Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Cognitive-behavioral therapy for patients with somatoform disorders: A pilot preliminary randomized controlled trial.

Background and objective: Cognitive-behavioral therapy (CBT) for somatoform disorders (SFDs) is understudied in China. Western findings may not be applicable to Chinese culture. This preliminary study evaluated the efficacy of CBT for patients in China, relative to treatment-as-usual (TAU). Methods: Seventy patients with SFDs randomly received either combined CBT and TAU (CBT + TAU), or TAU alone between January 2018 to May 2019. The CBT + TAU group received 12 weekly individual 50-minute CBT sessions. Participants were blindly assessed at 4 timepoints (baseline, week 6, end of treatment: week 12; 12 weeks post-treatment: week 24) using the following outcome measures: SQSS (Self-screening Questionnaire for Somatic Symptoms); PHQ-15 (Patient-Health-Questionnaire-15) and the WI (Whiteley Index); GAD-7 (General Anxiety Disorder-7); HAMD-17 (Hamilton Depression Rating Scale-17); Family Burden Interview Schedule (FBIS); Sheehan Disability Scale (SDS); and the Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). The primary endpoint was the difference between the SQSS total score at week 24 and the baseline. A mixed model for repeated measures was used to analyze inter- and intra-group changes from the baseline. Results: At week 24, The least-squares mean (LSM) change of the total score on the SQSS was -18.87 points and -9.69 points, respectively in the CBT + TAU group and in the TAU group (LSM difference, -9.18 points; 95% confidence interval, -15.72 to -2.64; P = 0.0068). At week 24, the LSM changes from baseline in the WI, HAMD, PHQ15, FBIS and SDS total scores were significantly different between the two groups, however, there was no significant difference in the Q-LES-Q-SF. The SQSS of group effect sizes were 0.63 at 24 weeks. The dropout rates of the CBT + TAU and TAU groups were comparable (22.9% and 19.3%). Conclusions: These preliminary findings suggest that CBT may be helpful for improving the symptoms of patients with SFDs in China.

Single-Atom Manganese-Catalyzed Oxygen Evolution Drives the Electrochemical Oxidation of Silane to Silanol.

The oxygen evolution reaction (OER), characterized by a four-electron transfer kinetic process, represents a significant bottleneck in improving the efficiency of hydrogen production from water electrolysis. Consequently, extensive research efforts have been directed towards identifying single-atom electrocatalysts with exceptional OER performance. Despite the comprehensive understanding of the OER mechanism, its application to other valuable synthetic reactions has been limited. Herein, we leverage the MOOH intermediate, a key species in the Mn-N-C single-atom catalyst (Mn-SA@NC), which can be cyclically delivered in the OER. We exploit this intermediate' s capability to facilitate electrophilic transfer with silane, enabling efficient silane oxidation under electrochemical conditions. The SAC electrocatalytic system exhibits remarkable performance with catalyst loadings as low as 600 ppm and an exceptional turnover number of 9132. Furthermore, the catalytic method demonstrates stability under a 10 mmol flow chemistry setup. By serving as an OER electrocatalyst, the Mn-SA@NC drives the entire reaction, establishing a practical Mn SAC-catalyzed organic electrosynthesis system. This synthesis approach not only presents a promising avenue for the utilization of electrocatalytic OER but also highlights the potential of SACs as an attractive platform for organic electrosynthesis investigations.

Within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men.

BACKGROUND: Parabens, as suspected endocrine disruptors, are widely used in personal care products and pharmaceuticals. However, variability, predictors, and risk assessments of human exposure to parabens are not well characterized. OBJECTIVE: To evaluate within-day variability, predictors, and risk assessments of exposure to parabens among Chinese adult men. METHODS: We measured four parabens including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) in repeated urine samples from 850 Chinese adult men. We examined the variability by intraclass correlation coefficients (ICCs) and identified the predictors by multivariable linear mixed models. We assessed risks of paraben exposures based on the estimated daily intake (EDI). RESULTS: The four parabens were detected in >76% of urinary samples. We observed fair to good to high reproducibility (ICCs: 0.71 to 0.86) for urinary paraben concentrations within one day. Use of facial cleanser was associated with higher four urinary paraben concentrations. Increasing age, taking medicine, intravenous injection, and interior decoration in the workplace were related to higher urinary concentrations of specific parabens. Smoking and drinking were associated with lower urinary concentrations of specific parabens. The maximum EDIs for the four parabens ranged from 13.76 to 848.68 µg/kg bw/day, and 0.9% of participants had the hazard quotient values > 1 driven by PrP exposure. CONCLUSIONS: Urinary paraben concentrations were less variable within one day. Several lifestyle characteristics including use of facial cleanser and pharmaceuticals may contribute to paraben exposures.

