A novel technique for avoidance of sternotomy, diaphragmic incision and cardiopulmonary bypass during cavoatrial tumor thrombectomy for renal cell carcinoma with intraatrial tumor thrombus: a case series at a single center.

BACKGROUND: Radical nephrectomy with thrombectomy in patients with renal cell carcinoma (RCC) and level IV thrombus extending to the right atrium (RA) offers improved survival. However, this procedure is associated with significant perioperative morbidity and mortality. In this report, we describe a novel milking technique for patients with RA tumor thrombus using abdominal access, which does not require diaphragmic incision, sternotomy, right atriotomy, or cardiopulmonary bypass (CPB). METHODS: Between January 2019 and January 2022, four patients underwent resection of renal cell carcinoma extending into RA by a milking technique developed to avoid diaphragmic incision, sternotomy, or CPB. Patient characteristics, perioperative data, pathological features, and survival were evaluated. RESULTS: Complete resection was successful through pure transabdominal access without diaphragmic incision, sternotomy, or CPB in all patients. CONCLUSION: We conclude that radical nephrectomy and thrombectomy in optimized cases with renal cell carcinoma extending into RA can be safely and effectively performed without diaphragmic incision, sternotomy, or CPB, avoiding serious perioperative complications while providing acceptable oncological outcomes.

Reconstruction strategies for intraoperative CSF leak in endoscopic endonasal skull base surgery: systematic review and meta-analysis.

BACKGROUND: Endoscopic endonasal surgery (EES) is one of the preferred options for skull base pathologies. Cerebrospinal fluid (CSF) leak is a significant complication of EES and neurosurgeons have proposed various reconstructive strategies to decrease this morbidity. We describe and compare the efficacy of these strategies. METHODS: We searched PubMed, Cochrane Library, and Web of Science for publications between 1990 and November 2019. We defined a reconstruction hierarchy of seven levels from inside to outside: fat graft, intracranial intradural layer (inlay), intracranial extradural layer (onlay), buttress, mucosal flap, nasal packing and lumbar drainage. A single-arm analysis was performed for the primary outcome of CSF leak rate. RESULTS: Of 3641 records identified, 48 studies met the inclusion criteria. Pituitary tumors had lower postoperative CSF leak rate than other diseases (1.8% vs. 6.5%, RD = -4.7% [-7.1%, -2.1%]). In high CSF flow group, the post-operative leak rate was reduced by application of mucosal flap (4.3% vs. without mucosal flap at 12.8%, RD = -8.5% [-15.1%, -1.9%]). The use of inlay showed potential of decreasing the post-operative leak rate (5.0% vs. 7.2%, RD = -2.2% [-7.7%, 3.3%]). In low CSF flow group, tampon was better than balloon for nasal packing (1.0% vs. 10.5%, RD = -9.5% [-16.5%, -2.4%]). CONCLUSIONS: Mucosal flap and inlay for high-flow intraoperative CSF leak and tampon (compared with balloon) for low-flow intraoperative CSF leak, improved the postoperative CSF leak rate. Further studies are required to establish more robust evidence.

Spatial analysis of metformin use compared with nicotine and caffeine consumption through wastewater-based epidemiology in China.

Monitoring the consumption of pharmaceuticals and licit drugs is important for assessing the needs of public health owing to the impact on individuals as well as society. The present work applied wastewater-based epidemiology to profile the spatial patterns of metformin, nicotine, and caffeine use and their correlations. Influent wastewater samples were collected from 27 wastewater treatment plants in 22 typical Chinese cities that covered all geographic regions of the country. The consumption of metformin ranged from 0.02 g/d/1000 inh to 8.92 g/d/1000 inh, whereas caffeine and nicotine consumption ranged from 4.33 g/d/1000 inh to 394 g/d/1000 inh and 0.17 g/d/1000 inh to 1.88 g/d/1000 inh, respectively. There were significant regional differences in the consumption of caffeine, with the highest consumption in East China and the lowest consumption in Northeast China. The consumption and concentration of caffeine were related to the gross domestic product and per capita disposable income of urban residents, respectively. There was a correlation between the concentrations of caffeine and cotinine (a nicotine metabolite), thereby indicating that individuals that use one of these substances are likely to use the other substance. A significant relationship was found between the concentration of metformin and cotinine, thereby implying that the use of tobacco may be correlated with type 2 diabetes. Co-analysis of these substances in wastewater may provide a more accurate picture of substance use situations within different communities and provide more information on human health, human behavior, and the economy. This report describes the newest study related to the consumption of metformin among the general population in China.

