The single cell immunogenomic landscape after neoadjuvant immunotherapy combined chemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK + effector memory T cells (Tem) were relatively enriched and CXCL13+ exhausted T cells (Tex) and regulator T cells (Treg) decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B + memory B cells (Bmem) suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK + Tem and TNFRSF13B + Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

The neuroprotective effect of near infrared light therapy in aged mice with postoperative neurocognitive disorder by upregulating IRF7.

BACKGROUND: Postoperative neurocognitive disorder (PND) is a common central nervous system complication after undergoing surgery and anesthesia especially in elderly patients, while the therapeutic options are very limited. This study was carried out to investigate the beneficial effects of transcranial near infrared light (NIRL) which was employed to the treatment of PND and propose the involved mechanisms. METHODS: The PND mice were established through left carotid artery exposure under isoflurane anesthesia and received transcranial NIRL treatment. Behavioral testing was performed to evaluate the cognitive function of PND mice after transcranial NIRL therapy. Changes in the transcriptomic profiles of prefrontal cortex (PFC) and hippocampus (HP) were identified by next generation sequencing (NGS), and the molecular mechanisms involved were examined by both in vivo mouse model and in vitro cell culture studies. RESULTS: We found that transcranial NIRL therapy effectively ameliorated learning and memory deficit induced by anesthesia and surgery in aged mice. Specifically, we identified down-regulation of interferon regulatory factor 7 (IRF7) in the brains of PND mice that was mechanistically associated with increased pro-inflammatory M1 phenotype of microglia and elevated neuroinflammatory. NIRL treatment produced protective effects through the upregulation of IRF7 expression and reversing microglial phenotypes from pro-inflammatory to neuroprotective, resulting in reduced brain damage and improved cognitive function in PND mice. CONCLUSION: Our results indicate that transcranial NIRL is an effective and safe therapy for PND via alleviating neuroinflammation, and IRF7 plays a key transcription factor in regulating the M1-to-M2 switch of microglia.

Significance of Gastrokine-1 Polymorphism Rs4254535 as a Prognostic Marker and its Association with Clinical Characteristics in Chinese Lung Cancer Patients.

Background: The single nucleotide polymorphism (SNP) of Gastrokine-1 (GKN1) is associated with lung cancer but its association with prognosis is not clear. Methods: Genomic DNA was extracted from the blood samples of 888 patients with lung cancer. The association between GKN1 polymorphism rs4254535 and prognostic was analyzed by the Kaplan-Meier (KM) method, Log-rank test, and Cox proportional hazards model. Results: In females and patients diagnosed with late-stage lung cancer, the CC genotype (CC vs TT, adjusted odds ratio [HR] = 0.57, 95% Confidence Interval [CI]: 0.33-0.99, P = 0.045; HR = 0.66, 95% CI: 0.48-0.92, P = 0.014) and recessive CC genotype (CC vs TT + TC, HR = 0.55, 95% CI: 0.32-0.94, P = 0.028; HR = 0.64, 95% CI: 0.47-0.89, P = 0.006) of rs4254535 conferred a better prognosis, compared with the TT and TT + TC genotype. Rs4254535 dominate TC + CC genotype, recessive CC genotype, and C allele who were adenocarcinoma patients had a significantly better prognosis. The recessive CC genotype of non-smoking patients has a better prognosis, compared to the TT + TC genotype. Additionally, in the dominant TT + TC genotype and C allele, no family history patients had a significantly better prognosis, compared to the TT genotype. Conclusion: For lung cancer patients, GKN1 polymorphism rs4254535 may be a protective genetic marker and predicts the prognosis of lung cancer patients.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Transport Property of Wrinkled Graphene Nanoribbon Tuned by Spin-Polarized Gate Made of Vanadium-Benzene Nanowire.

A series of four-terminal V7(Bz)8-WGNR devices were established with wrinkled graphene nanoribbon (WGNR) and vanadium-benzene nanowire (V7(Bz)8). The spin-polarized V7(Bz)8 as the gate channel was placed crossing the plane, the concave (endo-positioned) and the convex (endo-positioned) surface of WGNR with different curvatures via Van der Waals interaction. The density functional theory (DFT) and nonequilibrium Green's function (NEGF) methods were adopted to calculate the transport properties of these devices at various bias voltages (VS) and gate voltages (VG), such as the conductance, spin-polarized currents, transmission spectra (TS), local density of states (LDOS), and scattering states. The results indicate that the position of V7(Bz)8 and the bending curvature of WGNR play important roles in tuning the transport properties of these four-terminal devices. A spin-polarized transport property is induced for these four-terminal devices by the spin-polarized nature of V7(Bz)8. Particularly, the down-spin channel disturbs strongly on the source-to-drain conductance of WGNR when V7(Bz)8 is endo-positioned crossing the WGNR. Our findings on the novel property of four-terminal V7(Bz)8-WGNR devices provide useful guidelines for achieving flexible graphene-based electronic nanodevices by attaching other similar multidecker metal-arene nanowires.

