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 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.

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.

OBJECTIVES: To study the effect of CDC20 knockdown on proliferation, migration and invasion of cervical cancer cells and its underlying mechanism. METHODS: CDC20 expression in cervical cancer tissues was analyzed using the TCGA database, and the protein expressions of CDC20 and β-Catenin in clinical specimens of cervical cancer and adjacent tissues were detected using immunohistochemistry. A dual target sgRNA2&7 sequence for CDC20 gene was designed for CDC20 gene knockdown in cervical cancer C33A cells using CRISPR/Cas9 technology, and CDC20 mRNA and protein expression levels in the transfected cells were detected using qRT-PCR and Western blotting. The changes in proliferation, cell cycle, apoptosis, migration and invasiveness of the transfected cells were evaluated using colony-forming assay, fluorescence activated cell sorting (FACS) and Transwell assay. In the animal experiment, naïve C33A cells and the cells with CDC20 knockdown were injected subcutaneously into the left and right axillae of nude mice (n=5) to observe tumor growth. The expressions of CDC20 and β-Catenin proteins in transfected cells and the xenograft were analyzed using Western blotting, and their interaction was confirmed by co-immunoprecipitation (CoIP) and immunofluorescence co-localization assays. RESULTS: Cervical cancer tissues expressed significantly higher CDC20 and β‑Catenin levels than the adjacent tissues. C33A cells with CDC20 knockdown showed reduced proliferation, increased apoptosis, and lowered migration and invasion abilities. CDC20 knockdown significantly suppressed the growth of C33A cell xenograft in nude mice, and the tumor-bearing mice did not exhibit obvious body mass changes. CDC20 and β-Catenin levels were both significantly lowered in C33A cells with CDC20 knockdown. Co-immunoprecipitation and co-localization assays confirmed the interaction between CDC20 and β‑Catenin. CONCLUSIONS CDC20 is highly expressed in cervical cancer tissues, and CDC20 knockdown can suppress proliferation, invasion, and metastasis while enhancing apoptosis of C33A cells, which is closely related with the regulation of the Wnt/β-Catenin signaling pathway.
Humans ; Uterine Cervical Neoplasms/metabolism* ; Female ; Cdc20 Proteins/genetics* ; Cell Proliferation ; Animals ; Cell Movement ; Neoplasm Invasiveness ; Apoptosis ; Mice, Nude ; beta Catenin/metabolism* ; CRISPR-Cas Systems ; Mice ; Cell Line, Tumor ; Gene Knockout Techniques ; Neoplasm Metastasis

OBJECTIVES: To explore the mechanisms of Qingre Lidan Jiedu Recipe (QLJR) for improving cognitive dysfunction in rats with high copper load. METHODS: Seventy-five male SD rats were randomized into normal control group, model group, QLJR group, penicillamine (PCA) group, and QLJR+ PCA group. Except for those in the control group, all the rats were fed a high-copper diet for 12 weeks. The effects of the treatments on cognitive function of the rats were assessed using the Barnes maze and passive avoidance tests. Hippocampal expressions of NIX, FUNDC1 and LC3 of the rats were detected using Western blotting and immunofluorescence staining, and changes in mitochondrial morphology were observed with transmission electron microscopy. RESULTS: Behavioral tests showed prolonged target hole latency, shortened latency to enter the dark chamber, and increased error counts of the rats in the model group, which were significantly improved in QLJR+PCA group; the error counts were significantly lower in QLJR+PCA group than in either QLJR or PCA group. Among all the groups, the hippocampal expressions of NIX and FUNDC1 were the lowest and LC3 I/II expression the highest in the model group; NIX and FUNDC1 expressions were significantly higher and LC3 I expression was lower in QLJR+PCA group than in QLJR group and PCA group. Immunofluorescence staining revealed weakened NIX and FUNDC1 expressions and enhanced LC3 expression in the hippocampus of the rats in the model group as compared with those in the normal control and QLJR+PCA groups, but their expressions did not differ significantly between QLJR and PCA groups. The rats in the model group showed obvious structural disarray of the mitochondria, which were improved in all the treatment groups. CONCLUSIONS QLJR improves cognitive dysfunction in rats with high copper load possibly by regulating mitophagy.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Drugs, Chinese Herbal/therapeutic use* ; Copper/toxicity* ; Mitophagy/drug effects* ; Hippocampus/drug effects* ; Cognition Disorders/drug therapy* ; Cognitive Dysfunction/chemically induced*

BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*