Design and validation of a 3D-printed simulator for endoscopic third ventriculostomy.

BACKGROUND: Simulation-based training has been considered as the most promising curriculum for neurosurgical education to finally improve surgical skills with the greatest efficiency and safety. However, most of the simulators including physical models and virtual reality systems are relatively expensive, which limits their promotion. In this study, the authors tried to develop a realistic, low-cost, and reusable simulator for endoscopic third ventriculostomy (ETV) and evaluate its validity. METHODS: A 3D-printed rigid skull with the ventricular system originated from a de-identified patient with obstructive hydrocephalus was constructed. The third ventricular floor was designed as a replaceable module. Thirty-nine neurosurgeons tested the simulator and a rating system was established to assess their performance. All participants filled out questionnaires to evaluate the simulator after training. Five neurosurgical students were recruited to finish the whole training for ten times in order to explore the learning curve of ETV. RESULTS: We found that (1) the more experienced surgeons performed obviously better than the rather inexperienced surgeons which verified that our model could reflect the ability of the trainees; (2) as the training progressed, the scores of the post-graduates increased and the fifth training average score was obviously higher than their first training average score. The feedback questionnaires showed the average scores for value of the simulator as a training tool and global rating were 3.15 and 3.54 (on a 4-point scale). CONCLUSION: Our model was practical for ETV training. The results of our program showed that our model could precisely reflect the operators' ability to perform ETV and could make it more efficient to master basic skills.

A practical 3D printed simulator for endoscopic endonasal transsphenoidal surgery to improve basic operational skills.

PURPOSE: We aimed to present a practical three-dimensional (3D) printed simulator to comprehensively and effectively accelerate the learning curve of endoscopic endonasal transsphenoidal surgery (EETS). METHODS: The 3D printed simulator consists of three parts: (1) skull frame, (2) the nasal passage and the nasal alar of the face, and (3) a modified sella turcica. We aimed to improve three basic operational skills of surgeons: drilling, curetting, and aspirating. Eighteen neurosurgeons and five post-graduates were recruited and consented for the training. RESULTS: For trainees, (1) as the training progressed, the scores increased gradually, (2) a significant increase in the average scores was observed in the tenth training compared to the first training, and (3) there is a significant decrease in trainee variability in the shortening of the gap. The 18 neurosurgeons were divided into three groups: experts, assistants, and observers. For all three basic operations, (1) the average score of experts was obviously higher than that of the assistants, observers, and trainees' tenth training and (2) the average scores of assistants and observers were obviously higher than that of trainees' first training. A significant high in the average score between the assistants and the observers was seen for aspirating, but not for drilling or curetting. For curetting and aspirating, the tenth training average score of trainees was obviously higher than that of assistants and observers. CONCLUSION: This 3D printed simulator allows different endoscopic basic operations to be simulated and improves the EETS techniques of surgeons. We believed it to be a practical, simple, and low-cost simulator.

Knockdown of Nrf2 suppresses glioblastoma angiogenesis by inhibiting hypoxia-induced activation of HIF-1α.

Concerns were increasingly raised that several types of cancers overexpressed the nuclear factor erythroid 2-related factor 2 (Nrf2), which contributed strikingly to cancer biological capabilities and chemoresistance. However, the role of Nrf2 in the tumor vascular biology had yet to be mechanistically determined. Here, we investigated the involvement of Nrf2 in glioblastoma (GB) angiogenesis in hypoxia. First, we detected the overexpression of Nrf2 and correlated its protein level with microvessel density (MVD) in human GB tissues. Then, we established the stable RNAi-mediated Nrf2-knockdown cells and mimicked hypoxic condition in vitro. The knockdown of Nrf2 inhibited cell proliferation in vitro and suppressed tumor growth in mouse xenografts with a concomitant reduction in VEGF expression and MVD. Similar antiangiogenic effects were documented in endothelial tube formation assays. The downregulation of Nrf2 in glioma cells led to much lower accumulation of HIF-1α protein and limited expression of VEGF and other HIF-1α target genes in mimicking hypoxia. Mechanistic investigations suggested that HIF-1α degradation during hypoxia could be attributed to reduced mitochondrial O2 consumption in Nrf2-inhibited cells. It can be concluded that Nrf2, with its capacity for affecting the protein level of HIF-1α expression, has good reasons to be considered as a critical transcription factor for controlling glioma angiogenesis.