[Prediction of Cadmium Uptake Factor in Wheat Based on Machine Learning].

Applying machine learning methods to resolve the cadmium (Cd) uptake characteristics of regional soil-wheat systems can contribute to the accuracy and rationality of risk decisions. Based on a regional survey, we constructed a Freundlich-type transfer equation, random forest (RF) model, and neural network (BPNN) model to predict wheat Cd enrichment factor (BCF-Cd); verified the prediction accuracy; and assessed the uncertainty of different models. The results showed that both RF (R2=0.583) and BPNN (R2=0.490) were better than the Freundlich transfer equation (R2=0.410). The RF and BPNN were further trained repeatedly, and the results showed that the mean absolute error (MAE) and root mean square error (RMSE) of RF and BPNN were close to each other. Additionally, the accuracy and stability of RF (R2=0.527-0.601) was higher than that of BPNN (R2=0.432-0.661). Feature importance analysis showed that multiple factors led to the heterogeneity of wheat BCF-Cd, in which soil phosphorus (P) and zinc (Zn) were the key variables affecting the change in wheat BCF-Cd. Parameter optimization can further improve the accuracy, stability, and generalization ability of the model.

Identified optimal candidates for pulmonary resection in octogenarians with non-small cell lung cancer: a web-based predictive model.

Background: A survival benefit from pulmonary resection was observed in octogenarians with non-small cell lung cancer (NSCLC). Meanwhile, the identification of patients who can indeed benefit can be difficult. Therefore, we aimed to establish a web-based predictive model to identify optimal candidates for pulmonary resection. Methods: Octogenarians with NSCLC in Surveillance, Epidemiology and End Results (SEER) database were enrolled and split into the surgery and non-surgery groups based on whether they received pulmonary resection. Propensity-score matching (PSM) was utilized to eliminate the imbalance. Independent prognostic factors were identified. Patients in the surgery group who lived longer than the median cancer-specific survival (CSS) time of the non-surgery group were assumed to benefit from the surgery. The surgery group was further divided into the beneficial group and the non-beneficial group based on the median CSS time of the non-surgery group. Among the surgery group, a nomogram was established through a logistic regression model. Results: A total of 14,264 eligible patients were extracted, with 4,475 (31.37%) patients receiving pulmonary resection. Surgery was an independent favorable factor of prognosis after PSM (median CSS time: 58 vs. 14 months, P<0.001). A total of 750 (70.4%) patients lived longer than 14 months (beneficial group) in the surgery group. Factors including age, gender, race, histologic type, differentiation grade, and tumor-node-metastasis (TNM) stage were used to formulate the web-based nomogram. The precise discrimination and predictive capability of the model were validated through receiver operating characteristic curves, calibration plots, and decision curve analyses. Conclusions: A web-based predicted model was constructed to distinguish specific patients who can indeed benefit from pulmonary resection among octogenarians with NSCLC.

Individualized prediction of survival benefit from postoperative radiotherapy for patients with malignant pleural mesothelioma.

OBJECTIVES: The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme. MATERIALS AND METHODS: Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates. RESULTS: We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661). CONCLUSION: We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.

Kai-Xin-San Improves Cognitive Impairment via Wnt/ß-Catenin and IRE1/XBP1s Signalings in APP/PS1 Mice.

