Work Hard to Ensure Food,Drugs Safety for the People——An interview with Shao Mingli,director-general of the State Food and Drug Administration(SFDA)

Following is an interview given by Shao Mingli, director-general of China＇s State Food and Drug Administration to our reporter on what is being done to ensure food and drug safety in China. As everybody knows, food and drug safety is vital to people＇s lives.

Analysis of the Efficacy,Progression-Free Survival,and Safety of Anlotinib in Advanced Lung Cancer Treatment

Objective:To analyze the clinical efficacy,progression-free survival,and safety of anlotinib in the treatment of advanced lung cancer.Methods:A retrospective analysis was conducted using data from 60 patients with advanced lung cancer treated with anlotinib from May 2019 to May 2021.This analysis aimed to comprehensively evaluate the clinical efficacy,progression-free survival,and adverse reactions of anlotinib.Results:The median progression-free survival(PFS)for the 60 patients was 5.79 months,with an overall response rate(ORR)of 21%and a disease control rate(DCR)of 90%.In the first-line group,the median PFS was 6.20 months,ORR was 76.92%,and DCR was 84.61%.The second-line group showed a median PFS of 6.30 months,ORR of 28.57%,and DCR of 90.48%.In the third-line group,the median PFS was 5.34 months,ORR was 19.23%,and DCR was 92.30%.The single-agent group exhibited a median PFS of 5.09 months,ORR of 23.33%,and DCR of 76.67%.In the combination group,the median PFS was 6.53 months,ORR was 46.67%,and DCR was 100%.The combination group demonstrated a significantly higher medication effect than the single-drug group,and adverse drug reactions were mostly grade 1-2.Conclusion:Anlotinib exhibits a better disease control rate and survival benefit in the treatment of advanced lung cancer.The combination effect is superior to monotherapy,with relatively controllable adverse effects.

“Blind men and an elephant”:The need for animals in research,drug safety studies,and understanding civilizational diseases

Animal-based research and drug safety studies are essential to understanding the mysteries of nature and the long-term survival of humans.Due to the rapid increase in the global human population,conflict-and economically driven human migration,tourism-related activities,densely populated metropolitan areas,and local policies,humans will be affected by a multitude of novel disease-causing microorganisms and civilizational diseases.Despite disparities among countries,recent and planned changes in regulations concerning animal research and drug safety studies could have detrimental effects on both the animal research community and nations lacking sufficient social support systems.Based on existing scientific literature,I argue that we need animal research encompassing aspects such as animal development,behavior,drug safety studies,and for the understanding of future civilizational diseases.Depending on the nature of the research questions and local challenges,a suitable animal model organism should be made mandatory.

Indirect comparison of efficacy and safety of chiglitazar and thiazolidinedione in patients with type 2 diabetes:A meta-analysis

BACKGROUND Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors(PPAR)-α,δandγ,and has therapeutic potential for type 2 diabetes(T2D).However,to date,no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γagonist thiazolidinediones(TZDs).A meta-analysis concerning this topic is therefore required.AIM To compare the efficacy and safety of chiglitazar and TZD in patients with T2D.METHODS PubMed,Medline,Embase,the Cochrane Central Register of Controlled Trials,Reference Citation Analysis and Clinicaltrial.gov websites were searched from August 1994 to March 2022.Randomized controlled trials(RCTs)of chiglitazar or TZD vs placebo in patients with T2D were included.Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest.RESULTS We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo.For efficacy endpoints,the augmented dose of chiglitazar resulted in greater reductions in hemoglobin(Hb)A1c[weighted mean difference(WMD)=-0.15%,95%confidence interval(CI):-0.27 to-0.04%],triglycerides(WMD=-0.17 mmol/L,95%CI:-0.24 to-0.11 mmol/L)and alanine aminotransferase(WMD=-5.25 U/L,95%CI:-8.50 to-1.99 U/L),and a greater increase in homeostasis model assessment-β(HOMA-β)(WMD=17.75,95%CI:10.73-24.77)when compared with TZD treatment.For safety endpoints,the risks of hypoglycemia,edema,bone fractures,upper respiratory tract infection,urinary tract infection,and weight gain were all comparable between the augmented dose of chiglitazar and TZD.In patients with baseline HbA1c≥8.5%,body mass index≥30 kg/m^(2)or diabetes duration<10 years,the HbA1c reduction and HOMA-βincrease were more conspicuous for the augmented dose of chiglitazar compared with TZD.CONCLUSION Augmented dose of chiglitazar,a pan-activator of PPARs,may serve as an antidiabetic agent with preferable glycemic and lipid control,betterβ-cell function preserving capacity,and does not increase the risk of safety concerns when compared with TZD.

