B-Cell Maturation Antigen/CD19 Dual-Targeting Immunotherapy in Newly Diagnosed Multiple Myeloma.

Importance: Patients with high-risk newly diagnosed multiple myeloma (NDMM) often have poor outcomes with standard treatments, necessitating novel effective frontline therapies to enhance clinical outcomes. GC012F, a B-cell maturation antigen/CD19 dual-targeting chimeric antigen receptor (CAR) T-cell therapy, has been developed on the novel FasTCAR platform. Notably, its use as a frontline therapy for patients with high-risk NDMM who are eligible for transplant has not been thoroughly explored. Objective: To examine the safety, pharmacokinetics, and patient health and survival outcomes associated with GC012F in individuals with NDMM. Design, Setting, and Participants: Patients were enrolled in this single-arm, open-label phase 1 cohort study between June 28, 2021, and June 1, 2023 (the data cutoff date). All patients included in this study were treated at a single center, Shanghai Changzheng Hospital. The patients in the efficacy evaluation were followed up for a minimum period of 3 months. Intervention: Patients underwent 2 cycles of induction therapy, followed by GC012F infusion (at 1 × 105 cells/kg, 2 × 105 cells/kg, or 3 × 105 cells/kg). Main Outcomes and Measures: The primary goals were to assess the safety, efficacy, and pharmacokinetics of GC012F at various dose levels. Results: Of 22 patients receiving GC012F treatment, 6 experienced mild to moderate cytokine release syndrome (grade 1-2) and none experienced neurotoxic effects. Nineteen patients were included in the efficacy evaluation, and all 19 patients showed stringent complete responses and achieved minimal residual disease negativity. The treatment's effectiveness was consistent across different dose levels. GC012F demonstrated a rapid response, with a median time to first stringent complete response of 84 days (range, 26-267 days) and achieving minimal residual disease negativity within 28 days (range, 23-135 days). The CAR T-cell expansion was robust, with a median peak copy number of 60 652 copies/µg genomic DNA (range, 8754-331 159 copies/µg genomic DNA), and the median time to median peak copy number was 10 days (range, 9-14 days). Conclusions and Relevance: The findings of this single-arm, open-label phase 1 cohort study suggest that GC012F may be a safe treatment associated with positive health and survival outcomes for patients with high-risk NDMM eligible for transplant. Owing to the small sample size, further studies with larger cohorts and longer follow-up durations are needed.

Loss of heterozygosity for chromosomes 16q in Wilms tumors predicts outcomes: A meta-analysis.

BACKGROUND: The research findings suggest that the prognosis of children with Wilms tumor (WT) is affected by various factors. Some scholars have indicated that loss of heterozygosity (LOH) on chromosome 16q is associated with a poor prognosis in patients with WT. AIM: To further elucidate this relationship, we conducted a meta-analysis. METHODS: This meta-analysis was registered in INPLASY (INPLASY2023100060). We systematically searched databases including Embase, PubMed, Web of Science, Cochrane, and Google Scholar up to May 31, 2020, for randomized trials reporting any intrapartum fetal surveillance approach. The meta-analysis was performed within a frequentist framework, and the quality and network inconsistency of trials were assessed. Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT. RESULTS: Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT (I2 = 25%, P < 0.001). As expected, 16q LOH can serve as an effective predictor of event-free survival in patients with WT (risk ratio = 1.95, 95%CI: 1.52-2.49, P < 0.001). CONCLUSION: In pediatric patients with WT, there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis. Clinical detection of 16q chromosome LOH warrants increased attention to the patient's prognosis.

SreC-dependent adaption to host iron environments regulates the transition of trophic stages and developmental processes of Curvularia lunata.

Plant pathogens are challenged by host-derived iron starvation or excess during infection, but the mechanism of plant pathogens rapidly adapting to the dynamic host iron environments to assimilate iron for invasion and colonization remains largely unexplored. Here, we found that the GATA transcription factor SreC in Curvularia lunata is required for virulence and adaption to the host iron excess environment. SreC directly binds to the ATGWGATAW element in an iron-dependent manner to regulate the switch between different iron assimilation pathways, conferring adaption to host iron environments in different trophic stages of C. lunata. SreC also regulates the transition of trophic stages and developmental processes in C. lunata. SreC-dependent adaption to host iron environments is essential to the infectious growth and survival of C. lunata. We also demonstrate that CgSreA (a SreC orthologue) plays a similar role in Colletotrichum graminicola. We conclude that Sre mediates adaption to the host iron environment during infection, and the function is conserved in hemibiotrophic fungi.

