Personalised follow-up and management schema for patients with screen-detected pulmonary nodules: A dynamic modelling study.

BACKGROUND: Selecting the time target for follow-up testing in lung cancer screening is challenging. We aim to devise dynamic, personalized lung cancer screening schema for patients with pulmonary nodules detected through low-dose computed tomography. METHODS: We developed and validated dynamic models using data of pulmonary nodule patients (aged 55-74 years) from the National Lung Screening Trial. We predicted patient-specific risk profiles at baseline (R0) and updated the risk evaluation results in repeated screening rounds (R1 and R2). We used risk cutoffs to optimize time-dependent sensitivity at an early decision point (3 months) and time-dependent specificity at a late decision point (1 year). RESULTS: In validation, area under receiver operating characteristic curve for predicting 12-month lung cancer onset was 0.867 (95 % confidence interval: 0.827-0.894) and 0.807 (0.765-0.948) at R0 and R1-R2, respectively. The personalized schema, compared with National Comprehensive Cancer Network (NCCN) guideline and Lung-RADS, yielded lower rates of delayed diagnosis (1.7% vs. 1.7% vs. 6.9 %) and over-testing (4.9% vs. 5.6% vs. 5.6 %) at R0, and lower rates of delayed diagnosis (0.0% vs. 18.2% vs. 18.2 %) and over-testing (2.6% vs. 8.3% vs. 7.3 %) at R2. Earlier test recommendation among cancer patients was more frequent using the personalized schema (vs. NCCN: 29.8% vs. 20.9 %, p = 0.0065; vs. Lung-RADS: 33.2% vs. 22.8 %, p = 0.0025), especially for women, patients aged ≥65 years, and part-solid or non-solid nodules. CONCLUSIONS: The personalized schema is easy-to-implement and more accurate compared with rule-based protocols. The results highlight value of personalized approaches in realizing efficient nodule management.

The influence of respiratory movement on preoperative CT-guided localization of lung nodules.

AIM: To evaluate the motion amplitude of lung nodules in different locations during preoperative computed tomography (CT)-guided localization, and the influence of respiratory movement on CT-guided percutaneous lung puncture. MATERIALS AND METHODS: A consecutive cohort of 398 patients (123 men and 275 women with a mean age of 53.9 ± 10.7 years) who underwent preoperative CT-guided lung nodule localization from May 2021 to Apr 2022 were included in this retrospective study. The respiratory movement-related nodule amplitude in the cranial-caudal direction during the CT scan, characteristics of patients, lesions, and procedures were statistically analyzed. Univariate and multivariate logistic regression analyses were used to evaluate the influence of these factors on CT-guided localization. RESULTS: The nodule motion distribution showed a statistically significant correlation within the upper/middle (lingular) and lower lobes (p<0.001). Motion amplitude was an independent risk factor for CT scan times (p=0.011) and procedure duration (p=0.016), but not for the technical failure rates or the incidence of complications. Puncture depth was an independent risk factor for the CT scan times, procedure duration, technical failure rates, and complications (p<0.01). Female, prone, and supine (as opposed to lateral) positions were significant protective factors for pneumothorax, while the supine position was an independent risk factor for parenchymal hemorrhage (p=0.025). CONCLUSION: Respiratory-induced motion amplitude of nodules was greater in the lower lobes, resulting in more CT scan times/radiation dose and longer localization duration, but showed no statistically significant influence on the technical success rates or the incidence of complications during preoperative CT-guided localization.

[Current status and prospects for thoracic surgery].

The world today is undergoing revolutionary changes in science, technology, and industry. These changes have optimized the surgical procedure for lung cancer treatment into a more minimally invasive, precise, comprehensive, industrialized, and patient-centered manner. The definition of minimally invasive treatment for lung cancer has been expanded from simply reducing the size of the skin incision to reserve the lung function. The principle of precision surgery is emphasized throughout the whole process of patient management including diagnosis and treatment. Multimodality therapy helps narrow the gaps between different disciplines and thus provides more personalized treatment for lung cancer patients. Integration of industrial techniques such as visualization, surgical robot, and artificial intelligence into medical practice will potentially lead to a revolution in thoracic surgical procedure. Today, thoracic surgeons are responsible for establishing a self-reliant surgical practice for Chinese patients with lung cancer. It is necessary to attach great importance to patient-centered care, move forward to review minimally invasive surgical procedure, and foster better practice for lung cancer management by keeping up with cutting-edge research on science and technology in the context of changes and challenges.

