Programmed death-1 (PD-1) is an inhibitory immune checkpoint that binds to programmed death-ligand 1 (PD-L1) to regulate the immune response and maintain immune system homeostasis of the immune system. Through overexpression of PD-L1, tumor cells bind to PD-1 on the surface of immune cells, inhibiting the activity and function of immune cells, leading to immune escape of cancer cells and tumor progression. Gastrointestinal cancer is a common malignancy with a high mortality rate worldwide, and the effectiveness of current systematic treatment options is limited. In recent years, immune checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors have attracted much attention in cancer therapy. Immunotherapy has been incorporated into the treatment of some gastrointestinal malignancies. Different from traditional treatment, it uses various means to stimulate and enhance the immune function of the body to achieve the therapeutic purpose of controlling and eliminating tumor cells. However, although PD-1/PD-L1 inhibitors have shown potential in the treatment of gastrointestinal tumors, the efficacy of single inhibitor therapy is limited, which may be due to the ability of tumors to escape immune attack through other pathways after inhibitor treatment, or the presence of other immunosuppressive factors. For example, PD-1 and PD-L1 inhibitors can be combined with other immune checkpoint drugs, molecularly targeted drugs, or chemotherapy drugs to simultaneously act on different immune pathways and improve the comprehensive effect of immunotherapy. However, to achieve an effective combination therapy, we need to delve into the specific mechanisms of action of the PD-1/PD-L1 axis in the development and progression of gastrointestinal tumors, which can help to develop the best treatment strategy and provide individualized treatment options for the appropriate patient population. Therefore, future studies should focus on the regulatory mechanisms of PD-1/PD-L1 axis and evaluate the therapeutic effects of different treatment combinations on gastrointestinal tumors. In this paper, we review the research progress of PD-1/PD-L1 axis in tumorigenicity and its mechanism, and review the single and combined treatment strategies of PD-1 and PD-L1 inhibitors in gastrointestinal tumors.

Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus(SLE)mice.Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups:model group,Prednisone group,astragaloside Ⅳ group,astragaloside Ⅳ+CHPG[nuclear factor KappaB(NF-κB)pathway activator]group and astragaloside Ⅳ+Nigerian[NOD-like receptor family pyrin domain containing protein 3(NLRP3)activator]group,with eight mice in each group.Eight female MRL/MpJ mice were used as normal group.During the administration,the body mass was weighted.After administration,the spleen,thymus and kidney were weighted,and the organ index was calculated.The 24-hour urinary protein level in urine samples,the biochemical indexes of creatinine(SCr),blood urea nitrogen(BUN),autoantibodies[antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody,anti-snRNP/Sm antibody]and inflammatory mediators[interleukin(IL)-1β,IL-18]in blood samples were detected.The pathological damage of renal tissue was observed by hematoxylin-eosin(HE)staining,and the fibrosis of renal tissue was observed by Masson staining.The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot.Results Compared with the model group,the body mass of mice in prednisone group and astragaloside Ⅳ group increased,the spleen index,thymus index and kidney index were decreased,the serum levels of ANA antibody,anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased,the levels of SCr,BUN and 24-hour urine protein were decreased,the levels of IL-1 βand IL-18 wrere decreased,the ratios of p-p65/p65,p-IKBα/IKBα,cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased(all P＜0.05),and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated,there being no significant difference between the two administration groups(P＞0.05).NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent.Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice,reduce renal injury and inflammatory response,and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Toxoplasma gondii is a worldwide distribution of Apicom-plexans,which are widely parasitic in human and warm-blooded animals.Due to the factors such as host and geographical distribution,the population structure has rich genetic diversity.At present,the study of the genotype of Toxoplasma gondii and summary papers are relatively few.This paper reviews the biological information that has been reported in the world regarding the toxoplasmosis of birds such as domesticated chickens,ornamental birds,pet birds and wild rare birds,and to provide basis for further research on biological information such as epidemiology of bird toxoplasmosis and population structure of insects.

