Bentonite-supported nano zero-valent iron composite as a green catalyst for bisphenol A degradation: Preparation, performance, and mechanism of action.

Bisphenol A (BPA) is a toxic environmental pollutant commonly found in wastewater. Using non-toxic materials and eco-friendly technology to remove this pollutant from wastewater presents multiple advantages. Treatment of wastewater with clay minerals has received growing interest because of the environment friendliness of these materials. Bentonite is a 2:1 layered phyllosilicate clay mineral that can support nano-metal catalysts. It can prevent the agglomeration of nano-metal catalysts and improve their activity. In this article, a green catalytic nano zero-valent iron/bentonite composite material (NZVI@bentonite) was synthesized via liquid-phase reduction. The average size of NZVI was approximately 40-50 nm. Good dispersion and low aggregation were observed when NZVI was loaded on the surface or embedded into the nanosheets of bentonite. Degradation of BPA, a harmful contaminant widely found in wastewater at relatively high levels, by NZVI@bentonite was then investigated and compared with that by pristine NZVI through batch Fenton-like reaction experiments. Compared with pristine NZVI and bentonite alone, the NZVI@bentonite showed a higher BPA degradation ratio and offered highly effective BPA degradation up to 450 mg/g in wastewater under optimum operating conditions. Adsorption coupled with the Fenton-like reaction was responsible for BPA degradation by NZVI@bentonite. This work extends the application of NZVI@bentonite as an effective green catalyst for BPA degradation in aqueous environments.

[Transurethral 180 W front-firing GreenLight laser vaporization of the prostate for the treatment of benign prostatic hyperplasia].

OBJECTIVE: To evaluate the clinical effect and safety of transurethral 180 W front-firing GreenLight laser vaporization of the prostate (PVP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 61 BPH patients underwent 180W front-firing GreenLight laser PVP (n = 30, the PVP group) or transurethral plasmakinetic resection of the prostate (n = 31, the control group) from March to December 2019. We collected the pre-, intra- and post-operative clinical data and compared them between the two groups of patients. RESULTS: Operations were successfully completed in all the cases with no blood transfusion or serious complications. Compared with the controls, the patients of the PVP group showed remarkably less intra-operative blood loss (ï¼»62.3 ± 15.9ï¼½ vs ï¼»48.8 ± 9.6ï¼½ ml, P < 0.05), shorter operation time (ï¼»75.0 ± 9.9ï¼½ vs ï¼»57.5 ± 19.0ï¼½ min, P < 0.05), postoperative bladder lavage time (ï¼»64.4 ± 10.5ï¼½ vs ï¼»25.2 ± 11.5ï¼½ h, P < 0.05), catheter-indwelling time (ï¼»5.1 ± 0.5ï¼½ vs ï¼»2.5 ± 0.5ï¼½ d, P < 0.05) and hospitalization time (ï¼»7.3 ± 1.7ï¼½ vs ï¼»4.1 ± 0.6ï¼½ d, P < 0.05), and a lower incidence of postoperative hematuria (12.9% ï¼»4/31ï¼½ vs 0% ï¼»0/30ï¼½, P < 0.05). No statistically significant differences, however, were found between the two groups in the incidence rates of capsular perforation, transurethral resection syndrome (TURS), urinary incontinence, urethral stricture and post-extubation urinary retention. Significant improvement was observed in IPSS, QOL, Qmax and PVR in both groups post-operatively (P < 0.05). CONCLUSIONS: Compared with transurethral plasmakinetic resection of the prostate, 180W front-firing GreenLight laser PVP, with the advantages of less bleeding, shorter catheter-indwelling time and faster recovery, is safer and more effective for the treatment of BPH, with no need for drug withdrawal for those taking anticoagulants, and especially applicable to the elderly and high-risk patients.

Demonstration of patterned polymer-stabilized cholesteric liquid crystal textures for anti-counterfeiting two-dimensional barcodes.

We evaluated the feasibility of embedding periodically arranged squares with planar and vertical texture into a background with a developable-modulation (DM) type cholesteric liquid crystal (CLC) fingerprint texture by a two-step ultraviolet-induced polymerization method. Checker-patterned optical diffractive elements, which can be seen as a variation of a two-dimensional (2D) barcode, were first realized and the dependence of diffraction behaviors on incident light polarization and applied voltage were investigated. Taking advantage of the natural randomness and uncontrollable variations of a DM-type fingerprint textures, a polymer-stabilized CLC (PSCLC) graphic symbol with a 2D barcode pattern was then implemented with enhanced anti-counterfeiting features that are difficult to falsify or duplicate. The results indicate that the multiplexing of nonuniform DM-type fingerprint gratings, cross-polarized light readout, and unique polarization diffraction characteristics can improve the level of security.