Differentiation between atypical sinonasal non-Hodgkin's lymphoma and inverted papilloma.

AIM: To seek additional magnetic resonance imaging (MRI) features to improve the accuracy of differentiation between atypical sinonasal non-Hodgkin's lymphoma (NHL) and inverted papilloma (IP) using conventional MRI and apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: MRI examinations from 44 atypical cases (21 NHLs and 23 IPs) in sinonasal regions were reviewed retrospectively. Imaging features included tumour laterality, extension, T1-weighted imaging (WI)/T2WI signal intensity homogeneity and ratios, enhancement homogeneity and ratios, and ADCmean. RESULTS: In cases of NHL, homogeneous signal intensity was often observed on T2WI, which was homogeneous and significantly less enhanced than the turbinate, with lower ADCmean. Whereas in IPs, heterogeneous signal intensity was seen on T2WI, which was heterogeneous and of comparable enhancement to the turbinate, and higher ADCmean values were commonly seen. An ADCmean cut-off point of 1.10 × 10-3 mm2/s achieved 100% sensitivity, 90% specificity, and 90% accuracy. In addition, special features were observed that support the distinction between the two tumours, including intestinal pattern enhancement in NHL and spot-like appearance on T2WI and enhancement in IP. CONCLUSIONS: ADCmean was the most valuable metric for differentiating between the atypical sinonasal NHLs and IPs.

Prediction of acute toxicity to Daphnia magna and interspecific correlation: a global QSAR model and a Daphnia-minnow QTTR model.

Acute toxicity is an important basis for the assessment of hazardous chemicals, but currently there is a huge data gap in chemical toxicity information. The in silico Quantitative Structure Activity Relationship (QSAR) models can use the existing experimental data information to predict the missing chemical toxicity information data and thus reduce animal testing. In the present study, a global QSAR model for the prediction of acute Daphnia magna toxicity has been developed based on the five principles proposed by the Organization for Economic Co-operation and Development (OECD). Moreover, a Daphnia-minnow (referring specifically to the fathead minnow) Quantitative Toxicity-Toxicity Relationship (QTTR) prediction model has been developed based on the present study and our previous work on fathead minnow (Pimephales promelas). Both the QSAR and QTTR prediction models have good goodness-of-fit, robustness, and predictive ability. Finally, the acute toxicity mode of action (MOA) for fathead minnow and Daphnia magna was compared by toxicity ratio based on interspecies toxicity data. By comparison, Daphnia magna was found more sensitive to anilines and phosphorothioates than fathead minnow. The present models can fill the acute toxicity data gap and contribute to the chemicals risk assessment and priority setting.

A new antisarcoma strategy: multisubtype heat shock protein/peptide immunotherapy combined with PD-L1 immunological checkpoint inhibitors

Osteosarcoma, a common malignant tumor in orthopedics, often has a very poor prognosis after lung metastasis. Immunotherapy has not achieved much progress in the treatment because of the characteristics of solid tumors and immune environment of osteosarcoma. The tumor environment is rather essential for sarcoma treatment. Our previous study demonstrated that heat shock proteins could be used as antitumor vaccines by carrying tumor antigen peptides, and we hypothesize that an anti-osteosarcoma effect may be increased with an immune check point inhibitor (PD-L1 inhibitor) as a combination treatment strategy. The present study prepared a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine) and concluded that the mHSP/peptide vaccine was more effective than a single subtype heat shock protein, like Grp94. Therefore, we used the mHSP/peptide vaccine in combination with a PD-L1 inhibitor to treat osteosarcoma, and the deterioration of osteosarcoma was effectively hampered. The mechanism of combined therapy was investigated, and AKT expression participates with sarcoma lung metastasis. This study proposed an antisarcoma strategy via stimulation of the immune system as a further alternative approach for sarcoma treatment and elucidated the mechanism of combined therapy (AU)

Potential of Bradyrhizobia inoculation to promote peanut growth and beneficial Rhizobacteria abundance.

