As green, sustainable, and environmentally friendly material processing processes using biological cells or enzymes to achieve substance conversion, bioprocesses play an increasingly important role in biomanufacturing. It is difficult to optimize bioprocesses because of the complex relationship at multiple levels and multiple scales. The knowledge of mesoscale behaviors is the key to understanding the dynamics of bioprocesses and to sort out the complex relationships of parameter variations in the spatial-temporal domain. Mesoscale numerical simulation paves a way for understanding these phenomena, and the integration of artificial intelligence (AI) and mesoscale simulation offers new vitality into the optimization of bioprocesses. This article reviews the progress in mesoscale simulation and AI optimization of bioprocesses and discusses the possible development directions, aiming to promote the development of this field.
Artificial Intelligence ; Biotechnology/trends* ; Computer Simulation

Objective:To investigate the impact of early cleavage on the pregnancy and obstetric outcomes of fresh cycle single cleavage embryo and single blastocyst transfer.Methods:A retrospective study was conducted to analyze 794 patients who underwent single cleavage embryo transfer and 1466 patients who underwent single blastocyst transfer in the reproductive medicine center of our hospital from August 2018 to December 2022 during the fresh cycle treatment of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET).The patients were divided into two groups according to whether the transferred embryos underwent normal early cleavage.In the single cleavage embryo transfer,there were 383 cases in the normal early cleavage group(early cleavage group)and 411 cases in the non normal early cleavage group(non-early cleavage group);in the single blastocyst transfer,there were 815 cases in the early cleavage group and 651 cases in the non-early cleavage group.The pregnancy and obstetric outcomes of the early cleavage group and non-early cleavage group were compared in single cleavage embryo transfer and single blastocyst transfer.Results:In the single cleavage embryo transfer,the human chorionic gonadotropin(hCG)positive rate,clinical pregnancy rate,and live birth rate in the early cleavage group were significantly higher than those in the non-early cleavage group(64.0％vs.55.7％,P=0.018;54.6％vs.47.0％,P=0.032;46.7％vs.38.7％,P=0.022).There were no significant differ-ences in biochemical abortion rate,multiple pregnancy rate,abortion rate,early abortion rate,premature delivery rate,low birth weight rate,macrosomia rate,and birth defect rate compared with the non-early cleavage group(P＞0.05);in the single blastocyst transfer,there were no significant differences in pregnancy outcomes and obstetric indicators between the early cleavage group and the non-early cleavage group(P＞0.05).Multivariate Logistic regression analysis showed that after adjusting for confounding factors on pregnancy outcomes,in the single cleavage embryo transfer,the hCG positive rate(aOR 1.54,95％CI 1.12-2.11,P=0.008),clinical preg-nancy rate(aOR 1.49,95％CI 1.09-2.04,P=0.012),and live birth rate(aOR 1.53,95％CI 1.12-2.09,P=0.008)in the early cleavage group were significantly higher than those in the non-early cleavage group;in the sin-gle blastocyst transfer,there were no significant differences for these indicators between the early cleavage group and the non-early cleavage group(P＞0.05).Conclusions:Transplantation of single cleavage embryo with nor-mal early cleavage can significantly improve the clinical pregnancy rate and live birth rate.Early cleavage during single blastocyst transplantation had no significant effect on clinical pregnancy outcome.Early cleavage had no significant effect on the obstetric outcomes of single cleavage embryo and single blastocyst transfer.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

