Objective To provide valuable insights for improving China’s special drug approval system by conducting an in-depth analysis of the practices of the U.S. Food and Drug Administration （FDA） in granting Emergency Use Authorizations （EUAs） for drugs. Methods A retrospective analysis was conducted on the FDA’s EUA decision-making process for COVID-19 therapeutics between January 2020 and June 2023. Results During the COVID-19 pandemic, the FDA adopted a series of regulatory science approaches to facilitate rapid approval of COVID-19 therapeutic drugs. The FDA granted EUA for a total of 15 COVID-19 therapeutic drugs and 4 COVID-19 vaccines, including expanded indications for marketed drugs, EUA for investigational drugs, revocation of EUA, and marketing after EUA. The main mechods for the rapid approval of EUA drugs by the FDA included the use of existing clinical trial data, omission of animal efficacy testing, merging of phase 1 and phase 2 clinical trials, and the use of clinical outcomes as surrogate endpoints, among other regulatory science methods. Conclusion The practices of the FDA in Emergency Use Authorization (EUA) of drugs, particularly its incorporation of regulatory scientific methods into the EUA process and the establishment of proactive monitoring mechanisms for drugs granted EUA, are worthy of emulation by China. It is suggested that China consider the experience of the FDA in the EUA system for drugs to further optimize and improve its special approval system for drugs.

Objective:To explore the application value of laparoscopic contrast enhanced ultrasound in laparoscopic surgery for patients with hepatocellular carcinoma combined with cirrhosis.Methods:The clinical data of 71 patients with hepatocellular carcinoma combined cirrhosis from February 2018 to February 2020 in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. The patients underwent preoperative enhanced CT and multi-parameter MRI examination, followed by laparoscopic partial hepatectomy, and intraoperative laparoscopic contrast enhanced ultrasound examination. Based on histological examination and follow-up results, the diagnostic efficacy of preoperative imaging and preoperative imaging combined with intraoperative laparoscopic contrast enhanced ultrasound in patients with hepatocellular carcinoma combined with cirrhosis was compared.Results:Among the 71 patients, 69 completed laparoscopic surgery and 2 converted to open surgery. One hundred and ten HCC lesions were diagnosed by preoperative imaging examination, 105 lesions were detected by intraoperative ultrasound among them, of which 98 lesions were diagnosed as HCC by intraoperative laparoscopic contrast enhanced ultrasound. There were no statistically significant difference in sensitivity, specificity, accuracy, positive predictive value and negative predictive value between preoperative imaging and preoperative imaging combined with intraoperative laparoscopic contrast enhanced ultrasound in the diagnosis of malignant liver lesions: 94.4% (102/108) vs. 99.1% (107/108), 81.0% (34/42) vs. 66.7% (28/42), 90.6% (136/150) vs. 90.0% (135/150), 92.7% (102/110) vs. 88.4% (107/121) and 85.0% (34/40) vs. 96.6% (28/29), P>0.05. Laparoscopic contrast enhanced ultrasound revealed an additional 11 suspected malignant lesions, of which 5 lesions were histologically confirmed as HCC. Seven patients underwent surgical strategy changes. Conclusions:Laparoscopic contrast enhanced ultrasound in patients with HCC combined with cirrhosis during laparoscopic surgery can be used to detect, identify, accurately locate of the lesions and modify the surgical plan.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To investigate the effects of adenosine triphosphate-binding cassette,sub-family C,member 2(ABCC2)rs717620 G＞A polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate(MTX)in children with acute lymphoblastic leukemia(ALL).Methods Peripheral blood samples were obtained from children with ALL to extract genome DNA.Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to detect the genotypes of ABCC2 rs717620 G＞A polymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of ALL relapse and toxicities were recorded after chemotherapy with MTX.The associations of ABCC2 rs717620 G＞A polymorphisms with dose-adjusted serum concentrations(C/D ratios),relapse,and chemotherapy toxicities of MTX were analyzed.Results A total of 127 children were included in the present study.The frequencies of rs717620 GG,GA and AA genotypes were 82.68％,16.54％and 0.78％,respectively.The frequencies of G and A alleles were 90.94％and 9.06％,respectively.Children with the GG genotype had lower median C/D ratios of MTX in 24 h(11.94 μmol·L-1 per g·m-2),higher C/D ratios of MTX in 42 h(0.08 μmol·L-1 per g·m-2),and lower relapse rates(11.42％)than those in GA and AA genotype carriers(12.64 and 0.07 μmol·L-1 per g·m-2,and 18.18％,respectively).However,none of the above differences were statistically significant.The incidences of hematological(40.95％)and electrolyte disorders(21.90％)in children with the GG genotype were significantly higher than those in GA and AA genotype carriers(13.64％and 0.00％,respectively,P＜0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the GG genotype and patients with the GA and AA genotypes(all P＞0.05).Conclusion ABCC2 rs717620 GG might be a risk factor for hematological and electrolyte disorders in ALL children treated with MTX.

