Correlation of macrophage-related cytokines and silent information regulator 1 and forkhead box protein O3 levels in peripheral blood mononuclear cells in patients with active pulmonary tuberculosis / 中国热带医学

@#Abstract: Objective　To explore the correlation between the levels of silent information regulator 1 (SIRT1) and forkhead box protein O3 (FOXO3) in peripheral blood mononuclear cells of patients with active pulmonary tuberculosis (APTB) and macrophage-related cytokines-inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1). Methods　A total of 64 APTB patients who were treated in Yubei Hospital, the First Affiliated Hospital of Chongqing Medical University from January 2020 to December 2021 were gathered as the APTB group, 59 people with latent tuberculosis infection (LTBI) were gathered as the LTBI group, and 62 healthy people were gathered as the control group. Quantitative real-time PCR (qPCR) method was performed to measure the levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells. The enzyme-linked immunosorbent assay (ELISA) was performed to measure serum iNOS and Arg-1 levels; ROC curve was used to analyze the value of SIRT1 mRNA and FOXO3 mRNA levels in the differential diagnosis of LTBI and APTB; Pearson correlation was performed to analyze the correlation of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients with serum iNOS and Arg-1 levels. Results　The levels of SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells decreased in control group, LTBI group and APTB group, and the level of serum Arg-1 increased in turn (P<0.05). The AUCs of SIRT1 mRNA and FOXO3 mRNA in differential diagnosis of LTBI and APTB were 0.876 and 0.887, respectively, the sensitivity was 71.2% and 76.3%, and the specificity was 96.9% and 90.6% respectively. The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients were positively correlated (r=0.500, P<0.05), and they were positively correlated with serum iNOS and negatively correlated with serum Arg-1 (P<0.05). The SIRT1 mRNA, FOXO3 mRNA and serum iNOS in peripheral blood mononuclear cells of APTB patients after 6 months of treatment were higher than those before treatment, and serum Arg-1 was lower than before treatment (P<0.05). Conclusions　The levels of SIRT1 mRNA and FOXO3 mRNA in peripheral blood mononuclear cells of APTB patients are low, and they are positively correlated with macrophage-related cytokine iNOS and negatively correlated with Arg-1.

Dose-enhanced immunochemotherapy followed by first-line autologous peripheral blood stem cell transplantation for young patients with high-risk aggressive B-cell lymphoma: an efficacy and prognostic factor analysis / 中华血液学杂志

Objective: This study aimed to determine the efficacy of dose-enhanced immunochemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT) in young patients with newly diagnosed high-risk aggressive B-cell lymphoma. Methods: A retrospective study was conducted to examine the clinical and survival data of young patients with high-risk aggressive B-cell lymphoma who received dose-enhanced immunochemotherapy and ASCT as first-line treatment between January 2011 and December 2018 in Blood Diseases Hospital. Results: A total of 63 patients were included in the study. The median age range was 40 (14-63) years old. In terms of the induction therapy regimen, 52 cases received R-DA-EP (D) OCH, and the remaining 11 received R-HyperCVAD/R-MA. Sixteen (25.4% ) patients achieved partial response in the mid-term efficacy assessment, and ten of them were evaluated as complete response after transplantation. The median follow-up was 50 (8-112) months, and the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were (83.9±4.7) % and (90.4±3.7) % , respectively. Univariate analysis demonstrated that age-adjusted international prognostic index ≥2 scores was a negative prognostic factor for OS (P=0.039) , and bone marrow involvement (BMI) was an adverse prognostic factor for OS (P<0.001) and PFS (P=0.001) . However, multivariate analysis confirmed that BMI was the only independent negative predictor of OS (P=0.016) and PFS (P=0.001) . Conclusions: The use of dose-enhanced immunochemotherapy in combination with ASCT as first-line therapy in the treatment of young, high-risk aggressive B-cell lymphoma results in good long-term outcomes, and BMI remains an adverse prognostic factor.

Impact of inflammatory reaction levels and culprit plaque characteristics on preprocedural thrombolysis in myocardial infarction flow grade in patients with ST-segment elevation myocardial infarction / 中华心血管病杂志

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.