NIR-IIb fluorescence antiangiogenesis copper nano-reaper for enhanced synergistic cancer therapy.

The formation of blood vessel system under a relatively higher Cu2+ ion level is an indispensable precondition for tumor proliferation and migration, which was assisted in forming the tumor immune microenvironment. Herein, a copper ions nano-reaper (LMDFP) is rationally designed not only for chelating copper ions in tumors, but also for combination with photothermal therapy (PTT) to improve antitumor efficiency. Under 808 nm laser irradiation, the fabricated nano-reaper converts light energy into thermal energy to kill tumor cells and promotes the release of D-penicillamine (DPA) in LMDFP. Photothermal properties of LMDFP can cause tumor ablation in situ, which further induces immunogenic cell death (ICD) to promote systematic antitumor immunity. The released DPA exerts an anti-angiogenesis effect on the tumor through chelating copper ions, and inhibits the expression of programmed death ligand 1 (PD-L1), which synergizes with PTT to enhance antitumor immunity and inhibit tumor metastasis. Meanwhile, the nanoplatform can emit near-infrared-IIb (NIR-IIb) fluorescence under 980 nm excitation, which can be used to track the nano-reaper and determine the optimal time point for PTT. Thus, the fabricated nano-reaper shows powerful potential in inhibiting tumor growth and metastasis, and holds great promise for the application of copper nanochelator in precise tumor treatment.

Donor-derived Anti-CD19 CAR T cells GC007g for relapsed or refractory B-cell acute lymphoblastic leukemia after allogeneic HSCT: a phase 1 trial.

Background: Although chimeric antigen receptor-modified T cells (CAR T) cell therapy has been widely reported in improving the outcomes of B-cell acute lymphoblastic leukemia (B-ALL), less research about the feasibility and safety of donor-derived CAR T after allogeneic hematopoietic stem cell transplantation (allo-HSCT) was reported. Methods: This phase 1 clinical trial aims to evaluate safety and efficacy of donor-derived anti-CD19 CAR T cells (GC007g) in B-ALL patients who relapsed after allo-HSCT. This trial is registered with ClinicalTrials.gov, NCT04516551. Findings: Between 15 March 2021 and 19 May 2022, fifteen patients were screened, three patients were excluded due to withdraw of consent, donor's reason, and death, respectively. Patients received donor-derived CAR T cells infusions at 6 × 105/kg (n = 3) or 2 × 106/kg (n = 6) dose level. The median time from HSCT to relapse was 185 days (range, 81-2063). The median age of patients was 31 years (range 21-48). Seven patients (77.8%) had BCR-ABL fusion gene. CAR T cells expanded in vivo and the median time to reach Cmax was 9 days (range, 7-11). One patient had hyperbilirubinemia after GC007g infusion which was defined as a dose-limiting toxicity. All patients experienced CRS and hematological adverse events. Three patients had acute graft-versus-host-disease (grade I, n = 1; grade II, n = 1; grade IV, n = 1) and all resolved after treatment. They received CAR T cells from matched sister, haploidentical matched father and sisiter, respectively. At 28 days after infusion, all patients achieved complete remission with/without incomplete hematologic recovery (CRi/CR) with undetectable MRD. At a median follow-up of 475 days (range 322-732), seven patients remained in CR/CRi while two had CD19-negative relapse. The overall response rates (ORR) were 100% (9/9), 88.9% (8/9), and 75% (6/8) at 3 month, 6 month, and 12 month, respectively. The 1-year progression-free and overall survival were 77.8% and 85.7%, respectively. Interpretation: GC007g expanded and induced durable remission in patients with B-ALL relapsed after allo-HSCT, with manageable safety profiles. Funding: Gracell Biotechnologies Inc.

Efficacy and Safety of Distal Radial Artery Approach for Coronary Angiography: A Retrospective Study.

