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ObjectiveTo study whether Chaihu Longgu Mulitang can inhibit hypothalamic inflammation， mitigate anxiety-like behavior， and alleviate anxiety symptoms by regulating the p38 mitogen-activated protein kinase/nuclear factor-κB （p38 MAPK/NF-κB） signaling pathway in the rat model of generalized anxiety disorder （GAD）. MethodTwelve out of 74 Wistar rats were randomly selected as the blank group， and the remaining rats were subjected to chronic restraint stress for the modeling of GAD. The open field test （OFT） and elevated Porteus maze test （PMT） were conducted 14 days after modeling to detect the anxiety-like behaviors. Sixty successfully modeled rats were selected and randomized into model， low-， medium-， and high-dose （6， 12， and 24 g·kg-1， respectively） Chaihu Longgu Mulitang， and diazepam （1 mg·kg-1） groups （n=12） and administrated with corresponding drugs for 14 consecutive days. OFT and PMT were then carried out to examine the anxiety-like behaviors of the rats. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） in the hypothalamus and serum of rats were determined by the enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）was conducted to determine the mRNA levels of p38 MAPK， NF-κB p65， nuclear factor κB inhibitor α （IκBα）， and ionized calcium binding adaptor molecule 1 （Iba-1）. The protein levels of p38 MAPK， phosphorylated （p）-p38 MAPK， NF-κB p65， p-NF-κB p65， and IκBα in the hypothalamus of rats were determined by Western blot. The expression of Iba-1 in the hypothalamic microglia was detected by immunofluorescence assay. ResultCompared with the blank group， the model group had decreased body weight， scattered dark yellow fur， increased irritability， and preference to hibernation in the corner. In addition， the modeled rats showed increased edge movement distance and time in OFT （P<0.01） and decreased movement distance and time and the number of entries in the open arm in PMT （P<0.01）. The modeling increased the fluorescence intensity of Iba-1 in paraventricular nucleus of hypothalamus （P<0.01）， elevated the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamus （P<0.01）， up-regulated the protein and mRNA levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and down-regulated the protein and mRNA levels of IκBα （P<0.01） in the hypothalamus. Compared with the model group， medium- and high-dose Chaihu Longgu Mulitang and diazepam increased the body weight， improved the fur and behaviors， decreased the edge movement distance and time in OFT （P<0.05， P<0.01）， and increased the movement distance and time in the open arm in PMT （P<0.05， P<0.01）. Furthermore， they decreased the fluorescence intensity of Iba-1 in hypothalamic microglia （P<0.05， P<0.01）， lowered the levels of IL-1β， IL-6， and TNF-α in the serum and hypothalamic tissue （P<0.05， P<0.01）， down-regulated the mRNA and protein levels of p38 MAPK， NF-κB p65， p-p38 MAPK， p-NF-κB p65， and Iba-1 （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of IκBα （P<0.05， P<0.01） in the hypothalamus. ConclusionChaihu Longgu Mulitang can mitigate anxiety-like behaviors and relieve anxiety in GAD rats by inhibiting the p38 MAPK/NF-κB signaling pathway and reducing the activation of microglia and the levels of pro-inflammatory cytokines in the hypothalamus.
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Objective: This study investigates the extent of resection, duration of surgery, intraoperative blood loss, and postoperative complications in patients with high-grade glioma who received surgery with or without sodium fluorescein guidance. Methods: A single-center retrospective cohort study was conducted on 112 patients who visited our department and underwent surgery between July 2017 and June 2022, with 61 in the fluorescein group and 51 in the non-fluorescein group. Baseline characteristics, intraoperative blood loss, surgery duration, resection extent, and postoperative complications were documented. Results: The duration of surgery was significantly shorter in the fluorescein group than in the non-fluorescein group (P = 0.022), especially in patients with tumors in the occipital lobes (P = 0.013). More critically, the gross total resection (GTR) rate was significantly higher in the fluorescein group than in the non-fluorescein group (45.9% vs. 19.6%, P = 0.003). The postoperative residual tumor volume (PRTV) was also significantly lower in the fluorescein group than in the non-fluorescein group (0.40 [0.12-7.11] cm3 vs. 4.76 [0.44-11.00] cm3, P = 0.020). Particularly in patients with tumors located in the temporal and occipital lobes (temporal, GTR 47.1% vs. 8.3%, P = 0.026; PRTV 0.23 [0.12-8.97] cm3 vs. 8.35 [4.05-20.59] cm3, P = 0.027; occipital, GTR 75.0% vs. 0.0%, P = 0.005; PRTV 0.15 [0.13-1.50] cm3 vs. 6.58 [3.70-18.79] cm3, P = 0.005). However, the two groups had no significant difference in intraoperative blood loss (P = 0.407) or postoperative complications (P = 0.481). Conclusions: Fluorescein-guided resection of high-grade gliomas using a special operating microscope is a feasible, safe, and convenient technique that significantly improves GTR rates and reduces postoperative residual tumor volume when compared to conventional white light surgery without fluorescein guidance. This technique is particularly advantageous for patients with tumors located in non-verbal, sensory, motor, and cognitive areas such as the temporal and occipital lobes, and does not increase the incidence of postoperative complications.