Correlation between internal damage due to seven emotions in traditional Chinese medicine and pathogenesis of breast cancer from perspective of psychological stress / 中国中药杂志

Breast cancer is a major chronic disease threatening women's health. It has topped the global cancers as the diagnosed cases outnumbered lung cancer patients in 2020. Internal damage due to the seven emotions is an important cause of breast cancer and the disorders of hypothalamic-pituitary-adrenal(HPA) axis and endocrine system and the abnormal immune defense mechanism in response to psychological stress all affect the occurrence and development of breast cancer. It is noteworthy that the theory of seven emotions in traditional Chinese medicine and the psychological stress theory of modern medicine have something in common in some aspects. Therefore, this study explored the correlation between internal damage due to the seven emotions and psychological stress and analyzed the molecular biological mechanisms of psychological stress influencing breast cancer from the perspective of modern medicine, which is helpful to reasonably prevent breast cancer and other related tumors and improve the prognosis of breast cancer patients through emotion regulation.

The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.@*METHODS@#Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.@*RESULTS@#ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC@*CONCLUSION@#ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.

Candidate genes involved in the biosynthesis of lignan in Schisandra chinensis fruit based on transcriptome and metabolomes analysis / 中国天然药物

Schisandra chinensis Turcz. (Baill.) is a plant species with fruits that have been well known in Far Eastern medicine for a long time. It has traditionally been used as a stimulating and fortifying agent in cases of physical exhaustion and to inhibit fatigue. The major bioactive compounds found in S. chinensis are lignans with a dibenzocyclooctadiene skeleton, but little is known about their biosynthesis in plants. S. chinensis is the ideal medicinal plant for studying the biosynthesis of lignans, especially the dibenzocyclooctadiene skeleton. Genomic information for this important herbal plant is unavailable. To better understand the lignan biosynthesis pathway, we generated transcriptome sequences from the fruit during ripening and performed de novo sequence assembly, yielding 136 843 unique transcripts with N50 of 1778 bp. Putative functions could be assigned to 41 824 transcripts (51.57%) based on BLAST searches against annotation databases including GO (Gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). Furthermore, 22 candidate cytochrome P450 genes and 15 candidate dirigent proteins genes that were most likely involved in the lignan biosynthesis pathway were discovered based on transcriptome sequencing of S. chinensis. The genomic data obtained from S. chinensis, especially the identification of putative genes involved in the lignan biosynthesis pathway, will facilitate our understanding of lignan biosynthesis at the molecular level. The lignan metabolite profiles were analyzed by metabolomes, the accumulation patterns of 30 metabolites involved in the lignan pathway were studied. Co-expression network of lignan contents and transcriptional changes showed 355 strong correlations (correlation coefficient, R > 0.9) between 21 compounds and 153 transcripts. Furthermore, the comprehensive analysis and characterization of the genes involved in lignan pathways and the metabolite profiles of lignans are expected to provide better insight regarding the diversity of the chemical composition, synthetic characteristics, and regulatory mechanisms of this medical herb.

TOSO interacts with SYK and enhances BCR pathway activation in chronic lymphocytic leukemia / 中华医学杂志(英文版)