BACKGROUND: The distal radial artery approach has been employed as a potential alternative technique for coronary angiography. Nevertheless, its clinical implementation is significantly constrained by the narrow diameter of the radial artery. A comprehensive investigation of the efficacy and safety of the distal radial artery approach for coronary angiography is lacking. The objective of this study is to investigate the impact of the distal radial artery approach for coronary angiography and transradial artery access for interventional diagnosis and treatment. In addition, the effectiveness and safety of the distal radial artery approach for coronary artery angiography will be analyzed, for the wider adoption of this technique in clinical practice. METHODS: A total of 68 patients with coronary heart disease (CHD) who underwent coronary catheterization via the left distal radial artery approach from December 2020 to December 2022 using the Distal radial artery approach (TRA) comprised the case-control study group. Seventy-three CHD patients who underwent routine left Transradial Artery Access coronary catheterization were selected as the Regular TRA group during the same period. Clinical data including age, body mass index (BMI), gender, CHD risk factors, routine drug treatment, ultrasonic-related indicators and operation-related indicators were collected from electronic medical records and the catheterization database from the two groups of patients. RESULTS: The diameter and Endothelium-dependent vasodilation (noe FMD) of puncture vessels in the Distal TRA group were significantly lower than those in the Regular radial artery approach (TRA) group (p-value < 0.05). After a period of 48 hours following the catheterization, the puncture vessel diameter and flow-mediated dilation (FMD) of the Distal TRA group were significantly lower compared to those of the Regular TRA group (p-value < 0.05). The effectiveness of transradial artery access was then compared between the two groups. It was determined that the Distal TRA group exhibited significantly higher values in terms of the Visual Analog Scale (VAS) score, puncture time, and heparin usage, in comparison to the Regular TRA group (p-value < 0.05). The occurrence rates of local hematoma, mediastinal hematoma, retroperitoneal hematoma, pseudoaneurysm, arteriovenous fistula, vagal reflex, vasospasm, blood transfusion, and other complications among patients in the Distal TRA group were comparable to those in the Regular TRA group (p-value > 0.05). The incidence of puncture and X-ray radiation in the Distal TRA group was found to be marginally higher compared to the Regular TRA group. This study suggests that the safety profile of patients undergoing coronary artery catheterization via the distal radial artery is relatively higher than those undergoing the procedure via the transradial artery, although the difference was not statistically significant (p-value > 0.05). CONCLUSIONS: The Distal radial artery approach can be used for conducting comprehensive coronary interventional diagnosis and treatment procedures, offering benefits such as reduced postoperative compression time, better hemostasis through the distal radial artery approach, and enhanced patient comfort. This approach demonstrates favorable efficacy and safety, making it a suitable routine puncture method for clinical treatment.

CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies.

T-cell acute lymphoblastic leukemia (T-ALL) represents an area of highly unmet medical needs. Once relapsed, patients have limited treatment options and poor prognosis. T-ALL antigens such as CD7 is extensively expressed in normal T cells and natural killer (NK) cells, and extending the success of CAR-T therapy to T cell malignancies was challenged by CAR-T cell fratricide, high production cost, and potential product contaminations. GC027 is an "off-the-shelf" allogeneic CD7 targeted CAR-T therapeutic product for T cell malignancies. It demonstrated superior cell expansion and antileukemia efficacy in mouse xenograft model. In our previous study, we observed promising efficacy results in the first two relapsed and refractory(R/R) T-ALL patients treated with GC027. In the expanded study, 11 out of 12 patients had rapid eradication of T-lymphoblasts and reached complete response within 1-month after GC027 infusion. GC027 cells expanded quickly beginning at infusion and reached to peak around 5-10 days after infusion. For most patients with a response(9/11), GC027 could not be detected via flow cytometry or qPCR 4 weeks after infusion. One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies.

Artificial intelligence system-based histogram analysis of computed tomography features to predict tumor invasiveness of ground-glass nodules.

