Extracorporeal membrane oxygenation (ECMO) is primarily used in clinical practice to provide continuous extracorporeal respiratory and circulatory support for patients with severe heart and lung failure, thereby sustaining life. It is a key technology for managing severe heart failure and respiratory failure that are difficult to control. With the accumulation of clinical experience in ECMO for circulatory and/or respiratory support, as well as advancements in biomedical engineering technology, more portable and stable ECMO devices have been introduced into clinical use, benefiting an increasing number of critically ill patients. Although ECMO technology has become relatively mature, the timing of ECMO initiation, management of sudden complications, and monitoring and early warning of physiological indicators are critical factors that greatly affect the therapeutic outcomes of ECMO. This article reviews traditional methods and artificial intelligence techniques used in risk assessment related to ECMO, including the latest achievements and research hotspots. Additionally, it discusses future trends in ECMO risk management, focusing on six key areas: multi-center and prospective studies, external validation and standardization of model performance, long-term prognosis considerations, integration of innovative technologies, enhancing model interpretability, and economic cost-effectiveness analysis. This provides a reference for future researchers to build models and explore new research directions.
Extracorporeal Membrane Oxygenation ; Humans ; Artificial Intelligence ; Risk Assessment ; Respiratory Insufficiency/therapy* ; Heart Failure/therapy*

Actinomycetes are important producers of high-value natural products, and the engineering of actinomycetes to enhance the biosynthesis of target natural products has long been a hot research topic in the scientific community. However, non-rational engineering methods suffer from low beneficial mutation rates, which limit the efficiency of mutant screening. The integration of high-throughput screening (HTS) technologies can effectively enhance the screening efficiency of elite mutants and significantly shorten the cycle of actinomycete strain engineering. This review comprehensively discusses various HTS technologies suitable for the engineering of actinomycete strains and compares them in terms of application scenarios, advantages, and disadvantages. HTS technologies include microplate-based screening, antimicrobial activity screening, antibiotic resistance screening, fluorescence-activated cell sorting (FACS), and fluorescence-activated droplet sorting (FADS). Additionally, this review summarizes the applications of these technologies in assisting actinomycete strain engineering and enhancing the yields of target compounds. The development and application of HTS technologies have not only facilitated the exploration of natural product resources in actinomycetes but also provided strong support for the rapid and efficient construction of high-performance engineered actinomycete strains.
Actinobacteria/metabolism* ; High-Throughput Screening Assays/methods* ; Genetic Engineering/methods* ; Biological Products/metabolism* ; Flow Cytometry ; Metabolic Engineering/methods*