AIMS: To investigate the effects of three symbiotic Bradyrhizobium strains on peanut growth and on rhizobacterial communities in flowering and harvest stages in an organic farm, also to evaluate the role of plant development in influencing peanut rhizobacterial microbiota and correlations among the inoculants, rhizobacterial communities and plant growth. METHODS AND RESULTS: Peanut seeds were inoculated with three individual Bradyrhizobium strains, plant growth performance was measured in two developmental stages and rhizobacterial communities were analysed by Illumina sequencing of rpoB gene amplicons from peanut rhizosphere. The three bradyrhizobial inoculants significantly increased the nodule numbers and aboveground fresh weight of peanut plants regardless of the different growth stages, and the pod yields were increased to some extent and significantly positively correlated with Bradyrhizobium abundances in rhizosphere. Principal coordinate analysis indicated that the rhizobacterial communities were strongly influenced by the inoculation and peanut developmental stages. The bradyrhizobia inoculation increased relative abundances of potentially beneficial bacteria in peanut rhizosphere, and also altered rhizobacterial co-occurrence association networks and important network hub taxa. Similarly, plant development also significantly influenced the structure, composition and co-occurrence association networks of rhizobacterial communities. CONCLUSIONS: Bradyrhizobial inoculants increased peanut growth and yields, they and plant development affected the assembly of peanut rhizobacterial communities. SIGNIFICANCE AND IMPACT OF THE STUDY: Rhizobial inoculants improved the host plant performance that might also be associated with the dynamic changes in rhizobacterial community except enhancing the biological nitrogen fixation and helps to profoundly understand the mechanism how rhizobia inoculants improve plant growth and yields.

A new antisarcoma strategy: multisubtype heat shock protein/peptide immunotherapy combined with PD-L1 immunological checkpoint inhibitors.

Osteosarcoma, a common malignant tumor in orthopedics, often has a very poor prognosis after lung metastasis. Immunotherapy has not achieved much progress in the treatment because of the characteristics of solid tumors and immune environment of osteosarcoma. The tumor environment is rather essential for sarcoma treatment. Our previous study demonstrated that heat shock proteins could be used as antitumor vaccines by carrying tumor antigen peptides, and we hypothesize that an anti-osteosarcoma effect may be increased with an immune check point inhibitor (PD-L1 inhibitor) as a combination treatment strategy. The present study prepared a multisubtype mixed heat shock protein osteosarcoma vaccine (mHSP/peptide vaccine) and concluded that the mHSP/peptide vaccine was more effective than a single subtype heat shock protein, like Grp94. Therefore, we used the mHSP/peptide vaccine in combination with a PD-L1 inhibitor to treat osteosarcoma, and the deterioration of osteosarcoma was effectively hampered. The mechanism of combined therapy was investigated, and AKT expression participates with sarcoma lung metastasis. This study proposed an antisarcoma strategy via stimulation of the immune system as a further alternative approach for sarcoma treatment and elucidated the mechanism of combined therapy.

