Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Objective To investigate the sleep structure of Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) and its correlations with cognitive function, depressive state and motor function. Methods A total of 120 PD patients were enrolled in this study, and divided into PD+RBD group (n=45) and PD group (n=75) based on the presence or absence of RBD. Sleep structure was recorded for both groups. The scores of the Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Unified Parkinson's Disease Rating Scale Part Ⅲ (UPDRS-Ⅲ) and Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) were compared between the two groups. The correlations of MoCA, HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores with sleep structure in the PD+RBD group were analyzed. Results The PD+RBD group showed significantly higher percentage of non-rapideye movement (NREM) at stage 1, arousal index, periodic limb movements during sleep (PLMS) and apnea-hypopnea index (AHI) compared to the PD group, while the percentages of NREM at stage 3, rapid eye movement (REM) sleep, sleep efficiency and lowest oxygen saturation were significantly lower (P < 0.05). The PD+RBD group also had significantly higher HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and significantly lower MoCA scores compared to the PD group (P < 0.05). In the PD+RBD group, the percentages of NREM at stage 1, arousal index, PLMS and AHI were positively correlated with HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and negatively correlated with MoCA scores (P < 0.05). Conversely, the percentages of NREM at stage 3, REM sleep, sleep efficiency and lowest oxygen saturation were negatively correlated with HAMA, HAMD, UPDRS-Ⅲ and SCOPA-AUT scores, and positively correlated with MoCA scores (P < 0.05). Conclusion PD patients with RBD exhibit disrupted sleep structure, which is closely associated with cognitive function, depressive state, motor function, and autonomic nervous system function.

Glioblastoma is carcinogenesis of glial cells in central nervous system and has the highest incidence among primary brain tumors. Brain metastasis, such as breast cancer and lung cancer, also leads to high mortality. The available medicines are limited due to blood-brain barrier. Abnormal activation of phosphatidylinositol 3-kinases (PI3K) signaling pathway is prevalent in glioblastoma and metastatic tumors. Here, we characterized a 2-amino-4-methylquinazoline derivative XH30 as a potent PI3K inhibitor with excellent anti-tumor activity against human glioblastoma. XH30 significantly repressed the proliferation of various brain cancer cells and decreased the phosphorylation of key proteins of PI3K signaling pathway, induced cell cycle arrest in G1 phase as well. Additionally, XH30 inhibited the migration of glioma cells and blocked the activation of PI3K pathway by interleukin-17A (IL-17A), which increased the migration of U87MG. Oral administration of XH30 significantly suppressed the tumor growth in both subcutaneous and orthotopic tumor models. XH30 also repressed tumor growth in brain metastasis models of lung cancers. Moreover, XH30 reduced IL-17A and its receptor IL-17RA in vivo. These results indicate that XH30 might be a potential therapeutic drug candidate for glioblastoma migration and brain metastasis.

Formins are widely distributed in eukaryotes such as fungi, plants and animals. They play crucial roles in regulating the polymerization of actin, coordinating the synergistic interactions between actin and microtubules, and determining cell growth and morphology. Unlike formins from fungi and animals, plant formins have been evolved into two plant-specific types. Generally, type Ⅱ formins are believed to regulate the polarized growth of cells, and type Ⅰ formins may regulate the cell expansion and division processes. Recent studies on the function of plant formins suggest it is inappropriate to classify the function of formins purely based on their structures. This review summarizes the domain organization of formins and their corresponding functions, as well as the underpinning mechanisms. Furthermore, the unsolved or unexplored issues along with future perspectives on plant formins are proposed and discussed.
Actins ; Formins ; Microfilament Proteins ; Plant Cells ; Plant Development ; Plants

