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 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.

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 effect of methylene blue combined with ropivacaine for sa-phenous nerve block on the postoperative analgesia in patients undergoing total knee arthroplasty.Methods Sixty patients were selected for elective TKA,24 males and 36 females,aged 60-75 years,BMI 18.5-30.0 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were divided into two groups using randomized nu-merical table method:methylene blue combined with ropivacaine group(group MR)and ropivacaine group(group R),30 patients in each group.Ultrasound-guided saphenous nerve block was performed with 0.10％methylene blue+0.25％ropivacaine composite 20 ml in group MR,and ultrasound-guided saphenous nerve block was performed with 0.25％ropivacaine 20 ml in group R before the combined spinal-epidural anesthe-sia.The VAS pain scores at rest and during activity at 6,12,24,48,and 72 hours postoperatively,the maximum range of motion mobility(ROM)of the knee joint of the affected limb,the quadriceps unarmed manual muscle test(MMT)scores at 24,48,and 72 hours postoperatively,the effective number of analge-sic pump presses,and the time of the first additional time of the remedial analgesic were recorded.The com-plications related to nerve block,such as bleeding,infection,local anesthetic poisoning,nerve injury,and peripheral tissue injury were recorded.Results Compared with group R,the VAS pain score at rest was significantly lower in group MR at 12,24,48,and 72 hours postoperatively(P＜0.05).Compared with group R,the VAS pain scores during activity were significantly lower in the group MR at 48 and 72 hours postoperatively(P＜0.05).Compared with group R,ROM of the knee joint of the affected limb was signif-icantly greater in group MR at 24,48,and 72 hours postoperatively(P＜0.05).The effective number of analgesic pump presses and the rate of remedial analgesia were significantly lower in the group MR compared with group R(P＜0.05).There were no complications related to nerve block during hospital stay in both groups.Conclusion Ultrasound-guided methylene blue combined with ropivacaine for saphenous nerve block can enhance the postoperative analgesic effect,prolong the duration of analgesia,reduce the use of postoperative analgesics,and facilitate the functional exercise of the knee joint in the early postoperative pe-riod.

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 epidemiological characteristics of overseas imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021, so as to provide insights into the prevention and control of overseas imported arthropod-borne infectious diseases. Methods: The data pertaining to imported dengue fever and malaria cases in Yunnan Province from 2015 to 2021 were collected from the Chinese Disease Prevention and Control Information System, and the temporal distribution, regional distribution, population distribution, sources, diagnosis and treatment of imported dengue fever and malaria cases were descriptively analyzed. Results: Totally 4 332 overseas imported dengue fever cases and 2 011 overseas imported malaria cases were reported in Yunnan Province form 2015 to 2021, which accounted for 30.09% of all reported dengue fever cases and 98.53% of all reported malaria cases. The number of overseas imported dengue fever and malaria cases peaked from August to November (83.13% of all imported dengue fever cases) and from April to July (59.08% of all imported malaria cases), and the cases were predominantly reported in Dehong Prefecture (50.99% and 58.88%), with farmers as the predominant occupation (40.21% and 67.93%). The dengue fever and malaria cases were mainly imported from Southeast Asia (99.04% and 88.21%), and the proportions of definitive diagnosis of dengue fever and malaria were 88.33% and 97.80% at township hospitals, respectively. Conclusions The number of overseas imported dengue fever and malaria cases peaked from August to November and from April to July in Yunnan Province from 2015 to 2021, and the cases were predominantly reported in Dehong Prefecture and imported from Southeast Asia, with farmers as the predominant occupation.

Objective:To understand the genome and genetic evolution characteristics of influenza B virus (FluB) in Suzhou city from July 2021 to January 2022.Methods:Real-time fluorescence reverse transcription polymerase chain reaction (Real-Time RT-PCR) was used for the typing of influenza virus (Flu). The detected FluB strains were sequenced by Miseq high-throughput sequencing platform through whole genome capture and library construction. The FluB hemagglutinin (HA), neuraminidase (NA) and matrix protein (MP) gene phylogenetic trees were constructed by Neighbor-Joining method (NJ) with MEGA X software. The Potential N-glycosylation sites of HA and NA proteins were predicted by NetNGlyc 1.0 server software.Results:FluB was detected in 280 of the 1 500 throat swab samples, and the FluB genome sequence was completed in 53 strains. The nucleic acid identity of 8 gene fragments (PB1, PB2, PA, HA, NP, NA, MP, NS) in the FluB strains was 99.3%-100%, 98.1%-100%, 98.8%-100%, 98.0%-100%, 99.2%-100%, 98.4%-100%, 98.2%-100% and 99.0%-100%, respectively. Except for the 4 samples in July 2021, which belonged to the V1A.3 clade of FluB, the rest of the samples belonged to the V1A.3a.2 clade. Every amino acid sequence of HA protein of Flu B collected after October 2021 showed 9-11 substitutions compared with the reference strain (B/Washington/02/2019), which sharing 9 mutation sites (H122Q, A127T, R133G, P144L, N150K, G184E, N197D, K203R and R279K). No drug-resistant mutations associated with NA inhibitors such as oseltamivir were found. Respectively, 11 and 4 potential glycosylation sites were identified in HA and NA proteins of the FluB strains.Conclusions:From July 2021 to January 2022, V1A.3a2 was the dominant FluB strains in Suzhou city, and the amino acid sequences of HA and NA proteins showed multiple site mutations.

