Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes ...Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.展开更多
The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive val...The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive values of ANA antibodies.For this purpose,twelve thousand nine hundred sixty-seven(12,967)patients were analyzed for ANA with four hundred sixty-eight(468)healthy samples tested as control and four thousand seven hundred three(4,703)patients tested for ds-DNA antibodies.Retrospective data of all samples tested by indirect immunofluorescence(IF)for ANA antibodies and dsDNA antibodies was collected.To address positive and negative predictive values another control group(autoimmunity not suspected)of serum samples was taken from the healthy population.For the first group,age,gender,ANA antibodies and ds-DNA antibodies results(both tests performed by IIF)data was collected from a computer record cell;for the second control group,ANA antibodies were performed by IIF.12,967 and 4,703 samples(Group 1)were tested for ANA antibodies and dsDNA antibodies,respectively,during this period.1,119(9%)and 99(2%)were found positive for ANA antibodies and ds DNA antibodies.Among these positive samples,850(76%)and 73(74%)were females respectively.Gender predisposition towards autoimmunity(ANA)was found significant with a P value of(P=0.001).Relation of age was also found significant with anti-ANA antibodies with a P value of(P=0.001).This study shows a negative correlation between age(P=0.025)and gender(P=0.001)with anti-dsDNA which is also significant.High prevalence was found below the mean age of 38 years(SD±16.635)for ANA antibodies and the mean age of 35 years(SD±15.066)for ds-DNA antibodies.The age of ANA antibodies and dsDNA antibodies positive patients ranged from 1 year old to 98 years old and 2 years old to 95 years old respectively.In the second(autoimmunity-free)control group,a total of 468 samples were tested for ANA antibodies and 9(2%)were found positive.Positive predictive value(PPV)was 8.6%and negative predictive value(NPV)was 98%.ANA is a sensitive test for autoimmunity and it is significantly related to female gender and increasing age.The low prevalence of ANA antibodies among clinically suspected cases suggests that rationalization of test prescriptions is needed.Anti-ds-DNA is also a sensitive test for diagnosis of SLE and it is significantly related to female gender and increasing age.展开更多
Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The ai...Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.展开更多
P. A. M. Dirac conceived antimatter in 1928 as having negative energy by allowing a consistent representation of matter-antimatter annihilation into light. To achieve compatibility with special relativity, particle ph...P. A. M. Dirac conceived antimatter in 1928 as having negative energy by allowing a consistent representation of matter-antimatter annihilation into light. To achieve compatibility with special relativity, particle physics of the early 20th century made the theoretical assumption that antiparticles have positive energy, an assumption that remains in effect as of today. In this note we prove apparently for the first time a theorem stating that positive mass antiparticles violate Dirac’s particle-antiparticle annihilation into light. We then show the consequential unsettled character of the recent gravity test of the anti-Hydrogen atom due to the positive mass of its nucleus. We conclude by suggesting that a final scientific claim on matter-antimatter gravity requires tests on particles with clear antimatter character, such as the 1994 resolutory proposal for the comparative test of the gravity of very low energy electron and positron in horizontal flight on a supercooled vacuum tube.展开更多
Plants with bioactive properties are greatly useful in preventing and controlling blood-sucking and disease-vector invertebrates, particularly in developing countries and low-income communities. Their application is a...Plants with bioactive properties are greatly useful in preventing and controlling blood-sucking and disease-vector invertebrates, particularly in developing countries and low-income communities. Their application is a promising alternative to synthetic compounds whose use remains a health, environmental, and economic challenge. However, many are still unknown and unvalued, while others are becoming ignored and threatened. The main objective of this ethnobotanical study is to identify and characterize indigenous and locally grown plants against blood-sucking and disease-vector insects. Salient opportunities and challenges of using these plants are documented and discussed. Semi-structured interviews, using a prepared questionnaire, were conducted with 228 informants. The consensus index (CI) was calculated to analyze the reliability of the collected information. The identified 31 anti-insect plant species belong to 20 botanical families, four morphological categories, and six habitat types. They can be categorized as insecticidal plants (42% of the total), insect repellent (42% of the total), and both insecticidal and insect repellent (16% of the total). More than 54% of these are still abundant in the study area, while about 35.5% have become rare and difficultly accessible. Based on the numerical importance of related anti-insect plant species, the seven targeted blood-sucking insects range in the following decreasing order: Jiggers (16 species) > Fire Ants (9 species) > Flies (8 plants) > Mosquitoes (4 species) > Fleas (2 species) > Bedbugs (1 species) > lice (0 species). The three most commonly used plants, with the highest confirmation indices, are Tetradenia riparia (ICs = 0.712), Eucalyptus globulus subsp. maidenii (ICs = 0.302), and Solanum aculeastrum (ICs = 0.288). The antimicrobial role of many locally grown anti-insect plants and the multiple other associated valorization possibilities are ignored by most informants. Domesticating, propagating, protecting, and promoting the sustainable use of these plants would be an appropriate route for their conservation and continued availability.展开更多
基金Corresponding author.Address:Department of Gastroenterology,Shangrao People’s Hospital,Shangrao 334000,Jiangxi Province,China.E-mail address:zylinzy@qq.com(Z.-Y Lin)Department of Gastroenterology,Shangrao People’s Hospital,Shangrao 334000,Jiangxi Province,China.E-mail address:28535324@qq.com(H.-J.Lian).
