Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

A CT-based integrated model for preoperative prediction of occult lymph node metastasis in early tongue cancer.

Background: Occult lymph node metastasis (OLNM) is an essential prognostic factor for early-stage tongue cancer (cT1-2N0M0) and a determinant of treatment decisions. Therefore, accurate prediction of OLNM can significantly impact the clinical management and outcomes of patients with tongue cancer. The aim of this study was to develop and validate a multiomics-based model to predict OLNM in patients with early-stage tongue cancer. Methods: The data of 125 patients diagnosed with early-stage tongue cancer (cT1-2N0M0) who underwent primary surgical treatment and elective neck dissection were retrospectively analyzed. A total of 100 patients were randomly assigned to the training set and 25 to the test set. The preoperative contrast-enhanced computed tomography (CT) and clinical data on these patients were collected. Radiomics features were extracted from the primary tumor as the region of interest (ROI) on CT images, and correlation analysis and the least absolute shrinkage and selection operator (LASSO) method were used to identify the most relevant features. A support vector machine (SVM) classifier was constructed and compared with other machine learning algorithms. With the same method, a clinical model was built and the peri-tumoral and intra-tumoral images were selected as the input for the deep learning model. The stacking ensemble technique was used to combine the multiple models. The predictive performance of the integrated model was evaluated for accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC-ROC), and compared with expert assessment. Internal validation was performed using a stratified five-fold cross-validation approach. Results: Of the 125 patients, 41 (32.8%) showed OLNM on postoperative pathological examination. The integrated model achieved higher predictive performance compared with the individual models, with an accuracy of 84%, a sensitivity of 100%, a specificity of 76.5%, and an AUC-ROC of 0.949 (95% CI [0.870-1.000]). In addition, the performance of the integrated model surpassed that of younger doctors and was comparable to the evaluation of experienced doctors. Conclusions: The multiomics-based model can accurately predict OLNM in patients with early-stage tongue cancer, and may serve as a valuable decision-making tool to determine the appropriate treatment and avoid unnecessary neck surgery in patients without OLNM.

A novel simple laser guidance puncture system for intracerebral hematoma.

OBJECTIVE: Accurate localization and real-time guidance technologies for cerebral hematomas are essential for minimally invasive procedures, including minimally invasive hematoma puncture and drainage, as well as neuroendoscopic-assisted hematoma removal. This study aims to evaluate the precision and safety of a self-developed laser-guided device in localizing and guiding hematoma punctures in minimally invasive surgery for intracerebral hemorrhage (ICH). METHODS: We present the components of the device and its operational procedures. Subsequently, surgeons with different titles conduct hematoma puncture experiments using the device on skull models, comparing it to freehand puncture methods and recording the offset distance from the puncture needle tip to the hematoma center. Additionally, we report the application of this device in 10 patients with ICH, assessing its accuracy and safety in comparison with a neuro-navigation system. RESULTS: In simulated puncture experiments, the accuracy of the laser-guided group surpasses that of the freehand puncture group, with a significant statistical difference observed between the two groups (P < 0.05). In the laser-guided group, there is no statistically significant difference in puncture accuracy among the surgeons (P > 0.05). In clinical experiments, no relevant surgical complications were observed. The offset distance for the laser-guided group was 0.61 ± 0.18 cm, while the neuro-navigation group was 0.48 ± 0.13 cm. There was no statistically significant difference between the two groups in terms of offset distance (P > 0.05). However, there was a significant difference in surgical duration (P < 0.05), with the former being 35.0 ± 10.5 minutes and the latter being 63.8 ± 10.5 minutes. CONCLUSION: The current study describes satisfactory results from both simulated experiments and clinical applications, achieved through the use of a novel laser-guided hematoma puncture device. Furthermore, owing to its portability, affordability, and simplicity, it holds significant importance in advancing surgical interventions for ICH, especially in underdeveloped regions.

