A Prediction Rule for Occurrence of Chronic Thromboembolic Disease After Acute Pulmonary Embolism.

BACKGROUND: Occurrence of chronic thromboembolic disease (CTED) after 3 or 6 months of standard and effective anticoagulation is not uncommon in patients with acute pulmonary embolism (PE). To date, there has been no scoring model for the prediction of CTED occurrence. METHODS: A Prediction Rule for CTED (PRC) was established in the establishment cohort (n=1,124) and then validated in the validation cohort (n=211). Both original and simplified versions of the PRC score were provided by using different scoring and cut-offs. RESULTS: The PRC score included 10 items: active cancer (3.641; 2.338-4.944; p<0.001), autoimmune diseases (2.218; 1.545-2.891; p=0.001), body mass index >30 kg/m2 (2.186; 1.573-2.799; p=0.001), chronic immobility (2.135; 1.741-2.529; p=0.001), D-dimer >2,000 ng/mL (1.618; 1.274-1.962; p=0.005), PE with deep vein thrombosis (3.199; 2.356-4.042; p<0.001), previous venous thromboembolism (VTE) history (5.268; 3.472-7.064; p<0.001), thromboembolism besides VTE (4.954; 3.150-6.758; p<0.001), thrombophilia (3.438; 2.573-4.303; p<0.001), and unprovoked VTE (2.227; 1.471-2.983; p=0.001). In the establishment cohort, the sensitivity, specificity, Youden index (YI), and C-index were 85.5%, 79.7%, 0.652, and 0.821 (0.732-0.909) when using the original PRC score, whereas they were 87.9%, 74.6%, 0.625, and 0.807 (0.718-0.897) when using the simplified one, respectively (Kappa coefficient 0.819, p-value of McNemar's test 0.786). In the validation cohort, the sensitivity, specificity, YI, and C-index were 86.3%, 76.3%, 0.626, and 0.815 (0.707-0.923) when using the original PRC score, whereas they were 85.0%, 78.6%, 0.636, and 0.818 (0.725-0.911) when using the simplified one, respectively (Kappa coefficient 0.912, p-value of McNemar's test 0.937); both were better than that of the DASH score (72.5%, 69.5%, 0.420, and 0.621 [0.532-0.710]). CONCLUSIONS: A prediction score for CTED occurrence, termed PRC, predicted the likelihood of CTED occurrence after 3 or 6 months of standard anticoagulation in hospitalised patients with a diagnosis of acute PE.

Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies-pharmacovigilance database analysis with real-world data validation.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy combined with conventional therapies is being broadly applied in non-small cell lung cancer (NSCLC) patients. However, the risk of interstitial pneumonitis (IP) following a combined regimen is incompletely characterized. METHODS: A total of 46,127 NSCLC patients were extracted for disproportionality analyses of IP from the Food and Drug Administration's Adverse Event Reporting System (FAERS) database. A total of 1108 NSCLC patients who received ICI treatment at Nanfang Hospital of Southern Medical University were collected and utilized for real-world validation. RESULTS: Of the 46,127 patients with NSCLC, 3830 cases (8.3%; 95% confidence interval [CI], 8.05-8.56) developed IP. Multivariable logistic regression analyses revealed that the adjusted ROR of ICI combined with radiation (RT) was the highest (121.69; 95% CI, 83.60-184.96; P < 0.0001) among all therapies, while that of ICI combined with chemotherapy (CHEMO) or targeted therapy (TARGET) was 0.90 (95% CI, 0.78-1.04; P = 0.160) and 1.49 (95% CI, 0.95-2.23; P = 0.065), respectively, using ICI monotherapy as reference. Furthermore, analyses from our validation cohort of 1108 cases showed that the adjusted odds ratio of ICI combined with RT was the highest (12.25; 95% CI, 3.34-50.22; P < 0.01) among all the therapies, while that of ICI combined with CHEMO or TARGET was 2.32 (95% CI, 0.89-7.92; P = 0.12) and 0.66 (95% CI, 0.03-4.55; P = 0.71), respectively, using ICI monotherapy as reference. CONCLUSIONS: Compared with ICI monotherapy, ICI combined with RT, rather than with CHEMO or TARGET, is associated with a higher risk of IP in NSCLC patients. Hence, patients receiving these treatments should be carefully monitored for IP.