Background: The use of an artificial intelligence (AI)-based diagnostic system can significantly aid in analyzing the histogram of pulmonary nodules. The aim of our study was to evaluate the value of computed tomography (CT) histogram indicators analyzed by AI in predicting the tumor invasiveness of ground-glass nodules (GGNs) and to determine the added value of contrast-enhanced CT (CECT) compared with nonenhanced CT (NECT) in this prediction. Methods: This study enrolled patients with persistent GGNs who underwent preoperative NECT and CECT scanning. AI-based histogram analysis was performed for pathologically confirmed GGNs, which was followed by screening invasiveness-related factors via univariable analysis. Multivariable logistic models were developed based on candidate CT histogram indicators measured on either NECT or CECT. Receiver operating characteristic (ROC) curve and precision-recall (PR) curve were used to evaluate the models' performance. Results: A total of 116 patients comprising 121 GGNs were included and divided into the precancerous lesion and adenocarcinoma groups based on invasiveness. In the AI-based histogram analysis, the mean CT value [NECT: odds ratio (OR) =1.009; 95% confidence interval (CI): 1.004-1.013; P<0.001] and solid component volume (NECT: OR =1.005; 95% CI: 1.000-1.010; P=0.032) were associated with the adenocarcinoma and used for multivariable logistic modeling. The area under ROC curve (AUC) and PR curve (AUPR) were not significantly different between the NECT model (AUC =0.765, 95% CI: 0.679-0.837; AUPR =0.907, 95% CI: 0.825-0.953) and the optimal CECT model (delayed phase: AUC =0.772, 95% CI: 0.687-0.843; AUPR =0.895, 95% CI: 0.812-0.944). No significantly different metrics were observed between the NECT and CECT models (precision: 0.707 vs. 0.742; P=0.616). Conclusions: The AI diagnostic system can help in the diagnosis of GGNs. The system displayed decent performance in GGN detection and alert to malignancy. Mean CT value and solid component volume were independent predictors of tumor invasiveness. CECT provided no additional improvement in diagnostic performance as compared with NECT.

DNASE1L3 enhances antitumor immunity and suppresses tumor progression in colon cancer.

DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of antitumor immunity, the foundation of modern antitumor immunotherapy. In this study, we identify DNASE1L3 as a potentially new regulator of antitumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating DCs, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired antitumor immunity, as evidenced by a substantial reduction of cytotoxic T cells and a unique subset of DCs. Consistently, Dnase1l3-deficient DCs directly modulate cytotoxic T cells in vitro. To our knowledge, our study unveils a previously unknown link between DNASE1L3 and antitumor immunity and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anticancer therapy.

Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity.

Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8+ T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.

Application and progress of palliative therapy in advanced gastric carcinomas.

Gastric carcinomas have high morbidity and mortality. It produces no noticeable symptoms in the early stage while causing complex complications in its advanced stage, making treatment difficult. Palliative therapy aims to relieve the symptoms of cancer patients and focuses on improving their quality of life. At present, five palliative therapies for advanced gastric carcinomas are offered: resection, gastrojejunostomy, stenting, chemotherapy, and radiotherapy. In recent years, palliative therapy has been used in the clinical treatment of advanced gastric carcinomas and related complications because of its efficacy in gastric outlet obstruction and gastric bleeding. In the future, multimodal and interdisciplinary palliative therapies can be applied to control general symptoms to improve patients' condition, prolong their lifespan and improve their quality of life.

PDGFB-targeted functional MRI nanoswitch for activatable T1-T2 dual-modal ultra-sensitive diagnosis of cancer.

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off-on T1-T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1-T2 dual-mode MRI signals. The tumor-specific off-on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off-on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.

Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats.

OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

NIR-II Fluorescence Imaging-Guided Oxygen Self-Sufficient Nano-Platform for Precise Enhanced Photodynamic Therapy.