Selective Difunctionalization of Unactivated Aliphatic Alkenes Enabled by a Metal-Metallaaromatic Catalytic System.

The design of organometallic catalysts is crucial in the development of catalytic reactions. Herein, we describe a heterometallic [Os-Cu] complex with the characteristics of bimetallics, metallaaromatics, and pincer complexes. This complex serves as a highly effective catalyst for selective amino- and oxyselenation of unactivated alkenes. More than 80 examples including challenging substrates of unsymmetric aliphatic alkenes and amine-based nucleophiles in such reactions are provided. These reactions produce 1,2-difunctionalized products with good yields and high levels of chemo-, regio-, and stereoselectivity. Our studies revealed the following: (i) The usually inert osmium center activates the N- or O-centered nucleophiles. (ii) The copper-osmium bonding and its cooperative effects play essential roles in control the selectivity by bringing the reaction components into close proximity. (iii) The metallaaromatic moiety helps to stabilize the intermediate. These findings provide a versatile platform for catalyst design based on metal-metallaaromatic cooperative effects that have not been attained previously with bimetallic complexes.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Simulation and optimization of Fe resonance fluorescence lidar performance for temperature-wind measurement.

Fe resonance fluorescence lidar (Fe lidar) is considered an ideal candidate for temperature and wind measurement in the mesosphere and lower thermosphere region. However, considering the complexity of it, only a few Fe lidars have been operated in a few locations. To develop a Fe lidar with high performance, simulation work is the first important step. A simulation model is built in this paper. The expressions for the temperature-wind uncertainties are derived using the error propagation method. Within the limit of saturation effect, an index decomposition of the lidar and atmospheric parameters are performed. When the dwell time and central frequency shift are optimized to 0.205 and 932 MHz at night and 0.212 and 687 MHz during the day, night and daytime calibration curves are acquired, and after confirming the simulation parameters, the performance of Fe lidar is also evaluated. The simulation model could provide a valuable guidance for Fe lidar design.

Artificial intelligence for stepwise diagnosis and monitoring of COVID-19.

BACKGROUND: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course. METHODS: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models. RESULTS: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available. INTERPRETATION: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization. KEY POINTS: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration.

Exposure to disinfection by-products and reproductive hormones among women: Results from the Tongji Reproductive and Environmental (TREE) study.

BACKGROUND: Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. OBJECTIVE: To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. METHODS: We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (E2), total testosterone (T), progesterone (PRGE), and prolactin (PRL) were determined. Multivariate linear regression models were performed to assess the associations of urinary DCAA and TCAA concentrations with reproductive hormone levels. Dose-response relationships were investigated using natural cubic spline (NCS) and restricted cubic spline (RCS) models. RESULTS: After adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 µg/L and 6.30 µg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones. CONCLUSION: Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: Exploring associations and mediation effects.

Phenols have been shown to influence the cellular proliferation and function of thyroid in experimental models. However, few human studies have investigated the association between phenol exposure and thyroid cancer, and the underlying mechanisms are also poorly understood. We conducted a case-control study by age- and sex-matching 143 thyroid cancer and 224 controls to investigate the associations between phenol exposures and the risk of thyroid cancer, and further to explore the mediating role of oxidative stress. We found that elevated urinary triclosan (TCS), bisphenol A (BPA) and bisphenol S (BPS) levels were associated with increased risk of thyroid cancer (all P for trends < 0.05), and the adjusted odds ratios (ORs) comparing the extreme exposure groups were 3.52 (95% confidence interval (CI): 2.08, 5.95), 2.06 (95% CI: 1.06, 3.97) and 7.15 (95% CI: 3.12, 16.40), respectively. Positive associations were also observed between urinary TCS, BPA and BPS and three oxidative stress biomarkers measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), as well as between urinary 8-isoPGF2α and HNE-MA and the risk of thyroid cancer. Mediation analysis showed that urinary 8-isoPGF2α mediated 28.95%, 47.06% and 31.08% of the associations between TCS, BPA and BPS exposures and the risk of thyroid cancer, respectively (all P < 0.05). Our results suggest that exposure to TCS, BPA and BPS may be associated with increased risk of thyroid cancer and lipid peroxidation may be an intermediate mechanism. Further studies are warranted to confirm the findings.

