Cost-effectiveness analysis of sintilimab plus IBI305 versus sorafenib for unresectable hepatic cell carcinoma in China.

BACKGROUND: Sintilimab combined with IBI305 treatment regimen had potential clinical benefits than sorafenib in the first-line treatment of patients with unresectable hepatic cell carcinoma (HCC). However, whether sintilimab plus IBI305 has economic benefits in China remains unclear. METHODS: From the perspective of Chinese payers, we used the Markov model to simulate patients with HCC receiving treatment with sintilimab plus IBI305 and sorafenib. The transition probability between health states was estimated using the parametric survival model, and the cumulative medical costs and utility of the two treatment methods were estimated. Considering the incremental cost-effectiveness ratios (ICERs) as the evaluation index, sensitivity analyses were performed to explore the impact of uncertainty on the results. RESULTS: Compared to sorafenib, sintilimab plus IBI305 generated an additional $17552.17 and 0.33 quality-adjusted life years, resulting in an ICER of $52817.89. The analysis outcomes were most sensitive to the total cost of sintilimab plus IBI305. With a willingness-to-pay threshold of $38,334, sintilimab plus IBI305 showed a 1.28% probability of being cost-effective. The total cost of sintilimab plus IBI305 should be reduced by at least 31.9% to be accepted by Chinese payers. CONCLUSIONS: Regardless of whether the price of sintilimab plus IBI305 and sorafenib is covered by Medicare, sintilimab plus IBI305 is unlikely to be cost-effective for first-line treatment of patients with unresectable HCC.

Differences in survival prognosticators between children and adults with H3K27M-mutant diffuse midline glioma.

AIMS: H3K27M-mutant diffuse midline glioma (DMG) is a rare and aggressive central nervous system tumor. The biological behavior, clinicopathological characteristics, and prognostic factors of DMG have not yet been completely uncovered, especially in adult patients. This study aims to investigate the clinicopathological characteristics and identify prognostic factors of H3K27M-mutant DMG in pediatric and adult patients, respectively. METHODS: A total of 171 patients with H3K27M-mutant DMG were included in the study. The clinicopathological characteristics of the patients were analyzed and stratified based on age. The Cox proportional hazard model was used to determine the independent prognostic factors in pediatric and adult subgroups. RESULTS: The median overall survival (OS) for the entire cohort was 9.0 months. Significant differences were found in some clinicopathological characteristics between children and adults. The median OS was also significantly different between the pediatric and adult subgroups, with 7.1 months for children and 12.3 months for adults (p < 0.001). In the overall population, the multivariate analysis identified adult patients, single lesion, concurrent chemoradiotherapy/radiotherapy, and intact ATRX expression as independent favorable prognostic factors. In the age-stratified subgroups, the prognostic factors varied between children and adults, with intact ATRX expression and single lesion being independent favorable prognostic factors in adults, while infratentorial localization was significantly associated with worse prognosis in children. CONCLUSIONS: The differences in clinicopathological features and prognostic factors between pediatric and adult patients with H3K27M-mutant DMG suggest the need for further clinical and molecular stratification based on age.

Comparison of surgery with or without adjuvant radiotherapy in treating central neurocytoma: a single-center retrospective real-world study.

PURPOSE: To investigate the efficacy and safety of adjuvant radiotherapy (RT) in patients with central neurocytoma (CN). METHODS: The study included 68 patients with CN retrospectively, was further divided into surgery + RT group (31 patients) and surgery alone group (37 patients). Progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs) were compared between the two groups. RESULTS: The median follow-up duration was 82.2 (interquartile range, 64.7-104.5) months. Patients in the surgery + RT group tended to have longer PFS than those in the surgery alone group (5-year PFS rate: 92.7% vs. 86.3%; P = 0.074). There was no significant difference in OS between the two groups (5-year OS rate: 96.8% vs. 94.3%; P = 0.639). Subgroup analysis revealed a significant improvement in PFS in patients receiving RT after surgery in patients who underwent subtotal resection (STR) (P = 0.045). In the overall population, univariate multivariate analysis revealed that gross total resection (GTR) (P = 0.002), tumor location in the unilateral ventricle (P = 0.008), and MIB-1 (Ki-67) labeling index (LI) < 5% (P = 0.009) were favorable independent prognostic factors for PFS. Whereas tumor location in the unilateral ventricle (P = 0.043) was a favorable independent prognostic factor for OS. Moreover, RT patients experienced AEs (Grade 1-2, well-tolerated). CONCLUSION: Adjuvant RT in the treatment of CNs showed satisfactory safety, and postoperative RT could improve PFS in STR patients. Furthermore, GTR, tumor development in the unilateral ventricle, and MIB-1 LI < 5% were found to be favorable factors affecting the prognosis of CNs.

