Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers.

AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.

Efficacy and safety of esketamine versus propofol in electroconvulsive therapy for treatment-resistant depression: A randomized, double-blind, controlled, non-inferiority trial.

BACKGROUND: Electroconvulsive therapy (ECT) is a commonly used alternative for treatment-resistant depression (TRD). Although esketamine has a rapid pharmacological antidepressant action, it has not been studied as an ECT anesthetic. The objective of this study was to compare the efficacy and safety of esketamine with propofol when both are used as ECT anesthetic agents. METHODS: Forty patients with TRD were assigned to one of two arms in a double-blind, randomized controlled trial: esketamine or propofol anesthesia for a series of eight ECT sessions. Using a non-inferiority design, the primary outcome was the reduction in HAMD-17 depressive symptoms. The other outcomes were: rates of response and remission, anxiety, suicidal ideation, cognitive function, and adverse events. These were compared in an intention-to-treat analysis. RESULTS: Esketamine-ECT was non-inferior to propofol-ECT for reducing TRD symptoms after 8 sessions (adjusted Δ = 2.0, 95 % CI: -1.2-5.1). Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) rates but non-inferiority was not established. In four components of cognitive function (speed of processing, working memory, visual learning, and verbal learning) esketamine-ECT was non-inferior to propofol-ECT. The results for anxiety, suicidal ideation, and adverse events (all p's > .05) were inconclusive. CONCLUSION: Esketamine was non-inferior to propofol when both are used as anesthetics for TRD patients undergoing ECT. Replication studies with larger samples are needed to examine the inconclusive results. REGISTRATION NUMBER: ChiCTR2000033715.

The key point of transsphenoidal surgery for infradiaphragmatic craniopharyngioma：Better sellar diaphragm resection.

Background: Craniopharyngiomas have a high recurrence rate and a poor prognosis, and the key methods for reducing recurrences are unknown. The aim of this study was to explore the key points of microscopic or endoscopic transsphenoidal surgery used to treat infradiaphragmatic craniopharyngiomas. Methods: We reviewed the medical records of patients with infradiaphragmatic craniopharyngiomas who were admitted to Peking Union Medical College Hospital between 2011 and 2018. Results: When considering tumor location, all 34 patients had intrasellar tumors, with 19 of them exhibiting suprasellar extensions. Of the 34 patients, 24 patients underwent resection under the microscope and the remaining 10 patients underwent transsphenoidal endoscopic surgery. Gross total tumor resection was achieved in 16 patients. Twelve patients underwent invaded sellar diaphragm resection, while the remaining 22 patients were not. Cerebrospinal fluid leaks occurred during surgery in 18 patients. Visual acuity improved in two patients. After an average follow-up of 31.1 months, 13 patients experienced tumor recurrence. The short term recurrence rate in the sellar diaphragm resection group was significantly lower compared to the non-resected group (P < 0.001). Moreover, based on distinct surgical methods, the endoscope group displayed a reduced short term recurrence rate compared to the microscope group (P = 0.0048). Conclusion: Invaded sellar diaphragm resection emerges as a pivotal maneuver in craniopharyngioma surgery, substantively influencing tumor recurrence. Capitalizing on the advantageous angled lens of endoscopes, surgeons can achieve heightened visualization. Significantly, the endoscopic approach exhibits a superior capacity to curtail recurrence, while effectively managing potential complications, when contrasted with the microscope group.

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

Blood Glucose Levels Moderate the Associations Between IGF-1 Levels and Choroidal Metrics in Patients With Diabetes With Acromegaly Without Diabetic Retinopathy.

Purpose: To examine the effects of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) on choroidal structures with different blood glucose levels in patients with diabetes mellitus (DM) with acromegaly without diabetic retinopathy. Methods: Eighty-eight eyes of 44 patients with acromegaly were divided into a nondiabetic group (23 patients, 46 eyes) and a diabetic group (21 patients, 42 eyes). Forty-four age- and sex-matched healthy controls and 21 patients with type 2 DM without diabetic retinopathy were also included. Linear regression models with a simple slope analysis were used to identify the correlation and interaction between endocrine parameters and choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascular index (CVI). Results: Our study revealed significant increases in the ChT, LA, SA, and TCA in patients with acromegaly compared with healthy controls, with no difference in the CVI. Comparatively, patients with DM with acromegaly had greater ChT than matched patients with type 2 DM, with no significant differences in other choroidal parameters. The enhancement of SA, LA and TCA caused by an acromegalic status disappeared in patients with diabetic status, whereas ChT and CVI were not affected by the interaction. In the diabetic acromegaly, higher IGF-1 (P = 0.006) and GH levels (P = 0.049), longer DM duration (P = 0.007), lower blood glucose (P = 0.001), and the interaction between GH and blood glucose were associated independently with thicker ChT. Higher GH levels (P = 0.016, 0.004 and 0.007), longer DM duration (P = 0.022, 0.013 and 0.013), lower blood glucose (P = 0.034, 0.011 and 0.01), and the interaction of IGF-1 and blood glucose were associated independently with larger SA, LA, and TCA. As blood glucose levels increased, the positive correlation between serum GH level and ChT diminished, and became insignificant when blood glucose was more than 7.35 mM/L. The associations between serum IGF-1 levels and LA, SA, and TCA became increasingly negative, with LA, becoming significantly and negatively associated to the GH levels only when blood glucose levels were more than 8.59 mM/L. Conclusions: Acromegaly-related choroidal enhancements diminish in the presence of DM. In diabetic acromegaly, blood glucose levels are linked negatively with changes in choroidal metrics and their association with GH and IGF-1. Translational Relevance: We revealed the potential beneficial impacts of IGF-1 and GH on structural measures of the choroid in patients with DM at relatively well-controlled blood glucose level, which could provide a potential treatment target for diabetic retinopathy.