Multimodal image fusion-assisted endoscopic evacuation of spontaneous intracerebral hemorrhage.

PURPOSE: Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods. METHODS: This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Non-normally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher's exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. RESULTS: A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time (p < 0.001), less blood loss (p < 0.001), better hematoma evacuation (p = 0.003), and a shorter stay in the intensive care unit (p = 0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group (p = 0.014). CONCLUSIONS: Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

Application Research of Visible Near-Infrared Spectroscopy Technology for Detecting Intracerebral Hematoma.

OBJECTIVE: To explore the visible near-infrared spectroscopic (VNIRS) characteristics of intracerebral hematoma, and provide experimental basis for hematoma localization and residual detection in hypertensive intracerebral hemorrhage (HICH) surgery. METHODS: Using VNIRS, spectral data of cerebral hematoma and cortex were collected during HICH craniotomy, and characteristic spectra were matched with paired-sample T-test. A partial least squares (PLS) quantitative model for cerebral hematoma spectra was established. RESULTS: The reflectance of cerebral hematoma spectra in the 500-800 nm band was lower than that of the cortex, and there were statistically significant differences in the 510, 565, and 630 nm bands (P < 0.05). The calibration correlation coefficient of the PLS quantitative model for cerebral hematoma spectra was R2 = 0.988, the cross-validation correlation coefficient was R2cv = 0.982, the root mean square error of calibration was RMSEC = 0.101, the root mean square error of cross-validation was RMSEV = 0.122, the external validation correlation coefficient was CORRELATION = 0.902, and the root mean square error of prediction was RMSEP = 0.426, indicating that the model had high fitting degree and good predictive ability. CONCLUSIONS: VNIRS as a noninvasive, real-time and portable analysis technology, can be used for real-time detection of hematoma during HICH surgery, and provide reliable basis for hematoma localization and residual detection.

Endoscope-Assisted Resection of Benign Parotid Tumors via Concealed Post-Auricular Sulcus Incision.

OBJECTIVES: To investigate the feasibility, safety, and effectiveness of endoscopic-assisted resection of benign parotid tumors via concealed post-auricular sulcus incision. METHODS: Between October 2019 and March 2021, eligible patients with diagnosed benign parotid tumors were prospectively included and randomly assigned to two groups: the endoscope-assisted post-auricular sulcus incision group (endoscope group) and the conventional Blair "S" incision group (conventional group). RESULTS: A total of 45 patients were finally included, including 24 subjects in the endoscope group and 21 subjects in the conventional group. No obvious differences were observed in basic information between these two groups of patients. The surgical incision length in endoscope group patients was 4.0 ± 0.4 cm, which was significantly shorter than that in conventional group patients, 10.3 ± 1.6 cm (p < 0.001). The total intraoperative blood loss, the first post-operative day drainage volume, the total post-operative drainage volume, and the total drainage days were all significantly lower in endoscope group patients than in conventional group patients (all p < 0.05). Among 3 months follow-ups, no local recurrence or residual tumor were found in both groups of patients, and there were none of them had permanent facial paralysis or parotid fistula. The self-evaluated appearance satisfaction VAS scores of endoscope group patients were all 0, which was significantly lower than that of conventional group patients, 4.7 ± 1.6 (p < 0.001). CONCLUSION: Compared with the conventional Blair "S" incision surgery, the endoscope-assisted resection of the benign parotid tumors via concealed post-auricular sulcus incision was safe and effective and showed advantages of faster recovery and better self-assessments of appearance satisfaction. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:133-138, 2023.

Comparison of short-term recovery in children with obstructive sleep apnea undergoing tonsillotomy vs. tonsillectomy.

