Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the primary form of lung cancer, and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease. However, the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies. Consequently, it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments. AIM: To identify the metabolic signatures associated with neutrophil extracellular traps (NETs) and chemoimmunotherapy efficacy in NSCLC patients. METHODS: In total, 159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled. We first investigated the characteristics influencing clinical efficacy. Circulating levels of NETs and cytokines were measured by commercial kits. Liquid chromatography tandem mass spectrometry quantified plasma metabolites, and differential metabolites were identified. Least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest algorithms were employed. By using plasma metabolic profiles and machine learning algorithms, predictive metabolic signatures were established. RESULTS: First, the levels of circulating interleukin-8, neutrophil-to-lymphocyte ratio, and NETs were closely related to poor efficacy of first-line chemoimmunotherapy. Patients were classed into a low NET group or a high NET group. A total of 54 differential plasma metabolites were identified. These metabolites were primarily involved in arachidonic acid and purine metabolism. Three key metabolites were identified as crucial variables, including 8,9-epoxyeicosatrienoic acid, L-malate, and bis(monoacylglycerol)phosphate (18:1/16:0). Using metabolomic sequencing data and machine learning methods, key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy. CONCLUSION: The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Variations of organic carbon storage in vegetation-soil systems during vegetation degradation in the Gahai wetland, China.

Qinghai-Tibet Plateau wetland, an important component of terrestrial ecosystem, plays an essential role in global carbon cycling. To understand the variation of organic carbon storage in vegetation-soil system during vegetation degradation in the Gahai wetland we examined aboveground litter, root biomass and soil organic carbon content in different degradation stages (CK: no degradation, SD: light degradation, MD: moderate degradation, HD: heavy degradation). The results showed that except for HD, carbon storage of aboveground biomass was 99.58-205.64 g·m-2 and that of root biomass (0-40 cm) was 56.96-754.37 g·m-2. The carbon stocks of aboveground and roots decreased significantly with degradation. Soil bulk density increased first and then decreased with degradation. Soil bulk density of each layer under degraded wetland was greater than that of the control. The carbon storage of litter was 17.29-35.69 g·m-2, which was significantly higher in CK than in MD and HD. The carbon storage in the soil (0-40 cm) was 7265.06-9604.30 g·m-2, with the order of MD＞CK＞SD＞HD. The carbon storage in CK and MD as significantly higher than that in SD and HD. The total carbon storage in the vegetation-soil system was 7265.06-10389.94 g·m-2 under different degradation stages. The largest was in CK, followed by MD, SD, and HD. Organic carbon was mostly stored in soil, which accounted for over 90% of the storage. Moderate interference might benefit carbon sequestration of the alpine wetland ecosystems.

Results of multiple ligament injured knees operated by three different strategies.

BACKGROUND: Multiple ligament injured knee is generally described for a scenario when at least 2 of the 4 major ligaments are ruptured. The most effective treatment for these injuries remains controversial. This study presents the clinical outcome of 3 surgical strategies based on personalized treatment. MATERIALS AND METHODS: Thirty two patients with multiple ligament injured knee were treated by 3 surgical strategies in the acute phase. (1) One-stage: Twelve patients treated by repair and reconstruction of all ruptured ligaments in a single operation. (2) Staged: Eleven patients treated by repair or reconstruction of the extraarticular (EA) ligaments and then intraarticular ligaments in 2(nd) stage. (3) EA ligament repair: Nine patients underwent only EA ligaments repair. RESULTS: The patients were followed up for an average of 34.7 ± 12.1 months. Significant improvements in knee stabilities (P < 0.01), Lysholm score (P < 0.01) and International Knee Documentation Committee grade (P < 0.01) were noticed in all groups. Of the 32 patients, none had gross mal alignment or gait abnormalities at the latest followup. Comparing the 3 groups, a significant difference in Lysholm score was shown between the one stage group and the EA repair group (P = 0.040); additionally, significant differences were found in 2 subscales of knee injury and osteoarthritis outcome score (P < 0.05). CONCLUSION: Satisfactory clinical and functional outcomes could be achieved adopting the 3 surgical strategies based on personalized treatment. However, a combination of EA repair and intraarticular repair or reconstruction might be more reasonable options for the young and active patients.

High expression of Toll-like receptor 5 correlates with better prognosis in non-small-cell lung cancer: an anti-tumor effect of TLR5 signaling in non-small cell lung cancer.

PURPOSE: Toll-like receptor 5 (TLR5) is a pattern recognition receptor and plays key roles in inflammatory responses against pathogen infection. Recent evidence suggests that TLR5 is expressed in a wide variety of tumors and exhibits either pro-tumor or anti-tumor activities. In this study, we explored expression of TLR5 in the context of non-small-cell lung cancer (NSCLC) and evaluated the effects of TLR5 signaling in NSCLC cells. METHODS: The lung carcinoma samples were collected from 113 patients diagnosed as NSCLC at Tumor Hospital of Xiangya School of Medicine from January 2005 to December 2008. Immunohistochemistry was performed for TLR5 and the protein expression score was quantified using an established scoring system. Kaplan-Meier survival curves were generated for disease-free survival (DFS) and overall survival (OS) in all patients. TLR5 expression levels were correlated with DFS and OS using univariate and multivariate Cox regression analysis. Expression and subcellular localization of TLR5 were analyzed in NSCLC cell lines including SPC-A1, A549, H1975, and H1299 cells. Activation of TLR5 signaling pathway by flagellin was characterized by western blotting. Effects of flagellin on NSCLC cell proliferation, anchorage-independent growth, migration, and invasion were analyzed by BrdU incorporation assay, soft agar colony formation assay, wound-healing migration assay, and transwell invasion assay, respectively. RESULTS: High expression of TLR5 was significantly associated with better prognosis in patients with NSCLC. We further demonstrated that activation of TLR5 by flagellin in NSCLC cells inhibited cell proliferation, migration, and invasion in vitro. CONCLUSION: TLR5 may serve as a potential therapeutic target in NSCLC patients.

