[Research on the Correlation Between Soil Mineral Elements and NIR Fingerprint of Angelica sinensis].

Objective: To investigate the correlation between soil mineral elements and NIR fingerprint of Angelica sinensis. Methods: The fingerprint of 130 batches of Angelica sinensis from 12 production regions were determined by near infrared spectra with integrating sphere and diffuse device of near infrared spectrometer. The determination of 15 kinds of mineral elements in the corresponding origin of soil mass fraction were determined by atomic absorption spectrometry or inductively coupled plasma mass spectrometry, grey correlation analysis and multivariate nonlinear regression method were used to analyze. Results: The soil mineral elements and their contribution were Cu > Pb, which were the main influencing factors of Angelica sinensis NIR fingerprint maximum absorbance on peak 7 249cm-1; the contribution of mineral elements in soil were Cr > Fe > Zn > Cd > Ca on peak 6 996 cm-1,there were positive correlation between Cr and Cd, and negative correlation between Fe and Ca; on peak 5 900 cm-1were Cu; on peak 5 000 cm-1were K > Ca > Zn; on peak 4 762 cm-1were K > Sb; on peak 4 651 cm-1were Ca > K > As > Cr, there were positive correlation between Ca and K, and the positive correlation or negative correlation between the square of As and Cr; the contribution of mineral elements in soil on peak 4 545cm-1were Ni > Cu > As; on peak 4 347 cm-1were Cd > Ca > As > Fe > K > Sb, and there were positive correlation among Cd, K, As and Fe. Conclusion: Angelica sinensis NIR fingerprint spectrum characteristics associate with a variety of soil mineral elements, which show the multiplicity and interactivity.

[NIR Fingerprints of Different Medicinal Parts of Angelicae Sinensis Radix].

OBJECTIVE: To investigate the spectrum characteristics of near-intrared dittuse retlectance spectroscopy (NIR) fingerprint of different medicinal parts of Angelicae Sinensis Radix. METHODS: 96 batches of samples were collected from 14 counties of Gansu Province and Yunnan Province. The NIR fingerprints were collected by integrated sphere. Similarity analysis and partial least square discriminant analysis(PLS-DA) were used to analyze the fingerprint. RESULTS: The average spectrum of NIR fingerprint of different medicinal parts of Angelicae Sinensis Radix showed some differences; the absorbance in characteristic absorption was in a decreasing order of body > tail > head > whole. Most NIR fingerprint similarities of different medicinal parts of Angelicae Sinensis Radix exceeded 0. 95. The established model of PLS-DA could be used to accurately classify the medicinal parts of Angelicae Sinensis Radix. The differences of NIR fingerprints of different medicinal parts of Angelicae Sinensis Radix were mainly existing in the wave number ranges of 8,443 - 8,284 cm -1, 7,003 - 6,896 cm-1, 6,102 - 5,864 cm-1, 4,847 - 4,674 cm-1, and 4,386 - 4,208 cm-1. CONCLUSION: The different medicinal parts of Angelicae Sinensis Radix have some differences in chemical components.

[Correlation Analysis Between Common Peaks of Angelica sinensis HPLC Fingerprint and Mineral Elements in Its Growing Soil].

OBJECTIVE: To investigate the correlation between common peaks of Angelica sinensis HPLC fingerprint and mineral elements in its growing soil. METHODS: The fingerprints of 120 batches of Angelica sinensis from 12 habitats were determined by HPLC. The contents of Pb, As, Cr, Sb, Hg, Cu, Cd, Ni, Zn, Mg, Mn, Ca, Fe, Na and K in corresponding soil were determined by ICP-MS and AAS. Bivariate and multiple linear regression were used to analyze the correlation. RESULTS: There were significant ( P < 0. 01 or P < 0.05) positive and negative correlation between many common peaks in HPLC fingerprint of Angelica sinensis and mineral elements in its growing soil. The contribution of mineral elements in soil on peak 1 were Zn > K > Sb > Fe > Na; on peak 6 (3-butylphthalide) were Mn > Mg > Ca; on peak 7 were Cr > Zn; on peak 8 were Mn > Na; on peak 11 were As > K > Fe > Cd; on peak 12 were Zn > Mn > K; on peak 13 (Z-butylidenephthalide) were Mn > Zn > Cd; on peak 15 were Zn > K; on peak 16 were Fe > Ni; on peak 17 were Zn > Mn > Ni > Fe > K; on peak 18 were Zn > Na; peaks 2,3 (ferulic acid), 4 and 14 (Z-ligustilide) was mainly affected by As, Zn, Sb and Cu, respectively. CONCLUSION: The relationship between HPLC fingerprint peak of Angelica sinensis and mineral elements in its growing soil shows complexity, multiplicity and interactivity, which should be selectively examined during manuring micronutrient fertilizer and Angelica sinensis cultivation.

LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.

BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

SLUG is activated by nuclear factor kappa B and confers human alveolar epithelial A549 cells resistance to tumor necrosis factor-alpha-induced apoptosis.

BACKGROUND: The role of tumor necrosis factor alpha (TNF-α) in cancer is complex with both apoptotic and anti-apoptotic roles proposed. However the mechanism is not clear. In the study, we designed to investigate the effect of TNF-α on the activation and expression of nuclear factor kappa B (NF-κB)/p65/SLUG/PUMA/Bcl-2 levels in human lung cancer A549 cell line, and in conditions of TNF-α-induced apoptosis. METHODS: We have engineered three A549 cell lines that were transiently transfected with PUMA siRNA, SLUG siRNA and Bcl-2 siRNA, respectively. We have measured the in vitro effects of siRNA on apoptosis, and sensitivity to 20 ng/ml of TNF-α treatment for 24-48 h. RESULTS: We found the NF-κB activity and PUMA mRNA/protein was significantly increased after treatment of TNF-α for 24 h in untreated A549 cells, and led to a significant increase in TNF-α-induced apoptosis, no significant increase of SLUG and Bcl-2 level was shown. However, after treatment of TNF-α for 48 h in untreated A549 cells, SLUG and Bcl-2 level was significant increased, and PUMA level was significant decreased, and TNF-α-induced apoptosis was significantly decreased compared to the apoptosis level after treatment of TNF-α for 24 h. Inhibition of the NF-κB activity could effectively decrease the PUMA level and increase the SLUG and Bcl-2 level. PUMA silencing by siRNA led to a significant decrease in TNF-α-induced apoptosis after treatment of TNF-α for 24 h. Bcl-2 and SLUG silencing by siRNA led to a significant increase in TNF-α-induced apoptosis for 48 h. Furthermore, SLUG silencing increased PUMA level and decreased Bcl-2 level. CONCLUSIONS: The findings suggested that TNF-α treatment promoted apoptosis via the NF-κB-dependent PUMA pathway. The anti-apoptotic role of TNF-α was via NF-κB-dependent SLUG and Bcl-2 pathway at a later time.

Targeting the Immunoglobulin IGSF9 Enhances Antitumor T-cell Activity and Sensitivity to Anti-PD-1 Immunotherapy.

Immune checkpoints modulate the immune response and represent important immunotherapy targets for cancer treatment. However, as many tumors are resistant to current immune checkpoint inhibitors, the discovery of novel immune checkpoints could facilitate the development of additional immunotherapeutic strategies to improve patient responses. Here, we identified increased expression of the adhesion molecule immunoglobulin superfamily member 9 (IGSF9) in tumor cells and tumor-infiltrating immune cells across multiple cancer types. IGSF9 overexpression or knockout in tumor cells did not alter cell proliferation in vitro or tumor growth in immunocompromised mice. Alternatively, IGSF9 deficient tumor cells lost the ability to suppress T-cell proliferation and exhibited reduced growth in immunocompetent mice. Similarly, growth of tumor cells was reduced in IGSF9 knockout syngeneic and humanized mice, accompanied by increased tumor-infiltrating T cells. Mechanistically, the extracellular domain (ECD) of IGSF9 bound to T cells and inhibited their proliferation and activation, and the tumor-promoting effect of IGSF9 ECD was reversed by CD3+ T-cell depletion. Anti-IGSF9 antibody treatment inhibited tumor growth and enhanced the antitumor efficacy of anti-programmed cell death protein 1 immunotherapy. Single-cell RNA sequencing revealed tumor microenvironment remodeling from tumor promoting to tumor suppressive following anti-IGSF9 treatment. Together, these results indicate that IGSF9 promotes tumor immune evasion and is a candidate immune checkpoint target. SIGNIFICANCE: IGSF9 is an immune checkpoint regulator that suppresses T-cell activation in cancer and can be targeted to stimulate antitumor immunity and inhibit tumor growth.

Large-Scale Customized Production Scheduling of Multiagent-Based Medical 3D Printing.

