Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.

Objective:To assess the status of undernutrition and appropriate catch-up growth in extremely preterm infants within 24 months of corrected age (CA).Methods:A retrospective cohort study was conducted. A total of 422 extremely preterm infants born at Shenzhen Maternity and Child Healthcare Hospital, Women and Children's Medical Center, Southern Medical University from January 2017 to December 2022 and followed up until 24 months of CA were enrolled. The extremely preterm infants were grouped by gestational age at birth (<25, 25-26, 27 weeks), birth weight (<500, 500-749, 750-999,≥1 000 g), weight for gestational age (large for gestational age (LGA), appropriate for gestational age (AGA), small for gestational age (SGA)) and sex. Weight data within 24 months of CA were collected every 3 months. Nutritional insufficiency, growth rate, and achievement of adequate catch-up growth were analyzed during the period from 0 to 24 months of CA. Z-score method was used to analyze data. Fenton 2013 preterm growth charts (Fenton 2013) were used before 40 weeks of corrected gestational age, and World Health Organization child growth standards (2009) fitted Z-scores were applied from 40 weeks of CA. Changes in weight Z-scores of extremely preterm infants from 0 to 24 months of CA were observed and compared, the occurrence of moderate to severe malnutrition and growth retardation was determined, nutritional insufficiency was assessed, and growth rate as well as the achievement of appropriate catch-up growth were analyzed. The Lambda-mu-sigma method combined with the Z-score fitting model was used to fit and analyze the distribution characteristics of weight percentiles in extremely preterm infants. The Chi-square test was used to compare differences among groups.Results:A total of 422 extremely preterm infants were included, with a gestational age at birth of 26.3(25.4, 27.2) weeks and a birth weight of (880±177) g. Among them, 238 were males and 184 were females; 36 cases (8.5%) were LGA, and 16 cases (3.8%) were SGA. During follow-up within 24 month of CA, 89 cases (21.1%) developed moderate to severe malnutrition. When compared separately among different birth weight and gestational age at birth groups, there had both statistically differences in the incidence of moderate to severe malnutrition ( χ2=42.94 and 9.17, both P<0.05). The incidence was the highest in the birth weight of CA<500 g group and the <25 weeks gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks gestational age at birth group in their respective groups. Growth retardation occurred in 5.2% (22/422). However, there had statistically differences in the incidence of growth retardation among different birth weight and gestational age at birth groups, in each grouped time interval ( χ2=21.61 and 4.30, both P<0.05). The proportions of rapid growth were relatively high in the 0-3 months and 3-6 months of CA groups, which were 96 cases (27.4%) and 98 cases (26.6%), respectively. Overall, appropriate catch-up growth was achieved in 341 cases (80.8%) from 0 to 24 months of CA. There had statistically differences in the completion rate of appropriate catch-up growth among different birth weight and gestational age at birth groups ( χ2=23.65 and 7.08, both P<0.05). The completion rate was the highest in the birth weight of CA<500 g group and the <25 weeks of gestational age at birth group, while it was the lowest in the birth weight of CA≥1 000 g group and the 27 weeks of gestational age at birth group. Conclusions:The lower the birth weight and gestational age of extremely preterm infants, the higher the incidence of moderate to severe malnutrition and the lower the achievement rate of adequate catch-up growth within 24 months of CA. The period of 0-6 months of CA is the critical window for catch-up in extremely preterm infants.