The N-B Interaction through a Water Bridge: Understanding the Chemoselectivity of a Fluorescent Protein Based Probe for Peroxynitrite.

Boronic acid and esters have been extensively utilized for molecular recognition and chemical sensing. We recently reported a genetically encoded peroxynitrite (ONOO(-))-specific fluorescent sensor, pnGFP, based on the incorporation of a boronic acid moiety into a circularly permuted green fluorescent protein (cpGFP) followed by directed protein evolution. Different from typical arylboronic acids and esters, the chromophore of pnGFP is unreactive to millimolar concentrations of hydrogen peroxide (H2O2). The focus of this study is to explore the mechanism for the observed unusual chemoselectivity of pnGFP toward peroxynitrite over hydrogen peroxide by using site-directed mutagenesis, X-ray crystallography, (11)B NMR, and computational analysis. Our data collectively support that a His residue on the protein scaffold polarizes a water molecule to induce the formation of an sp(3)-hybridized boron in the chromophore, thereby tuning the reactivity of pnGFP with various reactive oxygen and nitrogen species (ROS/RNS). Our study demonstrates the first example of tunable boron chemistry in a folded nonnative protein, which offers wide implications in designing selective chemical probes.

A highly responsive and selective fluorescent probe for imaging physiological hydrogen sulfide.

The discovery of hydrogen sulfide (H2S) as a novel gasotransmitter for cell signaling and other pathophysiological processes has spurred tremendous interest in developing analytical methods for its detection in biological systems. Herein, we report the development of a highly responsive and selective genetically encoded H2S probe, hsGFP, for the detection of H2S both in vitro and in living mammalian cells. hsGFP bestows a combination of favorable properties, including large fluorescence responses, high efficiency in folding and chromophore formation, and excellent sensitivity and selectivity toward H2S. As a genetically encoded probe, hsGFP can be readily and precisely localized to subcellular domains such as mitochondria, cell nuclei, and ion channels. hsGFP was further utilized to image H2S enzymatically produced from l-cysteine in human embryonic kidney (HEK) 293T cells.

Effects of restoration years on soil stoichiometric ratios in subtropical secondary forests.

Soil stoichiometric ratios serve as valuable indicators for the composition and quality of soil organic matter. While available studies predominantly examine the soil stoichiometric ratios of carbon (C), nitrogen (N), and phosphorus (P), limited attention has been paid on the influence of forest restoration on soil stoichiometric ratios of potassium (K), calcium (Ca), and magnesium (Mg). We analyzed soil K, Ca, and Mg content, as well as elemental stoichiometric ratios, in secondary forests with varying restoration periods (5, 8, 21, 27 and 40 years) and a natural forest, in order to examine the impact of forest restoration on soil stoichiometry. The results showed that soil C and N contents decreased significantly with increasing soil layers. Soil stoichiometric ratios decreased significantly with increasing soil layers except for K:P, Mg:P, and P:Ca. With the increases of forest restoration years, soil C and N contents significantly increased in 0-10 cm soil layer, Ca content in 10-20 cm soil layer significantly increased, and total P content in 20-40 cm layer significantly decreased. However, soil K and Mg contents in each soil layer did not differ among five restoration ages. With the increases of restoration years, C:Ca, N:Ca and P:Ca in 0-10 cm soil layer significantly increased, and C:P, N:P, and K:P in 20-40 cm soil layer significantly increased, while P:Ca in 20-40 cm soil layer significantly decreased. In all soil layers, K:P and Mg:P were significantly and negatively correlated with soil total P content, and C:Ca and N:Ca were significantly and positively correlated with soil mineral N, available P, and available K content. With the increases of the restoration ages of secondary forests, soils are gradually P-limited and progressively restricted by Ca element in the later years, leading to the limitation of multiple nutrients.

Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

Genetically encoded fluorescent probe for the selective detection of peroxynitrite.

Peroxynitrite is a highly reactive molecule involved in cell signaling and pathological processes. We hereby report a novel genetically encoded probe, pnGFP, which can selectively sense peroxynitrite. A boronic acid moiety was site-specifically introduced into circularly permuted fluorescent proteins. By examining different protein templates followed with site-targeted random mutagenesis, we identified a selective peroxynitrite sensor, which is essentially unresponsive to other common cellular redox signaling molecules. The new probe has been genetically introduced into mammalian cells to image peroxynitrite at physiologically relevant concentrations.

