Objective To evaluate the efficacy of 0. 3％ sodium hyaluronate ophthalmic solution in mild.to. moderate dry eye patients. Methods A prospective,multicenter,and self.controlled clinical trial was performed on 200 patients who were diagnosed as mild.to.moderate dry eye from January 2015 to June 2017 in Eye Institute of Xiamen University,Eye &ENT Hospital of Fudan University,Zhongshan Ophthalmic Center,Xiangya Hospital Central South University, Eye Hospital of Wenzhou Medical University, and Beijing Tongren Hospital, Capital Medical University. The study protocol was approved by the Ethics Committees of Eye Institute of Xiamen University,written informed consent was obtained from each patient prior to any medical examination. All patients were treated with 0. 3％ sodium hyaluronate ophthalmic solution 6 times per day ( one drop each time) for 28 days. Corneal fluorescein sodium staining,tear film break.up time (BUT),SchirmerⅠtest (SⅠt),degree of conjunctival hyperemia,eyelid margin,meibomian gland secretion,secretory capacity of meibomian gland and subjective symptoms were assessed at baseline,on the 14th day and 28th day after treatment. Bulbar impression cytology was evaluated at baseline and on the 28th day after treatment. Irritation of 0. 3％ sodium hyaluronate ophthalmic solution was estimated on the 14th day and 28th day after treatment. Results The total score of subjective symptoms,BUT,SⅠt,degree of conjunctival hyperemia were significantly different among different treatment time points( F=108. 969,27. 598,16. 838,36. 750;all at P<0. 01). Compared with before treatment,the total score of subjective symptoms was significantly decreased, the degree of conjunctival hyperemia and the total corneal fluorescein sodium staining point number were significant decreased on the 14th day and 28th day after treatment. The total score of subjective symptoms,degree of conjunctival hyperemia and total corneal fluorescein sodium staining point number on the 28th day after treatment were significant lower than those on the 14th day after treatment. Compared with before treatment,the BUT was significantly longer and the SⅠt scores were significantly increased on the 14th day and 28th day after treatment. The BUT on the 28th day after treatment was significantly longer than that on the 14th day after treatment;no significant difference in SⅠt was observed between the 28th day and the 14th day after treatment. The scores of palpebral margin change,meibomian gland secretory ability and secretion characteristics were not significantly different among different treatment time points(H=0. 255,2. 356,0. 294;all at P>0. 05). The impression cytology grade on the 28th day after treatment was 1. 08±0. 74,which was significantly lower than 1. 53±0. 76 before treatment (t=5. 979, P<0. 01). The number of goblet cells on the 28th day after treatment was significantly higher than that before treatment(U=1806. 500,P<0. 01). On the 14th day after treatment,70％ of the patients indicated that the drug was non.irritating,and no patient had intolerable irritation affecting daily lives. All patients had good tolerance to this drug. Conclusions The use of 0. 3％ sodium hyaluronate eye drops can improve the symptoms and signs of mild to moderate dry eye,which can be widely used for mild.to.moderate dry eye patients in clinic.