Objective:To investigate the role of bone morphogenetic protein (BMP) 7 peptidomimetics THR123 in the regulation of proliferative vitreoretinopathy (PVR) and epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells.Methods:Primary human RPE cells were isolated from donor eyes.The RPE cells was cultured for 48 hours with conventional medium, medium containing 10 ng/ml transforming growth factor-β2 (TGF-β2), medium containing 10 ng/ml TGF-β2 and 5 μg/ml THR123, respectively, serving as negative control group, TGF-β2 stimulation group and THR123-treated group.The relative protein expression levels of E-cadherin, α-smooth muscle actin (α-SMA), fibronectin (FN) activin receptor-like kinase-2 (ALK2) and Snail family zinc finger transcription factor 1, Snail1) were detected by Western blot analysis in each group.RPE cell contractile function was detected by collagen gel contraction assay.RPE cell migration function was detected by transwell assay.RPE cell polarity was detected by transepithelial resistance.For the in vivo model, the rabbit PVR model was established by intravitreal injection of RPE cells and cytokine platelet-derived growth factor.The PVR rabbits were randomly divide into PVR group, 0.5 μg/ml THR123 group and 5 μg/ml THR123 group, and were intravitreally injected with corresponding concentration of THR123 on the day of modelling and 7 days after modelling.The fundus conditions of rabbits were observed every 7 days.Retinal detachment was checked by B-scan ultrasonography every 7 days, and PVR grading was performed on 14 and 28 days after modelling.On day 28 after modelling, the rabbit was sacrificed by air embolism and the eyeball was enucleated.Hematoxylin-eosin (HE) staining and α-SMA immunofluorescence staining were performed to compare the differences in PVR progression among groups.In the LDN inhibition group, BMP receptor inhibitor LDN193189 was added to primary RPE cells and the expression of EMT markers and cell functional differences of RPE cells were compared between negative control group and LDN inhibition group.Small interfering RNA of control and Snail1 was transfected into RPE cells of siNC+ TGF-β2 group and siSnail1+ TGF-β2 group, respectively, and the differences in EMT markers and function of RPE cells were compares.The protocol involving human specimens, cells and animals in this study was opproved by the Medical Ethics Committee of Shanghai General Hospital (No.2021SQ057). Results:There were statistically significant differences in gel contraction ratio, transepithelial resistance and relative expressions of E-Cadherin, FN and α-SMA proteins among the negative control group, TGF-β2 stimulation group and THR123-treated group ( F=28.38, 136.30, 38.50, 2.53, 53.54; all P<0.01).Compared with the negative control group and THR123-treated group, the gel contraction ratio, transepithelial resistance, and relative expression of E-cadherin in the TGF-β2 stimulation group decreased, and the relative expression of α-SMA and FN increased, with statistically significant differences (all P<0.01).On day 28 after modeling, the PVR grades in the PVR group, 5 μg/ml THR123 group and 5 μg/ml THR123 group were 4.00±0.45, 2.80±0.37, 1.80±0.37, respectively, with a statistically significant difference among groups ( F=7.583, P=0.007).The PVR grade of rabbit eyes was significantly lower in the 5 μg/ml THR123 group than in the PVR group ( P<0.05).HE staining showed that the number of preretinal proliferative membranes was less in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group, and no retinal detachment was found.Immunofluorescence staining showed that the expression of α-SMA in vitreous cavity and retina was significantly lower in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group.Compared with the negative control group and THR123-treated group, the relative expression of ALK2 protein in the TGF-β2 stimulation group was significantly decreased, and the relative expression of Snail1 protein was significantly increased (all P<0.01).Compared with the negative control group, the gel contraction ratio, transepithelial resistance and relative expression of E-cadherin protein in the LDN inhibition group were significantly reduced, and the relative expression of FN, α-SMA and Snail1 proteins were significantly increased (all P<0.01).Compared with the siNC+ TGF-β2 group, the gel contraction ratio and the relative expression of E-cadherin protein in the siSnail1+ TGF-β2 group were significantly increased, and the relative expression of FN, α-SMA and Snail1 proteins were significantly decreased (all P<0.05). Conclusions:THR123 can activate the BMP pathway to inhibit Snail1, thereby inhibiting the EMT process in RPE cells and PVR occurrence.It is expected to provide potential targets for PVR drug therapy.

