Tumor cells can use different strategies to suppress the immune system and disable them for killing tumor cells. Previous studies have shown that recombinant human peroxiredoxin-5 (hPRDX5) can activate the normal anti-tumor immune, so as to control and eliminate the tumor cells, but its exact mechanism of action needs to be studied in depth. The study aimed to investigate whether hPRDX5 exerts its anti-tumor activity by activating or reversing the polarization state of mouse macrophages RAW264. 7 cells. The results of CCK8 showed that different doses of hPRDX5 could significantly enhance the viability of macrophage compared with the control group (P < 0. 001); The results of Nitric oxide (NO) test showed that hPRDX5 significantly enhanced NO secretion levels in RAW264. 7 cells (P < 0. 001); ELISA experiments revealed that hPRDX5 promotes TNF-α (P<0. 01) and IL-6 (P<0. 001) secretion in RAW264. 7 cells; Flow cytometry revealed that hPRDX5 increased the expression of antigen differentiation cluster (CD) 80 (P < 0. 01) and inducible nitric oxide oxide synthase (iNOS) (P < 0. 001) in RAW264. 7 cells, and reduced the expression of CD206 (P < 0. 001) in RAW264. 7 cells induced by tumor conditional culture solution (TCS); Lactate dehydrogenase (LDH) experiments revealed that hPRDX5 can increase the killing activity of mouse macrophages on mouse pancreatic cancer Panc02 cells. hPRDX5 is able to activate mouse macrophage RAW264. 7 cells, promotes its M1-type polarization, reverses M2-type polarization, and exerts antitumor activity through the immune-enhancing effect.

Objective: To investigate the effect of berberine on programmed necrosis of hepatocytes induced by metabolic-associated fatty liver disease (MAFLD) in mice and its related molecular mechanism. Methods: Twenty male C57BL/6N mice were randomly divided into four groups (n=5 in each group): control group (S), fatty liver group (H), berberine group(B), nuclear factor erythroid 2-related factor 2 inhibitor group (Nrf2), and all-trans-retinoic acid (ATRA) group (A). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), triglycerides (TG), total cholesterol (TC), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) concentrations were detected at the end of week 12 to calculate fatty liver index (liver mass/body mass ratio). Liver tissue was stained with HE, Masson and Oil Red O, and SAF score was used to evaluate the degree of liver injury. The expression levels of hepatic programmed necrosis-related proteins, namely receptor-interacting protein kinase 3 (RIPK3), phosphorylated mixed series protease-like domain (p-MLKL) and Nrf2 were detected by Western blot method. One-way ANOVA was used for intragroup comparisons and LSD-t tests were used for intergroup comparisons. Results: Compared with S group, H group serum ALT, AST, LDH, TG, TC, TNF-α, IL-1β levels and fatty liver index were significantly increased. The liver tissue was filled with vacuolar-like changes and inflammatory cell infiltration. Numerous red lipid droplets were observed with oil red O staining. Collagen fiber hyperplasia was evident with Masson staining. SAF scores (6.60 ± 0.55 and 0.80 ± 0.45) were significantly increased. The expressions of RIPK3 and p-MLKL were up-regulated. Nrf2 level was relatively increased, and the differences were statistically significant (P < 0.05). Compared with H group, berberine intervention group liver biochemical indexes, lipid levels, pro-inflammatory mediator expression, fatty liver index, and SAF score were significantly reduced, and the expression of RIPK3 and p-MLKL were down-regulated, while Nrf2 levels were further increased, and the differences were statistically significant (P<0.05). Compared with B group, treatment with Nrf2 inhibitor had antagonized the protective effect of berberine on fatty liver. Serum ALT, AST, LDH, TG, TC and TNF-α, IL-1β levels, fatty liver index, and SAF scores were significantly increased and the expressions of RIPK3 and p-MLKL were relatively increased, and the differences were statistically significant (P < 0.05). Conclusion: Berberine can significantly improve the metabolic-associated fatty liver disease injury in mice, and its mechanism is related to activation of Nrf2 and inhibition of programmed necrosis of hepatocytes.
Animals ; Berberine/therapeutic use* ; Fatty Liver ; Male ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism* ; Necrosis

