Spatiotemporal Characteristics and Risk Factors for All and Severity-Specific Preterm Births in Southern China, 2014-2021: Large Population-Based Study.

BACKGROUND: The worldwide incidence of preterm births is increasing, and the risks of adverse outcomes for preterm infants significantly increase with shorter gestation, resulting in a substantial socioeconomic burden. Limited epidemiological studies have been conducted in China regarding the incidence and spatiotemporal trends of preterm births. Seasonal variations in risk indicate the presence of possible modifiable factors. Gender influences the risk of preterm birth. OBJECTIVE: This study aims to assess the incidence rates of preterm birth, very preterm birth, and extremely preterm birth; elucidate their spatiotemporal distribution; and investigate the risk factors associated with preterm birth. METHODS: We obtained data from the Guangdong Provincial Maternal and Child Health Information System, spanning from January 1, 2014, to December 31, 2021, pertaining to neonates with gestational ages ranging from 24 weeks to 42 weeks. The primary outcome measures assessed variations in the rates of different preterm birth subtypes over the course of the study, such as by year, region, and season. Furthermore, we examined the relationship between preterm birth incidence and per capita gross domestic product (GDP), simultaneously analyzing the contributing risk factors. RESULTS: The analysis incorporated data from 13,256,743 live births. We identified 754,268 preterm infants and 12,502,475 full-term infants. The incidences of preterm birth, very preterm birth, and extremely preterm birth were 5.69 per 100 births, 4.46 per 1000 births, and 4.83 per 10,000 births, respectively. The overall incidence of preterm birth increased from 5.12% in 2014 to 6.38% in 2021. The incidence of extremely preterm birth increased from 4.10 per 10,000 births in 2014 to 8.09 per 10,000 births in 2021. There was a positive correlation between the incidence of preterm infants and GDP per capita. In more developed economic regions, the incidence of preterm births was higher. Furthermore, adjusted odds ratios revealed that advanced maternal age, multiple pregnancies, and male infants were associated with an increased risk of preterm birth, whereas childbirth in the autumn season was associated with a protective effect against preterm birth. CONCLUSIONS: The incidence of preterm birth in southern China exhibited an upward trend, closely linked to enhancements in the care capabilities for high-risk pregnant women and critically ill newborns. With the recent relaxation of China's 3-child policy, coupled with a temporary surge in advanced maternal age and multiple pregnancies, the risk of preterm birth has risen. Consequently, there is a pressing need to augment public health investments aimed at mitigating the risk factors associated with preterm birth, thereby alleviating the socioeconomic burden it imposes.

The Effect of STAT3 Signal Pathway Activation on Retinopathy of Prematurity.

Objective: To investigate the mechanism of activation of the signal transducer and activator of transcription 3 (STAT3) signal pathway in the process of retinopathy of prematurity (ROP). Methods: Sixty newborn Sprague-Dawley (SD) rats were randomly separated into the hyperoxia and air control groups (n = 30/in each group). The serum hepcidin level on 21 d was measured using the enzyme-linked immunosorbent assay (ELISA). The expression of HAMP and STAT3 protein in the liver was determined using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Retinal neovasculature was evaluated by hematoxylin and eosin (HE) stain and fluorescein lectin. The retinal endothelial cells were treated with 250 µmol/L cobalt chloride for 72 h and added S3I-201. The STAT3 level was determined by western blotting. Results: The expression of STAT3 protein increased significantly after hyperoxia stimulation. The expression of HAMP mRNA in the hyperoxia group was significantly higher than that of the control group. The proliferation of retinal cells was inhibited, and the expression of STAT3 was increased. No significant difference was noted in vascular endothelial growth factor (VEGF) mRNA. The expression of STAT3 and VEGF mRNA was significantly reduced. Conclusion: The activation of the STAT3 signal pathway increased hepcidin expression, contributing to the pathogenesis of ROP. S3I-201 inhibited the expression of STAT3 and VEGF mRNA levels. This information provides potential novel therapeutic approach to the prevention and treatment of ROP.

Application of the SeDeM Expert System in Studies for Direct Compression Suitability on Mixture of Rhodiola Extract and an Excipient.