Comparison of VTE risk scores in guidelines for VTE diagnosis in nonsurgical hospitalized patients with suspected VTE.

BACKGROUND: The assessment of VTE likelihood with VTE risk scores is essential prior to imaging examinations during VTE diagnostic procedure. Little is known with respect to the disparity of predictive power for VTE diagnosis among VTE risk scores in guidelines for nonsurgical hospitalized patients with clinically suspected VTE. METHODS: A retrospective study was performed to compare the predictive power for VTE diagnosis among the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores in the leading authoritative guidelines in nonsurgical hospitalized patients with suspected VTE. RESULTS: Among 3168 nonsurgical hospitalized patients with suspected VTE, VTE was finally excluded in 2733(86.3%) ones, whereas confirmed in 435(13.7%) ones. The sensitivity and specificity resulted from the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores were (90.3%, 49.8%), (88.7%, 53.6%), (73.8%, 50.2%), (97.7%,16.9%), (80.9%, 44.0%), and (78.2%, 47.0%), respectively. The YI were 0.401, 0.423, 0.240, 0.146, 0.249, and 0.252 for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. The C-index were 0.694(0.626-0.762), 0.697(0.623-0.772), 0.602(0.535-0.669), 0.569(0.486-0.652), 0.607(0.533-0.681), and 0.609(0.538-0.680) for the Wells, Geneva, YEARS, PERC, Padua, and IMPROVE scores, respectively. Consistency was significant in the pairwise comparison of Wells vs Geneva(Kappa 0.753, P = 0.565), YEARS vs Padua(Kappa 0.816, P = 0.565), YEARS vs IMPROVE(Kappa 0.771, P = 0.645), and Padua vs IMPROVE(Kappa 0.789, P = 0.812), whereas it did not present in the other pairs. The YI was improved to 0.304, 0.272, and 0.264 for the PERC(AUC 0.631[0.547-0.714], P = 0.006), Padua(AUC 0.613[0.527-0.700], P = 0.017), and IMPROVE(AUC 0.614[0.530-0.698], P = 0.016), with a revised cutoff of 5 or less, 6 or more, and 4 or more denoting the VTE-likely, respectively. CONCLUSIONS: For nonsurgical hospitalized patients with suspected VTE, the Geneva and Wells scores perform best, the PERC scores performs worst despite its significantly high sensitivity, whereas the others perform intermediately, albeit the absolute predictive power of all isolated scores are mediocre. The predictive power of the PERC, Padua, and IMPROVE scores are improved with revised cutoffs.

Enhancing Idiopathic Scoliosis Patients' Outcomes Through Functional Rehabilitation Training in Combination with Orthosis.

Objective: This study aims to provide clinical evidence for the treatment of idiopathic scoliosis (IS) by assessing the therapeutic effectiveness of combining functional rehabilitation training with orthosis. Methods: We enrolled a total of 94 IS patients who were admitted to our hospital from April 2020 to February 2022. These patients were randomly assigned into two groups: a research group (RG; n=47) receiving functional rehabilitation training combined with orthosis and a control group (CG; n=47) receiving orthosis treatment alone. Clinical outcomes were evaluated one year after treatment. We also measured the Cobb angle, apical vertebral rotation (AVR), and the distance between the vertical line of the sacrum and the spinous process of the scoliosis parietal vertebra before and after treatment to determine apical vertebral translation (AVT) from the sacral midline and lumbar range of motion (ROM). Patient quality of life was assessed using the Short-Form 36 Item Health Survey (SF-36). Results: After treatment, the research group exhibited significantly lower Cobb angles, AVR, and AVT, along with a higher overall response rate and greater lumbar ROM compared to the control group (P < .05). Post-treatment SF-36 scores increased in both groups, with notably higher scores in the research group (P < .05). Conclusions: Combining functional rehabilitation training with orthosis is an effective approach for the treatment of IS and holds substantial clinical significance.

Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Clinical Phenotype and Genetic Analysis of Twins With Congenital Coagulation Factor V Deficiency.

