Comprehensive Analyses of PANoptosome with Potential Implications in Cancer Prognosis and Immunotherapy.

Cell death resistance significantly contributes to poor therapeutic outcomes in various cancers. PANoptosis, a unique inflammatory programmed cell death (PCD) pathway activated by specific triggers and regulated by the PANoptosome, possesses key features of apoptosis, pyroptosis, and necroptosis, but these cannot be accounted for by any of the three PCD pathways alone. While existing studies on PANoptosis have predominantly centered on infectious and inflammatory diseases, its role in cancer malignancy has been understudied. In this comprehensive investigation, we conducted pan-cancer analyses of PANoptosome component genes across 33 cancer types. We characterized the genetic, epigenetic, and transcriptomic landscapes, and introduced a PANoptosome-related potential index (PANo-RPI) for evaluating the intrinsic PANoptosome assembly potential in cancers. Our findings unveil PANo-RPI as a prognostic factor in numerous cancers, including KIRC, LGG, and PAAD. Crucially, we established a significant correlation between PANo-RPI and tumor immune responses, as well as the infiltration of diverse lymphoid and myeloid cell subsets across nearly all cancer types. Moreover, a high PANo-RPI was consistently associated with improved immunotherapy response and efficacy, as evidenced by re-analysis of multiple immunotherapy cohorts. In conclusion, our study suggests that targeting PANoptosome components and modulating PANoptosis may hold tremendous therapeutic potential in the context of cancer.

MYEF2: an immune infiltration-related prognostic factor in IDH-wild-type glioblastoma.

Glioblastoma (GBM) is the most malignant and prevalent primary brain tumor. In this study, weighted gene coexpression network analysis (WGCNA) was performed to analyze RNA binding protein (RBP) expression data from The Cancer Genome Atlas (TCGA) for the IDH-wild type GBM cohort. The CIBERSORT algorithm quantified the cellular composition of immune cells and was used to identify key modules associated with CD8+ T cell infiltration. Coexpression networks analysis and protein-protein interaction (PPI) network analysis was used to filter out central RBP genes. Eleven RBP genes, including MYEF2, MAPT, NOVA1, MAP2, TUBB2B, CDH10, TTYH1, PTPRZ1, SOX2, NOVA2 and SCG3, were identified as candidate CD8+ T cell infiltration-associated central genes. A Cox proportional hazards regression model and Kaplan-Meier analysis were applied to identify candidate biomarkers. MYEF2 was selected as a prognostic biomarker based on the results of prognostic analysis. Flow Cytometric Analysis indicated that MYEF2 expression was negatively correlated with dysfunctional CD8+ T cell markers. Kaplan-Meier survival analysis (based on IHC staining) revealed that GBM patients with elevated MYEF2 expression have a better prognosis. Knockdown of MYEF2 in GBM cells via in vitro assays was observed to promote cell proliferation and migration. Our study suggests that MYEF2 expression negatively correlates with T cell exhaustion and tumor progression, rendering it a potentially valuable prognostic biomarker for GBM.

Prognostic data analysis of surgical treatments for intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a commonly occurring disease in neurosurgery, yet its surgical treatment is controversial. This paper pertains to the study of the effects of different treatment regimens on the outcome of ICH population. Based on a globally shared third-party MIMIC-III database, the researchers firstly described the dissimilarities in survival probability, mortality, and neurological recovery among mainstream treatments for ICH; secondly, patient classification was determined by important clinical features; and outcome variations among treatment groups were compared. The 28-day, 90-day, and in-hospital mortality in the craniotomy group were significantly lower than minimally invasive surgery (MIS) and non-surgical group patients; and, the medium/long-term mortality in MIS group was significantly lower than the non-surgical group. The craniotomy group positively correlated with short-term GCS recovery compared with the MIS group; no difference existed between the non-surgical and MIS groups. The craniotomy group 90-day survival probability and short-term GCS recovery were superior to the other two treatments in the subgroups of first GCS 3-12; this tendency also presented in the MIS group over non-surgical group. For milder patients (first GCS > 12), the three treatment regimens had a minimal effect on patient survival, but the non-surgical group showed an advantage in short-term GCS recovery. Craniotomy patients have a lower mortality and a better short-term neurological recovery in an ICH population, especially in short-to-medium term mortality and short-term neurological recovery over MIS patients. In addition, surgical treatment is recommendable for patients with a GCS ≤ 12.

TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas.