The SeDeM expert system is used to reveal direct compression (DC) suitability of the active ingredients and excipients in preformulation. In this study, the system was used to predict compressibility of rhodiola extract (RhE) and its mixture with excipients. The parameter index (IP), parameter profile index (IPP), and good compressibility index (IGC) of RhE mixtures with different fillers were investigated. The results showed that RhE and mixture with lactose or starch were not suitable for DC according to the values of IP, IPP, and IGC, which can be corrected by pregelatinized starch (P-STA). The quality of tablets corrected by P-STA all satisfied the USP monograph limit. The findings from this study showed that the system is a useful tool to predict DC suitability on the mixture of RhE and an excipient.

DTX3L is upregulated in glioma and is associated with glioma progression.

Gliomas are the most common primary brain tumors of the central nervous system (CNS). Due to the poor prognosis of glioma patients, it is urgent to develop more effective therapies. Deltex-3-like (DTX3L), also known as B-lymphoma and BAL-associated protein (BBAP), has been reported to play an important role in the progression of many tumors. This study aimed to investigate the clinical significance and biological function of DTX3L in human glioma. Clinically, the protein expression level of DTX3L is increased in glioma tissues compared with that observed in normal brain tissues. Immunohistochemical analysis demonstrated that DTX3L was highly expressed in the glioma tissues and its level was correlated with the grade of malignancy. Multivariate analysis revealed the association between high expression of DTX3L and the poor prognosis of glioma patients. In addition, knockdown of DTX3L by siRNA transfection increased glioma cell apoptosis. Moreover, suppression of DTX3L expression was shown to significantly inhibit the migration and invasion of glioma cells. These data indicate that DTX3L plays an important role in the pathogenic process of glioma, suggesting that DTX3L could be a potential prognostic biomarker for glioma.

Up-regulation of Vps4A promotes neuronal apoptosis after intracerebral hemorrhage in adult rats.

Vps4, vacuolar protein sorting 4, belongs to ATPases Associated with diverse cellular Activities (AAA) protein family which is made up of Vps4A and Vps4B. Previous studies demonstrated that Vps4A plays vital roles in diverse aspects such as virus budding, the efficient transport of H-Ras to the PM (plasma membrane) and the involvement in the MVB (multivesiculate bodies) pathway. Interestingly, Vps4A is also expressed in the brain. However, the distribution and function of Vps4A in ICH diseases remain unclear. In this study, we show that Vps4A may be involved in neuronal apoptosis during pathophysiological processes of intracerebral hemorrhage (ICH). Based on the results of Western blot and immunohistochemistry, we found a remarkable up-regulation of Vps4A expression surrounding the hematoma after ICH. Double labeled immunofluorescence showed that Vps4A was co-expressed with NeuN but rarely with astrocytes and microglia. Morever, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with Vps4A. Additionaly, Vps4A knockdown in vitro specifically leads to decreasing neuronal apoptosis coupled with increased Akt phosphorylation. All datas suggested that Vps4A was involved in promoting neuronal apoptosis via inhibiting Akt phosphorylation after ICH.

Expression of Sam68 Associates with Neuronal Apoptosis and Reactive Astrocytes After Spinal Cord Injury.

Src-associated in mitosis (Sam68; 68 kDa) is a novel RNA-binding protein that belongs to the signal transduction and activation of RNA family involved in various biological processes. However, the expression and roles of Sam68 in the central nervous system remain unknown. In the present study, we performed a spinal cord injury (SCI) model in adult rats and found a significant increase of Sam68 protein levels in this model, which reached a peak at day 3 and then gradually returned to normal levels at day 14 after SCI. We use immunohistochemistry analysis revealing a widespread distribution of Sam68 in the spinal cord. In addition, double-immunofluorescence staining showed that Sam68 immunoreactivity was found predominantly in neurons and astrocytes. Moreover, colocalization of Sam68/active caspase-3 has been respectively detected in neuronal nuclei, and colocalization of Sam68/PCNA has been detected in glial fibrillary acidic protein. In vitro, we found that depletion of Sam68 by short interfering RNA inhibits neuronal apoptosis and astrocyte proliferation and decreases cyclin D1 protein levels. In conclusion, this is the first study to find the Sam68 expression in SCI. Our results suggest that Sam68 might be illustrated in the apoptosis of neurons and proliferation of astrocytes after SCI. This research will provide new drug targets for clinical treatment of SCI.

Expression of Dixdc1 and its Role in Astrocyte Proliferation after Traumatic Brain Injury.

