Amplifying T cell-mediated antitumor immune responses in nonsmall cell lung cancer through photodynamic therapy and anti-PD1.

Photodynamic therapy (PDT) is nowadays widely employed in cancer treatment. We sought to assess the efficacy of combining PDT with anti-programmed cell death protein 1 (PD1) and to investigate the associated mechanisms in nonsmall cell lung cancer (NSCLC). We established a xenograft tumor model in C57BL/6J mice using Lewis lung carcinoma (LLC) cells, recorded tumor growth, and quantified reactive oxygen species (ROS) levels using a ROS detection kit. Pathological changes were assessed through H&E staining, while immunofluorescence (IF) was used to determine the expression of CD8 and Foxp3. Transcriptomic analysis was conducted, analyzing differential expressed genes (DEGs) among control, PDT, and PDT combined with anti-PD1 (PDT+anti-PD1) groups. Functional enrichment analysis via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The Cancer Genome Atlas (TCGA) database was utilized to analyze the expression of aminolevulinate synthase gene (ALAS2), integrin alpha10 (ITGA10), ATP1A2, a disintegrin and metalloprotease 12 (ADAM12), and Lox1 in lung adenocarcinoma and adjacent tissues, with concurrent immune infiltration analysis. Quantitative real-time polymerase chain reaction and western blot were employed to measure mRNA and protein expression levels. Treatment with PDT combined with anti-PD1 significantly inhibited tumor growth and increased the number of CD8+ cells while decreasing Foxp3+ cells. Immune infiltration results presented ALAS2, ADAM12, and ITGA10 were associated with various types of T cells or macrophages. Additionally, the expression levels of EGFR, ERK, and PI3K/Akt were suppressed after PDT with anti-PD1 treatment. Our findings collectively suggest that PDT combined with anti-PD1 treatment could enhance the infiltration of CD8+ T cells, suppressing tumor growth, and this effect was associated with ALAS2, ITGA10, and ADAM12. The underlying mechanism might be linked to EGFR, ERK, and PI3K/Akt signaling. Overall, this study provides valuable insights into the application of PDT combined with anti-PD1 treatment in NSCLC.

The value of narrow-band imaging bronchoscopy in diagnosing central lung cancer.

Aims: This research aimed to study the value of narrow-band imaging(NBI) in the diagnosis of central lung cancer. Materials and methods: This study included 916 patients with clinical suspected of central lung cancer or follow-up of patients after curative lung cancer surgery. All of the patients were examined by Olympus Evis Lucera electronic bronchoscope system, any sites that were abnormal when viewed by white-light bronchoscopy (WLB) or NBI were biopsied, four to six biopsies were taken at each site of the abnormal region visualized as lesions, we record the endoscopic features of NBI and compared with histopathology results, to evaluate the diagnostic value of NBI for central lung cancer and the relationship between vascular patterns of NBI and histological types of lung cancer, and try to establish a multinomial logistic regression model for predicting the histological types of lung cancer. The biopsy specimens were examined by CD34 antibody through immunohistochemistry (IHC) method, CD34 marked microvessel density(MVD), compared the number of microvessels between benign and malignant diseases and the number between different histological types of lung cancer, to verify the results of NBI. Results: NBI provided high sensitivity (91.7%), specificity (84.9%), positive predictive value (97.6%), negative predictive value (61.5%), and agreement rate (90.7%). The predominant vascular patterns in the well-defined histological types of lung cancer were dotted blood vessels (121 patients), tortuous blood vessels (248 patients), and abrupt-ending blood vessels (227 patients). Logistic regression analysis of the results showed that smoking status of the patient, combined with vascular patterns under NBI, and age partly affect the histological types of lung cancer. Conclusions: NBI is highly accurate for the diagnosis of central lung cancer.

Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: A multicenter, open-label, randomized trial.

