Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, with limited second-line systemic therapy options, and represents an increasing disease burden in Japan. In the phase 3 RATIONALE-302 study, the anti-programmed cell death protein 1 antibody, tislelizumab, significantly improved overall survival (OS) versus chemotherapy as second-line treatment for advanced/metastatic ESCC. Here, we report the Japanese patient subgroup results. METHODS: Patients with advanced/metastatic ESCC, with disease progression during/after first-line systemic therapy were randomized 1:1 to open-label tislelizumab 200 mg every 3 weeks or investigator's choice of chemotherapy (paclitaxel/docetaxel). Efficacy and safety were assessed in all randomized Japanese patients. RESULTS: The Japanese subgroup comprised 50 patients (n = 25 per arm). Tislelizumab improved OS versus chemotherapy (median: 9.8 vs. 7.6 months; HR 0.59; 95% CI 0.31, 1.12). Among patients with programmed death-ligand 1 score ≥ 10%, median OS was 12.5 months with tislelizumab (n = 10) versus 2.9 months with chemotherapy (n = 6) (HR 0.31; 95% CI 0.09, 1.03). Tislelizumab improved progression-free survival versus chemotherapy (median: 3.6 vs. 1.7 months, respectively; HR 0.50; 95% CI 0.27, 0.95). Objective response rate was greater with tislelizumab (32.0%) versus chemotherapy (20.0%), and responses were more durable (median duration of response: 8.8 vs. 2.6 months, respectively). Fewer patients experienced ≥ grade 3 treatment-related adverse events with tislelizumab (24.0%) versus chemotherapy (47.8%). Tislelizumab demonstrated an improvement in health-related quality of life versus chemotherapy. CONCLUSIONS: As second-line therapy for advanced/metastatic ESCC, tislelizumab improved OS versus chemotherapy, with a favorable safety profile, in the Japanese patient subgroup, consistent with the overall population. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov: NCT03430843.

Differentiating total from subtotal arterial occlusion in lower extremities by using reverse attenuation gradient sign in CT angiography.

OBJECTIVES: To investigate the use of reverse attenuation gradient sign (RAGS) in CT angiography (CTA) to differentiate total from subtotal occlusion in lower extremities which poses different challenges for the procedure and carries different prognoses. METHODS: Eighty patients with 91 lesions in the lower extremities were divided into total occlusion (TO) group and subtotal occlusion (SO) group confirmed by digital subtraction angiography. The CT numbers of vascular lumen at the end of lesion (proximal, P) and at the first entrance (distal, D) of the lateral branch were measured and their difference (CT(PD) = CT(P) - CT(D)) of each lesion was calculated. The CT number gradient (G(DP) = 2 * CT(PD)/[CT(P) + CT(D)]) was calculated by dividing the CT number difference by the average CT number of the two points. The existence of RAGS where the CT number at the distal point is higher than that at the proximal point (CT(PD) and G(PD) < 0) was determined and the diagnostic efficacy of using RAGS in CTA for differentiating total from subtotal occlusive lesions in lower extremities was calculated. RESULTS: The SO group had higher CT numbers than the TO group (p < 0.001). More importantly, the SO group had positive CT number gradient (G(PD) > 0), while the gradient was negative (G(PD) < 0) in the TO group. The specificity and sensitivity of using RAGS (G(PD) < 0) in images for diagnosing TO of lower extremity were 97.6% and 92.0%, respectively, and 87.8% and 88.0% using the standard CTA images. CONCLUSION: The use of RAGS in CTA images has high diagnostic accuracy to differentiate TO from SO in lower extremities. KEY POINTS: • Total occlusions often exhibit higher CT number at distal point than at proximal point to the occlusion. • The reverse attenuation gradient sign (RAGS) may be determined using the CT number measurements between the proximal and distal points after occlusion. • RAGS can be used to improve the diagnostic efficiency in CTA to differentiate between total and subtotal occlusions of lower extremity arteries.

In vivo protective effects of chlorogenic acid against triptolide-induced hepatotoxicity and its mechanism.