Role of the active cycle of breathing technique combined with phonophoresis for the treatment of patients with chronic obstructive pulmonary disease (COPD): study protocol for a preliminary randomized controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by coughing, the production of excess sputum, and dyspnea. Patients with excessively thick sputum may have frequent attacks or develop more serious disease. The guidelines recommend airway clearance for patients with excessive sputum who are hospitalized with COPD. The active cycle of breathing technique is the most common non-pharmacological airway clearance technique used by physiotherapists. However, the effectiveness of the technique is not always guaranteed. Active cycle of breathing techniques require the initial dilution of the sputum, usually by inhalation drugs, which may have limited effects. Recent studies have found that phonophoresis decreases inflammation, suggesting the potential of the combined usage of active cycle of breathing techniques and phonophoresis. Therefore, the aim of this study is to explore the effectiveness and safety of combining active cycle of breathing technique and phonophoresis in treating COPD patients. METHODS AND ANALYSIS: We propose a single-blind randomized controlled trial using 75 hospitalized patients diagnosed with COPD with excessive sputum production. The patients will be divided into three groups. The intervention group will receive active cycle of breathing techniques combined with phonophoresis. The two comparison groups will be treated with active cycle of breathing techniques and phonophoresis, respectively. The program will be implemented daily for 1 week. The primary outcomes will be changes in sputum viscosity and production, lung function, and pulse oximetry. Secondary outcomes include the assessment of COPD and anxiety, measured by the COPD Assessment Test scale and the Anxiety Inventory for Respiratory Disease, respectively; self-satisfaction; the degree of cooperation; and the length of hospital stay. All outcome measures, with the exception of sputum production and additional secondary outcomes, will be assessed at the commencement of the study and after 1 week's intervention. Analysis of variance will be used to investigate differences between the groups, and a p-value of less than 0.05 (two-tailed) will be considered statistically significant. DISCUSSION: This study introduces a combination of active cycle of breathing techniques and phonophoresis to explore the impact of these interventions on patients hospitalized with COPD. If this combined intervention is shown to be effective, it may prove to be a better treatment for patients with COPD. TRIAL REGISTRATION: The trial was registered prospectively on the Chinese Clinical Trial Registry on 24 December 2019.ClinicalTrials.gov ChiCTR1900028506 . Registered on December 2019.

Bradyrhizobium arachidis mediated enhancement of (oxy)matrine content in the medicinal legume Sophora flavescens.

Effect of rhizobial inoculation and nitrate application on the content of bioactive compounds in legume plants is an interesting aspect for interactions among microbes, plants and chemical fertilizers, as well as for cultivated practice of legumes. In this study, nitrate (0, 5 and 20 mmol l-1 ) and Bradyrhizobium arachidis strain CCBAU 051107T were applied, individually or in combination, to the root rhizosphere of the medicinal legume Sophora flavescens Aiton (SFA). Then the plant growth, nodulation and active ingredients including (oxy)matrine of SFA were determined and compared. Rhizobial inoculation alone significantly increased the numbers and fresh weight of root nodules. Nodulation was significantly inhibited due to nitrate (5 and 20 mmol l-1 ). Only oxymatrine was detected in the control plants without rhizobial inoculation and nitrate supplement, while both oxymatrine and matrine were synthesized in plants treated with inoculation of B. arachidis or supplied with nitrate. The content of oxymatrine was the highest in plants inoculated solely with rhizobia and was not significantly altered by additional application of nitrate. Combinations of B. arachidis inoculation and different concentrations of nitrate did not significantly change the concentrations of (oxy)matrine in the plant. In conclusion, sole rhizobial inoculation was the best approach to increase the contents of key active ingredients oxymatrine and matrine in the medicinal legume SFA.

The gene NtMYC2a acts as a 'master switch' in the regulation of JA-induced nicotine accumulation in tobacco.

The biosynthesis and transport of nicotine has been shown to be coordinately upregulated by jasmonate (JA). MYC2, a member of basic helix-loop-helix (bHLH) transcription factor family, is well-documented as the core player in the JA signalling pathway to regulate diverse plant development processes. Four MYC2 genes were found in the tobacco genome, NtMYC2a/2b and 1a/1b. In this study, we tested whether one of them, NtMYC2a, acts as a 'master switch' in the regulation of nicotine biosynthesis and transport in tobacco. We generated NtMYC2a knockout tobacco plants using the CRISPR-Cas9 technique and analysed the effect of NtMYC2a knockout on expression of the nicotine biosynthesis genes (NtAO, NtQS, NtPMT1a, NtQPT2, NtODC2, NtMPO1, NtA622 and NtBBLa) and transport genes (NtMATE2 and NtJAT1), as well as leaf accumulation of nicotine in the NtMYC2a knockout plants. We found that all the nicotine biosynthesis and transport genes tested in this study were significantly downregulated (>50% reduction compared with wild-type control) in the NtMYC2a knockout plants. Moreover, the leaf nicotine content in knockout plants was dramatically reduced by ca 80% compared with the wild-type control. These results clearly show that NtMYC2a acts as a 'master switch' to coordinate JA-induced nicotine accumulation in tobacco and suggests that NtMYC2a might play an important role in tobacco nicotine-mediated defence against herbivory.