BACKGROUND: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. METHODS: In this study, we investigated TMEFF2 expression in surgical glioma tissue samples. In addition, we conducted bisulfite amplicon sequencing (BSAS) and methylation-specific PCR (MSP) to evaluate TMEFF2 methylation in glioblastoma (GBM) cells. Subsequently, we investigated the biological function of TMEFF2 in GBM cells. Moreover, we explored the prognostic significance of TMEFF2 in gliomas by analysing a cohort dataset from TCGA. RESULTS: Immunohistochemistry analysis of 75 paired glioma tumour and peritumoural tissues demonstrated that glioma tumour tissues expressed lower TMEFF2 levels than peritumoural tissues (P < 0.001). TMEFF2 promoter methylation levels were increased in glioblastoma cells compared with SVG p12 cells (P < 0.001). Inhibition of methylation reduced TMEFF2 methylation and increased its expression in LN229 and T98G cells (P < 0.05). Knockdown of TMEFF2 expression significantly promoted the proliferation of U87MG cells and primary GBM cells (P < 0.05). TMEFF2 methylation is negatively associated with IDH1, ATRX and TP53 mutations, and the subtype of glioma harbouring combined IDH1/ATRX/TP53 mutations was associated with low TMEFF2 methylation levels. Survival analysis confirmed that low TMEFF2 methylation levels are associated with good prognosis in glioma patients. CONCLUSIONS: Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas.

Treatment of Large and Complicated Scalp Defects with Free Flap Transfer.

BACKGROUND: Large scalp defects, especially those complicated by calvarial defects, titanium mesh exposure, or cerebrospinal fluid (CSF) leak, pose a challenge for the neurosurgeon and plastic surgeon. Here, we describe our experience of reconstructing the complex scalp defect with free flap transfer. METHODS: From October 2012 to September 2017, 8 patients underwent free flap transfer for the reconstruction of the scalp or complicated scalp and calvarial defects. Five patients presented with scalp tumor and the other 3 patients with scalp necrosis or ulceration (2 patients with titanium plate exposure). Seven anterolateral thigh flaps and one radial forearm flap were harvested and employed. The clinical data, including defect characteristics, flap type, complications, and outcomes, were recorded and analyzed. RESULTS: Five patients were pathologically diagnosed with malignant tumor, and 3 of them were given further radiotherapy. For the 2 patients with exposure of titanium plate, no titanium plate was removed. For the patient with scalp necrosis after decompressive craniectomy accompanied by CSF leakage, the CSF leak was stopped after reconstruction. The size of the flaps ranged from 3 to 14 cm in width and 4 to 18 cm in length. No flap failure occurred in these cases. From follow-up to the present, no ulceration or necrosis occurred. CONCLUSIONS: Free flap transfer is an ideal method for the reconstruction of large, complicated scalp defects with a one-stage operation. The anterolateral thigh flap is favored because of its durability, adjustability, water tightness, and infection prevention.

Crutchlike Incision Along the Mastoid Groove and Above the Occipital Artery Protects the Lesser Occipital Nerve and Occipital Artery in Microvascular Decompression Surgery.

BACKGROUND: Patients who have had microvascular decompression (MVD) surgery often report sensory discomfort around the surgical area. In most cases, injury of the lesser occipital nerve (LON) is responsible for this postoperative complication. This study aimed to explore an effective method to protect the LON and reduce postoperative discomfort. METHODS: Doppler was used to determine the course of the occipital artery (OA) and the incision. Direct LON identification and a novel crutchlike incision were performed from January 1, 2016, to February 1, 2017, to reduce postoperative sensory disturbance. Postoperative sensory disturbance was evaluated and retrospectively analyzed compared with previous linear incision cases (from January 1, 2015, to December 31, 2015). Anatomic information at the lateral occiput was measured and recorded. RESULTS: The difference in the amount of postoperative sensory disturbance at 3-month follow-up was significant (P = 0.008). Sensory disturbance was significantly lower in patients who had crutchlike incision (P = 0.002) and patients with direct LON identification (P = 0.035) compared with the previous linear incision cases. The distance from OA to the projection of the transverse sinus was 3.2 ± 0.6 cm at the mastoid groove and 2.5 ± 0.4 cm at a site 0.5-1.0 cm from the mastoid groove. CONCLUSIONS: A crutchlike incision at the mastoid groove superior to the OA reduced the incidence of postoperative sensory disturbance and OA injury. The mastoid groove and OA are simple landmarks for determination of the incision in microvascular decompression.

Intracisternal tuberculoma: a refractory type of tuberculoma indicating surgical intervention.