OBJECTIVE：To management recheck and sorting weight for finished intravenous solutions in PIVAS ，to provide reference for reducing dispensing error and improving the safety and quality of intravenous infusion therapy. METHODS ：The weight analysis method was used to determine the weight of main drug and solvent in the finished intravenous solutions and infusion bottle . The weight maintenance information was added in PIVAS information management system ，and the marked weight of finished intravenous solutions was calculated for the verification of finished intravenous solutions. Average daily check quantity of finished product ，checking time ，average checking time of finished products per bag ，detection rate of dispensing error ，external error and timeliness of finished infusion batch were compared before （Mar.-May，2019，n＝83 006）and after （Jun.-Aug.，2019， n＝83 173）management. The effects of weighting recheck management were evaluated. RESULTS ：Compared with before the implementation of weighting recheck management ，there were no significant differences in the average daily check quantity of finished products ，the detection rate of dispensing errors caused by wrong labeling of liquid ，or the times of delayed drug delivery batches after the implementation of weighting recheck management （P＞0.05）. The checking time of finished products ，average checking time of finished products per bag ，the number of bags added or subtracted error ，detection rate of dose dispensing error ， total error detection rate prolonged or increased significantly （P＜0.05），and the number of external error was decreased significantly（P＜0.05）. CONCLUSIONS ：The weighting recheck management improves the accuracy and safety of PIVAS preparation，effectively improves error detection rate ，reduces the occurrence of external error ，but prolongs the time of checking ， which are urgent to be solved by information and automation means.

Objective:To explore the attitudes of parents of critically ill children to resuscitation companionship and its influencing factors so as to provide a scientific basis for improving the experience of children and their families in the rehabilitation process.Methods:A cross-sectional survey method was used, and parents of critically ill children who were hospitalized in Children's Hospital Affiliated to Zhengzhou University from August 2018 to August 2019 were selected by convenience sampling. The general data questionnaire and Family Presence During Resuscitation Benefits-Risks (FPDR-BRS) were used to investigate the attitudes of parents of critically ill children to the resuscitation companion and influencing factors were analyzed. A total of 200 questionnaires were distributed, 189 of which were effective, with an effective recovery rate of 94.5%.Results:The total scores of FPDR-BRS of 189 parents of critically ill children were (74.75±22.54) points. Univariate analysis showed that the total scores of FPDR-BRS of parents of critically ill children had statistically significant differences in the relationship with children, parents' occupations, cultural level and presence or absence of resuscitation experience ( P<0.05) . Multiple linear regression analysis showed that the relationship with children, parents' occupation and cultural level were the influencing factors of attitude to resuscitation companionship ( P<0.05) . Conclusions:Parents of critically ill children have a moderate level of recognition for resuscitation companionship. The relationship with children, parents' occupation and cultural level are factors that influence the attitude to resuscitation companionship. Medical staff should formulate targeted interventions based on the influencing factors of attitude to resuscitation companionship so as to improve the experience of children and their families during the resuscitation process.

OBJECTIVE： To explore the effects of different primary processing methods on quality change of Polygonatum sibiricum， and to optimize primary processing method of P. sibiricum with different grades and shapes. METHODS： After processed with different drying methods， boiling method and steaming method， sulfuric acid-phenol method was used to determine the contents of indicator component P. sibiricum polysaccharide in samples. The contents of ethanol-soluble extract， water-soluble extract and total ash were investigated. The optimal primary processing methods were screened. RESULTS： After processed with different methods， the contents of polysaccharide （≥7％）， ethanol-soluble extract （≥45％） and total ash （≤4％） of samples at all levels conformed to the requirements of the 2015 edition of Chinese Pharmacopoeia （part Ⅰ）； from aspect of drying method， microwave drying method was better than oven drying method；for P. sibiricum with different morphologies （individual and lamellar）， the quality of lamellar samples of P. sibiricum was better than that of individual P. sibiricum. As primary processing method， steaming was better than boiling. The contents of P. sibiricum polysaccharide were in relatively high level， when the steaming and boiling time of gradeless and uniformly-priced goods of P. sibiricum were 20 and 15 minutes respectively. CONCLUSIONS： By discussing the different primary processing methods， high-efficient primary processing method for the individual and lamellar samples of P. sibiricum as well as gradeless and uniformly-priced goods of P. sibiricum are preliminarily obtained， which can provide a scientific basis for the effective utilization of P. sibiricum resources.