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota. Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq. Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336-0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34-0.55),which were mainly involved in neurodevelopment. Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6％(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4％in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.

Objective This paper intends to compare the efficacy and safety of high-dose dual regimens containing Vonoprazan and proton pump inhibitor in patients infected with Helicobacter pylori(H.pylori).Methods A prospective randomized controlled study was conducted.According to inclusion and exclusion criteria.,243 patients with H.pylori infection admitted to the Department of Gastroenterology,the First Hospital of Lanzhou University from February 2023 to December 2023 were enrolled as the research objects.They were randomly divided into two groups.The high-dose dual therapy containing Vonoprazan group(VPZ-HDDT group)was given Vonoprazan fumarate tablet 20mg twice daily plus amoxicillin 750 mg four times daily for 14 days and the high-dose combination group containing PPI(PPI-HDDT group)was given esomeprazole 40 mg twice daily plus amoxicillin 750 mg four times daily for 14 days.Patients were followed up and recorded by telephone or WeChat on the 7th and 14th day of starting treatment for drug intake and occurrence of adverse reactions.Patients were instructed to recheck the 13C or 14C urea breath test at least 1 month after the end of medication.Treatment by protocol(PP)analysis,modified intention to treat(mITT)and intention-to-treat(ITT)analysis were used for H.pylori eradication rates in both groups,and compliance and incidence of adverse reactions were compared between the two groups.Results The eradication rates of the VPZ-HDDT group and the PPI-HDDT group in the initial treatment were 94.0％and 88.5％(P=0.209)by PP analysis,and 91.8％and 87.5％(P=0.358)86.7％by mITT analysis,and 81.9％(P=0.377)by ITT analysis,respectively.In the retreated patients,the PP analysis and mITT analysis eradication rates in these two groups were consistent,87.0％and 84.2％(P=0.800),respectively,and 83.3％and 76.2％(P=0.550)by ITT analysis.For the refractory H.pylori patients,the PP analysis and mITT analysis eradication rates in these two groups were also consistent,71.4％and 50.0％(P=0.429),and the eradication rates of ITT analysis were 62.5％and 50.0％(P=0.640),respectively.In different stratifications,the eradication rates of the VPZ-HDDT group were higher than those of the PPI-HDDT group,but the differences were not statistically significant.The incidence of adverse reactions and compliance of the VPZ-HDDT group and the PPI-HDDT group were similar,with no statistically significant differences.Conclusion Both two combination regimens can achieve clinically acceptable eradication rates(＞85％)in the first-time treatment patients.For the retreated and refractory patients,the choice of vonoprazan is more beneficial.

Objective To investigate the prognosis of childhood T-lymphoblastic lymphoma(T-LBL)treated with acute lymphoblastic leukemia(ALL)regimen and related influencing factors.Methods A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen(ALL-2009 or CCCG-ALL-2015 regimen)from May 2010 to May 2022.Results The 29 children with T-LBL had a 5-year overall survival(OS)rate of 84％±7％and an event-free survival(EFS)rate of 81％±8％.The children with B systemic symptoms(unexplained fever＞38° C for more than 3 days;night sweats;weight loss＞10％within 6 months)at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms(P＜0.05).The children with platelet count＞400x109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates(P＜0.05).There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen(P＞0.05).Compared with the ALL-2009 regimen,the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections(P＜0.05).Conclusions The ALL regimen is safe and effective in children with T-LBL.Children with B systemic symptoms,platelet count＞400x109/L,and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis.Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections,but it does not affect prognosis.