CONTEXT: Triptolide (TP) has outstanding biological activities, but it induces toxicities, particular hepatotoxicity, severely limiting its clinical application. Chlorogenic acid (CGA) has prominently medicinal and nutritional values. However, until now, it is not known whether CGA could mitigate TP-induced hepatotoxicity. OBJECTIVE: This study explored the possible protection of CGA against TP-induced hepatotoxicity and its potential mechanisms, for the first time. MATERIAL AND METHODS: KM mice were treated orally with TP at a single dose of 1 mg/kg at 4 h after being treated with CGA (10, 20 and 40 mg/kg) for seven continuous days. Blood samples were collected at 24 h after TP administration for measurement of serum biomarkers, and hepatic tissues for analysis of potential mechanisms. RESULTS: TP treatment-induced acute hepatotoxicity manifested by the significant elevation in serum alanine transaminase (93.9 U/L), aspartate transaminase (185.8 U/L) and hepatic malondialdehyde (0.637 µmol/mg protein), and the remarkable reduction in hepatic glutathione (1.425 µg/mg protein), glutathione S-transferase, glutathione peroxidase, superoxide dismutase and catalase (91.7, 320.7, 360.6 and 140.7 U/mg protein, respectively). In contrast, pretreatment with CGA for 7 days effectively attenuated acute liver injury and oxidative stress caused by TP with each ED50 of 44.4, 57.1, 46.6, 22.2, 40.9, 58.1, 86.4 and 61.0 mg/kg, respectively. Furthermore, pretreatment with CGA promoted the accumulation of Nrf2 into the nucleus, and up-regulated mRNA expression of Nrf2-target downstream genes. DISCUSSION AND CONCLUSIONS: Combined CGA medication may probably reduce the risk of TP poisoning, and in-depth mechanisms can be developed around the signal molecules of Nrf2.

[Detection of p16 by fluorescence in-situ hybridization and immunohistochemistry in malignant mesothelioma].

OBJECTIVE: To study the role of p16 gene mutation status as detected by fluorescence in-situ hybridization (FISH) and p16 protein expression as detected by immunohistochemistry in differential diagnosis of malignant mesothelioma and benign mesothelial hyperplasia. METHODS: p16 gene mutation status and protein expression were detected by FISH and immunohistochemistry respectively in 55 cases of pleural malignant mesothelioma and 30 cases of benign mesothelial hyperplasia. RESULTS: FISH study showed that the rate of p16 deletion in malignant mesothelioma (81.8%,45/55) was higher than that in benign mesothelial hyperplasia (3.3%,1/30). The difference was statistically significant (P<0.05). Immunohistochemical study showed that the rate of p16 protein expression in malignant mesothelioma (23.6%) was lower than that in benign mesothelial hyperplasia (76.7%). The difference was also statistically significant. The sensitivity and specificity of FISH in distinguishing between mesothelioma and reactive mesothelial hyperplasia were higher than those of immunohistochemistry. CONCLUSIONS: In contrast to reactive mesothelial hyperplasia, p16 gene is deleted and p16 protein is not expressed in malignant mesothelioma. The sensitivity and specificity of FISH are higher than those of immunohistochemistry in the distinction.

[Exploration of lymph node metastasis and appropriate lymph node dissection modes in patients with clinical stage I non-small cell lung cancer].