Objective To investigate the value of the liver imaging reporting and data system v2018(LI-RADS v2018)and other imaging features in predicting preoperative risk and postoperative prognosis of isolated macrotrabecular-massive hepatocellular carcinoma(MTM-HCC).Methods Patients with isolated hepatocellular carcinoma(HCC)confirmed by pathology after preoperative MRI examination were selected,and all patients were randomly assigned to a training group(n=146)and a validation group(n=62)in a 7∶3 ratio.Least absolute shrinkage and selection operator(LASSO)regression and multivariate logistic regression were used to screen independent prognostic factors of MTM-HCC and construct a nomogram.Patients were stratified into high-risk and low-risk subgroups based on the nomogram scores.Kaplan-Meier survival curves and Log-rank tests were used to compare the recurrence-free survival(RFS)among different subgroups of patients.Results Multivariate logistic regression analysis revealed that intratumoral vessels[odds ratio(OR)=3.480,95％confidence interval(CI)1.110-10.912,P=0.032],arterial phase hypovascular component ≥20％(OR=4.615,95％CI 1.728-12.321,P=0.002),and corona enhancement(OR=4.814,95％CI 1.816-12.766,P=0.002)were independent predictors of MTM-HCC.The nomogram constructed based on these indicators demonstrated area under the curve(AUC)of the receiver operating characteristic(ROC)curve was 0.834 and 0.764 for predicting MTM-HCC in the training and validation groups,respectively.The RFS predicted by the nomogram was significantly different between the high-risk and low-risk subgroups and both the pathologically confirmed MTM-HCC positive and negative groups(P＜0.05).Conclusion Intratumoral vessels,arterial phase hypovascular component ≥20％,and corona enhancement are independent predictors of MTM-HCC.The constructed nomogram based on these predictors demonstrates good diagnostic efficacy for MTM-HCC and has significant prognostic value for patients'RFS.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective To investigate the effect of auditory brainstem response(ABR)in clinical detection and severity assessment of autism spectrum disorder(ASD)in children with normal hearing.Methods ① A total of 55 autistic children(110 ears)with normal hearing and 55 children(110 ears)with typical development(TD)who did not differ in sex composition ratio and average monthly age were divided into four sub-groups according to age:≤24 months group(22 ears),25～36 months group(40 ears),37～48 months group(28 ears)and＞48 months group(20 ears).The ABR latencies and interpeak latencies were compared between ASD children and age-matched TD children.② ASD children were graded by severity according to the Diagnostic and Statistical Manual of Mental Dis-orders(DSM-V),and the correlations between the ABR latencies and interpeak latencies in autistic children with normal hearing and the severity grading were studied.Results ① No statistically significant differences in ABR wave latencies and interpeak latencies were found in autistic children with normal hearing under 24 months of age compared to age-matched TD children(P＞0.05).② Compared with children with TD,autistic children with nor-mal hearing at 25～36 months of age had significantly longer wave Ⅲ latencies and the interpeak latencies of Ⅰ-Ⅲ andⅠ-Ⅴ;the significantly longer wave Ⅲ,Ⅴ latencies,the interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ and Ⅰ-Ⅴ in autistic chil-dren with normal hearing at 37～48 months of age.Autistic children with normal hearing in the＞48 months group had significantly longer wave Ⅴ latencies and interpeak latencies of Ⅲ-Ⅴ,Ⅰ-Ⅴ than age-matched TD children(P＜0.05).③ The higher the ASD severity grading the longer the wave Ⅲ and V latencies and the longer interpeak latencies of Ⅰ-Ⅲ,Ⅲ-Ⅴ,and Ⅰ-Ⅴ(P＜0.05).Conclusion Differences in the level of auditory brainstem pathway de-velopment emerged at 25 months of age,and autistic children with normal hearing had significantly lower levels of auditory brainstem development than age-matched TD children.There were correlations between the latencies and interpeak latencies of ABR in autistic children with normal hearing and the severity grading.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.

The pathogenesis of inflammatory bowel disease (IBD) is not fully elucidated. However, it has been considered that inflammatory macrophages may be involved in the imbalance of the intestinal mucosal immunity to regulate several signaling pathways, leading to IBD progression. The ratio of M1 to M2 subtypes of activated macrophages tends to increase in the inflamed intestinal section. There are challenges in the diagnosis and treatment of IBD, such as unsatisfactory specificity of imaging findings, low drug accumulation in the intestinal lesions, unstable therapeutic efficacy, and drug-related systemic toxicity. Recently developed nanoparticles may provide a new approach for the diagnosis and treatment of IBD. Nanoparticles targeted to macrophages can be used as contrast agents to improve the imaging quality or used as a drug delivery vector to increase the therapeutic efficiency of IBD. This article reviews the research progress on macrophage-targeting nanoparticles for the diagnosis and treatment of IBD to provide a reference for further research and clinical application.
Humans ; Inflammatory Bowel Diseases/therapy* ; Intestines ; Macrophages/metabolism* ; Intestinal Mucosa/pathology* ; Nanoparticles

