Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Objective:To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis).Methods:This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children′s Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test.Results:Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline( H=35.854, P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],( H=39.559, P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline ( H=79.695, P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline ( F=3.563, P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),( F=2.456, P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline( F=5.497, P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline( F=0.751, P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions:The combined diagnosis and management can significantly improve the control level of children′s airway allergic diseases, which should be implemented in the management of children′s airway allergic diseases.

Objective:To evaluate the clinical efficacy of the combined diagnosis and management in children with airway allergic diseases(bronchial asthma, allergic rhinitis).Methods:This observational study belongs to cluster sampling cases, which included the clinical data from children with airway allergic diseases in Allergy Department and Otorhinolaryngology Department of Beijing Children′s Hospital from April to December in 2015. They were followed up every three months during 12 months. All the subjects were required to continuously record daily symptom by diary card. ACT/c-ACT, VAS, treatment steps to control asthma, respiratory infections, wheeze, pulmonary function(FEV1%pred,FEV1/FVC,PEF%pred,FEF25%pred,FEF50%pred,FEF75%pred,MMEF%pred), FeNO were assessed in every visiting. The mean±standard deviation was used for the measurement data in accordance with normal distribution. Comparing the pulmonary function indexes at every point, the measurement data with normal distribution and uniform variance were analyzed by single factor analysis of variance, and the measurement data with uneven variance were tested by non-parametric rank sum test.Results:Among 147 recruited participants, 106 completed the combined diagnosis and management. The airway allergic diseases control rate was 87.7% at 12 months after the combined diagnosis and management. At every point, the average daily symptom score and VAS score which were significantly lower than at the baseline( H=35.854, P=0.000)[ 1.2(0.7,2.2),0.6(0.2,1.5),0.4(0.1,1.0),0.5(0.1,1.1) vs 2.0(1.0,3.5)],( H=39.559, P=0.000)[2.5(0.5,4.7),2.2(0.3,4.4),1.8(0.2,4.6),1.6(0.3,3.8) vs 6.9(4.1,9.8)]. ACT/c-ACT score at 3, 6, 9, 12 months were significantly higher than at the baseline ( H=79.695, P=0.000) [25.0(22.5,27.0),26.0(24.0,27.0),25.0(23.0,27.0),25.0(24.0,27.0) vs 20.0(17.0,22.0)]. FEV1%pred and FEF25%pred at 3, 6 months were significantly higher than at the baseline ( F=3.563, P=0.007)(104.7±12.6 vs 96.8±14.5,103.0±10.3 vs 96.8±14.5),( F=2.456, P=0.046)(96.6±22.0 vs 85.0±21.9,93.3±18.0 vs 85.0±21.9). PEF%pred at 3, 6, 9, 12 months after the combined diagnosis and management were significantly higher than at the baseline( F=5.497, P=0.000)(105.1±18.1,101.2±15.3,99.7±17.1,99.8±17.5 vs 90.3±17.8). FeNO at 3, 6, 9, 12 months respectively were no significantly differences at the baseline( F=0.751, P=0.558)(25.7±23.6 vs 30.7±25.6,25.9±16.5 vs 30.7±25.6,27.5±20.2 vs 30.7±25.6,30.6±19.6 vs 30.7±25.6).The respiratory infections rate were 69.8%(74/106),67.0%(71/106),60.4%(64/106),51.9%(55/106) at 3, 6, 9, 12 months respectively. The wheezing rate was 24.5%(26/106),14.2%(15/106),11.3%(12/106),7.5%(8/106) at 3, 6, 9, 12 months respectively. Conclusions:The combined diagnosis and management can significantly improve the control level of children′s airway allergic diseases, which should be implemented in the management of children′s airway allergic diseases.

Objective Toinvestigatethechangesofiron,fatandwatercontentinspleentissuesforacutepancreatitis(AP).Methods Atotal of44patientswithAP(experimentalgroup)and21healthysubjects(controlgroup)wererecruitedinthisstudy.RoutineupperabdominalMR scansandIDEAL-IQsequencescanwereperformed.TheR2?,Water,FatandFFvaluesofspleenwererespectivelymeasuredinthe experimentalgroupandcontrolgroup,andthedataofthetwogroupswereanalyzedstatistically.Results TheR2?value(P=0.011),Water value(P=0.003)andFatvalue(P=0.022)ofspleenintheexperimentalgroupandthecontrolgrouphadsignificantdifferences, whiletheFFvalue(P=0.861)didn’t.TherewerenosignificantdifferencesinR2?,WaterandFatvaluesinthemild,moderateand severeAP (P>0.05).aswellasintheyounggroup (14-44yearsold),themiddle-agedgroup (45-59yearsold)andtheelderly group (≥60yearsold)inAP (P>0.05).Conclusion APcanleadtothechangesofirondeposition,fatandwatercontentinspleen tissue,andIDEAL-IQtechnologycanquantitativelyevaluatethechangeofthem.

