ObjectiveTo evaluate pharmacological effects of Shengmai injection（SMI）on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham group， a model group， a low-dose SMI group（3 mL·kg^-1）， a middle-dose SMI group（6 mL·kg^-1）， a high-dose SMI group（12 mL·kg^-1）， and a Ginaton group（4 mL·kg^-1）according to the random number table method， with 12 rats in each group. The rat model of cerebral ischemia-reperfusion（MCAO/R）was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion， which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores， cerebral infarction area， hematoxylin-eosin （HE） staining， Nissl staining， terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining， and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay （ELISA）， Western blot， and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation（OGD/R）-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly decreased density of Nissl bodies and neurons（P<0.01）. Compared with the model group， the SMI groups exhibited significantly decreased neurological function scores， cerebral infarction area， neuronal apoptosis rate， and expression levels of apoptosis related proteins （P<0.05， P<0.01）and significantly increased density of Nissl bodies and neurons （P<0.05）. The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury， and the chloride intracellular channel protein 1 （CLIC1） was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced， compared with those in the model group（P<0.05， P<0.01）， and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 （NLRP3） decreased （P<0.01）. In addition， the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate（P<0.01） and significantly decreased the intracellular chloride ion concentration（P<0.05）. ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.

Objective To study the effects of sodium cantharidinate (SC) on the proliferation and apoptosis of gastric cancer cells through JAK2/ STAT3 pathway. Methods Gastric cancer cell line SGC-7901 was cultured and treated with different concentrations of SC (0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 μmol/L) and then transfected with control plasmid or JAK2 plasmid. Cell survival rate, apoptosis rate, and the expression levels of p-JAK2, p-STAT3, p-p38, p-ERK, and p-JNK were detected after 48 h of treatment. Results The results indicated that 1.0, 2.0, 4.0, 8.0, and 16.0 μmol/L of SC inhibited cell proliferation, and the survival rate decreased with an increase in SC concentration (P<0.05). SC doses of 1.0, 2.0, and 4.0 μmol/L were selected for the subsequent experiments. Compared with the control group, the apoptosis rate of the 1.0 μmol/L SC group exhibited no significant difference (P>0.05), while those of the 2.0 and 4.0 μmol/L SC groups increased significantly (P<0.05). The expression levels of p-JAK2 and p-STAT3 significantly decreased (P<0.05), while no significant difference was noted in the expression levels of p-p38, p-ERK, and p-JNK (P>0.05) in the 1.0, 2.0, and 4.0 μmol/L SC groups. The JAK2 plasmid was transfected simultaneously with the 4.0 μmol/L SC treatment; the expression levels of p-JAK2 and p-STAT3 and the survival rate increased, whereas the apoptosis rate decreased (P<0.05). Conclusion SC inhibits the growth and promotes the apoptosis of gastric cancer cells, and its mechanism may be related to the inhibition of JAK2/STAT3 pathway activation.

In order to improve the poor solubility and low bioavailability of paeonol (Pae), paeonol-nanoemulsion (Pae-NE) was prepared, and its effect on uptake of human umbilical vein endothelial cells (HUVECs) was investigated.Pae-NE was prepared by phase inversion composition (PIC), the formulation of Pae-NE was optimized by single factor method and central composite design-response surface method (CCD), and the pharmaceutical properties were further characterized.Moreover, MTT was applied to evaluate the toxicity of Pae-NE on HUVECs, and the cellular uptake efficiency of Pae-NE was detected by fluorescence microscopy and flow cytometry.The results showed that the optimal formulation of Pae-NE was 20 mg of Pae, 55.1 mg of LCT, 144.9 mg of MCT, 600 mg of HS15, and 200 mg of 1,2 propylene glycol.The Pae-NE appearance was a light blue emulsion, and the average particle size is (25.69 ± 0.03) nm, with PDI of 0.182 ± 0.09, Zeta potential of -(4.01 ± 0.30) mV and good stability.The drug loading of Pae-NE was (1.967 ± 0.28) mg/mL and encapsulation rate of (99.36 ± 0.1)%.Pae-NE performed no significant effect on HUVECs growth in the Pae concentration range of 10-1-10-3 μg/mL.Moreover, NE as a drug delivery carrier significantly enhanced the uptake efficiency of Pae on HUVECs.In conclusion, Pae-NE preparation method was simple and stable, and promotes HUVECs uptake efficiency of Pae, suggesting that NE was a better dosage form reference for the lipid-soluble drug of Pae.