Objective To explore the effect of collaborative mode of adopting infection prevention and control(IPC)and antimicrobial stewardship(AMS)by medical institutions on reducing bacterial resistance.Methods Healthcare-associated infection(HAI)management and antimicrobial-related indicators,as well as multidrug-resis-tant organism(MDRO)detection rates of all hospitalized patients in a hospital from January 1,2015 to December 31,2022 were collected.The effectiveness of collaborative mode of IPC and AMS was evaluated.Results Compared with 2015-2016,the incidence of MDRO HAI in 2021-2022 decreased from 0.22％to 0.16％(P＜0.05),anti-microbial use density in hospitalized patients decreased from 48.48 to 42.17,antimicrobial use rate decreased from 49.45％to 45.21％(P＜0.05).The use rate of prophylactic antimicrobial agents in class Ⅰ incision surgery de-creased from 48.62％to 33.13％(P＜0.05).Compared with 2017-2018,pathogen detection rate before antimi-crobial therapy increased from 60.73％to 72.18％in 2021-2022(P＜0.05).Compared with 2015-2016,except the detection rate of vancomycin-resistant Enterococcus faecalis slightly increased in 2021-2022,detection rates of other common MDRO decreased,especially methicillin-resistant Staphylococcus aureus,carbapenem-resistant Acine-tobacter baumannii,carbapenem-resistant Pseudomonas aeruginosa,broad-spectrum β-lactamase-producing Kleb-siella pneumoniae,broad-spectrum β-lactamase-producing Escherichia coli and fluoroquinolone-resistant Escherichia coli,differences were all statistically significant(all P＜0.05).Conclusion The collaborative mode of IPC and AMS can effectively promote the rational use of antimicrobial agents,decrease the occurrence and transmission of MDRO,and decrease bacterial resistance.

Objective:To explore the value of REG3α,sST2 and TNFR1 in peripheral blood for risk stratification and prognostic evaluation of acute graft-versus-host disease(aGVHD)after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in children.Methods:From January 2020 to March 2022,70 children with aGVHD after allo-HSCT in the First Affiliated Hospital of Zhengzhou University were selected as the research objects,of which 50 cases were mild aGVHD(grade Ⅰ-Ⅱ)and 20 cases were severe aGVHD(grade Ⅲ-Ⅳ).30 healthy children who underwent physical examinations in our hospital during the same period were selected as the control group.Luminex platform was used to detect the protein expression levels of REG3α,sST2 and TNFR1 during aGVHD occurrence,and the differences between the three groups were analyzed by one-way ANOVA.According to the outcome of aGVHD treatment within 28 days,the patients were divided into a good prognosis group of 58 cases and a poor prognosis group of 12 cases.The ROC curve was used to analyze the value of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD.Results:The peripheral blood levels of REG3α,sST2 and TNFR1 in the mild aGVHD and severe aGVHD groups were significantly higher than those in the control group(P＜0.05),and those in the severe aGVHD group were significantly higher than those in the mild aGVHD group(P＜0.05).Compared with the good prognosis group,the peripheral blood levels of REG3α,sST2 and TNFR1 in the poor prognosis group were significantly higher(t=9.27,3.33,2.97;P＜0.01).ROC curve analysis showed that the area under the curve(AUC),sensitivity and specificity of the combined detection of REG3α,sST2 and TNFR1 in predicting the prognosis of children with aGVHD were higher than those of the above indicators detected alone or in pairs.Conclusion:The expression levels of REG3α,sST2 and TNFR1 were related to the severity of aGVHD.The combination of REG3α,sST2 and TNFR1 has a high clinical value in predicting the prognosis of children with aGVHD,which is expected to provide a reliable reference for clinical evaluation of the prognosis of children with aGVHD.