Objectives: To compare the pain levels, degrees of pharyngeal swelling, and weight loss after tonsillectomy vs. tonsillotomy in children clinically diagnosed with obstructive sleep apnea (OSA) over the first seven postoperative days, and to determine which procedure was associated with better recovery in the early postoperative period. Methods: Between April 2021 and December 2021, 121 children with OSA (80 males and 41 females), ranging from 3 to 12 years of age with an average age of 6.7 years, were prospectively enrolled in this study conducted at Zhengzhou Central Hospital Affiliated to Zhengzhou University. The patients were randomly divided into two groups: a tonsillotomy group with 63 cases (40 males and 23 females) and a tonsillectomy group with 58 cases (40 males and 18 females). The patients' pain levels [as indicated by Parents' Postoperative Pain Measure (PPPM) scores] and degrees of pharyngeal swelling were recorded for seven days postoperatively, and the patients' body weights were recorded on postoperative day seven. Results: In the tonsillotomy group, the PPPM scores were the highest on the day of surgery and on the first postoperative day; the patients' pain levels gradually decreased.The PPPM scores in the tonsillectomy group were higher than those in the tonsillotomy group from the day of surgery to the seventh postoperative day (p < 0.05). The degree of pharyngeal swelling was lower in the tonsillotomy group than in the tonsillectomy group. Weight loss was lower in the tonsillotomy group than in tonsillectomy group on the 7th day after surgery (p < 0.05). On the fifth, sixth, and seventh postoperative days, compared with preschool children, school-age children who had undergone tonsillotomy experienced more pain relief than those who had undergone tonsillectomy (p < 0.05). Conclusion: Children with OSA experienced less pain, less pharyngeal swelling, and less weight loss with tonsillotomy than with tonsillectomy. On the fifth, sixth, and seventh postoperative days, compared with preschool children, tonsillotomy in school-age children is more advantageous in school-age children.

Circ_0001588 Upregulates ERBB4 to Promote Glioma Malignant Progression Through Sponging miR-1281.

Circular RNA (circRNA) plays a crucial part in glioma progression. However, the function of circ_0001588 in glioma development is still unknown. The study aims to reveal the role of circ_0001588 in glioma malignant progression and the inner molecular mechanism. The RNA expressions of circ_0001588, microRNA-1281 (miR-1281), and erb-b2 receptor tyrosine kinase 4 (ERBB4) were detected by qRT-PCR. Protein expression was checked by western blot analysis or immunohistochemistry assay. Cell proliferation was investigated by cell counting kit-8 and colony formation assays. Flow cytometry, transwell, and tube formation assays were used to detect cell apoptosis, cell migration, and invasion as well as angiogenesis, respectively. The binding relationship between miR-1281 and circ_0001588 or ERBB4 was identified by dual-luciferase reporter and RNA immunoprecipitation assays. Mouse model assay was performed to confirm the effect of circ_0001588 knockdown on tumor formation in vivo. Circ_0001588 and ERBB4 expressions were significantly upregulated, while miR-1281 was downregulated in glioma tissues and cells compared with control groups. Circ_0001588 expression was closely related to tumor size and WHO grade of glioma. Decreased expression of circ_0001588 in glioma cells led to significant decreases of cell proliferation, migration, invasion, and tube formation and an increase of cell apoptosis. Additionally, downregulation of miR-1281, a target miRNA of circ_0001588, rescued circ_0001588 knockdown-mediated effects. MiR-1281 also inhibited glioma malignant progression by targeting ERBB4. Importantly, circ_0001588 regulated ERBB4 expression by interacting with miR-1281. Furthermore, circ_0001588 depletion suppressed tumor formation in vivo. Circ_0001588 acted as an oncogene in glioma malignant progression by miR-1281/ERBB4 pathway, suggesting the potential of circ_0001588 as a therapeutic target for glioma.

Exogenous brain-derived neurotrophic factor attenuates neuronal apoptosis and neurological deficits after subarachnoid hemorrhage in rats.