DIX domain containing 1 (Dixdc1), a positive regulator of Wnt signaling pathway, is recently reported to play a role in the neurogenesis. However, the distribution and function of Dixdc1 in the central nervous system (CNS) after brain injury are still unclear. We used an acute traumatic brain injury (TBI) model in adult rats to investigate whether Dixdc1 is involved in CNS injury and repair. Western blot analysis and immunohistochemistry showed a time-dependent up-regulation of Dixdc1 expression in ipsilateral cortex after TBI. Double immunofluorescent staining indicated a colocalization of Dixdc1 with astrocytes and neurons. Moreover, we detected a colocalization of Ki-67, a cell proliferation marker with GFAP and Dixdc1 after TBI. In primary cultured astrocytes stimulated with lipopolysaccharide, we found enhanced expression of Dixdc1 in parallel with up-regulation of Ki-67 and cyclin A, another cell proliferation marker. In addition, knockdown of Dixdc1 expression in primary astrocytes with Dixdc1-specific siRNA transfection induced G0/G1 arrest of cell cycle and significantly decreased cell proliferation. In conclusion, all these data suggest that up-regulation of Dixdc1 protein expression is potentially involved in astrocyte proliferation after traumatic brain injury in the rat.

MEKK1 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage.

The JNKs have been implicated in a variety of biological functions in mammalian cells, including apoptosis and the responses to stress. However, the physiological role of these pathways in the intracerebral hemorrhage (ICH) has not been fully elucidated. In this study, we identified a MAPK kinase kinase (MAPKKK), MEKK1, may be involved in neuronal apoptosis in the processes of ICH through the activation of JNKs. From the results of western blot, immunohistochemistry and immunofluorescence, we obtained a significant up-regulation of MEKK1 in neurons adjacent to the hematoma following ICH. Increasing MEKK1 level was found to be accompanied with the up-regulation of p-JNK 3, p53, and c-jun. Besides, MEKK1 co-localized well with p-JNK in neurons, indicating its potential role in neuronal apoptosis. What's more, our in vitro study, using MEKK1 siRNA interference in PC12 cells, further confirmed that MEKK1 might exert its pro-apoptotic function on neuronal apoptosis through extrinsic pathway. Thus, MEKK1 may play a role in promoting the brain damage following ICH.

Up-Regulation of Interferon Regulatory Factor 3 Involves in Neuronal Apoptosis After Intracerebral Hemorrhage in Adult Rats.

Interferon regulatory factor 3 (IRF3) is a member of IRF family which plays a significant role in the innate immune response, apoptosis, and oncogenesis. Mounting evidence has demonstrated that IRF3 was involved in central nervous system disease such as cerebral ischemic injury through promoting neuronal apoptosis. However, it remains unclear about the underlying mechanisms of IRF3 upon neuronal apoptosis following intracerebral hemorrhage (ICH). In the present study, we established an adult rat ICH model by injecting autologous whole blood into the right basal ganglia and evaluated their neurological deficits by behavioral tests. IRF3 protein level was up-regulated adjacent to the hematoma following ICH when compared with the sham brain cortex by western blot and immunohistochemistry. Immunofluorescent staining indicated IRF3 was mainly localized in neurons, a few in astrocytes. In addition, we also detected that IRF3 co-localized with active caspase-3 which is a neuronal apoptosis marker. Furthermore, in vitro study, knocking down IRF3 by using IRF3 interference in primary cortical neurons reduced the expression of active caspase-3 and Bax while increased Bcl-2. In conclusion, we speculated that IRF3 might exert pro-apoptotic function in neurons after ICH.

The role of Alix in the proliferation of human glioma cells.

Apoptosis-linked-gene-2-interacting protein 1 (Alix) is involved in the endosome-lysosome system in the cytoplasm. The normal function of Alix may be altered by ALG-2 toward a destructive role during active cell death. Alix also may play a role in regulation of cell proliferation. However, the role of Alix in human glioma has not been elucidated yet. This study intended to clarify the relationship between Alix and glioma pathologic grades and its role in the proliferation of glioma cells. Our findings showed that Alix protein concentrations were significantly elevated in high-grade glioma tissue compared with low-grade glioma (P < .0001). Immunohistochemical study revealed that Alix was overexpressed in 75 resected glioma tissues and may forecast poor survival. Alix expression was increased in resting serum-stimulated glioma cells. Additionally, we reduced Alix expression in U251MG cells and then found that cell viability was decreased significantly when p21 expression increased. Colony formation assay and flow cytometry analysis demonstrated that reduced Alix expression may lead to growth inhibition and cell cycle arrest. In summary, our findings suggest that Alix plays an important role in the proliferation of glioma cells and may be a novel therapeutic target.

