Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective To investigate the expression of long non-coding RNA(LncRNA)nuclera-enriched autosomal transcript(NEAT1)in children with retinoblastoma(Rb)and the effect of down-regulation of NEAT1 in Rb cell Y79 on cell biological function.Methods A total of 83 children with Rb who were diagnosed and treated in Huangshi Central Hospital from March 2015 to March 2021 were collected as the research object.During the same period,50 healthy children(control group)were selected in the children's health center.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of NEAT1 in serum.The differences in the expressions of NEAT1 in serum between Rb children and the control group,and the differences in the expressions of NEAT1 in serum among Rb children with different clinical indicators,were analyzed.Y79 cells were cultured and were divided into si-NEAT1 group(transfected with interference sequence of NEAT1),si-NC group(transfected with control sequence)and Ctl group(only add transfection reagent).The qRT-PCR,MTT,flow cytometry and Transwell were used to detect the NEAT1 expression,cell proliferation,apoptosis,migration and invasion.Results The expression level of NEAT1 in the serum of children with Rb(1.43±0.28)was higher than that in the control group(1.01±0.21),with significant difference(t=9.116,P＜0.001).The expression levels of NEAT1 in serum of children with Rb with Intraocular International Retinoblastoma classification(IIRC)stage CDE,poor differentiation,optic nerve infiltration and lymph node metastasis were higher than those in children with Rb with AB,medium to high differentiation,no optic nerve infiltration and lymph node metastasis,with significant differences(t=2.190～3.693,all P＜0.05).The area under the curve for diagnosing Rb based on NEAT1 expression in serum was 0.882(95％CI:0.826～0.937).When the expression level of NEAT1 was 1.20,the sensitivity and specificity were 80.00％and 79.52％,respectively.Compared with the si-NC group(1.03±0.09)and the Ctl group(1.02±0.15),the expression level of NEAT1 in the si-NEAT1 group(0.35±0.06)was decreased,with significant differences(t=14.829,9.994,all P＜0.001).The absorbance A values in the si-NEAT1 group at 24,48,72 and 96h were significantly lower than those in the si-NC group and the Ctl group(t=si-NC=2.796～4.362,tCtl=2.641～5.555,all P＜0.05),while the apoptosis rate in the si-NEAT1 group was significantly higher than those in the si-NC group and the Ctl group,and the differences were statistically significant(t=4.999,3.915,all P＜0.05).Compared with the si-NC group and the Ctl group,the number of migrating cells(116.50±9.35 vs 132.00±7.32,134.00±7.95)and the number of invasive cells(96.33±8.94 vs 117.67±12.39,119.17±10.05)in the si-NEAT1 group were reduced,and the differences were statistically significant(tsi-NC=3.196,3.421,tCtl=3.492,4.159,all P＜0.05).Conclusion The expression level of NEAT1 in the serum of children with Rb was elevated,which may have a certain diagnostic value for children with Rb.Silencing the expression of NEAT1 in Y79 cells could reduce cell proliferation,accelerate cell apoptosis,and inhibit cell migration and invasion.

Objective To observe the effect of Danshen injection (DSI) on pulmonary fibrosis in silicosis mice, and to analyze the differential metabolic pathway on pulmonary fibrosis in silicosis using DSI by urine metabolomics. Methods The specific pathogen free C57BL/6J mice were randomly divided into control group, silicosis model group, DSI prevention group and DSI treatment group. The mice in the last three groups were given 1 mL silica suspension with a mass concentration of 50 g/L by the one-time non-exposed tracheal method, and the mice in the control group were not given any treatment. Subsequently, mice in the DSI prevention group and the DSI treatment group were given intraperitoneal injection of DSI with a dose of 5 mL/kg body weight from 24 hours after exposure to dust and from the 29th day after exposure to dust, respectively, once per day until the 56th day after exposure. Mice in the other two groups were not treated. After DSI intervention, the lung histopathological changes of mice in all groups were evaluated. The components of mouse urine metabolites were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-fight mass spectrometry method. Human Metabolome Database was used to screen the potential differential metabolites (DMs). The related metabolic pathways were analyzed using MetaboAnanlyst 5.0 Web analytics platform. Results The result of hematoxylin-eosin staining and Van Gieson staining of mouse lung tissues showed that the pulmonary alveolar structure destroyed, typical fibrotic nodules appeared, collagen fiber deposition increased, and clumpy accumulation in the silicosis model group, compared with the control group. Compared with the silicosis model group, the degree of pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI prevention group was obviously reduced to close to the control group, while pulmonary alveolar inflammation and fibrosis in the lung tissues of mice in the DSI treatment group were also reduced, although the outcome was not as good as that in the DSI prevention group. The result of urine metabolomics analysis identified four DMs in the model group and control group, seven DMs were identified in the DSI prevention group and silicosis model group, seven DMs were identified in the DSI treatment group and silicosis model group. A total of three DMs pathways related to pulmonary fibrosis in silicosis model group and the protective effect of DSI prevention group were identified, including D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways (all P<0.01). Conclusion DSI treatment in any time point can interfere the process of pulmonary fibrosis in the silicosis mice, while the interference is more effective in the DSI group treated right after dust-exposure. DSI interferes with the urinary metabolism pathway of silicosis mice, and the D-arginine and D-ornithine metabolism, folic acid biosynthesis and metabolism, pantothenate and succinyl coenzyme A biosynthesis pathways may participate in the inhibiting process of early pulmonary fibrosis in silicosis mice by DSI.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1β, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.