The Problems of the Safety Evaluation of Biotechnology Derived Drugs

Recent years have witnessed rapid advances in the toxicologic assessment of biotechproducts.Safety assessment of a biotech product is a complex and multiple process.This includes a knowledge of its pharmaco-biological characteristics,and identifyingthe target patient population and the proposed clinical application. To make a decision on the safe human application(the products are administering tohumans for therapeutic purposes),besides the identity and purity of the final product,

Drug Usage Safety from Drug Reviews with Hybrid Machine Learning Approach

With the increasing usage of drugs to remedy different diseases,drug safety has become crucial over the past few years.Often medicine from several companies is offered for a single disease that involves the same/similar substances with slightly different formulae.Such diversification is both helpful and danger-ous as such medicine proves to be more effective or shows side effects to different patients.Despite clinical trials,side effects are reported when the medicine is used by the mass public,of which several such experiences are shared on social media platforms.A system capable of analyzing such reviews could be very helpful to assist healthcare professionals and companies for evaluating the safety of drugs after it has been marketed.Sentiment analysis of drug reviews has a large poten-tial for providing valuable insights into these cases.Therefore,this study proposes an approach to perform analysis on the drug safety reviews using lexicon-based and deep learning techniques.A dataset acquired from the‘Drugs.Com’contain-ing reviews of drug-related side effects and reactions,is used for experiments.A lexicon-based approach,Textblob is used to extract the positive,negative or neu-tral sentiment from the review text.Review classification is achieved using a novel hybrid deep learning model of convolutional neural networks and long short-term memory(CNN-LSTM)network.The CNN is used at thefirst level to extract the appropriate features while LSTM is used at the second level.Several well-known machine learning models including logistic regression,random for-est,decision tree,and AdaBoost are evaluated using term frequency-inverse docu-ment frequency(TF-IDF),a bag of words(BoW),feature union of(TF-IDF+BoW),and lexicon-based methods.Performance analysis with machine learning models,long short term memory and convolutional neural network models,and state-of-the-art approaches indicate that the proposed CNN-LSTM model shows superior performance with an 0.96 accuracy.We also performed a statistical sig-nificance T-test to show the significance of the proposed CNN-LSTM model in comparison with other approaches.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Safety of the long-term use of proton pump inhibitors

The proton pump inhibitors (PPIs) as a class are remarkably safe and effective for persons with peptic ulcer disorders. Serious adverse events are extremely rare for PPIs, with case reports of interstitial nephritis with omeprazole, hepatitis with omeprazole and lansoprazole, and disputed visual disturbances with pantoprazole and omeprazole. PPI use is associated with the development of fundic gland polyps (FGP); stopping PPIs is associated with regression of FGP. In the absence of Helicobacter pylori infection, the long-term use of PPIs has not been convincingly proven to cause or be associated with the progression of pre-existing chronic gastritis or gastric atrophy or intestinal metaplasia. Mild/modest hypergastrinemia is a physiological response to the reduction in gastric acid secretion due to any cause. The long-term use of PPIs has not been convincingly proven to cause enterochromaff in-like cell hyperplasia or carcinoid tumors. PPIs increase the risk of community acquired pneumonia, but not of hospital acquired (nosocomial) pneumonia. There is no data to support particular care in prescribing PPI therapy due to concerns about risk of hip fracture with the long-termuse of PPIs. Long-term use of PPIs does not lead to vitamin B12 def iciencies, except possibly in the elderly, or in persons with Zollinger-Ellison Syndrome who are on high doses of PPI for prolonged periods of time. There is no convincingly proven data that PPIs increase the risk of Clostridium difficile-associated diarrhea in persons in the community. The discontinuation of PPIs may result in rebound symptoms requiring further and even continuous PPI use for suppression of symptoms. As with all medications, the key is to use PPIs only when clearly indicated, and to reassess continued use so that long-term therapy is used judiciously. Thus, in summary, the PPIs are a safe class of medications to use longterm in persons in whom there is a clear need for the maintenance of extensive acid inhibition.