Effect of low-temperature stress on the survival of Meloidogyne incognita and its application in greenhouse of northern China.

We examined the effects of low temperature on egg hatching and killing rate of the 2nd instars of Meloi-dogyne incognita (J2) in the laboratory. We further evaluated the effects of two soil treatment methods on the survival rate of M. incognita in northern China in a field experiment. The results of laboratory experiment showed that survival rate of J2 was 0 after being subjected to -7 ℃ for 24 hours, and that egg hatching was completely inhibited 24 hours after being subjected to -9 ℃. The survival rate of J2 was 0 after being subjected to -1, -2, -3, and -4 ℃ for 8, 5, 3, and 1.5 d, respectively. Egg hatching was completely inhibited after being subjected to -2, -3, -4, and -5 ℃ for 9, 6, 4, and 1 d, respectively. Results of the fitting analysis showed that both the relationships between the temperature and the lethal time of J2 as well as the temperature and the non-hatching time of the eggs followed exponential functions. The results of field test showed that death rate of M. incognita in 0-50 cm soil layer after ridging treatment and 0-30 cm soil layer after leveling treatment could reach 100%, while the disease index of the former in 30-40 cm and 40-50 cm was 84.9% and 75.8%, respectively, which was lower than that in the greenhouse. Our results suggest that preventing and controlling M. incognita in greenhouses through low-tempe-rature in winter could achieve a better control effect in Yulin City and the northward region. The proposed technique is convenient and has high potential for popularization.

[Correlation between spinous process deviation and lumbar disc herniation in young patients].

OBJECTIVE: To explore the relationship between spinous process deviation and lumbar disc herniation in young patients. METHODS: From March 2015 to January 2022, 30 treated young (under the age of 30) patients with lumbar disc herniation were included as the young group. In addition 30 middle-aged patients (quinquagenarian group) with lumbar disc herniation and 30 patients with non-degenerative spinal diseases (young non-degenerative group) were selected as control groups. The angle of the spinous process deviation was measured on CT and statistically analyzed by various groups. All the data were measured twice and the average value was taken and recorded. RESULTS: The average angle of spinous process deviation in the degenerative lumbar vertebra of young patients were (3.89±3.77) degrees, similar to the (3.72±2.98) degrees of quinquagenarian patients(P=0.851). The average angle of s spinous process deviation young non-degenerative group were (2.20±2.28) degrees, significantly less than young group(P=0.040). The spinous process deviation angle of the superior vertebral of the degenerative lumbar in the young group was (4.10±3.44) degrees, which similar to the (3.47±2.87) degrees in the quinquagenarian group (P=0.447). A total of 19 young patients had the opposite deviation direction of the spinous process of the degenerative lumbar vertebra and upper vertebra, while only 7 quinquagenarian patients had this condition(P=0.02). The type of lumbar disc herniation in young patients had no significant relationship with the direction of spinous process deflection of the degenerative or upper lumbar vertebra (P>0.05). CONCLUSION: Spinous process deviation is a risk factor of young lumbar disc herniation patients. If the deviation directions of adjacent lumbar spinous processes are opposite, it will increase the incidence of lumbar disc herniation in young patients. There was no significant correlation between the type of disc herniation and the deviation direction of the spinous process of the degenerative or upper lumbar vertebra. People with such anatomical variation can strengthen the stability of spine and prevent lumbar disc herniation through reasonable exercise.