Alzheimer's disease (AD) is the most common type of dementia with an insidious onset and slow progression. Kai-Xin-San (KXS) has been reported to be effective in improving cognitive impairment in AD. However, the mechanism is still confused. In this study, we employed APP/PS1 mice to explore the neuroprotective mechanism of KXS. Forty-eight male APP/PS1 mice were randomly divided into model group, KXS groups (0.7, 1.4, and 2.8 g/kg/d, p.o.) and the wild-type mice were assigned to the normal control group (n = 12 in each group). Y-maze and novel object recognition tests were carried out after continuous intragastric administration for 2 months. The abilities of learning, memory, and new object recognition in the APP/PS1 mice were enhanced significantly after KXS treatment. KXS can reduce the deposition of Aß40 and Aß42 in APP/PS1 mice brain. KXS decreased the levels of serum inflammatory cytokines, tumor necrosis factor-α, interleukin-1ß, and interleukin-6. KXS increased the activities of superoxide dismutase and glutathione peroxidase significantly, whereas it inhibited the contents of reactive oxygen species and malondialdehyde significantly. In addition, we also detected Wnt/ß-catenin signaling related proteins, such as Wnt7a, ß-catenin, low-density lipoprotein receptor-related protein 6 (LRP6), glycogen synthase kinase-3ß (GSK-3ß), nuclear factor kappa-B (NF-κB), postsynaptic density 95 (PSD95), microtubule associated protein-2 (MAP-2), and endoplasmic reticulum stress (IRE1 pathway) related proteins, such as inositol-requiring enzyme 1 (IRE1), phosphorylated IRE1(p-IRE1), spliced X-box-binding protein 1 (XBP1s), immunoglobulin binding protein (BIP), and protein disulfide isomerase (PDI) in the hippocampus. Results showed that KXS decreased the expression of GSK-3ß, NF-kB, p-IRE1/IRE1 ratio, XBP1s, and BIP; increased the expression of Wnt7a, ß-catenin, LRP6, PSD95, MAP2, and PDI. In conclusion, KXS improved cognitive impairment by activating Wnt/ß-catenin signaling, inhibiting the IRE1/XBP1s pathway in APP/PS1 mice.

The diagnostic significance of cerebrospinal fluid cytology and circulating tumor DNA in meningeal carcinomatosis.

Objective: The objective of this research is to investigate the clinical application value of cerebrospinal fluid (CSF) cytology and circulating tumor DNA (ctDNA) in lung adenocarcinoma (LUAD) meningeal metastasis-meningeal carcinomatosis (MC), and to further explore the possible molecular mechanisms and drug treatment targets of LUAD meningeal metastasis by next-generation sequencing (NGS). Methods: We retrospectively analyzed LUAD with MC in 52 patients. CSF cytology was carried out using the slide centrifugation precipitation method and May-Grüwald-Giemsa (MGG) staining. Tumor tissue, plasma and CSF ctDNA of some MC patients were detected by NGS. Results: Of the 52 MC patients, 46 (88.46%) were positive for CSF cytology and 34 (65.38%) were positive for imaging, with statistically significant differences in diagnostic positivity (P < 0.05). In 32 of these patients, CSF cytology, cerebrospinal fluid ctDNA, plasma ctDNA and MRI examination were performed simultaneously, and the positive rates were 84.38, 100, 56.25, and 62.50% respectively, the difference was statistically significant (P < 0.001). Analysis of the NGS profiles of tumor tissues, plasma and CSF of 12 MC patients: the mutated gene with the highest detection rate was epidermal growth factor receptor (EGFR) and the detection rate were 100, 58.33, and 100% respectively in tumor tissues, plasma and CSF, and there were 6 cases of concordance between plasma and tissue EGFR mutation sites, with a concordance rate of 50.00%, and 12 cases of concordance between CSF and tissue EGFR mutation sites, with a concordance rate of 100%. In addition, mutations not found in tissue or plasma were detected in CSF: FH mutation, SETD2 mutation, WT1 mutation, CDKN2A mutation, CDKN2B mutation, and multiple copy number variants (CNV), with the most detected being CDKN2A mutation and MET amplification. Conclusion: CSF cytology is more sensitive than traditional imaging in the diagnosis of meningeal carcinomatosis and has significant advantages in the early screening and diagnosis of MC patients. CSF ctDNA can be used as a complementary diagnostic method to negative results of CSF cytology and MRI, and CSF ctDNA can be used as an important method for liquid biopsy of patients with MC, which has important clinical significance in revealing the possible molecular mechanisms and drug treatment targets of meningeal metastasis of LUAD.

Clinical effects of Chemotherapy combined with Immunotherapy in patients with advanced NSCLC and the effect on their nutritional status and immune function.