BACKGROUND@#TOSO, also named Fas inhibitory molecule 3 (FAIM3), has recently been identified as an immunoglobulin M (IgM) Fc receptor (FcμR). Previous studies have shown that TOSO is specifically over-expressed in chronic lymphocytic leukemia (CLL). However, the functions of TOSO in CLL remain unknown. The B-cell receptor (BCR) signaling pathway has been reported to be constitutively activated in CLL. Here, we aimed to investigate the functions of TOSO in the BCR signaling pathway and the pathogenesis of CLL.@*METHODS@#We over-expressed TOSO in B-cell lymphoma cell lines (Granta-519 and Z138) by lentiviral transduction and knocked down TOSO by siRNA in primary CLL cells. The over-expression and knockdown of TOSO were confirmed at the RNA level by polymerase chain reaction and protein level by Western blotting. Co-immunoprecipitation with TOSO antibody followed by liquid chromatography coupled with tandem mass spectrometry (IP/LCMS) was used to identify TOSO interacting proteins. Western blotting was performed to detect the activation status of BCR signaling pathways as well as B-cell lymphoma 2 (BCL-2). Flow cytometry was used to examine the apoptosis of TOSO-over-expressing B lymphoma cell lines and TOSO-down-regulated CLL cells via the staining of Annexin V and 7-AAD. One-way analyses of variance were used for intergroup comparisons, while independent samples t tests were used for two-sample comparisons.@*RESULTS@#From IP/LCMS, we identified spleen tyrosine kinase (SYK) as a crucial candidate of TOSO-interacting protein and confirmed it by co-immunoprecipitation. After stimulation with anti-IgM, TOSO over-expression increased the phosphorylation of SYK, and subsequently activated the BCR signaling pathway, which could be reversed by a SYK inhibitor. TOSO knockdown in primary CLL cells resulted in reduced SYK phosphorylation as well as attenuated BCR signaling pathway. The apoptosis rates of the Granta-519 and Z138 cells expressing TOSO were (8.46 ± 2.90)% and (4.20 ± 1.21)%, respectively, significantly lower than the rates of the control groups, which were (25.20 ± 4.60)% and (19.72 ± 1.10)%, respectively (P < 0.05 for both). The apoptosis rate was reduced after knocking down TOSO in the primary CLL cells. In addition, we also found that TOSO down-regulation in primary cells from CLL patients led to decreased expression of BCL-2 as well as lower apoptosis, and vice versa in the cell line.@*CONCLUSIONS@#TOSO might be involved in the pathogenesis of CLL by interacting with SYK, enhancing the BCR signaling pathway, and inducing apoptosis resistance.

Accurate positioning and analysis on health function of high frequency anti-fatigue herbal medicines / 中国中药杂志

Fatigue is a widespread and complex physiological phenomenon. Chronic fatigue can lead to cardiovascular dysfunction, mental disorders and other serious pathological reactions. Therefore, how to relieve fatigue accurately and effectively is an important proposition to implement the concept of "Healthy China" in the new era. As an important part of Chinese medicine health industry, Chinese medicine health food has been developing rapidly in recent years. At present, there are 1 157 kinds of anti-fatigue health food on the market in China, most of which are single Chinese medicine and its compound. However, their functions are generally labeled as "anti-fatigue", and their function positioning is too extensive and unclear. With the deepened understanding of fatigue classification and its physiological and pathological basis, it is urgent to be combined with the progress of modern chemical and pharmacological stu-dies to differentiate and precisely position the anti-fatigue health effects of traditional Chinese medicine. For this purpose, the classifications of fatigue were summarized in this paper, and the mechanism of fatigue was explained from the aspects of energy metabolism, accumulation of metabolites, oxidative stress, inflammation, hypothalamus pituitary adrenal axis and so on. We selected 10 traditional Chinese medicines which are most frequently used in health food, analyzed their anti-fatigue effect mechanisms, and summarized the best types of anti-fatigue food, so as to promote the scientific development of anti-fatigue health food industry, expand the market application scope of anti-fatigue health food, better respond to the construction of a healthy China and serve for people's health.

Content Determination of Total Flavonoids and Shikimic Acid in Pine Needles of Pinus massoniana Lamb. in Wudang Area / 中国中医药信息杂志

Objective To establish a method to determine the contents of total flavonoids and shikimic acid in pine needles of Pinus massoniana Lamb.in Wudang Area.Methods Rutin was used as reference standard,and the content of total flavonoids in pine needles of Pinus massoniana Lamb. was determined by UV spectrometry at wavelength of 500 nm. The content of shikimic acid was determined by HPLC-DAD. The Fortis Xi C8 column (5 μm, 250 mm × 4.6 mm) was adopted with acetonitrile - 0.4% phosphoric acid solution (8:92, V/V) as mobile phase at the flow rate of 0.9 mL/min. The detection wavelength was 213 nm; the column temperature was 30 ℃; the injection volume was 20 μL. Results The linear range was 8.26-49.54 μg for rutin (r=0.999 4) with an average recovery of 99.2%, RSD=1.94%. The linear range was 10.26-61.56 μg for shikimic acid (r=0.999 4) with an average recovery of 99.5%,RSD=1.93%.The contents of total flavonoids in pine needles of Pinus massoniana Lamb.was 28.33 mg/g, and shikimic acid was 15.25 mg/g, respectively. Conclusion The method is simple, rapid, accurate and reproducible. It can be used for the content determination of total flavonoids and shikimic acid in pine needles of Pinus massoniana Lamb. in Wudang Area.