OBJECTIVE: To investigate the factors that influence the progression-free survival time (PFS) of patients with non-squamous cell carcinoma type non-small cell lung cancer (NSCLC) after first chemotherapy, and to provide reference for the formulation of clinical individual treatment regimen. METHODS: Clinical information of 84 patients with non-squamous cell carcinoma type NSCLC after first chemotherapy were selected from our hospital during Jan. 2012-Dec. 2014. The effects of patient's factors [gender, age, performance status (PS) score], disease factors [tumor staging, tumor marker (TM) level] and treatment factors (chemotherapy regimen and treatment course, chemotherapy efficacy) on PFS were analyzed retrospectively. RESULTS: All patients were followed up for 11. 933 months averagely (final follow-up time of Jun. 30th, 2017), and their median PFS was 4. 017 months. The median PFS of male was slightly shorter than that of female; the median PFS of patients aged more than 65 year-old was slightly shorter than that of patients aged below 65 year-old; the median PFS of patients with PS score of 0-1 was slightly longer than that of patients with PS score of 2-4, without statistical significance (P＞0. 05). The median PFS of Ⅱ -Ⅲ stage patients was significantly longer than that of Ⅳ stage patients; the median PFS of patients with at least one TM index was 10 times higher than the upper limit of the normal value was significantly shorter than that of patients with four TM indexes were all 10 times lower than the upper limit of the normal value; the median PFS of patients underwent 1-3 treatment courses was significantly shorter than that of patients underwent 4-6 treatment courses; the median PFS of patients with progressive disease efficacy was significantly shorter than that of patients with stable disease efficacy or above, with statistical significance (P＜0. 05). Among 84 patients, 81 patients selected PP regimen (pemetrexed disodium+platinum), and other patients chose non-PP regimen. Due to the large difference in the number of cases, the effect of the chemotherapy regimen on the patient' s PFS was not investigated. CONCLUSIONS: The disease factor and treatment factor of patients may be associated with PFS. Tumor staging, at least one TM index was 10 times higher than the upper limit of the normal value, the number of completed chemotherapy treatment course, chemotherapy efficacy are independent influential factors of PFS in patients with non-squamous cell carcinoma type NSCLC.

Objective To evaluate the effect of morphine preconditioning on the expression of miR-133b-Sp and Fas in rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R).Methods Cardiomyocytes were isolated from healthy adult male Sprague-Dawley rats by using Langendorff perfusion.The cells were seeded into 24-well plates or 60 mm diameter dishes and randomly divided into 3 groups (n =24 each) using a random number table:control group (group C),group H/R,and morphine preconditioning group (group MPC).The cells in group C were cultured in normal culture atmosphere.In H/R and MPC groups,the cells were exposed to 95％ N2-5％ CO2 for 90 min followed by 120 min reoxygenation.In group MPC,the cells were cultured for 10 min in serum-free DMEM liquid culture medium containing morphine 1 μmol/L,and then were cultured for 30 min in morphine-free DMEM liquid culture medium before hypoxia.At 120 min of reoxygenation,the cells in 24-well plates were selected to detect the cell viability (by MTT),lactate dehydrogenase (LDH) activity in the culture medium,and cell apoptosis (by Hoechst 33234 staining).Apoptosis rate was calculated.Total RNA and protein were extracted from the cells in 60 mm dishes to detect the expression of miR-133b-5p and Fas mRNA (by quantitative real-time PCR) and Fas protein (by Western blot).Results Compared with C group,the cell viability was significantly decreased,LDH activity and apoptosis rate were increased,the expression of miR-133b-Sp was down-regulated,and the expression of Fas mRNA and protein was up-regulated in H/R group.Compared with H/R group,the cell viability was significantly increased,LDH activity and apoptosis rate were decreased,the expression of miR-133b-5p was up-regulatcd,and the expression of Fas mRNA and protein was down-regulated in MPC group.Conclusion The mechanism by which morphine preconditioning reduces H/R injury to rat cardiomyocytesis related to up-regulation of the expression of miR-133b-Sp and down-regulation of the expression of Fas.

Aim To screen the differentially expressed microRNAs ( miRNAs ) induced by hypoxia precondi-tioning ( HPC ) in adult rat cardiomyocytes, and pre-dict miRNAs-regulated target genes and their func-tions. Methods Cardiomyocytes were isolated from a-dult rat ventricular myocardium and cultured ( in vitro) . The cells were divided into 2 groups: control group ( CON ) and hypoxia preconditioning group ( HPC) . The cardiomyocytes in HPC group were sub-jected to 10 min hypoxia followed by 30 min reoxygen-ation, while the cells in CON group were cultured un-der normal condition. After that, total RNA was ex-tracted and then subjected to miRNA microarray to screen differentially expressed miRNAs. The microar-ray results were further validated by quantitative RT-PCR ( qRT-PCR ) . Bioinformatics analysis was per-formed to predict the miRNAs-regulated target genes and analyze the enriched gene ontology ( GO) and sig-naling pathway ( Pathway) . Results HPC caused sig-nificant changes in miRNAs expression in cardiomyo-cytes as compared to CON group. A total of 12 miR-NAs were up-regulated and 14 miRNAs were down-reg-ulated ( P <0. 01 , FDR <0 . 05 ) . The differentially expressed 7 miRNAs with a fluorescent signal intensity>500 were selected for further bioinformatics analysis. The expression of miR-133b-5p, miR-664-1-5p and miR-6216 detected by qRT-PCR exhibited the similar patterns of up or down regulation to those shown in mi-croarray results. Bioinformatics analysis revealed that miRNAs-regulated target genes were significantly en-riched in 27 GOs and 6 signal pathways. Conclusion
The expression profile of miRNAs in rat cardiomyo-cytes is significantly affected by HPC. These differenti-ally expressed miRNAs might participate in HPC-in-duced cardioprotection by regulating their target genes in rat cardiomyocytes.