Temozolomide and irradiation combined treatment-induced Nrf2 activation increases chemoradiation sensitivity in human glioblastoma cells.

Resistance to chemoradiotherapy is a major obstacle to successful treatment of glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing chemoradiation sensitivity has been reported in several types of cancers. Here, we investigated whether temozolomide (TMZ) and irradiation (IR) combined treatment induced Nrf2 activation in human glioblastoma cells. And we further performed a preliminary study about the effect of Nrf2 on chemoradiation sensitivity. Immunohistochemical staining for Nrf2 in paired clinical specimens showed that TMZ and IR combined treatment increased the expression and nuclear localization of Nrf2 in human glioblastoma tissues. Moreover, we found nuclear Nrf2 expression in the glioblastoma tissues obtained from the patients undergoing TMZ and IR combined treatment was associated with the time to tumor recurrence. In vitro, we further verified these findings. First, we detected increased nuclear localization of Nrf2 following treatment with TMZ+IR in human glioblastoma cell lines. Second, we demonstrated TMZ+IR increased the levels of Nrf2 protein in both nuclear and cytoplasmic fractions of U251 cells and induced Nrf2 target genes expression. Finally, downregulating Nrf2 expression increased TMZ+IR-induced cell death in the U251 cells. These findings suggest TMZ+IR combined treatment induces Nrf2 activation in human glioblastoma cells. The activation of Nrf2 may be associate with enhancing chemoradiation sensitivity in human glioblastoma cell. Blocking Nrf2 activation may be a promising method enhancing chemoradiation sensitivity of glioblastoma cells.

Puerarin ameliorates oxidative stress in a rodent model of traumatic brain injury.

BACKGROUND: A wealth of evidence has suggested that oxidative stress is involved in the secondary brain injury after traumatic brain injury (TBI). Recently, numerous in vivo and in vitro studies were reported that puerarin could inhibit oxidative stress through the activation of phosphatidylinositol 3-kinase (PI3K)-Akt pathway. It is unknown, however, whether puerarin can provide neuroprotection and reduce oxidative stress after TBI. The present study investigated the effects of puerarin on the TBI-induced neurodegeneration, oxidative stress, and the possible role of PI3K-Akt pathway in the neuroprotection of puerarin, in a rat model of TBI. MATERIALS AND METHODS: Rats were randomly distributed into various subgroups undergoing the sham surgery or TBI procedures. Puerarin (200 mg/kg) was given intraperitoneally at 10 min before injury and PI3K-Akt pathway inhibitor LY294002 was also administered intracerebroventricular in one subgroup. All rats were killed at 24 h after TBI for examination. RESULTS: Our data indicated that puerarin could significantly reduce TBI-induced neuronal degeneration, accompanied by the partial restoration of the redox disturbance and enhanced expression of phospho-Akt in the pericontusional cortex after TBI. Moreover, PI3K-Akt pathway inhibitor LY294002 could partially abrogate the neuroprotection of puerarin in rats with TBI. CONCLUSIONS: These results indicate that puerarin can ameliorate oxidative neurodegeneration after TBI, at least in part, through the activation of PI3K-Akt pathway.

Comparison of the Endoscopic Endonasal Approach with the Endoscopic Supraorbital Keyhole Approach to the Tuberculum Sellae Region: A Quantitatively Cadaveric Study.

