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.

OBJECTIVES: There is currently no consensus on whether extra-gastrointestinal stromal tumors (EGISTs) and gastrointestinal stromal tumors (GISTs) are the same type of tumor, and whether the diagnosis and treatment of EGISTs can directly replicate the current diagnostic and treatment standards for GISTs. This study aims to further elucidate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of EGISTs by analyzing the research results of domestic scholars in the field of EGISTs in the past decade. METHODS: A review was conducted on original Chinese and English research articles published from 2013 to 2022 focusing on EGISTs. A descriptive approach was used to extract key information from the literature, including patient demographics, tumor location, tumor diameter, mitotic figures, risk stratification, immunohistochemical markers, cell type, and prognostic factors. The data were subjected to statistical analysis. RESULTS: A total of 12 articles containing 780 EGIST patients were included. The male-to-female incidence of EGISTs was 0.92꞉1. The most common sites of EGISTs were mesentery (30.96%), peritoneum or retroperitoneum (28.53%), omentum (20.32%), and pelvic cavity (12.52%). 52.77% of EGISTs had tumor diameters greater than 10 cm, and the proportions of EGISTs with nuclear fission patterns greater than 5/50 high power field (HPF) and greater than 10/50 HPF were 51.24% and 26.11%, respectively. The proportion of high-risk EGISTs was 79.05%. The positive rates of immune markers CD117, CD34, and DOG-1 in EGISTs were 82.3%, 69.0%, and 79.5%, respectively. The proportion of Ki-67 >5% was 49.2%, and the proportion of Ki-67 >10% was 24.8%. The proportions of EGISTs in spindle cells, epithelial cells, and mixed cells were 74.4%, 14.8%, and 13.1%, respectively. The diameter of the tumor, resection method, risk level, Ki-67 index, mitotic counts, presence of rupture/bleeding/necrosis/peripheral tissue invasion/recurrence and metastasis, as well as the use of imatinib treatment after surgery were important factors affecting the prognosis of EGISTs. CONCLUSIONS Current medical research is relatively well cognizant of GISTs with primary sites in the gastrointestinal tract. Compared with GISTs, EGISTs have large tumor diameters, high mitotic counts, a high percentage of high-risk grades, relatively unique molecular expression, and high aggressiveness. EGISTs differ from GISTs in clinicopathological characteristics. Whether EGISTs and GISTs share a common origin remains unclear. If they are distinct tumor entities, separate diagnostic and treatment guidelines for EGISTs should be established. If EGISTs are ultimately confirmed to be a special subtype of GISTs, then directly applying existing GIST-based standards to EGISTs may be inappropriate. A more scientific approach would involve subclassifying EGISTs based on anatomical location and then tailoring treatment strategies accordingly with reference to GIST guidelines.
Humans ; Gastrointestinal Stromal Tumors/epidemiology* ; Male ; Female ; Prognosis ; Proto-Oncogene Proteins c-kit/metabolism*

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P＜0.05 or P＜0.01),and the rate of EdU positive cells increased(P＜0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P＜0.05),and the myotube fusion index was raised(P＜0.05 or P＜0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P＜0.05 or P＜0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P＜0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P＜0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P＜0.05 or P＜0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.

Objective To express the protein enconded by the Rv3432c gene of Mycobacterium tuberculosis(M.tb)in vitro by prokaryotic expression,to analyze the structure of the Rv3432c protein by using bioinformatics software,and to explore for new drug targets against M.tb.Methods The Rv3432c gene was amplified by PCR using the genomic DNA of the inactivated M.tb strain H37Rv as the template and a recombinant plasmid was constructed with the expression vector pET-28a.The expression products were analyzed by SDS-PAGE and purified using affinity chromatography.The biological properties of Rv3432c were analyzed with Protparam,the Pfam online tool,SOMPA,Protscale,TMHMM Signalp 6.0,NetPhos3.1,SUMOsp 2.0,and SWISS-MODEL.Results pET-28a-Rv3432c recombinant plasmid sequencing results were fully consistent with those of the target gene.SDS-PAGE analysis showed that the fusion protein existed in the form of a soluble protein with a relative molecular mass of about 55×103,which matched the expected size.ProtParam analysis showed that the Rv3432c protein was hydrophilic(showing a GRAVY value of-0.079).Rv3432c was a protein with no transmembrane structural domains or signal peptide.The secondary structure of Rv3432c mainly consisted of random coils(39.78%)and α-helix(39.57%)and was relatively loosely structured.Conclusion We successfully constructed a prokaryotic expression plasmid of the Rv3432c protein and analyzed its structure using bioinformatics,laying the foundation for further research on the role of Rv3432c in the pathogenesis and progression of tuberculosis as well as the identification of new drug targets against M.tb.

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.

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 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

Objective To investigate the incidence of leukemia in infants, and to understand the status of this disease in recent years. Methods A total of 5802 children aged median 6 years (0-12 years) with first time bone marrow biopsy from January 2009 to December 2015 were retrospectively analyzed, and the results of bone marrow image analysis were analyzed retrospectively to investigate the incidence of leukemia. Results Of the 5802 cases, 480 (8.27 %) cases were children with leukemia. Among them, 381 (79.38 %) cases were acute lymphocytic leukemia (ALL), 99 (20.62 %) cases were acute myeloid leukemia (AML). The proportion of children with leukemia with first time marrow puncture was 5.33%(40/750), 4.92%(36/731), 7.06%(58/821), 8.34%(78/935), 10.13%(88/868), 10.89%(92/845), and 10.33%(88/852) from 2009 to 2015, respectively. The proportion of male patients per year was more than female, and the incidence in preschool and school-age children was higher [33.75 % (162/480) and 34.79 % (167/480), respectively]. Conclusion The proportion of children's leukemia in children with the first time bone marrow aspiration in Shanxi Children's Hospital increases year by year, and its risk factors need to be further analyzed.

Objective To discuss the efficacy of neural endoscopic and surgical operation in patients with cerebral hemorrhage induced by hypertension.Methods Sixty cases with cerebral hemorrhage induced by hypertension admitted at the People′s Hospital of Bortala from January 2015 to June 2016 were divided into the control group(n=32) and research group(n=28) according to cerebral hemorrhage surgical method.The patients of the control group were given conventional surgical operation treatment while the observation group were given neural endoscopic treatment.The operative time and intraoperative blood loss,and situation of hematoma absorption before and after operation and prognosis between the two groups were compared.Results The operative time and intraoperative blood loss of the two groups were respectively (132.6±35.4) min,(49.8±12.3) ml and (236.5±46.2) min,(263.5±49.8) ml,the observation group were obviously lower than that of the control group,the differences were statistically significant(t=6.532,9.548,all P<0.05).The preoperative hematoma volume,postoperative hematoma volume and hematoma clearance of the two groups were respectively (6.8±1.5) ml,(82.7±6.3)% and (16.3±3.1) ml,(57.8±5.2)%,the postoperative hematoma volume of observation group were obviously lower than that of the control group while the hematoma clearance obviously increased,the differences were statistically significant(t=6.584,-5.263,all P<0.05).The ADL assessment in patients of observation group was better than the control group and the death rate was lower than that of control group,the differences were statistically significant(3.6%(1/28) vs.21.9%(7/32),χ2=10.580,4.329,all P<0.05).Conclusion The efficacy of neural endoscopic applied in patients with cerebral hemorrhage induced by hypertension is remarkable,it causes little damage to the body and can obviously improve the effect of prognosis,it is worth popularization and application.