With the rapid advancement of science and technology， human organoid technology has demonstrated immense potential in medical research and treatment， but it has also raised complex ethical issues. Ethical research on human organoid has gradually become a hot field of concern in the international academic community. Taking 262 papers from the Web of Science core database from 2016 to 2024 as a sample， this paper employed bibliometrics and visualization methods to analyze the hotspots and evolutionary trends of international research on the ethics of human organoid. The results showed that international research on the ethics of human organoid exhibited a significant growth trend， going through three phases： a slow accumulation period， a sustained explosion period， and a circuitous growth period. The primary research forces were concentrated in the United States， China， the United Kingdom， and Italy， with China gradually emerging in this domain. The research hotspots were mainly focused on the following aspects. The first was the research of classical ethical issues， encompassing an overview of the overall ethical issues in the research and application of human organoid technology， and the ethical issues of organoid biobanks. The second was the new challenges in ethical issues， including the moral status and ethical governance of brain organoids， embryoid bodies， and gonadal organoids. The third was ethical issues arising from cross-disciplinary applications， covering the ethical challenges posed by chimeras formed through transplanting human brain organoid into non-human animals and hybrids created by connecting human brain organoid with artificial intelligence （AI）， robots， and other non-biological entities. As technology continues to advance， the complexity and importance of ethical issues related to human organoid will persistently increase， and research in this field will continue to deepen and expand in the future.

Objective: To investigate the current status of screen exposure among preschool children in Shanghai and its association with family screen environment, so as to provide a scientific basis for family screen management. Methods: Using a convenient sampling method, a total of 349 preschool children aged 4-6 years were selected from 36 kindergarten classes in Xuhui District and Pudong New Area in Shanghai during April to June in 2023. Demographic characteristics and family screen environment were surveyed through an online questionnaire. Screen exposure of children was assessed using a diary method, with parents recording the activities over a 7day period. Multiple Logistic regression analysis was employed to identify factors influencing childrens screen content. Results: The average daily screen exposure time for children was (61.2±40.2) minutes, with an average of (12.4±17.6) minutes spent on educational screen content, 80.8% predominantly watched noneducational screen content. The percentages of time spent on educational screen content for 4yearold boys, 4yearold girls, 5yearold boys, 5yearold girls, 6yearold boys, and 6yearold girls were 20.1%, 14.7%, 21.3%, 21.9%, 20.6%, and 26.9%, respectively. Multivariate Logistic regression showed that children aged 5yearold (OR=0.49, 95%CI=0.25-0.96) and 6yearold (OR=0.45, 95%CI=0.21-0.95) were negatively associated with more noneducational screen content (P<0.05). However, occasional (OR=2.02, 95%CI=1.09-3.75) and sometimes (OR=4.50, 95%CI=1.70-11.90) using electronic devices to calm young child when crying, as well as children using electronic devices without adult supervision (OR=1.81, 95%CI=1.01-3.24) were positively associated with more noneducational screen content (P<0.05). Conclusions Preschool children in Shanghai exhibit high exposure to noneducational screen content, and family screen environment and parentchild interaction are associated with noneducational screen exposure. Strategies for family screen management should be developed to regulate childrens screen exposure behaviors, allowing electronic devices to play a positive role in their developmental process.

Objective To assess the viability and efficacy of employing automated segmentation for whole breast radiotherapy with simultaneous integrated boost to the medial tumor beds,a comparative analysis was conducted on the disparities in geometry,dosimetry,and working time between the auto-segmentation(AS)and manual segmentation(MS)groups.Methods A total of 30 patients with early breast cancer,who had undergone conserving surgery and received hypofractionated radiotherapy with a boost to the medial tumor bed,were enrolled from the First People's Hospital of Zunyi.AccuContour software was used in the AS group to obtain the whole breast planning target volume and cardiopulmonary structure.Geometric differences between AS and MS groups were assessed using Dice similarity coefficient(DSC)and 95%Hausdorff distance(95HD).Subsequently,a comparison was made between the two groups regarding target and cardiopulmonary dosimetry for PlanA and PlanM.Additionally,the time spent by each group was also compared.Results The DSC of PGTV,PTV,lung,and heart were 0.94(0.91,0.96),0.88(0.86,0.91),0.98(0.97,0.98)and 0.94(0.93,0.95),respectively.And the 95 HD(cm)were 0.25(0.20,0.33),0.99(0.56,1.20),0.29(0.25,0.35)and 0.50(0.50,0.59)respectively.The dosimetric results showed that the V95,D95,and Dmean of PGTV and PTV in the AS group were significantly lower than those in the MS group(P<0.05);while the V20 and MLD of the left lung were significantly higher(P<0.05).No significant difference was observed in cardiac dose between the two groups.The mean absolute differences of PGTV and cardiopulmonary dose parameters between the two groups were less than 1 Gy/1%,respec-tively.In terms of work efficiency,the AS approach substantially reduced contouring and planning time with over 70%of cases approved within two days.Conclusions The differences in geometric and dosimetric parameters between the auto-segmentation and manual segmentation groups were found to be negligible for whole breast radiotherapy with medial tumor bed boost patients.It is recommended that the PTV be manually modified prior to plan optimiza-tion,leading to a significant improvement in work efficiency.