This study steps through four key principles, four open problems and future perspectives of Chinese materia medica(CMM) ecological agriculture by presenting the historical development, existing theories and practice outcomes. Then, it focuses on refining the main principles of CMM ecological agriculture:(1)the principles of ecological niche associated with yield and comprehensive income;(2)principles of biological diversity associated with the integrated control of diseases, pests and weeds;(3)principles of adversity effects associated with the quality improvement of CMM;(4)principles of structural stability associated with the sustainable development of CMM ecological agriculture. On this basis, four burning issues of CMM ecological agriculture were obtained,(1)ecological planting mode and supporting technologies need to be perfect;(2)multi-integrated industrial coupling remains to strengthen;(3) quality assurance system of CMM ecological agriculture and high-quality and favorable price model remains to be formed;(4)awareness of the demonstration and extension of CMM ecological agriculture needs to be desired. Finally, suggestions for the sustainable development of CMM ecological agriculture are put forward:(1)strengthen the national planning and layout, develop CMM ecological agriculture accor-ding to local conditions;(2)pay equal attention to inheritance and innovation, and strengthen the theory and practical technology research of CMM ecological agriculture;(3)strengthen industrial coupling and realize the transformation of CMM ecological agriculture from a production-based to a multi-in-one compound model;(4)intensify standards and brands, building a quality assurance system for CMM ecological products;(5) publicize the demonstration and popularization of CMM ecological agriculture. In summary, the development of CMM ecological agriculture possessed a firmer theory and practice foundation, although there is still much room for improvement. A better field of Chinese medicine agricultural development with immense economic and social benefits will not a question of "if" but "when" by accurately grasp the way forward.
Agriculture ; China ; Drugs, Chinese Herbal ; Materia Medica ; Medicine, Chinese Traditional

Fusarium is the major pathogen of root rot of Pseudostellaria heterophylla. This study aims to explain the possible distribution of Fusarium species and the contamination of its toxin-chemotypes in tuberous root of P. heterophylla. A total of 89 strains of fungi were isolated from the tuberous root of P. heterophylla. Among them, 29 strains were identified as Fusarium by ITS2 sequence, accounting for 32.5%. They were identified as five species of F. avenaceum, F. tricinctum, F. fujikuroi, F. oxysporum, and F. graminearum based on β-Tubulin and EF-1α genes. LC-MS/MS detected 18, 1, and 5 strains able to produce ZEN, DON, and T2, which accounted for 62.1%, 3.4%, and 17.2%, respectively. Strain JK3-3 can produce ZEN, DON, and T2, while strains BH1-4-1, BH6-5, and BH16-2 can produce ZEN and T2. PCR detected six key synthase genes of Tri1, Tri7, Tri8, Tri13, PKS14, and PKS13 in strain JK3-3, which synthesized three toxins of ZEN, DON, and T2. Four key synthase genes of Tri8, Tri13, PKS14, and PKS13 were detected in strains BH1-4-1, BH6-5, and BH16-2, which were responsible for the synthesis of ZEN and T2. The results showed that the key genes of toxin biosynthesis were highly correlated with the toxins produced by Fusarium, and the biosynthesis of toxin was strictly controlled by the genetic information of the strain. This study provides a data basis for the targeted prevention and control of exo-genous mycotoxins in P. heterophylla and a possibility for the development of PCR for rapid detection of toxin contamination.
Caryophyllaceae ; Chromatography, Liquid ; Fusarium/genetics* ; Mycotoxins ; Tandem Mass Spectrometry

This paper analyzed life form, habitats and environmental stresses of medicinal plants and algal fungi collected in Chinese Pharmacopoeia(2015). ①It was found that only 0.94% of the medicinal plants mainly cultivated in field. The most common habitats of medicinal plants are divided into two types: those whose natural habitats are forest margins/undergrowth(about 42.53%) and those whose natural habitats are roadside, hillside, wasteland/sand(about 43.78%). The former mainly faces environmental stresses such as weak light, pests and diseases; the latter often faces the main environmental stresses of drought, strong light, ultraviolet radiation, high temperature, low temperature(day and night or annual temperature difference is large), nutrient deficiency, pests and so on. ②Based on analyzing the strategies of medicinal plants to adapt to environmental stresses, it is pointed out that the synthesis and accumulation of secondary metabolites are the most important strategies of medicinal plants to protect against environmental stresses. In the process of long-term adaptation to specific stress, the accumulation of relevant genetic variation and epigenetic inheritance has become an important condition for the formation of quality of medicinal plants. ③It is proposed that "simulative habitat cultivation" has obvious advantages in balancing growth and secondary metabolism and guaranting the quality of traditional Chinese medicinal materials.
Drugs, Chinese Herbal ; Ecosystem ; Medicine, Chinese Traditional ; Plants, Medicinal ; Ultraviolet Rays