[Case-control studies on therapeutic effects of arthroscopic reconstruction of anterior cruciate ligament with preservation of remnant through outside-in and transtibial tunel].

OBJECTIVE: To compare the properties and clinical outcomes of arthroscopic reconstruction of anterior cruciate ligament (ACL) with preservation of remnant through outside-in and transtibial tunel. METHODS: From June 2005 to January 2012, 145 patients were treated with arthroscopic reconstruction of ACL with preservation of remnant. Among the patients, 88 patients were treated with outside-in techniques (outside-in group), including 55 males and 33 females, ranging in age from 18 to 52 years, with a mean of (29.22 +/- 7.31) years; 57 patients were treated with transtibial technique (transtibial group), including 35 males and 22 females, ranging in age from 18 to 51 years, with a mean of (29.28 +/- 8.07) years. The Lysholm, VAS and IKDC scores were compared between two groups before operation, after operation and at the latest follow-up time. RESULTS: The average operation time was (76.94 +/- 10.83) min in the outside-in group, and (70.35 +/- 10.11) min in the transbibial group, there was a significant difference between two groups. There was no significant difference of hydrops articuli scores at the early stage between the two groups (P = 0.065). At follow-up from 18 to 60 months, there were great improvements in the knee stabilities in each group compared with the preoperative data respectively. The Lysholm score improved from 54.75 +/- 10.58 preoperatively to 95.80 +/- 5.16 at the follow-up in the outside-in group; and improved from 52.51 +/- 11.38 preoperatively to 94.86 +/- 5.50 at follow-up in the transtibial group. Additionally, IKDC grades also improved in both groups. However, no significant differences were seen in stabilities shown by pivot shift test, Lachman test and anterior drawer test. And there also no significant differences of Lysholm scores and IKDC grades between two groups after operation. CONCLUSION: The outside-in technique has advantages to create an anatomical femoral tunnel easily with minimal intra-articular interference, and disadvantages of complicated manipulation. The transtibial technique is easy to operate and gain time. Using either of responding technique according to the actual situation, satisfactory outcome could be archived.

Knockdown of TRB3 induces apoptosis in human lung adenocarcinoma cells through regulation of Notch 1 expression.

The upregulation of tribbles homolog 3 (TRB3), a pseudokinase in mammals, has been observed in several types of malignant cancer, including thyroid, ovarian, liver and colorectal cancer. However, the pathological role and the regulatory mechanism of TRB3 in cancer remain unknown. In the current study, we demonstrated that the expression of TRB3 was upregulated in non-small cell lung cancer (NSCLC), correlating with tumor metastasis, disease recurrence and poor survival in patients. Knocking down TRB3 in aggressive lung cancer cell lines was demonstrated to significantly inhibit their malignant behaviors, including in vitro invasion and cell proliferation, as well as in vivo metastasis and tumor growth. The correlation between TRB3 and Notch 1 expression revealed that Notch 1 was downregulated by the knockdown of TRB3 in the lung adenocarcinoma cell lines. These results have provided insights into the correlation between TRB3 expression and lung cancer progression, and thus may have potential for the prognosis and therapy of lung cancer.

[Application of computer-aided design in preoperative planning in total hip replacement].

OBJECTIVE: To investigate the advantages of using the preoperative computer-aided design system (CAD) in total hip replacement (THR). METHODS: From March 2002 to September 2005, 182 patients who underwent primary THR were screened and divided into 2 groups randomly. CAD and traditional preoperative templating were used in preoperative planning respectively. RESULTS: In group using CAD, the migration of the center of acetabulum was smaller, and the discrepancy of the limb length and the abductor force lever arm were fewer. All the differences above were significantly different. CONCLUSIONS: CAD helps remove much of the guesswork during surgery, and the implant can be more precise fitting to the patient. And equal limb lengths and balanced abductor force can be restored more accurately.

[Mortality analyses for tungsten miners].

OBJECTIVE: To investigate the mortality from main causes of death in 6 tungsten miners and explore the effects of cumulative dust exposure on standardized mortality ratios (SMRs) from main causes. METHODS: A cohort of 18027 workers registered in the employment record from 6 tungsten mines located in Hunan and Jiangxi province and working for at least 1 year was identified for this study. SMRs were calculated based on Chinese national mortality. Trend analysis was used to analyze the effect of cumulative dust exposure on SMRs of main causes of death. RESULTS: The cohort was followed up from 1972 to 2003 with an accumulative of 470 722.21 person-years. A total of 6135 workers died, and the mortality was 13.03 per thousand. Cardiovascular disease, respiratory disease, malignant neoplasm and pulmonary tuberculosis accounted for 79.32% of all death. The mortalities of all-causes, pneumoconiosis, pulmonary tuberculosis, nasopharyngeal carcinoma, infectious disease, respiratory disease, cardiovascular disease and liver cancer were found to be significantly higher than the national average level. Positive dose-response relationship between SMRs and cumulative dust exposure was observed in all-causes, pneumoconiosis, pulmonary tuberculosis, respiratory disease, cardiovascular disease (P < 0.01). CONCLUSION: The mortality from main causes of death for the dust-exposed workers are higher than that for non dust-exposed workers. Positive dose-response relationships are observed between cumulative dust exposure and SMRs from all-causes, respiratory disease (including silicosis), pulmonary tuberculosis and cardiovascular disease.