Objectives: To evaluate the clinical effects of chemotherapy combined with immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and the effect on their nutritional status and immune function. Methods: Total 120 patients with advanced NSCLC admitted to Affiliated Hospital of Hebei University from May 2019 to October 2021 were randomly divided into two groups (n= 60, respectively). Patients in the control group were treated by chemotherapy with cisplatin-paclitaxel (TP) alone: 120 mg/m2 paclitaxel was used on d1; and 25mg/m2 cisplatin (CDDP) was used for more than two hour, once every 14 days, for three consecutive three cycles. Patients in the study group were additionally given 200 mg sindilizumab by intravenous drip, once every three weeks. The contrastive analysis of clinical effects, the incidence of adverse reactions, improvement of the nutrient index and the changes in levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in T-lymphocyte subsets was performed between the two groups. Result: The overall response rate (ORR) was 80% and 61% in the study group and the control group, respectively; and the difference was statistically significant (p=0.03); the contrast analysis of the incidence of post-treatment adverse drug reactions (ADRs) in patients in the two groups suggested that the incidence of adverse reactions was 33.3% and 45% in the study group and the control group, respectively; and the difference was not statistically significant (p=0.19). After the treatment, the improvement of hemoglobin, albumin, serum iron and ferritin levels in the study group was more significant than that in the control group; and the difference was statistically significant (p < 0.05). After the treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the study group were much higher than those in the control group; and the difference was statistically significant (p < 0.05). Conclusion: Chemotherapy combined with immunotherapy is effective in treating patients with advanced NSCLC without increasing the incidence of adverse reactions, and can significantly improve their nutritional status and T-lymphocyte function. This therapeutic regimen is of much higher clinical value than the chemotherapy-only regimen.

Cadmium stress interacts with nutrient availability and light condition to affect the growth of Hydrocotyle vulgaris.

Heavy metal pollution is becoming a serious problem in wetland and often co-occurs with nutrient availability and light conditions variation. We hypothesized that nutrient availability and light condition can affect the growth of wetland plants under heavy metal stress. To test this hypothesis, single ramets of a common, clonal wetland plant Hydrocotyle vulgaris were grown for four weeks at three levels of cadmium with three levels of nutrient availability under 30% or 100% light conditions. High level of nutrient availability and high light condition overall promoted growth of H. vulgaris under Cd stress. Under the two light conditions, responses of H. vulgaris to Cd treatments differed among three nutrient levels. Under 30% light condition, 2 mg L-1 Cd2+ treatment decreased total mass at the low nutrient level and decreased ramet number at the medium nutrient level; 0.5 and 2 mg L-1 Cd2+ treatments decreased leaf mass ratio at the low and the medium nutrient levels. Under 100% light condition, 2 mg L-1 Cd2+ treatments significantly decreased total mass at the high level of nutrients; 2 mg L-1 Cd2+ treatment decreased ramet number at the medium and the high nutrient levels and decreased leaf mass ratio at the medium nutrient levels. Our results suggested that Cd stress can interact with nutrient availability and light condition to affect the performance of wetland plants such as H. vulgaris.

Promising Therapeutic Functions of Bone Marrow Mesenchymal Stem Cells Derived-Exosome in Asthma.

Asthma is a chronic inflammatory disturbance of the airways in which many cells and cellular elements are involved. Wheezing, breathlessness, chest tightness, and coughing, especially at night or in the early morning, are typical symptoms of asthma. At present, inhaled corticosteroid (ICS) and long-acting ß-agonists (LABAs) are standard treatments for regular management. Oral corticosteroids (OCSs) were recommended for controlling asthma exacerbation but only for a short-term treatment because of the side effects on organs. Biologic therapies have achieved exciting and notable effects in clinical treatment but are not applicable for all phenotypes of asthma. At present, some new approaches are under exploration to lessen side effects and improve curative effects. Studies have revealed that bone marrow mesenchymal stem cells (BMMSCs) hold various curative effects in asthma and may benefit in the long term with high safety. Extracellular vesicles (EVs) enriched in body fluid were characterized as subcomponents of extracellular vesicles and delivered carriers combined with genetic messages in vivo. The therapeutic potential of exosomes has become a research hotspot in many diseases. BMMSC-derived exosomes were considered as the dominant part of BMMSCs in cell-to-cell communications and playing curative effects. Points also hold that BMMSC-Exo could interfere with airway inflammation and airway remolding in asthma via modulating the immune response, regulating gene expression, adjusting the phenotype of macrophage, etc. However, BMMSC-Exo still lacked more clinical trials for evaluating the effects on asthma, and the technology of extraction and purification still needs to be improved for wide use. This review aims to draw the relationship among asthma, BMMSC, and exosome, which may provide innovate ideas for treatment of asthma, and arouse attention about the curative potential of BMMSC-Exo.

