China, the East Asian giant, now faces a growing problem of illicit drug use, which is deeply harmful to its stability. The outcome of intensive enforcements, named ＂People＇s anti-drug war＂, though reaching some ac...China, the East Asian giant, now faces a growing problem of illicit drug use, which is deeply harmful to its stability. The outcome of intensive enforcements, named ＂People＇s anti-drug war＂, though reaching some accomplishments, is still insufficient to settle this increasingly serious problem. This essay, therefore, highlights the four limits of China＇s current lawful enforcement through examining the outcome of ＂anti-drug war＂ launched in 2015. Furthermore, the essay provides four potential recommendations for the adjustment in China＇s anti-drug strategy, in terms of its particular political system and geographical environment. With the increasing younger-age trend and geographical expansion of illicit drug problem, the serious situation is calling for a more flexible and artful regulatory framework in China.展开更多
BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of respons...BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.展开更多
The drug problem has gradually penetrated into Mexican politics,economy,culture,and other fields since the 20th century,and has become an important factor affecting Mexico’s development.Enrique Pe?a Nieto took office...The drug problem has gradually penetrated into Mexican politics,economy,culture,and other fields since the 20th century,and has become an important factor affecting Mexico’s development.Enrique Pe?a Nieto took office in 2012,and implemented a new anti-drug policy.His government has made reducing violence a major goal of the anti-drug operation,using the national gendarmerie to counter the drug violence,and reforming the judiciary to prevention crime.Enrique Pe?a Nieto’s anti-drug policy has achieved certain results at the beginning of his term.However,the weakness of the national gendarmerie,corruption,and the sluggish economic development have affected the anti-drug policy,and caused it to fail.The drug problem in Mexico is affected by multiple factors,and its solution is a long one.展开更多
Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB...Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SSIP modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies （ADA）, whereas mice immunized with SSIP, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.展开更多
Concerning the continued increase in the number of youth drug abuse, even the trend of total number of drug abuse in Hong Kong is decreasing, government has tried to take certain actions to strengthen the anti-drug ef...Concerning the continued increase in the number of youth drug abuse, even the trend of total number of drug abuse in Hong Kong is decreasing, government has tried to take certain actions to strengthen the anti-drug efforts in school. In the following part, it will list out how government responded to the mentioned problem, especially the drug abuse problem in school and how the government changed its efforts during the past few years.展开更多
Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical dru...Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical drugs,contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs,because of their complex structure and comprehensive mechanisms of action.While the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies,the pathogenesis of irAEs in advanced biologics,such as cell and gene therapy,remains to be further delineated.In the current study,I present an updated profile regarding the untoward immune effects of medications,covering various material categories systematically,with the underlying mechanisms to inspire risk mitigation in biopharmaceutical development and application.展开更多
文摘China, the East Asian giant, now faces a growing problem of illicit drug use, which is deeply harmful to its stability. The outcome of intensive enforcements, named ＂People＇s anti-drug war＂, though reaching some accomplishments, is still insufficient to settle this increasingly serious problem. This essay, therefore, highlights the four limits of China＇s current lawful enforcement through examining the outcome of ＂anti-drug war＂ launched in 2015. Furthermore, the essay provides four potential recommendations for the adjustment in China＇s anti-drug strategy, in terms of its particular political system and geographical environment. With the increasing younger-age trend and geographical expansion of illicit drug problem, the serious situation is calling for a more flexible and artful regulatory framework in China.
