Extended endoscopic endonasal approach for resecting anterior intrinsic third ventricular craniopharyngioma.

Background: The surgical treatment of the extended endoscopic endonasal approach (EEEA) is a safe and effective treatment for suprasellar craniopharyngiomas. However, due to damage to the hypothalamus and third ventricle floor (TVF), EEEA is generally regarded as unsuitable in treating intrinsic third ventricle craniopharyngioma (ITVC) that is entirely within the third ventricle. Until now, there have been only a small number of reports using EEEA to treat TVC via a supra-infrachiasmatic approach. Given that the translamina terminalis (TLT) corridor was used in the transcranial subfrontal approach, EEEA via a suprachiasmatic approach may be feasible and practical to treat ITVC. In the current study, we accumulated experience applying the suprachiasmatic translamina terminalis (STLT) corridor for anterior treatment of ITVC. Methods: From March 2016 to December 2020, 14 patients with ITVC in our center were analyzed retrospectively. All patients underwent surgery by EEEA via an STLT corridor. The multilayer reconstruction technique was adopted to achieve skull base reconstruction. Data concerning the patient's tumor resection, vision, hypophyseal hormone, and complications were collected. Results: Gross-total resection was achieved in 13 (92.8%) of14 patients, with achievement of near-total (90%) resection in the remaining 1 patient. Nine cases (64.3%) were papillary craniopharyngiomas, and the other 5 cases were adamantinomatous subtypes. Postoperatively, 3 patients with pituitary insufficiency received hormone replacement therapy. No permanent diabetes insipidus or hypothalamic obesity was found. All pairs showed significant improvement or stability in vision except 1 patient who encountered visual deterioration. No other neurological deficit occurred postoperatively. Observation results for the exudation of nasal tissue and the length of hospitalization were satisfactory. After a mean follow-up period of 26.2 months, tumor recurrence was not observed. Conclusion: TLT is a minimally invasive corridor used in EEEA for treating anterior ITVC without increasing risks of visual and hormonal deficits. The multilayered reconstruction technique we used is a safe and effective method for achieving watertight closure and avoiding cerebrospinal fluid leaks and infection. The endonasal approach via STLT provides a new, safe and efficacious operative strategy that should be considered a surgical alternative in treating ITVC.

Transgenerational inheritance of promoter methylation changes in extrauterine growth restriction-induced pulmonary arterial pressure disorders.

BACKGROUND: This study aimed to investigate the influence of extrauterine growth restriction (EUGR) on pulmonary arterial pressure (PAP) and the transgenerational inheritance of promoter methylation changes in pulmonary vascular endothelial cells (PVECs) of 2 consecutive generations under EUGR stress. METHODS: After modeling, PAP values of F1 and F2 pups were investigated at 9-week-old. The methyl-DNA immune precipitation chip was used to analyze DNA methylation profiling. Differential enrichment peaks (DEPs) and regions of interest (ROIs) were identified, based on which Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and reactome pathway enrichments were analyzed. RESULTS: The F1 male rats in the EUGR group had significantly increased PAP levels compared to the control group; however, this increase was not observed in female rats. Interestingly, in F2 female rats, the EUGR group had decreased PAP. In the X chromosome of the F1 males, there were 16 differential ROI genes in the F1 generation, while in F2 females, there were 86 differential ROI genes. Similarly, there were 105 DEPs in the F1 generation and 38 DEPs in the F2 generation. In combination with the 5 common ROIs and 14 common DEPs, 18 genes were regarded as the key candidate genes associated with hereditable PAP variation in the EUGR model. Enrichment analysis showed that synaptic and neurotransmitter relative pathways might be involved in the process of EUGR-induced PAH development. Among common DEPs, Smad1 and Serpine1 were also found in 102 PAH-associated genes in the MalaCards database. CONCLUSIONS: Together, there is a transgenerational inheritance of promoter methylation changes in the X chromosome in EUGR-induced PAP disorders, which involves the participation of synaptic and neurotransmitter relative pathways. Also, attenuated methylation of Smad1 and Serpine1 in the promoter region may be a partial driver of PAH in later life.

