Pharmacokinetics, Bioavailability, and Tissue Distribution of the Kirsten Rat Sarcoma Inhibitor Adagrasib in Rats Using UPLC-MS/MS.

Purpose: Adagrasib is a selective and reversible inhibitor of KRAS G12C, which significantly delays the progression of solid tumors. However, the absorption, distribution, metabolism, and excretion of adagrasib in vivo are unclear. This study explores the absorption and distribution of adagrasib in vivo. Methods: An ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of adagrasib in the rat plasma and tissue. Sprague-Dawley rats were intravenous administrated (5 mg/kg) and oral administrated (30 mg/kg) with adagrasib, and the plasma concentration of adagrasib was determined. After single oral administration of adagrasib (30 mg/kg), the heart, liver, spleen, lung, kidney, intestine, and pancreas were excised. The organs were homogenized with saline solution, and the concentration of adagrasib in tissues was determined. Results: The intra- and inter-day accuracy were from 84.90% to 113.47%, and the precision was within ±15%. The matrix effect and recovery were within ±15%. The maximum plasma concentration (Cmax) of adagrasib was 677.45 ± 58.72 ng/mL. The elimination half-life time (t1/2) was 3.50 ± 0.21 h after oral administration and 2.08 ± 0.54 h after intravenous administration. The oral bioavailability was 50.72%. The highest concentrations of adagrasib in liver was 5047.80 ± 676.48 ng/g at 2 h after administration, and it was still detectable at 24 hours after administration. Conclusion: Adagrasib was slowly absorbed and cleared rapidly, and it was also widely distributed in vivo. This study provides a potential reference for adagrasib in clinical studies.

Treatment of brainstem and fourth ventricle lesions by the full neuroendoscopic telovelar approach.

OBJECTIVE: To explore the surgical techniques, advantages, and disadvantages of neuroendoscopic telovelar approach in the treatment of brainstem and fourth ventricle lesions. METHODS: The clinical data of 5 patients treated by neuroendoscopic telovelar approach from March 2020 to March 2022 were analyzed retrospectively. RESULTS: Among the 5 patients, there were 3 cavernous hemangiomas in pontine arm and 2 tumors in brainstem and fourth ventricle. All patients could successfully complete the operation, and 4 patients recovered well, other 1 patient discharged automatically for serious complications of other systems after the operation. CONCLUSION: The telovelar approach has gained popularity as a safe and effective strategy for lesions in fourth ventricular and brainstem. However, without removing the posterior arch of the atlas, it is difficult to enter the upper part of the fourth ventricle under a microscope. Transcranial neuroendoscopy can effectively compensate for the shortcomings of microscopy, whether used as an auxiliary measure for microsurgery or alone with proficient endoscopic techniques, it will provide greater application in minimally invasive surgery for fourth ventricle and brainstem lesions. By utilizing the excellent degree of freedom of transcranial neuroendoscopy, there is no need to open the posterior arch of the atlas, making the surgery more minimally invasive. However, the sample size of this study is small, and it was completed under the very mature neuroendoscopic technology of our team. Its general safety and practicality still require extensive clinical research validation.

Surgical Clipping of Intracranial Aneurysms Using a Transcranial Neuroendoscopic Approach.

OBJECTIVE: This retrospective study was performed to evaluate the feasibility and safety of surgically clipping intracranial aneurysms using a transcranial neuroendoscopic approach. METHODS: A total of 229 patients with cerebral aneurysms were included in our study, all of whom were treated with clamping surgery at Wuhan University People's Hospital. They were divided into neuroendoscopic and microscopic groups, according to whether or not neuroendoscopy was used for the clamping surgery. We statistically analyzed the patients' baseline data, surgical outcomes, and complications, which were then evaluated to assess the treatment effect. RESULTS: The baseline characteristics were not statistically significant, except for gender, for which the proportions of female patients in the two groups were 69 (56.1%) and 46 (43.4%). There were no patients with incomplete aneurysm clamping or parent vessel occlusion in the neuroendoscopic group, and there were 4 (3.8%) and 2 (1.9%) in the microscopic group, respectively; however, there was no statistically significant difference in the comparison of the two groups. The mean operative times of the two groups were 181 min and 154 min, respectively, and were statistically different. However, the mRS scores of the two groups showed no significant difference in patient prognosis. The differences in complications (including limb hemiplegia, hydrocephalus, vision loss, and intracranial infection) were not statistically significant, except for cerebral ischemia, for which the proportions of patients in the two groups were 8 (6.5%) and 16 (15.1%). CONCLUSIONS: Neuroendoscopy can provide clear visualization and multi-angle views during aneurysm clipping, which is helpful for ensuring adequate clipping and preventing complications.

