Objective:To analyze the effects of highdose methotrexate(HD-MTX)and lenalidomide as central nervous system(CNS)prophylaxis strategies in patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of DLBCL patients with high risk of CNS recurrence who were initially treated in Fujian Provincial Hospital and Fujian Cancer Hospital from January 2012 to June 2022 were analyzed retrospectively.The patients were divided into HD-MTX group and lenalidomide group according to different prophylaxis strategies.Each group was further divided into high-risk group and medium-risk group based on CNS-IPI score and/or testicular involvement.The CNS relapse-free survival(CRFS)rate,adverse effects,and the effects of different prophylaxis strategies on overall survival(OS)rate and progression-free survival(PFS)rate were evaluated in different groups and subgroups.Results:There were 200 patients enrolled in this study,80 cases in lenalidomide group and 120 cases in HD-MTX group.According to the delivery timing of prophylactic HD-MTX,the patients in HD-MTX group were further divided into two groups:80 cases at the end of induction chemotherapy and 40 cases during chemotherapy interval.At a median follow-up of 48(14-133)months,the 4-year CRFS rate,4-year PFS rate,and 4-year OS rate of the HD-MTX group was 93.6％,57.2％,and 68.8％,respectively,while that of the lenalidomide group was 90.4％,69.4％and 75.6％.There were no significant differences in 4-year CRFS rate,4-year PFS rate,and 4-year OS rate between HD-MTX group and lenalidomide group(all P＞0.05),but lenalidomide group showed a trend of improvement in PFS.Further subgroup analysis showed that there was no significant difference in 4-year CRFS rate between high-risk patients of the two groups(91.7％vs 83.4％,P＞0.05),while 4-year PFS rate showed difference(49.5％vs 64.2％,P＜0.05).A total of 248 cycles were collected for adverse reaction analysis in the HD-MTX group,and 25 cycles occurred neutropenia accompanied with infection(10.1％),while in lenalidomide group 240 cycles were collected in which 20 cycles occurred neutropenia accompanied with infection(8.3％).Both the two groups had no treatment-related deaths.Conclusion:Compared with HD-MTX,lenalidomide combined with immunochemotherapy can prevent CNS relapse,at the same time,improve prognosis,which is a safe and well tolerated central prophylaxis strategy.

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.
Humans ; Nitric Oxide ; Uric Acid ; Hyperuricemia ; Biological Availability ; Cytokines

Objective:To investigate the effects of heme oxygenase-1 (HO-1) on hepatic sinusoidal endothelial cells (LSECs) proliferation, migration, and hepatocyte proliferation.Methods:Eighteen male C57BL/6 mouse aged 6-8 weeks old were underwent partial hepatectomy. Cell proliferation and HO-1 expression in residual liver tissue were detected by immunofluorescence histochemistry at 0 d, 2 d and 4 d after operation. In vitro, LSECs were transfected with adenovirus carrying HO-1 gene (HO-1 group), and the cells were transfected with empty vector adenovirus and the non-transfected cells were used as control. In addition, LSECs from different transfection groups were co-cultured with hepatocyte without contact to evaluate the effect of HO-1 expression on promoting hepatocyte proliferation. Western Blotting and RT-PCR were used to detect the protein and mRNA expression of HO-1, inhibitor of DNA binding and or differentiation (Id1), hepatocyte growth factor (HGF) and Wnt2. Cell proliferation was detected by EdU. The ability of cell migration was detected by Transwell migration assay.Results:Compared with 0 d after hepatectomy, LSECs proliferation and HO-1 expression within LSECs were increased significantly at 4 d after surgery. EdU positive rate of LSECs in HO-1 group (27.20±4.80)% was higher than that in empty vector group (12.47±3.30)% and non-transfected group (15.97±2.50)%. The number of LSECs migration in HO-1 group (258.70±36.56) was higher than that in empty vector group (122.00±38.16) and non-transfected group (107.70±30.01). The protein and mRNA expression level of HO-1, Id1, HGF and Wnt2 in HO-1 group were higher than that in empty vector group and non-transfected group. EdU positive rate of hepatocytes that co-cultured with LSECs in HO-1 group (18.33±2.52) % was higher than that in empty vector group (11.33±1.53)% and non-transfected group (11.7±2.08)%. The differences were statistically significant (all P<0.05). Conclusion:Up-regulation of HO-1 promoted LSECs proliferation and migration of, as well as up-regulation of HO-1 in LSECs enhanced the capacity of LSECs to promote hepatocyte proliferation.