Aim To investigate the brain targeting of ginkgolide B prodrug (PGB ) and its mechanism. Methods The liquid chromatography tandem mass spectrometry (LC-MS /MS)method was applied to in-vestigate the pharmacokinetics of PGB in rat brain tis-sue after intravenous injection of PGB.Also the brain targeting was evaluated on the basis of the pharmacoki-netic parameter of PGB.The incomplete cerebral is-chemia model was induced in mouse,the effect of PGB on cerebral capillary permeability was observed by Ev-ans blue method.High performance liquid chromatog-raphy (HPLC)was used to determine the partition co-efficients (logP)of PGB in octanol-water system.PGB and P-glycoprotein (P-gp)was docked by using Mole-gro Virtual Docker (MVD)software to predict its bind-ing abilities with P-gp.The interaction of PGB with ATPase activity of human P-gp membrane was esti-mated by measuring inorganic phosphate liberation. Results The brain targeting of PGB was evaluated by treatment effective (TA ) and drug targeting index (DTI),the calculated value were 6.87 and 4.1 4 re-spectively.Preventive medication of PGB could signifi-cantly decrease cerebral capillary permeability (P <0.05).The lipo-hydropartition coefficient of PGB was higher than that of GB,their logP data were 1 .03 and 0.61 respectively.PGB displayed the stronger binding affinity with P-gp than GB according to the molecular docking calculations,their MolDock Score toward P-gp were -1 43.36 and -1 1 6.40KJ·mol -1 respectively. ATP-hydrolisis showed that PGB increased ATPase activity with a Km of approximately 237.75 μmol · L -1 ,however GB with a Km of approximately 841 .24μmol·L -1 .PGB might interact with P-gp with a high-er affinity and exhibit more effect than GB.Conclu-sion PGB is characterized by its brain targeting. Higher liposolubility of PGB results in good blood-brain permeability,which is advantageous to its brain targe-ting.Besides,PGB can effectively inhibit the efflux effect of P-gp to GB because of its increased P-gp AT-Pase activity.

OBJECTIVE: To understand the relationship between porosity, collagen fiber orientation and strength of the plated bone after rigid plate fixation and removal. METHODS: Seventy-two New Zealand white rabbits were used in this experiment. Eight animals served as control and the other sixty-four were plated on their intact left tibiae with stainless steel (316L) 4-hole plates to induce early osteoporosis. The plates were removed 2 months after internal fixation in 40 plated animals, 8 of which were sacrificed immediately following plate removal and the other 32 were killed in successive groups with 8 in each group 1, 2, 3 and 4 months after plate removal. The remaining 24 plated animals were killed at 3, 4 and 6 months after plate fixation. After sacrifice, the samples of plated bone were prepared for light microscope, quantitative histological analysis, polarized light microscope and biomechanical test. RESULTS: The internal fixation with a rigid plate could induce the regional osteoporosis which manifested both bone loss and disorganized bone structure (loss of the orientation of the collagen fibers) leading to decreased strength of the plated bone. Although the regional osteoporosis could recover gradually after plate removal, the bone structure remained disorderly even when the bone mass returned to normal. Delayed restoration of bone structure was related to delayed restoration of bone strength. CONCLUSIONS: Besides the bone loss, the disorganized bone structure is the main cause of decrease of bone strength after rigid plate fixation and removal.