Correlative Study between Detection of Human Serum Helicobacter Pylori SodB Antibody and the Occurrence of Gastric Cancer / 现代检验医学杂志

Objective To investigate the relationship between the level of serum iron-cofactored superoxide dismutase (SodB) antibody encoded by Helicobacter pylori (H.pylori) genome in infected populations of H.pylori and the occurrence of gastric cancer.Methods Serum samples from 114 cases and 104 control were collected.Indirect ELISA was used to detect serum SodB antibody level in case group and control group.The relationship between serum SodB antibody level and GC risk was analyzed by conditional logistic regression.The value of SodB in serological screening of gastric cancer was analyzed and evaluated by the receiver operating characteristic (ROC) curve.Results The level of serum SodB antibody was correlated with the occurrence of gastric cancer in subjects with OR=2.287 (95％CI:1.191～4.391)(P＜0.05).The optimal cutoff value of SodB for screening gastric cancer was determined by using receiver operating characteristic (ROC) curve,and it was 0.028 0.The area under the ROC curve for subjects was 0.575 (95 ％ CI:0.501 ～ 0.649).Conclusion The level of serum H.pylori SodB antibody was associated with the occurrence of gastric cancer.SodB alone was not effective in screening gastric cancer.It might be used in combination with other biomarkers of gastric cancer to improve further screening of gastric cancer.

Inhibitory effect and mechanism of licochalcone A on NLRP3 inflammasome / 药学学报

Lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs), treated with licochalcone A (LCA) and retreated with inflammasome inducers respectively (ATP and nigericin), were used to construct the inflammasome model of NLRP3 (NOD-like receptor family, pyrin domain containing 3), to investigate the inhibitory effect and the molecular mechanism of LCA on the activity of NLRP3 inflammasome. The secretion of mature interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and caspase-1 in the supernatants were analyzed by ELISA and the Caspase-Glo® 1 Inflammasome Assay. Supernatants and cell lysates were analyzed for the expression of pro-caspase-1, pro-IL-1β, ASC, NLRP3, IL-1β, caspase-1 by immunoblotting. The study shows that LCA inhibited the activity of caspase-1 and the secretion of IL-1β, and suppressed the activity of NLRP3 inflammasome. There was also slight inhibition of NLRC4 inflammasome induced by Lfn-Flic, but no effect on poly(dA:dT)-induced the absent in melanoma 2 (AIM2) inflammasome. Western blot showed that LCA had no effect on the protein expression of NLRP3 and pro-IL-1β, which was mediated by NF-κB pathway. In summary, LCA can inhibit the cleavage of pro-caspase-1 and suppress the secretion of IL-1β to reduce the inflammation response. The study was carried out under the approval of the Scientific Investigation Board of 302 Hospital of PLA.

Study on the mechanism of PPAR-γ dependent immunological idiosyncrasy liver injury induced by Polygonum multiflorum / 药学学报