Clinical analysis of 12 patients with primary lymphoepithelial carcinoma of the parotid gland.

BACKGROUND AND PURPOSE: The WHO recently designated salivary gland lymphoepithelial carcinoma as a unique malignant tumor that most commonly occurs in the parotid gland. This is a rare cancer and there are few reports in the literature. Among 854 patients with parotid gland tumors who were admitted to our institution, we diagnosed 12 patients (1.41%) with parotid lymphoepithelial carcinoma. METHODS: Retrospective analysis of 12 patients with parotid lymphoepithelial carcinoma diagnosed by the Department of Pathology, Xiangya Hospital of Central South University. RESULTS: All 12 patients had unilateral parotid gland disease and 8 had cervical lymph node metastasis. Five patients received PCR testing for the Epstein-Barr virus and two were positive. All patients received surgical treatment, two received surgical resection alone, nine received surgery and postoperative radiotherapy and chemotherapy, and one received surgery and postoperative chemotherapy. The postoperative follow-up time ranged from 13 to 77 months. As of the last follow-up, eight patients were tumor-free, one patient was lost to follow-up, and three patients died. The main cause of death was local tumor recurrence and multiple metastases throughout the body. CONCLUSION: Parotid lymphoepithelial carcinoma is a malignant neoplasm characterized by proliferation, invasion, and inclusion of poorly differentiated or undifferentiated carcinoma, and a high rate of metastasis to ipsilateral cervical lymph nodes. The comprehensive treatment method consists of radical resection combined with postoperative radiotherapy and chemotherapy. After this comprehensive treatment, the 1-year, 3-year, and 5-year overall survival rates of our patients were 100%, 78.8%, and 39.4%.

KLF2 protects BV2 microglial cells against oxygen and glucose deprivation injury by modulating BDNF/TrkB pathway.

Cerebral ischemia injury is common in cerebral ischemic disease, and treatment options remain limited. Krueppel-like factor 2 (KLF2) is reported to negatively regulate inflammation in several ischemic diseases. Our study aimed to investigate the effects and underlying mechanism of KLF2 in BV2 microglial cells exposed to oxygen and glucose deprivation (OGD). We first found decreased KLF2 and toll-like receptor 2 (TLR2)/TLR4 in these cells. OGD also led to decrease in cell viability and increase in LDH release, apoptosis, the Bax/Bcl-2 ratio, and caspase3/9 expression, as well as production of inflammatory cytokines (e.g., TNFα, IL-1ß and IL-6), reactive oxygen species (ROS), and TLR2/TLR4. To examine KLF2's effects on these OGD effects, we infected BV2 microglial cells with an ad-KLF2 or negative control vector, and we found that KLF2 reversed all of the effects of OGD exposure. Furthermore, KLF2 significantly increased levels of BDNF and TrkB in these cells, but these effects were blocked by K252a, a BDNF/TrkB inhibitor. K252a also decreased cell viability and increased apoptosis, inflammatory factors, ROS production, and TLR2/TLR4 expression in OGD-exposed BV2 cells that were treated with KLF2, were implying that K252a could reverse the effects of KLF2 on these cells. Taken together, our study results indicate that KLF2 may protect BV2 microglial cells against OGD injury by activating the BDNF/TrkB pathway.

Screening of significant biomarkers related with prognosis of liver cancer by lncRNA-associated ceRNAs analysis.

