First Affiliated Hospital of Bengbu Medical College

BACKGROUND: The macrophage, one of the several key immune cell types, is believed to be involved in tumorigenesis. However, the mechanism of macrophages promoting tumor progression is largely unknown. METHODS: The differentially secreted proteins of M1 and M2 macrophages were analyzed by mass spectrometry. We performed GST pull-down assay for the identification of cell-membrane receptors that interact with chitinase 3-like protein 1 (CHI3L1) protein. The mouse model was used to validate the function of CHI3L1 in cancer metastasis in vivo. Protein phosphorylation and gene expression were performed to study the signaling pathway activation of cancer cells after CHI3L1 treatment. RESULTS: M2 macrophage-secreted CHI3L1 promoted the metastasis of gastric and breast cancer cells in vitro and in vivo. The CHI3L1 protein functioned by interacting with interleukin-13 receptor α2 chain (IL-13Rα2) molecules on the plasma membranes of cancer cells. Activation of IL-13Rα2 by CHI3L1 triggered the activation of the mitogen-activated protein kinase signaling pathway, leading to the upregulated expression of matrix metalloproteinase genes, which promoted tumor metastasis. The results of this study indicated that the level of CHI3L1 protein in the sera of patients with gastric or breast cancer was significantly elevated compared with those of healthy donors. CONCLUSIONS: Our study revealed a novel aspect of macrophages with respect to cancer metastasis and showed that CHI3L1 could be a marker of metastatic gastric and breast cancer in patients.

Abstract The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti‐allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP3‐driven diseases.

BACKGROUND: The liver is frequently subject to insult because of viral infection, alcohol abuse, or toxic chemical exposure. Extensive research has been conducted to identify blood markers that can better discern liver damage, but little progress has been achieved in clinical practice. Recently, circulating microRNAs (miRNAs) have been reported as potential biomarkers for the noninvasive diagnosis of cancer. In this study, we investigated whether plasma miRNAs have diagnostic utility in identifying liver disease. METHODS: The study was divided into 2 phases: marker selection by real-time quantitative PCR analysis of a small set of plasma samples, and marker validation with a large set of plasma samples from 83 patients with chronic hepatitis B viral infections, 15 patients with skeletal muscle disease, and 40 healthy controls. Two mouse model systems, d-galactosamine- and alcohol-induced liver injury, were also developed to evaluate whether differences in miRNA concentration were associated with various liver diseases. RESULTS: Among the miRNA candidates identified, miR-122 presented a disease severity-dependent change in plasma concentration in the patients and animal models. Compared with an increase in aminotransferase activity in the blood, the change in miR-122 concentration appeared earlier. Furthermore, this change was more specific for liver injury than for other organ damage and was more reliable, because the change was correlated with liver histologic stage. CONCLUSIONS: Our findings suggest that circulating miR-122 has potential as a novel, predictive, and reliable blood marker for viral-, alcohol-, and chemical-induced liver injury.

PURPOSE Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months ( P = .0570). The objective response rate was 4.6% v 2.7% ( P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Abstract Purpose: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. Patients and Methods: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft-part sarcoma (ASPS), and clear cell sarcoma (CCS). Participants were treated with anlotinib. The primary endpoint was progression-free rate at 12 weeks (PFR12 weeks). Results: A total of 166 patients were included in the final analysis. Overall, the PFR12 weeks was 68%, and objective response rate was 13% (95% confidence interval, 7.6%–18%). The median progression-free survival (PFS) and overall survival (OS) were 5.6 and 12 months, respectively. The PFR12 weeks, median PFS and OS were: 58%, 4.1 and 11 months for UPS (n = 19); 63%, 5.6 and 13 months for LPS (n = 13); 75%, 11 and 15 months for LMS (n = 26); 75%, 7.7 and 12 months for SS (n = 47); 81%, 5.6 and 12 months for FS (n = 18); 77%, 21 and not reached for ASPS (n = 13); 54%, 11 and 16 months for CCS (n = 7); and 44%, 2.8 and 8.8 months for other sarcoma (n = 23), respectively. The most common clinically significant grade 3 or higher adverse events were hypertension (4.8%), triglyceride elevation (3.6%), and pneumothorax (2.4%). No treatment-related death occurred. Conclusions: Anlotinib showed antitumor activity in several STS entities. The toxicity was manageable. Clin Cancer Res; 24(21); 5233–8. ©2018 AACR.