Treatment of SARS-CoV-2(COVID-19):A safety perspective

The goal of this review is to report a balanced perspective of current evidence for efficacy of treatments for coronavirus disease 2019(COVID-19)against the historical safety of these treatments as of May 2021.We preselected therapies of interest for COVID-19 based on national guidelines and modified over time.We searched PubMed and Medline for these specific COVID-19 treatments and data related to their efficacy.We also searched for prior randomized controlled trials of each therapy to assess adverse effects,and we obtained the Food and Drug Administration Approval label for this information.Several drugs have been approved for the treatment of COVID-19,and many more are under study.This includes dexamethasone,remdesivir,hydroxychloroquine/chloroquine,lopinvir/ritonavir,interferon or interleukin inhibitors,convalescent plasma and several vitamins and minerals.The strongest evidence for benefit is mortality benefit with dexamethasone in patients with COVID-19 and hypoxemia,although there is a signal of harm if this is started too early.There are several other promising therapies,like interleukin inhibitors and ivermectin.Hydroxychloroquine/chloroquine,lopinvir/ritonavir,and convale-scent plasma do not have enough evidence of benefit to outweigh the known risks of these drugs.

Analysis on Epidemiology Causality Relationship Theory under Food and Drug Safety Context

Violation of food and drug safety and other hazard crimes have the features of long latency and multiple factors. Traditional criminal law causality theory is no controversy to determine causality of criminal responsibility, thus it is necessary to introduce the epidemiology causality theory-it is a kind of causality theory based on epidemic diseases, and it is the high degree of probability in the determination of causality in criminal laws so as to solve the traditional attribution problem, but the theory also exists applicable restriction conditions in judicial practice.

Drug Safety Assessment:An Urgent Task

A CAS scientist has pointed out at an international symposium that it is important for China to step up its efforts in drug safety assessment to address a hidden peril in China's pharmaceuticals industry.

BARN:Behavior-Aware Relation Network for multi-label behavior detection in socially housed macaques

Quantification of behaviors in macaques provides crucial support for various scientific disciplines,including pharmacology,neuroscience,and ethology.Despite recent advancements in the analysis of macaque behavior,research on multi-label behavior detection in socially housed macaques,including consideration of interactions among them,remains scarce.Given the lack of relevant approaches and datasets,we developed the Behavior-Aware Relation Network(BARN)for multi-label behavior detection of socially housed macaques.Our approach models the relationship of behavioral similarity between macaques,guided by a behavior-aware module and novel behavior classifier,which is suitable for multi-label classification.We also constructed a behavior dataset of rhesus macaques using ordinary RGB cameras mounted outside their cages.The dataset included 65?913 labels for19 behaviors and 60?367 proposals,including identities and locations of the macaques.Experimental results showed that BARN significantly improved the baseline SlowFast network and outperformed existing relation networks.In conclusion,we successfully achieved multilabel behavior detection of socially housed macaques with both economic efficiency and high accuracy.

In silico off-target profiling for enhanced drug safety assessment

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent phases.However,the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is substantial.Drug off-target interactions,along with the adverse drug reactions they induce,are significant factors affecting drug safety.To assess the liability of candidate drugs,we developed an artificial intelligence model for the precise prediction of compound off-target interactions,leveraging multi-task graph neural networks.The outcomes of off-target predictions can serve as representations for compounds,enabling the differentiation of drugs under various ATC codes and the classification of compound toxicity.Furthermore,the predicted off-target profiles are employed in adverse drug reaction(ADR)enrichment analysis,facilitating the inference of potential ADRs for a drug.Using the withdrawn drug Pergolide as an example,we elucidate the mechanisms underlying ADRs at the target level,contributing to the exploration of the potential clinical relevance of newly predicted off-target interactions.Overall,our work facilitates the early assessment of compound safety/toxicity based on off-target identification,deduces potential ADRs of drugs,and ultimately promotes the secure development of drugs.

Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo

Background:Since RNA sequencing has shown that induced pluripotent stem cells(iPSCs)share a common antigen profile with tumor cells,cancer vaccines that focus on iPSCs have made promising progress in recent years.Previously,we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia(T-ALL)have a gene expression profile similar to that of T-ALL cell lines.Methods:Mice with T-ALL were treated with dendritic and T(DC-T)cells loaded with intact and complete antigens from T-ALL-derived iPSCs(T-ALL-iPSCs).We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry,cytokine release assay,acute toxicity experiments,long-term toxicity experiments,and other methods.Results:Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity.Conclusion:T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

Paricalcitol in hemodialysis patients with secondary hyperparathyroidism and its potential benefits

BACKGROUND Secondary hyperparathyroidism(SHPT)is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients.SHPT can increase bone fragility and calcification of blood vessels and soft tissues,which greatly increases the risk of death.AIM To discuss the outcome,safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT.METHODS We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019.They received paricalcitol injection for 24 wk(starting dose,0.06–0.08μg/kg),three times per week.They were followed up at the baseline(week 0),week 4,week 12 and week 24.The primary outcome indicator was the percentage of patients with a>30%decrease in intact parathyroid hormone(iPTH)levels at week 24 compared with the baseline.The secondary outcome indicators included percentage decrease in iPTH levels at week 24,standard-reaching rate of iPTH(percentage of patients with iPTH down to 130–585 pg/mL),changes in serum levels of calcium(Ca),phosphate(P),Ca×P product,alkaline phosphatase(ALP),creatinine(Cre),hemoglobin(Hb),and C-reactive protein(CRP),and incidence of adverse events(AEs).RESULTS After 24 wk of treatment,iPTH levels decreased significantly(598.88±381.29 pg/mL vs 888.84±376.88 pg/mL,P<0.05).More than 30%decrease of iPTH was found in 21 of 36(58.33%)patients.The average decrease in iPTH levels was 32.16±4.33%;the standard-reaching rate of iPTH levels was 66.67%(24/36);and ALP levels decreased significantly compared with the baseline(113.72±41.73 IU/L vs 133.45±56.86 IU/L)(t=2.798,P<0.05).There were no significant differences in the serum levels of calcium,Hb,Cre and CRP compared with the baseline(P>0.05).After 24 wk of treatment,serum P levels decreased compared with the baseline(1.91±0.40 mmol/L vs 2.16±0.66 mmol/L)(t=2.830,P<0.05).Ca×P product decreased significantly compared with the baseline(56.38±13.22 mg2/dL2 vs 63.97±20.30 mg2/dL2)(t=2.717,P<0.05).No serious adverse events occurred.CONCLUSION Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT.It decreased serum levels of iPTH,ALP and P and maintained stability of serum Ca levels.

Antibiotic susceptibility of strains in Chinese medical probiotic products

Objective： To investigate the susceptibility of strains separated from probiotic products for medical purpose to 14 antimicrobial agents. Methods：The single aerobic strains were isolated from these products respectively and disc agar diffusion assay was proceeded to determine the susceptibility. Results： Probiotics tested in the study mostly showed multiresistant to the agents. Lactobacillus acidophilus LAP, LAB, Lactobacillus bulgaricus LBJ and Streptococcus therrnophilus STJ were resistant to vancomycin. Conclusion： Drug resistance exists in most of commercial probiotics. The evaluation and monitoring of safety of probiotic products for medical purpose should be paid great attention.

Regulatory evaluation of efficacy and safety of new drugs in China

Accessibility, availability, and rational use of medicines are widely recognized priorities for guaranteeing equity in health care. Commercial pressure can twist health policy if pharmaceutical companies are allowed to promote and impose their products beyond clear public-health interest. National regulatory

Exploratory research on drug safety in China

The article defines the concept of drug safety,summarizes the problems and causes in the area of drug safety in China, and proposes relevant measures to solve the problems.

No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014.Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer.The primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.Results:A total of 337 patients diagnosed with AAN were included in this study.From the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with cancer.No cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary cancer.Conclusions:No cases of liver cancer were observed at the end of follow-up.However,a high prevalence of urinary cancer was observed in AAN patients.Establishing a direct causality between AA and HCC is challenging.

Development and Application of Network Toxicology in Safety Research of Chinese Materia Medica

Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica （CMM）. The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.