Objective To investigate the effects of chronic intermittent hypoxia(CIH)on hippocampal neuronal injury in rats,and to clarify the role of endoplasmic reticulum(ER)stress-related apoptotic pathways.Methods Male Sprague-Dawley rats were randomly assigned to a control group(n=8)or a CIH group(n=8).The CIH group was exposed to intermittent hypoxia for 8 h/day over 8 weeks.Hippocampal neuronal morphology was examined by hematoxylin-eosin staining and transmission electron microscopy.Neuronal apoptosis was assessed using the TUNEL assay.Intracellular Ca2? levels were measured by flow cytometry.The mRNA and protein expression of ER stress-related factors(GRP78,CHOP)and the apoptotic effector Caspase-3 were quantified by qPCR and Western blot.Results Compared with controls,rats in the CIH group exhibited marked hippocampal neuronal damage,including disrupted cytoarchitecture,cytoplasmic dissolution,and swollen rough ER.Ultrastructural analysis revealed nuclear deformation and organelle disruption.TUNEL assay demonstrated a significant increase in apoptotic cells(P<0.05).Flow cytometry showed elevated intracellular Ca2? levels(P<0.05).GRP78,CHOP,and Caspase-3 were significantly upregulated at both mRNA and protein levels in the CIH group(all P<0.05).Conclusion CIH induces pronounced hippocampal neuronal injury and apoptosis in rats,associated with Ca2? dysregulation and activation of ER stress-mediated apoptotic pathways.These findings provide experimental evidence for elucidating the mechanisms of OSAHS-related neuronal injury and identifying potential therapeutic targets.

Objective:To investigate the role of bone morphogenetic protein (BMP) 7 peptidomimetics THR123 in the regulation of proliferative vitreoretinopathy (PVR) and epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells.Methods:Primary human RPE cells were isolated from donor eyes.The RPE cells was cultured for 48 hours with conventional medium, medium containing 10 ng/ml transforming growth factor-β2 (TGF-β2), medium containing 10 ng/ml TGF-β2 and 5 μg/ml THR123, respectively, serving as negative control group, TGF-β2 stimulation group and THR123-treated group.The relative protein expression levels of E-cadherin, α-smooth muscle actin (α-SMA), fibronectin (FN) activin receptor-like kinase-2 (ALK2) and Snail family zinc finger transcription factor 1, Snail1) were detected by Western blot analysis in each group.RPE cell contractile function was detected by collagen gel contraction assay.RPE cell migration function was detected by transwell assay.RPE cell polarity was detected by transepithelial resistance.For the in vivo model, the rabbit PVR model was established by intravitreal injection of RPE cells and cytokine platelet-derived growth factor.The PVR rabbits were randomly divide into PVR group, 0.5 μg/ml THR123 group and 5 μg/ml THR123 group, and were intravitreally injected with corresponding concentration of THR123 on the day of modelling and 7 days after modelling.The fundus conditions of rabbits were observed every 7 days.Retinal detachment was checked by B-scan ultrasonography every 7 days, and PVR grading was performed on 14 and 28 days after modelling.On day 28 after modelling, the rabbit was sacrificed by air embolism and the eyeball was enucleated.Hematoxylin-eosin (HE) staining and α-SMA immunofluorescence staining were performed to compare the differences in PVR progression among groups.In the LDN inhibition group, BMP receptor inhibitor LDN193189 was added to primary RPE cells and the expression of EMT markers and cell functional differences of RPE cells were compared between negative control group and LDN inhibition group.Small interfering RNA of control and Snail1 was transfected into RPE cells of siNC+ TGF-β2 group and siSnail1+ TGF-β2 group, respectively, and the differences in EMT markers and function of RPE cells were compares.The protocol involving human specimens, cells and animals in this study was opproved by the Medical Ethics Committee of Shanghai General Hospital (No.2021SQ057). Results:There were statistically significant differences in gel contraction ratio, transepithelial resistance and relative expressions of E-Cadherin, FN