Brain-derived neurotrophic factor (BDNF) is a growth factor crucial for neuronal survival, while its role in subarachnoid hemorrhage (SAH)-induced neuronal apoptosis remains unclear. The aim of the present study was to investigate whether administering exogenous BDNF can protect against neuronal apoptosis and neurological deficits following SAH in a rat model. The BDNF level was found to be significantly decreased in the basal cortex at 6, 12, 24, 48 and 72 h following SAH. Exogenous BDNF significantly decreased the expression of Bax and reduced activation of caspase-3 and caspase-9 and the number of apoptotic neurons. Moreover, exogenous BDNF treatment significantly improved the neurological deficits at 72 h and long-term behavioral deficits (day 14) following SAH in a rat model. These findings indicate that exogenous BDNF attenuated SAH-induced neuronal injury in rats.

Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells.

BACKGROUND: Gliomas are highly malignant brain tumors. Aberrant activation of NF-κB plays a crucial role in tumor progression. METHOD: ELISA assay was used to detect NF-κB activity in glimoas cells with different treatments. PPP3CC expression was evaluated by qRT-PCR and western blot assay. Kaplan-Meier analysis estimated the overall survival rates according to the protein level of PPP3CC. Transwell and MTS assay were performed to determine cell invasion and growth. Chromatin immunoprecipitation combined with luciferase reporter assays illustrated the transcriptional regulation of PPP3CC. RESULTS: We showed that PPP3CC decrease was responsible for constitutive activation of NF-κB in gliomas. Restored PPP3CC expression inhibited activation of NF-κB. PPP3CC was frequently decreased in gliomas and that repression of the expression of PPP3CC correlated glioma progression. The ectopic expression of PPP3CC inhibited the invasive potential of glioma cells, and inhibited glioma cells proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E-box-binding homeobox 1(ZEB1) was increased in gliomas and was negatively correlated with clinical outcomes of glioma patients. ZEB1 inversely correlated with the expression of PPP3CC. ZEB1 was also confirmed to physically bind to the PPP3CC promoter. ZEB1 knockdown resulted in an increase in the expression of PPP3CC and elevation of PPP3CC promoter activity in glioma cells. CONCLUSION: These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-κB is a critical oncogenic event in gliomas.

Repression of the expression of TET2 by ZEB1 contributes to invasion and growth in glioma cells.

Malignant gliomas are the most common and aggressive type of brain tumor. The suppressive role of ten-eleven translocation 2 (TET2) has been implicated in certain types of cancer, however, its role in gliomas remains to be elucidated. The present study aimed to determine the expression pattern and biological role of TET2 in glioma, using RT-qPCR and immunohistochemistry, and its results indicated that the expression of TET2 was frequently decreased in gliomas and that repression of the expression of TET2 correlated with the progression of glioma. The ectopic expression of TET2 inhibited the invasive potential of glioma cells, and inhibited glioma cell proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E­box­binding homeobox 1 (ZEB1) was increased in gliomas and was positively correlated with progression, but inversely correlated with the expression of TET2. ZEB1 was also confirmed to physically bind to the TET2 promoter. ZEB1 knockdown resulted in an increase in the expression of TET2 and elevation of TET2 promoter activity in glioma cells. These findings indicated that the downregulation of TET2 by ZEB1 is a critical oncogenic event in gliomas.

Risk Factors for Poor Outcome in Hypertensive Intraventricular Hemorrhage Treated by External Ventricular Drainage with Intraventricular Fibrinolysis.