BACKGROUND: The endoscopic endonasal approach (EEA) and the endoscopic supraorbital keyhole approach (eSKA) provide minimally invasive access to tuberculum sellae (TS) tumors. Evaluation of the operating maneuverability is helpful for approach selection. Herein, we compared the two approaches and aimed to provide quantitative anatomic data for surgical decision-making in the management of TS lesions. METHODS: Fifteen dissections were performed on five silicone-injected cadaveric heads. The EEA and eSKA (both right and left) were performed on each head. Surgical freedom and working angles in the axial and sagittal planes were calculated using the stereotactic navigation system in the selected six targets: the midpoint of the leading edge of the sphenoid sinus (leSS), the midpoint of the edge of the dorsum sellae (eDS), the ipsilateral medial opticocarotid recess (imOCR), the contralateral medial opticocarotid recess (cmOCR), the ipsilateral lateral opticocarotid recess (ilOCR), and the contralateral lateral opticocarotid recess (clOCR). RESULTS: The surgical freedom at the ilOCR and the axial working angles at the leSS, ilOCR, and imOCR (imOCR with excessive manipulation of the optic apparatus) were greater in the eSKA. The EEA provided greater surgical freedom and/or working angles at most targets than eSKA (the surgical freedom at the imOCR, cmOCR, clOCR, and eDS; the axial working angles at the cmOCR and clOCR; and the sagittal working angles at the leSS, imOCR, cmOCR, clOCR, and eDS). CONCLUSION: The EEA provides greater surgical freedom and working angles for paramedian lesions, whereas the eSKA provides better surgical maneuverability for lesions with lateral extension.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Elevated histone deacetylase 10 expression promotes the progression of clear cell renal cell carcinoma by Notch-1-PTEN signaling axis.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most common pathological subtype of kidney cancer, accounts for approximately 70% to 80% of all cases. Histone deacetylase 10 (HDAC10) belongs to the HDAC class IIb subgroup, one of the histone deacetylases (HDAC) family. Previous studies suggest that HDAC10 may regulate the development of multiple tumor types. The specific molecular mechanisms employed by HDAC10 in the etiology of ccRCC still need to be discovered. METHODS: The analysis included examining HDAC10 expression levels and their clinical importance within a cohort of inpatients and ccRCC patients documented in the Tumor Genome Atlas (TCGA). Moreover, the biological functions and underlying molecular mechanisms of HDAC10 were investigated. RESULTS: HDAC10 showed increased expression in ccRCC tumor tissues. Subsequent analysis revealed overexpression of HDAC10 was associated with advanced clinical phenotype and unfavorable prognosis. The absence of HDAC10 significantly decreased ccRCC cell proliferation and migration capabilities. Mechanistic research suggests that HDAC10 may promote RCC development by activating the Notch-1 pathway and downregulating PTEN expression levels. CONCLUSION: In summary, HDAC10 can modulate critical biological processes in ccRCC, including proliferation, migration, and apoptosis. Notably, the Notch-1 pathway and PTEN serve as crucial signaling pathways and target genes through which HDAC10 regulates the progression of ccRCC. These findings offer a novel outlook for ccRCC treatment.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Activation of metabotropic glutamate receptor 5 reduces the secondary brain injury after traumatic brain injury in rats.

A wealth of evidence has shown that microglia-associated neuro-inflammation is involved in the secondary brain injury contributed to the poor outcome after traumatic brain injury (TBI). In vitro studies were reported that activation of metabotropic glutamate receptor 5 (mGluR5) could inhibit the microglia-associated inflammation in response to lipopolysaccharide and our previous study indicated that mGluR5 was expressed in activated microglia following TBI. However, there is little known about whether mGluR5 activation can provide neuro-protection and reduce microglia-associated neuro-inflammation in rats after TBI. The goal of the present study was to investigate the effects of mGluR5 activation with selective agonist CHPG, on cerebral edema, neuronal degeneration, microglia activation and the releasing of pro-inflammatory cytokines, in a rat model of TBI. Rats were randomly distributed into various subgroups undergoing the sham surgery or TBI procedures, and 250 nmol of CHPG or equal volume vehicle was given through intracerebroventricular injection at 30 min post-TBI. All rats were sacrificed at 24 h after TBI for the further measurements. Our data indicated that post-TBI treatment with CHPG could significantly reduce the secondary brain injury characterized by the cerebral edema and neuronal degeneration, lead to the inhibition of microglia activation and decrease the expression of pro-inflammatory cytokines in both mRNA transcription and protein synthesis. These results provide the substantial evidence that activation of mGluR5 reduces the secondary brain injury after TBI, in part, through modulating microglia-associated neuro-inflammation.

Nrf2 is required to maintain the self-renewal of glioma stem cells.