BACKGROUNDDrug resistance to targeted therapies occurs in lung cancer, and resistance mechanisms related to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are continuously being discovered. We aimed to establish a novel method for highly parallel multiplexed detection of genetic mutations related to EGFR TKI-resistant lung cancer using Agena iPLEX chemistry and matrix-assisted laser desorption ionization time-of-flight analysis on the MassARRAY mass spectrometry platform.

METHODSA review of the literature revealed 60 mutation hotspots in seven target genes (EGFR, KRAS, PIK3CA, BRAF, ERBB2, NRAS, and BIM) that are closely related to EGFR TKI resistance to lung cancer. A total of 183 primers comprised 61 paired forward and reverse amplification primers, and 61 matched extension primers were designed using Assay Design Software. The detection method was established by analyzing nine cell lines, and by comparison with LungCarta™ kit in ten lung cancer specimens. EGFR, KRAS, and BIM genes in all cell lines and clinical samples were subjected to Sanger sequencing for confirming reproducibility.

RESULTSOur data showed that designed panel was a high-throughput and robust tool, allowing genotyping for sixty hotspots in the same run. Moreover, it made efficient use of patient diagnostic samples for a more accurate EGFR TKIs resistance analysis. The proposed method could accurately detect mutations in lung cancer cell lines and clinical specimens, consistent with those obtained by the LungCarta™ kit and Sanger sequencing. We also established a method for detection of large-fragment deletions based on single-base extension technology of MassARRAY platform.

CONCLUSIONSWe established an effective method for high-throughput detection of genetic mutations related to EGFR TKI resistance based on the MassARRAY platform, which could provide more accurate information for overcoming cancers with de novo or acquired resistance to EGFR-targeted therapies.

Objective To explore the survival time and its influencing factors of patients in Guizhou Province after they received antiretroviral therapy(ART)for treating human immunodeficiency virus (HIV)infection and acquired immunodeficiency syndrome (AIDS).Methods A retrospective cohort analysis was conducted to analyze survival time of AIDS patients who received ART in Guizhou Province in 2005-2016,life table method was used to calculate the survival probability,Cox proportional hazards regression model was used to analyze the influencing factors of survival time.Results A total of 15921 patients were included in the study,the median age at the beginning of therapy was(42.13±14.40)years old,58.61% of patients were married/housemate.The length of ART follow-up was (median[P 25 -P 75 ]:15.96[6.00 - 33.00])months.9.77% of the follow-up cases died,59.29% of the deaths occurred within 12 months of initiation of treatment;survival rates in the first,fifth,and tenth year were 93.00%,82.00%,and 74.00% respectively.Cox proportional hazards regression model analysis showed that fe-male patients were 0.58 times more likely to die than male patients(95% CI :0.49-0.68);the risk of death in-creased with increase of ages;the higher the baseline CD4+ T lymphocyte count,the lower the risk of death;the risk of death in patients without symptoms or signs before therapy was 0.70 times than those with symptoms or signs(95% CI :0.60-0.81).Conclusion The antiviral therapy of AIDS patients in Guizhou Province is generally well,patients with high risk factors for death should be paid high attention,it is suggested that medical level and service quality should be improved when patients are treated.

Objective: To explore the relationship between ABO blood group and acute non-ST-segment elevation myocardial infarction (NSTEMI) occurrence. Methods: Our research included 2 groups: NSTEMI group, 1039 relevant patients treated in Anzhen hospital from 2013-01 to 2014-12 were retrospectively enrolled; Control group, 1039 subjects with normal coronary artery which was confirmed by coronary angiography. The Baseline condition including age, previous disease history and ABO blood group was studied. Logistic regression model was used to conduct single and multivariate analysis. Results: In NSTEMI group and Control group, blood type A was 287/1039 (27.6％) vs 259 (24.9％), type B was 345 (33.3％) vs 356 (34.3％), type AB was 102 (9.8％) vs 114 (11.0％) and type O was 305 (29.4％) vs 310 (29.8％), ABO blood group distribution for A and non-A, B and non-B, AB and non-AB blood group, O and non-O had no statistic meaning between 2 groups, P>0.05. Logistic regression analysis indicated that with adjusted risk factors of MI such as age, gender, hypertension, diabetes, hyperlipemia, cerebrovascular disease and smoking, the patients with blood types A, B and AB had the similar risk for NSTEMI occurrence than type O patients; there was no relationship between ABO blood group and NSTEMI occurrence. Conclusion: ABO blood group had no relationship to NSTEMI occurrence.