BCL2A1 is associated with tumor-associated macrophages and unfavorable prognosis in human gliomas.

B-cell lymphoma 2-related protein A1 (BCL2A1) is a member of the BCL-2 family. Previous studies have shown that BCL2A1 is closely related to the tumorigenesis and resistance to chemotherapy of multiple solid tumors, such as breast cancer. However, the expression pattern and potential biological function of BCL2A1 in glioma remain unknown. For the first time, we found that the expression of BCL2A1 was higher in human glioma tissues than in normal brain tissues (NBTs) in both public datasets and an in-house cohort. High BCL2A1 expression was associated with advanced WHO grade, IDH 1/2 wild type and the mesenchymal (ME) subtype, and its overexpression in glioma predicted resistance to temozolomide (TMZ) chemotherapy and unfavorable prognosis. In addition, Gene set enrichment analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that BCL2A1 was significantly correlated with the immune response and immune-related pathways, and BCL2A1 expression was positively correlated with microenvironmental parameters (immune, stromal, and ESTIMATE scores) and macrophage infiltration. Interestingly, bioinformatic prediction and immunohistochemical/immunofluorescence staining analysis revealed that BCL2A1 expression was obviously associated with the tumor-associated macrophages (TAMs) markers CD68 and CCL2. Notably, knockdown of BCL2A1 significantly inhibited cell proliferation of U87 and U251 in vitro, induced smaller tumor size and prolonged survival time of mice in vivo. Co-culture experiments of macrophages and GBM cells showed that BCL2A1 knockdown inhibited macrophage migration. Meanwhile, knockdown of BCL2A1 was associated with low expression of CD68 and CCL2 in intracranial xenograft model. This may suggest that BCL2A1 promotes the progression of glioma and influences the prognosis of patients by participating in TAMs infiltration. In conclusion, these findings suggest that BCL2A1 could serve as a promising prognostic indicator and immunotherapy target in gliomas.

Ursolic Acid Alleviates Neuroinflammation after Intracerebral Hemorrhage by Mediating Microglial Pyroptosis via the NF-κB/NLRP3/GSDMD Pathway.

The neuroinflammatory response after intracerebral hemorrhage (ICH) causes a large amount of neuronal loss, and inhibiting the inflammatory response can improve the prognosis. In previous laboratory studies and clinical trials, ursolic acid (UA) inhibited the inflammatory response, but whether it can be administered to inhibit the neuroinflammatory response after cerebral hemorrhage is unknown. The aim of this study was to investigate the effects of ursolic acid after cerebral hemorrhage. Online databases were used to obtain potential therapeutic targets of ursolic acid for the treatment of cerebral hemorrhage, and possible mechanisms were analyzed by KEGG, GO, and molecular docking. A rat model of cerebral hemorrhage was established using collagenase, and an in vitro cerebral hemorrhage model was constructed by adding hemin to BV2 cell culture medium. Enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), immunofluorescence, TUNEL staining, and calcein/PI staining were used to investigate the degree of microglial M1 polarization, changes in the levels of inflammatory factors, activation of the NF-κB pathway, and changes in the indicators of cellular death after ursolic acid treatment. In addition, phorbol 12-myristate 13-acetate (PMA) was used to activate the NF-κB pathway to verify that ursolic acid exerts its anti-neuroinflammatory effects by regulating the NF-κB/NLRP3/GSDMD pathway. Network pharmacology and bioinformatics analyses revealed that ursolic acid may exert its therapeutic effects on cerebral hemorrhage through multiple pathways. Together, in vivo and in vitro experiments showed that ursolic acid inhibited microglial M1 polarization and significantly reduced the levels of p-NF-κB, GSDMD-N, cleaved caspase-1, TNF-α, IL-6, and IL-1ß, which were significantly inhibited by the use of PMA. Ursolic acid inhibits microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway to alleviate neuroinflammatory responses after cerebral hemorrhage.