BACKGROUND: Glioblastomas are deadly cancers that display a functional cellular hierarchy maintained by self-renewing glioma stem cells (GSCs). Self-renewal is a complex biological process necessary for maintaining the glioma stem cells. Nuclear factor rythroid 2-related factor 2(Nrf2) plays a significant role in protecting cells from endogenous and exogenous stresses. Nrf2 is a key nuclear transcription factor that regulates antioxidant response element (ARE)-containing genes. Previous studies have demonstrated the significant role of Nrf2 in the proliferation of glioblastoma, and in their resistance to radioactive therapies. We examined the effect of knocking down Nrf2 in GSCs. METHODS: Nrf2 expression was down-regulated by shRNA transinfected with lentivirus. Expression levels of Nestin, Nrf2, BMI-1, Sox2 and Cyclin E were assessed by western blotting, quantitative polymerase chain reaction (qPCR) and immunohistochemistry analysis. The capacity for self-renewal in vitro was assessed by genesis of colonies. The capacity for self-renewal in vivo was analyzed by tumor genesis of xenografts in nude mice. RESULTS: Knockdown of Nrf2 inhibited the proliferation of GSCs, and significantly reduced the expression of BMI-1, Sox2 and CyclinE. Knocking down of Nrf2 changed the cell cycle distribution of GSCs by causing an uncharacteristic increase in the proportion of cells in the G2 phase and a decrease in the proportion of cells in the S phase of the cell cycle. CONCLUSIONS: Nrf2 is required to maintain the self-renewal of GSCs, and its down-regulation can attenuate the self-renewal of GSCs significantly.

Endoscopic endonasal transsphenoidal surgery for the cavernous sinus hemangioma: Surgical application and review of the literature.

Aim: Cavernous sinus hemangiomas (CSHs) are hypervascular malformations and the surgical treatment is technically demanding. Although some articles have reported resection of CSHs using endoscopic endonasal transsphenoidal surgery (EETS), most of them were encountered for a lack of preoperative strategy guidance. Herein, we reported gross total resection (GTR) of intrasellar CSHs in two patients undergoing strategical EETS and compared EETS with frontotemporal craniotomy (FC) and stereotactic radiosurgery by literature review. Material and methods: Two patients with CSHs who underwent EETS were reported. The literature review was conducted to exhaust studies that reported surgical treatment for CSHs. The tumor resection rate, and the postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were extracted. Results: GTR was achieved with no postoperative complications in the two cases. Nine articles reported 14 cases undergoing EETS for CSHs and twenty-three articles reported 195 cases undergoing FC for CSHs. The GTR rates of EETS and FC were 57.14% (8/14) and 78.97% (154/195) respectively. The postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were 0% (0/7) and 0% (0/6) for the EETS group, and 57% (57/100) and 18.18% (18/99) for the FC group. According to the previous meta-analysis, stereotactic radiosurgery resulted in remarkable tumor shrinkage in 67.80% (40/59) of patients and partial shrinkage in 25.42% of patients. Discussion: The results showed that the intrasellar type of CSHs could be removed safely by EETS without crossing the nerves in the CS.

Fucoxanthin ameliorates traumatic brain injury by suppressing the blood-brain barrier disruption.

Fucoxanthin is the most abundant marine carotenoid extracted from seaweed. Our previous study has shown that fucoxanthin inhibited oxidative stress after traumatic brain injury (TBI). However, the effects of fucoxanthin on TBI-induced blood-brain barrier (BBB) destruction have not been well understood. In the present study, we found that fucoxanthin improved neurological dysfunction, reduced brain edema, attenuated cortical lesion volume, and decreased dendrites loss after TBI in vivo. Moreover, fucoxanthin suppressed BBB leakage, preserved tight junction (TJ) and adherens junction (AJ) proteins, and inhibited MMP-9 expression. Furthermore, fucoxanthin alleviated apoptosis and ferroptosis, and activated mitophagy in endothelial cells (ECs) after TBI. However, the protection of fucoxanthin on BBB was attenuated when mitophagy was inhibited. Importantly, fucoxanthin also provided protective effects in bEnd.3 cells after TBI. Taken together, our results suggested that fucoxanthin played a key role in the protection of BBB after TBI through mitophagy.