Infectious and inflammatory diseases are important diseases threatening human health. Without timely control, a series of complications will occur in patients, such as sepsis, inflammatory factor storm, and even lead to death. It has been found that cytochrome P4501A1 (CYP1A1) plays a key role in the development of infectious and inflammatory diseases through aromatic hydrocarbon receptor (AhR) dependent and non-dependent pathways in different cells and organs induced by different substances. The non AhR dependent regulatory mechanism of CYP1A1 and the different roles of CYP1A1 in infection and inflammation is reviewed in order to provide reference for further research on the relationship between CYP1A1 and infection and inflammation.

Objective To determine the inhibitory effects of Ellipticine (ELL) on inflammation in lipopolysaccharide (LPS)-induced RAW264.7 cells of mouse and explore its molecular mechanism.Methods The RAW264.7 cells in log phase were challenged by LPS (10 mg/L) to induce inflammation and then treated with ELL (0.05, 0.5, 5μmol/L). At the same time the cells treated with ELL (5μmol/L) were considered as ELL control group while without any stimulation as control group. After 12 hours intervention, the content of inflammatory factors in cell supernatant was detected by enzyme linked immunosorbent assay (ELISA), and then confirmed the most suitable concentration for the next experiment. After LPS of 10 mg/L was used to challenged RAW264.7 cells to cause inflammation, 5μmol/L ELL was used for intervention, and the mRNA expressions of inflammatory cytokines were detected by reverse transcription-polymerase chain reaction (RT-PCR) after 2, 4, 6 and 12 hours; the nuclear translocation of nuclear factor-κB p65 (NF-κB p65) as well as the phosphorylation levels of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinases (p38MAPK), c-Jun N-terminal kinase (JNK), c-jun, c-fos were detected by Western Blot after 15 minutes, 30 minutes, 1 hour and 2 hours.Results ① The different proliferative potential of RAW264.7 treated with LPS (10 mg/L) and ELL (0.05, 0.5, 5μmol/L) had no significant difference comparing with control group, which indicated that ELL had no cytotoxicity with experimental concentration and had no effect on the cell proliferative potential as the result of drug interaction. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in supernatant were significantly increased after induced by LPS comparing with control group. However, the different concentrations of ELL could dose-dependently reverse the production of inflammatory factors, and 5μmol/L was the optimum concentration of anti-inflammatory. ② Compared with control group, the mRNA expressions of TNF-α, IL-6 were significantly increased, the nuclear translocation level of NF-κB p65 increased as well as the phosphorylation levels of ERK, p38MAPK, JNK, c-fos, c-jun after stimulated by LPS. While, the different concentration of ELL could reverse the mRNA of TNF-α, IL-6 and phosphorylation levels of JNK, c-fos, c-jun [TNF-αmRNA (2-ΔCt): 2.45± 0.19 vs. 3.41±0.32 after 2 hours, 1.20±0.11 vs. 2.11±0.21 after 4 hours, 1.68±0.09 vs. 2.51±0.31 after 6 hours;IL-6 mRNA (2-ΔCt): 3.41±0.52 vs. 4.10±0.38 after 6 hours, 1.61±0.08 vs. 3.91±0.25 after 12 hours; p-JNK/GAPDH:0.557±0.034 vs. 1.049±0.056 after 1 hour, 0.439±0.040 vs. 0.855±0.038 after 2 hours; p-c-fos/GAPDH: 0.158± 0.030 vs. 0.741±0.035 after 1 hour, 0.156±0.015 vs. 0.932±0.030 after 2 hours; p-c-jun/GAPDH: 0.425±0.036 vs. 0.802±0.059 after 1 hour, 0.345±0.075 vs. 0.952±0.068 after 2 hours; allP < 0.05]. However, it had no significant effect on the nuclear translocation level of NF-κB p65 and the phosphorylation level of ERK and p38MAPK. Conclusion ELL inhibited the production of IL-6, TNF-α inflammatory factors in LPS-induced RAW264.7 cells through suppression the phosphorylation of JNK and activator protein-1 (AP-1).

Over the past two decades, multiple drug-resistant infections have escalated globally with the significantly increased morbidity and mortality due to the unreasonable uses of antimicrobial agents in areas such as animal husbandry, industry and medicine. As the situation of drug resistance has been progressively serious, anti-drug-resistant clinical strategies have attracted widely social concerns. This review will report the current status of antibiotic resistance and the mechanism of antibiotic-resistance all over the world. The anti-drug resistance strategies are the emphasis of our report, including the new indication of old antibiotics, the combination of existing antibiotics, the development of new antibiotics, nano-antibiotics, and non-infection treatment with immunomodulators and phage. This review aims to further understand the current situation of drug resistance, which optimizes the strategies of drug-resistant bacteria and clinical services.