Objective:To explore the clinical characteristics and genetic basis for a child with global developmental delay and autism.Methods:A child who had presented at West China Second University Hospital of Sichuan University on April 13, 2021 was selected as the study subject. Clinical manifestations, laboratory examination and result of genetic testing were analyzed.Results:The main symptoms of the child had included cognitive, language and motor delay, autism and epilepsy. Electroencephalogram revealed multiple focal discharges in both waking and sleeping stages, with the remarkable one seen at the sleeping stage. Cranial MRI showed pachygyria and local cortical thickening, Whole exome sequencing (WES) revealed that the child has harbored a heterozygous c. 1589_1595dup (p.Gly533Leufs*143) frameshifting variant in the TBR1 gene (OMIM 604616). Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PS2+ PVS1_Supporting+ PM2_Supporting). After treated with levetiracetam and rehabilitation training, the child did not have seizure in the past 5 months, and his motor development has also significantly improved. Conclusion:The c. 1589_1595dup variant of the TBR1 gene probably underlay the disease in this patient.

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool

Objective:To investigate the birth weight (BW) of infants born to pregnant women living with human immunodeficiency virus (HIV) and its associated factors, and to provide more evidence for the prevention of mother-to-child transmission (PMTCT) in China.Methods:This study was a retrospective cohort study. Between January 2004 and December 2021, pregnant women living with HIV and their infants in Hubei Province were recruited and followed up, and clinical data were collected through hospital medical records and HIV/acquired immunodeficiency syndrome comprehensive response information management system. The multivariable linear regression was performed on the collected data to investigate associated influencing factors of BW.Results:In total, 531 pregnant women living with HIV (581 pregnancies) and 581 infants were enrolled. Of the 581 infants, 36 were HIV-positive, with a PMTCT rate of 6.2%. The mean BW of the infants was (3 075.0±470.2) gram. Protease inhibitor (PI) based-anti-retroviral therapy (ART) ( β=-0.1, 95% confidence interval ( CI)-188.2 to -37.1, P=0.004), ART in the first trimester( β=-0.1, 95% CI -201.9 to -65.5, P<0.001), infant HIV infection ( β=-0.1, 95% CI -310.4 to -68.2, P=0.002), hepatitis C virus infection ( β=0.1, 95% CI 71.2 to 410.4, P=0.005) and gestational age ( β=0.6, 95% CI 155.9 to 191.5, P<0.001) were associated with decreased BW. Conclusions:While improving the effectiveness of PMTCT for HIV, more attention should be paid to pregnant women who received ART in the first trimester and PI-based ART for preventing lower BW and improving maternal and infantile health.

Objective:To investigate the clinical efficacy and adverse reactions of linezolid in the treatment of gram-positive coccal infections after chemotherapy in older adult patients with leukemia.Methods:Ninety-two older adult patients with leukemia complicated by gram-positive coccal infections, who received treatment in Yiwu Central Hospital from January 2017 to December 2019, were included in this study. They were randomly assigned to receive routine anti-infection treatment (control group, n = 46) or linezolid treatment (observation group, n = 46). Clinical efficacy, the time required for body temperature restoring to normal, and medication time were compared between the two groups. Results:Total response rate was significantly higher in the observation group than in the control group [95.65% (44 /46) vs. 78.26% (36/46), χ2 = 6.13, P = 0.013]. The time required for body temperature restoring to normal and medication time in the observation group were (7.98 ± 1.04) days and (8.58 ± 1.31) days, respectively, which were significantly shorter than those in the control group [(8.85 ± 1.47) days, (9.46 ± 2.52) days, t = 3.27, 2.10, P = 0.001, 0.019). The incidence of adverse reactions was significantly lower in the observation group than in the control group [4.35% (2/46) vs. 19.57% (9/46), χ2 = 5.05, P < 0.05]. Conclusion:Linezolid is highly effective on gram-positive coccal infections after chemotherapy in older adult patients with leukemia. Linezolid treatment requires comparatively shorter time required for body temperature restoring to normal and shorter medication time and is safer than routine anti-infection treatment.

