Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

BACKGROUND: There are few multi-city studies on the association between temperature and mortality in basin climates. This study was based on the Sichuan Basin in southwest China to assess the association of basin temperature with non-accidental mortality in the population and with the temperature-related mortality burden. METHODS: Daily mortality data, meteorological and air pollution data were collected for four cities in the Sichuan Basin of southwest China. We used a two-stage time-series analysis to quantify the association between temperature and non-accidental mortality in each city, and a multivariate meta-analysis was performed to obtain the overall cumulative risk. The attributable fractions (AFs) were calculated to access the mortality burden attributable to non-optimal temperature. Additionally, we performed a stratified analyses by gender, age group, education level, and marital status. RESULTS: A total of 751,930 non-accidental deaths were collected in our study. Overall, 10.16% of non-accidental deaths could be attributed to non-optimal temperatures. A majority of temperature-related non-accidental deaths were caused by low temperature, accounting for 9.10% (95% eCI: 5.50%, 12.19%), and heat effects accounted for only 1.06% (95% eCI: 0.76%, 1.33%). The mortality burden attributable to non-optimal temperatures was higher among those under 65 years old, females, those with a low education level, and those with an alternative marriage status. CONCLUSIONS Our study suggested that a significant association between non-optimal temperature and non-accidental mortality. Those under 65 years old, females, and those with a low educational level or alternative marriage status had the highest attributable burden.
Female ; Humans ; China/epidemiology* ; Cities ; Cold Temperature ; Hot Temperature ; Mortality ; Temperature ; Time Factors ; Middle Aged ; Male

Objective:To study the protective effect of Ophiopogonin D on lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 and its related mechanism.Methods:Mouse macrophage RAW264.7 cells were cultured and divided into normal control group, model group and Ophiopogonin D pretreatment group according to random number table method. The activity of Ophiopogonin D on RAW264.7 cells was detected by CCK-8 method; the protein levels of TNF-α, IL-1β, IL-6, reactive oxygen species (ROS), MDA and SOD were detected by ELISA; the protein expression of NF-κB, TLR4, NF-E2-related factor2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by Western Blot.Results:Compared with model group, the levels of TNF-α, IL-1β, IL-6, ROS and MDA in cell supernatant of Ophiopogonin D group were decreased ( P<0.05), and the level of SOD was increased ( P<0.05). The protein expressions of NF-κB (0.76±0.10 vs. 2.26±0.17) and TLR4 (0.98±0.09 vs. 1.74±0.19) significantly decreased ( P<0.05). The protein expressions of Nrf2 (0.85±0.03 vs. 0.54±0.03) and HO-1 (0.97±0.11 vs. 0.37±0.04) significantly increased ( P<0.05). Conclusion:Ophiopogonin D may reduce inflammatory response by reducing TLR4/NF-κB pathway, and activate Nrf2/HO-1 pathway to reduce oxidative damage and play a protective role.

Objective: To investigate the effect of tripartite motif containing 59(TRIM59) on the biological function of human colorectal cancer HCT116 cells and its possible mechanism. Methods: The recombinant TRIM59 interference plasmid(si-TRIM59) was constructed and transfected into colorectal cancer cell line HCT116 by liposome transfection. The transfection efficiency was verified by RT-qPCR and Western blot. The effects of TRIM59 gene silencing on the proliferation, colony-formation ability and cell cycle of colorectal cancer cells were detected by CCK-8 method, colony formation assays and flow cytometry respectively. Western blot was used to detect the expression level of CDK4 and cyclinD1. Results: The expression levels ofTRIM59mRNA and protein in colorectal cancer cells were significantly higher than those in normal colorectal mucosa cells(P<0. 05). After knockdown of TRIM59expression, the proliferation activity and colony forming ability of HCT116 cells were significantly inhibited(P<0. 05), and the cell cycle was arrested in G0/G1 phase. At the same time, the expression levels of CDK4and CyclinD1 significantly decreased(P<0. 05). Conclusion TRIM59was highly expressed in colorectal cancer cells. Down regulation ofTRIM59expression can inhibit the proliferation and clone formation of colorectal cancer cells, suggesting thatTRIM59may become a new target for gene therapy of colorectal cancer.

In order to screen African swine fever virus (ASFV) diagnostic antigen with the best enzyme linked immunosorbent assay (ELISA) reactivity. By establishing the ELISA method, the diagnostic antigen of ASFV p30 protein expressed by baculovirus-insect cell expression system as reference, we explored the antigenic properties and diagnostic potential of ASFV p35 protein expressed by prokaryotic expression system as a diagnostic antigen. The results of Western blotting and immunofluorescence show that the molecular weight of the recombinant p35 protein and p30 protein obtained was 40 kDa and 30 kDa, respectively, and these two proteins had good immuno-reactivity with ASFV positive serum. Recombinant p30 and p35 proteins were used as diagnostic antigens to establish ELISA, and the sensitivity and repeatability of these methods were tested. The results show that although the detection sensitivity of the p30-ELISA established in this study was higher than that of the p35-ELISA, the sensitivity of p35-ELISA was 95.8%, and variations in intra- and inter-assay repeatability of the two methods were less than 10%. The coincidence rate between the p35-ELISA and the imported kit was 97.2%. Results show that p35-ELISA was sensitive and stable, and could detect specific antibodies against ASFV.
African Swine Fever/diagnosis* ; African Swine Fever Virus/genetics* ; Animals ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Recombinant Proteins/genetics* ; Swine