This study aimed to identify significant biomarkers related to the prognosis of liver cancer using long noncoding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) analysis. Differentially expressed mRNA and lncRNAs between liver cancer and paracancerous tissues were screened, and the functions of these mRNAs were predicted by gene ontology and pathway enrichment analyses. A ceRNA network consisting of differentially expressed mRNAs and lncRNAs was constructed. LncRNA FENDRR and lncRNA HAND2-AS1 were hub nodes in the ceRNA network. A risk score assessment model consisting of eight genes (PDE2A, ESR1, FBLN5, ALDH8A1, AKR1D1, EHHADH, ADRA1A, and GNE) associated with prognosis were developed. Multivariate Cox regression suggested that both pathologic_T and risk group could be regarded as independent prognostic factors. Furthermore, a nomogram model consisting of pathologic_T and risk group showed a good prediction ability for predicting the survival rate of liver cancer patients. The nomogram model consisting of pathologic_T and a risk score assessment model could be regarded as an independent factor for predicting prognosis of liver cancer.

A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/ß-catenin pathway.

Hepatocellular carcinoma (HCC) is a prevalent solid tumor with a high global death rate. SRY box 9 (SOX9) has been reported as an oncogene in HCC by several studies, but the underlying mechanism remains largely unexplored. Here, we confirmed upregulation of SOX9 in HCC tissues and cell lines and validated that SOX9 facilitates proliferation, migration and invasion in HCC. We subsequently identified that the long non-coding RNA (lncRNA) SOX9 antisense RNA 1 (SOX9-AS1) is a neighbor gene to SOX9; SOX9-AS1 is also upregulated in HCC, and its expression is positively correlated with that of SOX9. In addition, SOX9-AS1 appears to have prognostic significance in HCC patients. We showed that SOX9-AS1 aggravates HCC progression and metastasis in vitro and in vivo. We demonstrated that SOX9-AS1 sponges miR-5590-3p to elevate SOX9 expression, and that SOX9 in turn transcriptionally activates SOX9-AS1. Moreover, we verified that SOX9-AS1 regulates SOX9 and its known downstream Wnt/ß-catenin pathway so as to facilitate epithelial-to-mesenchymal transition. The results of our rescue assays suggest that SOX9-AS1 regulates HCC progression through SOX9 and the Wnt/ß-catenin pathway. In conclusion, our study demonstrates that a SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in HCC through the Wnt/ß-catenin pathway, suggesting SOX9-AS1 as a novel potential prognostic and treatment target for HCC.

c-Fos/microRNA-18a feedback loop modulates the tumor growth via HMBOX1 in human gliomas.

Glioma is one of the most aggressive and lethal human cancers in central nervous system (CNS). Recent studies have identified many dysregulated microRNAs (miRNA, miR) in human glioma, which are a class of small non-coding RNA molecules. Increasing data have shown that miR-18a plays significant roles in several tumors. However, its effects on glioma are unclear. In this study, we found the elevated expression of c-Fos and miR-18a in tissues of human glioma patients and glioma cells. Then the miR-18a inhibitor or c-Fos siRNA were transfected into glioma cells line H4 to determine their effects on H4 cells. MTT assay showed that both miR-18a inhibitor and si-c-Fos suppressed the H4 cell proliferation. Transwell assay showed the reduced cell migration by miR-18a inhibitor and si-c-Fos in H4 cells. The increased level of H4 cells apoptosis by miR-18a inhibitor and si-c-Fos was also determined. Moreover, knockout of c-Fos decreased the miR-18a level, while miR-18a inhibitor reduced the c-Fos level in H4 cells. Added with the results of ChIP assay, this report showed a positive feedback between c-Fos and miR-18a. Finally, luciferase assay showed that HMBOX1 was directly targeted by miR-18a in H4 cells, and the HMBOX1 siRNA reversed the effects of miR-18a inhibitor on cell proliferation, migration and apoptosis of H4 cells. In conclusion, our study determine that c-Fos/miR-18a feedback loop promotes the tumor growth of gliomas by HMBOX1, providing important clues for understanding the key roles of transcription factor mediated mRNA-miRNA functional network in the regulation of gliomas.

Distinguishing Intracerebral Hemorrhage from Acute Cerebral Infarction through Metabolomics.

