OBJECTIVE To analyze the current research status and development trends in the field of biosecurity both domestically and internationally,and to provide references for biosecurity-related research and evaluation.METHODS Using CiteSpace software,bibliometrics was employed to collect thematic research on bios-ecurity published in the Science Citation Index database from 2004 to 2024.Research trends,keyword clustering and emergence research were investigated,with visual analysis conducted on the number of publications,contribu-ting countries and keywords.RESULTS A total of 13 108 articles were included in this study.Research on biosecu-rity both domestically and internationally was in a phase of rapid growth,with related fields exhibiting an"expo-nential"growth trend.China ranked first in terms of the number of publications(35.62％),followed by the Unit-ed States(19.33％)and Australia(10.38％).Analysis of keyword clustering revealed 20 clusters,including risk assessment,antibacterial drug resistance,green synthesis,gene therapy,one health,drug delivery,invasive spe-cies,bovines,emergency animal diseases and highly pathogenic avian influenza.Regarding antibacterial drug re-sistance,the focus was primarily on the transmission mechanisms of drug-resistant pathogens in poultry farming,while exploring novel antibacterial technologies such as biomaterials and probiotic alternatives to address the chal-lenge of drug-resistant bacteria.In terms of strategies,research was primarily conducted on the development,ap-plication and safety of agricultural biotechnology and genetically modified crops.Keywords burst analysis indicated that different research topics had certain temporal research popularity,with carbon nanotubes,Anopheles ste-phensi,coronaviruses and one health being recent emerging themes.CONCLUSION China achieves certain pro-gress in the field of biosecurity research,and conducts certain exploratory research on prevention,diagnosis,treatment and intervention of biosecurity.Biosecurity risk assessment,as a research hotspot,deserves close attention.

OBJECTIVE To analyze the current research status and development trends in the field of biosecurity both domestically and internationally,and to provide references for biosecurity-related research and evaluation.METHODS Using CiteSpace software,bibliometrics was employed to collect thematic research on bios-ecurity published in the Science Citation Index database from 2004 to 2024.Research trends,keyword clustering and emergence research were investigated,with visual analysis conducted on the number of publications,contribu-ting countries and keywords.RESULTS A total of 13 108 articles were included in this study.Research on biosecu-rity both domestically and internationally was in a phase of rapid growth,with related fields exhibiting an"expo-nential"growth trend.China ranked first in terms of the number of publications(35.62％),followed by the Unit-ed States(19.33％)and Australia(10.38％).Analysis of keyword clustering revealed 20 clusters,including risk assessment,antibacterial drug resistance,green synthesis,gene therapy,one health,drug delivery,invasive spe-cies,bovines,emergency animal diseases and highly pathogenic avian influenza.Regarding antibacterial drug re-sistance,the focus was primarily on the transmission mechanisms of drug-resistant pathogens in poultry farming,while exploring novel antibacterial technologies such as biomaterials and probiotic alternatives to address the chal-lenge of drug-resistant bacteria.In terms of strategies,research was primarily conducted on the development,ap-plication and safety of agricultural biotechnology and genetically modified crops.Keywords burst analysis indicated that different research topics had certain temporal research popularity,with carbon nanotubes,Anopheles ste-phensi,coronaviruses and one health being recent emerging themes.CONCLUSION China achieves certain pro-gress in the field of biosecurity research,and conducts certain exploratory research on prevention,diagnosis,treatment and intervention of biosecurity.Biosecurity risk assessment,as a research hotspot,deserves close attention.

Epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI)represent a class of small-molecule targeted therapeutics for oncology treatment,and serve as first-line therapy for advanced non-small cell lung cancer(NSCLC)with EGFR-sensitive mutations,with representative agents including gefitinib,dacomitinib,and osimertinib.In clinical practice,dose adjustment of EGFR-TKI may be required for cancer patients under special circumstances such as drug combinations or hepatic/renal impairment.Physiologically-based pharmacokinetic(PBPK)model,capable of predicting pharmacokinetic(PK)processes in humans,has emerged as a vital tool for clinical dose optimization.This article sorts the modeling methodologies,workflows,and commonly used software tools for PBPK model,and summarizes the current applications of PBPK model in EGFR-TKI precision therapy as of June 30,2024.Findings demonstrate that PBPK modeling methods commonly employ the"bottom-up"approach and the middle-out approach.The process typically involves four steps:parameter collection,compartment selection,model validation,and model application.Commonly used software for modeling includes Simcyp,GastroPlus,and open-source software such as PK-Sim.PBPK model can be utilized for predicting drug-drug interactions of EGFR-TKI co-administered with metabolic enzyme inducers or inhibitors,acid-suppressive drugs,or traditional Chinese and Western medicines.It can also adjust dosages in conjunction with genomics,predict PK processes in special populations(such as patients with liver or kidney dysfunction,pediatric patients),evaluate the efficacy and safety of drugs,and extrapolate PK predictions from animal models to humans.

Objective:To investigate personal exposures to nitrogen oxides(NOX)and nitrogen di-oxide(NO2)and the influence of baseline personal characteristics,living environment and daily activity patterns of the participants on the exposures among adults over 35 in Tianjin and Shanghai.Methods:In this panel study,91 healthy nonsmoking adults aged over 35 from Tianjin and Shanghai participated in our study.The study was conducted in summer and winter.The participants were followed for three times with an interval of at least two weeks.Only participants in Shanghai were followed once in winter because of the COVID-19 pandemic.Twenty-seven participants completed follow-up visits in both seasons.We measured their 24 h personal exposures to NOX and NO2and collected their baseline and time-activity in-formation through questionnaire/diary.The linear mixed model was used to analyze the associations be-tween potential influencing factors and personal NOX and NO2 exposure levels.Results:There were 349 follow-up visits with valid 24 h personal NO2 and NOX exposure measurements in the two cities.The ave-rage 24 h personal exposures to NO2 and NOX(volume fraction)in Tianjin participants were 18.0 x 10-9 and 26.2 × 10-9 in summer,and 31.0 x 10-9 and 54.9 x 10-9in winter,respectively;and the average 24 h personal exposures to NO2 and NOX in Shanghai participants were 38.7 x 10-9and 100.0x10-9in summer,and 45.5 x10-9 and 139.2 x 10-9 in winter,respectively.The results of univariate regression analysis showed that their personal NOX exposure levels were significantly associated with city,season,gender,average daily cooking times,and ambient NO2 concentrations measured at fixed-site monitoring stations.In addition to the above factors,the personal NOX exposure levels were also significantly associ-ated with educational level and the personal NO2 exposure levels were also significantly associated with passive smoking,average daily home time,cooking energy type,residential distance from main traffic road,and use of kitchen ventilators.Multivariate regression analysis showed that the personal exposure levels of NO2 and NOX were significantly lower in Tianjin than that in Shanghai,were significantly lower in summer than that in winter,and were significantly and positively associated with ambient NO2 concen-trations measured at fixed-site monitoring stations.In addition,personal NOX exposure levels were signifi-cantly lower in females than in males,and personal NO2 exposure levels were significantly positively asso-ciated with average daily cooking times and significantly inversely associated with average daily home time.For every interquartile range(IQR)increase(12.7 × 10-9)in ambient NO2,the personal NO2 exposure levels increased by 27.5％(95％CI:17.0％-38.9％),and personal NOX exposure levels in-creased by 16.1％(95％CI:7.1％-25.8％).Conclusion:Season,city and ambient NO2 concentra-tions are significant influencing factors of personal exposure levels of NO2and NOX At the same time,the personal exposures levels of NO2 are also affected by lifestyle factors.Our study provides scientific evi-dence for making precise air pollution control decisions and reducing the exposure levels of NOX in the population.