BACKGROUND: Non-small cell lung carcinomas (NSCLC) are prevalent, lethal cancers with especially grim prospects due to late-stage detection and chemoresistance. Circular RNAs (circRNAs) are non-coding RNAs that participate in tumor development. However, the role of circRNAs in NSCLC is not well known. This study investigated the role of one circRNA - circPTPRA- in NSCLC and characterized its molecular mechanism of action. METHODS: circPTPRA expression was analyzed in human NSCLC tumors and matched healthy lung tissue. We performed functional characterization in NSCLC cell lines and a mouse xenograft model of NSCLC to elucidate the molecular role of circPTPRA in epithelial-mesenchymal transitioning (EMT). We also assessed the regulatory action of circPTPRA on the microRNA miR-96-5p and its target the tumor suppressor Ras association domain-containing protein 8 (RASSF8). FINDINGS: circPTPRA was significantly downregulated in NSCLC tumors relative to matched healthy lung tissue. Lower circPTPRA levels correlated with metastasis and inferior survival outcomes in NSCLC patients. circPTPRA suppressed EMT in NSCLC cell lines and reduced metastasis in the murine xenograft model by sequestering miR-96-5p and upregulating RASSF8. Correlation analyses in patient-derived NSCLC tumor specimens supported the involvement of the circPTPRA/miR-96-5p/RASSF8/E-cadherin axis dysregulation in NSCLC tumor progression. INTERPRETATION: circPTPRA suppresses EMT and metastasis of NSCLC cell lines by sponging miR-96-5p, which upregulates the downstream tumor suppressor RASSF8. The circPTPRA/miR-96-5p/RASSF8/E-cadherin axis can be leveraged as a potential treatment avenue in NSCLC. FUND: The Key research and development projects of Anhui Province (201904a0720079), the Natural Science Foundation of Anhui Province (1908085MH240), the Graduate Innovation Program of Bengbu Medical College (Byycx1843), the National Natural Science Foundation of Tibet (XZ2017ZR-ZY033) and the Science and Technology Project of Shannan (SNKJYFJF2017-3) and Academic Subsidy Project for Top Talents in Universities of Anhui in 2019 (gxbjZD16).

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-α, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.

Compared with the traditional teaching method. The case teaching method is a more effective teaching method to improve the ability of problem-solving for graduate students in medical oncology.

BACKGROUND: Anastomotic leakage is a serious complication associated with anterior resection for rectal cancer, the long-term effects of which are unclear. Therefore, a systematic review and meta-analysis were conducted to evaluate the impact of anastomotic leakage on disease recurrence and survival. METHODS: We searched PubMed, Embase, and the Cochrane Library databases from their inception to January 2016. Studies evaluating the oncologic impact of anastomotic leakage were included in the meta-analysis. Outcome measures were local recurrence, overall survival, cancer-specific survival, and distant recurrence. Pooled hazard ratio (HR) with 95 % confidence interval (CI) was calculated using random effects models. RESULTS: Fourteen studies containing 11,353 patients met inclusion criteria. Anastomotic leakage was associated with a greater local recurrence (HR 1.71; 95 % CI 1.22-2.38) and decreased in both overall survival (HR 1.67; 95 % CI 1.19-2.35) and cancer-specific survival (HR 1.30; 95 % CI 1.08-1.56); anastomotic leakage did not increase distant recurrence (HR 1.03; 95 % CI 0.76-1.40). CONCLUSIONS: Anastomotic leakage was associated with high local recurrence and poor survival (both overall and cancer-specific), but not with distant recurrence.

Tumor-associated macrophages (TAMs) in the tumor microenvironment have been associated with enhanced tumor progression. In this study, we investigated the role and molecular mechanisms of MALAT1 in TAMs derived from thyroid cancer. The expression of MALAT1 and FGF2 in thyroid cancer tissues and cells were measured by quantitative real-time PCR and Western blot. TAMs were transfected with indicated constructs. Then the culture medium (CM) from TAMs was harvested for assay. Secreted FGF2 protein levels and TNF-α, IL-12, and IL-10 levels were detected by ELISA. The cell proliferation, migration, and invasion of FTC133 cells were determined with a CCK-8 assay and a Transwell assay, respectively. In addition, HUVEC vasculature formation was measured by matrigel angiogenesis assay. The higher levels of MALAT-1 and FGF2 were observed in thyroid cancer tissues and in thyroid cancer cells compared to that in the control. Besides, in the presence of si-MALAT1, the levels of TNF-α and IL-12 were significantly up-regulated whereas IL-10 was down-regulated in the CM from TAMs. Moreover, down-regulation of MALAT1 in TAMs reduced proliferation, migration, and invasion of FTC133 cells and inhibited angiogenesis. However, overexpression of FGF2 blocked the effects of MALAT1 siRNAs on cell migration, invasion, and angiogenesis. Our results suggest that MALAT1-mediated FGF2 protein secretion from TAMs inhibits inflammatory cytokines release, promotes proliferation, migration, and invasion of FTC133 cells and induces vasculature formation. J. Cell. Biochem. 118: 4821-4830, 2017. © 2017 Wiley Periodicals, Inc.