BACKGROUND: Acute cerebral infarction (ACI) and intracerebral hemorrhage (ICH) are potentially lethal cerebrovascular diseases that seriously impact public health. ACI and ICH share several common clinical manifestations but have totally divergent therapeutic strategies. A poor diagnosis can affect stroke treatment. OBJECTIVE: To screen for biomarkers to differentiate ICH from ACI, we enrolled 129 ACI and 128 ICH patients and 65 healthy individuals as controls. METHODS: Patients with stroke were diagnosed by computed tomography/magnetic resonance imaging, and their blood samples were obtained by fingertip puncture within 2-12 h after stroke initiation. We compared changes in metabolites between ACI and ICH using dried blood spot-based direct infusion mass spectrometry technology for differentiating ICH from ACI. RESULTS: Through multivariate statistical approaches, 11 biomarkers including 3-hydroxylbutyrylcarnitine, glutarylcarnitine (C5DC), myristoylcarnitine, 3-hydroxypalmitoylcarnitine, tyrosine/citrulline (Cit), valine/phenylalanine, C5DC/3-hydroxyisovalerylcarnitine, C5DC/palmitoylcarnitine, hydroxystearoylcarnitine, ratio of sum of C0, C2, C3, C16, and C18:1 to Cit, and propionylcarnitine/methionine were screened. An artificial neural network model was constructed based on these parameters. A training set was evaluated by cross-validation method. The accuracy of this model was checked by an external test set showing a sensitivity of 0.8400 (95% confidence interval [CI], 0.7394-0.9406) and specificity of 0.7692 (95% CI, 0.6536-0.8848). CONCLUSION: This study confirmed that metabolomic analysis is a promising tool for rapid and timely stroke differentiation and prediction based on differential metabolites.

Effective Prevention for Portal Venous System Thrombosis After Splenectomy: A Meta-Analysis.

PURPOSE: Portal venous system thrombosis (PVST) is a common and potentially life-threatening complication of splenectomy for portal hypertension due to cirrhosis. METHODS: A meta-analysis was conducted to study the necessity of pharmacologic prophylaxis of PVST after splenectomy and how to select the feasible treatment method. Articles were searched through the PubMed, EMBASE, Cochrane Library databases, and CNKI. RESULTS: Overall, 404 articles were initially identified, and 11 of them were eligible. Among these selected articles, 7 articles were associated with the necessity of anticoagulation for prevention of PVST, while 5 were about the drug selection. We first demonstrated that the incidence of PVST after splenectomy was significantly lower in patients who received the preventive measures than in those who did not (odds ratio [OR]: 0.22, 95% confidence interval [CI]: 0.13-0.39, P < .00001). Then, we compared the new-style treatment with the conventional treatment and found that patients with new therapy method had lower incidence of PVST than those who received conventional treatment (OR: 0.37, 95% CI: 0.27-0.51, P < .00001). Also, some studies (n = 4) reported that early and combination use of anticoagulation drugs can lead to better outcome for patients with splenectomy and devascularization. CONCLUSION: Preventative use of anticoagulant drugs might decrease the incidence of PVST after splenectomy in patients with portal hypertension, new anticoagulant drugs such as low-molecular-weight heparin should be used, and early or combination use of anticoagulation drugs might lead to lower PVST incidence for patients.

[Clinical analysis of microsurgical treatment of giant intracranial arteriovenous malformations].

OBJECTIVE: To explore the clinical features and microsurgical treatment strategies of giant intracranial arteriovenous malformations (AVM). METHODS: A total of 15 cases of giant intracranial AVM treated with microsurgery were analyzed retrospectively. According to the Spetzler-Martin grade, there were 4 cases of grade Ⅳ, 11 cases of grade Ⅴ. Pre-operative endovascular embolizations were carried out in 3 AVMs. RESULTS: All the included patients were confirmed as giant intracranial AVM by magnetic resonance angiography (MRA), digital subtraction angiography (DSA), 3-dimensional CT angiography (3D-CTA) before surgery. All the resected tissues were sent for pathological examination, and the diagnoses were confirmed as AVM. The average operation time of the 15 patients was 10.3 ±6.9 hours. After 1-3 months, all the patients were rechecked by DSA, the large vascular malformations in 12 cases were completely resected, 3 cases had a small amount of residual further treated with gamma knife treatment. Magnetic resonance imaging (MRI) and MRA examination indicated that the residual AVM was occluded after 12 months. Patients were followed up at 6, 12 and 24 months after operation, and assessed by Glasgow outcome scale (GOS) score: 13 cases good, 1 cases mild disability, 1 cases severe disability; the good rate was 86.6%, with no dead case. CONCLUSION: Sufficiently preoperative preparation, appropriate operative methods and skills are necessary to treat giant intracranial arteriovenous malformation.