Objective:To investigate the workflow, feasibility and advantages of respiratory navigator-guided stereotactic body radiation therapy (SBRT) of liver malignancies on the magnetic resonance linear accelerator (MR-linac).Methods:Clinical data of 10 patients with liver cancer treated with respiratory navigator-guided SBRT on the MR-linac from September to December 2021 were analyzed retrospectively. All patients underwent CT and MR simulated localization, and plain, enhanced and 4D CT scan, and T 1 3D MR and T 2 3D MR images were collected. The expiratory 4D CT was chosen to design the reference plan. The T 2 3D navigator MR image (end-exhalation) was collected before treatment, the target position was adjusted or the target shape was modified in combination with the real-time monitoring 2D MR image and appropriate online adaptive planning process was selected. Then, the ability of CT, T 2 3D and T 2 3D navigator MR images to display the tumor was evaluated by naked eye. The changes of target volume were calculated. Dosimetric differences between the adaptive and reference plans were compared. The efficacy and adverse reactions of patients were evaluated. Results:In the free breathing state, the T 2 3D navigator MR image was significantly better than T 2 3D MR image to clearly display the tumor and its boundary. The adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) adopted by 10 patients was 37 times and 22 times respectively. The tumor subsided significantly in 3 patients. The average target conformal index (CI) of the adaptive plans was no different from that of the reference plans, but the gradient index (GI) was higher ( P<0.05), especially in the ATS plans. Compared to the reference plans, the normal liver V 5 Gy, V 10 Gy and D mean were almost the same, but the average MU was increased with a significant difference in the ATP adaptive plans ( P<0.05). The average of MU, segments and normal liver D mean and V 10 Gy in the ATS adaptive plans were lower than those in the reference plans, and the liver V 5 Gy was slightly increased. Seven patients were evaluated after 1 month and 3 months. The local control of lesions was promising. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusion:Respiratory navigator on MR-linac improves the visual clarity of tumors and online MR images, and shows its advantages to guide the adaptive precision radiotherapy of liver tumors, especially in SBRT.

Objective:To explore the efficacy of bibliotherapy to improve stigma and social function for patients with schizophrenia in rehabilitation.Methods:From June, 2018 to June, 2020 at Shandong Mental Health Center, a total of 115 patients with schizophrenia in rehabilitation were randomly divided into study group (58 cases) and control group (57 cases). The study group received bibliotherapy and the control group received general rehabilitation nursing based on original antipsychotic treatment and routine nursing. They were assessed with Link Disgrace Scale (LDS) and Inpatient Psychiatric Rehabilitation Outcome Scale (IPROS) before and after intervention.Results:There was no significant difference in the scores of all factors and total scores of LDs and IPROS before intervention between the two groups ( P>0.05). After intervention, the scores of all factors and total scores of LDS in the study group were 29.08±3.25, 63.69 ± 4.09, 12.54 ± 2.15, 105.31 ± 5.22 respectively, which were lower than those in the control group 37.17 ± 3.41, 74.00 ± 4.63,20.17 ± 2.89, 131.33 ± 8.51, there were significant differences between the two groups ( t values were 5.91-9.30, all P<0.05). After intervention, the scores of all factors and total scores of IPROS in the study group were 3.92 ± 1.32, 5.38 ± 1.56, 5.15 ± 1.63, 4.69 ± 1.44, 4.46 ± 1.66, 23.62 ± 3.31 respectively, which were lower than those in the control group 5.58 ± 2.11, 7.33 ± 2.67, 6.83 ± 1.12, 6.75 ± 2.73, 6.42 ± 2.31, 32.92 ± 5.07, there were significant differences between the two groups ( t values were 2.25-5.48, all P<0.05). Conclusions:Bibliotherapy can effectively improve the stigma and social function of patients with schizophrenia in rehabilitation.

China ; Humans ; Lenalidomide/therapeutic use* ; Multiple Myeloma/drug therapy* ; Thalidomide ; Therapeutic Equivalency

Objective: To investigate the epidemiological data of ventilator-associated pneumonia(VAP) occurred in adults after cardiac surgery and exploring the relationship between ventilator-associated pneumonia related factors, and all purpose is to provide strong theoretical advice and technical guidance for prevent the occurrence of ventilator-associated pneumonia in post-cardiac surgery patients. Methods: Using literature research method to determine 55 VAP related factors, and 21 nursing experts were selected to conduct 2 rounds of enquiries. Based on the results of the consultation, a retrospective questionnaire was formed. A total of 150 patients who underwent ICU mechanical ventilation after cardiac surgery from September 2016 to August 2017 were retrospectively selected. The related factors of VAP and its etiological characteristics were retrospectively observed. Results: Delphi experts consultation results: the response rate two rounds were 86.4% and 100.0% respectively; the coefficient of reliability ascertained the authority of evaluation was 0.857 and 0.903 respectively; Kendall’s W were 0.406 and 0.304 respectively (P all < 0.01). The average incidence of VAP was 25.10/1 000 ventilation days. In the VAP infection group, a total of 84 strains were detected, in which gram-negative bacteria accounted for 69.05% (58/84), fungi 26.19% (22/84), and gram-positive bacteria 4.76% (4/84).The most of them were Acinetobacterbaumannii 27.38% (23/84). Multiple infections were more than the proportion of 48%. Univariate analysis showed that there were 26 statistically significant items (P all < 0.01). Non-conditional binary logistic regression analysis showed that there were 4 independent risk factors with statistical significance: length of ventilator using> 5 days, length of cardiopulmonary ≥2h, perioperative blood transfusion >1 200 ml and perioperative using of acid inhibitors. Conclusions The study showed that most of the predictable VAP factors cannot be artificially intervened. Basing on the occurrence and development of VAP and the status of nursing interventions, Medical staff should take enhanced measures to prevent the occurrence of VAP and improve the quality of medical care