Objective:To investigate the epidemiological characteristics and trends of birth defects related to assisted reproductive technology (ART) in Jiangxi Province from 2014 to 2023, and to explore the correlation factors of birth defect occurrence.Methods:A retrospective collection of ART treatment data and follow-up results from January 2014 to December 2023 across 18 reproductive centers in Jiangxi Province was conducted. The trend of birth defects and the rank order of defect types were analyzed. Exact probability methods were used to estimate the 95% confidence intervals ( CI) of the incidence rates, and Poisson regression was applied to identify independent correlation factors. Results:A total of 65 003 ART offspring were included in this study, comprising 2 025 offspring from intrauterine insemination (IUI) and 62 978 from in vitro fertilization and embryo transfer (IVF-ET). The overall incidence of birth defects was 13.46‰ (95% CI: 12.59‰-14.38‰), with 9.38‰ (95% CI: 5.66‰-14.61‰) for IUI and 13.59‰ (95% CI:12.70‰-14.53‰) for IVF-ET. The incidence of birth defects showed a decreasing trend from 2014 to 2023 (17.11‰ to 11.47‰, Ptrend=0.003). The top three birth defect types were circulatory system defects (3.71‰, 95% CI: 3.25‰-4.21‰), musculoskeletal system defects (2.37‰, 95% CI: 2.01‰-2.77‰), and congenital malformations of the face, ears, eyes, and neck (1.23‰, 95% CI: 0.98‰-1.53‰). Univariate analysis indicated that male offspring from IVF-ET had a higher incidence of birth defects than that in female offspring (14.72‰ vs. 12.31‰, P=0.009). Additionally, gestational age, birth weight, fetal number, cause of infertility, and year of delivery were significantly associated with birth defect incidence in IVF-ET offspring ( P<0.001, P<0.001, P<0.001, P=0.025, P=0.037). Multivariate analysis showed that in singleton pregnancies, male offspring, gestational age 32-36 weeks birth weight <1 500 g, and infertility with bilateral factors were independent risk factors for birth defects ( OR=1.21, 95% CI: 1.00-1.47, P=0.046; OR=1.90,95% CI: 1.41-2.56, P<0.001; OR=3.37, 95% CI: 1.33-8.51, P=0.010; OR=1.38, 95% CI: 1.12-1.69, P=0.003), while in multiple pregnancies, male offspring, gestational age <32 weeks, gestational age 32-36 weeks, birth weight <1 500 g, birth weight 1 500-2 499 g, maternal age 25-29 years and maternal age 30-34 years were independent risk factors ( OR=1.25, 95% CI: 1.03-1.52, P=0.023; OR=2.06, 95% CI: 1.35-3.15, P=0.001; OR=1.32,95% CI: 1.05-1.66, P=0.016; OR=1.98,95% CI: 1.19-3.28, P=0.009; OR=2.06,95% CI: 1.64-2.60, P<0.001; OR=2.00, 95% CI: 1.31-3.06, P=0.001; OR=1.90,95% CI: 1.24-2.92, P=0.003). Conclusion:Over the past 10 years, the incidence of birth defects in ART offspring in Jiangxi Province has shown a decreasing trend annually, with circulatory system malformations being the most common. The occurrence of birth defects in IVF offspring is primarily associated with maternal and infant characteristics, such as gender, gestational age, birth weight, number of fetuses, and cause of infertility, independent of ART treatment factors.

Objective:To investigate the impact of early cleavage on the pregnancy and obstetric outcomes of fresh cycle single cleavage embryo and single blastocyst transfer.Methods:A retrospective study was conducted to analyze 794 patients who underwent single cleavage embryo transfer and 1466 patients who underwent single blastocyst transfer in the reproductive medicine center of our hospital from August 2018 to December 2022 during the fresh cycle treatment of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET).The patients were divided into two groups according to whether the transferred embryos underwent normal early cleavage.In the single cleavage embryo transfer,there were 383 cases in the normal early cleavage group(early cleavage group)and 411 cases in the non normal early cleavage group(non-early cleavage group);in the single blastocyst transfer,there were 815 cases in the early cleavage group and 651 cases in the non-early cleavage group.The pregnancy and obstetric outcomes of the early cleavage group and non-early cleavage group were compared in single cleavage embryo transfer and single blastocyst transfer.Results:In the single cleavage embryo transfer,the human chorionic gonadotropin(hCG)positive rate,clinical pregnancy rate,and live birth rate in the early cleavage group were significantly higher than those in the non-early cleavage group(64.0％vs.55.7％,P=0.018;54.6％vs.47.0％,P=0.032;46.7％vs.38.7％,P=0.022).There were no significant differ-ences in biochemical abortion rate,multiple pregnancy rate,abortion rate,early abortion rate,premature delivery rate,low birth weight rate,macrosomia rate,and birth defect rate compared with the non-early cleavage group(P＞0.05);in the single blastocyst transfer,there were no significant differences in pregnancy outcomes and obstetric indicators between the early cleavage group and the non-early cleavage group(P＞0.05).Multivariate Logistic regression analysis showed that after adjusting for confounding factors on pregnancy outcomes,in the single cleavage embryo transfer,the hCG positive rate(aOR 1.54,95％CI 1.12-2.11,P=0.008),clinical preg-nancy rate(aOR 1.49,95％CI 1.09-2.04,P=0.012),and live birth rate(aOR 1.53,95％CI 1.12-2.09,P=0.008)in the early cleavage group were significantly higher than those in the non-early cleavage group;in the sin-gle blastocyst transfer,there were no significant differences for these indicators between the early cleavage group and the non-early cleavage group(P＞0.05).Conclusions:Transplantation of single cleavage embryo with nor-mal early cleavage can significantly improve the clinical pregnancy rate and live birth rate.Early cleavage during single blastocyst transplantation had no significant effect on clinical pregnancy outcome.Early cleavage had no significant effect on the obstetric outcomes of single cleavage embryo and single blastocyst transfer.