OBJECTIVE: To explore the pattern of lymph node metastasis and evaluate the modes and extent of mediastinal lymph node dissection in patients with ≤ 3 cm, clinical stage I primary non-small cell lung cancer (NSCLC). METHODS: Data of 270 eligible patients who underwent pulmonary resection with systematic lymph node dissection in our hospital between March 2012 and August 2013 were retrospectively analyzed in order to investigate the relationship between the clinicopathological features and lymph node metastatic patterns. Patients with multiple primary carcinomas or non-primary pulmonary malignancies and those who received any chemotherapy or radiotherapy or did not undergo systematic nodal dissection were excluded. The criteria of systematic nodal dissection included the removal of at least six lymph nodes from at least three mediastinal stations, one of which must be subcarinal. The data were analyzed and compared using Chi-square test. RESULTS: The postoperative morbidity rate was 14.8% and no death occurred in this series. The imaging findings showed 34 cases of pure ground glass opacity lesions, 47 partial solid nodules, and 189 solid nodules. Apart from 34 p-GGO lesions, among the other 236 cases, ≤ 1 cm lesions were in 22 cases, 1 cm- ≤ 2 cm lesions in 138 cases, and >2 cm- ≤ 3 cm lesions in 76 cases based on radiologic findings. The pathological types included adenocarcinoma (n = 245), squamous cell carcinoma (n = 18) and other rare types (n = 7). The overall lymph node metastasis rate was 18.9% (51/270), and the incidence of lymph node involvement was 0(0/34) in cancers with p-GGO, 2.1% (1/47) in mixed solid nodules, 26.5% (50/189) in solid nodules, 18.2% (4/22) in nodules ≤ 1 cm, 14.5% (20/138) in 1 cm < nodules ≤ 2 cm, and 35.5% (27/76) in 2 cm < nodules ≤ 3 cm. The metastasis rates of non-specific tumor-draining region lymph nodes detected in the patients with positive and negative lobe-specific lymph node involvement were 20.0%-50.0% vs. 0-2.9% (P < 0.001). CONCLUSIONS: Usually NSCLC with p-GGO nodules has no lymph node metastasis, therefore, systematic nodal dissection may be not necessary. The larger the tumor size is, the higher the lymph node metastatic rate is for mixed or solid nodules. Intraoperative frozen-section examination of the lobe-specific lymph nodes should be performed routinely in patients with ≤ 2 cm stage I NSCLC, and systematic nodal dissection should be done if positive, but it may be not necessary if negative. However, the effectiveness of the systematic selective lymph node dissection still needs to be further confirmed.

Comparison of mid-outcome among bare metal stent, atherectomy with or without drug-coated balloon angioplasty for femoropopliteal arterial occlusion.

This study evaluated the outcomes of a bare metal stent (BMS), DCB alone, atherectomy plus a drug-coated balloon (AT + DCB) and AT alone for the treatment of femoropopliteal artery occlusion. Four groups were included in this retrospective cohort study: 119 patients underwent the BMS procedure, 89 patients underwent DCB alone, 52 patients underwent AT + DCB, and 61 patients underwent AT alone. Patients were followed-up at 1, 6, 12 and 24 months after the procedure, the clinical outcomes and complications were assessed, and the primary outcomes were primary patency and restenosis. AT + DCB showed a lower bailout stent, and BMS displayed a higher retrograde puncture, flow-limiting dissection and postdilation (p < 0.05). For all procedures, the walking distance, ABI and pain score post-procedure were significantly improved compared with the pre-procedure values (p < 0.001). The restenosis rate was higher in BMS (21.0%) and AT alone (24.6%) than in DCB (10.1%) alone and AT + DCB (11.5%) (p = 0.04); there was no difference in amputation or clinically driven target lesion revascularization among procedures. The primary patency rates were 77.7%, 89.4%, 88.0% and 73.7% in the BMS, DCB alone, AT + DCB and AT alone groups at 24 months, respectively (p = 0.03), while the secondary patency and main adverse events (stroke, MI and death) were similar. Proximal concavity, proximal target vessel diameter ≥ 5 mm, runoff number ≥ 2 and DCB use were protective factors for primary patency. Our results suggested that AT + DCB and DCB alone were associated with higher primary patency, and DCB devices (combined with/without AT) should be the preferred choice for FP lesions.

Tislelizumab in advanced/metastatic esophageal squamous cell carcinoma: health-related quality of life in Asian patients.

OBJECTIVE: Post-hoc analysis examined health-related quality of life and esophageal squamous cell carcinoma (ESCC) symptoms in the Asian subgroup of patients in RATIONALE-302 (NCT03430843). METHODS: Patients were randomized 1:1 to either tislelizumab or investigator-chosen chemotherapy (paclitaxel, docetaxel, or irinotecan). Health-related quality of life was measured using the EORTC QLQ-C30 and the QLQ-OES18. Least-squares mean score changes from baseline to weeks 12 and 18 in health-related quality-of-life scores were assessed using a mixed model for repeated measurements. Reported nominal p-values are for descriptive purposes only. RESULTS: Of the 512 patients, this analysis was conducted in 392 Asian patients (tislelizumab, n = 192; investigator-chosen chemotherapy, n = 200). The tislelizumab arm had stable global health status/quality of life, but fatigue scores worsened in both arms. The change from baseline was similar for physical functioning in both arms at weeks 12 and 18. Eating and dysphagia scores remained stable in the tislelizumab arm. Reflux improved at week 12 in the tislelizumab arm and worsened in the investigator-chosen chemotherapy arm. CONCLUSIONS: Overall, the health-related quality of life and ESCC-related symptoms of patients receiving tislelizumab in the Asian subgroup remained stable or improved, while patients receiving investigator-chosen chemotherapy experienced worsening. These results in Asian patients corroborate the findings in the intent-to-treat population, suggesting tislelizumab is a potential new second-line treatment option for patients with advanced or metastatic ESCC. TRIAL REGISTRATION: The RATIONALE-302 study is registered on clinicaltrials.gov as NCT03430843.

