Long noncoding RNA TPT1-AS1 downregulates the microRNA-770-5p expression to inhibit glioma cell autophagy and promote proliferation through STMN1 upregulation.

Through the microarray analysis, long noncoding RNA TPT1-AS1 (TPT1-AS1) was identified in the development of glioma. However, the specific effect of TPT1-AS1 on glioma autophagy in the recent years has not fully been investigated. Therefore, the purpose of our present study is to investigate the function of TPT1-AS1 on affecting autophagy of glioma cells through regulation of microRNA-770-5p (miR-770-5p)-mediated stathmin 1 (STMN1). Initially, the expression of TPT1-AS1, miR-770-5p, and STMN1 were determined in glioma cell lines, followed by the prediction and validation of their interaction. After that, the effects of TPT1-AS1, miR-770-5p, and STMN1 on the in vitro glioma cell proliferation and autophagy were assessed using EdU assay and macrophage-derived chemokine (MDC) and on the in vivo tumor development and autophagy were evaluated using a nude mouse xenograft tumor assay and immunofluorescence assay. In comparison with the normal cells, the glioma cells displayed upregulated expression of TPT1-AS1 and STMN1, but a downregulated miR-770-5p expression. miR-770-5p, which directly targeted STMN1, could be downregulated by TPT1-AS1. Subsequently, in glioma cells, TPT1-AS1 can function to competitively bind to miR-770-5p, thus regulatEing STMN1 expression. Moreover, glioma cell proliferation and autophagy could be mediated through the TPT1-AS1/miR-770-5p/STMN1 axis. From our data we conclude an inhibitory function of TPT1-AS1 in glioma cell autophagy by downregulating miR-770-5p and upregulating STMN1, which may be instrumental for the therapeutic targeting and clinical management of glioma.

Formation mechanisms, structure, solution behavior, and reactivity of aminodiborane.

A facile synthesis of cyclic aminodiborane (NH2B2H5, ADB) from ammonia borane (NH3·BH3, AB) and THF·BH3 has made it possible to determine its important characteristics. Ammonia diborane (NH3BH2(µ-H)BH3, AaDB) and aminoborane (NH2BH2, AoB) were identified as key intermediates in the formation of ADB. Elimination of molecular hydrogen occurred from an ion pair, [H2B(NH3) (THF)](+)[BH4](-). Protic-hydridic hydrogen scrambling was proved on the basis of analysis of the molecular hydrogen products, ADB and other reagents through (2)H NMR and MS, and it was proposed that the scrambling occurred as the ion pair reversibly formed a BH5-like intermediate, [(THF)BH2NH2](η(2)-H2)BH3. Loss of molecular hydrogen from the ion pair led to the formation of AoB, most of which was trapped by BH3 to form ADB with a small amount oligomerizing to (NH2BH2)n. Theoretical calculations showed the thermodynamic feasibility of the proposed intermediates and the activation processes. The structure of the ADB·THF complex was found from X-ray single crystal analysis to be a three-dimensional array of zigzag chains of ADB and THF, maintained by hydrogen and dihydrogen bonding. Room temperature exchange of terminal and bridge hydrogens in ADB was observed in THF solution, while such exchange was not observed in diethyl ether or toluene. Both experimental and theoretical results confirm that the B-H-B bridge in ADB is stronger than that in diborane (B2H6, DB). The B-H-B bridge is opened when ADB and NaH react to form sodium aminodiboronate, Na[NH2(BH3)2]. The structure of the sodium salt as its 18-crown-6 ether adduct was determined by X-ray single crystal analysis.

Thyroid Metastases from Triple-Negative Breast Cancer with High PD-L1 Expression - A Rare Presentation.

Thyroid metastases secondary to triple-negative breast cancer are sporadic. Diagnosis usually requires fine needle aspiration biopsy (FNAB) and immunohistochemistry. There are no treatment guidelines for this type of cancer, and to date, reports of chemotherapy combined with immunotherapy in thyroid metastases are very rare. Here, we first report the effectiveness of anti-PD-1 inhibitor in combination with chemotherapy for the treatment of metastatic thyroid cancer secondary to advanced triple-negative breast cancer with high expression of programmed cell death ligand 1 (PD-L1). Following six cycles of albumin paclitaxel (400mg d1/21 days) plus PD-1 antibody inhibitor (Sindilizumab 200mg d1/21 days), the patient experienced significant relief of neck swelling and obstructive feeding, both the thyroid metastases and the right breast lesion regressed completely following six cycles of treatment. Chemotherapy combined with immunotherapy may provide a new direction for unresectable advanced thyroid metastases.

Real­world evidence of advanced non­small cell lung carcinoma treated with an immune checkpoint inhibitor plus chemotherapy.