BACKGROUND: The clinical characteristics and treatment of patients who tested positive for COVID-19 after recovery remained elusive. Effective antiviral therapy is important for tackling these patients. We assessed the efficacy and safety of favipiravir for treating these patients. METHODS: This is a multicenter, open-label, randomized controlled trial in SARS-CoV-2 RNA re-positive patients. Patients were randomly assigned in a 2:1 ratio to receive either favipiravir, in addition to standard care, or standard care alone. The primary outcome was time to achieve a consecutive twice (at intervals of more than 24 h) negative RT-PCR result for SARS-CoV-2 RNA in nasopharyngeal swab and sputum sample. RESULTS: Between March 27 and May 9, 2020, 55 patients underwent randomization; 36 were assigned to the favipiravir group and 19 were assigned to the control group. Favipiravir group had a significantly shorter time from start of study treatment to negative nasopharyngeal swab and sputum than control group (median 17 vs. 26 days); hazard ratio 2.1 (95% CI [1.1-4.0], p = 0.038). The proportion of virus shedding in favipiravir group was higher than control group (80.6% [29/36] vs. 52.6% [10/19], p = 0.030, respectively). C-reactive protein decreased significantly after treatment in the favipiravir group (p = 0.016). The adverse events were generally mild and self-limiting. CONCLUSION: Favipiravir was safe and superior to control in shortening the duration of viral shedding in SARS-CoV-2 RNA recurrent positive after discharge. However, a larger scale and randomized, double-blind, placebo-controlled trial is required to confirm our conclusion.

Effect of low-dose ethanol on NLRP3 inflammasome in diabetes-induced lung injury.

To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.

A High Percentage of Patients Recovered From COVID-19 but Discharged With Abnormal Liver Function Tests.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has become the most severe global health issue. Abnormal liver functions are frequently reported in these patients. However, liver function abnormality was often overlooked during COVID-19 treatment, and data regarding liver functions after cure of COVID-19 is limited. This study aimed to reveal the changes of liver function tests (LFTs) during hospitalization, and its clinical significance in patients with COVID-19. METHODS: In this retrospective, bi-center study, a total of 158 hospitalized patients diagnosed with COVID-19 in China were included from January 22nd, 2020 to February 20th, 2020. Clinical features, laboratory parameters including LFTs, and treatment data were collected and analyzed. LFTs included alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin. Patients were considered with abnormal LFTs when any value of these tests was higher than upper limit of normal. RESULTS: Of 158 patients with COVID-19, 67 (42.41%) patients had abnormal LFTs on admission and another 50 (31.65%) patients developed abnormal LFTs during hospitalization. The incidence of LFTs abnormality in severe COVID-19 cases was significantly higher than non-severe cases. All LFTs in COVID-19 patients were correlated with oxygenation index. There was no statistical difference in treatment between the patients with or without liver test abnormalities. By the time of discharge, there were still 64 (40.50%) patients with abnormal LFTs. Logistic regression analysis identified younger age, hypertension and low lymphocyte counts as independent risk factors for persistent abnormal LFTs during hospitalization. CONCLUSION: Liver function tests abnormality was common in COVID-19 patients and was more prevalent in severe cases than in non-severe cases. A substantial percentage of patients still had abnormal LFTs by the time of discharge.

Thermo-responsive polymer encapsulated gold nanorods for single continuous wave laser-induced photodynamic/photothermal tumour therapy.

Owing to strong and tunable surface plasmon resonance (SPR) effect and good biocompatibility, gold nanoparticles have been suggested to be a versatile platform for a broad range of biomedical applications. In this study, a new nanoplatform of thermo-responsive polymer encapsulated gold nanorods incorporating indocyanine green (ICG) was designed to couple the photothermal properties of gold nanorods (AuNRs) and the photodynamic properties of ICG to enhance the photodynamic/photothermal combination therapy (PDT/PTT). In addition to the significantly increased payload and enhancing photostability of ICG, the polymer shell in the nanoplatform also has thermo-responsive characteristics that can control the release of drugs at tumour sites upon the laser irradiation. On the basis of these improvements, the nanoplatform strongly increased drug aggregation at the tumour site and improved the photothermal/photodynamic therapeutic efficacy. These results suggest that this nanoplatform would be a great potential system for tumour imaging and antitumour therapy.