Association between problematic social networking use and anxiety symptoms: a systematic review and meta-analysis.

A growing number of studies have reported that problematic social networking use (PSNU) is strongly associated with anxiety symptoms. However, due to the presence of multiple anxiety subtypes, existing research findings on the extent of this association vary widely, leading to a lack of consensus. The current meta-analysis aimed to summarize studies exploring the relationship between PSNU levels and anxiety symptoms, including generalized anxiety, social anxiety, attachment anxiety, and fear of missing out. 209 studies with a total of 172 articles were included in the meta-analysis, involving 252,337 participants from 28 countries. The results showed a moderately positive association between PSNU and generalized anxiety (GA), social anxiety (SA), attachment anxiety (AA), and fear of missing out (FoMO) respectively (GA: r = 0.388, 95% CI [0.362, 0.413]; SA: r = 0.437, 95% CI [0.395, 0.478]; AA: r = 0.345, 95% CI [0.286, 0.402]; FoMO: r = 0.496, 95% CI [0.461, 0.529]), and there were different regulatory factors between PSNU and different anxiety subtypes. This study provides the first comprehensive estimate of the association of PSNU with multiple anxiety subtypes, which vary by time of measurement, region, gender, and measurement tool.

COVID-19 symptoms, internet information seeking, and stigma influence post-lockdown health anxiety.

Background: With the lifting of Zero-COVID policies in China, rapid transmission of the virus has led to new challenges for patients' health anxiety. This study aimed to evaluate the relationship between COVID-19 symptoms and health anxiety, as well as the mediation paths between them in individuals infected with COVID-19. Method: A cross-sectional study was conducted in December 2022, following the relaxation of anti-COVID measures in China. A validated online questionnaire was used to collect data from COVID-19 patients on the number and severity of symptoms, health anxiety, internet health information-seeking behavior (IHISB), and perceived stigma. Structural equation modeling was used to examine the mediation model in which COVID-19 symptoms would affect health anxiety via IHISB and perceived stigma. Results: Overall, 1,132 participants (women, 67.6%) were included, with a mean (SD) age of 28.12 (10.07) years. Participants had an average of seven COVID-19 symptoms, with cough (91.3%), nasal congestion (89.1%) and fatigue (87.8%) being the most common. The number and severity of COVID-19 symptoms, IHISB, perceived stigma, and health anxiety were positively correlated with each other after adjusting for covariates (r ranging from 0.10 to 0.81, all p < 0.05). IHISB (effect = 0.14, p < 0.001) and perceived stigma (effect = 0.04, p < 0.001) fully mediated the relationship between COVID-19 symptoms and health anxiety. Conclusion: Interventions for health anxiety reduction during and after pandemics should target improving the quality of online health information, enhancing individuals' online healthy literacy, and reducing stigma.

Occupational stress and mental health among civil servants during COVID-19 in China: The mediation effect of social support and work-family conflict.

Mental health problems of various populations during the COVID-19 pandemic have received high attention, but there is little research on the mental health of Chinese civil servants. The present study investigated occupational stress, mental health problems (i.e., anxiety, depression, and insomnia), social support, and work-family conflict in Chinese civil servants during the COVID-19 pandemic. A total of 327 civil servants in Wenzhou city, China, participated in an online survey, which collected data on socio-demographic characteristics, occupational stress, mental health problems (i.e., anxiety, depression, and insomnia), social support, and work-family conflict. Data were analyzed using non-parametric tests and a multiple mediation model. Self-reported risk at work and support from mental health workers were relatively low. Anxiety, depression, and insomnia prevalence were 49.24 %, 47.1 %, and 20.48 %, respectively. Those who held higher ranks at work had lower levels of anxiety and depression. In addition, those who felt bad about their health status had more mental health problems. Social support and work-family conflict mediated the relationship between occupational stress and mental health problems significantly. Stress management training, organizational-level improvement in work arrangements, and professional mental health services are warranted for Chinese civil servants during the pandemic.