Tumor hypoxia and systemic toxicity seriously affect the efficacy of photodynamic therapy (PDT) and are considered as the "Achilles' heel" of PDT. Herein, to combat such limitations, an intelligent orthogonal emissions LDNP@SiO2 -CaO2 and folic acid-polyethylene glycol-Ce6 nanodrug is rationally designed and fabricated not only for relieving the hypoxic tumor microenvironment (TME) to enhance PDT efficacy, but also for determining the optimal triggering time through second near-infrared (NIR-II) fluorescence imaging. The designed nanodrug continuously releases a large amount of O2 , H2 O2 , and Ca2+ ions when exposed to the acidic TME. Meanwhile, under downshifting NIR-II bioimaging guidance, chlorine e6 (Ce6) consumes oxygen to produce 1 O2 upon excitation of upconversion photon. Moreover, cytotoxic reactive oxygen species (ROS) and calcium overload can induce mitochondria injury and thus enhance the oxidative stress in tumor cells. As a result, the NIR-II bioimaging guided TME-responsive oxygen self-sufficient PDT nanosystem presents enhanced anti-tumor efficacy without obvious systemic toxicity. Thus, the fabricated nanodrug offers great potential for designing an accurate cancer theranostic system.

Chinese guideline on the application of anti-seizure medications in the perioperative period of supratentorial craniocerebral surgery.

Seizures are a common symptom of craniocerebral diseases, and epilepsy is one of the comorbidities of craniocerebral diseases. However, how to rationally use anti-seizure medications (ASMs) in the perioperative period of craniocerebral surgery to control or avoid seizures and reduce their associated harm is a problem. The China Association Against Epilepsy (CAAE) united with the Trauma Group of the Chinese Neurosurgery Society, Glioma Professional Committee of the Chinese Anti-Cancer Association, Neuro-Oncology Branch of the Chinese Neuroscience Society, and Neurotraumatic Group of Chinese Trauma Society, and selected experts for consultancy regarding outcomes from evidence-based medicine in domestic and foreign literature. These experts referred to the existing research evidence, drug characteristics, Chinese FDA-approved indications, and expert experience, and finished the current guideline on the application of ASMs during the perioperative period of craniocerebral surgery, aiming to guide relevant clinical practice. This guideline consists of six sections: application scope of guideline, concepts of craniocerebral surgery-related seizures and epilepsy, postoperative application of ASMs in patients without seizures before surgery, application of ASMs in patients with seizures associated with lesions before surgery, emergency treatment of postoperative seizures, and 16 recommendations.

Iron redistribution induces oxidative burst and resistance in maize against Curvularia lunata.

MAIN CONCLUSION: ΔClnps6 induced iron redistribution in maize B73 leaf cells and resulted in reactive oxygen species (ROS) burst to enhance plant resistance against Curvularia lunata. Iron is an indispensable co-factor of various crucial enzymes that are involved in cellular metabolic processes and energy metabolism in eukaryotes. For this reason, plants and pathogens compete for iron to maintain their iron homeostasis, respectively. In our previous study, ΔClnps6, the extracellular siderophore biosynthesis deletion mutant of Curvularia lunata, was sensitive to exogenous hydrogen peroxide and virulence reduction. However, the mechanism was not studied. Here, we report that maize B73 displayed highly resistance to ΔClnps6. The plants recruited more iron at cell wall appositions (CWAs) to cause ROS bursts. Intracellular iron deficiency induced by iron redistribution originated form up-regulated expression of genes involved in intracellular iron consumption in leaves and absorption in roots. The RNA-sequencing data also showed that the expression of respiratory burst oxidase homologue (ZmRBOH4) and NADP-dependent malic enzyme 4 (ZmNADP-ME4) involved in ROS production was up-regulated in maize B73 after ΔClnps6 infection. Simultaneously, jasmonic acid (JA) biosynthesis genes lipoxygenase (ZmLOX), allene oxide synthase (ZmAOS), GA degradation gene gibberellin 2-beta-dioxygenase (ZmGA2OX6) and ABA degradation genes abscisic acid hydroxylase (ZmABH1, ZmABH2) involved in iron homeostasis were up-regulated expression. Ferritin1 (ZmFER1) positive regulated maize resistance against C. lunata via ROS burst under Fe-limiting conditions. Overall, our results showed that iron played vital roles in activating maize resistance in B73-C. lunata interaction.

A Retrospective Study of Parietal Lobe Epilepsy: Functional Anatomy and Surgical Treatment.