To investigate the effects of peroxisome proliferator-activated receptor gamma(PPAR-γ)on the liver injury of Polygonum multiflorum, we established a model of immunological idiosyncrasy liver injury induced by lipopolysaccharide. The 70 Sprague-Dawley(SD)rats were randomly divided into control group, LPS group(2.8 mg·kg-1), PM group(crude drug, 2.16 g·kg-1), PPAR-γ agonist group(pioglitazone, 0.5 mg·kg-1), PM+LPS group(crude drug 2.16 g·kg-1, 2.8 mg·kg-1), PPAR-γ agonist+LPS group(0.5 mg·kg-1, 2.8 mg·kg-1)and PM+LPS+PPAR-γ agonist group(crude drug, 2.16 g·kg-1, 2.8 mg·kg-1, 0.5 mg·kg-1). The rats were orally given PM, once a day for consecutive 2 days. The control rats were given the same amount of distilled water. Liver injury was induced by intravenous injection of LPS. Sodium pentobarbital was injected intraperitoneally for anesthesia, and liver samples were collected together with blood. The plasma levels of alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6)and interferon-γ(IFN-γ)were measured. Pathological changes and hepatocellular apoptosis were examined by liver biopsy, and immunohistochemical observation of liver tissue expression of PPAR-γ and NF-κB p65. A negative correlation was observed between the expression of PPAR-γ in hepatic tissue and liver injury of Polygonum multiflorum. PPAR-γ agonist significantly reduced the PM-induced idiosyncratic liver injury in rats according to serum ALT and AST(P < 0.05), reduced liver pathological injury and hepatocyte apoptosis, decreased serum TNF-α and other inflammatory cytokines(P < 0.05), liver tissue PPAR-γ expression, and inhibited expression of NF-κB p65(P < 0.05). The results suggest that the occurrence of immunological idiosyncrasy liver injury of PM is related to inhibition of the PPAR-γ pathway and elevation of inflammatory factors. PPAR-γ agonist can reverse the idiosyncratic liver injury induced by PM, and provide a reference for elucidating mechanism of idiosyncratic liver injury induced by Polygonum multiflorum.

Chronic Lymphocytic Leukemia Prognostic Index: A New Integrated Scoring System to Predict the Time to First Treatment in Chinese Patients with Chronic Lymphocytic Leukemia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The established clinical staging systems (Rai/Binet) of chronic lymphocytic leukemia (CLL) cannot accurately predict the appropriate treatment of patients in the earlier stages. In the past two decades, several prognostic factors have been identified to predict the outcome of patients with CLL, but only a few studies investigated more markers together. To predict the time to first treatment (TTFT) in patients of early stages, we evaluated the prognostic role of conventional markers as well as cytogenetic abnormalities and combined them together in a new prognostic scoring system, the CLL prognostic index (CLL-PI).</p><p><b>METHODS</b>Taking advantage of a population of 406 untreated Chinese patients with CLL at early and advanced stage of disease, we identified the strongest prognostic markers of TTFT and, subsequently, in a cohort of 173 patients who had complete data for all 3 variables, we integrated the data of traditional staging system, cytogenetic aberrations, and mutational status of immunoglobulin heavy chain variable region (IGHV) in CLL-PI. The median follow-up time was 45 months and the end point was TTFT.</p><p><b>RESULTS</b>The median TTFT was 38 months and the 5-year overall survival was 80%. According to univariate analysis, patients of advanced Rai stages (P < 0.001) or with 11q- (P = 0.002), 17p- (P < 0.001), unmutated IGHV (P < 0.001), negative 13q- (P = 0.007) and elevated lactate dehydrogenase levels (P = 0.001) tended to have a significantly shorter TTFT. And subsequently, based on multivariate Cox regression analysis, three independent factors for TTFT were identified: advanced clinical stage (P = 0.002), 17p- (P = 0.050) and unmutated IGHV (P = 0.049). Applying weighted grading of these independent factors, a CLL-PI was constructed based on regression parameters, which could categorize four different risk groups (low risk [score 0], intermediate low [score 1], intermediate high [score 2] and high risk [score 3-6]) with significantly different TTFT (median TTFT of not reached (NR), 65.0 months, 36.0 months and 19.0 months, respectively, P < 0.001).</p><p><b>CONCLUSIONS</b>This study developed a weighted, integrated CLL-PI prognostic system of CLL patients which combines the critical genetic prognostic markers with traditional clinical stage. This novel modified PI system could be used to discriminate among groups and may help predict the TTFT and prognosis of patients with CLL.</p>

Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia / 中国医学科学院学报

Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic leukemia (CLL). Methods The clinical data of CLL patients receiving fludarabine,cyclophosphamide±rituximab (with or without rituximab) regimen or cyclophosphamide,vincristine,and prednisone±doxorubicin±rituximab regimen in our hospital from March 2000 to February 2015 were analyzed retrospectively. Therapeutic efficacies and survivals of patients treated with different regimens were evaluated and compared. Results The complete response (CR) rate and the overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were significantly higher than those treated without rituximab (38.9% vs. 21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9) months,and the median PFS and OS for patients treated without rituximab were 28.0 (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically significant (P=0.094,P=0.109). According to the cytogenetic features,patients were further divided into high-risk subgroup (with chromosome 17p deletion or 11q deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of patients treated with rituximab was 86.4%,which was significantly higher than that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk subgroup,the PFS was marginally prolonged in patients treated with rituximab,but the difference was not statistically significant(P=0.050). Conclusions Compared with traditional chemotherapy,the chemoimmunotherapies with rituximab result in higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q deletion,the use of rituximab can marginally prolong PFS.

Systematic evaluation of Liuweiwuling Tablets for treatment of liver fibrosis resulting from chronic hepatitis B / 中草药

Objective: To systematicly evaluate the efficacy and safety of Liuweiwuling Tablets combined with nucleotide drugs for the treatment of liver fibrosis resulting from chronic hepatitis B. Methods: Major databases (such as Pubmed, Embase, Cochrane Library (Issue 9, 2015), Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and WanFang Data were searched from their inception to September 9, 2015 to collect comprehensively randomized controlled trials (RCT) of Liuweiwuling Tablets combined with nucleotide drugs on the treatment of liver fibrosis resulting from chronic hepatitis B. After two reviewers separately screened literature according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies, data were analyzed with RevMan 5.3 software. Results: The total seven RCTs were included. Among all 1 021 patients involved, 529 cases were in the treatment group, while the other 492 cases were in the control group. The findings showed that compared with using nucleotide drugs alone for antiviral treatment, Liuweiwuling Tablets combined with nucleotide drugs were more efficiently in downregulating serum liver fibrosis index HA [SMD = -1.26, 95% CI (-1.92, -0.59), P = 0.000 2], LN [SMD = -1.55, 95% CI (-2.27, -0.83), P < 0.000 1], PC-III [SMD = -1.39, 95% CI (-2.21, -0.58), P = 0.000 8], IV-C [SMD = -1.49, 95% CI (-2.25, -0.72), P = 0.0001]; improved the liver function ALT [SMD = -1.17, 95% CI (-1.41, -0.94), P < 0.000 01], AST [SMD = -1.25, 95% CI (-1.54, -0.96), P < 0.000 01], TBIL [SMD = -0.87, 95% CI (-1.21, -0.53), P < 0.000 01]; increased total clinical effective rate [OR = 4.59, 95% CI (2.05, 10.25), P = 0.000 2]. While no advantage was found in reducing the incidences of HBV DNA overcast [OR = 1.51, 95% CI (0.96, 2.39), P = 0.08]; No significant adverse reactions were reported. Conclusion: Liuweiwuling Tablets combined with nucleotide drugs could be effective in improving liver function, controlling liver fibrosis, and increasing total clinical effective rate while its antiviral efficacy approximate with using the nucleotide drugs alone, less adverse reaction, and better tolerability; Although in recent years, the quantity and quality of RCTs research have a rising trend year by year, but still need to be from the clinical design of scientific, the standardization of the report, and many other links to improve research level.

Protective effects of oxymatrine against H2O2-induced damage in L02 cells / 中国中药杂志

To investigate the protective effects of oxymatrine (OMT) against H2O2-induced damage in L02 cells and research the mechanism,L02 cells were used as the research object. The oxidative stress model of L02 was established by hydrogen peroxide (H2O2). CCK-8 was used to detect the cell activation of L02 cells treated by different OMT. FCM (flow cytometry) assay was used to evaluate the cell proliferation of L02 cells treated by OMT. The apoptosis of L02 cells was detected using Annexin-V/7-AAD apoptosis detection kit. The level of ROS was detected by DCFH-DA fluorescence probe. The GSH-PX and SOD were detected by micro plate and colorimetric method. Results showed that when the concentration of OMT is between 6.25 and 100 mg•L⁻¹, it could promote the production of NADPH and strengthen the activity of GSH-PX and SOD to get rid of the ROS to protect the L02 cell from the apoptosis of L02 cell induced by H2O2.

