OBJECTIVE:The effects of zinc fructose diphosphate(ZnFDP)in different concentrations on the growth of cultured newborn mouse cerebral cortex neurons were observed METHODS:The newborn mice cerebral cortex neurons were cultured and different dosages of ZnFDP were added with final concentrations of 2 5?g/ml,12 5?g/ml and 125?g/ml The convert phase microscope was used to observe the growth of dendrites and cell bodies of neurons The survival neuron count and LDH assay were carried out to investigate the effect of ZnFDP on the growth and development of neurons in different culture periods RESULTS:After 48h,the number and the length of neural dendrites in 12 5?g/ml ZnFDP group were increased but the maximum diameter of cell bodies of neurons showed no change There were no significant differences in all parameters observed between 2 5?g/ml group and control group,while 125?g/ml ZnFDP obviously inhibited the differentiation of neurons The survival neurons on 12 5?g/ml ZnFDP group outnumbered those in the control group after 3d,7d and 10d culture,and the LDH activity in 12 5?g/ml ZnFDP group was lower than that in control group after 7d and 10d culture CONCLUSION:This study suggests that a suitable dose of ZnFDP can promote the growth and development of cerebral cortex neurons

Objective To investigate the change characteristics of serum ferritin(SF)and parathormone (PTH)levels in differ-ent stages of chronic kidney disease(CKD)and their correlation with serum beta 2-microglobulin(β2-MG).Methods The levels of serum PTH,SF andβ2-MG in different stages of CKD were detected and the detection results were compared with those in the con-trol group.The correlation between serum SF and PTH withβ2-MG in each stage of CKD was analyzed.Results The level of ser-um PTH,SF andβ2-MG in the compensation group had no statistical difference compared with the control group (P >0.05),while which had statistical differences among the decompensation group,renal failure group and uremia group (P <0.05)The correlation analysis showed that serum PTH was positively correlated with serumβ2-MG in 145 cases(r=0.92,P <0.05),and the serum SF level was also positively correlated with serumβ2-MG level(r=0.92,P <0.05).Conclusion Detecting serum PTH,SF andβ2-MG levels possesses the important clinical significance for understanding CKD condition and prognosis.

Objective To analyse the expression of alpha-fetoprotein variant-L3(AFP-L3)and glypican-3(GPC-3)in primary he-patic carcinoma(PHC)with different concentration of alpha-fetoprotein (AFP),so as to provide references for the diagnosis of PHC.Methods 240 cases of outpatients,inpatients and individuals on physical examination were selected as subjects and serum levels of AFP-L3 and GPC-3 were detected.All of the subjects were divided into negative group(0≤AFP<20 ng/mL),low concen-tration group(20≤AFP<400 ng/mL)and high concentration group(AFP≥400 ng/mL)according to the serum levels of AFP.Ser-um levels of AFP-L3 and GPC-3 were compared among the three groups.And the sensitivity,specificity and accuracy of single de-tection of AFP-L3 or GPC-3 and those of combined detection of AFP-L3 and GPC-3 were compared as well.Results The serum levels of AFP-L3 and GPC-3 in the low concentration group and high concentration group were both higher than those in the nega-tive group,and those in the high concentration group were also higher than those in the low concentration group,had statistically significant differences(P < 0.05 ).The sensitivity,specificity and accuracy of combined detection of AFP-L3 and GPC-3 were 84.4%,95.9% and 93.8% respectively,which were higher than those of single detection of AFP-L3 or GPC-3.Conclusion Com-bined detection of AFP-L3 and GPC-3 could improve the sensitivity,specificity and accuracy for diagnosis of PHC,which has clinical significance for the diagnosis of PHC.

Objective: To observe the effects of manganese( Ⅲ ) meso-tetrakis (N, N'-diethylimidazolium-2-yl) porphyrin (MnTDM) in treatment of early Parkinson's disease(PD) mouse model induced by subcutaneous injection of 1-methyl-4-phenyl1, 2, 3, 6-tetrahydropyridine(MPTP) and to discuss its possible mechanism. Methods:Forty male C57BL/6 mice were evenly randomized into 4 groups: MPTP model group(subcutaneous injection of 25 mg/kg MPTP for 3 days), MnTDM+ MPTP group (15 mg/kg MnTDM was subcutaneously injected 1 h before MPTP injection), MnTDM control group, and normal saline group. Performance of animals in the pole and swimming test was observed 3 days after the last injection. Levels of dopamine (DA) and its metabolites(3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) in the striatum of animals were measured by high-performance liquid chromatography with an electrochemical detector(HPLC-ECD). Thiobarbituric acid (TBA) method was used to examine the levels of malondialdehyde(MDA). Results: Acute injection of MPTP could be used for establishment of PD model. The striatal levels of DA, DOPAC and HVA in MPTP group were significantly lower(P＜0.01)and the striatal level of MDA was significantly higher(P＜0.05) than those of the control group. MPTP had no obvious effect on the behavioral performance of the animals in a short term. MnTDM could partly inhibit the above effects of MPTP. Compared with MPTP group, MnTDM+ MPTP group had significantly higher DA, DOPAC, and HVA levels and significantly lower MDA level(all P＜0.05). There was no significant difference in the behavioral indices of animals between the 4 groups. Conclusion:MnTDM can inhibit lipid peroxidation and promote DA production; it has preventive and therapeutic effects on MPTP induced PD.