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Objective To explore the relationship of changes in bone mineral density and bone me-tabolism indicators with osteoporosis in elderly patients with hemiplegia after cerebral infarction.Methods A total of 197 elderly patients suffering post-stroke hemiplegia admitted to our hospital were enrolled between February 2018 and February 2021.Their bone mineral density and bone metabolism indicators were analyzed based on gender,disease course and hemiplegia severity.According to disease severity,they were divided into mild group(112 cases),moderate group(62 cases)and severe group(32 cases).Results Among the 197 elderly patients,83(42.13％)had osteoporosis.The males had significantly higher bone mineral density of proximal femur and levels of bone alkaline phosphatase(BALP)and osteocalcin,and lower levels of serum type Ⅰ collagen(CICP)and C-terminal telopeptides of type Ⅰ collagen(CTXI)than the females(P＜0.01,P＜0.05).Compared with the patients with hemiplegia course for 3-6 months,bone mineral density values of greater trochanter and total hip,and levels of BALP and osteocalcin were obviously de-creased,while levels of CICP and CTXI were notably increased in those with the course of 7-12 months and 13-24 months(P＜0.05).Compared with the mild group,bone mineral density val-ues of greater trochanter and total hip,and levels of BALP and osteocalcin were significantly de-creased,while levels of CICP and CTXI were significantly increased in moderate group and severe group(P＜0.05).Compared with the moderate group,bone mineral density values of greater tro-chanter,intertrochanteric site and total hip were significantly decreased in the severe group(P＜0.05).The bone mineral density of above parts was negatively correlated with CICP levels(r=-0.458,r=-0.403,r=-0.355,r=-0.482,P＜0.01)and CTXI levels(r=-0.305,r=-0.291,r=-0.273,r=-0.384,P＜0.05,P＜0.01),while positively correlated with BGP level(r=0.476,r=0.428,r=0.386,r=0.518,P＜0.01).Conclusion The incidence of osteoporosis is quite higher in the elderly patients with post-stroke hemiplegia.There exist bone mineral density decline and abnormal bone metabolism,and their changes are related to gender,course and severi-ty of hemiplegia.
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Objective:To observe the regulatory effect of p38 mitogen-activated protein kinase (p38 MAPK) on aquaporin 4 (AQP4) in rats after hydrocephalus, and to explore its significance in hydrocephalus prevention.Methods:Fifty SD rats were randomly divided into sham-operated group ( n=10), hydrocephalus group ( n=20), and hydrocephalus+inhibitor (SB203580) group (SB group, n=20). The rat models of hydrocephalus in the latter two groups were prepared by intracerebroventricular injection of kaolin suspension; rats in the sham-operated group were injected with same amount of normal saline into the lateral ventricle. The p38 MAPK specific inhibitor SB203580 (10 mg/kg) was intraperitoneally injected into the rats of SB group on the 8 th d of modeling for 7 consecutive d; same volume of dimethylsulfoxide was given to the rats of hydrocephalus group on the 8 th d of modeling for 7 consecutive d; rats in the sham-operated group did not give any treatment. The severity of hydrocephalus in these rats was observed by MRI. The inflammatory factor tumor necrosis factor (TNF)-α level in the cerebrospinal fluid was detected by enzyme-linked immunosorbent assay (ELISA). The AQP4 and TNF-α mRNA expressions were detected by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The phosphorylated p38 MAPK and AQP4 expressions in the periventricular brain tissues were detected by Western blotting and immunohistochemistry. Results:No hydrocephalus developed in sham-operated group and hydrocephalus developed in the latter two groups. As compared with sham-operated group, hydrocephalus group and SB group had significantly increased lateral ventricle volume, significantly aggravated periventricular edema, significantly higher EVAN's index, and statistically increased brain water content ( P<0.05). Two weeks after modeling, the TNF-α expression levels in cerebrospinal fluid of sham-operated group, hydrocephalus group and SB group were (20.49±0.96), (42.04±3.17), and (28.00±3.71) pg/mL, respectively, with significant differences ( F=186.000, P<0.001); the TNF-α expression level in SB group was significantly higher than that in sham-operated group and significantly lower than that in hydrocephalus group ( P<0.05). Two weeks after modeling, the TNF-α and AQP4 mRNA expression levels in brain tissues of the three groups were significantly different ( P<0.05); the TNF-α and AQP4 mRNA expression levels in hydrocephalus group were significantly higher than those in sham-operated group and SB group ( P<0.05). Correlation analysis showed that there was a positive linear correlation between AQP4 mRNA expression and TNF-α mRNA expression in hydrocephalus group ( r=0.511, P=0.026), and there was a positive linear correlation between AQP4 protein expression and phosphorylated p38 MAPK protein expression in hydrocephalus group and SB group ( r=0.560, P=0.013; r=0.463, P=0.030). Immunohistochemical staining results showed that AQP4 expression was abundant in glial cells of the three groups; the p38 MAPK distribution was uniform and non-polar; the phosphorylated p38 MAPK protein expression in the hydrocephalus group was significantly higher than that in the sham-operated group, and that in the SB group returned to the level of the sham-operated group. Conclusion:The p38 MAPK pathway is involved in the positive regulation of AQP4 expression, which could be inhibited by SB203580.