Protective effects of Liuwei Wuling tablet on acute alcoholic-induced liver injury in mice / 中国中药杂志

The protective action and the relevant mechanism of Liuwei Wuling tablet on acute alcoholic hepatic injury in mice were investigated. All the C57BL/6 mice were divided randomly into 7 groups including blank, model, bifendate (150 mg•kg⁻¹, positive control) and experimental groups consisted of extremely low dose (0.1 g•kg⁻¹), low (0.5 g•kg⁻¹), upper (4 g•kg⁻¹) and high dose (8 g•kg⁻¹) of Liuwei Wuling tablet groups. The acute liver injury model was induced by modified method that the model, positive control and experimental groups were orally administrated 56% alcohol (6 g•kg⁻¹) twice at 12 hour intervals on the fifth day after drugs administration. After 12 hours, the mice were sacrificed to contribute blood and liver for biochemical and histological examinations. Compared with the model, the activities of ALT and AST in serum decreased significantly in different Liuwei Wuling tablet groups. Meanwhile, in liver tissue, the levels of TG, MDA, TNF-α and IL-1β reduced obviously while the GSH and SOD activities showed markedly increase with a dose-dependent manner. Correspondingly, the microscopically pathological differences of the liver tissue observed by HE and oil red O staining indicated that the liver cell swelling, hydropic degeneration and lipid droplets formation induced by alcohol were significantly improved, which suggested the Liuwei Wuling tablet can reduce the liver injure. In conclusion, the Liuwei Wuling tablet had the protective effect on acute alcoholic hepatic injury which maybe depended on the mechanism of relieving lipid peroxidation, elevating antioxidant enzymes activity, inhibiting oxidative stress and reducing inflammation factors expression.

Divergence Analysis of Hepatitis Virus Infection between Aggressive and Indolent B Cell Non-Hodgkin's Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence rate of hepatitis B virus(HBV)and hepatitis C virus(HCV)between aggressive and indolent B cell non-Hodgkin's lymphoma (B-NHL), and to compare the different infection rate of Hepatifis Virus between the 2 groups.</p><p><b>METHODS</b>Integrated clinical information of 733 newly diagnosed indolent B-NHL patients and 148 aggressive B-NHL patients from January 1994 to January 2014 was retrospectively analyzed. The difference of hepatitis virus infection was compared between the 2 groups.</p><p><b>RESULTS</b>The positive rate of HCV-Ab was 1.8% in 881 newly diagnosed B-NHL patients. The HCV prevalence was 1.9% and 1.35% in the indolent and aggressive B-NHL group respecitvely. Compared with general population, the HCV positive rate was significantly higher in the whole B-NHL group and the indolent group(1.8% vs 0.4%,1.9% vs 1.4%)(P<0.01), while it was not significantly different in the aggressive group (1.35% vs 0.4%)(P=0.068). The positive rate of HCV-Ab was not significantly different between the indolent and the aggressive group (1.9% vs 1.35%)(P=0.639). The HBs-Ag positive rate in the whole B-NHL group was 9.0%, which was significantly higher than that in the general population (9.0% vs 7.2%)(P<0.05). The positive rate of HBs-Ag in the indolent and aggressive B-NHL group was 7.9% and 14.2%, respectively. It was significantly higher in the aggressive group than that in the indolent one (14.2% vs 7.2%)(P<0.01). Compared with the general population, the aggressive group had significantly higher prevalence rate of HBV. However, it was not significantly different between the indolent group and the general population (7.9% vs 7.2%)(P>0.05).In the aggressive B-NHL group,the co-expression of HBs-Ag,HBe-Ag and anti-HBc-Ab was 4.4%, which was higher than that in the indolent one (4.7% vs 1.2%)(P<0.01). However, compared with the indolent group, the co-expression of HBs-Ag, anti-HBe-Ab and anti-HBc-Ab was not significantly different in the aggressive group (5.5% vs 6.1%)(P>0.05).</p><p><b>CONCLUSION</b>The HCV is more relevant with indolent B-NHL, the HBV has more relevance with the aggressive patients.</p>