Objective To observe the complications and mortality of hyponatremia in patients with acute exacerbation of chronic obstructive pulmonary disease.Methods The patients with acute exacerbation of chronic obstructive pulmonary disease were selected and divided into non -hyponatremia group(252 cases)and hyponatremia group(65 cases).The differences in the general status,serum ions,blood gas,APACHE Ⅱ score,complications dur-ing the hospitalization,using of ventilator and mortality between the two groups were compared,and drew the receiver operating characteristic(ROC)curve,to acquire higher serum sodium cut -off values.Results In the hyponatremia group,the body weight was (68.3 ±14.4)kg,BMI was (25.5 ±4.9)kg/m2 ,those in the non -hyponatremia group were (74.9 ±15.9)kg and (28.2 ±5.3)kg/m2 respectively,there were statistically significant differences(t =2.009,8.494,all P <0.05).The incidence rate of pneumonia in the hyponatremia group was 23.1%,which was higher than 13.1% in the non -hyponatremia group(χ2 =4.007,P =0.045).The hospital days of the hyponatremia group was (13.1 ±8.9)d,which was longer than (7.8 ±4.9)d of the non -hyponatremia group(t =15.638,P =0.000).The invasive ventilation days of the hyponatremia group was (1.1 ±0.4)d,which was longer than (0.9 ± 0.1)d of the non -hyponatremia group(t =2.885,P =0.004).The non invasive ventilation days of the hyponatremia group was (3.1 ±0.8)d,which was longer than (0.8 ±0.3)d of the non -hyponatremia group (t =2.984,P =0.003).The hospital mortality rate of the hyponatremia group was 12.3%,which was higher than 3.1% of the non -hyponatremia group(χ2 =7.189,P =0.007).The 90 -day mortality rate of the hyponatremia group was 29.2%, which was higher than 15.1% of the non -hyponatremia group(χ2 =7.017,P =0.008).When the serum sodium cut-off value was 128.8mmol/L by drawing ROC curve,the mortality rate in patients with lower than this value was 26.3%,while the mortality rate in patients with higher than the value was 3.7%.Conclusion Hyponatremia is related with the severity and prognosis of acute exacerbation of chronic obstructive pulmonary disease.It is most important to prevent and correct hyponatremia at early disease stage.

Objective To evaluate the effect of transversus abdominis plane (TAP) block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia.Methods Forty-eight male patients undergoing laparoscopic tension-free repair of inguinal hernia under general anesthesia,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with body mass index of 20-28 kg/m2,were divided into 2 groups (n =24 each) using a random number table method:TAP block combined with general anesthesia group (group TG) and general anesthesia group (group G).Anesthesia was induced with midazolam,cisatracurium besylate,sufentanil and etomidate,and the patients were mechanically ventilated after laryngeal mask airway insertion.TAP block was performed through the anterior superior iliac spine approach,and 0.25％ ropivacaine 30 ml was injected in group TG.Anesthesia was maintained by target-controlled infusion of propofol and remifentanil and muscle relaxation by intravenously injecting cisatracurium.The occurrence of cerebral regional oxygen saturation (rSO2) and low rSO2 events (rSO2 ＜60％) was recorded at 1 min before anesthesia induction (T0),5 min after inserting the laryngeal mask airway (T1),at skin incision (T2),30 min after skin incision (T3),and at the end of surgery (T4).The consumption of propofol and remifentanil was recorded during surgery.Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of patients at 1 day before surgery and 7 days after surgery,and the development of postoperative cognitive dysfunction (POCD,MoCA scores＜ 26) was recorded.Results Compared with group G,the intraoperative consumption of propofol and remifentanil was significantly reduced,rSO2 was increased at T2~,and the incidence of low rSO2 events was decreased,MoCA scores were increased at 7 days after surgery,and the incidence of POCD was decreased in group TG (P＜0.05).Conclusion TAP block can reduce the incidence of POCD in elderly patients undergoing laparoscopic surgery under general anesthesia.

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Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Drug Delivery Systems ; Proteins ; Transcriptome