ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

Objective To explore the functional changes of the glial lymphatic system in patients with spontaneous intracerebral hemorrhage(sICH)by MR diffusion tensor imaging(DTI).Methods The clinical and imaging data of 32 sICH patients(sICH group)and 31 healthy volunteers(control group)were retrospectively collected,and the diffusivity values of DTI in different direc-tions were collected from all the subjects,the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS)index was calculated,the difference of DTI-ALPS index values between the sICH group and the control group was compared,the changes in the function of the glial lymphatic system in sICH patients were evaluated,and the correlation between DTI-ALPS index and clinical indi-cators in sICH patients was further analyzed.Results The DTI-ALPS index of cerebral hemispheres on the lesions side of sICH group was significantly lower than that on the unaffected side(P＜0.01,t=-5.03),and lower than that on the left side of control group(P＜0.01,t=-9.85)and the right side(P＜0.01,t=-8.80).In addition,vascular endothelial growth factor(VEGF)tes-ting was performed in 8 of the 32 patients,and the levels[(187.40±19.11)pg/mL]were significantly higher than the normal range(0-142.20 pg/mL).Conclusion Through the quantitative analysis of the DTI-ALPS index,the damage to the function of the glial lymphatic system of sICH can be reflected,and perhaps the mechanism of pathophysiological changes in the brain after sICH can be reflected from a new perspective by using MR DTI technology.

Objective:To investigate the efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

Objective:To evaluate the inhibitory effect of a retinoid derivative ECPIRM on proliferation of a cutaneous T-cell lymphoma (CTCL) cell line HH, and to explore its potential mechanisms.Methods:Cultured HH cells were treated with ECPIRM at different concentrations of 0 (control group) , 5, 10 and 20 μmol/L separately for 72 hours, cell counting kit-8 (CCK8) assay was performed to evaluate the effect of ECPIRM on the proliferative activity of HH cells, and flow cytometry to investigate the effect of ECPIRM on apoptosis of HH cells. Some HH cells were treated with 10 μmol/L ECPIRM for 72 hours, transcriptome sequencing was performed to investigate gene expression changes triggered by ECPIRM in HH cells, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and gene ontology (GO) enrichment analysis were then performed to analyze differentially expressed genes in HH cells induced by ECPIRM. Reverse transcription-qPCR was subsequently conducted to verify changes in key gene expression in related pathways. Intergroup differences were analyzed by using one-way analysis of variance, and least significant difference (LSD) - t test was used for multiple comparisons. Results:CCK8 assay showed that the 50% inhibitory concentration (IC50) of ECPIRM on HH cells was 4.91 ± 2.48 μmol/L, the viability of HH cells significantly differed among the control group, and 5-, 10-and 20-μmol/L ECPIRM groups (100.00% ± 2.87%, 49.58% ± 4.53%, 48.36% ± 2.88%, 31.44% ± 2.46%, respectively, F=162.86, P < 0.001) , and was significantly lower in the 5-, 10-and 20-μmol/L ECPIRM groups than in the control group ( t=15.36, 15.73, 20.89, respectively, all P < 0.001) . Flow cytometry showed that there was a significant difference in the apoptosis rate among the 4 groups (11.51% ± 1.84%, 23.83% ± 5.72%, 36.19% ± 8.33%, 49.75% ± 4.10%, respectively, F=17.62, P < 0.001) , and the 10-and 20-μmol/L groups showed significantly increased apoptosis rates compared with the control group ( t=4.46, 6.92 respectively, both P < 0.01) . Transcriptomics analysis revealed that the inhibitory effect of ECPIRM on the cellular proliferative activity may be related to the metabolic regulation of steroids. As reverse transcription-qPCR revealed, the 10-μmol/L ECPIRM group showed significantly decreased mRNA expression of L-amino acid oxidase (IL4I1) , acetyl-coenzyme A acetyltransferase 2 (ACAT2) , 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1) , mevalonate diphosphate decarboxylase (MVD) , 3-β-hydroxysteroid-8,7-isomerase (EBP) , very low-density lipoprotein receptor (VLDLR) , 3-hydroxy 3-methylglutaryl-CoA reductase (HMGCR) compared with the control group (all P < 0.05) . Conclusion:The retinoid derivative ECPIRM exerted marked anti-proliferative and apoptosis-inducing effects on HH cells, which may be related to the decreased expression of key genes involved in steroid metabolism.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Objective: To make etiological diagnosis and evaluate the protective effects of post-exposure prophylaxis(PEP) in an event of one dog injured seven persons. Methods: Direct immunofluorescence assay (DFA) and nested polymerase chain reaction (PCR) were employed to detect nucleoprotein and nucleoprotein(N) gene of rabies virus in the brain tissues of the dog, the positive samples were sequenced for the full length of N gene of rabies virus, then the homology of the N gene of rabies virus was analyzed after the phylogenetic tree was constructed. Rapid fluorescent focus inhibition test (RFFIT) was applied to detect the rabies virus neutralizing antibodies(RVNA) on day 0, 14 and 40 after PEP. Results: The cerebral, cerebellar and hippocampal tissues were positive by DFA and nested PCR. The phylogenetic tree indicated the rabies virus belonged to the rabies virus genotype I. The homology of the nucleotide and amino acid of the rabies virus N gene were over 86% with the vaccine strains. The titer of the RVNA increased significantly from the day 0 to day 14 after PEP, the lowest was 5.78 IU/ml and the highest was 26.15 IU/ml. On the day 40, the highest RVNA titer was 51.96 IU/ml. No rabies cases occurred in a one year follow-up visit. Conclusions Normative PEP can effectively prevent the occurrence of rabies cases.