CT and MRI features of giant cell tumours with prominent aneurysmal bone cysts in the extremities: a comparison with primary aneurysmal bone cysts.

AIM: To test the hypothesis that computed tomography (CT) and magnetic resonance imaging (MRI) could help distinguish between giant cell tumours with prominent aneurysmal bone cysts (GABCs) and primary aneurysmal bone cysts (PABCs) of the extremities. MATERIALS AND METHODS: CT and MRI features of 13 patients with GABCs and 13 patients with PABCs in the extremities were analysed retrospectively. The ages and sex of the patients were also recorded. Independent-samples t-tests were used for continuous variables and Fisher's exact tests were used for categorical variables to compare the differences between the two groups. Diagnostic accuracy, sensitivity, and interobserver agreement were calculated. RESULTS: The average age of patients with GABCs (38.2±15.8 years) was higher than that of patients with PABCs (19.3±12.7 years; p=0.003). The transverse/longitudinal diameter ratio was different between GABCs (0.8±0.3) and PABCs (0.6±0.2; p=0.007). Subchondral bone involvement (92.3% versus 30.8%, p=0.004) and deep lobulation (38.5% versus 0%, p=0.039) were more likely to be noted in patients with GABCs. Surrounding blood vessels were identified in six cases of PABCs (6/13), but not in GABCs (p=0.015). The following characteristics were suggestive of GABCs, older patient age, higher transverse/longitudinal diameter ratio, subchondral bone involvement, and deep lobulation indicated a sensitivity of 84.6%, 76.9%, 75%, and 100%, and a specificity of 84.6%, 69.2%, 90%, and 61.9%, respectively. Conversely, surrounding blood vessels were suggestive of PABCs, with a sensitivity of 46.2% and specificity of 100%. The concordance between the two readers was moderate to nearly perfect. CONCLUSION: Age, subchondral bone involvement, lobulation, transverse/longitudinal diameter ratio, and surrounding blood vessels can be used to distinguish GABCs from PABCs.

Spatiotemporal characteristics of neural activity in tibial nerves with carbon nanotube yarn electrodes.

BACKGROUND: Reliable interfacing with peripheral nervous system is essential to extract neural signals. Current implantable peripheral nerve electrodes cannot provide long-term reliable interfaces due to their mechanical mismatch with host nerves. Carbon nanotube (CNT) yarns possess excellent mechanical flexibility and electrical conductivity. It is of great necessity to investigate the selectivity of implantable CNT yarn electrodes. NEW METHOD: Neural interfaces were fabricated with CNT yarn electrodes insulated with Parylene-C. Acute recordings were carried out on tibial nerves of rats, and compound nerve action potentials (CNAPs) were electrically evoked by biphasic current stimulation of four toes. Spatiotemporal characteristics of neural activity and spatial selectivity of the electrodes, denoted by selectivity index (SI), were analyzed in detail. RESULTS: Conduction velocities of sensory afferent fibers recorded by CNT yarn electrodes varied between 4.25 m/s and 37.56 m/s. The SI maxima for specific toes were between 0.55 and 0.99 across seven electrodes. SIs for different CNT yarn electrodes are significantly different among varied toes. COMPARISON WITH EXISTING METHODS: Most single CNT yarn electrode with a ∼ 500 µm exposed length can be sensitive to one or two specific toes in rodent animals. While, it is only possible to discriminate two non-adjacent toes by multisite TIME electrodes. CONCLUSION: Single CNT yarn electrode exposed ∼ 500 µm showed SI values for different toes comparable to a multisite TIME electrode, and had high spatial selectivity for one or two specific toes. The electrodes with cross section exposed could intend to be more sensitive to one specific toe.