Bibliometric analysis of scientific publications on cryptorchidism: Research hotspots and trends between 2000 and 2022.

Background: Cryptorchidism is defined as failure of unilateral or bilateral testicular descent, which increases the risk of infertility and testicular carcinoma. Although there is much research on cryptorchidism, few studies have used the bibliometric analysis method. The purpose of this study was to conduct a comprehensive analysis of cryptorchidism from muti-dimensional perspectives to summarize the research hotspots and trends in cryptorchidism research. Methods: Relevant studies on cryptorchidism were retrieved from the Web of Science Core Collection (WoSCC) database from 2000 to 2022. A comprehensive bibliometric analysis of cryptorchidism was performed by using the CiteSpace, Tableau Public, and VOSviewer software, including the annual distributions of publications, countries, authors, institutions, journals, references, and keywords. Results: From January 1st, 2000 to May 17th, 2022, a total of 5023 papers concerning cryptorchidism were identified for analysis. The USA contributed the most publications (n = 1193) in this field, and the annual number of publications rose rapidly in China. The University of Melbourne published the largest number of papers (n = 131). "Hutson, John M." was the most core author ranked by publications (n = 51), and "Skakkebaek, Niels E." enjoyed the largest number of citations (4441). The JOURNAL OF UROLOGY published the largest number of papers (n = 225), while the average citations per publication of the 75 papers in HUMAN REPRODUCTION reached 62.38. Additionally, burstness analysis of references and keywords showed that cryptorchidism research was mainly focused on the exploration of the optimal mode of treatment for cryptorchidism, including hypogonadism such as Kallmann syndrome and Klinefelter syndrome. Conclusion: Cryptorchidism has attracted continuous attention from the scientific community concerned. International collaboration in the field has witnessed significant growth in recent years and remains essential to further enhance collaborative efforts between scholars from different countries. In addition, the exploration of the optimal treatment modality for cryptorchidism, especially in the prevention of adult infertility, remains a major focus of future research. High-quality follow-up studies are also needed in the future. The pathogenesis (especially at the genetic level) and treatment of hypogonadism such as Kallmann syndrome and Klinefelter syndrome have attracted increasing attention recently, which may usher in some breakthroughs in coming years.

Catalytic Asymmetric Reverse Prenylation of Indol-2-one Enabled a Synthesis of (-)-Debromoflustramine A.

A catalytic asymmetric nucleophilic reverse prenylation of indol-2-ones in situ generated from 3-bromooxindoles with prenyltributylstannane promoted by Ni(II)/chiral N,N'-dioxide was developed. This reaction provides facile access to C3 reverse-prenylated oxindoles in good to excellent enantioselectivities, which enabled the asymmetric synthesis of debromoflustramine A in five steps.

Post-operative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage: factors and clinical outcomes.