Immunotherapy is an effective treatment strategy for patients with advanced non-small cell lung cancer (NSCLC). Although clinical trials on immunotherapy have provided promising results, real-world research in clinical practice is needed to assess the effectiveness and safety of immunotherapy. The present study aimed to characterize real-world outcomes in patients with advanced NSCLC treated with immune checkpoint inhibitor (ICI)-based regimens. The medical records of patients with advanced NSCLC, who were treated with programmed cell death protein-1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) inhibitors, were reviewed for data collection. The primary objectives were to evaluate progression-free survival (PFS) and overall survival (OS). Therefore, multiple Cox regression models were used to investigate the predictive factors for survival outcomes. Furthermore, survival curves for PFS and OS were created using Kaplan-Meier estimates and compared using the log-rank test. The present study included a total of 133 patients with advanced NSCLC who received therapy with ICIs between January 1, 2019 and December 31, 2022. The final follow-up date was August 24, 2023. The median PFS and OS times were 9.8 and 27.2 months, respectively. Univariate Cox regression analysis demonstrated that sex, clinical stage, PD-L1 status, previous systemic therapy, and brain and liver metastases were associated with PFS, while Eastern Cooperative Oncology Group (ECOG) status, clinical stage, PD-L1 status and brain metastasis were associated with OS. Furthermore, multivariate Cox regression analysis demonstrated that a PD-L1 tumor proportion score (TPS) of ≥50% was an indicator of favorable PFS and OS. An ECOG performance status score of ≥1 was also associated with poor OS but not with PFS. Furthermore, brain metastasis was an indicator for poor PFS and OS, while liver metastasis was only associated with a poor PFS. Finally, the results of the present study demonstrated that PD-L1 status was an independent predictor for PFS and OS in patients with advanced NSCLC, especially adenocarcinoma, who were treated with ICIs plus chemotherapy. The results also suggested that patients with a PD-L1 TPS of ≥50% could benefit when the aforementioned regimens were administrated as a first-line or later-line therapy.

Squamous cell carcinoma of ascending colon with pMMR/MSS showed a partial response to PD-1 blockade combined with chemotherapy: A case report.

Primary colon squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. Moreover, there is no treatment guideline for this disease. Proficient mismatch repair/microsatellite-stable (pMMR/MSS) colorectal adenocarcinoma is refractory to immune monotherapy. Although the combination of immunotherapy with chemotherapy in pMMR/MSS colorectal cancer (CRC) is currently under investigation, the clinical activity of this approach in colorectal SCC remains unknown. In this article, we report the case of a pMMR/MSS CRC patient with ascending colon SCC who had high programmed cell death-ligand 1 (PD-L1) expression and the a missense mutation in codon 600 of the B-Raf proto-oncogene (BRAF V600E) mutation. The patient exhibited a significant response to the combination of immunotherapy and chemotherapy. After eight cycles of treatment with the combination of sintilimab and mFOLFOX6 (oxaliplatin, fluorouracil, and leucovorin), computed tomography-guided microwave ablation of the liver metastasis was performed. The patient achieved excellent durable response and continues to experience a good quality of life. The present case indicates that programmed cell death 1 blockade combined with chemotherapy may be an effective therapy for patients with pMMR/MSS colon SCC and high PD-L1 expression. Furthermore, PD-L1 expression may be a biomarker for immunotherapy in patients with colorectal SCC.

Tidal breathing lung function analysis of wheezing and non-wheezing infants with pneumonia: A retrospective observational study.

To compare lung function in wheezing and non-wheezing infants with pneumonia through tidal breathing analysis and explore the correlation between tidal breathing lung function and clinical characteristics. This retrospective observational study included infants with pneumonia hospitalized in the Affiliated Hospital of Guizhou Medical University between January 2018 and December 2018. Medical records were used to obtain the demographic characteristics, clinical characteristics, tidal breathing lung function results before and after a bronchodilator test, and positive remission rates after the bronchodilator test for each patient. Eighty-six wheezing infants (64 males, aged 6.5 [4.8, 9] months) and 27 non-wheezing infants (18 males, aged 7 [5, 12] months) were included. Non-wheezing infants were more likely to have normal airway function compared to wheezing infants (44.4% vs 23.3%, P = .033). Peak tidal expiration flow/tidal expiratory flow (TEF)25 in wheezing infants was significantly higher than that in non-wheezing infants (162.4 [141.2, 200.7] vs 143.3 [131, 178.8], P = .037). The positive remission rate of tidal inspiratory flow (TIF50)/TEF50 (53.5% vs 29.6%, P = .03) and TEF50 (58.1% vs 33.3%, P = .024) were significantly higher in the wheezing infants compared to non-wheezing infants (P = .03 and P = .024, respectively). Furthermore, respiratory rate, tidal volume, peak expiration flow, TEF25, TEF50, and TEF75 were significantly correlated to the age, height, weight, and platelet counts of infants in both the wheezing and non-wheezing infants (all P < .05). Wheezing infants with pneumonia were more likely to have worse tidal breathing lung function compared to non-wheezing infants with pneumonia. The tidal breathing lung function parameter (respiratory rate, tidal volume, peak expiration flow, TEF25, TEF50, and TEF75) were correlated to the age, height, weight, and platelet counts of both wheezing and non-wheezing infants.