Rhynchophylline inhibits methamphetamine dependence via modulating the miR-181a-5p/GABRA1 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a plant species that is routinely devoted in traditional Chinese medicine to treat central nervous system disorders. Rhynchophylline (Rhy), a predominant alkaloid isolated from Uncaria rhynchophylla (Miq.) Miq. ex Havil., has been demonstrated to reverse methamphetamine-induced (METH-induced) conditioned place preference (CPP) effects in mice, rats and zebrafish. The precise mechanism is still poorly understood, thus further research is necessary. AIM OF STUDY: This study aimed to investigate the role of miRNAs in the inhibitory effect of Rhy on METH dependence. MATERIALS AND METHODS: A rat CPP paradigm and a PC12 cell addiction model were established. Microarray assays were used to screen and identify the candidate miRNA. Behavioral assessment, real-time PCR, dual-luciferase reporter assay, western blotting, stereotaxic injection of antagomir/agomir and cell transfection experiments were performed to elucidate the effect of the candidate miRNA and intervention mechanism of Rhy on METH dependence. RESULTS: Rhy successfully reversed METH-induced CPP effect and the upregulated miR-181a-5p expression in METH-dependent rat hippocampus and PC12 cells. Moreover, suppression of miR-181a-5p by antagomir 181a reversed METH-induced CPP effect. Meanwhile, overexpression of miR-181a-5p by agomir 181a in combination with low-dose METH (0.5 mg/kg) elicited a significant CPP effect, which was blocked by Rhy through inhibiting miR-181a-5p. Finally, the result demonstrated that miR-181a-5p exerted its regulatory role by targeting γ-aminobutyric acid A receptor α1 (GABRA1) both in vivo and in vitro. CONCLUSION: This finding reveals that Rhy inhibits METH dependence via modulating the miR-181a-5p/GABRA1 axis, which may be a promising target for treatment of METH dependence.

Reaction-based genetically encoded fluorescent hydrogen sulfide sensors.

The detection of hydrogen sulfide (H(2)S), a toxic gas and an important biological signaling molecule, has been a long-time challenge. Here we report genetically encoded fluorescent protein (FP)-based probes that can selectively detect H(2)S. By expanding the genetic codes of E. coli and mammalian cells, FP chromophores were modified with the sulfide-reactive azide functional group. These structurally modified chromophores were selectively reduced by H(2)S, resulting in sensitive fluorescence enhancement detectable by spectroscopic and microscopic techniques. Exploration of a circularly permuted FP led to an improved sensor with faster responses, and the feasibility of using such a genetically encoded probe to monitor H(2)S in living mammalian cells has also been demonstrated.

Thin Nano Cages with Limited Hollow Space for Ultrahigh Sulfur Loading Lithium-Sulfur Batteries.

Owning to its various advantages, the lithium-sulfur battery is one of the research hot spots for new energy storage systems. Diverse hollow structures with specific morphologies have been used as the sulfur host materials to adsorb or/and catalyze the polysulfides, and can in particular concurrently inhibit the volume expansion during electrochemical processes in lithium-sulfur batteries. However, hollow space with a large volume will restrict the performance of the cell under high sulfur area loading, which is a very important indicator for the practical applications of the lithium-sulfur battery. Here, we report a nano thin cage cobalt acid zinc (ZnCo2O4) with limited hollow space as the cathode catalyst for lithium-sulfur batteries, which greatly reduces the electrode volume occupied by the hollow structure. The hollow volume of these thin cages is much smaller than those of the normally reported hollow materials in the literatue. The electrochemical performance of lithium-sulfur batteries with ZnCo2O4 thin cages could greatly improve due to the unique structure and the synergistic adsorption/catalytic effect of Zn/Co sites, especially at an ultrahigh S area load. Under a high S loading of 8 mg cm-2, the cell could keep a reversible capacity of 600 mAh g-1 after 500 cycles. Even at a sulfur loading of 10 mg cm-2, the cell still releases a discharge capacity of 1000 mAh g-1 which is equivalent of an area capacity of 10 mAh cm-2. This work provides a feasible way to develop lithium sulfur batteries with a high area sulfur load. This idea provides a possible solution to develop a Li-S battery at high area S loading and move one step closer to the practical applications.

A Comparison of the Performances of Artificial Intelligence System and Radiologists in the Ultrasound Diagnosis of Thyroid Nodules.