OBJECTIVE: To explore factors affecting postoperative rebleeding in patients with spontaneous supratentorial intracerebral hemorrhage (SSICH). METHODS: We retrospectively analyzed data from 724 patients with SSICH treated at Renmin Hospital of Wuhan University from December 2018 to October 2021. Finally, 294 people were eligible to be included in this study. Hematoma locations were classified as basal ganglia, thalamus, subcortex, or intraventricular. Surgery was categorized as neuroendoscopic surgery, burr hole (stereotactic drilling and drainage), or open craniotomy. Postoperative rebleeding was recorded. The incidence, risk factors, and prognosis of postoperative rebleeding were evaluated. RESULTS: All procedures were successfully completed. Postoperative rebleeding occurred in 57 patients (19.83%, 57/294). Univariate logistic regression analysis identified these risk factors for rebleeding: admission Glasgow Coma Scale (GCS) score, irregular hematoma morphology by preoperative Computed Tomography (CT), postoperative hypertension, hematoma location, surgical method (P<0.05), and preoperative hematoma volume (P<0.1). Multivariate logistic regression analysis confirmed admission GCS score, irregular hematoma morphology by preoperative CT, postoperative hypertension, hematoma location, and surgical method as significant risk factors (P<0.05). Burr hole surgery and basal ganglia hematomas were associated with increased odds of rebleeding, and the mortality rates in patients with rebleeding versus no rebleeding were 7.02% versus 0.84%. CONCLUSIONS: Neuroendoscopic surgery, craniotomy, and burr hole are all effective for treating SSICH, but burr hole surgery was an important risk factor for rebleeding and an adverse outcome. Admission GCS score, irregular hematoma morphology, blood pressure control, hematoma location, and surgical method are affected the risk of postoperative rebleeding. 3D Slicer-assisted neuroendoscopic surgery may be the most effective treatment for many patients with SSICH.

Global research status and hotspots of radiotherapy for prostate cancer: a bibliometric analysis based on Web of Science from 2010-2022.

Background: Radiotherapy (RT) is one of the important treatments for various cancer types and its application to prostate cancer (PCa) has also gradually gained increasing attention. However, there is a lack of comprehensive and objective studies on the overall status of research on RT for PCa. This article aims to summarize and quantify the dynamic trends of RT in PCa by using bibliometrics. Methods: Studies on RT for PCa were screened from the Web of Science Core Collection (WoSCC) database between 1 January 2010 and 21 November 2022 to collate and quantify information characteristics by analyzing parameters including annual publications, countries/regions, institutions and authors with the aid of the bibliometric software CiteSpace and VOSviewer. In addition, research trends and hotspots were explored by analyzing keywords and co-cited references. Results: A total of 21338 documents were retrieved. The United States of America (USA) ranked first and maintained the leading position among all countries in the number of publications (8489) and total citations (266342). The University of Toronto was the most active institution in total publications (n=587). Paul L Nguyen enjoyed the most publications (n=179), and Michael J Zelefsky enjoyed the most co-citations (n=3376). INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS published the most papers (n=1026), and was the most frequently co-cited journal (n=78550). The largest and closest cluster in the reference cluster analysis was "oligorecurrent prostate cancer". The timeline view of keywords reveals that cluster "biochemical recurrence(BCR)" is ongoing. Moreover, keywords burstness analysis showed that "radiation dosimetry", "dose rate brachytherapy(BT)", "salvage radiotherapy", "stereotactic body radiotherapy(SBRT)", "guideline", and "multicenter" were the terms with great bursts in the past a few years. Conclusion: The application of RT targeting oligometastatic prostate cancer(OMPC) has garnered considerable attention among researchers. SBRT and BT have become hot topics in the field. Additionally, the BCR of PCa has long been a critical issue requiring extensive research and resolution, and salvage radiotherapy has currently emerged as a closely related research focus. Related large-scale multicenter studies have been conducted over the past few years, providing valuable insights. More high-quality research is expected to be employed to guide clinical decision-making.

Perihematomal edema after minimally invasive surgery: a matter of concern to neurosurgeons.

