PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

Aim To detect the non-coding RNA(ncRNA)expression profile of neuroglioma cells via whole transcriptome sequencing,establish the ceRNA network and reveal the molecular mechanism of ncRNA participating in the inhibition of neuroglioma cell prolif-eration by melatonin.Methods Neuroglioma cells were intervened with by 0,2,4,6 and 8 mmol·L-1 melatonin for 24,48 and 72 h,and the inhibitory effect of melatonin on cell proliferation was detected via CCK-8;after the intervention of 0 and 4 mmol·L-1 melatonin to U251 cells for 24 h,differentially ex-pressed miRNA(DEmiRNA),lncRNA(DElncRNA)and mRNA(DEmRNA)were detected through whole transcriptome sequencing,along with GO and KEGG enrichment analysis of DEmRNA;the ceRNA network was constructed,and the key gene expression of ceR-NA was verified through qRT-PCR.Results Melato-nin exerts a time-dose-dependent inhibitory effect on the proliferation of neuroglioma cells;a total of 5049 DEmRNA,635 DElncRNA and 146 DEmiRNA in 0 and 4 mmol·L-1 melatonin groups were screened out via whole transcriptome sequencing;DEmRNAs were mainly enriched in cancer-related signaling pathways,such as ferroptosis,mTOR signaling pathway,FoxO signaling pathway and cell cycle;the ceRNA network included 4 lncRNAs,3 miRNAs and 48 mRNAs.As verified through real-time PCR,the expressions of hsa-miR-129-5p,hsa-miR-362-5p,LINC00707 and SLC16A1-AS1 of U251 cells were consistent with the sequencing results,and the gene expression of U87 cells was basically consistent with the sequencing re-sults.Conclusions Melatonin affects cancer-related signaling pathways through the differential expression of ncRNA so as to inhibit the proliferation of U251 cells;the ceRNA network composed of LINC00707,SLC16A1-AS1,hsa-miR-129-5p and hsa-miR-362-5p may take a part in the molecular mechanism of melato-nin in inhibiting neuroglioma cell proliferation.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Aim To detect the non-coding RNA(ncRNA)expression profile of neuroglioma cells via whole transcriptome sequencing,establish the ceRNA network and reveal the molecular mechanism of ncRNA participating in the inhibition of neuroglioma cell prolif-eration by melatonin.Methods Neuroglioma cells were intervened with by 0,2,4,6 and 8 mmol·L-1 melatonin for 24,48 and 72 h,and the inhibitory effect of melatonin on cell proliferation was detected via CCK-8;after the intervention of 0 and 4 mmol·L-1 melatonin to U251 cells for 24 h,differentially ex-pressed miRNA(DEmiRNA),lncRNA(DElncRNA)and mRNA(DEmRNA)were detected through whole transcriptome sequencing,along with GO and KEGG enrichment analysis of DEmRNA;the ceRNA network was constructed,and the key gene expression of ceR-NA was verified through qRT-PCR.Results Melato-nin exerts a time-dose-dependent inhibitory effect on the proliferation of neuroglioma cells;a total of 5049 DEmRNA,635 DElncRNA and 146 DEmiRNA in 0 and 4 mmol·L-1 melatonin groups were screened out via whole transcriptome sequencing;DEmRNAs were mainly enriched in cancer-related signaling pathways,such as ferroptosis,mTOR signaling pathway,FoxO signaling pathway and cell cycle;the ceRNA network included 4 lncRNAs,3 miRNAs and 48 mRNAs.As verified through real-time PCR,the expressions of hsa-miR-129-5p,hsa-miR-362-5p,LINC00707 and SLC16A1-AS1 of U251 cells were consistent with the sequencing results,and the gene expression of U87 cells was basically consistent with the sequencing re-sults.Conclusions Melatonin affects cancer-related signaling pathways through the differential expression of ncRNA so as to inhibit the proliferation of U251 cells;the ceRNA network composed of LINC00707,SLC16A1-AS1,hsa-miR-129-5p and hsa-miR-362-5p may take a part in the molecular mechanism of melato-nin in inhibiting neuroglioma cell proliferation.