OBJECTIVETo evaluate the effect of water pollution with dexamethasone on intestinal flora in mice.

METHODSTwenty Balb/c mice were randomly divided into control group and low-, moderate- and high-dose dexamethasone groups. The mice in dexamethasone groups were exposed to dexamethasone sodium phosphate in drinking water at doses of 0.035, 0.225, and 2.25 ng for 36 days. The changes in behaviors, fur condition, and feces of the mice were observed daily. All the mice were sacrificed at 36 days and the tissues in the ileocecal region was collected for denaturant gradient gel electrophoresis (DGGE) of 16S rDNA V6 variable regions of microbes and sequence analysis with BLAST.

RESULTSThe mice in the 3 dexamethasone groups all showed aggressive behaviors. Cluster analysis of DGGE graph showed relatively stable floras in the ileocecal region in all the mice, but principal component analysis identified differences in the dominating flora among the groups. Diversity analysis of the flora revealed significantly increased amount and types of bacteria in the intestinal flora in all the 3 dexamethasone groups (P<0.05 or 0.01) compared with the control group. Sequence analysis of 16S rDNA V6 regions showed 15 common bacterial species and 2 differential species between the dexamethasone groups and the control group with changes in the type and proportion of the dominating bacterium in the dexamethasone groups. Lactobacillus colonization was detected in the control group but not in moderate- and high-dose dexamethasone groups, and Shigella species were found in the latter two groups.

CONCLUSIONSWater contamination with dexamethasone can affect the nervous system of mice, cause changes in the types and amounts of intestinal bacteria and the dominating bacteria, and inhibit the colonization of probiotics in the intestinal floras to increase the risk of invasion by intestinal pathogenic bacteria.

Animals ; Bacteria ; classification ; Dexamethasone ; pharmacology ; Drinking Water ; chemistry ; Feces ; Gastrointestinal Microbiome ; drug effects ; Lactobacillus ; isolation & purification ; Mice ; Mice, Inbred BALB C ; Probiotics ; RNA, Bacterial ; genetics ; RNA, Ribosomal, 16S ; genetics ; Shigella ; isolation & purification

OBJECTIVETo evaluate the application value of magnetic resonance diffusion-weighted imaging (DWI) combined with routine T2WI sequence in the determination of pathological complete response (pCR) after neoadjuvant therapy for rectal cancer.

METHODSClinical data of 51 cases with locally advanced mid-low rectal cancer undergoing neoadjuvant therapy plus radical resection in the Rectal Cancer Center at The Sixth Affiliated Hospital of Sun Yat-sen University from June 2012 to April 2013 were analyzed retrospectively. Magnetic resonance DWI and T2WI sequences scanning were performed within 1 week before neoadjuvant therapy and within 1 week before operation. Routine single T2WI sequence and DWI combined with T2WI sequence were used separately to predict the residual tumor and to compare with postoperative pathological examination. The prediction values of two methods were compared.

RESULTSOf 51 patients, 12 cases had pathological complete response (pCR). Prediction of DWI combined T2WI sequence was correct in 8 cases of pCR, whose sensitivity and specificity were higher than those of routine single T2WI sequence (66.7%, 94.9% vs. 33.3%, 84.6%). Prediction value of DWI combined T2WI sequence for pCR was significantly higher as compared to routine single T2WI sequence (AUC, 0.808 vs. 0.590, P=0.001).

CONCLUSIONCompared with the routine single T2WI sequence, DWI combined with T2WI sequence can improve the prediction accuracy of pathological complete response.

Adult ; Aged ; Aged, 80 and over ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Predictive Value of Tests ; Rectal Neoplasms ; pathology ; therapy ; Retrospective Studies ; Sensitivity and Specificity