Abstract First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m 2 ) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m 2 ) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53–0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov ( NCT03958890 ).

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Objectives: This study examined the effectiveness of Cognitive Behavioural Therapy (CBT) in relieving patients' psychological distress during the COVID-19 epidemic. Methods: Ninety-three eligible participants selected by cluster sampling were randomized to an intervention group (N=47) and a control group (N=46). Participants in the control group received routine treatment according to the Chinese Management Guidelines for COVID-19, while participants in the intervention group received routine treatment with additional CBT. The Chinese Version of Depression Anxiety and Stress Scale-21 (DASS-21) was used to evaluate depression, anxiety and stress for all participants at baseline and post-intervention. Two-sided t-test, and proportion tests were used to examine the differences between the intervention and control group for each DASS-21 indicator. Univariate linear regression was used to examine the association between chronic disease status and change in each DASS-21 indicator after intervention. Two-way scatter plots were generated to show the association of the length of hospital stay and the changes of each DASS-21 indicator by intervention and control groups. Results: Significant decreases in means were found for scales of depression, anxiety, stress and total DASS-21 in both intervention (p&lt;0.001) and control group (p=0.001), with participants in the intervention group having a bigger reduction in means. After the intervention, more participants in the intervention group had no depression or anxiety symptoms than in the control group, but no statistical differences were found (p&gt;0.05). Compared with participants with chronic disease, participants with no chronic disease had a significantly larger reduction of total DASS-21 scale (coefficient= -4.74, 95% CI: -9.31; -0.17).The length of hospital stay was significantly associated with a greater increase in anxiety scale in the intervention group (p=0.005), whilst no significant association was found in the control group (p=0.29). Conclusions: The patients with COVID-19 experienced high levels of anxiety, depression and stress. Our study result highlights the effectiveness of CBT in improving the psychological health among patients with COVID-19, also suggests that CBT should be focused on patients with chronic disease and those who have longer hospital stays. These results have important implications in clinical practice in improving psychological health in the context of COVID-19 pandemic.

Parkinson’s disease (PD) is the second-most common neurodegenerative disease after Alzheimer’s disease. The most important pathological feature of PD is the irreversible damage of dopamine neurons, which is related to autophagy and neuroinflammation in the substantia nigra. Previous studies found that the activation of NAcht Leucine-rich repeat Protein 3 (NLRP3) inflammasome/pyroptosis and cell division protein kinase 5 (CDK5)-mediated autophagy played an important role in PD. Bioinformatics analyses further predicted that microRNA (miR)-188-3p potentially targets NLRP3 and CDK5. Adipose-derived stem cell (ADSC)-derived exosomes were found to be excellent vectors for genetic therapy. We assessed the levels of injury, autophagy, and inflammasomes in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-induced PD mice models and neurotoxin 1-methyl-4-phenylpyridinium (MPP+)-induced cell models after treating them with miR-188-3p-enriched exosomes. miR-188-3p-enriched exosome treatment suppressed autophagy and pyroptosis, whereas increased proliferation via targeting CDK5 and NLRP3 in mice and MN9D cells. It was revealed that mir-188-3p could be a new therapeutic target for curing PD patients. Parkinson’s disease (PD) is the second-most common neurodegenerative disease after Alzheimer’s disease. The most important pathological feature of PD is the irreversible damage of dopamine neurons, which is related to autophagy and neuroinflammation in the substantia nigra. Previous studies found that the activation of NAcht Leucine-rich repeat Protein 3 (NLRP3) inflammasome/pyroptosis and cell division protein kinase 5 (CDK5)-mediated autophagy played an important role in PD. Bioinformatics analyses further predicted that microRNA (miR)-188-3p potentially targets NLRP3 and CDK5. Adipose-derived stem cell (ADSC)-derived exosomes were found to be excellent vectors for genetic therapy. We assessed the levels of injury, autophagy, and inflammasomes in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-induced PD mice models and neurotoxin 1-methyl-4-phenylpyridinium (MPP+)-induced cell models after treating them with miR-188-3p-enriched exosomes. miR-188-3p-enriched exosome treatment suppressed autophagy and pyroptosis, whereas increased proliferation via targeting CDK5 and NLRP3 in mice and MN9D cells. It was revealed that mir-188-3p could be a new therapeutic target for curing PD patients.