Chronic visceral hypersensitivity is an important type of chronic pain with unknown etiology and pathophysiology. Recent studies have shown that epigenetic regulation plays an important role in the development of chronic pain conditions. However, the role of miRNA-325-5p in chronic visceral pain remains unknown. The present study was designed to determine the roles and mechanism of miRNA-325-5p in a rat model of chronic visceral pain. This model was induced by neonatal colonic inflammation (NCI). In adulthood, NCI led to a significant reduction in the expression of miRNA-325-5p in colon-related dorsal root ganglia (DRGs), starting to decrease at the age of 4 weeks and being maintained to 8 weeks. Intrathecal administration of miRNA-325-5p agomir significantly enhanced the colorectal distention (CRD) threshold in a time-dependent manner. NCI also markedly increased the expression of CCL2 (C-C motif chemokine ligand 2) in colon-related DRGs at the mRNA and protein levels relative to age-matched control rats. The expression of CXCL12, IL33, SFRS7, and LGI1 was not significantly altered in NCI rats. CCL2 was co-expressed in NeuN-positive DRG neurons but not in glutamine synthetase-positive glial cells. Furthermore, CCL2 was mainly expressed in isolectin B4-binding- and calcitonin gene-related peptide-positive DRG neurons but in few NF-200-positive cells. More importantly, CCL2 was expressed in miR-325-5p-positive DRG neurons. Intrathecal injection of miRNA-325-5p agomir remarkably reduced the upregulation of CCL2 in NCI rats. Administration of Bindarit, an inhibitor of CCL2, markedly raised the CRD threshold in NCI rats in a dose- and time-dependent manner. These data suggest that NCI suppresses miRNA-325-5p expression and enhances CCL2 expression, thus contributing to visceral hypersensitivity in adult rats.

Objective: To obtain purified and functional CDNF-his recombinant protein and prepare its polyclonal antibodies.Methods:Preparation of recombinant CDNF-his was carried out in HEK 293 T cells with pVR1012-CDNF-his successfully constructed transfected into them.Then,the recombinant protein was purified by Ni-NTA immunoaffinity chromatography.The purity was analyzed by SDS-PAGE and the protein′s identity was tested by Western blot.MTT was used to verify the biological function of the protein purified.New Zealand white rabbits were immunized with purified CDNF-his protein for preparation of polyclonal antibodies.Results:pVR1012-CDNF-his expressed successfully in HEK 293 T cells.The purity of protein was up to more than 90%after purification.MTT showed that CDNF-his was able to protect PC 12 cells from damage by 6-OHDA.The polyclonal antibody was detected at the end of animal immunizing process.Conclusion: A method to express and purify protein using HEK 293T cell and following Ni-NTA immunoaffinity chromatography has been built.CDNF-his with biological activity is obtained based that.Finally, polyclonal antibodies of CDNF were generated successfully.

Objective To investigate the expression of Pim‐1 in non small cell lung cancer and adjacent normal tissues ,and study the relationship between c‐Myc and Pim‐1 in the corresponding tissue gene expression .Methods Totally 30 cases of non small cell lung cancer tissue and adjacent normal lung tissues were collected by surgical operation in department of thoracic surgery . Clinical data were statisticed and tracking late pathologic results ,using RT‐PCR ,qRT‐PCR and immunohistochemical method to de‐tect Pim‐1 mRNA ,c‐Myc and Pim‐1 protein expression in lung cancer and adjacent normal tissue ,and to analyze the relationship be‐tween the expression of Pim‐1 and c‐Myc .Results The positive rate of Pim‐1 mRNA and protein expression in non small cell lung cancer was obviously higher than that in adjacent normal tissue ,the mRNA expression levels were 0 .798 ± 0 .083 and 0 .394 ± 0 .107 (P<0 .01) ,the protein positive cases were 18 cases and 6 cases (P=0 .002) .The expression of Pim‐1 protein had no relationship on age ,gender ,smoking history ,pathological types and degree of differentiation of patients with non‐small cell lung cancer (P>0 .05) ,bue had related to ymph node metastasis and TNM stages of tumor (P<0 .05) ,with lymph node metastasis and TNM sta‐ges increases ,its expression quantity also rise .There was a positive correlation between Pim‐1 and c‐Myc protein expression ,corre‐lation coefficient (r) was 0 .433 (P=0 .017) .Conclusion High expression of Pim‐1 in non small cell lung cancer gene and is also increased with lymph node metastasis and TNM stages ,Pim‐1 and c‐Myc expression has positive correlation ,this could provide clues to the early diagnosis and prognosis evaluation of non small cell lung cancer ,and also provides a new train of thought and to find a new target for gene therapy of lung cancer .