Study on selection of native greening plants based on eye-tracking technology.

The selection of native greening plants to improve rural greening technology is crucial for enriching methods of building rural plant landscapes. However, there are few studies from the perspective of visual preference using quantitative methods. By using eye-tracking technology, this study studies students in the Central South University of Forestry and Technology and villagers in Changkou Village, Fujian Province, employing pictures of plant organs-leaves, flowers, and fruits-as stimulating materials to analyze five indicators: the total duration of fixations, the number of fixations, average duration of fixations, average pupil size and average amplitude of saccades. A number of findings came from this research First, people visually prefer leaves, followed by flowers and fruits. In terms of species, Photinia × fraseri, Metasequoia glyptostroboides, Photinia serratifolia, Cunninghamia lanceolata and Koelreuteria bipinnata have higher overall preference. Families such as Malvaceae, Fabaceae, Araliaceae, Myricaceae and Cupressaceae have stronger visual attraction than others. Second, there are distinct differences in the preference of shapes and textures of leaves: aciculiform, strip, cordiform, sector and jacket-shape are more attractive; leather-like leaves have a higher visual preference than paper-like leaves; different colors and whether leaves are cracked or not have little effect on leaf observation. Third, the preference for flowers with different inflorescence and colors is significant. Capitulum, cymes and panicles are more attractive; purple is the most preferred color, followed by white, yellow and red. Finally, there are significant differences in preferences for fruit characteristics, with medium-sized fruits and black fruits preferred, while kidney-shaped and spoon-shaped fruits are considered more attractive. Pomes, pods, samaras, and berries have received relatively more attention.

Visual preference of plant features in different living environments using eye tracking and EEG.

Plants play a very important role in landscape construction. In order to explore whether different living environment will affect people's preference for the structural features of plant organs, this study examined 26 villagers and 33 college students as the participants, and pictures of leaves, flowers and fruits of plants as the stimulus to conduct eye-tracking and EEG detection experiments. We found that eye movement indicators can explain people's visual preferences, but they are unable to find differences in preferences between groups. EEG indicators can make up for this deficiency, which further reveals the difference in psychological and physiological responses between the two groups when viewing stimuli. The final results show that the villagers and the students liked leaves best, preferring aciculiform and leathery leaves; solitary, purple and capitulum flowers; and medium-sized, spathulate, black and pear fruits. In addition, it was found that the overall attention of the villagers when watching stimuli was far lower than that of the students, but the degree of meditation was higher. With regard to eye movement and EEG, the total duration of fixations is highly positively correlated with the number of fixations, and the average pupil size has a weak negative correlation with attention. On the contrary, the average duration of fixations has a weak positive correlation with meditation. Generally speaking, we believe that Photinia×fraseri, Metasequoia glyptostroboides, Photinia serratifolia, Koelreuteria bipinnata and Cunninghamia lanceolata are superior landscape building plants in rural areas and on campuses; Pinus thunbergii, Myrica rubra, Camellia japonica and other plants with obvious features and bright colours are also the first choice in rural landscapes; and Yulania biondii, Cercis chinensis, Hibiscus mutabilis and other plants with simple structures are the first choice in campus landscapes. This study is of great significance for selecting plants for landscape construction and management according to different environments and local conditions.

Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study.

PURPOSE: Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy. PATIENTS AND METHODS: In this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%. RESULTS: In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P = .0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P = .0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy. CONCLUSION: Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.

The potential contributions to organic carbon utilization in a stable acetate-fed Anammox process under low nitrogen-loading rates.