and α-SMA proteins among the negative control group, TGF-β2 stimulation group and THR123-treated group ( F=28.38, 136.30, 38.50, 2.53, 53.54; all P<0.01).Compared with the negative control group and THR123-treated group, the gel contraction ratio, transepithelial resistance, and relative expression of E-cadherin in the TGF-β2 stimulation group decreased, and the relative expression of α-SMA and FN increased, with statistically significant differences (all P<0.01).On day 28 after modeling, the PVR grades in the PVR group, 5 μg/ml THR123 group and 5 μg/ml THR123 group were 4.00±0.45, 2.80±0.37, 1.80±0.37, respectively, with a statistically significant difference among groups ( F=7.583, P=0.007).The PVR grade of rabbit eyes was significantly lower in the 5 μg/ml THR123 group than in the PVR group ( P<0.05).HE staining showed that the number of preretinal proliferative membranes was less in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group, and no retinal detachment was found.Immunofluorescence staining showed that the expression of α-SMA in vitreous cavity and retina was significantly lower in the 5 μg/ml THR123 group than in the PVR group and the 0.5 μg/ml THR123 group.Compared with the negative control group and THR123-treated group, the relative expression of ALK2 protein in the TGF-β2 stimulation group was significantly decreased, and the relative expression of Snail1 protein was significantly increased (all P<0.01).Compared with the negative control group, the gel contraction ratio, transepithelial resistance and relative expression of E-cadherin protein in the LDN inhibition group were significantly reduced, and the relative expression of FN, α-SMA and Snail1 proteins were significantly increased (all P<0.01).Compared with the siNC+ TGF-β2 group, the gel contraction ratio and the relative expression of E-cadherin protein in the siSnail1+ TGF-β2 group were significantly increased, and the relative expression of FN, α-SMA and Snail1 proteins were significantly decreased (all P<0.05). Conclusions:THR123 can activate the BMP pathway to inhibit Snail1, thereby inhibiting the EMT process in RPE cells and PVR occurrence.It is expected to provide potential targets for PVR drug therapy.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Objective:To compare the effects of using cone beam CT (CBCT) and oral scanning registration on implant positional accuracy during robot-assisted implant surgery, and to provide a basis for selecting the appropriate registration for robot-assisted implant surgical options.Methods:One patient with dentition defect, specifically missing teeth at positions 21 and 26 and having natural teeth adjacent mesially and distally to the edentulous area, who visited the Department of Oral Implantology, School of Hospital of Stomatology Wuhan University in 2024 were selected. Based on reconstructed imaging data, 30 identical jaw models were printed. These models were divided into a CBCT registration group and an intra-oral scanning registration group (15 models per group). An associate chief physician with extensive experience in implant surgery performed preoperative registration using the implant robot and completed the implant surgeries. Postoperative CBCT scans were used to determine the three-dimensional position of the implants. The deviations between the planned implant position and the actual position were evaluated, including deviations at the implantation point, apical point, and angular deviation. The differences between the two groups were compared.Results:The implantation deviation was 0.675 (0.490) mm, apical deviation was (0.680±0.272) mm, and the angular deviation was 0.566°±0.147° in the CBCT registration group, and in the intra-oral scanning registration group, implantation deviation was 0.695 (0.313) mm, apical deviation was (0.667±0.217) mm, and the angular deviation was 0.523°±0.168°. There was no statistically significant error in implant precision between the two groups ( P>0.05). Conclusions:This in vitro experiment found that the use of intra-oral scanning registration in robot-assisted implant surgery can achieve similar implant placement accuracy as CBCT registration.