Efficacy comparison of high-frequency oscillatory ventilation with continuous nasal positive airway pressure in neonatal respiratory distress syndrome treatment.

OBJECTIVES: To compare the treatment efficacy of high-frequency oscillatory ventilation (HFOV) with nasal continuous positive airway pressure (NCPAP) in the treatment of neonatal respiratory distress syndrome (NRDS) and its effect on the expression of high-mobility group protein B1 (HMGB1). METHODS: A total of 180 infants with NRDS admitted to our hospital were included and randomly assigned into the HFOV group (receiving conventional therapy and HFOV), the NCPAP group (receiving conventional therapy and NCPAP), and the conventional group (receiving conventional therapy). Qi and blood indicators, heart rate, respiratory frequency, PCO2, and PaO2 were observed and recorded before and after treatment, together with complications after treatment. ELISA was performed for HMGB1 Results: A distinctly lower partial pressure of carbon dioxide (PCO2) but higher arterial partial pressure of oxygen (PaO2) was observed in the HFOV and NCPAP groups than in the conventional group (P < 0.05), whereas infants in the HFOV group exhibited slight differences in these two indicators from their counterparts in the NCPAP group (P > 0.05). The serum HMGB1 levels in both groups were significantly higher than those in the conventional group (P < 0.05). DISCUSSION: Both HFOV and NCPAP are feasible in the treatment of NRDS and may play a role in the inhibition of HMGB1.

Circular RNA-HIPK3 regulates human pulmonary artery endothelial cells function and vessel growth by regulating microRNA-328-3p/STAT3 axis.

The proliferation and migration of pulmonary artery endothelial cells are the pathological basis of pulmonary vascular remodeling with pulmonary hypertension. Recent studies have shown that circular RNA (circRNA) regulates biological processes in various vascular diseases, including pulmonary arterial hypertension. It has been reported that circRNA regulates the vascular endothelial cells' function. Therefore, circRNA may have crucial roles in human pulmonary artery endothelial cells (hPAECs) proliferation, migration, and tube formation in pulmonary arterial hypertension. In this study, we aimed to discover the role and mechanism of circular RNA HIPK3 (circHIPK3) in the proliferation and migration of pulmonary hypertension hPAECs. First, we used platelet-derived growth factor-stimulated hPAECs as a cellular model of pulmonary arterial hypertension. The results showed that platelet-derived growth factor promoted hPAECs proliferation, migration, and tube formation. Notably, platelet-derived growth factor upregulated the expression of circHIPK3 in hPAECs and regulated their proliferation, migration, and angiogenesis. Mechanistically, we confirmed miR-328-3p was copiously pulled down by circHIPK3 in hPAECs. Luciferase reporter and RNA immunoprecipitation assays further indicated the cytoplasmic interactions between circHIPK3 and miR-328-3p. Subsequently, we found that circHIPK3 might increase the expression of STAT3 by sponging miR-328-3p. Collectively, our results demonstrated that the circHIPK3-miR-328-3p-STAT3 axis contributed to the pathogenesis of pulmonary arterial hypertension by stimulating hPAECs proliferation, migration, and angiogenesis. The circHIPK3 has an accelerated role in pulmonary arterial hypertension development, implicating the potential values of circHIPK3 in pulmonary arterial hypertension therapy.

Exosomal miR-22-3p from human umbilical cord blood-derived mesenchymal stem cells protects against lipopolysaccharid-induced acute lung injury.

