AIM: To analyze the changes of retinal structure and function before and after panretinal photocoagulation(PRP)in patients with proliferative diabetic retinopathy(PDR).METHODS: Prospective study. Totally 98 cases(98 eyes)of PDR patients who underwent PRP in Eye Hospital of Wenzhou Medical University from January 2022 to May 2023 were included. Optical coherence tomography angiography(OCTA)was used to detect central retinal thickness(CRT), central macular thickness(CMT), subfoveal choroidal thickness(SFCT), foveal avascular zone(FAZ), deep vascular complex(DVC)blood flow density, superficial vascular complex(SVC)blood flow density before and at 1 wk, 1 and 3 mo after PRP. During the follow-up, 1 eye underwent vitrectomy, 2 eyes were lost to follow-up, and finally 95 eyes completed 1 a follow-up, with a loss rate of 3%. According to the visual prognosis at 1 a after treatment, the patients were divided into two groups: 73 eyes in good prognosis group and 22 eyes in poor prognosis group(including 9 eyes of visual disability and 13 eyes of visual regression). The changes in retinal structure and function before and after PRP treatment were compared between the two groups of patients, and the receiver operating characteristic(ROC)curve and decision curve were used to analyze the predictive value of retinal structure and function for PDR treatment.RESULTS: There were statistical significant differences in PDR staging, CRT, CMT, SFCT, DVC blood flow density, and SVC blood flow density between the two groups of patients before treatment(all P<0.05). At 1 wk, 1 and 3 mo after treatment, the FAZ area of both groups decreased compared to before treatment, while the blood flow density of DVC and SVC increased compared to before treatment(both P<0.05). However, there was no significant difference in the blood flow density of FAZ, DVC, and SVC between the two groups at 1 wk, 1 and 3 mo after treatment(all P>0.05). The CRT, CMT and SFCT of the two groups at 1 wk after treatment were higher than those before treatment(all P<0.05), but there were no significant differences between the two groups(all P>0.05). The CRT, CMT and SFCT at 1 and 3 mo after treatment were lower than those at 1 wk after treatment and before treatment in both groups. The CRT, CMT and SFCT in the poor prognosis group at 3 mo after treatment were higher than those at 1 mo after treatment, and were higher than those in the good prognosis group(all P<0.05). ROC analysis showed that, at 3 mo after laser treatment in PDR patients, the area under the curve of the CRT, CMT, and SFCT alone or in combination after treatment for 1 a was 0.788, 0.781, 0.783, and 0.902, respectively, and the combined prediction value was better(P<0.05). Decision curve analysis showed that the combined detection of CRT, CMT, and SFCT in PDR patients at 3 mo after treatment can improve the predictive value of visual prognosis.CONCLUSION: The optimal time for retinal structure and function recovery in PDR patients after PRP treatment is between 1 wk and 1 mo. OCTA measurement of CRT, CMT, and SFCT at 3 mo after treatment can predict the visual prognosis during the 1 a treatment period.

ObjectiveTo analyze the impact of maternal postpartum depression (PPD) at 2 months postpartum on caregiving for infants aged2 to 24 months, and to provide a scientific basis for future maternal and infant healthcare services. MethodsBased on the Shanghai Maternal-Child Pairs Cohort, 1 060 mother-child pairs were selected from those fully participating in follow-up visits at 2, 6, 12, and 24 months postpartum. Pregnancy and childbirth-related information was collected using standardized questionnaire surveys and hospital obstetric and maternity records. The Edinburgh postpartum depression scale was used to assess the maternal postpartum depressive symptoms at 2 months postpartum. At 2, 6, 12, and 24 months postpartum, questionnaire survey was used to evaluate the maternal responsiveness in caregiving and the provision of early learning opportunities for infants. Scores for responsive caregiving and early learning opportunities at 2, 6, 12, and 24 months were grouped based on the 25th percentile (P₂₅) of total scores. The mixed-effects model was used to analyze the longitudinal impact of maternal postpartum depression at 2 months on the caregiving of 2 to 24-month-old infants. ResultsThe longitudinal results from the mixed-effects model did not show an impact of maternal PPD on infant responsive caregiving within 12 months and early learning opportunities within24 months. However, cross-sectional analysis revealed that, compared to the non-PPD group, the risk of low responsive caregiving at 2 months in the PPD group was 93% higher (OR=1.931, 95%CI: 1.113‒3.364, P=0.019). The risks for low provision of early learning opportunities at2 months and 24 months increased by 59% (OR=1.589, 95%CI: 1.082‒2.324, P=0.017) and 60% (OR=1.598, 95%CI:1.120‒2.279, P=0.010), respectively. ConclusionMaternal postpartum depression increases the risk of low responsive caregiving at 2 months, but its long-term effects warrant further research.

ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E₂) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E₂ levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

Objective:To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia.Methods:A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively.Results:The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46, X, psu idic(X)(q21.3)[40]/mos 45, X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45, X karyotype and the location of the breaking point.Conclusion:46, X, psu idic(X)(q21.3)/45, X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.

Objective:To explore the clinical phenotype and pathogenesis of a child with partial duplication in the long arm of chromosome 10 (10q), and conduct a review of relevant literature.Methods:A child presented at Lianyungang Maternal and Child Health Care Hospital in April 2018 for growth retardation, intellectual disability, and autism spectrum disorder (ASD) was selected as the study subject. Peripheral blood samples were collected from the child and his parents for G-banded chromosomal karyotyping analysis. Genomic DNA was also extracted for chromosomal microarray analysis (CMA). The clinical phenotype and relevant genes were searched in the Online Mendelian Inheritance in Man (OMIM) and the UK Database of Genomic Variation and Phenotype in Humans using Ensembl Resources (DECIPHER). The pathogenicity of chromosomal variation was analyzed based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Relevant literature was searched from the CNKI, Wanfang Data, and PubMed databases by using keywords such as " 10q" " duplication" and " trisomy", with the time set as from the establishment of database to December 1, 2023. This study has been approved by the Medical Ethics Committee of the Lianyungang Maternal and Child Health Care Hospital (No. XM2023030).Results:The clinical phenotype of child had included growth retardation, intellectual disability, and ASD. G-banded chromosomal analysis suggested that the child has a karyotype of 46, XY, dup(10)(q23.31q24.33), whilst both of his parents were normal. CMA analysis of the child revealed that the child was arr[19]10q23.31q24.33(87603382_104948862)×3, with a 17.34 Mb duplication in the 10q23.31q24.33 region. Search of the OMIM database suggested that the duplicated segment has contained 171 genes associated with various diseases, and search of the DECIPHER database has identified cases with overlapping with the duplication. A search of the PubMed database has identified 2 publications involving 2 patients with chromosomal duplications overlapping the 10q23.31q24.33 region with a segment length of > 10 Mb. The 2 patients had mainly manifested growth retardation, intellectual disability, ASD, and facial and limb malformations. The main pathogenic genes had included PTEN, WNT8B, LZTS2, NFKB2, PAX2, KIF11, FRA10AC1, and CNNM2. No similar case was retrieved from the CNKI and Wanfang Data databases. Conclusion:The partial 10q duplication as a novel CNV involving genes such as PTEN and WNT8B probably underlay the growth retardation, intellectual disability and ASD in the child. This study has enriched the genotype-phenotype spectrum of patients with partial 10q23.31q24.33 duplications.

Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.

Objective To evaluate the effects of combining immune checkpoint inhibitors,trastuzumab,and chemotherapy on the left and right ventricular function in patients with advanced gastric adenocarcinoma expressing human epidermal growth factor receptor 2(HER2).Methods 25 patients with advanced HER2-positive gastric adenocarcinoma who received HER2-ASTRUM therapy(sruili monoclonal antibody combined with trastuzumab and DOS regimen)underwent echocardiographic examinations at baseline(T1),after completion of 4 cycles(T2),and 6 cycles(T3)of chemotherapy.Left ventricular strain,left ventricular myocardial work,right ventricular strain,and ejection fraction were further analyzed.Results Compared with T1,both T2 and T3 showed a decrease in left ventricular ejection fraction(LVEF),(T1,T2,and T3 were[67.3±2.7]％,[63.0±2.9]％and[61.3±3.2]％,P＜0.05).T3 showed a decrease in right ventricular ejection fraction(RVEF),([59.3±7.8]％vs[43.7±6.6]％,P＜0.05),while T2 showed no significant change in RVEF.Both right ventricular global longitudinal strain(RVGLS),(T1,T2,and T3 were[-25.7±5.7]％,[-22.4±5.3]％and[-19.1±3.6]％,respectively;P＜0.05)and right ventricular free-wall longitudinal strain(RVFWLS),(T1,T2,and T3 were[-20.9±4.7]％,[-18.9±4.1]％and[-16.1±3.9]％,P＜0.05)decreased in all three time points.The global work index(GWI)was lower in T2 and T3 than in T1(P＜0.05),while the global constructive work(GCW),global wasted work(GWW),and global work efficiency(GWE)did not show significant changes.Conclusions Combination of trastuzumab,immune checkpoint inhibitors,and chemotherapy has an impact on left ventricular strain,LVEF,and right ventricular strain,as well as GWI,in HER2-positive patients with gastric adenocarcinoma.Left ventricular global longitudinal strain(LVGLS),RVFWLS,and RVGLS can more sensitively monitor cardiac function and detect cardiac dysfunction related to cancer treatment in a timely manner.