The phenotype of peri-implant soft tissue is crucial to the long-term treatment outcome of implant restoration, but soft tissue phenotype deficiencies are common in clinical practice and need to be improved through soft tissue augmentation. Although autologous soft tissue graft is still the gold standard for soft tissue augmentation, it has limitations such as limited donor area, increased trauma, and low patient acceptance. Plasmatrix has sufficient sources, is easy to prepare, and has a scaffold structure, growth factors, and cell components that support soft tissue growth. It can be used to improve the phenotype of peri-implant soft tissue. However, there are currently limited clinical studies on the application of plasmatrix in improving the phenotype of peri-implant soft tissue, and there is a lack of consensus conclusions, which makes the majority of clinicians feel confused when using plasmatrix. This article will try to combine existing clinical studies and the clinical experience of the author′s team to explain the classification of peri-implant soft tissue phenotypes and the application of plasmatrix in improving soft tissue phenotypes, in order to provide a reference for related clinical treatments.

The 2024 American Society of Clinical Oncology(ASCO)Annual Meeting was held in Chicago,the United States,from May 31 to June 4 in 2024.In recent years,antibody-drug conjugates(ADCs)have become one of the most popular targeted therapies because of their high specificity,efficacy,and low toxicity,making them a focal point in this ASCO meeting.Currently,over 100 ADCs are under investigation,demonstrating the considerable development potential of ADCs in the field of targeted cancer therapy.The aforementioned conference reported several recent research advancements regarding ADCs for the treatment of breast cancer(BC).This review summarizes the latest progress of ADCs in BC treatment discussed at the confer-ence.

Objective:To analyze the clinical characteristics, treatment response, and prognosis of patients newly diagnosed with immunoglobulin A multiple myeloma (IgA MM), and to ascertain whether the IgA isotype remains a poor prognostic factor in the bortezomib era.Methods:This study retrospectively enrolled 155 patients newly diagnosed with IgA MM and 420 with non-IgA MM admitted to the Department of Hematology, the First Affiliated Hospital of Nanchang University from March 2014 to December 2021. We compared the two groups in terms of their clinical characteristics, prognoses, and progression-free survival (PFS) and overall survival (OS) following different treatment regimens.Results:Compared with the non-IgA group, the IgA group presented with more aggressive clinical features, including a higher proportion of patients with hemoglobin<85 g/L (61.3% vs 51.4%, P=0.035), extramedullary manifestations (20.0% vs 11.4%, P=0.008), and gain/amp (1q21) (48.6% vs 36.7%, P=0.032). Efficacy analysis revealed a lower overall response rate (ORR) in the IgA group than in the non-IgA group (83.2% vs 92.4%, P=0.001). Among patients treated with bortezomib-based regimens, the ORR was 91.2% in the IgA group and 94.8% in the non-IgA group, but the difference was nonsignificant ( P=0.146). Survival analysis showed that the median PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[23.5 (95% CI: 17.4-29.5) months and 48.8 (95% CI: 30.1-67.5) months vs 40.7 (95% CI: 33.8 - 47.6) months and not reached, respectively; P<0.001 and P=0.002]. In the subgroup of patients who received bortezomib-based therapy without subsequent autologous hematopoietic stem cell transplantation (auto-HSCT), the PFS and OS were significantly shorter in the IgA group compared with the non-IgA group[25.4 (95% CI: 18.7-32.1) months and 53.5 (95% CI: 35.4-71.6) months vs 41.0 (95% CI: 33.7-48.3) months and not reached; P=0.001 and P=0.011]. In patients who underwent bortezomib-based induction therapy followed by auto-HSCT, the 1-, 3-, and 5-year OS rates for the IgA group were 96%, 81%, and 81%, respectively, compared with 93%, 89%, and 79% for the non-IgA group, but the difference was nonsignificant ( P=0.758) . Conclusion:In the bortezomib era, IgA MM is still associated with a poorer overall prognosis than non-IgA MM, likely due to its inherent high-risk biological characteristics. Although bortezomib-based regimens effectively improve the treatment response, they fail to completely bridge the survival gap between the two disease isotypes. Therefore, bortezomib-based therapy followed by auto-HSCT may be a key strategy to overcome the poor prognosis of IgA MM, potentially enabling these patients to achieve long-term survival comparable to that of their non-IgA counterparts.