Objective To investigate whether the inhibition of caveolin-1 (Cav-1) phosphorylation will regulate effectively nuclear factor-erythroid 2-related factor (Nrf2) signal pathway and downstream effector molecules and protest against ventilation induced lung injury (VILI) in an animal model in vivo. Methods Ninety male Sprague-Dawley (SD) rats were randomly divided into nine groups (each n = 10): sham group in which rats did not receive ventilation but received tracheotomy; lung protective ventilation (PV) for 1 hour or 2 hours group; mechanical ventilation (MV) at high volume tidal (VT, 40 mL/kg) for 1 hour or 2 hours group; protein tyrosine kinase inhibitor PP2 or rosiglitazone (Rsg) pretreatment + high VT ventilation for 1 hour or 2 hours groups. The two pretreatment groups were given intraperitoneal injection PP2 15 mg/kg or intragastric administration of Rsg 5 mg/kg 1 hour before ventilation respectively. The rats were sacrificed after model reproduction, and bronchoalveolar lavage fluid (BALF) was collected. Pulmonary vascular permeability was measured by Evans blue (EB). The levels of tumor necrosis factor-α (TNF-α), activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and interleukin-8 (IL-8) in BALF were determined by enzyme linked immunosorbent assay (ELISA). Then the lung tissues were collected, the lung wet/dry ratio (W/D) was calculated, the changes in pathology was observed with light microscope, and myeloperoxidase (MPO) activity was determined by colorimetric analysis. Nrf2 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of Cav-1 tyrosine residues 14 phosphorylation (pCav-1-Y14), Cav-1, peroxisome proliferators-activated receptor γ (PPARγ) and claudin-5 as well as Nrf2 in cytoplasm and nucleus were determined by Western Blot. The positive expressions of PPARγ and claudin-5 in lung tissues were assayed with immunohistochemistry staining. Results There were no obvious pathological changes in the lung tissue in sham group and PV groups, and there were no significant differences in all the parameters between the two groups either. However, the injury in lung tissue was severe in the high VT groups in which W/D ratio, EB contents, MPO activity, and TNF-α, AP-1, IL-8, NF-κB levels in BALF as well as the protein expressions of Cav-1 and pCav-1-Y14 were significantly higher than those of sham group and PV groups, and the protein expressions of PPARγ and claudin-5 were significant lower than those of sham group and PV groups with a dose-dependent manner; but Nrf2 expressions in cytoplasm and nucleus did not show a statistical increase. After pretreatment of PP2 or Rsg, W/D ratio, MPO activity, EB contents, TNF-α, AP-1, IL-8, and NF-κB in BALF were significantly decreased as compared with those of high VT group, and RT-PCR showed significant up-regulation of Nrf2 mRNA in lung tissues too. Moreover, there was a statistically significant increase in expressed Nrf2 proteins in nucleus in PP2 or Rsg groups as compared with those of high VT groups [Nrf2 in nucleus (gray value): 0.61±0.06, 0.56±0.06 vs. 0.31±0.02 at 1 hour, 0.38±0.06, 0.43±0.07 vs. 0.22±0.03 at 2 hours; all P < 0.05], but no significant difference was found in the expression of Nrf2 protein in the cytoplasm among all groups. The protein expressions of pCav-1-Y14 in PP2 pretreatment groups were significantly lower than those of high VT groups (gray value: 0.89±0.04 vs. 1.48±0.02 at 1 hour, 0.86±0.02 vs. 1.31±0.01 at 2 hours; both P < 0.05); but expressed PPARγ proteins and expressed claudin-5 proteins in PP2 or Rsg pretreatment groups were significantly higher than those of high VT groups [PPARγ (gray value): 0.34±0.07, 0.42±0.13 vs. 0.17±0.07 at 1 hour, 0.38±0.09, 0.33±0.07 vs. 0.16±0.03 at 2 hours; claudin-5 (gray value): 0.33±0.05, 0.38±0.07 vs. 0.14±0.03 at 1 hour; 0.30±0.06, 0.31±0.04 vs. 0.17±0.04 at 2 hours; all P < 0.05]. Conclusions The inhibition of Cav-1-Y14 phosphorylation can increase the expression of Nrf2 in the nucleus, then result in an increase in the protein expressions of PPARγ and claudin-5 of its effector molecules. This effect can reduce the inflammation and capillary permeability of lung tissue in the model of VILI.