Antidepressant-like activity of oroxylin A in mice models of depression: A behavioral and neurobiological characterization.

Depression is a mood disorder which causes a huge economic burden to both families and societies. However, those monoamine-based antidepressants used in clinical practice have been found to have various limitations. Therefore, currently it is very necessary to explore novel antidepressant targets and medications. As a main active component extracted from Scutellariae radix, oroxylin A possesses many pharmacological functions such as anti-cancer, anti-inflammation and neuroprotection. Here, the present study aims to investigate whether oroxylin A possess antidepressant-like actions using the chronic unpredictable mild stress (CUMS) and chronic restraint stress (CRS) models of depression, forced swim test, tail suspension test, open field test, sucrose preference test, western blotting, immunofluorescence and viral-mediated gene interference. Our results revealed that treatment of oroxylin A fully prevented both the CUMS-induced and CRS-induced depressive-like behaviors in mice. Moreover, the protecting effects of oroxylin A against CUMS and CRS on mice behaviors were accompanied with a significant enhancement on the levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase B (pTrkB), phosphorylated cAMP-response element binding protein (pCREB) and neurogenesis in the hippocampus. Furthermore, genetic knockdown of BDNF and TrkB in the hippocampus remarkably abolished the antidepressant-like efficacy of oroxylin A in both the CUMS and CRS models of depression, proving that the hippocampal BDNF-TrkB system participates in the antidepressant mechanism of oroxylin A. In summary, our findings are the first evidence showing that oroxylin A possesses potential of being an antidepressant candidate.

N6-Methyladenosine Reader YTHDF2 Enhances Non-Small-Cell Lung Cancer Cell Proliferation and Metastasis through Mediating circ_SFMBT2 Degradation.

Objective: circ_SFMBT2 was reported to facilitate malignant progression in various cancers, but its function in non-small-cell lung cancer (NSCLC) has not been fully uncovered. This study aimed to investigate the effects of N6-methyladenosine (m6A) methylation of circ_SFMBT2 (circ_0017628) on non-small-cell lung cancer (NSCLC) and its underlying mechanisms. Methods: Paired tumor and noncancerous tissues from NSCLC patients were surgically collected from January 2020 to March 2021 in our hospital. The levels of circ_SFMBT2 and LATS2 in NSCLC and human bronchial epithelial cells were assayed with qRT-PCR. Overexpression or silencing of circ_SFMBT2, LATS2, or YTHDF2 was performed in the NSCLC cells. CCK-8, colony-forming, and transwell assays were performed to analyze cell proliferation, viability, and migration, respectively. Meanwhile, the expression of MMP-9, E-cadherin, vimentin, and the Hippo/YAP pathway components was examined by western blotting. The m6A enrichment in circ_SFMBT2 was verified using methylated RNA immunoprecipitation, and interaction between circ_SFMBT2 and YTHDF2 was assessed by RNA pull-down and immunoprecipitation assays. Results: Both circ_SFMBT2 and LATS2 were lowly expressed in NSCLC cells and tissues. A positive correlation of circ_SFMBT2 with LATS2 was identified, and circ_SFMBT2 was localized predominantly in the cytoplasm. circ_SFMBT2 overexpression negatively regulated cell proliferation, viability, migration, and epithelial-mesenchymal transition while promoting the Hippo/YAP pathway activation. Notably, knockdown of LATS2 effectively abrogated the inhibitory effects of circ_SFMBT2 overexpression on NSCLC cell malignancies. Besides, m6A was specifically enriched in circ_SFMBT2, and circ_SFMBT2 could bind to YTHDF2. Silencing of YTHDF2 led to an increase in circ_SFMBT2 expression while inhibiting the malignancy of cancer cells. Conclusion: Our results showed that YTHDF2 could facilitate NSCLC cell proliferation and metastasis via the Hippo/YAP pathway activation by mediating circ_SFMBT2 degradation.

Nanomaterials-based photosensitizers and delivery systems for photodynamic cancer therapy.

