dropped from 15.81％ before to - 23.07％ after,reducing 245.94％.The total standard workload has increased 61.77％.Average medical expense per outpatient and per inpatient has reduced 32.85％ and 57.18％,from 71.44yuan and 2642.08 yuan before to 48.33 yuan and 1131.28 yuan after respectively.ConclusionThe deficit rise and higher percentage of drug revenue at primary healthcare organizations deserve attention.A comprehensive reform is recommended to establish a regular government financial support mechanism,further adjust the revenue-expenditure structure,set up the system of rational drug use,and effectively reduce the medical expense of patients.