Objective:To discuss the effect of urolithin C(UC)on the proliferation,apoptosis,and autophagy of the acute myeloid leukemia(AML)HL-60 cells,and to clarify its mechanism.Methods:The HL-60 cells were divided into different concentrations(20,40,60,80,and 100 μmol·L-1)of urolithin A(UA)groups,urolithin B(UB)groups,and UC groups.CCK-8 assay was used to detect the proliferation activity of the cells in various groups;the morphology of the cells in different concentrations of UC groups was observed under optical microscope.The HL-60 cells were divided into different concentrations(0,20,40,and 80 μmol·L-1)of UC groups and 3-methyladenine(3-MA)combined with different concentrations(0,20,40,and 80 μmol·L-1)of UC groups.CCK-8 assay was used to detect the proliferation activities of the cells in various groups.The HL-60 cells were divided into control group(0 μmol·L-1)and different concentrations(20,40,and 80 μmol·L-1)of UC groups.The live/dead cell staining method was used to detect the dead rates of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups;the autophagy of the cells was detected by autophagy staining kit(monodansylcadaverine,MDC)method;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of Beclin 1,autophagy related gene 9(ATG9),and autophagy related gene 7(ATG7)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of cysteinyl aspartate specific proteinase-3(Caspase-3),cleaved cysteinyl aspartate specific proteinase-3(Cleaved Caspase-3),microtubule-associated protein 1 light 3(LC-3),extracellular regulated protein kinases(ERK),phosphorylated ERK(p-ERK),AMP-activated protein kinase(AMPK),and phosphorylated AMPK(p-AMPK)in the cells in various groups.Results:The CCK-8 assay results showed that after cultured for 24,48,and 72 h,compared with 0 μmol·L-1 UA,UB,and UC groups,the proliferation activities of the cells in different concentrations of UA,UB,and UC groups were decreased(P＜0.01)with a concentration-and time-dependent manner;at 48 h,compared with UA and UB,the half-maximal inhibitory concentration(IC50)of UC was the lowest.The cell morphology observation results showed that compared with control group,the intercellular connection and the number of the cells were decreased with the increasing of UC concentration,and the cell fragment was increased.The CCK-8 assay results showed that compared with 40 and 80 μmol·L-1 UC groups,the proliferation activities of the cells in 3-MA combined with 40 and 80 μmol·L-1 UC groups were increased(P＜0.05 or P＜0.01).The live/dead cell staining results showed that compared with control group,the dead rates of the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).The flow cytometry results showed that compared with control group,the apoptotic rate of the cells in 80 μmol·L-1 UC group was increased(P＜0.01).The MDC method results showed that with the increasing of UC concentration,the green fluorescence in the cells in different concentrations of UC groups was gradually intensified.The RT-qPCR results showed that compared with control group,the expression levels of Beclin 1,ATG9,and ATG7 mRNA in the cells in 80 μmol·L-1 UC group were increased(P＜0.01).The Western blotting results showed that compared with control group,the expression levels of Cleaved Caspase-3 protein in the cells in 20,40,and 80 μmol·L-1 UC groups were increased(P＜0.01),the ratio of membrane LC3/cytoplasmic LC3(LC3-Ⅱ/LC3-Ⅰ)in the cells in 80 μmol·L-1 UC group was increased(P＜0.05),and the ratios of p-AMPK/AMPK and p-ERK/ERK in the cells in 40 and 80 μmol·L-1 UC groups were increased(P＜0.01).Conclusion:UC can inhibit the proliferation of the AML HL-60 cells,induce the apoptosis and autophagy,and increase the phosphorylation levels of ERK and AMPK proteins in the cells.

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.