Comprehensive analysis of m6A subtype classification for immune microenvironment of pituitary adenomas.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment (IME) have an essential role in tumor development. However, their relationships in pituitary adenomas (PAs) remains unclear. METHODS: PA datasets from the Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EMBL-EBI) were used. We utilized hierarchical clustering algorithms based on the m6A regulator gene set to identify m6A subtypes. ESTIMATE and CIBERSORT algorithms were applied to explore the compositions of stromal and immune cells. A nomogram model was constructed for the prediction of m6A subtypes in PAs. Immunohistochemistry and multiplex immunofluorescence staining were used to analyze the expression level of m6A regulator YTHDF2 in relation to M2 macrophages and immune checkpoints in PAs. RESULTS: We concluded the IME landscape of m6A subtype classification and characterized two emerging m6A subtypes. Different IME between these two m6A subtypes were identified. Simultaneously, a polygenic nomogram model was constructed for predicting m6A subtype classification, with excellent predictive performance (training set, AUC = 0.984; validation set, AUC = 0.986). YTHDF2 was highly expressed in PAs and accompanied by upregulated M2 macrophages and expression of PD-L1. CONCLUSIONS: We proposed two novel m6A subtypes in PAs for the first time and constructed a reliable and clinically accessible nomogram model for them. Meanwhile, YTHDF2 was first identified as a promising biomarker for immunotherapy and potential molecular target in PAs.

A Preoperative Nomogram for Prediction of Postoperative Hypocortisolism in Patients with Pituitary Adenomas: A Single-Center Retrospective Cohort Study.

BACKGROUND: Patients with pituitary adenomas (PAs) are at an increased risk preoperatively and postoperatively for hypopituitarism. Postoperative hypocortisolism is associated with increased mortality and morbidity as well as poor quality of life. However, research about the risk factors for postoperative hypocortisolism is limited, and a predictive nomogram for postoperative hypocortisolism has not yet been developed. We aimed to investigate the predictive factors for postoperative hypocortisolism and construct a dynamic online nomogram. METHODS: Our database included 438 consecutive PA patients who were hospitalized and treated with transsphenoidal surgery by experienced neurosurgeons from the different medical teams in the Neurosurgery Department, Jinling Hospital, between January 2018 and October 2020. The final study group included 238 eligible patients. Data on possible predictors, including age, sex, treatment history of PAs, preoperative signs and symptoms, primary recurrence subtype, and clinical subtypes, were collected. Univariable and multivariable logistic regression analyses were applied to identify independent predictors, which were included in constructing the nomogram model. The calibration curve and receiver operating characteristic curve were computed to evaluate the predictive performance of the nomogram model. RESULTS: The incidence of postoperative hypocortisolism was 12.08%. Three preoperative predictors were identified to construct the nomogram: surgical type (microscopic or endoscopic, with endoscopic surgery proven to be the protective factor) (odds ratio, 0.24; 95% confidence interval [CI], 0.093-0.610; P = 0.003), prothrombin time (odds ratio, 2.40; 95% CI, 1.332-4.326; P = 0.004), and basophil cell count (odds ratio, 5.25; 95% CI, 1.270-21.816; P = 0.022,). The area under the curve of receiver operating characteristic curve for the constructed nomogram was 0.749 (95% CI, 0.640-0.763); a well-fixed calibration curve was generated for the nomogram model. An interactive web-based dynamic nomogram application was also constructed. CONCLUSIONS: In this study, surgical type, prothrombin time, and basophil cell count were the most relevant predictive factors for postoperative hypocortisolism. A predictive nomogram that can preoperatively assess the risk of hypocortisolism after surgical treatment of PAs was developed. This nomogram could be helpful in identifying high-risk patients who require close monitoring of serum cortisol levels and initiating clinical procedures for patients requiring cortisol administration therapy as a lifesaving strategy.

Advances in Optogenetics Applications for Central Nervous System Injuries.

Injuries to the central nervous system (CNS) often lead to severe neurological dysfunction and even death. However, there are still no effective measures to improve functional recovery following CNS injuries. Optogenetics, an ideal method to modulate neural activity, has shown various advantages in controlling neural circuits, promoting neural remapping, and improving cell survival. In particular, the emerging technique of optogenetics has exhibited promising therapeutic methods for CNS injuries. In this review, we introduce the light-sensitive proteins and light stimulation system that are important components of optogenetic technology in detail and summarize the development trends. In addition, we construct a comprehensive picture of the current application of optogenetics in CNS injuries and highlight recent advances for the treatment and functional recovery of neurological deficits. Finally, we discuss the therapeutic challenges and prospective uses of optogenetics therapy by photostimulation/photoinhibition modalities that would be suitable for clinical applications.