Expression and clinical role of RBQ3 in gliomas.

RBQ3, also known as RBBP5 (RB-binding protein 5), was an RB-binding protein. Besides, it was one of core components of MLL1 (mixed lineage leukemia 1), which were required for H3K4 methyltransferase activity. MLL1 dysfunction was found to be associated with the progression of some cancers such as acute leukemias. However, the precise role of RBQ3 in tumor progression remains obscure. In this study, we explored the expression and clinical role of RBQ3 in gliomas. Our results showed that RBQ3 was significantly upregulated in clinical glioma specimens by Western blot and immunohistochemistry. Moreover, its level was significantly associated with the pathology grades. High RBQ3 expression was suggested to be an independent prognostic factor for glioma patients' survival by univariate and multivariate analyses. Serum starvation and refeeding assay indicated that the expression of RBQ3 increased 8h after serum-stimulation, together with percentage of cells at S phase. In addition, knockdown of RBQ inhibited U87-MG cell proliferation with CCK8 kit, flow cytometry assays and colony formation analyses; while the depletion of RBQ3 induced the apoptosis of U87-MG cells. All the findings suggested that RBQ3 might play an important role in glioma, and RBQ3 inhibitors might be novel anti-tumor agents.

TCTP Expression After Rat Spinal Cord Injury: Implications for Astrocyte Proliferation and Migration.

Translationally controlled tumor protein (TCTP) is a ubiquitous and highly conserved protein which plays a role in cell proliferation and growth, apoptosis, and cell cycle regulation. However, its expression and function in spinal cord injury (SCI) are still unknown. Here, we demonstrated that expression of TCTP was dynamic changed after acute spinal cord injury. Our results showed that TCTP gradually increased, reached a peak at 3 day, and then declined to basal levels at 14 days after spinal cord injury. Upregulation of TCTP was accompanied with an increase in the levels of proliferation proteins such as PCNA. Immunofluorescent labeling also showed that TCTP located in astrocytes and traumatic SCI induced TCTP colocalizated with PCNA. These results indicated that TCTP might play an important role in astrocyte proliferation. To further probe the role of TCTP, TCTP-specific siRNA-transfected astrocytes showed significant decrease of primary astrocyte proliferation. Surprisingly, TCTP knockdown also reduced primary astrocyte migration, as the reorganization of microtubules and F-actin was disturbed after siRNA transfection. All above indicated that TCTP might play a crucial role in astrocyte proliferation and migration. Collectively, our data suggested that TCTP might play important roles in CNS pathophysiology after SCI.

Up-regulation of PSMB4 is associated with neuronal apoptosis after neuroinflammation induced by lipopolysaccharide.

Proteasomes are major intracellular extralysosomal organelle for protein degradation and a central source of antigenic peptides in the endogenous pathway. Proteasome beta-4 subunit (PSMB4) was recently identified as potential cancer driver genes in several tumors. However, information regarding its regulation and possible function in the central nervous system is still limited. The present study was designed to elucidate dynamic changes in PSMB4 expression and distribution in the cerebral cortex in a lipopolysaccharide (LPS)-induced neuroinflammation rat model. It was found that PSMB4 expression was increased significantly in apoptotic neurons in the brain cortex after LPS injection. Moreover, there was a concomitant up-regulation of active caspase-3, cyclin D1, and CDK4 in vivo and vitro studies. In addition, these three proteins in cortical primary neurons were decreased after knocking down PSMB4 by siRNA. Collectively, these results suggested that PSMB4 may be involved in neuronal apoptosis in neuroinflammation after LPS injection.

Knockdown of PFTK1 Inhibits the Migration of Glioma Cells.

The prognosis of glioma patients is generally poor, so it is urgent to find out the underlying molecular mechanisms. PFTK1 is a member of cyclin-dependent kinases (Cdks) family and has been reported to contribute to tumor migration and invasion. In this study, we aimed to explore the expression and function in human glioma. Western blot and immunohistochemistry were used to evaluate the expression of PFTK1. PFTK1 expression was higher in glioma tissues compared with normal brain tissues, and its level was associated with the WHO grade in Western blot analysis. The suppression of PFTK1 expression by RNA interference was shown to inhibit the migration of glioma cells. Knockdown of PFTK1 increases E-cadherin expression and decreases vimentin expression. These data show that PFTK1 may participate in the pathogenic process of glioma, suggesting that PFTK1 can become a potential therapeutic strategy for gastric cancer.