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective:To investigate the role of vitamin E succinate (VES) in inducing autophagy of human gastric cancer cells by activating calcium redistribution through inositol 1, 4, 5-trisphosphate receptors (IP 3R) pathway. Methods:Human gastric cancer lines MKN28 (moderately differentiated) and MKN45 (poorly differentiated) cells were cultured in vitro in March 2022. Gastric cancer cells were treated with VES at different doses for 24 h, and cell viability was measured by CCK-8 method to determine VES dose for subsequent study. The experiment was set up with solvent control group (0.1% ethanol), VES dose groups, 100 nmol/L rapamycin (RAPA) as autophagy positive control group (RAPA group), 15 μg/ml tunicamycin (TM) was used as the endoplasmic reticulum stress (ERS) positive control group (TM group), 10 μmol/ml 2-aminoethyl diphenylborinate (2-APB group) was used to inhibit IP 3R (2-APB group) and VES+2-APB group. The occurrence of autophagosomes in gastric cancer cells was observed by transmission electron microscopy, and microtubule associated protein 1 light chain 3 (LC3), Beclin1, IP 3R, glucose-regulated protein 75 (Grp75), voltage-dependent anion channel 1 (VDAC1) protein expression was detected by western blotting. Fluo-4 AM was used to label intracellular calcium ions, Rhod-2 AM was used to label mitochondrial calcium ions, and the fluorescence intensity of calcium ions was observed by fluorescence microscope. One-way analysis of variance was used to compare the means among multiple groups, and LSD- t method was used for pairwise comparison. Results:CCK-8 results showed that compared with solvent control group, the proliferation rates of MKN28 cells in 10-100 μg/ml VES group and MKN45 cells in 20-100 μg/ml VES group were significantly decreased ( P<0.05). Subsequent VES dosages were determined according to the growth curve, MKN28 was 5, 10, 20, 40 μg/ml, and MKN45 was 10, 20, 40, 80 μg/ml. The results of transmission electron microscopy and fluorescence showed that autophagosomes were formed in MKN28 cells in 5 and 20 μg/ml VES groups and MKN45 cells in 10 and 40 μg/ml VES groups, and the fluorescence intensity of calcium ions in cytoplasm and mitochondria was significantly higher than that in solvent control group ( P<0.05). Compared with solvent control group, LC3, Beclin1, IP 3R, Grp75 and VDAC1 protein expressions of MKN28 cells in 20 and 40 μg/ml VES groups and MKN45 cells in 40 and 80 μg/ml VES groups were significantly increased ( P<0.05). After inhibiting IP 3R with 2-APB, the expression levels of IP 3R, Grp75 and VDAC1 in two kinds of gastric cancer cells in VES+2-APB group were significantly decreased compared with VES group ( P<0.05). The fluorescence results showed that the fluorescence intensity of cytoplasmic and mitochondrial calcium ions in VES+2-APB groups was significantly lower than that in VES group ( P<0.05). Compared with VES group, LC3 and Beclin1 protein expressions in two kinds of gastric cancer cells in VES+2-APB groups were significantly decreased ( P<0.05) . Conclusion:VES may activate intracellular calcium redistribution through IP 3R-Grp75-VDAC1 calcium channel and induce autophagy in gastric cancer cells.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective To analyze the peripheral neurotoxicity of utidelone(UTD-1)in patients with human epidermal growth factor receptor 2(HER-2)negative advanced breast cancer and its related factors.Methods The patients with HER-2 negative advanced breast cancer treated by UTD-1 were collected.The patients were divided into control group(low neurotoxicity group,grade 0-1 peripheral neurotoxicity)and treatment group(high neurotoxicity group,grade 2-4 peripheral neurotoxicity)according to cohort method.The data involve age,body mass index(BMI),related indicators of metabolic syndrome(MS)before chemotherapy,hormone receptor expression status of tumor,number of treatment lines,and whether combined with capecitabine were collected.The highest level of neurotoxicity after UTD-1 was collected for each patient,and the possible related factors were analyzed.Results There were 83 cases in the treatment group and 84 cases in the control group.The BMI of treatment and control groups were(24.81±1.93)and(22.82±2.19)kg·m-2,the fasting plasma glucose(FPG)levels were(6.45±1.37)and(5.42±0.79)mmol·L-1,the C-reaction protein(CRP)levels were 11.10 and 1.60 mg·L-1,respectively,and the differences were statistically significant(allP＜0.01).Multi-factor Logistics stepwise regression analysis showed that the high neurotoxicity group was independently correlated with high BMI,high FPG and high CRP(odds ratios were 11.51,7.78 and 6.88).Conclusion BMI,CRP and FPG may be independent risk factors for high peripheral neurotoxicity iduced by UTD-1.