Condensed Osmaquinolines with NIR-II Absorption Synthesized by Aryl C-H Annulation and Aromatization.

The structural design and tuning of properties of metallaaromatics are crucial in materials and energy science. Herein, we describe the rapid synthesis of tetracyclic metallaaromatics containing quinoline and pentalene motifs fused by a metal-bridged fragment. These unique compounds display remarkably broad absorption, enabling for the first time the absorption of metallaaromatics to reach the second near-infrared (NIR-II) bio-window. The formation of osmaquinoline unit involves an unconventional C(sp2 )-C(sp3 ) coupling promoted by AgBF4 to achieve [3+3] cycloaddition. The introduction of cyclic dπ -pπ conjugation and extension of the aromatic π-framework can effectively shrink the HOMO-LUMO gap, thus broadening the absorption window. The considerable photothermal conversion efficiency (PCE) in both the NIR-I and NIR-II windows, the high photothermal stability and the excellent electrochemical behavior suggest many potential applications of these condensed metallaquinolines.

Urinary biomarker of strontium exposure is positively associated with semen quality among men from an infertility clinic.

Experimental studies have shown that nonradioactive strontium (Sr), in the form of Sr2+, have a positive effect on semen quality, but human evidence is lacking. This study aimed to examine the associations between nonradioactive Sr exposure and semen quality in Chinese men (n = 394). We recruited men who presented at an infertility clinic in Wuhan, China to seek for semen parameter analyses. Urinary Sr concentration as an exposure biomarker was measured using inductively coupled plasma mass spectrometer. We estimated the associations between urinary Sr concentrations and semen parameters using multivariable logistic and linear regression models. In multivariable linear regressions models, positive dose-response associations were estimated for sperm concentration, motility, and count across increasing urinary Sr quartiles (all p for trends<0.05), and the consistent positive associations were also observed for urinary Sr concentration modeled as a continuous exposure. In multivariable logistic models, decreased risks of below-reference sperm concentration, motility, and count were also estimated across increasing urinary Sr quartiles (all p for trends<0.05). Our results suggest that nonradioactive Sr exposure may have a beneficial effect on semen quality, but more investigations are warranted to confirm the results.

Andrographolide attenuates epithelial-mesenchymal transition induced by TGF-ß1 in alveolar epithelial cells.

Andrographolide (Andro), a component from Chinese medicinal herb Andrographis paniculata, could alleviate pulmonary fibrosis in rodents. Yet, whether and how Andro mitigates epithelial-mesenchymal transition (EMT) induced by TGF-ß1 remain unknown. This study aimed to explore the effect of Andro on TGF-ß1-induced EMT in human alveolar epithelial cells (AECs) and the mechanisms involved. We illustrated that Andro inhibited TGF-ß1-induced EMT and EMT-related transcription factors in alveolar epithelial A549 cells. Andro also reduced TGF-ß1-induced cell migration and synthesis of pro-fibrotic factors (ie CCN-2, TGF-ß1), matrix metalloproteinases (ie MMP-2, MMP-9) and extracellular matrix (ECM) components (ie collagen 1), implying the inhibiting effect of Andro on TGF-ß1-induced EMT-like cell behaviours. Mechanistically, Andro treatment not only repressed TGF-ß1-induced Smad2/3 phosphorylation and Smad4 nuclear translocation, but also suppressed TGF-ß1-induced Erk1/2 phosphorylation and nuclear translocation in A549 cells. And treatment with ALK5 inhibitor (SB431542) or Erk1/2 inhibitors (SCH772984 and PD98059) remarkably reduced EMT evoked by TGF-ß1. In addition, Andro also reduced TGF-ß1-induced intracellular ROS generation and NOX4 expression, and elevated antioxidant superoxide dismutase 2 (SOD2) expression, demonstrating the inhibiting effect of Andro on TGF-ß1-induced oxidative stress, which is closely linked to EMT. Furthermore, Andro remarkably attenuated TGF-ß1-induced down-regulation of sirtuin1 (Sirt1) and forkhead box O3 (FOXO3), implying that Andro protects AECs from EMT partially by activating Sirt1/FOXO3-mediated anti-oxidative stress pathway. In conclusion, Andro represses TGF-ß1-induced EMT in AECs by suppressing Smad2/3 and Erk1/2 signalling pathways and is also closely linked to the activation of sirt1/FOXO3-mediated anti-oxidative stress pathway.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Is the Glasses-Free 3-Dimensional Display System More Effective for Complex Video-Assisted Thoracic Surgery? A Self-Controlled Study Ex Vivo.