AIM:To optimize the clinical dosage and administration regimen of a novel long-acting injectable aripiprazole microsphere(LZMT05)using plasma concentration data from two clinical trials.METHODS:Plasma concentrations were collected from 196 schizophrenia patients administered LZMT05,and a population pharmacokinetic(Pop-PK)model was developed.The therapeutic window was defined as the steady-state trough-to-peak concentration range(94.0-534 ng/mL)of oral ar-ipiprazole.Multiple clinical scenarios were simulat-ed to identify the optimal regimen.RESULTS:A one-compartment model with dual first-order ab-sorption and first-order elimination characterized LZMT05 pharmacokinetics.Covariates like sex and CYP2D6 genotype were integrated into the final model.Simulations demonstrated that switching from 10 mg oral aripiprazole to 350 mg LZMT05 ev-ery 4 weeks sustained concentrations within the therapeutic window with minimal peak-to-trough fluctuations.CONCLUSION:The PopPK-guided opti-mized LZMT05 regimen maintained drug exposure within the therapeutic window,suggesting favor-able efficacy and safety.

A retrospective analysis was made on clinical data of a case of familial dysalbuminemic hyperthyroxinemia (FDH) treated at Hebei Children′s Hospital in August 2021.The patient, female, 4 years and 2 months old, was diagnosed with growth retardation.Genetic sequencing of the child and her immediate family revealed a heterozygous mutation, c.725G>A(p.R242H) in exon 7 of the albumin gene, which confirmed the diagnosis of FDH.The growth and development of the girl were monitored regularly.Early identification and diagnosis of FDH can prevent misdiagnosis or improper antithyroid medication from affecting children′s growth and development, and growth hormone therapy is effective for children with FDH who are slow growing.

Objective:To explore the correlations among contrast-enhanced ultrasound(CEUS)enhancement,time to peak and resolution time,and pathological grading and alpha fetoprotein(AFP)in diagnosing hepatocellular carcinoma(HCC),so as to provide scientific basis for the CEUS application.Methods:A total of 350 HCC patients who admitted to Kailuan General Hospital of Tangshan City,Hebei Province from June 2018 to February 2020 were selected.All patients underwent routine CEUS scanning and AFP detection that was performed by using Roche e411 electrochemiluminescence immunoassay analyzer.Using World Health Organization(WHO)Category Classification and Diagnostic Criteria Series to complete grading for liver cancer.The COX regression analysis was adopted to analyze the correlation between CEUS characteristic parameters and age,AFP,tumor grading,tumor size and gender.Results:The diameter of liver nodules of 304 HCC patients ranged from 9.0 to 146.2 mm,which maximum average diameter was 42.5 mm.The COX analysis indicated that serum AFP level was important influencing factor on CEUS examination results at arterial phase(HR=1.83,P<0.05).The blood supply artery within the tumor appeared positive correlation with serum AFP level,and the tumor size appeared positive correlation with the CEUS enhancement at arterial phase(r=0.231,0.483,P<0.05),and the correlation between CEUS enhancement at arterial phase and tumor size was strongest.Conclusion:The serum AFP level is correlated with the measured results of CEUS enhancement at arterial phase,time to peak and resolution time,which expression level is often influenced by some factors such as serum AFP and tumor size.It can provide reference for subsequent diagnosis and treatment.

Objective To investigate the prevalence of zika virus(ZIKV),dengue virus(DENV)and chikungunya virus(CHIKV)infections in blood donors in Kunming,China.Methods A total of 10 662 samples from blood donors in Kunming from August 2022 to October 2023 were randomly collected,and ZIKV RNA,DENV RNA and CHIKV RNA were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction(RT-qPCR).Results Effec-tive test results were obtained from 10 554 samples,and no positive case of ZIKV RNA,DENV RNA and CHIKV RNA was found in this investigation.Conclusion The risk of ZIKV,DENV and CHIKV infections among blood donors in Kunming is low,and there is no immediate need for routine screening for these viruses among blood donors in this region.