OBJECTIVE: The aim was to investigate the clinical characteristics and molecular pathogenic mechanism of twins with congenital factor V (FV) deficiency. METHODS: We comprehensively analyzed the clinical manifestations and laboratory test results of a set of twins and their parents and performed point mutation analysis with direct high-throughput exon sequencing. RESULTS: The prothrombin time and activated partial thromboplastin time were prolonged for both probands, and the FV activity levels were 13.0% and 9.8%. Next-generation sequencing showed that the affected individuals harbored a paternal c.5113A>C (p.S1705R) and a maternal c.4949C>T (p.A1650V) heterozygous variants in the FV gene, which conformed to an autosomal recessive inheritance pattern. This is the first report of these point mutations. The older boy also had a congenital patent foramen ovale. CONCLUSION: In this set of twins, missense mutations of the FV gene were related to congenital FV deficiency but unrelated to the patent foramen ovale observed in the older boy.

Notch1 activation of Jagged1 contributes to differentiation of mesenchymal stem cells into endothelial cells under cigarette smoke extract exposure.

BACKGROUND: Mesenchymal stem cells (MSCs) have shown therapeutic potential for engraftment to, differentiation into, endothelial cells (ECs). However, low-efficiency yields hinder their use as ECs for therapeutic vascularization. METHODS: The Notch1 signaling pathway is key to optimal pulmonary development. Recent evidence has shown that this pathway participated in angiogenesis. Herein, we found that in MSCs, Jagged1 was a target for Notch 1, resulting in a positive feedback loop that propagated a wave of ECs differentiation. RESULTS: In vitro, Jagged1 was found to be activated by Notch1 in MSCs, resulting in the RBP-Jκ-dependent expression of Jagged1 mRNA, a response that was blocked by Notch1 inhibition. Notch1 promoted the formation of cord-like structures on Matrigel. However, cigarette smoke extract inhibited this process, compared to that in control groups. Moreover, Notch1-overexpressing cells upregulated the expressing of HIF-1α gene. The HIF-1α was an angiogenic factor that clustered with Notch1, underscoring the critical role of Notch1 pathway in vessel assembly. Interestingly, this was abrogated by incubation with Notch1 shRNA. CONCLUSIONS: Notch signaling pathway promotes differentiation of MSCs in to ECs. It also regulates angiogenesis and transcription of specific markers on ECs. These results provide a mechanism that regulates differentiation of MSCs into ECs phenotypes.

Latissimus dorsi myocutaneous flap repair is effective after neoadjuvant chemotherapy for locally advanced breast cancer.

OBJECTIVE: To describe the clinical outcome and physical condition of patients with locally advanced breast cancer (LABC) who received neoadjuvant chemotherapy followed by mastectomy and latissimus dorsi myocutaneous flap repair. METHODS: A retrospective review of 142 patients with locally advanced breast cancer was selected from 1156 breast cancer patients in the South and North areas of The Affiliated Calmette Hospital of Kunming Medical University between May 2008 and December 2018. RESULTS: All participants (n = 142) were women aged 40-55 years (average age 47.35 ± 0.43 years) who received neoadjuvant chemotherapy followed by mastectomy and latissimus dorsi flap repair. The median follow-up period was 16 months (range 12-24 months). For stage of disease, there were 19 cases (13%) in stage IIB, 31 cases (22%) in stage IIIA, 39 cases (28%) in stage IIIB, and 53 cases (37%) in stage IIIC, which were statistically significant with the physical condition of patients (≤ 0.001). Neoadjuvant chemotherapy was administered to shrink the tumors, and an average tumor size decrease from 10.05 ± 1.59 cm × (8.07 ± 1.54) cm to 6.11 ± 1.72 cm × (3.91 ± 1.52) cm (P < 0.001) was considered statistically significant. A t test was used for the ECOG score statistics, and the results showed that the scores were statistically significant (≤ 0.001) before and after neoadjuvant chemotherapy and after surgery. CONCLUSIONS: Neoadjuvant chemotherapy is an accepted treatment option for patients with locally advanced breast cancer, and the use of a latissimus dorsi musculocutaneous flap for post-mastectomy reconstruction may improve the patients' physical condition. Our results indicated that this strategy was safe and feasible.