Objective. Considering the demerits of a high-definition 2-dimensional (HD-2D) system, with its lack of stereopsis, and a conventional 3-dimensional (C-3D) system, which results in a dimmed image, we have recently developed a glasses-free 3-dimensional (GF-3D) display system for reconstruction surgeries such as video-assisted thoracic surgery (VATS) for tracheal reconstruction. Methods. Thoracic surgeons were invited to complete thoracoscopic continuous suture of a transected porcine trachea using the HD-2D, C-3D, and GF-3D systems on separate mornings in randomized order. The duration, numbers of stitches, and distance between every 2 stitches were recorded for every procedure. The surgeons' spontaneous eye blink rate was recorded for 5 minutes before the procedure and the last 5 minutes of the procedure. Results. Fifteen volunteers successfully completed the tracheal reconstruction procedures in this study. Both C-3D (0.403 ± 0.064 stitch/min, P < .001) and GF-3D (0.427 ± 0.079 stitch/min, P < .001) showed significant advantages in speed compared with HD-2D (0.289 ± 0.065 stitch/min). Both C-3D (2.536 ± 2.223 mm, P < .001) and GF-3D (2.603 ± 2.159 mm, P < .001) showed significant advantages in accuracy compared with HD-2D (3.473 ± 3.403 mm). Both HD-2D (1.240 ± 0.642, P < .001) and GF-3D (1.307 ± 0.894, P < .001) showed significant advantages in eye fatigue compared with C-3D (3.333 ± 1.44). Conclusions. All 3 available display systems are efficient for complex VATS. With the help of stereopsis, surgeons can achieve faster operation using C-3D and GF-3D systems in a thoracoscopic simulated setting. GF-3D may be a more effective display system for VATS reconstruction in terms of speed, accuracy, and eye fatigue during operations.

Development and clinical validation of a circulating tumor DNA test for the identification of clinically actionable mutations in nonsmall cell lung cancer.

Molecular analysis of potentially actionable mutations has become routine practice in oncological pathology. However, testing a wide range of oncogenes and mutations can be technically challenging because of limitations associated with tumor biopsy. Circulating tumor DNA (ctDNA) is a potential tool for the noninvasive profiling of tumors. In this study, we developed a next-generation sequencing (NGS)-based test for the detection of clinically relevant mutations in ctDNA and evaluated the feasibility of using this ctDNA NGS-based assay as an alternative to tissue genotyping. Tissue and matched blood samples were obtained from 72 patients with advanced nonsmall cell lung cancer (NSCLC). NGS-based testing was performed using plasma cell-free DNA (cfDNA) samples of all 72 patients as well as tumor DNA samples of 46 patients. Of the remaining 26 patients, tDNA was tested by amplification refractory mutation system PCR (ARMS-PCR) because of insufficient tissue sample or quality for NGS. Of the 46 patients who had tDNA and cfDNA NGS performed, we found 20 patients were concordant between tDNA and ctDNA alterations and 21 sample pairs were discordant because of additional alterations found in tDNA. Considering all clinically relevant alterations, the concordance rate between tDNA and ctDNA alterations was 54.9% with a sensitivity of 53.2% and a specificity of 75.0%. Our findings demonstrate that targeted NGS using cfDNA is a feasible approach for rapid and accurate identification of actionable mutations in patients with advanced NSCLC, and may provide a safe and robust alternative approach to tissue biopsy.

Preoperative localisation of pulmonary ground-glass opacity using medical adhesive before thoracoscopic resection.

OBJECTIVES: To evaluate the safety and efficiency of computed tomography (CT)-guided medical adhesive, α-cyanoacrylate, for preoperative localisation of pulmonary ground-glass opacity (GGO) used for guiding the video-assisted thoracoscopic surgical (VATS) excision METHODS: The procedure was performed on 188 consecutive patients with solitary GGO (pure GGO = 90 cases; mixed GGO = 98 cases) prior to the thoracoscopic procedure. The complications and efficacy of this method were analysed. The resected GGO was analysed pathologically. RESULTS: The mean duration of the procedure was 16.3 ± 5.2 min. The preoperative localisation was 100% successful. All GGOs were successfully resected by VATS. Asymptomatic pneumothorax was developed in 16/188 patients (8.5%) and mild pulmonary haemorrhage occurred in 15 cases (7.9%) post-localisation. None of the patients required any further treatment for the complications. CONCLUSION: Preoperative localisation using CT-guided medical adhesive, α-cyanoacrylate, is a safe and short-duration procedure, with high accuracy and success rates with respect to VATS resection of GGO. KEY POINTS: • Preoperative localisation is crucial for successful resection of GGO by VATS. • Preoperative adhesive localisation provides an up to 100% successful localisation rate with few complications. • Preoperative adhesive localisation enabled VATS resection in 100% of the GGO. • Preoperative adhesive localisation is safe and effective for VATS resection of GGO.