AIMS: The purpose of this paper is to prospectively evaluate the performance of an artificial intelligence (AI) system in diagnosing thyroid nodules and to assess its potential value in comparison with the performance of radiologists with different levels of experience, as well as the factors affecting its diagnostic accuracy. BACKGROUND: In recent years, medical imaging diagnosis using AI has become a popular topic in clinical application research. OBJECTIVE: This study aimed to evaluate the performance of an AI system in diagnosing thyroid nodules and compare it with the performance levels of different radiologists. METHODS: This study involved 426 patients screened for thyroid nodules at the First Affiliated Hospital of Guangzhou Medical University between July 2017 and March 2019. All of the nodules were evaluated by radiologists with various levels of experience and an AI system. The diagnostic performances of two junior and two senior radiologists, an AI system, and an AI-assisted junior radiologist were compared, as were their diagnostic results with respect to nodules of different sizes. RESULTS: The senior radiologists, the AI system, and the AI-assisted junior radiologist performed better than the junior radiologist (p < 0.05). The area under the curves of the AI system and the AI-assisted junior radiologist were similar to the curve of the senior radiologists (p > 0.05). The diagnostic results concerning the two nodule sizes showed that the diagnostic error rates of the AI system, junior radiologists, and senior radiologists for nodules with a maximum diameter of ≤1 cm (Dmax ≤ 1 cm) were higher than those for nodules with a maximum diameter of 1 cm (Dmax > 1 cm) (23.4% vs. 12.1%, p = 0.002; 26.6% vs. 7.3%, p < 0.001; and 38.3% vs. 14.6%, p < 0.001). CONCLUSION: The AI system is a decision-making tool that could potentially improve the diagnostic efficiency of junior radiologists. Micronodules with Dmax ≤ 1cm were significantly correlated with diagnostic accuracy; accordingly, more micronodules of this size, in particular, should be added to the AI system as training samples. Other: The system could be a potential decision-making tool for effectively improving the diagnostic efficiency of junior radiologists in the community.

Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial.

Importance: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear. Objective: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. Design, Setting, and Participants: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1. Interventions: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy. Main Outcomes and Measures: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis-free survival, locoregional relapse-free survival, overall survival, tumor response, and safety. Results: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group. Conclusions and Relevance: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile. Trial Registration: ClinicalTrials.gov Identifier: NCT02940925.

A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report.

Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, he developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript's submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patient with LM carrying EGFR G719S and L861Q.

Germinomas of the basal ganglia and thalamus: Four case reports.

BACKGROUND: The early diagnosis of basal ganglia and thalamus germinomas is often difficult due to the absence of elevated tumor markers, and atypical clinical symptoms and neuroimaging features. CASE SUMMARY: Four male children aged 8 to 15 years were diagnosed with germinomas in the basal ganglia and thalamus by stereotactic biopsy from 2017 to 2019. All patients developed hemiplegia except patient 4 who also had cognitive decline, speech disturbance, nocturnal enuresis, polydipsia, polyuria, precocious puberty and abnormalities of thermoregulation. All four cases were alpha-fetoprotein and beta-human chorionic gonadotrophin (ß-HCG) negative except patient 3 who had slightly elevated ß-HCG in cerebrospinal fluid (CSF). No malignant cells were detected in the patients' CSF. Brain magnetic resonance imaging findings were diverse in these patients with the exception of the unique and common characteristics of ipsilateral hemisphere atrophy, especially in the cerebral peduncle. All patients were diagnosed with germinomas of the basal ganglia and thalamus by stereotactic brain biopsy. CONCLUSION: Stereotactic brain biopsy is necessary to confirm the diagnosis of ectopic germinomas. Serial neuroimaging studies can not only differentiate disease but also determine the biopsy site.

Tim-3 Expression and MGMT Methylation Status Association With Survival in Glioblastoma.

BACKGROUND: A profound understanding of the molecular landscape of glioblastoma multiforme (GBM) will make it possible to develop better and more intelligent therapies directed toward specific molecular targets and may one day yield better prognostic capabilities. Immune checkpoint molecules have inspired the emergence of immune checkpoint-targeting therapeutic strategies. However, the prognostic significance of the immune checkpoint molecule T cell immunoglobulin mucin-3 (Tim-3) on tumor-infiltrating immune cells (TIICs) and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status has not yet been fully elucidated. We aimed to develop an MGMT promoter methylation status-associated immune prognostic signature for GBM. PATIENTS AND METHODS: A total of 84 patients with newly diagnosed GBM were included in this study. MGMT promoter methylation status was retrospectively analyzed, and the expression level of Tim-3 was investigated using immunohistochemistry (IHC). The correlation between Tim-3 expression combined with MGMT promoter methylation status and prognosis was explored. RESULTS: Tim-3 expression varied in GBM patients. Mesenchymal expression of Tim-3 in GBM tissues was present 73.81% (62/84) of patients, and these were subdivided into groups based on low 15.48% (13/84), moderate 7.14% (6/84), or strong expression 51.19% (43/84). Forty-eight patients had tumors that tested positive for MGMT promoter methylation, while the remaining 36 patients tested negative. CONCLUSIONS: We profiled the immune status of MGMT promoter methylation in GBM and established a local immune signature for GBM that could independently identify patients with a favorable prognosis, indicating a relationship between prognosis and GBM immune signature. MGMT promoter methylation with lower Tim-3 expression was significantly associated with better survival.