Circular RNA (circRNA) is a newly described type of non-coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.

INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. CONCLUSIONS: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.

Drug delivery systems (DDSs) based on nanomaterials have shown a promise for cancer chemotherapy; however, it remains a great challenge to localize on-demand release of anticancer drugs in tumor tissues to improve therapeutic effects and minimize the side effects. In this regard, photoresponsive DDSs that employ light as an external stimulus can offer a precise spatiotemporal control of drug release at desired sites of interest. Most photoresponsive DDSs are only responsive to ultraviolet-visible light that shows phototoxicity and/or shallow tissue penetration depth, and thereby their applications are greatly restricted. To address these issues, near-infrared (NIR) photoresponsive DDSs have been developed. In this review, the development of NIR photoresponsive DDSs in last several years for cancer photo-chemotherapy are summarized. They can achieve on-demand release of drugs into tumors of living animals through photothermal, photodynamic, and photoconversion mechanisms, affording obviously amplified therapeutic effects in synergy with phototherapy. Finally, the existing challenges and further perspectives on the development of NIR photoresponsive DDSs and their clinical translation are discussed.

Long non-coding RNAs (lncRNAs) are frequently dysregulated in multiple malignancies, demonstrating their potential oncogenic or tumor-suppressive roles in tumorigenesis. Herein, we reported the identification of a novel lncRNA, linc00665 (ENST00000590622), which was markedly upregulated in lung adenocarcinoma (LUAD) tissues and might serve as an independent predictor for poor prognosis. Functional assays indicated that linc00665 reinforced LUAD cell proliferation and metastasis in vitro and in vivo. Mechanistically, transcription factor SP1 induced the transcription of linc00665 in LUAD cells, which exerted its oncogenic role by functioning as competing endogenous RNA (ceRNA) for miR-98 and subsequently activating downstream AKR1B10-ERK signaling pathway. Together, our study elucidates oncogenic roles of linc00665-miR98-AKR1B10 axis in LUAD tumorigenesis, which may serve as potential diagnostic biomarkers and therapeutic targets.

BACKGROUND: We aimed to determine and compare the effects of music therapy and music medicine on depression, and explore the potential factors associated with the effect. METHODS: PubMed (MEDLINE), Ovid-Embase, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Clinical Evidence were searched to identify studies evaluating the effectiveness of music-based intervention on depression from inception to May 2020. Standardized mean differences (SMDs) were estimated with random-effect model and fixed-effect model. RESULTS: A total of 55 RCTs were included in our meta-analysis. Music therapy exhibited a significant reduction in depressive symptom (SMD = -0.66; 95% CI = -0.86 to -0.46; P<0.001) compared with the control group; while, music medicine exhibited a stronger effect in reducing depressive symptom (SMD = -1.33; 95% CI = -1.96 to -0.70; P<0.001). Among the specific music therapy methods, recreative music therapy (SMD = -1.41; 95% CI = -2.63 to -0.20; P<0.001), guided imagery and music (SMD = -1.08; 95% CI = -1.72 to -0.43; P<0.001), music-assisted relaxation (SMD = -0.81; 95% CI = -1.24 to -0.38; P<0.001), music and imagery (SMD = -0.38; 95% CI = -0.81 to 0.06; P = 0.312), improvisational music therapy (SMD = -0.27; 95% CI = -0.49 to -0.05; P = 0.001), music and discuss (SMD = -0.26; 95% CI = -1.12 to 0.60; P = 0.225) exhibited a different effect respectively. Music therapy and music medicine both exhibited a stronger effects of short and medium length compared with long intervention periods. CONCLUSIONS: A different effect of music therapy and music medicine on depression was observed in our present meta-analysis, and the effect might be affected by the therapy process.