BACKGROUND: Central nervous system (CNS) tuberculoma is a rare disease with severe neurological deficits. This retrospective research is to review the data of patients diagnosed as CNS tuberculoma. Surgeries were performed in all patients. The clinical features especially the neurological image and the anatomical characters of the tuberculomas were concerned. METHODS: Totally 11 patients diagnosed as CNS tuberculoma were admitted in Guangzhou First People's Hospital (7cases) and Changzheng Hospital (4 cases) during 2006-2015. The data including preoperative condition, neurological imaging, and surgical findings was collected and analyzed. RESULTS: The lesions of nine patients (9/11) were totally or subtotally excised and two (2/11) were partially excised. Neurological functions of all patients were improved after surgery without secondary infection. Lesions of nine (9/11) patients preoperatively progressed as a result of paradoxical reaction. Of the 9 patients demonstrated paradoxical progression, all lesions were partially or totally located at the cisterns or the subarachnoid space. Preoperative ATTs lasted 2 to 12 months and tuberculomas were not eliminated. The arachnoid was found thickened and tightly adhered to the lesions during surgeries. Of the 2 cases that paradoxical reaction were excluded, both patients (case 6, intramedullary tuberculoma; case 11, intradural extramedullary tuberculoma) were admitted at onset of the disease. ATTs were preoperatively given for 1 week as neurological deficits aggravated. The tuberculous lesions of CNS or other system showed no obvious change and paradoxical reaction could not be established in both cases. CONCLUSIONS: Exudates of tuberculosis is usually accumulated in the cisterns and frequently results in the paradoxical formation of tuberculoma. Intracisternal tuberculoma is closely related to paradoxical reaction and refractory to anti-tuberculosis therapy. Micro-surgical excision is safe and effective. Early surgical intervention may be considered in the diagnosis of intracisternal tuberculoma especially when paradoxical reaction participates in the development of tuberculoma.

Periostin: a novel prognostic predictor for meningiomas.

The expression and role of periostin in meningiomas remains unknown. Tissue specimens of 175 convexity meningiomas were immunohistochemically examined with antibodies against periostin and Ki67. The expression levels of periostin and Ki67 were compared among different WHO groups. The role of periostin and Ki67 in postoperative prognosis of meningiomas was also analyzed. Negative (-) expression of Ki67 was observed in 101 (57.7 %) cases of all the surgical tissue samples. The Ki67 expressions differed significantly among the WHO groups (P < 0.001) and correlated positively with the WHO grade (r = 0.673, P < 0.001). Low/negative staining of periostin was observed in 116 (66.3 %) cases. The periostin expressions differed significantly among the WHO groups (P < 0.001). Periostin expression correlated positively with the WHO grade (r = 0.742, P < 0.001). There was a positive correlation between Ki67 expression and periostin (r = 0.513, P < 0.001). Both Ki67 expression and periostin expression was found statistically different between brain invasion tumor and non-invasion tumor (p < 0.001). The recurrence rate and PFS rate in both varied Ki67 expression groups and periostin expression groups was statistically different (P < 0.001). The survival time and PFS time in both varied Ki67 expression groups and periostin expression groups was also statistically different (P < 0.001). Periostin was expressed in tumor stroma of meningiomas. Both periostin and Ki67 may behave as a maker in predicting the grade and prognosis in meningiomas. Drugs that targets periostin aims at reducing invasion of meningioma patients should be further researched.

Analysis of the status of subject recruitment in clinical trials in Shandong, China.

Although subject recruitment for clinical trials in Shandong has been carried out with an awareness of international regulatory and ethical frameworks, there have been some defects in the recruitment process. The objective of this study is to analyze the current status of subject recruitment in Shandong. We conducted a survey among 198 principal investigators (PIs) and 543 subjects. The results were summarized and calculated as a percentage according to the responses to each question by PIs and subjects. This survey indicated that the ethics committee should strengthen the review of subject recruitment and enhance ethics training among board members. PIs should seek to improve the recruitment process.

Toward a Confucian family-oriented health care system for the future of China.

Recently implemented Chinese health insurance schemes have failed to achieve a Chinese health care system that is family-oriented, family-based, family-friendly, or even financially sustainable. With this diagnosis in hand, the authors argue that a financially and morally sustainable Chinese health care system should have as its core family health savings accounts supplemented by appropriate health insurance plans. This essay's arguments are set in the context of Confucian moral commitments that still shape the background culture of contemporary China.