OBJECTIVETo compare the clinical efficacy on vascular cognitive impairment with no dementia (VCIND) between the combined therapy of auricular acupuncture and acupuncture and the simple acupuncture.

METHODSOne hundred patients of VCIND were randomized into a combined therapy of auricular acupuncture and acupuncture group (a combined therapy group) and an acupuncture group, 50 cases in each one. The basic internal medicine treatment was applied in the two groups. Additionally, in the combined therapy group, auricular acupuncture and's three needling therapy were used. pizhixia (AT), xin (CO), shen (CO), gan (CO), erzhong (HX) were selected in auricular acupuncture, once every Monday, Wednesday and Friday;,andwere selected in's three needling therapy, once a day. In the acupuncture group,'s three needling therapy was just provided, once a day. The treatment was given for 4 weeks in the two groups. Montreal cognitive assessment (MoCA) and social function activities questionnaire (FAQ) were adopted for the evaluation comparison before treatment and in 2 weeks and 4 weeks after treatment in patients of the two groups.

RESULTSCompared with those before treatment, the total scores of MoCA were improved in 2 and 4 weeks after treatment in the two groups (all<0.01). The score in the combined therapy group was improved more apparently as compared with that in the acupuncture group (<0.01). FAQ score was reduced in the two groups (all<0.05). The score in the combined therapy group was reduced more apparently as compared with that in the acupuncture group (<0.05). As compared with the result in 2 weeks of treatment, MoCA score was improved in the two groups in 4 weeks of treatment (both<0.01), the improvements in the combined therapygroup were more obvious than those in the acupuncture group (<0.05) and FAQ score was reduced in the two groups (<0.05), but the difference was not significant between the two groups (>0.05).

CONCLUSIONSThe combined therapy of auricular acupuncture and acupuncture effectively improve the cognitive function and social function, which are better than the effects of simple acupuncture in VCIND. The improvement of the combined therapy in social function is more advantageous in the treatment of the first two weeks.

Objective] To analyze the clinical experience of associate professor Huang Lixing in the treatment of cough in children.[Method] By following teacher Huang Lixing clinical studies,organizing the relevant case data,to summarize the academic thoughts and clinical experience of professor Huang in treating infantile cough,and for proven cases. [Results] Associate professor of Huang Lixing believes that the children of delicate organs,coupled with parents nursing or treating improper,vulnerable to the formation of phlegm damp retention in the lung,complex sense of cold cough syndrome.The treatment is to eliminate the cold outside and remove the phlegm dampness.The evidence is based on treatment mechanism and flexible use of medicine,it has achieved good results. [Conclusion] According to the special characteristics of children's diseases,Huang dialectically uses the treatment of Xingsu San,and expands its application range.It is worth the majority of doctors for reference.

Objective To determine the effect of lipoxins (LX) A4 and its agonist (BML-111) on the survival of RAW264.7 macrophage cells and TLR4/NF-κB signaling pathway. Methods RAW264.7 cells were treated with different concentrations of LPS, then the effect of LX A4 and BML-111 on the survival rate of these cells was observed. Cytotoxicity were detected by CCK-8 method and RT-PCR was used to detect the TLR4 and TRAF6 mRNA. The protein levels of TLR4 and pNF-κB p65 in RAW264.7 were determined by Western Blot. Results The survival rates of macrophage treated with LPS for 6 h in 1 000 ng/mL LPS in LX A4 group and BML-111 group were significantly higher than that in control group (P < 0.05). In the present of LPS, the TLR4 mRNA levels in RAW264.7 cells from LX A4 group and BML-111 group were significantly higher than those in the corresponding non-LPS groups. And the TRAF6 mRNA levels in each LPS stimulation group were higher than those in the corresponding non-LPS groups (P<0.05), while the protein level of TRAF6 in LX A4 and BML-111 groups were significantly lower than that in control group (P < 0.05). Stimulated with LPS, the protein levels of pNF-κB p65 in the LX A4 group and BML-111 group were all significantly lower than that in control group (P<0.05), and pNF-κB p65 expression level in control group was also significantly higher than the corresponding non-LPS groups (P < 0.05). Meanwhile, no significant difference was found between LX A4 and BML-111 group (P > 0.05). Conclusion LX A4 and BML-111 could inhibit the cytotoxicity of LPS on the RAW264.7 macrophage cells through the inhibition of the activation of TLR4/NF-κB signaling pathway, then reduce the inflammation. And this stable BML-111 may appear as another promising treatment for IBD disease.