Background::The increasing burden of non-alcoholic fatty liver disease (NAFLD) worldwide imposes an emerging public health issue. We perform the current study to estimate the global prevalence, incidence, disease progression, and clinical outcomes of NAFLD.Methods::A systematic search was conducted in Medline, Embase, Web of Science, Google Scholar, and Cochrane CENTRAL that screened articles in English language published from January 2000 to December 2021. NAFLD prevalence, incidence, rate of disease progression, and outcomes were calculated with the DerSimonian-Laird random effects model with arcsine transformation.Results::Our search identified 59,156 records, of which 578 studies fulfilled our inclusion criteria. The overall prevalence of NAFLD was 29.38% (95% confidence interval [CI] 28.09–30.69) regardless of the diagnostic techniques. Looking at the group in which the diagnosis was made by ultrasound exclusively, the pooled prevalence was 30.49% (95% CI 29.55–31.43). NAFLD has become more prevalent during the year 2011–2021 (31.63%, 95% CI 30.23–33.04) compared with year 2000–2010 (27.94%, 95% CI 26.23–29.69). The pooled estimation of non-alcoholic steatohepatitis prevalence was 8.26% (95% CI 1.13–21.01), 46.49% (95% CI 35.93–57.20), and 46.72% (95% CI 37.57–55.98) in general population, NAFLD patients, and severe/morbidly obese patients, respectively. Based on a total of 110,142 newly developed NAFLD patients, the pooled incident rate was estimated as 46.24 cases per 1000 person-years (95% CI 43.21–49.30). In patients with NAFLD, the incident rate of hepatocellular carcinoma was 1.46 (95% CI 0.90–2.03) cases per 1000 person-years. The overall pooled estimate of NAFLD related mortality was 23.91 (95% CI 13.55–37.18) death per 1000 person-years.Conclusions::The prevalence of NAFLD is increasing globally. It is contributing to poor clinical outcomes including hepatocellular carcinoma and death. Rising awareness and urgent actions are warranted to control the NAFLD pandemic across the globe.Registration::PROSPERO, No. CRD42020171104.

Objective:To summarize the clinical and genetic characteristics of catecholaminergic polymorphic ventricular tachycardia (CPVT) in children caused by CASQ2 gene variants. Methods:The clinical data of 8 children (4 males and females, respectively) with CPVT caused by CASQ2 gene variants admitted to Beijing Children′s Hospital, Capital Medical University from January 2017 to November 2018 were retrospectively analyzed.The targeted next generation sequencing was employed to identify CASQ2 variants and Sanger sequencing was conducted to conform the candidate variants and determine the parental origin. Results:As for 8 children in this study, the average age of onset was 6.4 years, the mean age at diagnosis was 9.4 years, and the average interval from onset to diagnosis was 3 years.Only 2 cases had clearly diagnosis at onset, other 6 cases had a delay to diagnosis and 3 cases of them were diagnosed at other hospitals as having epilepsy and did not respond to anti-epileptic therapy.During physical activity and/or emotional stress, 8 cases presented with recurrent syncope and were able to regain consciousness after a few minutes.They had no a history of sudden cardiac death or family history.There was no abnormality on resting electrocardiogram during the paroxysmal interval in 6 cases and mild sinus bradycardia in 2 cases.Typical bidirectional ventricular tachycardia (VT) and/or polymorphic VT were detected in 8/8 cases and 5/5 cases, respectively, based on Holter electrocardiography and cardiac stress test.The CASQ2 gene variant was found in all children, with 6 cases carrying compound heterozygous variants and 2 cases carrying homozygous variants.A total of 9 different CASQ2 variants were detected in 8 cases, of which 5 had not been previously reported.According to the family-line verification, all of them had a familial variant, with no novel variants.All 8 cases were treated orally with β-blockers, with asymptomatically recurrent episodes, with a mean follow-up of 1.5 years, during which implantable cardioverter defibrillation was performed in 1 case owing to severe sinus bradycardia.There was no death case among them. Conclusions:CPVT with CASQ2 variants is characterized by early onset before preschool age, recurrent syncope after exercise or emotional stress and bidirectional/polymorphic VT.Early diagnosis of CPVT remains challenging due to delayed diagnosis or misdiagnosis.Treatment with β-blockers can achieve favorable effectiveness and safety.Five novel variants in this study would further expand the database of CASQ2 genes.

Objective:To investigate the viral molecular mutations of 2019 novel coronavirus (2019-nCoV) and host adaptability in Suzhou City.Methods:The throat swab specimens from nine local cases and six imported cases with 2019-nCoV viral nucleic acid test positive in Suzhou City were sequenced for the whole genome of the virus, and the Wuhan-Hu-1 strain was used as the reference sequence for alignment and analysis. The phylogenetic tree of the viral whole genome sequence was constructed by MEGA 7.0 software.Results:According to the Chinese typing method, Nextstrain typing method, Pangolin classification method and Global Initiative on Sharing All Influenza Data (GISAID) typing method, the 15 2019-nCoV genome sequences could be divided into seven types, six types, eight types and five subtypes, respectively. Compared with Wuhan-Hu-1 strain, the median number of amino acid sequence mutation sites based on nucleotide translation was three (ranging from 0 to 12). D614G mutation of spike protein was identified from all six imported viral strains, which could enhance the transmissibility. No Alpha, Beta, or Gamma mutants, which also could enhance the transmissibility, was found in the genomic sequences of the imported cases. The median number of nucleotide mutation sites in 15 sequences was eight (ranging from three to 23).Conclusions:2019-nCoV is constantly mutating, and a variety of evolutionary lineages/genotypes have been derived. All imported viruses in Suzhou City carry mutations that can increase infectivity.