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Objective:To explore the differentially expressed genes in glioblastoma development and their functions and roles as to identify the target genes influencing biological behaviors of glioblastoma.Methods:Original gene expression profiles of GSE70231 dataset obtained from Gene Expression Omnibus database were screened for differentially expressed genes by GEO2R software. DAVID database was used to conduct gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for these differentially expressed genes. STRING database was used to construct protein-protein interaction (PPI) network of these differentially expressed genes; target genes were selected from PPI network by cytoHubba and MCODE plug-ins; GEPIA online was used to analyze the expressions of target genes in glioblastoma and their influences in overall survival of glioblastoma patients (sample data collecting from The Cancer Genome Atlas database). Finally, the selected target genes were verified using RNA-seq dataset GSE50021 from human tissues.Results:Totally, 520 differentially expressed genes were identified, including 305 up-regulated genes and 215 down-regulated ones. GO analysis showed that the differentially expressed genes were mainly enriched in biological processes (signal transduction, cell adhesion, and positive regulation of cell proliferation), cytological components (extracellular exosomes, cytoplasm, and cytoplasmic membrane), and molecular function (protein binding). KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in mitogen activated protein kinase signal pathway, proteoglycans in cancer, oxytocin signal pathway and calcium signal pathway. Totally, 17 target genes were selected by MCODE and cytoHubba plug-ins from the PPI network of differentially expressed genes; functional analysis and clinical sample verification showed 8 target genes ( VCAM1, SPP1, ITGB1, CTGF, VIM, ITGAV, COL1A1, and BCL2A1) could affect the biological behaviors of glioblastoma; the correlations of ITGAV, COL1A1, and BCL2A1 with glioma had been rarely reported, and GSE50021 dataset verified that their expressions in glioblastoma tissues were significantly higher than those in normal brain tissues ( P<0.05). Conclusion:These 8 target genes concluded from this research, especially BCL2A1, COL1A1 and ITGAV, may be important targets for exploring the pathogenesis, diagnosis and treatment of glioblastoma in the future.
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Objective:To explore the application value of individualized three-dimensional (3D) printing positioning guides in localization and resection of intracranial lesions.Methods:Fifteen patients with intracranial space occupying lesions underwent resection in our hospital from March 2021 to May 2021 were selected in our study. Brain images by CT and MRI as raw data were used to design individual positioning guides. The positioning guides were placed on the patient's skin before resection to mark the location and boundary of the lesions with a marker, and neuro-navigation was used to verify the accuracy. During the resection, the location of the lesions was identified through microscope by the surgeons. Postoperative CT and MRI were used to evaluate the lesion resection.Results:The individualized positioning guides of 15 patients fit the skin well, and the skin incision and bone window were designed to meet the surgical requirements. All surgeries were completed in one time, and the lesion tissues were successfully removed. During the surgeries, the skin incision was not adjusted for secondary expansion. Brain MRI reexamination within 48 h of surgery showed that the lesions of 11 patients with tumors were removed satisfactorily (total resection in 9 and subtotal resection in 2); brain CT reexamination within 12 h showed that the clearance rate of hematomas in 3 patients was above 80% and that in 1 patient was 70%. No patients had cerebrospinal fluid leakage, intracranial hematoma, intracranial infection or other serious complications. All patients recovered well during the 1-3 months of outpatient/telephone follow-up.Conclusion:The positioning method with personalized 3D printing guides is simple and convenient, enjoying accurate positioning results, which can assist the clinicians to optimize the preoperative planning, optimize the surgical incision design, and is worthy of promotion and application in primary hospitals.
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Objective To discuss the techniques and methods of surgery for brain gliomas located in eloquent areas at awake anesthesia. Methods Nineteen patients with brain gliomas in eloquent areas, admitted to our hospital from December 2014 to May 2017, were operated under awake anesthesia with neuronavigation and intraoperative ultrasonography for locating the lesions and intraoperative direct electrical stimulation for functional mapping of the eloquent areas. All patients were followed up from 3 to 18 months; the surgical efficacies were analyzed. Results Of 19 patients, 18 (94.74％) were achieved awake and alert during brain mapping and resection of the tumors;17 (89.47％) were detected the motor areas by intraoperative direct electrical stimulation, 6 (31.58％) were detected the sensory cortex and 12 (63.16％) were detected language related cortex. Of 19 patients, MR imaging 2-3 months after surgery indicated that 5 (26.32％) received total resection of lesions, 9 (47.37％) subtotal resection of lesions and 5 (26.32％) partial resection of lesions. Seven patients (36.84％) had transitory postoperative aphasia, 4 (21.05％) were with transitory postoperative dyskinesia and one (5.26％) with permanent dyskinesia. Conclusion Comprehensive applications of awake anesthesia, neuronavigation, intraoperative ultrasonography and intraoperative direct electrical stimulation technologies allow maximum safe resection of gliomas in eloquent areas and protection of brain function.