OBJECTIVE: External ventricular drainage (EVD) combined with intraventricular fibrinolysis (IVF) is a commonly accepted surgical approach for some cases of hypertensive intraventricular hemorrhage (HIVH). We aimed to investigate the association between preoperative factors and outcome in patients with HIVH treated by EVD plus IVF. METHODS: Records from March 2010 to March 2016 were searched for HIVH treated by EVD plus IVF. We divided this population into the favorable outcome group and the unfavorable outcome group according to the Glasgow Outcome Scale. Preoperative demographic data, radiologic findings, and clinical factors were compared in each group. Univariate and multivariable logistic regression were used to assess the relationship between factors and outcome in HIVH. RESULTS: Of 267 patients included in this study, 136 had a favorable outcome and 131 had a poor outcome. Multivariate analyses showed that age (odds ratio [OR], 18.229; 95% confidence interval [CI], 1.503-221.16), Glasgow Coma Scale score (OR, 12.686; 95% CI, 1.5-107.312), blood neuron specific enolase (OR, 9.463; 95% CI, 1.178-76.012), third ventricle hematoma (OR, 15.311; 95% CI, 1.287-497.914), and fourth ventricle hematoma (OR, 25.258; 95% CI, 1.851-125.767) were associated with poor outcome of EVD in patients with HIVH. CONCLUSIONS: Fourth ventricle hematoma, third ventricle hematoma, high blood neuron specific enolase value, low Glasgow Coma Scale score, and old age were risk factors for poor outcome in HIVH treated with EVD plus IVF. EVD was not suitable, particularly in patients with brainstem compression caused by fourth ventricle hemorrhage, regardless of use of IVF.

Prolonged hydrocephalus induced by intraventricular hemorrhage in rats is reduced by curcumin therapy.

Prolonged hydrocephalus is a major cause of severe disability and death of intraventricular hemorrhage (IVH) patients. However, the therapeutic options to minimize the detrimental effects of post-hemorrhagic hydrocephalus are limited. Curcumin has been reported to confer neuroprotective effects in numerous neurological diseases and injuries, but its role in IVH-induced hydrocephalus has not been determined. The aim of present study was to determine whether curcumin treatment ameliorates blood brain barrier (BBB) damage and reduces the incidence of post-hemorrhagic hydrocephalus in IVH rat model. Autologous blood intraventricular injection was used to establish the IVH model. Our results revealed that repeated intraperitoneal injection of curcumin ameliorated IVH-induced learning and memory deficits as determined by Morris water maze and reduced the incidence of post-hemorrhagic hydrocephalus in a dose-dependent manner at 28 d post-IVH induction. Further, the increased BBB permeability and brain edema induced by IVH were significantly reduced by curcumin administration. In summary, these findings highlighted the important role of curcumin in improving neurological function deficits and protecting against BBB disruption via promoting the neurovascular unit restoration, and thus it reduced the severity of post-hemorrhagic hydrocephalus in the long term. It is believed that curcumin might prove to be an effective therapeutic component in prevent the post-IVH hydrocephalus in the near future.

Genetic and Epigenetic Changes in Oilseed Rape (Brassica napus L.) Extracted from Intergeneric Allopolyploid and Additions with Orychophragmus.

Allopolyploidization with the merger of the genomes from different species has been shown to be associated with genetic and epigenetic changes. But the maintenance of such alterations related to one parental species after the genome is extracted from the allopolyploid remains to be detected. In this study, the genome of Brassica napus L. (2n = 38, genomes AACC) was extracted from its intergeneric allohexaploid (2n = 62, genomes AACCOO) with another crucifer Orychophragmus violaceus (2n = 24, genome OO), by backcrossing and development of alien addition lines. B. napus-type plants identified in the self-pollinated progenies of nine monosomic additions were analyzed by the methods of amplified fragment length polymorphism, sequence-specific amplified polymorphism, and methylation-sensitive amplified polymorphism. They showed modifications to certain extents in genomic components (loss and gain of DNA segments and transposons, introgression of alien DNA segments) and DNA methylation, compared with B. napus donor. The significant differences in the changes between the B. napus types extracted from these additions likely resulted from the different effects of individual alien chromosomes. Particularly, the additions which harbored the O. violaceus chromosome carrying dominant rRNA genes over those of B. napus tended to result in the development of plants which showed fewer changes, suggesting a role of the expression levels of alien rRNA genes in genomic stability. These results provided new cues for the genetic alterations in one parental genome that are maintained even after the genome becomes independent.