Research on the relation between hydro-chemical and geological characteristics in karst area: Case study in Zhong Liang Mountain, Southwest China.

Karst groundwater, which is one of most important drinking water sources, is vulnerable to be polluted as its closed hydraulic relation with surface water. Thus, it is very important to identify the groundwater source to control groundwater pollution. The Pearson correlation coefficient among major ions (Na + K+, Ca2+, Mg2+, HCO3 -, SO4 2-, and Cl-) was employed to deduce the groundwater types in Zhong Liang Mountain, Southwest China. Then, the combined method of principal component analysis and cluster analysis were employed to identify the groundwater sources in a typical karst region of southwest China. The results shown that (1) the high positive correlation between cations and anions indicated the water-rock reaction of Ca-HCO3, Ca-SO4, (Na + K)-Cl, and Mg-SO4. (2) The major two principal components that would represent water-rock reaction of CaSO4 and Ca-HCO3 would, respectively, explain 60.41% and 31.80% of groundwater information. (3) Based on the two principal components, 33 groundwater samples were clustered into eight groups through hierarchical clustering, each group has similar water-rock reaction. The findings would be employed to forecast the surge water, that was an important work for tunnel construction and operation. PRACTITIONER POINTS: The components of groundwater was highly correlated with water-rock reaction. The principal component analysis screens the types of groundwater. The cluster analysis identifies the groundwater sources.

Deep transcranial magnetic stimulation for schizophrenia: a systematic review.

Background: The efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia. Methods: A systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted. Results: Three randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10). Conclusion: This systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings.

Narrative Review and Consensus Recommendations for the Use of Transnasal Humidified Rapid-Insufflation Ventilatory Exchange in Modified Electroconvulsive Therapy.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is a safe, effective, and novel technique that is currently being used in electroconvulsive therapy (ECT). This study aimed to summarize the clinical practices of THRIVE use in ECT to aid physicians and institutions in implementing the best practice guidelines for ECT. Thus, we reviewed the current literature and presented our consensus on the application of THRIVE in ECT in daily clinical practice. This consensus provides information regarding THRIVE use in ECT, including its safety, effectiveness, procedures, precautions, special case management, and application in special populations. Moreover, it guides the standardized use of THRIVE in ECT.

Sex Differences in the Antidepressant and Neurocognitive Effects of Nonconvulsive Electrotherapy in Patients with Treatment-Refractory Depression.

Objective: The objective of this study was to examine sex differences in the antidepressant and neurocognitive effects of adjunctive nonconvulsive electrotherapy (NET) in patients with treatment-refractory depression (TRD), which has not yet been thoroughly investigated. Methods: The study enrolled 20 patients with TRD, comprising 11 males and 9 females, who underwent a series of 6 NET sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depressive symptoms, response, and remission at baseline and after the first, third, and sixth NET sessions. The Wisconsin Card Sorting Test (WCST) was used to assess neurocognitive function at baseline and after the sixth NET session. Results: After completing 6 NET sessions, female patients experiencing TRD exhibited a higher inclination toward achieving an antidepressant response (77.8% vs. 45.5%, P = .197) and antidepressant remission (22.2% vs. 0%, P = .189) when compared to their male counterparts. No significant differences were observed in changes in the HAMD-17 and WCST subscale scores (all P > .05), including completing classification number, total error number, persistent error number, and random error number between males and females. Additionally, no significant correlations were observed between baseline WCST subscale scores and changes in HAMD-17 scores or endpoint scores, irrespective of sex (all P > .05). Conclusion: These pilot findings suggest that female patients with TRD exhibited increased rates of achieving antidepressant response and remission after undergoing NET. However, further studies should be conducted to confirm these findings.

Artificial neural network identified a 20-gene panel in predicting immunotherapy response and survival benefits after anti-PD1/PD-L1 treatment in glioblastoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. OBJECTIVE: To screen glioblastoma patients who may benefit from immunotherapy. METHODS: Eighty-one patients receiving anti-PD1/PD-L1 treatment from a large-scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI-treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder-relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. RESULTS: We defined two groups of ICI-treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder-relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN-predicted responders had significantly better OS rates than nonresponders. CONCLUSION: The 20-gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI-treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.