Objective: To investigate the factors influencing the postoperative resolution of varicocele-associated scrotal pain. METHODS: Using the keywords "varicocele", "testicular pain", "scrotal pain", "painful varicocele", "ligation", and "varicocelectomy", we searched the PubMed, Embase, Cochrane Collaboration's Database, CNKI, Wanfang, and VIP Database up to October 2016 for the studies relating to surgical treatment of varicocele-associated scrotal pain. We assessed the quality of the cohort studies included using the Newcastle-Ottawa Scale and that of the randomized controlled trials included with the Cochrane Collaboration's tool. We conducted a meta-analysis using the RevMan software. RESULTS: Finally 14 studies were included in this meta-analysis, of which, 2 involved the history of disease, 8 involved the nature of pain, 2 involved the intensity of pain, 9 involved the grade of varicocele, 3 involved the side of varicocele, 9 involved surgical approaches, 3 involved surgical techniques, and 4 involved postoperative recurrence. The pain resolution rate was significantly higher after subinguinal ligation than after high or inguinal ligation (RR = 0.82, 95% CI: 0.76－0.89, P <0.01; RR = 0.92, 95% CI: 0.86－0.99, P = 0.02), and so was it after microsurgery than after laparoscopic varicocelectomy (RR = 0.77, 95% CI: 0.60－0.99, P = 0.04). CONCLUSIONS Subinguinal varicocelectomy and microsurgery are more effective options than laparoscopic and high or trans-inguinal ligation of the spermatic vein for resolution of varicocele-associated scrotal pain, while the history of disease, the nature and intensity of pain, the grade and side of varicocele, or postoperative recurrence cannot be regarded as the influencing factors.
Adult ; Genital Diseases, Male ; prevention & control ; Humans ; Laparoscopy ; Ligation ; Male ; Microsurgery ; Pain, Postoperative ; prevention & control ; Pain, Procedural ; prevention & control ; Recurrence ; Scrotum ; Testis ; Treatment Outcome ; Varicocele ; surgery ; Vascular Surgical Procedures ; Veins

This study aims to investigate the relationship between odor and contents of the chemical compounds in Lonicera japonica, including chlorogenic acid, galuteolin and polyphenols. High performance liquid chromatography (HPLC) was applied to determine the contents of chlorogenic acid and galuteolin in L. japonica. The ponptent of polyphenols was determined by UV-Vis Spectrophotometry. Electronic nose was used to extract and measure the odor of L. japonica. Then SPSS 17.0 software was employed for data processing. There is a significant positive correlation between the comprehensive index value of aroma and the contents of chlorogenic acid and polyphenols. The regression equations have been established. However, the relationship between the comprehensive index value and the content of galuteolin is not obvious. This is proof that the odor of L. japonica has close connection with the chemical compounds. Therefore, this research offered a new method for initially determine or predict the content of the chemical composition in L. japonica,
Chlorogenic Acid ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Electronic Nose ; Lonicera ; chemistry ; Odorants ; analysis ; Polyphenols ; chemistry ; Smell

It is of vital significance to conduct active post-marketing surveillance of Chinese medicine, as an active response to laws, rules and guidelines issued by the China food and drug administration. The standards for technological specifications based on expert consensus have been drafted. These will provide technological support in evaluating adverse drug reactions (ADRs) or adverse drug events (ADEs). The technological specifications for post-marketing surveillance focus on two surveillance designs; one is a large sample registry study to explore general population ADR/ADE characteristics, the other is a nested case-control study to explore the characteristic and mechanisms of ADRs.
China ; epidemiology ; Drug Monitoring ; adverse effects ; standards ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; standards ; Hospital Information Systems ; Humans ; Product Surveillance, Postmarketing ; methods ; standards

Objective To investigate the difference of blood sampling methods from heparin maintained arterial catheter for blood gas analysis and activated partial thromboplastin time (APTT).Methods Conventional and modified arterial catheter blood sampling methods were applied at the same period of time to 30 cases with arterial pressure measurement.3-5 ml blood containing heparin was disposed in conventional method.No blood was disposed for the modified method.The samples were used for blood gas analysis and APTT.The operation time of the sampling by two methods were compared.Results No significant difference was seen for the blood gas analysis and APTT from the blood samples collected by two different methods (P ＞ 0.05).The operation time of modified method was significantly shorter than that of the conventional method [(187.87 ±15.05)s vs (275.73 ±14.75)s,t =22.84;P＜0.01].Conclusions Arterial catheter blood sampling from heparin maintained blood by the modified method gives accurate clinical laboratory results,in this case,the blood gas analysis and the APTT.No blood is wasted and the operation time for the nurses is reduced.The modified method could be an alternative to the conventional blood collection method.