The distribution and structural fingerprints of metals from particulate matters (PM) deposited in human lungs.

This work investigated the distribution and chemical fingerprints of 24 metals in particulate matter (PM) deposited in nonoccupational human lungs. Metals in the pulmonary PM can be grouped by the mean concentration as > 5 × 103 µg/g (Al/Fe/Ca/Mg/Zn), 1-5 × 103 µg/g (Ti/Ba/Pb/Mn), 0.2-1 × 103 µg/g (Cu/Cr/As/V) and < 100 µg/g (Ni/Sn/Cd/Sb). Three parameters (LFL, LR, EFP) were defined to predict different metal leaching behaviors. The leaching factor (LFL) of metals was 10-60 for Pb/Sb/Cd/Co/Cu and decreased to 1-2 for Ni/Cr/Mg/Al/Fe. Metals showed a divergent extent of lung retention (LR), including high retention (LR>10, Al/Cd/Cr/Ba/Ni/Ti/Sn/V/Sb), moderate retention (2 

Surfactant protein A modulates the activities of the JAK/STAT pathway in suppressing Th1 and Th17 polarization in murine OVA-induced allergic asthma.

Asthma is an allergic inflammatory lung disease affecting nearly 300 million people worldwide. To better understand asthma, new regulators must be identified. We conducted a study to investigate the effect and mechanisms of action of surfactant protein A (SPA) in OVA-induced asthmatic mice. Treatment with SPA delayed the onset of asthma, decreased its severity, as well as notably suppressed pro-inflammatory cytokine production. Furthermore, SPA-treated mice possessed more leukocytes; more CD4+ T cells infiltrated the spleen in the SPA-treated mice than in the control mice, and there were decreased percentages of Th1 and Th17 cells in vivo. In addition, expression levels of the T-bet (Th1 transcription factor) and RORγt (Th17 transcription factor) genes were significantly downregulated by SPA treatment. Moreover, SPA reduced the production and mRNA expression of pro-inflammatory cytokine mRNAs in activated T cells in vivo. Mechanistically, SPA could inhibit STAT1/4 and STAT3 phosphorylation, resulting in the differentiation of Th1 and suppression of Th17 cells, respectively. In the presence of CD3/CD28 expression, STAT1/4 and STAT3 were activated but suppressed by SPA, which was responsible for the augmentation of Th1 and Th17 differentiation. This result showed that SPA can effectively modulate the JAK/STAT pathway by suppressing Th1 and Th17 differentiation, thus preventing asthma. The present study reveals the novel immunomodulatory activity of SPA and highlights the importance of further investigating the effects of SPA on asthma.

Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Optimal authoritative risk assessment score of Cancer-associated venous thromboembolism for hospitalized medical patients with lung Cancer.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) is common in patients with primary lung cancer. It has been understudied which authoritative risk assessment score of cancer-associated VTE is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer. METHODS: Patients with lung cancer who had undergone computed tomography pulmonary angiography (CTPA), compression ultrasonography (CUS) of lower and upper extremities, and/or planar ventilation/perfusion (V/Q) scan to confirm the presence or absence of VTE during a medical hospitalization were retrospectively reviewed. Based on the actual prevalence of VTE among all patients, the possibility of VTE were reassessed with the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score, to compare their assessment accuracy for VTE development. RESULTS: A total of 1263 patients with lung cancer were incorporated into the final analysis. With respect to assessment efficiency for VTE occurrence, the scores with adjusted agreement from highest to lowest were the ONKOTEV score (78.6%), the PROTECHT score (73.4%), the CONKO score (72.1%), the COMPASS-CAT score (71.7%), the Khorana score (70.9%), and the CATS/MICA score (60.3%). The ONKOTEV score had the highest Youden index which was 0.68, followed by the PROTECHT score (0.58), the COMPASS-CAT score (0.56), the CONKO score (0.55), the Khorana score (0.53), and the CATS/MICA score (0.23). CONCLUSIONS: Among the Khorana score, the PROTECHT score, the CONKO score, the ONKOTEV score, the COMPASS-CAT score, and the CATS/MICA score which are approved by authoritative guidelines, the ONKOTEV score is optimal for the assessment of VTE development in hospitalized medical patients with lung cancer.