Context: Parietal lobe epilepsy (PLE) accounts for approximately 5% of all focal epilepsies worldwide,1 and few PLE patients have undergone epilepsy surgery in the past. With the introduction of functional neuroimaging methods, such as interictal fluorodeoxyglucose-positron emission tomography (FDG-PET), stereotactic electroencephalograms (SEEGs), and high-resolution magnetic resonance imaging (MRI), more patients with intractable neocortical epilepsy have been considered for surgical treatment. Objective: The study intended to characterize the clinical features, aura, and presurgical evaluations of patients with PLE, by investigating their demographic and clinical characteristics, and to evaluate the prognostic value of the four diagnostic modalities-MRI, FDG-PET, scalp EEG, and SEEG-in terms of the localization of epileptogenic area. Design: The research team performed a retrospective analysis of outcomes for PLE patients who underwent resistive brain surgery. Setting: The study took place in the Neurosurgery Department of Epilepsy at the Second Hospital of Hebei Medical University in Shijiazhuang, China. Participants: Participants were 9 PLE patients, 4 males and 5 females, who underwent epilepsy surgery at the hospital between 2017 and 2019. Outcome Measures: The measures included demographic data, seizure data, electroencephalogram (EEG) recordings, magnetic resonance imaging (MRI) of the brain, positron emission tomography (PET), and stereotactic electroencephalogram (SEEG). The pathological findings were reviewed. Results: The five participants who had a PET all had positive results. Eight participants who had parietal lobe lesions had an MRI, and four had a stereotactic electroencephalogram (SEEG) that localized the epileptogenic zone. The interictal scalp EEG recordings for seven participants showed an abnormality, and six participants who had ictal surface EEG recordings showed parietal ictal EEG onset. Conclusions: Surgical excision of epileptogenic foci is the main treatment for drug-resistant PLE. Parietal functional anatomy is the basis for understanding and diagnosing PLE. Aura, semiology, interictal EEG, and PET are an important foundation for evaluation of PLE patients, and the SEEG is the most valuable tool, allowing localization of the epileptogenic zone.

Intestinal epithelial glucocorticoid receptor promotes chronic inflammation-associated colorectal cancer.

Synthetic immunosuppressive glucocorticoids (GCs) are widely used to control inflammatory bowel disease (IBD). However, the impact of GC signaling on intestinal tumorigenesis remains controversial. Here, we report that intestinal epithelial GC receptor (GR), but not whole intestinal tissue GR, promoted chronic intestinal inflammation-associated colorectal cancer in both humans and mice. In patients with colorectal cancer, GR was enriched in intestinal epithelial cells and high epithelial cell GR levels were associated with poor prognosis. Consistently, intestinal epithelium-specific deletion of GR (GR iKO) in mice increased macrophage infiltration, improved tissue recovery, and enhanced antitumor response in a chronic inflammation-associated colorectal cancer model. Consequently, GR iKO mice developed fewer and less advanced tumors than control mice. Furthermore, oral GC administration in the early phase of tissue injury delayed recovery and accelerated the formation of aggressive colorectal cancers. Our study reveals that intestinal epithelial GR signaling repressed acute colitis but promoted chronic inflammation-associated colorectal cancer. Our study suggests that colorectal epithelial GR could serve as a predictive marker for colorectal cancer risk and prognosis. Our findings further suggest that, although synthetic GC treatment for IBD should be used with caution, there is a therapeutic window for GC therapy during colorectal cancer development in immunocompetent patients.

Near-Infrared Inorganic Nanomaterials for Precise Diagnosis and Therapy.

Traditional wavelengths (400-700 nm) have made tremendous inroads in vivo fluorescence imaging. However, the ability of visible light photon penetration hampered the bio-applications. With reduced photon scattering, minimal tissue absorption and negligible autofluorescence properties, near-infrared light (NIR 700-1700 nm) demonstrates better resolution, high signal-to-background ratios, and deep tissue penetration capability, which will be of great significance for in-vivo determination in deep tissue. In this review, we summarized the latest novel NIR inorganic nanomaterials and the emission mechanism including single-walled carbon nanotubes, rare-earth nanoparticles, quantum dots, metal nanomaterials. Subsequently, the recent progress of precise noninvasive diagnosis in biomedicine and cancer therapy utilizing near-infrared inorganic nanomaterials are discussed. In addition, this review will highlight the concerns, challenges and future directions of near-infrared light utilization.