Corrigendum: Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

[This corrects the article DOI: 10.3389/fimmu.2018.02916.].

Effects of Occupational Stress on Blood Lipids, Blood Sugar and Immune Function of Doctors.

BACKGROUND: We aimed to investigate the effects of occupational stress on blood lipids, blood glucose and immune function of doctors. METHODS: In 2017, 1291 doctors (565 males, 726 females) in The First Hospital Affiliated with Harbin Medical University (Harbin, China) were enrolled based on the principle of convenience of sampling and cluster sampling. Questionnaires were used to investigate demographic characteristics and occupational stress related factors. Level of glycated hemoglobin was detected by immunoturbidimetric method. Concentration of triglyceride was determined by glycerol phosphate oxidase end point method. Total cholesterol concentration in serum was determined by total cholesterol oxidase end point method. Concentration of serum immunoglobulin was detected by immunoturbidimetry. RESULTS: Levels of glycated hemoglobin and triglyceride in high tension group were higher than those in the low tension group. Levels of IgG and IgM in high tension group were lower than those in low tension group. The risk of elevated glycated hemoglobin levels in > 50-yr-old age group was higher than that of the =<35-yr-old age group. Those in the high coping strategy group was higher in the low coping strategy group. The risk of elevated total cholesterol levels in drinkers is 1.158 times that of non-drinkers. The risk of IgG concentration reduction in smokers was 0.428 times that of non-smokers. The risk of a decrease in IgA concentration in doctors with good sleep quality is 1.527 times that of those with poor sleep quality. CONCLUSION: Occupational stress can lead to increased blood lipids and sugar levels as well suppression of immune function in doctors.

Previous Radiotherapy Increases the Efficacy of IL-2 in Malignant Pleural Effusion: Potential Evidence of a Radio-Memory Effect?

Preclinical and clinical studies have shown that prior receipt of radiotherapy enhances antitumor immune responses, a phenomenon we call the "radio-memory effect." However, all of the evidence regarding this effect to date comes from work with PD1/PDL1 inhibitors. Here we explored whether this effect also occurs with other forms of immune therapy, specifically interleukin-2 (IL-2). We retrospectively assessed outcomes in patients with malignant pleural effusion (MPE) who had previously received radiotherapy for non-small-cell lung cancer (NSCLC) within 18 months before the intrapleural infusion of IL-2 or cisplatin. Radiotherapy sites included lungs, thoracic lymph nodes, and intracranial. All patients received intrapleural infusion of IL-2 or cisplatin, and most had had several cycles of standard chemotherapy for NSCLC. We identified 3,747 patients with MPE (median age 64 years [range 29-88)) treated at one of several institutions from August 2009 through February 2015; 642 patients had been treated with IL-2 and 1102 with cisplatin and had survived for at least 6 months afterward. Among those who received IL-2, 288 had no radiotherapy, 324 had extracranial (i.e., thoracic) radiotherapy, and 36 had intracranial radiotherapy. The median follow-up time for surviving patients was 38 months. Patients who had received extracranial radiotherapy followed by IL-2 had significantly longer PFS than patients who had not received extracranial radiotherapy (i.e., either no radiotherapy or intracranial radiotherapy). Patients who had received intracranial or extracranial radiotherapy followed by IL-2 had significantly longer OS than did other patients. No survival advantage was noted for prior radiotherapy among patients who received intrapleural cisplatin. We speculate that previous radiotherapy could enhance the efficacy of subsequent intrapleural infusion of IL-2, a "radio-memory" effect that could be beneficial in future studies.

Hydroboration of CO2 catalyzed by bis(phosphinite) pincer ligated nickel thiolate complexes.

We report the hydroboration of CO2 with catecholborane catalyzed by a series of bis(phosphinite) pincer ligated nickel thiolate complexes. Turnover frequencies (TOFs) up to 2400 h-1 were achieved at room temperature under an atmospheric pressure of CO2. This represents the highest TOF value known to date for the reduction of CO2 to the methoxide level under mild conditions.