Objective:To perform cross-cultural adaption of the KING′s Parkinson′s Disease Pain Scale (KPPS), explore its reliability and validity in Chinese Parkinson′s disease (PD) patients, and to create the new version of the pain scale which adapts to the Chinese PD patients.Methods:This study enrolled 225 patients, including 121 men and 104 women who were selected from the Outpatient Center of Movement Disorders Clinic of the Second Affiliated Hospital of Soochow University from July 2018 to July 2020. All patients completed the evaluation of the Chinese Version of KPPS (KPPS-CV). According to the preliminary evaluation results, the expert group modified KPPS-CV after discussion, and developed a Modified KPPS-CV (MKPPS-CV). These patients then completed the MKPPS-CV evaluation during the 3-month follow-up. Cross-cultural adaptation was performed according to published international guidelines that include translation, back-translation, expert review, and pretesting. The following psychometric properties were evaluated: basic item analysis; floor and ceiling effects; construct validity; content validity; criterion validity (Spearman′s rho between the KPPS-CV and Numeric Rating Scale); internal consistency reliability (Cronbach′s alpha); test-retest reliability (intra-class correlation coefficient, ICC).Results:In item analysis, 50% of the items had poor discrimination (critical ratio<3.0), and floor effect was found in all domains (proportion of 0 point>15%). The items were reclassified after exploratory factor analysis. The content validity of item 3, item 10 and item 11 was low (item-level content validity index<0.78). Criterion validity showed the highest correlations (Spearman′s rho>0.88) between the KPPS-CV and Numeric Rating Scale. While overall scale reliability was minimally acceptable at 0.46, which showed a poor reliability of this scale. Test-retest reliability was excellent for each item (Spearman's rho>0.85). The Cronbach′s alpha of MKPPS-CV (0.76) was higher than that of KPPS-CV (0.46). It showed a great improvement after the modifying.Conclusions:When using scales that are not developed for local populations, differences in culture and clinical practices should be taken into account. MKPPS-CV is an acceptable, valid measure to evaluate pain in Chinese PD patients, which is more suitable for Chinese people.

OBJECTIVE: To analyze the clinical characteristics and ZBTB18 gene variant in a child with epilepsy and global developmental delay. METHODS: Clinical data and laboratory examination of the patient were reviewed. Whole exome sequencing (WES) was also carried out for the family trio. RESULTS: The main manifestations of the child included global developmental delay, short stature, epileptic seizures. EEG revealed frequent occurrence of sharp (slow) waves in the right central region during sleeping, with sharp waves occasionally seen in the frontal and right posterior temporal regions. Cranial MRI has shown no obvious abnormality. WES has identified a de novo pathogenic variant in the ZBTB18 gene [NM_205768.3: exon 2: c.1282_1283del (p.Phe428Leufs*72)]. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PVS1_Moderate+PM2_Supporting). Following treatment with levetiracetam and rehabilitation, the seizures have been controlled for nearly half a year, with improvement of the psychomotor and language development. So far 28 children have been discovered with ZBTB18 gene mutations, and there was a significant difference in the clinical phenotypes of motor retardation, language retardation and epilepsy between those harboring frameshift/nonsense mutations and missense mutations. CONCLUSION The c.1282_1283del (p.Phe428leufs *72) variant of the ZBTB18 probably underlay the autosomal dominant mental disorder type 22 in this child. Compared with missense mutations, frameshift/nonsense mutations may predispose more to motor retardation, delayed language development and epilepsy.
Codon, Nonsense ; Epilepsy/genetics* ; Humans ; Intellectual Disability/genetics* ; Mutation ; Whole Exome Sequencing

OBJECTIVE: To analyze the clinical and genetic characteristics of a child featuring Xia-Gibbs syndrome. METHODS: Whole exome sequencing was carried out for the child. RESULTS: The patient has presented with developmental delay, hypotonia, strabismus and snoring. Cranial MRI revealed hypomyelination, while the EEGs were normal. Genetic testing revealed a de novo variant of the AHDC1 gene, namely c.730delA (p.Ile244Serfs*16), which was classified as pathogenic (PVS1+PS2+PM2). Together with 60 cases from the literature, individuals harboring a AHDC1 variant commonly have delayed motor milestones, speech delay, facial dysmorphism and hypotonia. Dysgenesis of corpus callosum is also common. In total 47 AHDC1 variants have been reported, among which truncating variants were the most common type. CONCLUSION The c.730delA (p.Ile244Serfs*16) variant of the AHDC1 gene probably underlay the Xia-Gibbs syndrome in this patient. Above finding has provided a basis for the clinical diagnosis.
Abnormalities, Multiple/genetics* ; Child ; DNA-Binding Proteins/genetics* ; Humans ; Intellectual Disability/genetics* ; Muscle Hypotonia ; Mutation ; Whole Exome Sequencing