The purpose of this study is to explore the evolution of brain edema after minimally invasive surgery in deep spontaneous cerebral hemorrhage (DSICH) treatment and to analyze the differences in edema after different surgical methods. The clinical data of 105 patients with DSICH treated at Renmin Hospital of Wuhan University from January 2020 to June 2022 were analyzed retrospectively. Among them, 54 patients were treated with minimally invasive puncture and drainage surgery (MIPDS group), and 51 were treated with neuroendoscopic surgery (NES group). Continuous computed tomography images of patients in the hospital and 3D Slicer software were used to quantitatively calculate the edematous area to explore the changes in perihematomal edema volume in the two groups after the operation. The peak volume of postoperative edema (37.36±10.51 mL) in the MIPDS group was more extensive than that in the NES group, and its net increase in edema volume was 16.86±10.01 mL more than that in the NES group. The relative edema index (0.86±0.26) was lower in the NES group than in the MIPDS group (P < 0.05). The peak of postoperative edema in the MIPDS group was at 6-8 days after the operation, and that in the NES group was most often at 3-5 days after the operation. There are differences in perihematomal edema of DSICH treated by different minimally invasive methods. Compared with the MIPDS group, the NES group showed earlier peak of cerebral edema and lower degree of cerebral edema. The absolute regression volume of edema in the MIDPs group was greater than that in the NEs group, but there was no difference in the regression rate of edema between the two groups.

Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Role of Glucose Metabolic Reprogramming in Breast Cancer Progression and Drug Resistance.

The involvement of glucose metabolic reprogramming in breast cancer progression, metastasis, and therapy resistance has been increasingly appreciated. Studies in recent years have revealed molecular mechanisms by which glucose metabolic reprogramming regulates breast cancer. To date, despite a few metabolism-based drugs being tested in or en route to clinical trials, no drugs targeting glucose metabolism pathways have yet been approved to treat breast cancer. Here, we review the roles and mechanisms of action of glucose metabolic reprogramming in breast cancer progression and drug resistance. In addition, we summarize the currently available metabolic inhibitors targeting glucose metabolism and discuss the challenges and opportunities in targeting this pathway for breast cancer treatment.

Effect of Anthropogenic Disturbances on the Microbial Relationship during Bioremediation of Heavy Metal-Contaminated Sediment.

Soil, sediment, and waters contaminated with heavy metals pose a serious threat to ecosystem function and human health, and microorganisms are an effective way to address this problem. In this work, sediments containing heavy metals (Cu, Pb, Zn, Mn, Cd, As) were treated differently (sterilized and unsterilized) and bio-enhanced leaching experiments were carried out with the addition of exogenous iron-oxidizing bacteria A. ferrooxidans and sulfur-oxidizing bacteria A. thiooxidans. The leaching of As, Cd, Cu, and Zn was higher in the unsterilized sediment at the beginning 10 days, while heavy metals leached more optimally in the later sterilized sediment. The leaching of Cd from sterilized sediments was favored by A. ferrooxidans compared to A. thiooxidans. Meanwhile, the microbial community structure was analyzed using 16S rRNA gene sequencing, which revealed that 53.4% of the bacteria were Proteobacteria, 26.22% were Bacteroidetes, 5.04% were Firmicutes, 4.67% were Chlamydomonas, and 4.08% were Acidobacteria. DCA analysis indicated that microorganisms abundance (diversity and Chao values) increased with time. Furthermore, network analysis showed that complex networks of interactions existed in the sediments. After adapting to the acidic environmental conditions, the growth of some locally dominant bacteria increased the microbial interactions, allowing more bacteria to participate in the network, making their connections stronger. This evidence points to a disruption in the microbial community structure and its diversity following artificial disturbance, which then develops again over time. These results could contribute to the understanding of the evolution of microbial communities in the ecosystem during the remediation of anthropogenically disturbed heavy metals.

TMEM2 induces epithelial-mesenchymal transition and promotes resistance to temozolomide in GBM cells.