In this study, network pharmacology research and animal experiments were used to predict and validate the potential targets of ShengMaiSan (SMS) in the treatment of diabetic cardiomyopathy. The active components of SMS were obtained through TCMSP and BATMAN databases. The potential targets of the active components and diabetic cardiomyopathy were predicted by Swiss Target Prediction and GeneCards databases, respectively. The protein-protein interaction (PPI) network was constructed by String database. Cytoscape software was adopted to perform topological analysis to select the core action target. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed using Metascape platform. To validate the potential targets, a type I diabetic rat model which induced by intraperitoneal injection of streptozotocin (STZ) was prepared. Rats were divided into sham group, model group, SMS group and trimetazidine (TMZ) group. Left ventricular hemodynamics was detected after 4 weeks administrated of SMS or TMZ. Myocardial contraction and calcium transients were detected synchronously in cardiomyocytes, as well as sarcoplasmic reticulum calcium content, calcium leak level and ryanodine receptor 2 (RyR2) expression were detected. Based on network pharmacology, 1 288 targets of SMS, 1 066 targets of diabetic cardiomyopathy, and 180 overlapped targets were obtained. The 39 core targets were screened, and 159 pathways including calcium signaling pathway were screened by KEGG pathway analysis. According to the previous studies and focusing on the contractility of diabetic cardiomyopathy, this study was involved calcium signaling regulation pathway in the SMS protection mechanism. The results showed that, compared with sham group, the systolic function of left ventricular and myocardial cells were decreased, and the calcium transport was in disorder in model group; compared with model group, both SMS group and TMZ group increased the maximum systolic pressure of left ventricle and the maximum systolic rate of left ventricular contraction. In addition, SMS group and TMZ group increased the contraction amplitude of cardiomyocytes, decreased the diastolic calcium concentration, the sarcoplasmic reticulum calcium leak and decreased the phosphorylation level of RyR2. There was no significant difference between SMS and TMZ groups. In summary, SMS could reduce the calcium leak of the sarcoplasmic reticulum and enhance the myofilament sensitivity of calcium to increasing contractile function of diabetic rats. The animal welfare and experiment procedures of this study were in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences.

italic>Bupleurum L. (Apiaceae) is an economically important genus, in which many species are of medicinal value. In this study, the complete plastid genomes (plastomes) of B. chinense DC. and B. boissieuanum H. Wolff were sequenced and their characteristics were investigated. Comparative and phylogenetic analyses were conducted with other published Bupleurum plastomes. The complete plastomes of B. chinense and B. boissieuanum were 155 458 and 155 800 bp in length, and both exhibited the typical quadripartite circular structure consisting of a large single copy region (LSC, 85 343 and 85 804 bp), a small single copy region (SSC, 17 495 and 17 410 bp), and a pair of inverted repeat regions (IRa/b, 26 310 and 26 293 bp), respectively. A total of 129 genes, including 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes were identified from each of the two plastomes. Repeat sequences detected were similar in types and distribution patterns, but the numbers were slightly different. Comparative analyses revealed that the Bupleurum plastomes were highly conserved in length, structure, the guanine and cytosine (GC) content, and gene content and order, both intraspecifically and interspecifically, and no obvious expansion or contraction of the inverted repeat regions occurred. Sequence variation was lower within the same species than among different species, noncoding sequences (including intergenic regions and introns) showed a higher divergence than the protein-coding sequences, and sequences in the LSC and SSC regions were more divergent than those in the IR regions. In addition, 11 sequences with higher nucleotide diversity among species were detected in the LSC and SSC regions. All studied Bupleurum species were inferred forming a monophyletic group with a 100% bootstrap value. Bupleurum chinense and B. boissieuanum were phylogenetically closest to B. commelynoideum and B. falcatum, separately, with all three B. chinense accessions clustered into a distinct clade. These results provide genetic information for further species identification, phylogenetic resolution, and will assist in exploration and utilization of medicinal Bupleurum species.

Child ; Hepatic Artery ; Humans ; Liver ; Liver Transplantation/adverse effects* ; Living Donors ; Retrospective Studies ; Thrombosis/etiology*

Objective:To explore the efficacy and mechanism of Qingfei Huatan Tang on chronic obstructive pulmonary disease (COPD). Method:The rat model of COPD was established through smoke inhalation combined with lipopolysaccharide (LPS) and pulmonary compound injection. After successful modeling, the rats were randomly divided into 6 groups, namely the control group, the COPD model group, low, medium and high-dose Qingfei Huatan Tang groups and the ambroxol group. After 28 days of modeling, the drug was administered. Low, medium and high-dose Qingfei Huatan Tang (7.5, 15, 30 g·kg^-1) and ambroxol (35 mg·kg^-1) were administered continuously for 14 days. Immunohistochemistry and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect protein expression and mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in pulmonary fibrosis. NCI-H292 cells were induced by LPS to establish a mucus hypersecretion model. The experiment was divided into 8 groups, namely the blank control group, LPS group, LPS+10% fetal bovine serum group, LPS+ physiological serum group, LPS+5% drug serum group, LPS+10% drug serum group, LPS+20% drug serum group and LPS+AG490 group. Immunofluorescence, Western blot and Real-time PCR were used to observe the protein and mRNA expressions of CFTR in NCI-H292 cells after LPS stimulation, and western blot was used to detect the expression of tyrosine kinase 2/transcription factor 3 (JAK2/STAT3) signaling pathway in NCI-H292 cells after LPS stimulation. Result:There were a large number of brown particles around the lumen of lung tissues in the normal group, with increased COPD expression. There were a few brown particles around the lumen of lung tissues in the model group compared with the normal group, with decreased COPD expression. Compared with the normal group, mRNA and protein expressions of CFTR in the lung tissues of the COPD model group were significantly decreased (P<0.05). Compared with the model group, mRNA and protein expressions of CFTR in the lung tissues of low, medium and high-dose Qingfei Huatan Tang groups (P<0.05). Compared with the blank control group, mRNA and protein expressions of CFTR in NCI-H292 cells of the LPS group (P<0.05), with significant increases in protein expressions of p-JAK2 and p-STAT3 (P<0.05). Compared with the model group, 5%, 10%, 20% Qingfei Huatan Tang-containing serum groups showed significant increases in mRNA and protein expressions of CFTR, but with significant decreases in p-JAK2, p-STAT3 protein expressions (P<0.05, P<0.01). Conclusion:Qingfei Huatan Tang up-regulated CFTR in the treatment of COPD by inhibiting JAK2/STAT3 pathway.