[Clinical features of patients with venous thromboembolism: 177 case analysis in 10 years].

OBJECTIVE: To analyze the clinical characteristics and risk factors of patients with confirmed venous thromboembolism (VTE) in order to improve recognition of VTE, and reduce the rate of missed diagnosis and wrong diagnosis. METHODS: A retrospectively review was performed for 205 patients diagnosed with VTE confirmed by CT pulmonary angiography (CTPA), radionuclide pulmonary ventilation/perfusion (V/Q) imaging, lower extremity deep vein ultrasound or venography in the First Affiliated Hospital of Bengbu Medical College from January 2009 to December 2018. The clinical manifestations, laboratory examination results, imaging results, treatment and prognosis of patients diagnosed with VTE were analyzed. The clinical possibility was assessed by pulmonary thromboembolism (PTE) simplified Wells score and deep venous thrombosis (DVT) Wells score. 130 non-VTE patients admitted in the same period were enrolled as controls, and the risk factors of VTE were screened by multivariate Logistic regression analysis. RESULTS: Among 205 VTE patients, 14 cases had incomplete data, 2 cases were complicated with other diseases deteriorated, 2 cases were excluded because of economic reasons, 10 cases abandoned treatment because of serious illness, and finally 177 cases were included in the analysis. The main clinical symptoms of VTE patients were chest tightness (36.16%), followed by chest pain (29.94%), dyspnea (29.38%) and hemoptysis (24.29%). Swelling or tenderness of unilateral/bilateral lower extremities (38.98%) and lung moist rale (20.90%) were the most common signs. ST-T changes were the main changes in electrocardiogram (ECG, 49.15%), followed by SIQIIITIII or QIIITIII changes (35.03%). Only 5.65% of the patients had plasma D-dimer less than 0.5 mg/L. 31.07% (55/177) patients had normal arterial blood gas results. Of the 177 VTE patients, 175 were diagnosed as PTE by CTPA, with bilateral/multi-lobar pulmonary artery embolism and its branches being the main type [44.57% (78/175)]. Two cases were diagnosed as PTE by V/Q imaging. Among them, 112 cases were received lower extremity deep venous ultrasound or lower extremity deep venography, 51 cases were diagnosed as lower extremity DVT, with thrombosis of popliteal and above vein as common [68.63% (35/51)]. The clinical possibility assessment showed that 67.23% (119/177) patients might have PTE (PTE simplified Wells score greater than or equal to 2), 38.98% (69/177) patients might have lower extremity DVT (DVT Wells score greater than or equal to 2). Multivariate Logistic regression analysis showed that operation less than 4 weeks [odds ratio (OR) = 5.503, 95% confidence interval (95%CI) = 1.577-19.206, P = 0.007], trauma or fracture less than 3 months (OR = 6.771, 95%CI = 1.510-30.370, P = 0.012), VTE history (OR = 0.072, 95%CI = 0.009-0.549, P = 0.011) were independent risk factors for VTE occurrence. Thrombolytic therapy was administered in 13 cases while anticoagulant therapy alone was prescribed in 164 cases. 176 patients recovered, while 1 case died. CONCLUSIONS: VTE clinical manifestations are not specific. Patients with risk factors should be vigilant, be strengthen with diagnostic awareness, paid attention to the evaluation of clinical possibilities. Timely thrombolytic or anticoagulant treatment after diagnosis, can improve the survival rate.

Aspirin attenuates monocrotaline-induced pulmonary arterial hypertension in rats by suppressing the ERK/MAPK pathway.