Diagnostic performance of D-dimer in predicting pulmonary embolism in tuberculous pleural effusion patients.

BACKGROUND: Tuberculous pleural effusion (TPE) patients usually have elevated D-dimer levels. The diagnostic performance of D-dimer in predicting pulmonary embolism (PE) in the TPE population is unclear. This study aimed to assess the diagnostic performance of D-dimer for PE in the TPE population and explore its potential mechanism. METHODS: We retrospectively analysed patients who were admitted to Xinhua Hospital and Weifang Respiratory Disease Hospital with confirmed TPE between March 2014 and January 2020. D-dimer levels were compared between patients with and without PE. To test the diagnostic performance of D-dimer in predicting PE, receiver operating characteristic curve analysis was performed. Positive predictive value (PPV) and negative predictive value (NPV) were also reported. To explore the potential mechanism of PE in TPE, inflammatory biomarkers were compared between PE and non-PE patients. RESULTS: This study included 248 patients (170 males and 78 females) aged 43 ± 20.6 years. Elevated D-dimer levels (≥ 0.5 mg/L) were detected in 186/248 (75%) patients. Of the 150 patients who underwent computed tomography pulmonary angiography, 29 were diagnosed with PE. Among the TPE population, the PE patients had significantly higher D-dimer levels than the non-PE patients (median, 1.06 mg/L vs. 0.84 mg/L, P < 0.05). The optimal cut-off value for D-dimer in predicting PE in TPE was 1.18 mg/L, with a sensitivity of 89.7% and a specificity of 77.8% (area under curve, 0.893; 95% confidence interval 0.839-0.947; P < 0.01). The PPV was 49.1%, while the NPV was 96.9% at a D-dimer cut-off of 1.18 mg/L for PE. PE patients had lower median WBC and interleukin (IL)-8 values (5.14 × 109/L vs. 6.1 × 109/L, P < 0.05; 30.2 pg/ml vs. 89.7 pg/ml, P < 0.05) but a higher median IL-2 receptor value (1964.8 pg/ml vs. 961.2 pg/ml, P < 0.01) than those in the non-PE patients. CONCLUSIONS: D-dimer is an objective biomarker for predicting PE in patients with TPE. A D-dimer cut-off of 1.18 mg/L in the TPE population may reduce unnecessary radiological tests due to its excellent sensitivity, specificity, and NPV for PE. The imbalance of prothrombotic and antithrombotic cytokines may partly be attributed to the formation of pulmonary emboli in patients with TPE.

The association between pulmonary embolism and the cancer-related genomic alterations in patients with NSCLC.

To date, the association between the acute pulmonary embolism (PE) and the currently existing cancer-related genomic alterations in patients with non-small cell lung cancer (NSCLC) has been understudied. We reviewed patients with a confirmed histopathological diagnosis of NSCLC who underwent computed tomography pulmonary angiography (CTPA) and molecular tests including ALK, ROS1, EGFR, BRAF V600E as well as PD-L1 during the diagnosis of NSCLC, to explore the association between the genomic alterations and PE. The results showed that, for the patients with positive results of genomic alterations, the proportion of positive ALK (13.6%vs8.5%, P<0.001) and PD-L1 (24.7%vs19.9%, P = 0.001) in PE group were more than those in Non-PE group. The patients with positive ALK and PD-L1 had the most (19.0%) and second most (15.4%) incidence of PE among all the patients being studied. A multivariate Logistic regression analysis showed that the positive ALK [1.685(1.065-2.215)(P<0.001)] and PD-L1[1.798(1.137-2.201)(P<0.001)] were correlated with the occurrence of PE. The positive results of ALK and PD-L1 genomic alterations may indicate an increased risk of pulmonary embolism in patients with NSCLC.

An authoritative algorithm most appropriate for the prediction of pulmonary embolism in patients with AECOPD.

