Blood Coagulation-Inspired Fibrin Hydrogel for Portable Detection of Thrombin Based on Personal Glucometer.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0-0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.

Maternal exposure to ambient ozone and fetal conotruncal heart defects in China: A multicenter cohort study.

BACKGROUND: The relationships between maternal genetic and environmental exposure and conotruncal heart defects (CTDs) have been extensively investigated. Nevertheless, there is limited knowledge regarding the impact of ozone (O3) on the risk of CTDs. OBJECTIVE: To explore the correlation between maternal exposure to O3 and CTDs in China. METHODS: Pregnant women who underwent fetal echocardiography at Beijing Anzhen Hospital between January 2013 and December 2021 were enrolled. Their sociodemographic characteristics and lifestyle information, along with fetal data, were systematically collected. Fetal echocardiography was used to detect CTDs. Maternal exposure to ambient O3 during the embryonic period, the first trimester, the three months preceding the last menstrual period, and the perinatal period was estimated using residential addresses or hospital addresses associated with prenatal visits. The concentration of O3 was divided by quartiles, with the first quartile serving as a reference. Adjusted logistic regression models were employed to examine the associations between every 10 µg/m3 increase or quartile increase in ambient O3 exposure and CTDs. RESULTS: Among 24,278 subjects, 1069 exhibited fetuses with CTDs. Maternal exposure to ambient O3 during three pregnancy periods was associated with increased CTD risk. The adjusted odds ratio (OR) and 95% confidence interval (CI) were 1.271 (1.189-1.360) per 10 µg/m3 increase in O3 during the perinatal period. For each quartile of O3, the risk increased with increasing exposure concentration, particularly during the perinatal period (OR = 2.206 for quartile 2, 2.367 for quartile 3, and 3.378 for quartile 4, all P<0.05). CONCLUSIONS: Elevated maternal exposure to O3 during pregnancy, particularly in the perinatal period, is linked to an increased risk of fetal CTDs. Further longitudinal analyses are needed to validate these results.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

Augmentation of scleral glycolysis promotes myopia through histone lactylation.

Myopia is characterized of maladaptive increases in scleral fibroblast-to-myofibroblast transdifferentiation (FMT). Scleral hypoxia is a significant factor contributing to myopia, but how hypoxia induces myopia is poorly understood. Here, we showed that myopia in mice and guinea pigs was associated with hypoxia-induced increases in key glycolytic enzymes expression and lactate levels in the sclera. Promotion of scleral glycolysis or lactate production induced FMT and myopia; conversely, suppression of glycolysis or lactate production eliminated or inhibited FMT and myopia. Mechanistically, increasing scleral glycolysis-lactate levels promoted FMT and myopia via H3K18la, and this promoted Notch1 expression. Genetic analyses identified a significant enrichment of two genes encoding glycolytic enzymes, ENO2 and TPI1. Moreover, increasing sugar intake in guinea pigs not only induced myopia but also enhanced the response to myopia induction via the scleral glycolysis-lactate-histone lactylation pathway. Collectively, we suggest that scleral glycolysis contributes to myopia by promoting FMT via lactate-induced histone lactylation.

En bloc resection of an extremely giant mediastinal immature teratoma with somatic-type malignancy: A case report with a brief review of the literature.

Primary mediastinum immature teratoma with somatic-type malignant transformation (SM) is extremely rare, and the clinical prognosis is poor. Immature teratoma with SM is difficult to eradicate by chemotherapy due to poor sensitivity; therefore, surgical resection is recommended whenever possible because it may offer better survival.

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis.

Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.

[Updated Interpretation of the NCCN Clinical Practice Guidelines (Version 3. 2023) 
for Non-small Cell Lung Cancer].

Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China.
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Enhanced interface stability of ammine magnesium borohydride by in situ decoration of MgBr2·2NH3 nanoparticles.