Objective To explore the effect of the recombinant plasmid pcDNA3.1/C-sis on fulminant hepatic failure (FHF) in rats.Methods 48 h after recombinant plasmid pcDNA3.1/C-sis being imported into rat liver by using the method of fluid mechanics,FHF in rats was induced by endotoxin (LPS)+D-galactosamine (D-GaIN).With fluorescence quantitative PCR and Western blotting,C-sis expression was tested.The apoptosis of rat liver was detected by using HE staining and measuring Caspase-3 activity.The expression changes of Bcl-2 and Bax were examined through using Western blotting.The mortality rate of rats was calculated during 24 h observation period.Resnlts Compared with the normal control group and FHF+ empty plasmid group,C-sis mRNA and protein expression levels were increased significantly in the FHF+C-sis plasmid group,there were statistically significant differences (P＜0.01).Compared with the normal control group,the apoptotic hepatocytes were increased in the FHF + Ringer's solution injection group and FHF+ empty plasmid group;compared with FHF+ empty plasmid group,the apoptotic hepatocytes in the FHF+C-sis plasmid group were decreased.Compared with the normal control group,Caspase-3 expression level was increased in the FHF+ Ringer's solution injection group (P＜0.01);compared with the FHF+ empty plasmid group,Caspase-3 expression level in the FHF+C-sis plasmid group was decreased (P＜0.05).Compared with the normal control group,Bcl-2 expression level was decreased significantly (P＜0.01),and Bax expression level was increased significantly (P＜0.01) in the FHF+Ringer's solution injection group;compared with the FHF+ empty plasmid group,the Bcl-2 expression level was increased (P＜0.05),and Bax expression was decreased (P＜0.05)in the FHF+C-sis plasmid group.During the 24 h observation period,all rats in the normal control group were alive;the mortality rates of the FHF+ Ringer's solution injection group and FHF+ empty plasmid group were 70.0％ and 80.0％ respectively,while that of the FHF+C-sis plasmid group was only 20.0％.Conclusion C-sis gene could inhibit FHF in rats induced by LPS+D-GalN.

Objective To investigate the levels of the mRNA expression of TIM-3 and Galectin-9 in peripheral blood mono-cytes (PBMCs)of acute exacerbation asthma patients and their clinical significances.Methods 60 patients with acute exac-erbation asthma (eliminating 15 cases of non-conform to the regulations)and 30 cases of healthy subjects were collected from January to October of 2014.Used fluorescence quantitative real-time reverse transcription-polymerase chain reaction to measure the mRNA expression of TIM-3 and Galectin-9 in PBMCs of patients with asthma and healthy controls.Results The expression of TIM-3,Galectin-9 and IFN-γmRNA in the PBMCs from acute exacerbation asthma patients were all ab-normally higher than healthy controls (U =458.5,P =0.019;U =437.5,P =0.010;U =260,P <0.001).There were statis-tically significant differences between them.Conclusion TIM-3/Galectin-9 pathway may participate in the occurrence,devel-opment of asthma.TIM-3 or (and)Galectin-9 may prove to be an important target for treatments to asthma.