BACKGROUND: Contemporarily authoritative algorithms for the prediction of acute pulmonary embolism (PE) comprise the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, the PERC algorithm, and the PEGeD algorithm. To date, little is known with respect to which algorithm is most appropriate for the PE prediction in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: The patients with AECOPD who underwent the confirmed chest imaging investigations of PE due to the likelihood of PE predicted by the Standard algorithm were retrospectively reviewed. The patients were reassessed by the other four algorithms to reveal which algorithm had the best diagnostic accuracy for the likelihood prediction of PE for patients with AECOPD. RESULTS: The results showed that the PEGeD algorithm(88.6, 80.7, 50.4, 97.0%, 4.591, 0.141, 0.693, 82.1%) performed better overall in the sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, Youden index, and diagnostic accuracy, in comparison with the Age-adjusted algorithm (78.6, 74.1, 40.1, 94.0%, 3.034, 0.289, 0.527, 74.9%), the YEARS algorithm (71.4, 76.6, 40.3, 92.4%, 3.051, 0.373, 0.480,75.6%), the PERC algorithm (98.6, 1.6, 18.2, 83.3%, 1.002, 0.875, 0.002, 19.2%). The difference of number of patients who were necessary to undergo chest imaging examinations and missed diagnoses resulted from each algorithm between the PEGeD algorithm and the Standard algorithm, the Age-adjusted algorithm, the YEARS algorithm, as well as the PERC algorithm were [- 789 (- 68.1%), N/A], [- 42 (- 3.6%),-21 (- 1.8%)], [- 3 (- 0.3%),-36 (- 3.1%)],[- 771 (- 66.6%), 21 (1.8%)], respectively. CONCLUSIONS: To date, the PEGeD algorithm is the most appropriate strategy among the authoritative algorithms for the likelihood prediction of pulmonary embolism in patients with AECOPD.

Peripheral nerve pathology in VAPB-associated amyotrophic lateral sclerosis with dysautonomia in a Chinese family.

Mutations of the vesicle-associated membrane protein-associated protein B (VAPB) gene have been identified in familial amyotrophic lateral sclerosis (ALS) with dysautonomia. Here we report the peripheral nerve pathology in ALS with dysautonomia caused by the p.Pro56Ser mutation of the VAPB gene in a Chinese family. The clinical features in all patients were camptocormia, fasciculation, and weakness in all limbs. Two patients developed symptoms of dysautonomia, including abdominal bloating, orthostatic hypotension, constipation, frequent urination, decreased sweating, and burning feet. Electromyography showed widespread neuropathic damage. The sympathetic skin response was absent in the soles of the feet. Sural nerve biopsy revealed loss of nerve fibers, especially unmyelinated fibers. Electron microscopy revealed regional loss of unmyelinated fibers with numerous collagen pockets. This report indicates that VAPB-associated ALS may be accompanied by multifocal autonomic nerve damage.

Comprehensive analysis of circular RNA expression profiles in cisplatin-resistant non-small cell lung cancer cell lines.

Platinum-based drugs such as cisplatin are widely used in combination chemotherapy for non-small cell lung cancer (NSCLC) owing to their high clinical response rate; however, acquired resistance to cisplatin is eventually inevitable. Circular RNAs (circRNAs) are involved in the development of diverse types of cancers, but their connection to cisplatin-resistance in NSCLC has not been studied. In the present study, two cisplatin-resistant NSCLC cell lines (A549/DDP and PC9/DDP) were established by gradually increasing concentrations of cisplatin in the media. The resulting cell lines possessed high resistance to cisplatin and strong proliferation, migration, and colony formation abilities compared to the parental cells. Microarray analysis identified 19,161 circRNAs that were dysregulated in cisplatin-resistant cell lines (fold change abs>2), including 11,915 up-regulated and 7246 down-regulated circRNAs. The expression of the top five up-regulated and down-regulated circRNAs was validated using real-time quantitative polymerase chain reaction. A circRNA-micro RNA (miRNA) network of the top 20 dysregulated circRNAs and their predicted miRNAs was constructed using Cytoscape. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that the host genes of the identified circRNAs were involved in the regulation of MAP kinase kinase kinase kinase activity, 6-phosphofructo-2-kinase activity, focal adhesion, ErbB signaling, and ECM-receptor interactions, which may contribute to cisplatin resistance in NSCLC. In summary, this is the first report on circRNA profiling in cisplatin-resistant NSCLC cells and it provides new potential targets for the reversal of cisplatin resistance in NSCLC.