A novel Mg(BH4)2·1.9NH3-MgBr2·2NH3 composite was demonstrated as a solid-state Mg2+ electrolyte. The in situ decoration of MgBr2·2NH3 nanoparticles with an average size of 3.7 nm on the surface of Mg(BH4)2·1.9NH3 improves the Mg2+ conductivity to 2.1 × 10-4 S cm-1 at 50 °C and offers long-term stability towards the Mg metal anode.

The impact of previous extrapulmonary malignancies on survival of surgically treated primary lung cancer: a comprehensive systematic review and meta-analysis.

Whether a history of previous extrapulmonary malignancies had an impact on the survival of surgically treated primary lung cancer patients remains unknown. To better answer this question, we, therefore, conducted the first meta-analysis to compare the survival of lung cancer patients after surgical resection with previous extrapulmonary malignancies and those without. We systematically searched PubMed, Embase, and the Cochrane Library to identify relevant studies up to April 1, 2022. Data for analysis were obtained directly from the text results or calculated from the Kaplan-Meier survival curve, which mainly included 5-year overall survival (OS) and recurrence-free survival (RFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed by the fixed-effect model test or standard random-effect model test depending on the heterogeneity of the included studies. The Q-test and I2-test were used to assess heterogeneity. Sensitivity analysis was performed to examine the stability of the pooled results. We finally included 7 retrospective studies consisting of 19,723 surgically treated primary lung cancer patients with (7.7%) or without (92.3%) previous extrapulmonary malignancies. The final results showed that lung patients with previous extrapulmonary malignancies had an inferior OS (HR 1.18, 95% CI [1.07, 1.31], P = 0.001) than those without, but no significant difference in RFS (HR 1.15, 95% CI [0.89-1.47], P = 0.29) was observed between the two groups. Moreover, when only focusing on stage-I primary lung cancer patients with or without previous extrapulmonary malignancies, the results still held true (OS: HR 1.39, 95% CI [1.04, 1.85], P = 0.02; RFS: HR 1.10, 95% CI [0.82-1.49], P = 0.51, respectively). No significant heterogeneities or publication bias were observed among these studies. Our meta-analysis showed that surgically treated primary lung cancer patients with a previous extrapulmonary cancer history had a worse overall survival than those without. However, a history of previous extrapulmonary cancer was not associated with postsurgical lung cancer recurrence, and more large-scale prospective studies should be encouraged to update our conclusions.

Surgical resection versus radiotherapy for clinical stage IA lung cancer ≤1 cm in size: A population-based study.

OBJECTIVE: With the increasing incidence of stage IA lung cancer ≤1 cm in size, the optimal primary treatment remains to be controversial, and thus, we compared the survival of these patients treated with radiotherapy, wedge resection, segmentectomy, or lobectomy in a large population. METHODS: We identified patients with stage IA lung cancer ≤1 cm in size between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival (OS) via Kaplan-Meier analysis and conducted Cox regression analysis via propensity score matching (PSM) method to identify the relative hazard ratio (HR) and difference of OS among these treatments in the subgroup stratified by four variables (age, total number of tumors, pathological grade, and histology). RESULTS: A total of 5435 patients were included with a median age of 68 years (range, 6-94 years), of which 2131 (39.2%) were male, and 3510 (64.6%) were adenocarcinoma. The 5-year OS rate was 67.1%, 34.5%, 61.6%, 72.1%, and 75.0% for the entire study population, radiotherapy, wedge resection, segmentectomy, and lobectomy, respectively. In PSM analysis, wedge resection and segmentectomy were all superior to radiotherapy (P < 0.001), and segmentectomy was superior to wedge resection (P = 0.043), while segmentectomy was comparable with lobectomy (P = 0.058). In patients with multiple tumors, radiotherapy brought similar survival to surgery (wedge resection versus radiotherapy, P = 0.323; segmentectomy versus radiotherapy, P = 0.170; lobectomy versus radiotherapy, P = 0.796). CONCLUSIONS: Among stage IA lung cancer with ≤1 cm, segmentectomy and lobectomy were identified as the potential effective treatments, with segmentectomy more preferred, while radiotherapy would be recommended in those with multiple tumors, which requires further verification.