The increasing cancer morbidity and mortality requires the development of high-efficiency and low-toxicity anticancer approaches. In recent years, photodynamic therapy (PDT) has attracted much attention in cancer therapy due to its non-invasive features and low side effects. Photosensitizer (PS) is one of the key factors of PDT, and its successful delivery largely determines the outcome of PDT. Although a few PS molecules have been approved for clinical use, PDT is still limited by the low stability and poor tumor targeting capacity of PSs. Various nanomaterial systems have shown great potentials in improving PDT, such as metal nanoparticles, graphene-based nanomaterials, liposomes, ROS-sensitive nanocarriers and supramolecular nanomaterials. The small molecular PSs can be loaded in functional nanomaterials to enhance the PS stability and tumor targeted delivery, and some functionalized nanomaterials themselves can be directly used as PSs. Herein, we aim to provide a comprehensive understanding of PDT, and summarize the recent progress of nanomaterials-based PSs and delivery systems in anticancer PDT. In addition, the concerns of nanomaterials-based PDT including low tumor targeting capacity, limited light penetration, hypoxia and nonspecific protein corona formation are discussed. The possible solutions to these concerns are also discussed.

The impact of station 4L lymph node dissection on short-term and long-term outcomes in non-small cell lung cancer.

OBJECTIVE: The optimal extent of lymph node dissection (LND) remains controversial. We aimed to investigate whether the addition of station 4L lymph node dissection (S4L-LND) was beneficial for non-small cell lung cancer (NSCLC). METHODS: Data on 1040 left-sided NSCLC patients undergoing rigorous systematic LND were retrospectively reviewed. Multivariate logistic regression analysis determined risk factors of station 4L (S4L) nodal involvement to facilitate risk stratified analysis of the significance of S4L-LND. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics between S4L-LND group and no-S4L-LND group. Recurrence-free survival (RFS), overall survival (OS), and postoperative complications were compared. RESULTS: S4L-LND was performed in 586 (56.3%) patients. The S4L nodal involvement rate was 15.5% (91/586). Aortopulmonary zone nodes involvement (P < 0.001), N1 nodes involvement (P < 0.001), and advanced T stage (P = 0.015) were independent risk factors of S4L nodal involvement. Patients with ≥ 2 risk factors of S4L nodal involvement were classified as high risk group, and the others were classified as low risk group. Among patients with negative aortopulmonary zone nodes and inferior mediastinal nodes (n = 425), only 28 (6.6%) patients had S4L involvement. After PSM, a total of 416 pairs were well matched. There was no significant survival difference between S4L-LND group and no-S4L-LND group (OS, P = 0.247; RFS, P = 0.569). When stratified by risk subgroup, S4L-LND group did not demonstrate superior survival than no-S4L-LND group in the high risk group (OS, P = 0.273; RFS, P = 0.754) or the low risk group (OS, P = 0.558; RFS, P = 0.319). S4L-LND group demonstrated significantly greater risk of postoperative complications than no-S4L-LND group (9.6% vs. 5.8%; P = 0.037). CONCLUSIONS: S4L involvement was not rare and usually occurred with multiple nodal stations involvement. Routine dissection of aortopulmonary zone and inferior mediastinal nodes was sufficient to ensure staging accuracy. The addition of S4L-LND did not improve survival, but might increase the risk of postoperative complications.

Advanced lung cancer patient with isolated heparin-induced thrombocytopenia: A case report.

RATIONALE: Heparin-induced thrombocytopenia (HIT), a potentially devastating form of drug-induced thrombocytopenia, occurs in patients receiving heparin for thrombosis prevention or treatment. An isolated HIT is characterized by decreased platelet counts without thrombosis, which are atypical and difficult to clinically find. SYMPTOMS AND CLINICAL FINDINGS: A 33-year-old female patient's admission examination revealed elevated D-dimer levels. After prophylactic anticoagulation using low-molecular weight heparin, her blood platelet counts were rapidly decreased, whereas her D-dimer levels increased, followed by presentations of chest tightness, abdominal pain, and skin itching without thrombosis. After excluding all the other causes of thrombocytopenia, HIT was suspected. Her 4Ts score was 5 points, and enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was positive, indicating isolated HIT. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: The patient was diagnosed with advanced lung cancer presenting with isolated HIT. We immediately stopped low-molecular weight heparin and initiated rivaroxaban for anticoagulation. We administered thrombopoietin (TPO) and avatripopal maleate tablets to increase blood platelet counts, whereas intravenous immunoglobulin (IVIG) was administered to stimulate her immune system. The patient's thrombocytopenia was successfully treated without thrombosis and bleeding complications. LESSONS: Rivaroxaban is a potential option for tumor preventive anticoagulation and HIT treatment. Early HIT identification is necessary. After identification, the 4Ts score as well as PF4/heparin antibodies should be assessed and appropriate anticoagulants selected based on patients' conditions.