The unique ability of Anammox bacteria to metabolize short-chain fatty acids have been demonstrated. However, the potential contributions of active Anammox species to carbon utilization in a mixotrophic Anammox-denitrification process are less well understood. In this study, we combined genome-resolved metagenomics and DNA stable isotope probing (DNA-SIP) to characterize an Anammox process fed with acetate under COD/TN ratios of around 0.30-0.40 and low nitrogen-loading rates. A draft genome of "Candidatus Jettenia caeni" and a novel species that was phylogenetically close to "Candidatus Brocadia sinica" were recovered. Essential genes encoding the key enzymes for acetate metabolism and dissimilatory nitrate reduction to ammonium were identified in the two Anammox draft genomes. The DNA-SIP revealed that Ignavibacterium, "Candidatus Jettenia caeni," Thauera, Denitratisoma, and Calorithrix predominantly contributed to organic carbon utilization in the acetate-fed Anammox process. In particular, the "Candidatus Jettenia caeni" accounted for a higher proportion of 13C-DNA communities than "Candidatus Brocadia sinica." This result well confirmed the theory of maintenance energy between the interspecies competition of the two Anammox species under low nitrogen-loading rates. Our study revealed its potential important role of the Anammox genus "Candidatus Jettenia" in the treatment of wastewater containing low organic matter and ammonia.

Lobe-specific Lymph Node Dissection in Clinical Stage IA Solid-dominant Non-small-cell Lung Cancer: A Propensity Score Matching Study.

BACKGROUND: Lobectomy with systematic lymph node dissection (SND) remains the standard procedure for resectable non-small-cell lung cancer (NSCLC), whereas lobe-specific lymph node dissection (LSND) was reported to have more advantages in perioperative recovery and complication reduction in treating early-stage diseases. Survival outcomes after LSND remains controversial compared with SND. PATIENTS AND METHODS: From 2014 to 2017, data of 546 patients with clinical stage IA solid-dominant NSCLC and who underwent curative lobectomies with LSND (n = 100) or SND (n = 446) at our institution were collected. Propensity score matching was conducted to eliminate the biases. Five-year disease-free survival and overall survival were compared between the groups. Perioperative parameters and postoperative complications were also analyzed. RESULTS: Lobectomies with LSND or SND were performed in 100 patients and 446 patients, respectively. After matching, there were 100 patients in each group and no significant differences in 5-year overall survival (P = .473) and disease-free survival (P = .789) were found between the groups. Recurrence patterns were also similar (P = .733). Perioperative parameters were similar, whereas the incidence of postoperative complications in the SND group was found to be significantly higher than that in the LSND group (P = .003). CONCLUSIONS: Our study demonstrated that LSND has similar efficiency to SND in terms of survival, recurrence, lymph node dissection, and perioperative recovery of patients with clinical stage IA solid-dominant NSCLC, as well as significant advantages in reducing postoperative complications. Therefore, curative lobectomies with LSND may be more suitable and practical for clinical stage IA solid-dominant patients with NSCLC.

Combined genome-centric metagenomics and stable isotope probing unveils the microbial pathways of aerobic methane oxidation coupled to denitrification process under hypoxic conditions.

Obligate aerobic methanotrophs have been proven to oxidize methane and participate in denitrification under hypoxic conditions. However, this phenomenon and its metabolic mechanism have not been investigated in detail in aerobic methane oxidation coupled to denitrification (AME-D) process. In this study, a type of hypoxic AME-D consortium was enriched and operated for a long time in a CH4-cycling bioreactor with strict anaerobic control and the nitrite removal rate reached approximately 50 mg N/L/d. Metagenomics combined with DNA stable-isotope probing demonstrated that the genus Methylomonas, which constitutes type I aerobic methanotrophs, was the dominant member and contributed to methane oxidation and partial denitrification. Metagenomic binning recovered a near-complete (98%) draft genome affiliated with the family Methylococcaceae containing essential genes that encode nitrite reductase (nirK), nitric oxide reductase (norBC) and hydroxylamine dehydrogenase (hao). Metabolic reconstruction of the selected Methylococcaceae genomes also revealed a potential link between methanotrophy and partial denitrification.

Erratum: Spread through air spaces predicts a worse survival in patients with stage I adenocarcinomas >2 cm after radical lobectomy.

[This corrects the article DOI: 10.21037/jtd.2018.09.22.].