The predictive value of the preoperative systemic immune-inflammation index in the occurrence of postoperative pneumonia in non-small cell lung cancer: A retrospective study based on 1486 cases.

BACKGROUND: To investigate the correlation between the preoperative systemic immune-inflammation index (pSII) and postoperative pneumonia (POP) in surgical non-small cell lung cancer patients. METHODS: Patients who underwent lung cancer surgery at West China Hospital of Sichuan University were retrospectively included. The indicators were collected, including basic information of patients, surgery-related variables and POP rate. The predictive value of the pSII in the occurrence of POP was analyzed. RESULTS: A total of 1486 patients (male: 748, 50.3%; female: 738, 49.7%; mean age: 58.2 ± 9.7 years; median age: 59 years old, interquartile range: 51-65 years old) were finally included in the study, of which 142 patients had POP with an incidence of 9.5% (142/1486), 9.2% (69/748) in males, and 9.9% (73/738) in females. The proportion of patients with diabetes in the pneumonia group was significantly higher than that in the nonpneumonia group (9.8%, 14/142 vs. 5.6%, 75/1344, p = 0.041). Compared with the nonpneumonia group, the level of the preoperative body mass index (24.2 [21.9, 26.1] vs. 23.1 [21.1, 25.2], p = 0.003) and SII (487 [350, 673] vs. 345 [230, 500], p < 0.001) in the pneumonia group were significantly higher. Multiple factor analysis showed that the pSII (odds ratio: 1.001, 95% confidence interval: 1.000-1.001, p < 0.001) was an independent risk factor for POP (487 [350, 673] vs. 345 [230, 500], p < 0.001); receiver operating characteristic curve analysis showed that the pSII was effective in predicting POP (area under curve: 0.751, p < 0.001). CONCLUSION: The pSII is closely related to and can effectively predict the occurrence of POP after lung cancer surgery.

The safety and feasibility of preoperative induction therapy of Savolitinib in non-small cell lung cancer patients with MET exon 14 skipping mutation.

PURPOSE: Neoadjuvant therapy followed by surgical resection is one of the preferred treatment option for locally advanced non-small cell lung cancer (NSCLC). For patients with mesenchymal-epithelial transition (MET) factor exon 14 skipping (METex14) mutations, the use of MET-tyrosine kinase inhibitors (TKIs) showed high efficiency and reduced toxicity compared with first-line standard chemotherapy. However, it is unknown whether preoperative induction targeted therapy of MET-TKIs is feasible and safe. METHODS: Here, we reported 3 cases of locally advanced unresectable NSCLC with METex14 mutations receiving induction therapy of MET-TKI savolitinib as first-line therapy or second-line therapy when they experienced disease progression after preoperative chemotherapy. RESULTS: All these 3 patients achieved significant tumor size shrinkage and their unresectable tumors became resectable after the treatment of savolitinib. No serious adverse events were observed during the treatment. They recovered well postoperatively, and no significant events were identified. CONCLUSIONS: Preoperative induction treatment with MET-TKI savolitinib showed its safety and effectiveness and may be an alternative option for neoadjuvant therapy for NSCLC patients with METex14 mutations.

Lobe-specific lymph node dissection in early-stage non-small-cell lung cancer: An overview.

Lymph node dissection is a vital part of surgical treatment for early-stage non-small cell lung cancer (NSCLC). Lobectomy with systematic lymph node dissection (SLND) still remains the gold standard surgical treatment for early-stage NSCLC patients. However, an increasing number of studies have demonstrated that lobe-specific lymph node dissection (L-SLND) can be used as an alternative therapy for SLND in carefully selected patients with early-stage NSCLC. However, there are no currently available evidences of review summarizing the role of L-SLDN in treating early-stage NSCLC. Therefore, we performed this literature review by summarizing the existing literatures on the lymph node drainage pattern, definition, scope and role of L-SLND in patients with early-stage NSCLC, aiming to provide evidence for the application of L-SLND in patients with early-stage NSCLC.