MiR-9 accelerates epithelial-mesenchymal transition of ovarian cancer cells via inhibiting e-cadherin.

OBJECTIVE: To investigate the influence of micro-ribonucleic acid (miR)-9 on epithelial-mesenchymal transition (EMT) of ovarian cancer cells by targeted inhibition on E-cadherin (CDH1). PATIENTS AND METHODS: The human ovarian cancer cells were cultured and miR-9 was repressed by inhibitors and overexpressed by miRNA mimics. The expression of EMT-related proteins was measured via Western blotting (WB). The action target of miR-9 was determined through the dual-luciferase reporter gene assay. The changes in protein levels were detected using WB. RESULTS: The expression of miR-9 was markedly up-regulated in ovarian cancer tissues, that is, the expression level of serum miR-9 in ovarian cancer patients was higher than that in control group. After the inhibition of miR-9, the expression level of epithelial indicator CDH1 was increased, while that of interstitial indicator Vimentin was decreased. MiR-9 contained a complementary site in the 3'-untranslated region (UTR) of CDH1 messenger RNA (mRNA) and the mRNA and protein expressions of CDH1 in the cells were down-regulated obviously by miR-9 overexpression. CONCLUSIONS: MiR-9 promotes the EMT of ovarian cancer cells through the targeted inhibition on CDH1.

Inhibition of the NF-κB signaling pathway on endothelial cell function and angiogenesis in mice with acute cerebral infarction.

This study was aimed to investigate whether interferon (IFN)-induced protein 35 (IFI35) affects the signaling pathway of nuclear factor-kappa B (NF-κB) and to observe the effect of different expressions of IFI35 on the proliferation of endothelial cells and angiogenesis in rats with acute cerebral infarction. A suture method was adopted to prepare a mouse model of permanent middle cerebral artery occlusion (PMCAO). After the treatment of cerebral artery occlusion in 200 healthy male mice (weighting 20g-40g), 47 mice were selected and the double luciferase assay was used to identify different structural domains of IFI35; for the remaining 153 mice, RT-PCR and immunohistochemical assays were used to detect the mRNA expression of glioma-associated oncogene homolog 1 (Gli1), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and CD105 (endoglin). The results showed that IFI35 could reduce the level of p65 protein (REL-A) in the nucleus while affecting the production of p-p65 in the cytoplasm. At the same time, IFI35 could be used in combination with a NID1 protein domain + Nmi protein to inhibit the signaling pathway of NF-κB. Expressions of Gli1, VEGF, bFGF, and CD105 in the IFI35 treatment group were all significantly reduced (P less than0.05). In conclusion, IFI35 could suppress the activation of the NF-κB signaling pathway, reduce the proliferating potential of vascular endothelial cells, and lower the expression of vascular growth factors, thereby inhibiting angiogenesis in mice with acute cerebral infarction.

Phospholipase C signaling is involved in porcine reproductive and respiratory syndrome virus infection in cell cultures.

The phospholipase C (PLC) is a family of kinases that hydrolyze phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to generate two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which stimulate distinct downstream signaling. Recently, it has been reported that PLC signaling is activated by multiple viruses for efficient replication and the virus-induced inflammatory response. In this study, we demonstrated that PLC-specific inhibitor U73122 strongly suppressed porcine reproductive and respiratory syndrome virus (PRRSV) productive infection in cell cultures. The inhibitor affected both viral post-binding cell entry and post-entry processes. The virus infection led to an early transient activation of PLCγ-1 at 0.5 h post-infection (hpi), and sustained event at a stage from 4 to 16 hpi in MARC-145 cells. In addition, U73122 inhibited the activation of p38 MAPK signaling stimulated by PRRSV infection, suggesting that PLC signaling may be associated with the virus infection-induced inflammatory response. Taken together, these studies suggested that PLC signaling played an important role in PRRSV infection or pathogenesis. Keywords: PRRSV; U73122; phospholipase C; PLCγ-1.