The current optimal multimodality treatments for oesophageal squamous-cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Multimodality treatments including definitive chemoradiotherapy (dCRT) and neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by surgery (S) are frequently used to improve prognosis in locally advanced oesophageal squamous-cell carcinoma (LAESCC), while the optimal multimodality regimen has yet to be defined; therefore, this systematic review and meta-analysis aimed to find out the current best multimodality regimen for LAESCC. METHODS: We conducted a systematic search of PubMed, Embase, Ovid and Cochrane Library databases for studies comparing nCRT + S with nCT + S or dCRT. The primary outcome was overall survival. The secondary outcomes were the rates of R0 resection, pathologic complete response (pCR), tumor-free lymph nodes (pN0) and postoperative recurrence. RESULTS: Five studies comparing nCRT + S with nCT + S and fourteen studies comparing nCRT + S with dCRT were finally included. Meta-analysis showed that nCRT + S had higher rates of R0 resection (OR 1.84, 95% CI 1.03-3.29), pCR (OR: 2.90 95% CI 1.37-6.14) and pN0 (OR: 2.55 95% CI 1.54-4.24) with a significant survival advantage (HR 0.72; 95% CI 0.52-0.99) when compared with nCT + S in LAESCC. When nCRT + S was compared with dCRT, nCRT + S yielded a significant survival benefit (HR 0.65; 95% CI 0.56-0.76) and had a significantly lower rate of local recurrence (OR: 0.35 95% CI 0.22-0.57). CONCLUSION: Current evidence suggests that CRT + S may be the optimal potential curative treatment mode for patients with LAESCC as long as they are suitable for this multimodality regimen.

Predictors of lymph node metastasis and possible selective lymph node dissection in clinical stage IA non-small cell lung cancer.

BACKGROUND: The pathologic stages of lymph nodes usually differ from preoperatively predicted in lung cancers and it is difficult to predict the metastasis of lymph nodes for the patients diagnosed as clinical stage IA non-small cell lung cancers (NSCLC). This study aimed to investigate the patterns of lymph node metastasis and the risk factors predicting lymph node metastasis in the patients with clinical stage IA NSCLCs. METHODS: All patients diagnosed as clinical stage IA NSCLC from July 2013 to June 2017 in our center were retrospectively reviewed, and a total number of 1,543 patients who underwent anatomical lobectomy with systematic lymph node dissection were enrolled in this study. Multivariate logistic regression analysis was performed to identify the risk factors predicting lymph node metastasis, and Fisher's exact test was used to confirm the lymph node spread mode according to the locations of primary tumors. RESULTS: Totally, lymph node metastases presented in 131 patients (8.5%) in this series. Sixty-three patients presented N1 diseases, 17 patients showed only skipped N2 diseases, and 51 patients had simultaneous N1 and N2 positive lymph nodes. No lymph node metastasis was found in the patients with pure ground grass opacity (GGO). When patients were arbitrarily divided into six groups by the longest tumor diameter of ≤0.5, 0.6-1, 1.1-1.5, 1.6-2.0, 2.1-2.5, 2.6-3 cm, the lymph node metastasis rates of each group were 0% (0/20), 1.5% (4/264), 4.7% (20/429), 8.6% (29/336), 13.1% (38/290), 19.6% (40/204), respectively. When the patients with pure GGO were excluded, the lymph node metastasis rates in the patients with partial or total solid tumors were 0% (0/10), 2.4% (4/164), 6.6% (20/303), 11.7% (29/249), 16.0% (38/238) and 23.1% (40/173). The cut off value showed by receiver operating characteristic (ROC) curve for tumor size was 1.95 cm, and the area under the curve (AUC) was measured as 0.681 (P<0.001, 95% CI: 0.630-0.726). Multivariate logistic regression analysis indicated that male patients [odds ratio (OR) =3.34, P=0.012], smoking history (OR =14.12, P<0.001), solid components (OR =3.34, P=0.01), large tumor size (OR =1.9, P<0.001), poor differentiation (OR =2.25, P=0.013), lymphovascular invasion (OR =58.45, P<0.001), visceral pleural invasion (OR =48.37, P<0.001) were significantly associated with lymph node metastasis in clinical stage IA NSCLC. The rate of non-lobe specific lymph node metastasis was 15.8-40.0% when any of the lobe specific lymph nodes was positive, while it was only 0-2.2% when all lobe specific lymph nodes were negative. CONCLUSIONS: Tumor size, solid components, poor differentiation, lymphovascular invasion, visceral pleural invasion and smoking history were significant factors predicting lymph node metastasis of clinical stage IA NSCLC. Patients with negative lobe-specific lymph node have very low risk of metastasis to the non-lobe specific lymph nodes. Lobe-specific lymph node dissection may become an alternative lymph node dissection mode for clinical stage IA NSCLC, especially for tumors ≤2 cm.