OBJECTIVE To exc avate and evaluate the adverse reaction signals of 4 kinds of imported programmed cell death 1 （PD-1）and its ligand （PD-L1）inhibitors，and to guide rational drug use in clinic. METHODS OpenVigil 2.1 software was used to obtain the adverse event reports of four drugs as nivolumab ，pembrolizumab，atezolizumab and durvalumab from the first quarter of 2013 to the fourth quarter of 2020 in the US FDA adverse event reporting system. The reporting odds ratio and proportional reporting ratio were used for signal mining to evaluate new or potential adverse reaction signals. RESULTS A total of 46 840 reports of adverse events with PD- 1/PD-L1 inhibitors as the primary suspected drug were collected ，including 28 896 reports of nivolumab，13 298 reports of pembrolizumab ，3 398 reports of atezolizumab ，and 1 248 reports of durvalumab. From the general characteristics of these reports ，the gender distribution was more men than women ，and the age distribution was mainly in the range of 51-85 years old. The reporting year was mainly in the nearly 4-5 years，and the main reporting countries were the US and Japan，with“death”and“hospitalization or prolonged hospitalization ”as the main serious adverse events which were over 50％ of the whole of 4 kinds of adverse events. A total of 1 597 adverse reaction signals were obtained ，involving 26 systems，focusing on “benign，malignant and unspecified neoplasms （cystic and polypoid tumor ）”，“infections and infestations ”and“investigations”， etc. The analysis of the top 50 adverse reaction signals showed that the largest number of report was endocrine system disease ，the most frequency signal was “malignant neoplasm progression ”and the strongest adverse reaction signal was “radiation pneumonitis ”. And it was also found that 13 adverse reaction signals ，such as “radiation pneumonitis ”“cholangitis”“fulminant type 1 diabetes mellitus” “blood creatine phosphokinase increased ” “disseminated intravascular coagulation ”“cardiac failure ”and “cerebral infarction ”，etc.，were not reported in the drug instructions. CONCLUSIONS PD-1/PD-L1 inhibitors mediate a large number of adverse reaction signals，resulting in high safety risks in “benign，malignant and unspecified neoplasms （cystic and polypoid tumor ）”，“infections and infestations ”and “investigations”，etc. The newly discovered 13 adverse reaction signals ，such as “radiation pneumonitis ”“cholangitis”“blood creatine phosphokinase increased ”“cardiac failure ”and“cerebral infarction ”are of great significance for guiding rational drug use in clinic.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective To analyze the effects of different thyroid stimulating hormone (TSH) cut-off values on the screening of congenital hypothyroidism (CH) in newborns in Guangxi.Methods The TSH results of 83 608 newborns tested by Genetic Screening Processor (GSP) from the Genetic Metabolism Center of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region from May 2017 to April 2018 were collected.Using the percentile method and the receiver operating characteristic (ROC) curve method,the TSH cut-off values were calculated and compared with the assumed cut-off values 9.00 or 10.00 mU/L,to analyze the effects of four different TSH cut-off values on CH screening.Results Using GSP,the TSH results of 83 608 newborns showed a positive skewed distribution,TSH cut-off value of the percentile method (P99) was 7.96 mU/L,836 cases were suspicious,43 cases were diagnosed with CH (6 cases were missed diagnosis),and 65 cases were high TSH (21 cases were missed diagnosis);TSH cut-off value of the ROC curve method was 6.45 mU/L,1 480 case were suspicious,49 cases were diagnosed with CH,and 86 cases were high TSH,both were no missed diagnosis;when TSH cut-off values were 9.00 or 10.00 mU/L,the suspicious were 478 and 305 cases,respectively,and the confirmed CH were 37 and 35 cases (missed diagnosis were 12 and 14 cases,respectively),high TSH were 46 and 33 cases (missed diagnosis were 40 and 53 cases,respectively).The CH incidence of the ROC curve method was compared with the percentile method and using the cut-off values 9.00 and 10.00 mU/L,the differences were statistically significant (P ＜ 0.05).Conclusions The GSP and ROC curve method were used to successfully establish the TSH cut-off value on the screening of CH in newborns in Guangxi.The cut-off value can not only ensure the accuracy of screening,but also avoid missed diagnosis and reduce birth defects.