Glioblastoma multiforme (GBM) is the most common intracranial malignant tumor and is notorious for its poor prognosis. An important element in the short overall survival of GBM patients is the lack of understanding the pathogenesis and progression of tumor and deficiency biomarkers that can be used for early diagnosis and therapeutic sensitivity monitoring. Studies have shown that transmembrane protein 2 (TMEM2) is participated in tumorigenesis of various human tumors, including rectal and breast cancers. Although Qiuyi Jiang et al. have reported that TMEM2 combined with IDH1/2 and 1p19q can predict the survival time of glioma patients based on bioinformatics, its expression and biological role of glioma remain unclear. In our study, we investigated the effect of TMEM2 expression level on glioma malignancy in public datasets and an independent internal dataset. We revealed TEMM2 expression was higher in GBM tissues than in non-tumor brain tissues (NBT). Moreover, the increase in TMEM2 expression level was closely related to tumor malignancy. The survival analysis showed that TMEM2 high expression reduces survival time in all glioma patients, including GBM and LGG patients. Subsequent experiments demonstrated that knockdown TMEM2 inhibited proliferation of GBM cells. In addition, we analyzed TMEM2 mRNA levels in different GBM subtypes, and demonstrated that TMEM2 expression was upregulated in mesenchymal subtype. Meanwhile, bioinformatics analysis and transwell assay indicated that knockdown TMEM2 suppressed epithelial-mesenchymal transition (EMT) in GBM. Importantly, Kaplan-Meier analysis demonstrated that TMEM2 high expression reduced the treatment response to TMZ in GBM patients. Knockdown of TMEM2 alone did not reduce apoptosis GBM cells, but significant apoptotic cells were observed in the group treated with additional TMZ. These studies may contribute to improving the accuracy of early diagnosis and evaluating the effectiveness of TMZ treatment in GBM patients.

3D slicer combined with neuroendoscope in treatment of a distal segment aneurysm of the anterior choroidal artery complicated intraventricular hemorrhage: A case report and literature review.

Introduction: Pure ventricular hemorrhage is often secondary to Moyamoya disease, rarely caused by rupture of ventricular aneurysm. The surgical treatment of the latter is very challenging. 3D Slicer reconstruction technology can accurately locate small intracranial lesions and combined with minimally invasive surgery with transcranial neuroendoscope is a new attempt to treat the above diseases. Case presentation: We report a case of pure intraventricular hemorrhage secondary to rupture of a distal segment aneurysm of the anterior choroidal artery. Brain computed tomography (CT) before admission showed pure ventricular hemorrhage, and brain CT angiography (CTA) before operation showed a distal segment aneurysm of the anterior choroidal artery. We used 3D Slicer reconstruction and precise location of the focus before the operation and used the minimally invasive surgery technique with transcranial neuroendoscope to completely remove the hematoma in the ventricle, and found the responsible aneurysm located in the ventricle. Conclusion: Pure intraventricular hemorrhage requires vigilance against the distal segment aneurysm of the anterior choroidal artery. At present, conventional microscopic craniotomy and intravascular interventional therapy have limitations, and 3D Slicer reconstruction and precise positioning technology combined with transcranial neuroendoscope minimally invasive surgery may be a good choice.

[Corrigendum] ND­09 inhibits chronic myeloid leukemia K562 cell growth by regulating BCR­ABL signaling.

Subsequently to the publication of this paper, the authors have realized that an error was made during the compilation of Fig. 2A as it appeared on p. 4. Essentially, the partial Q2­3 images of the '1.56 µm' group were inadvertently copied across to the Q2­3 images of the '3.12 µm' group, leading to the cell number of the Q2­3 quadrant being the same for both the 1.56 µm and the 3.12 µm groups, and also leading the total cell number of the 3.12 µm group being calculated as 106.97%, which was clearly incorrect (the total percentage should have added up to 100%). The corrected version of Fig. 2, showing the correct data for the Q2­3 images in the '3.12 µm' group, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of Oncology Reports for allowing them this opportunity to publish a corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 46: 136, 2021; DOI: 10.3892/or.2021.8087].

Construction of an Immunity and Ferroptosis-Related Risk Score Model to Predict Ovarian Cancer Clinical Outcomes and Immune Microenvironment.