ObjectiveTo determine whether the inhibition of caveolin-1 tyrosine residues 14 (Cav-1-Y14) phosphorylation with protein tyrosine kinase inhibitors (PP2) will upregulate heme oxygenase-1 (HO-1) activity to protect against ventilation induced lung injury in vivo of an animal model.Methods Fifty-four male Sprague-Dawley (SD) rats were randomly divided into nine groups (eachn = 6). Group A served as normal control group, in which rats did not receive ventilation but tracheotomy. Groups B1 and B2 received lung protective ventilation respectively for 1 hour or 2 hours. Groups C1 and C2 received high tidal volume (40 mL/kg) ventilation for 1 hour or 2 hours, respectively. The group D1 or D2 also received high tidal volume ventilation for 1 hour or 2 hour respectively, but they were given PP2 1 hour before high tidal volume ventilation. The groups E1 and E2 also received high tidal volume ventilation respectively for 1 hour or 2 hours, but tyrosine kinase inhibitor PP2 and HO-1 inhibitor zinc protoporphyrinⅨ(ZnPPⅨ) were given to animals 18 hours before high tidal volume ventilation. All the animals were sacrificed after ventilation, and the specimens of lung tissues and bronchoalveolar lavage fluid (BALF) were harvested. Then the changes in pathology of lung tissue was observed, and diffuse alveolar damage scores (DAD) were calculated, myeloperoxidase (MPO) activity was measured by colorimetric analysis, lung wet/dry ratio (W/D) was estimated. The expressions of phosphorylated caveolin-1 (P-Cav-1-Y14), caveolin-1 (Cav-1) and HO-1 were determined by Western Blot. The expressions of high mobility group B1 (HMGB1) and advanced glycation end product receptor (RAGE) in lung tissues were assayed with immunohistochemistry staining. The levels of tumor necrosis factor-α(TNF-α) in BALF were measured by enzyme linked immunosorbent assay (ELISA).Results There was no significant difference in all the parameters between group A and groups B. Compared with group B1, DAD score, W/D ratio, the activity of MPO and the concentration of TNF-α in BALF in group C1 were significantly increased [DAD score:7.97±0.59 vs. 0.55±0.13, W/D ratio: 5.70±1.61 vs. 5.04±0.63, MPO (U/g): 1.82±0.14 vs. 0.77±0.26, TNF-α(ng/L): 370.10±29.61 vs. 54.38±8.18, allP< 0.05], and the injury in ventilation 2 hours group was more serious than that in ventilation 1 hour group. Compared with groups C, all the parameters in groups D were significantly decreased. The parameters in groups E were significantly higher than those in groups A, B, and D, but no significant difference was found as compared with groups C. Compared with groups B, the protein expressions of Cav-1 and P-Cav-1-Y14 (gray value) in groups C were significantly increased (1 hour: 1.49±0.02 vs. 1.26±0.13, 1.34±0.02 vs. 0.87±0.04;2 hours: 1.58±0.02 vs. 1.27±0.27, 1.31±0.01 vs. 0.95±0.02, allP< 0.05), and the expression of HO-1 protein (gray value) was significantly decreased (1 hour: 0.59±0.02 vs. 1.10±0.01, 2 hours: 0.49±0.01 vs. 1.20±0.02, both P< 0.05). No significant difference in Cav-1 protein expression between groups D as well as groups E and groups C. The protein expression of P-Cav-1-Y14 in groups D and E was significantly lower than that in groups C. The protein expression of HO-1 in groups D was significantly higher than that in groups C, but the phenomenon was not found in groups E as compared with groups C. Compared with group A, the positive expression of HMGB1 and RAGE in lung tissue in groups C and E was significantly increased, but no significant difference was found between groups B as well as groups D and group A.Conclusion Cav-1-Y14 phosphorylation is the key factor for ventilator induced lung injury, which can not only lead to a decrease in vascular barrier function, but also inhibit the activity of HO-1 enzyme, thus further aggravates inflammatory injury of the lung as induced by mechanical ventilation.