Does the division of the inferior pulmonary ligament in upper lobectomy result in improved short-term clinical outcomes and long-term survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does the division of the inferior pulmonary ligament (IPL) in upper lobectomy result in improved short-term clinical outcomes and long-term survival?'. Altogether 43 papers were found using the reported search, of which 6 studies represented the best evidence to answer the clinical question, including a previous best evidence topic study, a meta-analysis and 4 retrospective cohort studies. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Most of the enrolled studies reported that there is no significant difference between the division groups and the preservation groups in terms of drainage time, drainage volume, postoperative dead space and complications. While 3 cohort studies revealed unfavoured postoperative pulmonary function in the division groups, including lung volume, forced vital capacity and forced expiratory volume in 1 s. The previous meta-analysis and a recent cohort study also found that the division of IPL might lead to increased bronchus angle change or torsion. Moreover, 2 cohort studies found that the division of IPL could not improve the long-term survival of patients undergoing upper lobectomy. Current evidence showed that dividing the IPL could not result in clinical benefits but might lead to decreased pulmonary function instead. Therefore, we recommended not dissecting the IPL routinely during upper lobectomy.

Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for non-small-cell lung cancer after neoadjuvant treatment?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for patients with non-small cell lung cancer following neoadjuvant therapy intended for anatomical lung resection?'. Altogether 655 papers were found using the reported search, of which 12 studies represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Almost all of the enrolled cohort studies reported that video-assisted thoracoscopic surgery (VATS) was comparable with thoracotomy in negative surgical margin rate, postoperative mortality, complication rate, overall survival and disease-free survival. Moreover, 7 studies found patients in the VATS group had a significantly shorter hospital stay. Furthermore, in these well-matched cohort studies (6 studies), it still held true that VATS was comparable with thoracotomy in long-term prognosis with enhanced recovery. However, the issue regarding surgical radicality and intraoperative conversion to thoracotomy still should be noted carefully among these patients receiving VATS surgery because all the current available evidence was retrospective based on relatively small sample sizes. Nevertheless, thoracic surgeons should not consider VATS inferior to thoracotomy for patients after neoadjuvant treatment. VATS surgery could be an alternative for selected patients with locally advanced but relatively small, peripheral, fewer positive N2 lymph nodes and non-squamous NSCLC intended for anatomic lung resection.

Characteristics and prognosis of primary pulmonary osteosarcoma: a pooled analysis.

BACKGROUND: Primary pulmonary osteosarcoma (PPOS) is an uncommon malignancy originating from the lung with low incidence, and its clinical characteristics and prognosis have not been systematically reported. Therefore, we aimed to recognize the prognostic factors and constructed a survival prediction model for PPOS. METHODS: We collected the data from the Surveillance, Epidemiology, and End Results database and systematic review of previous studies. Demographical and clinical characteristics, radiographic manifestations, treatment modalities, and prognosis were analyzed. A prediction model via nomogram was constructed and then evaluated by the concordance index (C-index) and the receiver operating characteristic (ROC) curve. RESULTS: A total of 49 cases were included for analysis with a median age of 67 years old (range 33-94 years), of which 32 (65.3%) were male. The median size was 6 cm (range 1.8-25 cm), and the median overall survival (OS) was eight months (interquartile range 4.5-12 months) with a 1-year OS rate of 30.8%. Tumor size over 7 cm (hazard ratio [HR] = 2.98; P = 0.018) and those without microscopic findings of osteoid found in the tumors (HR = 2.11; P = 0.048) were referred to a poor OS, while surgery was associated with an improved OS (HR = 0.20; P < 0.001). The C-index of the nomogram prediction model was 0.771, and the area under curve, sensitivity and specificity of the ROC curve were 0.818, 0.848 and 0.800, respectively. CONCLUSIONS: Patients with PPOS had a poor prognosis, and tumor size was mostly prognostic. Surgery seemed to be an effective treatment, and the prediction model with a nomogram in our study could effectively predict the prognosis of patients with PPOS.