BACKGROUND: Ovarian cancer (OV) is a severe and common gynecological disease. Ferroptosis can regulate the progression and invasion of tumors. The immune system is a decisive factor in cancer. The present study aimed to use gene expression data to establish an immunity and ferroptosis-related risk score model as a prognostic biomarker to predict clinical outcomes and the immune microenvironment of OV. METHODS: Common gene expression data were searched from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Immunity-related genes and ferroptosis-related genes were searched and downloaded from the ImmPort and FerrDb databases, followed by the analysis of the overall survival of patients with OV and the identification of genes. Subsequently, the status of the infiltration of immune cells and the association between immune checkpoints and risk score were assessed. RESULTS: A total of 10 prognostic genes (C5AR1, GZMB, IGF2R, ISG20, PPP3CA, STAT1, TRIM27, TSHR, RB1, and EGFR) were included in the immunity and ferroptosis-related risk score model. The high-risk group had a higher infiltration of immune cells. The risk score, an independent prognostic feature of OV was negatively associated with each immune checkpoint. The risk score may thus help to predict the response to immunotherapy. CONCLUSIONS: The immunity and ferroptosis-related risk score model is an independent prognostic factor for OV. The established risk score may help to predict the response of patients to immunotherapy.

Applications and advancements of CRISPR-Cas in the treatment of lung cancer.

Lung cancer is one of the most malignant diseases and a major contributor to cancer-related deaths worldwide due to the deficiency of early diagnosis and effective therapy that are of great importance for patient prognosis and quality of life. Over the past decade, the advent of clustered regularly interspaced short palindromic repeats/CRISPR associated protein (CRISPR/Cas) system has significantly propelled the progress of both fundamental research and clinical trials of lung cancer. In this review, we review the current applications of the CRISPR/Cas system in diagnosis, target identification, and treatment resistance of lung cancer. Furthermore, we summarize the development of lung cancer animal models and delivery methods based on CRISPR system, providing novel insights into clinical diagnosis and treatment strategies of lung cancer.

Applications of CRISPR screening to lung cancer treatment.

Lung cancer is an extremely aggressive and highly prevalent disease worldwide, and it is one of the leading causes of cancer death. Deciphering intrinsic genetic mechanism, finding new targets, and overcoming drug resistance are the key to lung cancer treatment. High-throughput CRISPR screening has been extensively used to obtain the genes related to cancers including lung cancer. This review describes CRISPR/Cas9 or CRISPR/dCas9-based technologies for high-throughput screening. We summarize the applications of CRISPR screening technology in exploring the mechanism of lung cancer development in vivo or in vitro, overcoming drug resistance, improving the effect of immunotherapy, and discovering new therapeutic targets. This review highlights the potential of CRISPR screening in combination with tumor barcoding and high-throughput sequencing (Tuba-seq) to precisely quantify the impact of alterations in many tumor suppressor genes on lung cancer.

Clinical application of 3D-Slicer + 3D printing guide combined with transcranial neuroendoscopic in minimally invasive neurosurgery.

To explore the clinical advantages of 3D-Slicer + 3D printing guide combined with transcranial neuroendoscopic in minimally invasive neurosurgery. By collecting the datum of patients who underwent craniotomy under 3D-Slicer + 3D printing guide plate positioning combined with transcranial neuroendoscopic in our hospital from October 2021 to February 2022, this paper introduces the accurate planning and positioning lesions of patients before operation and the minimally invasive operation of intraoperative neuroendoscopic and analyses clinical data such as lesion size and surgical bone window size. We collected the case datum of 16 patients who underwent craniocerebral surgery with 3D-Slicer + 3D printing guide combined with transcranial neuroendoscopic, including 5 males and 11 females, aged 46-76 years, including 6 brain tumors (3 meningiomas, 1 glioblastoma, 2 lung cancer brain metastases), 2 cavernous hemangioma, 7 hydrocephalus and 1 chronic subdural hematoma. The lesions of the 16 patients were located accurately before operation and the target areas were reached quickly during operation. Postoperative imaging datum confirmed that the lesions was removed fully, and the ventricular end of shunt tube was in good position. The technology of 3D-Slicer + 3D printing guide plate combined with transcranial neuroendoscopic is not difficult, which has many advantages such as inexpensive equipment, simple operation, easy learning, accurate positioning, and minimally invasive surgery. It is considered to be a practical technology that is feasible, reliable, convenient for diagnosis, preoperative planning and minimally invasive surgery. It is suitable for promotion in neurosurgery and other surgical departments of all medical institutions.