Objective To explore the relationship between HBV infection and the genotypes and allele frequencies of CⅡTA G-944C gene polymorphism in three minority populations(Jinuo,Dai and Aini population)in Xishuangbanna district,Yunnan province.Methods Polymerase chain reaction and sequencing method were used to study the genotypes and allele frequencies distributions of CⅡTA G-944C gene polymorphism in those three populations.Relationship between the genotypes distribution and HBV infection results were also analyzed.Results The rates on HBV infection and HBsAg carrier status in Aini minority population were 89.2% and 16.3%,which were significantly higher than in Jinuo(27.9% and 3.9%,χ~2=135.196 and 10.361,P=0.000 and 0.001)and Dai population(44.9% and 6.6% χ~2=96.783 and 8.748,P=0.000 and 0.003)while among Aini population it was significantly different with the other two minority populations.The CC genotype and C allele frequencies were more distributed in Aini population than in the other two minority populations.In contrast,the GG genotype and G allele frequencies were lower than the other two minority populations,with χ~2 rates between Aini and Jinuo population were 11.841 and 12.208 and the P as 0.003 and 0.000 respectively while the χ~2 rates between Ami and Dai population were 23.902 and 20.220 with P value as 0.000 and 0.000.The genotypes frequencies of CⅡTA G-944C was significantly different in the infected individuals(IF)group and health control(HC)group in Jinuo population(χ~2=6.150 and 4.911,P=0.046 and 0.027).When compared with HBsAg+ group and HBsAg~- group,the genotypes and allele frequencies were different in Aini population and the total three minority populations(χ~2 rates in Jinuo minority were 8.650 and 5.034 with P values as 0.013 and 0.025).However,the χ~2 rates in the whole population were 13.047 and 9.416 with P values as 0.001 and 0.002,respectively.The distribution of CC genotype and C allele gene in HBsAg~+ group was increasing.Data from non-condition logistic regression analysis and adjusting for confounding factors,the HBsAg~+ group had a significantly increase of HBsAg~- group under the C allele Recessive Model(P=0.000;OR=2.964;95% CI:1.609-5.460).Conclusion The genotypes and allele frequencies distribution of CⅡTA G-944C were different in the three ethnic populations.Polymorphism of this gene was closely associated with HBsAg carrier.The CC genotype patients were more easily to become HBsAg carrier.

OBJECTIVE: To determine an optimal clinical dose of ketamine after comparing the efficacy and security of 3 low dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia. METHODS: Eighty ASA (American Society of Anesthesiologists) I-II patients scheduled for elective gynecological surgery under general anesthesia were divided randomly into 4 groups (n=20): Group B received butorphanol 3 microg/(kg x h);Group BK1 received butorphanol 2 microg/(kg x h) mixed with ketamine 60 microg/(kg x h); Group BK2 received butorphanol 2 microg/(kg x h) mixed with ketamine 90 microg/(kg.h); and Group BK3 received butorphanol 2 microg/(kg x h) mixed with ketamine 120 microg/(kg x h). Continuous intravenous infusion pump was used when the patients had obvious pain (visual analgesia scale of five), and the bolus infusion (4 mL) was given before the operation, and continuous infusion at 2 mL/h. In the postoperative period, pain was assessed using visual analogue scale (VAS) at 2,6,12,24, and 48 h.At the same time, Ramsay scores and adverse effects were recorded. RESULTS: There was no significant difference in the adverse effects and the postoperative mean arterial pressure, heart rate, respiratory rate values, and pulse oxygen among the 4 groups. Postoperative VAS values in Group BK3 was the lowest, followed by Group BK2. There was no significant difference between Group BK1 and Group B. The incidence of somnolence in Group B was higher than that in Group BK1, BK2 and BK3(P<0.05). CONCLUSION Ketamine in subanaesthetic dose added to butorphanol for postoperative continuous intravenous infusion has a better postoperative analgesic effect and sedation. It can effectively spare butorphanol consumption without increasing adverse effects. The optimal combined dose is 90-120 microg/(kg x h).
Adult ; Analgesia ; methods ; Analgesics ; administration & dosage ; Butorphanol ; administration & dosage ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Gynecologic Surgical Procedures ; Humans ; Infusions, Intravenous ; Ketamine ; administration & dosage ; Pain, Postoperative ; drug therapy