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 and analyze the influencing factors and intervention strategy preferences of preoperative dental anxiety in patients undergoing oral implant surgery, and to provide a basis for the clinical formulation and implementation of targeted interventions. Methods: This study was approved by the Hospital Medical Ethics Committee, and written informed consent was obtained from all participants. Using convenience sampling, a cross-sectional survey was conducted from January to October 2025 among 210 patients in the Department of Implantology of a tertiary dental hospital. All participants had been clinically diagnosed and were scheduled to undergo oral implant surgery on the day of the survey. The survey was conducted using a General Information Questionnaire, the Modified Dental Anxiety Scale (MDAS), and an Anxiety Cause Questionnaire. The General Information Questionnaire collected data on patients’ gender, age, presence of systemic diseases, dental treatment history, number of implants, whether bone augmentation was required. The MDAS was used to assess patients’ dental anxiety levels via MDAS scores, with a score ≥ 12 defined as dental anxiety. The Anxiety Cause Questionnaire covered the following items: fear of pain, concern that the instruments might cause permanent damage to their teeth, concern about the dentist’s technique and inability to achieve ideal results, fear of local anesthesia, concern about cross-infection, financial pressure, exposure to an unfamiliar environment and strangers, and previous unpleasant dental experiences. The MDAS scores of the items in the Anxiety Cause Questionnaire and General Information Questionnaire were analyzed using the Mann-Whitney U test or Kruskal-Wallis H test for univariate analysis, and factors with statistical significance in the univariate analysis were further analyzed using binary logistic regression for multivariate analysis. An Intervention Strategy Preference Questionnaire was used to survey patients’ preferences for the following interventions: understanding the surgical procedure, verbal reassurance from medical staff, distraction methods such as listening to music or using stress balls, staying in a physically and mentally relaxing environment, and others. Results: The average preoperative MDAS score of patients undergoing oral implant surgery was 10.91 ± 3.40, and the incidence of dental anxiety (MDAS ≥ 12) was 34.8% (73/210). Univariate analysis showed that female patients, patients aged < 45 years, had significantly higher MDAS scores (P < 0.05). Patients who selected “fear of pain” (79.0%), “fear of local anesthesia” (21.0%), and “exposure to an unfamiliar environment and strangers” (4.8%) as causes of their anxiety had higher MDAS scores than those who did not select these items (P < 0.05). Multivariate logistic regression analysis showed that patient's age (OR = 0.420), fear of pain (OR = 4.234), and exposure to an unfamiliar environment and strangers (OR = 8.220) were independent influencing factors of preoperative dental anxiety in patients undergoing oral implant surgery (P < 0.05). The Intervention Strategy Preference Questionnaire showed that “verbal reassurance from medical staff” (45.2%), “distraction” (43.3%), and “understanding the surgical procedure” (39.5%) were the most preferred intervention strategies among patients. Conclusions Preoperative dental anxiety is common among some patients undergoing oral implant surgery, particularly young and middle-aged patients, those treated by less experienced physicians, and those experiencing anxiety due to a fear of pain or exposure to an unfamiliar environment and strangers. Clinical attention should focus on these patient populations, and systematic preoperative education and psychological counseling should be provided accordingly.

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

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.

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*

Objective:To evaluate the relationship between postoperative delirium (POD) and concentrations of phosphatidylethanolamine-binding protein 1 (PEBP1) in cerebrospinal fluid (CSF) of elderly patients undergoing total knee and hip arthroplasty.Methods:In this case-control study, 375 elderly patients of both sexes, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia at Haian Hospital Affiliated to Nantong University from November 2022 to June 2024, were selected. The perioperative clinical data were collected. CSF was drawn before anaesthesia for determination of the concentrations of PEBP1, Abeta 42 (Aβ 42), total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay. The occurrence of postoperative delirium was evaluated using the Confusion Assessment Method at 1-7 days after operation. The severity of POD was assessed using a Memorial Delirium Assessment Scale. The patients were divided into POD group and non-POD group based on whether POD occurred. The influencing factors of POD were analyzed using multivariate logistic regression. Mediating effects were assessed to determine whether the levels of Aβ 42, p-tau and t-tau in CSF mediated PEBP1′s effect on POD. The accuracy of CSF PEBP1 concentration in predicting POD was evaluated using the receiver operating characteristic curve. Results:Decreased concentration of Aβ 42 in CSF, decreased ratios of Aβ 42/p-tau and Aβ 42/t-tau in CSF, and increased concentrations of PEBP1, p-tau and t-tau in CSF were independent risk factors for POD ( P<0.05). The results of mediation analysis showed that the relationship between PEBP1 and POD was partially mediated by CSF Aβ 42 (15.0%) and Aβ 42/t-tau ratio (14.9%). The receiver operating characteristic curve showed that the accuracy of CSF PEBP1 concentrations in predicting the occurrence of POD was high (AUC=0.846, P<0.001). Conclusions:Preoperative elevated CSF PEBP1 concentration is a risk factor for POD. CSF Aβ 42 concentration and Aβ 42/t-tau ratio serve as key mediators in the the association between PEBP1 and POD. PEBP1 concentration is more accurate in predicting POD.

Balo′s concentric sclerosis (BCS) is a rare demyelinating disease of the central nervous system, once considered a variant of multiple sclerosis. It is characterized by alternating layers of demyelinated and myelinated regions in a concentric pattern, resembling tree rings. The disease typically has an acute onset and diverse clinical manifestations. In the past, diagnosis of BCS primarily relied on autopsy; however, with the widespread application of magnetic resonance imaging, the number of confirmed cases has gradually increased, significantly improving the efficiency of clinical diagnosis and treatment. Nevertheless, most reports both domestically and internationally remain limited to individual cases. This article provides a review of the epidemiology, etiology, predisposing factors, pathogenesis, neuropathological features, clinical manifestations, differential diagnosis, relationship with multiple sclerosis, auxiliary examinations, and treatment of BCS.

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.

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.