An Extended-Spectrum Beta-Lactamase-Producing Hybrid Shiga-Toxigenic and Enterotoxigenic Escherichia coli Strain Isolated from a Piglet with Diarrheal Disease in Northeast China.

Shiga-toxigenic Escherichia coli (STEC) and enterotoxigenic E. coli (ETEC) can cause diarrhea in piglets. This is the first report and complete genome sequence of an extended-spectrum ß-lactamase-producing hybrid STEC/ETEC strain isolated from a piglet with diarrhea on a swine farm in China. We investigated the virulence genes and phylogenetic diversity with publicly available E. coli genomes. Both E. coli strains S17-13 and S17-20 harbored multiple virulence genes, mainly including stx2e and eastA genes. Other important virulence genes (estIa, estIb, fedABCDEF, and hlyABCD) were located in the plasmid p1713-1 of S17-13, which could be transferred from E. coli S17-13 to S17-20 by conjugation. The presence of virulence genes associated with different pathogroups (STEC or ETEC) confirmed the hybrid status of E. coli strain S17-13. Phylogenetic analysis showed that STEC/ETEC S17-13, STEC S17-20, avian pathogenic E. coli (APEC) O78, and APEC ACN001 are located in the same evolutionary branch, indicating that they may originate from a common ancestor. It is crucial to understand the phylogeny of pathogenic bacteria to evaluate how they have evolved and to monitor the emergence of potential new pathogens. The emergence of novel hybrid E. coli strains presents a new public health risk. More attention must be paid to these hybrid pathogens during typing and epidemiological surveillance of E. coli infections, which challenges the traditional diagnostics of E. coli infections.

A review of removal technology for antimony in aqueous solution.

Antimony (Sb) and its compounds, toxic metalloid, have been classified as high-priority pollutants. Increasing Sb released into the water environment by natural processes and anthropogenic activities, which exposure threatens to human health and ecosystems. Therefore, it is of unquestionable importance to remove Sb from polluted water. Keeping in view the extreme importance of this issue, we summarize the source, chemistry, speciation, distribution, toxicity, and polluted situation of Sb about aqueous solution. Then, we provide the recent and common technology to remove Sb, which are based on adsorption, coagulation/flocculation, electrochemical technology, membrane technology, ion exchange, etc. In this review, we focus in detail on the adsorption method, researchers at present have been investigating to discover more advanced, cost-effective, eco-friendly, reusable adsorbents. However, to date the Sb-containing wastewater treatment technologies are not sufficiently developed and most of research have been tested only in controlled lab conditions. Few reports are available that include field studies and applications. We critically analyzed the salient features and removal mechanisms, evaluating benefits and limitations of these technologies, hoping to provide more references for further research. Finally, we considered the Fe- or Mn-based technologies was the most promising technique to remove Sb for field application.

TNF-TNFR2 Signaling Inhibits Th2 and Th17 Polarization and Alleviates Allergic Airway Inflammation.

BACKGROUND: TNF-TNFR2 signaling has been indicated to be involved in CD4+ T lymphocyte differentiation. However, its role in allergic airway inflammation is not well understood. OBJECTIVES: The aim of this study was to investigate the role of TNF-TNFR2 signaling in allergic airway inflammation. METHODS AND RESULTS: In this study, we used an allergen-induced asthma model to show that TNF-TNFR2 signaling alleviated allergic airway inflammation by reducing the airway infiltration of eosinophils and neutrophils. Activated TNF-TNFR2 signaling decreased the expression of Th2 and Th17 cytokines in serum and bronchoalveolar lavage fluid. Furthermore, TNF-TNFR2 signaling inhibited Th2 and Th17 polarization but promoted Th1 and CD4+CD25+ T cell differentiation in vivo. CONCLUSIONS: Our study indicates that TNF-TNFR2 signaling alleviates allergic airway inflammation through inhibition of Th2 and Th17 cell differentiation.