Isolation, identification and full-length genome sequence analysis of encephalomyocarditis virus from local aardvarks / 病毒学报

Encephalomyocarditis virus (EMCV) is a natural epidemic zoonotic pathogen. However, no reports have been published regarding the isolation, identification and full-length genome of EMCV from a local aardvark population. In present study, an EMCV isolate HNXX13 was isolated from aardvarks named Huainan-pig in Henan Province. The systematic identification, full-length genome sequencing and molecular characteristic analysis of the isolate HNXX13 were conducted. The result showed that the isolate was spherical with a diameter of 24-30 nm, neither heat- nor acid-resistant, sensitive to trypsin, insensitive to chloroform, not protected by bivalent cationic, and the specific fluorescence was observed in the cytoplasm of BHK-21 cells infected with the isolate by using indirect fluorescence assay. The full-length genome of EMCV HNXX13 generated a 7 725bp sequence (GenBank: F771002), with 81.0%-99.9% nucleotide identity to reference strains from different animals, and 99.5% with a Chinese reference strain isolated earlier from a commercial pig herd. The phylogenetic tree based on the full-length genome and ORF sequences identified that all EMCV strains were divided into three groups G1, G2 and G3, and strain HNXX13 belonging to the G1 group with other Chinese reference strains. The result also identified that this EMCV infection could cause severe clinical signs in a local aardvark population, and enriches the molecular epidemiological data of EMCV in China. Regional differences exist in EMCV genome and transmission is limited within a certain area. However, the cross-infection and transmission of EMCV between aardvark and mice appears most likely. Mutations have occurred in some amino acids of EMCV strain HNXX13 during the transmission in local aardvark herd and these mutations might make the virus easier to infect the aardvark.

Investigation of etiology of massive infection with porcine pseudorabies virus in Henan and neighboring Provinces / 病毒学报

In early 2011, the serious outbreak of porcine pseudorabies virus (PRV) infection suddenly recurred in Henan and neighboring Provinces. To investigate the etiology of massive infection with PRV, 16 800 serum samples, 905 porcine epidemic diarrhea virus (PEDV) back-feeding tissues, and 56 PR gene deleted live vaccines were colleted from January 2011 to May 2013 to detect PRV field infection using a PRV gE antibody test kit. The gE and TK genes of 11 new epidemic PRV strains were sequenced by PCR, and their molecular characteristics were analyzed. Moreover, virus titer determination, protective test against PRV, and vaccine potency testing were performed. The results showed that the detection rate of PRV field infection-positive pig farms was 68.06%, and the overall positive rate of PRV field infection in serum was 38.47%; the positive rates in breeding sows, breeding boars, reserve pigs, and commercial pigs were 40.12%, 30.88%, 54.67%, and 26.52%, respectively. The new epidemic strains were in the same evolutionary branch and belonged to the virulent strain group. Compared with the classical PRV strain, the virulence of new epidemic strains changed a little. The length of gE gene was 1 787 bp, and the length of TK gene was 963 bp. The nucleotide homologies of gE and TK genes to Chinese reference strains were 98.2%-99.8% and 98.90%-99.6%, respectively, and the amino acid homologies were 97.1%-99.8% and 97.5%-99.4%, respectively. Commercial vaccine had a 100% protective effect against the new epidemic strains. The positive rate of PRV field infection was 0% in vaccine and 40.44% in back-feeding tissues. The results confirmed that PRV field infection rates were rising sharply among pigs in Henan and neighboring Provinces after 2011. The main virulence genes of new epidemic PRV strains did not change significantly over the years. PR gene deleted live vaccines had no PRV field infection and could completely resist the attack of new strains. The virus carriage of breeding boars and reserve pigs and the serious PRV field infection in PEDV back-feeding tissues were the main causative factors for massive infection with PRV and epidemic outbreak in Henan and neighboring Provinces from 2011 to 2013.