This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway.

Expression of survivin and patients survival in non-small cell lung cancer: a meta-analysis of the published studies.

Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44-2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.

Meta-analysis for cyclin E in lung cancer survival.

BACKGROUND: To assess the prognosis value of cyclin E expression in survival of patients with lung cancer (LC), we performed a systematic review of the literature with meta-analysis. METHODS: Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95% confidence interval (95% CI) was used to estimate the strength of the association of cyclin E expression with survival of LC patients. Heterogeneity and publication bias were also assessed. RESULTS: Fourteen studies (2606 cases) were eligible and subjected to analysis. Cyclin E over-expression was found to be a strong predictor of poor prognosis in LC patients (HR: 1.38, 95% CI: 1.07-1.79; P=0.014). When only non-small cell lung cancer (NSCLC) was considered, the combined HR was 1.53 (95% CI: 1.19-1.97, P=0.001). A significant association was also evident when the analysis was limited to studies involving adenocarcinoma (AD), but not squamous cell carcinoma (SQ). Publication bias was absent. Sensitivity analyses suggested that the summary statistics obtained should approximate the actual average.

[The DNA binding activity of nuclear factor-ΚB in patients with severe pneumonia and the intervention effects of Xuebijing injection].

OBJECTIVE: To investigate the role of nuclear factor-ΚB (NF-ΚB) in severe pneumonia and observe the effects of Xuebijing injection in its treatment. METHODS: Thirty hospitalized patients with severe pneumonia were divided into the routine therapy group (n=14) and Xuebijing therapy group (n=16) in whom with Xuebijing injection 100 ml was given once daily for 7 days besides routine therapies, according to the random numeral. The DNA binding activity of NF-ΚB in human monocytes was detected before and 3 days and 7 days after administration, the contents of tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were determined, and the changes in coagulatory and fibrinolytic parameters were assayed at the same time. Acute physiology and chronic health evaluationII (APACHEII) score was also recorded. Ten healthy volunteers served as the healthy control group. RESULTS: The DNA binding activities of NF-ΚB, the contents of TNF-α, PCT, CRP, fibrinogen (Fib), D-dimer in hospitalized subjects with severe pneumonia were higher before treatment than those in healthy control group, while the prothrombin time (PT), thrombin time (TT) were significantly lower (P<0.05 or P<0.01). Compared with the routine therapy group, the DNA binding activity of NF-ΚB (grey level) at the 7 days (66.60±36.23 vs. 79.90±39.11) was notably decreased in Xuebijing therapy group; the levels of TNF-α (ng/L, 25.81±11.67 vs. 33.78±13.36), PCT (µg/L, 1.91±1.09 vs. 2.96±1.80), CRP (mg/L, 20.01±7.21 vs. 26.59±10.66), Fib (g/L, 4.02±1.26 vs. 5.09±1.43), D-dimer (mg/L, 0.24±0.06 vs. 0.31±0.11) were significantly lower in Xuebijing therapy group, and APACHEII score (15.81±3.47 vs. 17.93±3.05) was obviously lowered (all P<0.05). There was statistical difference of the TT (s) between two groups at 3 days (15.68±1.89 vs. 14.65±1.33,P<0.05). There was a significant positive correlation between NF-ΚB DNA binding activity and the levels of TNF-α (r(1)=0.373, r(2)=0.362, r(3)=0.419), PCT (r (1)=0.800, r(2)=0.716, r(3)=0.920) or CRP (r(1)=0.368, r(2)=0.441, r(3)=0.366, all P<0.05) before and 3 days and 7 days after the treatment. CONCLUSION: NF-ΚB activation and coagulopathy were observed in patients with severe pneumonia, and NF-ΚB was involved in the process of inflammatory response. Inflammatory response was partly alleviated by Xuebijing injection. These effects of Xuebijing injection may be mediated by inhibition of the activation of NF-ΚB and its anticoagulation property.