文摘Systemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma(HCC)whose treatment options are limited.However,the long-term patient response to drugs and the survival outcomes remain a concern.With increasing exploration of the HCC microenvironment,particularly in terms of T lymphocyte immunity,a new era of immunomolecular targeted therapy,based on molecular signaling,has arrived for advanced HCC.In the study of immune tolerance of the intrinsic HCC microenvironment,we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors,such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy,have improved clinical outcomes in some patients with advanced HCC.Furthermore,various combination therapies have been investigated,and HCC types have been categorized into different types based on anti–programmed cell death protein 1(PD-1)/ligand of programmed cell death protein 1(PD-L1)treatment.In this paper,we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC.We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy.Thereafter,we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors,anti–T lymphocyte–related signaling pathways in HCC,and other anti-CD8+T cell immune checkpoints.In this way,this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC,in order to provide better individualized treatments for patients with advanced HCC.
文摘The study was designed to find the prevalence of ANA antibodies and anti-dsDNA antibodies in samples tested at AFIP Rawalpindi and their correlation with age and gender and to find positive and negative predictive values of ANA antibodies.For this purpose,twelve thousand nine hundred sixty-seven(12,967)patients were analyzed for ANA with four hundred sixty-eight(468)healthy samples tested as control and four thousand seven hundred three(4,703)patients tested for ds-DNA antibodies.Retrospective data of all samples tested by indirect immunofluorescence(IF)for ANA antibodies and dsDNA antibodies was collected.To address positive and negative predictive values another control group(autoimmunity not suspected)of serum samples was taken from the healthy population.For the first group,age,gender,ANA antibodies and ds-DNA antibodies results(both tests performed by IIF)data was collected from a computer record cell;for the second control group,ANA antibodies were performed by IIF.12,967 and 4,703 samples(Group 1)were tested for ANA antibodies and dsDNA antibodies,respectively,during this period.1,119(9%)and 99(2%)were found positive for ANA antibodies and ds DNA antibodies.Among these positive samples,850(76%)and 73(74%)were females respectively.Gender predisposition towards autoimmunity(ANA)was found significant with a P value of(P=0.001).Relation of age was also found significant with anti-ANA antibodies with a P value of(P=0.001).This study shows a negative correlation between age(P=0.025)and gender(P=0.001)with anti-dsDNA which is also significant.High prevalence was found below the mean age of 38 years(SD±16.635)for ANA antibodies and the mean age of 35 years(SD±15.066)for ds-DNA antibodies.The age of ANA antibodies and dsDNA antibodies positive patients ranged from 1 year old to 98 years old and 2 years old to 95 years old respectively.In the second(autoimmunity-free)control group,a total of 468 samples were tested for ANA antibodies and 9(2%)were found positive.Positive predictive value(PPV)was 8.6%and negative predictive value(NPV)was 98%.ANA is a sensitive test for autoimmunity and it is significantly related to female gender and increasing age.The low prevalence of ANA antibodies among clinically suspected cases suggests that rationalization of test prescriptions is needed.Anti-ds-DNA is also a sensitive test for diagnosis of SLE and it is significantly related to female gender and increasing age.
文摘Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.
文摘P. A. M. Dirac conceived antimatter in 1928 as having negative energy by allowing a consistent representation of matter-antimatter annihilation into light. To achieve compatibility with special relativity, particle physics of the early 20th century made the theoretical assumption that antiparticles have positive energy, an assumption that remains in effect as of today. In this note we prove apparently for the first time a theorem stating that positive mass antiparticles violate Dirac’s particle-antiparticle annihilation into light. We then show the consequential unsettled character of the recent gravity test of the anti-Hydrogen atom due to the positive mass of its nucleus. We conclude by suggesting that a final scientific claim on matter-antimatter gravity requires tests on particles with clear antimatter character, such as the 1994 resolutory proposal for the comparative test of the gravity of very low energy electron and positron in horizontal flight on a supercooled vacuum tube.
文摘Plants with bioactive properties are greatly useful in preventing and controlling blood-sucking and disease-vector invertebrates, particularly in developing countries and low-income communities. Their application is a promising alternative to synthetic compounds whose use remains a health, environmental, and economic challenge. However, many are still unknown and unvalued, while others are becoming ignored and threatened. The main objective of this ethnobotanical study is to identify and characterize indigenous and locally grown plants against blood-sucking and disease-vector insects. Salient opportunities and challenges of using these plants are documented and discussed. Semi-structured interviews, using a prepared questionnaire, were conducted with 228 informants. The consensus index (CI) was calculated to analyze the reliability of the collected information. The identified 31 anti-insect plant species belong to 20 botanical families, four morphological categories, and six habitat types. They can be categorized as insecticidal plants (42% of the total), insect repellent (42% of the total), and both insecticidal and insect repellent (16% of the total). More than 54% of these are still abundant in the study area, while about 35.5% have become rare and difficultly accessible. Based on the numerical importance of related anti-insect plant species, the seven targeted blood-sucking insects range in the following decreasing order: Jiggers (16 species) > Fire Ants (9 species) > Flies (8 plants) > Mosquitoes (4 species) > Fleas (2 species) > Bedbugs (1 species) > lice (0 species). The three most commonly used plants, with the highest confirmation indices, are Tetradenia riparia (ICs = 0.712), Eucalyptus globulus subsp. maidenii (ICs = 0.302), and Solanum aculeastrum (ICs = 0.288). The antimicrobial role of many locally grown anti-insect plants and the multiple other associated valorization possibilities are ignored by most informants. Domesticating, propagating, protecting, and promoting the sustainable use of these plants would be an appropriate route for their conservation and continued availability.