Objective:To observe and analyze the ocular clinical features and pathogenic genes of Alstr?m syndrome (ALMS).Methods:A retrospective clinical study. From October 2020 to July 2022, 3 patients and 5 normal family members from 2 families affected with ALMS who visited in the Ophthalmology Department of Henan Children's Hospital were enrolled in the study. These 2 families were without blood relationship. The medical history and family history were inquired. Best corrected visual acuity (BCVA), fundus color photography, full-field electroretinogram (ERG), frequency domain optical coherence tomography (OCT) and systemic examination were performed. 3 ml peripheral venous blood of patients and their family members were collected, and the whole genomic DNA was extracted. The second generation sequencing analysis was performed on these members. The suspected pathogenic mutation sites were verified by Sanger, and the pathogenicity of the gene mutation sites were determined by bioinformatics analysis.Results:Three patients from two families all developed nystagmus and photophobia in infancy. In the family 1, the BCVA of both eyes of the proband was no light perception. The fundus examination revealed vascular attenuation and retinal pigment abnormality. OCT showed retinal thinning, loss of photoreceptor layer and atrophy of the retinal pigment epithelium layer. ERG examination showed extinguished. The BCVA of the proband’s younger brother was 0.04 in the right eye and 0.02 in the left eye. The fundus examination revealed vascular attenuation but the pigment distribution was roughly normal. OCT showed blurred photoreceptor layers in both eyes. ERG examination showed extinguished. Two patients developed sensorineural deafness, obesity, acanthosis nigricans, insulin resistance/diabetes, and abnormal liver function. In addition, the proband also had left heart enlargement, hyperlipidemia and abnormal kidney function. The results of genetic testing showed that the proband and his younger brother had compound heterozygous mutations in exon 8 (c.1894C>T/p.Gln632*, M1) and exon 10 (c.9148_9149delCT/p.Leu 3050 Leufs*9, M2) of ALMS1, which were both known mutations. The father of the proband was a carrier of M1 and the mother of the proband was a carrier of M2. The proband of the family 2 had a normal fundus at 23 months old. The amplitude of ERG b wave under the stimulation of the dark adaptation 0.01 and a, b wave under the stimulation of dark adaptation 0.3 were all mild reduced. The amplitude of ERG a, b wave under the stimulation of the light adaptation 0.3 was severity decreased. At 4 years old, the BCVA was 0.01 in the right eye and 0.05 in the left eye. The fundus examination revealed vascular attenuation and bilateral blunted foveal reflex. In addition to severely diminished of a, b wave under the stimulation of dark adaptation 0.3, the rest showed extinguished. There were no systemic abnormalities. The results of genetic testing showed that the proband had compound heterozygous mutations in exon 11 (c.9627delT/p.Pro3210Glnfs*22, M3) and exon 5 (c.1089delT/p.Asp364Ilefs*13, M4) of ALMS1, which were both novel mutations. The father of the proband was a carrier of M3 and the mother of the proband was a carrier of M4. Conclusions:Nystagmus and photophobia are often the first clinical manifestations of ALMS. In the early stage, the fundus can be basically normal. As the disease progresses, the fundus examination reveals vascular attenuation and retinal pigment abnormality, and the reflection of the fovea is unclear. OCT shows the photoreceptor cell layers are blurred or even lost. The final ERG is extinguished. M1, M2, and M3, M4 compound heterozygous mutations may be the pathogeny for family 1 and family 2, respectively.

Objective:To observe the ocular clinical features of infantile cytomegalovirus (CMV) infection.Methods:A retrospective clinical study. From March 2019 to July 2021, 876 eyes of 438 children with CMV infection who visited Department of Ophthalmology of Henan Provincial Children's Hospital were included in the study. Among them, there were 254 males and 184 females; the age ranged from 3 days to 11 months; the gestational weeks were 28 to 42 weeks; the birth weight was 1 120 to 8 900 g. There were 384 and 54 full-term and premature infants, respectively. Fundus examination was performed in 385 cases (770 eyes) after medical consultation; 53 cases (106 eyes) of premature infants were routinely screened. CMV retinitis (CMVR) was divided into granular type and fulminant type. Patients with CMV-related diseases with moderate to severe symptoms were given intravenous drip and/or oral ganciclovir; patients with severe fundus vasculitis were combined with intravitreal injection of ganciclovir. The follow-up period was from 4 to 28 months, and the characteristics of eye lesions, systemic comorbid diseases and treatment outcomes were observed.Results:There were 516 eyes of 258 cases with normal fundus (58.9%, 258/438); 291 eyes of 180 cases with CMVR (41.1%, 180/438), of which binocular and monocular were 111 (61.7%, 111/180) and 69 (38.3%, 69/180) cases. Among the 291 eyes of CMVR, 281 eyes (96.6%, 281/291) of granular type; yellow-white point-like opacity and/or retinal hemorrhage; 10 eyes (3.4%, 10/291) of fulminant type; fundus Showed a typical "cheese ketchup-like" and vascular white sheath-like changes. Among the 180 children with CMVR, 72 patients (118 eyes) were given systemic intravenous drip and/or oral ganciclovir; 5 patients (10 eyes) were given intravitreal ganciclovir, all of which were fulminant CMVR. At the last follow-up, fundus lesions regressed significantly in 100 eyes of 61 cases; 18 eyes of 11 cases had old lesions or uneven retinal pigment; 108 cases were not treated.Conclusion:The most common fundus manifestation of CMV infection in infants is granular retinitis, and fulminant retinitis is more severe, and the lesions can be significantly regressed after timely antiviral treatment.