文摘BACKGROUND Treatment of infantile-onset inflammatory bowel disease(IO-IBD)is often challenging due to its aggressive disease course and failure of standard therapies with a need for biologics.Secondary loss of response is frequently caused by the production of anti-drug antibodies,a well-known problem in IBD patients on biologic treatment.We present a case of IO-IBD treated with therapeutic drug monitoring(TDM)-guided high-dose anti-tumor necrosis factor therapy,in which dose escalation monitoring was used as a strategy to overcome anti-drug antibodies.CASE SUMMARY A 5-mo-old boy presented with a history of persistent hematochezia from the 10th d of life,as well as relapsing perianal abscess and growth failure.Hypoalbuminemia,anemia,and elevated inflammatory markers were also present.Endoscopic assessment revealed skip lesions with deep colic ulcerations,inflammatory anal sub-stenosis,and deep fissures with persistent abscess.A diagnosis of IO-IBD Crohn-like was made.The patient was initially treated with oral steroids and fistulotomy.After the perianal abscess healed,adalimumab(ADA)was administered with concomitant gradual tapering of steroids.Clinical and biochemical steroid-free remission was achieved with good trough levels.After 3 mo,antibodies to ADA(ATA)were found with undetectable trough levels;therefore,we optimized the therapy schedule,first administering 10 mg weekly and subsequently up to 20 mg weekly(2.8 mg/kg/dose).After 2 mo of high-dose treatment,ATA disappeared,with concomitant high trough levels and stable clinical and biochemical remission of the disease.CONCLUSION TDM-guided high-dose ADA treatment as a monotherapy overcame ATA production.This strategy could be a good alternative to combination therapy,especially in very young patients.
文摘The drug problem has gradually penetrated into Mexican politics,economy,culture,and other fields since the 20th century,and has become an important factor affecting Mexico’s development.Enrique Pe?a Nieto took office in 2012,and implemented a new anti-drug policy.His government has made reducing violence a major goal of the anti-drug operation,using the national gendarmerie to counter the drug violence,and reforming the judiciary to prevention crime.Enrique Pe?a Nieto’s anti-drug policy has achieved certain results at the beginning of his term.However,the weakness of the national gendarmerie,corruption,and the sluggish economic development have affected the anti-drug policy,and caused it to fail.The drug problem in Mexico is affected by multiple factors,and its solution is a long one.
文摘Antibodies against the toxin portion of recombinant immunotoxins （RIT） reduce their efficacy and pose a potential safety risk. To overcome this problem we mutated the very immunogenic immunotoxin SSIP to produce LMB-T20, a de-immunized RIT that has the eight human T-cell epitopes in SSIP modified or removed. To determine the effect of T-cell epitope removal in vivo we mapped the T-cell epitopes in immune-competent BALB/c mice and found that these mice recognize two epitopes. One corresponds to the human immunodominant T-cell epitope and the other to a human subdominant epitope; both were eliminated in LMB-T20. We found that mice immunized with LMB-T20 did not have T-cell activation and did not develop anti-drug antibodies （ADA）, whereas mice immunized with SSIP, showed T-cell activation, and developed ADA detected by both ELISA and drug neutralizing assays. The ability of the mice treated with LMB-T20 to respond to other antigens was not compromised. We conclude that elimination of T-cell epitopes is sufficient to prevent formation of antibodies to an immunogenic foreign protein.
文摘Concerning the continued increase in the number of youth drug abuse, even the trend of total number of drug abuse in Hong Kong is decreasing, government has tried to take certain actions to strengthen the anti-drug efforts in school. In the following part, it will list out how government responded to the mentioned problem, especially the drug abuse problem in school and how the government changed its efforts during the past few years.
文摘Immune-related adverse events(irAEs)represent an increasingly concerning challenge in the assessment of biopharmaceutical products.In contrast to historically rare allergic reactions associated with small chemical drugs,contemporary biotherapeutics exhibit a significantly higher morbidity of irAEs,because of their complex structure and comprehensive mechanisms of action.While the immunogenicity of protein-based compounds is associated with the induction of anti-drug antibodies,the pathogenesis of irAEs in advanced biologics,such as cell and gene therapy,remains to be further delineated.In the current study,I present an updated profile regarding the untoward immune effects of medications,covering various material categories systematically,with the underlying mechanisms to inspire risk mitigation in biopharmaceutical development and application.