[Experimental Study on Soil Moisture Remote Sensing Based on Polarization Spectrum].

As a novel remote sensing technique, polarimetric detecting technology is a useful supplement to traditional hyperspectral remote sensing technology, which provides more information for remote sensing. By taking advantage of the polarization characteristics of the surface reflecting light of soil with different moisture, the polarization spectral method is applied to measure soil moisture. The spectropolarimeter was used to measure the polarized reflectance spectrum of different soil moisture. The correlation between soil moisture and polarization spectrum was analyzed. The polarization characteristics of soil surface reflecting light in different viewing angles were surveyed by experiments. The experimental results show that: in the higher soil moisture conditions, the polarization spectrum and soil moisture have a certain connection, especially in the 500～700 nm band and soil moisture is directly proportional to the degree of polarization; but in low soil moisture conditions, the correlation of polarization spectrum and soil moisture is not obvious; in addition, the polarization spectrum are influenced by viewing angles, for example, when the incident angle of source light is fixed at 50°, while the viewing angle of instrument is between 20° and 60°, the degree of polarization increases with the viewing angle. When the viewing angle becomes wider,, the degree of polarization changed more significantly with the soil moisture.

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells.

The Ezh2 gene is an important member of the polycomb-group (PcG) family. As a newly identified oncogene, the expression of Ezh2 has been shown to be significantly increased in prostate cancer, breast cancer, renal cell carcinoma and hepatic cancer; however, a role for Ezh2 in the occurrence of glioma has not yet been reported. In this study, we found that the Ezh2 gene is highly expressed in U87 human glioma cells. Using RNA interference, we demonstrated that the downregulation of Ezh2 expression in U87 human glioma cells resulted in apoptosis and a cell cycle arrest in the G0/G1 phase. In addition, we found that silencing of the Ezh2 gene altered the mitochondrial membrane potential and promoted the release of cytochrome c from the mitochondria. Furthermore, the reduced expression of Ezh2 altered the Bax and Bcl-2 protein levels and led to the activation of caspase 9 and 3. These results indicate that the apoptosis induced in U87 human glioma cells by the silencing of the Ezh2 gene is related to the mitochondrial pathway.

Characteristics and endovascular treatment of intracranial vertebral artery aneurysms.

OBJECTIVE: The clinical and angiographic characteristics of vertebral artery (VA) aneurysm were evaluated to demonstrate the safety and efficacy of endovascular techniques of VA aneurysms. MATERIALS AND METHODS: Case records of 38 consecutive patients with 40 VA aneurysms admitted during a 2-year period were reviewed. The data analyzed included age, sex, size of aneurysm, ruptured or unruptured, endovascular techniques, angiographic results after embolization, duration of follow-up, angiographic follow-up results and Glasgow Outcome Score at follow-up. RESULTS: Of the 38 patients, 33 patients had 35 dissecting aneurysms and five patients had five saccular aneurysms. Seventeen (42.5%) aneurysms were ruptured. Of the 34 patients treated with endovascular techniques, immediate post-procedural angiograms showed complete and subtotal occlusion (>90%) of 27 (67.5%) aneurysms and incomplete and no occlusion of 13 (32.5%) aneurysms, including four conservatively treated aneurysms. A clinical improvement or stable outcome was achieved in all the patients (100%) during a mean 12.1-month follow-up. There was no complication related to endovascular treatment and no rebleeding during the follow-up period. Angiographic follow-up (mean of 7.2 months, range 1-18 months) was available in all the patients. Complete and subtotal occlusion was observed in 31 (81.6%) patients, including one spontaneous thrombosis of a conservatively treated VA dissecting aneurysm. Recanalization in two patients (5.9%) at 6 and 9 months did not require retreatment. CONCLUSION: This series demonstrates the safety and efficacy of multimodality of endovascular techniques for VA aneurysms.