BACKGROUND: Mesenchymal stem cells (MSCs) are widely applied in various clinical disorders, including acute lung injury (ALI). We aimed to investigate the effects of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs)-derived exosomal microRNA-22-3p (miR-22-3p) on lipopolysaccharid (LPS)-induced ALI via regulating frizzled class receptor 6 (FZD6). METHODS: Rat lung cells were selected to construct the LPS-induced ALI cell model. The LPS-treated cells were transfected with restored miR-22-3p and depleted FZD6 for investigating their roles in ALI. Human UCB-MSCs were cultured and exosomes were extracted. Rat lung cells were co-cultured with exosomes that had been transfected with restored miR-22-3p and upregulated FZD6 to detect their roles in inflammatory reaction, oxidative stress, cell proliferation activity and apoptosis. The ALI rat model was established through LPS inhalation and the rats were respectively treated. Then, the pathology, apoptosis and expression of the NF-κB signaling pathway-related factors in rat lung tissues were determined. RESULTS: miR-22-3p expression was reduced and FZD6 expression was enhanced in LPS-treated rat lung cells while exosomes raised miR-22-3p expression and decreased FZD6 expression. In LPS-treated cells, up-regulating miR-22-3p or depleting FZD6 reduced inflammatory reaction and oxidative stress response, raised rat lung cell proliferation activity and inhibited cell apoptosis rate. In the in vivo ALI model, exosomes suppressed pathological changes, apoptosis and NF-κB expression in LPS-treated rats. Upregulated miR-22-3p further attenuated ALI. CONCLUSION: Our study highlights the potential of UCB-MSC-exosomal miR-22-3p in preventing ALI. This study may provide further insights into ALI therapy.

Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

Expression and clinical significance of CXC chemokines in the glioblastoma microenvironment.

BACKGROUND: Glioblastoma (GBM) is the most common subtype of brain cancer, encompassing 16% of all primary brain cancers. The prognosis of GBM is poor, with a 5-year-survial of approximately 5%. Increasing evidence has revealed that chemokines in the tumor microenvironment (TME) are often altered, thus affecting tumor proliferation and metastasis. METHOD: Multi-omics and bioinformatics tools were utilized to clarify the role of CXC chemokine in GBM. RESULT: Most CXC chemokines were found to be differentially regulated in GBM, which correlated with patient prognosis. CXC chemokines were found to activate cancer-related signaling pathways, thus affecting immune infiltration. Interestingly, this was found to be associated with drug resistance. Most CXC chemokines were significantly correlated with abundance of B cells, CD8+ cells and dendritic cells. Furthermore, somatic copy number alterations of CXC chemokines can inhibit dendritic cell infiltration. Moreover, CXCL1 was selected as a hub gene, and several kinase, miRNA and transcription factor targets of CXCL1 were identified. CONCLUSION: our study provides novel insights into CXC chemokine expression and their role in the GBM microenvironment. These results are able to provide more data about prognostic biomarkers and therapeutic targets of GBM.

[Epidemiological study on group infection of Angiostrongylus cantonensis in Changle City].

OBJECTIVE: To make etiological and epidemiological investigation on the infection of Angiostrongylus cantonensis in 8 pupils in Changle City. METHODS: 1. CSF of patients was examined with the conventional method to detect pathogens and eosinophiles. 2. The fecal samples of wild rodents were collected from the spot and examined microscopically to discover the first stage larvae of A. cantonensis. 3. Snails (Pila gigas) were collected in the spot. The smashed head tissue was examined for the third stage larvae of A. cantonensis. 4. The patient's clinical symptoms and physical signs were recorded with an emphasis on central nervous system. RESULTS: 1. Two larvae of the third stage of A. cantonensis were found in CSF of one patient. Eosinophiles occupied 68% of the cell number in average (ranged from 47% to 83%) in CSF of the 8 patients. 2. The infection rate of the first stage larvae of A. cantonensis was 39.3% (44/112) in feces of the rodents. 3. The infection rate of the third stage larvae of A. cantonensis was 40.0% (82/205) in the snails. 4. Major clinical manifestations in the 8 patients included: severe headache(8/8), dizziness(8/8), nausea(8/8), vomiting(8/8), lethargy(7/8), lower limb hypodynamia(7/8). CONCLUSION: The confirmation of severe infection of A. cantonensis in 8 child patients demonstrated that a natural nidus of angiostrongyliasis is present in Chengle City.