RNA editing of AZIN1 induces the malignant progression of non-small-cell lung cancers.

RNA editing is a widespread post-transcriptional mechanism that confers specific and reproducible nucleotide changes in selected RNA transcripts and plays a critical role in many human cancers. However, little is known about how RNA editing operates in non-small-cell lung cancers. Here, we measured the sequence and expression level of genes of antizyme inhibitor 1 and adenosine deaminase acting on RNA family in 30 non-small-cell lung cancer patient samples and 13 cell lines and revealed RNA editing S367G in antizyme inhibitor 1 is a high-frequent molecular events. We determined overexpression of antizyme inhibitor 1 with RNA editing, implying the oncogenic function of this alteration. We also detected the association of adenosine deaminase acting on RNA overexpression with RNA editing occurred in antizyme inhibitor 1. Furthermore, the RNA editing could cause a cytoplasmic-to-nuclear translocation of antizyme inhibitor 1 protein and conferred the malignant phenotype of non-small-cell lung cancer cells. The in vivo experiment confirmed that this RNA editing confers higher capacity of tumor migration as well. In conclusion, antizyme inhibitor 1 RNA editing and its involvement in tumorigenesis of non-small-cell lung cancer pave a new way for potential clinical management of non-small-cell lung cancer.

Coevolution with pollinating resin midges led to resin-filled nurseries in the androecia, gynoecia and tepals of Kadsura (Schisandraceae).

Background and Aims: Resin is a defence against herbivores and a floral reward in a few African and South American species whose bee pollinators collect it for nest construction. Here we describe a new role for floral resin from the Asian genus Kadsura (Schisandraceae). Kadsura tepals tightly cover a globe formed by carpels (in females) or near-fused stamens with fleshy connectives (in male flowers of most, but not all species). Methods: We carried out field observations at four sites in China and used pollinator behavioural assays, chemical analyses and time-calibrated insect and plant phylogenies to investigate the specificity of the interactions and their relationship to floral structure. Key Results: Nocturnal resin midges ( Resseliella , Cecidomyiidae) walk around on the flowers' sexual organs to oviposit, thereby transferring pollen and wounding tissues. The larvae then develop in resin-filled chambers. Male and female floral scents are dominated by α-pinene, while the resinous exudate is dominated by caryophyllene. As revealed by barcoding of multiple midge larvae per flower species, the mutualisms are species specific and appear to have evolved over the past 6-9 million years. Conclusions: Resin feeding, not pollen or ovule feeding, by midge larvae explains the abundant Kadsura exudates, highlighting the poorly known world of nocturnal flower-fly interactions.

Variants of FGFR2 and their associations with breast cancer risk: a HUGE systematic review and meta-analysis.

Extensive epidemiological studies have demonstrated that there are associations between variants in intron 2 of FGFR2 and the breast cancer risk in various populations; however, the relationships are not yet conclusively established. To comprehensively review the epidemiological studies showing associations between the variants of FGFR2 and the breast cancer risk, and to establish correlations via a meta-analysis. The PubMed and MEDLINE databases were searched for eligible studies. The associations between the variants and breast cancer risk were evaluated using a random-effects model. The heterogeneity among the studies and the potential publication bias were also evaluated. Fifty-three studies with a total of 121,740 cases and 198,549 controls have examined the associations between 23 variants in intron 2 of FGFR2 and the breast cancer risk. The relationships for the 10 most frequently evaluated variants-rs1078806, rs11200014, rs1219648, rs2420946, rs2981578, rs2981579, rs2981582, rs3135718, rs10736303, and rs3750817-were synthesized based on a meta-analysis. Interestingly, we found that all 10 variants were significantly associated with the risk of breast cancer. In studies stratified by ethnicity, we found that the associations were more notable in Caucasians and Asians compared to Africans. Similar pooled results were found in population-based and hospital-based case-control studies and in studies with small and large sample sizes. FGFR2 is a breast cancer susceptibility gene, and various variants of FGFR2 are significantly associated with the breast cancer risk. However, the biological mechanisms underlying the associations need to be elucidated in future studies.