Endovascular embolization of small ruptured intracranial aneurysms using a biplane angiographic system with three-dimensional rotational digital subtraction angiography.

Endovascular coiling of small, ruptured intracranial aneurysms is controversial because of technical difficulties. We analyzed the clinical and angiographic effects of endovascular treatment of 39 small (5mm) ruptured intracranial aneurysms (in 37 patients) at our institution between March 2004 and March 2007. Procedures were carried out on a biplane angiographic system with three-dimensional rotational digital subtraction angiography. Immediately after embolization, 30 aneurysms were completely occluded and nine had a residual neck. The volumetric percentage occlusion was 45.2+/-9.7%. Angiographic and clinical follow-up was at 6.1 months and 15.9 months, respectively. Delayed rebleeding was not observed. Complications directly related to the procedure were encountered in two patients (one coil migration and one intraoperative rupture). For 34 patients, the final outcome was excellent or good, one suffered a moderate disability, one a severe disability and one patient died. The results suggest that endovascular embolization is effective and safe for patients with small ruptured intracranial aneurysms.

The pre-treatment effect on brain injury during restoration of normal perfusion pressure with hemodilution in a new rat model of chronic cerebral hypoperfusion.

OBJECTIVES: To investigate the effect of hemodilution with high-concentration human serum albumin (HSA) on brain injury in a rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations. METHODS: The animal model was established by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein and the ipsilateral common carotid artery, followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. The agent (20% HSA) or control solution (0.9% sodium chloride) was administered intravenously at a dosage of 1% body weight 24 hours before ligation of the fistula. Blood-brain barrier (BBB) disruption was judged by extravasation of Evans blue (EB) dye. EB, water content and the changes of myeloperoxidase (MPO) activity and superoxide dismutase (SOD) activity in rat brains 24 hours after ligation of the fistula were determined. RESULTS: EB and water content in rat brains of the pre-treated group were significantly decreased compared with the control group accompanied by reduction of MPO activity and enhancement of SOD activity. DISCUSSION: Hemodilution with high-concentration HSA has a certain pre-treatment effect on brain injury after ligation of the fistula in rat model of chronic cerebral hypoperfusion, which may be resulted from improved microcirculation, decrease in inflammatory cell infiltration and inactivation of oxygen free radicals.

[Treatment of dural arteriovenous fistula by transarterial embolization with low dose of N-butyl-2-cyanoacrylate].

OBJECTIVE: To evaluate the efficacy of treatment of dural arteriovenous fistula (DAVF) by transarterial embolization with low dose of N-butyl-2-cyanoacrylate (NBCA). METHODS: Eighteen patients, 6 males and 12 females, aged 47.5 (23-72), with DAVF, 12 with carotid cavernous fistula and 6 with fistula in parietal lobe, underwent transarterial embolization with low dose of NBCA (10%-20%). The key point of transarterial embolization with low dose of NBCA was that low dose NBCA was injected and embolized the veins and then was reversed into the other supplying arteries. RESULTS: Seventeen patients with DAVF in cavernous region and 6 patients with DAVF in parietal lobe were cured anatomically, with the clinical syndromes disappearing. In 1 patient with DAVF in cavernous region the clinical syndrome were moderately improved after transarterial embolization, however, worsened 2 days later. Cerebrovascular angiography demonstrated that the vein was not completely embolized and the draining vein was broadened, and the clinical syndromes were moderately improved again after carotid artery compression therapy for 10 days. CONCLUSION: Convenient and fast, and with low cost and satisfying efficacy, transarterial embolization with low dose of NBCA is a better choice for treatment of DAVF in some cases. The key point of this approach is that the tip of microcatheter is close as much as possible to the fistulae, and NBCA is injected into the fistulae and make the vein diffused well. Attention should be paid to avoid dangerous anastomosis.