To screen the best genotypeⅠJapanese encephalitis virus subunit vaccine candidate antigens, the prMEIII gene, the polytope gene and the prMEIII-polytope fusion gene of the GenotypeⅠJapanese encephalitis virus GS strain were cloned into prokaryotic expression vector pET-30a. The recombinant proteins were obtained after the induction and purification. The prepared recombinant proteins were immunized to mice, and the immunogenicity of the subunit vaccine candidate antigens was evaluated through monitoring the humoral immune response by ELISA, detecting the neutralizing antibody titer by plaque reduction neutralization test, and testing the cell-mediated immune response by lymphocyte proliferation assay and cytokine profiling. The recombinant proteins with the molecular weights of 35 (prMEIII), 28 (polytope antigen) and 57 kDa (prMEIII-polytope) induced strong humoral and cellular immune responses in mice. Compared with prMEIII-polytope and polytope proteins, the prMEIII protein induced a significant expression of IL-2 and IFN-γ (P<0.05) and the significant lymphoproliferation of splenocytes (P<0.05). The neutralizing antibody titer induced by the prMEIII protein was close to that induced by the commercial attenuated vaccine SA14-14-2 (P>0.05). The study suggests that the prMEIII protein can be used for the development of the Japanese encephalitis virus subunit vaccine.
Animals ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Encephalitis Virus, Japanese ; immunology ; Encephalitis, Japanese ; immunology ; prevention & control ; Immunogenicity, Vaccine ; Mice ; Mice, Inbred BALB C ; Vaccines, Subunit ; immunology ; Viral Vaccines ; immunology

BACKGROUND: The injectable carboxymethyl glycosaminoglycan anti-adhesion gel prepared in the previous study combines the advantages of anti-adhesion membrane and anti-adhesion liquid. It can form soft gel in situ in a relatively short time, which is not affected by body position, bear the pressure of surrounding tissues and can be used without compression. OBJECTIVE: To evaluate the biocompatibility of medical injectable carboxymethyl glycosaminoglycan anti-adhesion gel. METHODS: Logarithmic growing L929 cells were used as test cells, and the cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was detected by MTT method. The intradermal stimulation test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was carried out in Japanese big ear rabbits. Guinea pigs were used as experimental animals to carry out intradermal induction and local induced delayed hypersensitivity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. Wistar rats were used as experimental animals to carry out the subchronic toxicity test of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract. RESULTS AND CONCLUSION: The cytotoxicity of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract was grade 1, meeting the standard requirements. Injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract had no potential intradermal stimulation and no potential skin sensitization. In the subchronic toxicity test, the rats were subjected to the tail vein injection of injectable carboxymethyl glycosaminoglycan anti-adhesion gel extract for 28 continuous days, and there was no obvious subchronic systemic toxicity in body mass, hematology, coagulation function, blood biochemistry and visceral pathology. These results indicate that the injectable carboxymethyl glycosaminoglycan anti-adhesion gel has good biosafety.

Objective To research the optimal preparation technology of salinomycin micelle.Methods DSPE-PEG2000 was selected as the carrier.Salinomycin was selected as the model drug.The film dispersion method, the ethanol injection method and the dialysis method were used to prepare salinomycin micelles respectively.The comprehensive evaluation indexes included entrapment rate and drug-loading rate, release capacity and vitro cytotoxicity test in order to select the most suitable preparation technology of salinomycin micelle .Results The film dispersion method is the most suitable preparation technology of salinomycin micelle in the three methods.Its average grain diameter was (14 ±2.3) nm, entrapment rate was (82 ± 2.6)%, drug-loading rate was (6.3 ±2.1)%, IC50 to HepG2 tumor cells was 16.10 ±3.71.Conclusion The film dispersion method of salinomycin micelles has the advantages with the smallest size, the highest entrapment rate and the largest drug-loading rate, which has the function to kill tunmor cells and release slowly.

Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.

Objective To investigate the risk factors of fetal death in patients with severe preeclampsia Methods Clinical data of 70 cases with severe preeclampsia were analyzed retrospectively,including 53 cases of fetal survival and 17 cases of death.Results There was shorter pregnancy duration in fetal death group (P ＜ 0.05) but there were no significant differences in the age,serum albumin level,systolic blood pressure,diastolic blood pressure and mean arterial pressure in 2 groups (P ＞ 0.05).Pulmonary edema was correlated to gestational week (P ＜ 0.05);the higher the gestational age was,the higher the occurrence of pulmonary edema.Conclusion Earlier onset of severe preeclampsia predicts higher rate of fetal death.