Three-dimensional (3D) printing, also known as additive manufacturing, has unique advantages over traditional manufacturing technologies; thus, it has attracted widespread attention in the medical field. Especially in the context of the frequent occurrence of major public health events, where the medical industry's demand for large-scale and customized production is increasing, traditional 3D printing production scheduling methods take a long time to handle large-scale customized medical 3D printing (M-3DP) production and have weak intelligent collaboration ability in the face of job-to-device matching under multimaterial printing. Given the problem caused by M-3DP large-scale customized production scheduling, an intelligent collaborative scheduling multiagent-based method is proposed in this study. First, a multiagent-based optimization model is established. On this basis, an improved genetic algorithm embedded with the product mix strategy and the intelligent matching mechanism is designed to optimize the completion time and load balance between devices. Finally, the effectiveness of the proposed method is evaluated using numerical simulation. The simulation results indicated that compared with the simple genetic algorithm, particle swarm optimization, and snake optimizer, the improved genetic algorithm could better reduce the M-3DP mass customization production scheduling time, optimize the load balance between devices, and promote the "intelligent manufacturing" process of M-3DP mass customization.

Fruit and vegetable consumption and risk of lung cancer: a dose-response meta-analysis of prospective cohort studies.

OBJECTIVES: A meta-analysis was conducted to summarize evidence from prospective cohort studies about the association of fruit and vegetable consumption with the risk of lung cancer. MATERIALS AND METHODS: Pertinent studies were identified by a search of Embase and PubMed databases to October 2014. A random-effects model was used to combine study-specific relative risks and 95% confidence interval [RR (95% CI)]. Dose-response relationship was assessed by restricted cubic spline. RESULTS: The RR (95% CI) of lung cancer for highest versus lowest category of fruit and vegetable (FV) consumption was 0.87 (0.79-0.95) (8 studies including 12,942 cases among 1,571,494 subjects), and the effect was 0.84 (0.79-0.90) for fruit (16 studies including 15,421 cases among 1,791,469 subjects) and 0.90 (0.84-0.96) for vegetable (19 studies including 16,422 cases among 1,877,375 subjects). The above-mentioned associations did not differed significantly in subgroup analysis by country, age, number of covariates adjusted, quality score, sex, smoking status and histological subtypes; however, studies with follow-up duration of ≥10 years and with FV assessed by interview showed a stronger association than those of <10 years and by self-administrated food frequency questionnaires, respectively. The risk of lung cancer decreased by 3% (P=0.07), 5% (P<0.01) and 3% (P=0.09) for every 1 serving/day increment in FV, fruit and vegetable consumption, respectively. There was a threshold around 2 servings/day of fruit and 2 servings/day of vegetable, respectively, after which the risk of lung cancer did not reduce further. CONCLUSIONS: Fruit and vegetable consumption are inversely associated with risk of lung cancer.

Expression of ADAM12 is regulated by E2F1 in small cell lung cancer.

Our previous study reported that ADAM12 was highly expressed in small cell lung cancer (SCLC) and could be an effective marker for diagnosis and prognosis. Yet, the reason for the high expression of ADAM12 in SCLC requires further elucidation. Transcription factor E2F1 has been receiving increasing attention due to the complexity and diversity of its function in cancer. In the present study, the expression of ADAM12 was significantly decreased following silencing of E2F1 expression by siRNA, thus indicating that E2F1 may regulate the expression of ADAM12 at the level of transcription. Chromatin immunoprecipitation-to-sequence analysis identified three binding sites for E2F1 in the locus for ADAM12. They were Chr10: 128010444-128011026, located in the intron of ADAM12, named seq0; Chr10: 128076927­128078127, located in the promoter of ADAM12, named seq1; and Chr10: 128086195­128086876, located in the upstream 20 kb from the transcription start site of ADAM12, named: seq2. Dual­luciferase reporter experiments revealed that seq1 not seq0 and seq2 was able to promote the expression of luciferase. Notably, co-transfection of E2F1 significantly increased the activity of seq1 not seq0 and seq2, but quantitative polymerase chain reaction results showed that seq0, seq1 and seq2 could recruit E2F1, indicating that the influence of E2F1 in regulating the expression of ADAM12 was complex. Sequence analysis clarified that seq1 was a part of the ADAM12 promoter, yet the functions of seq0 and seq2 were unknown. Fusion fragments containing seq0-seq1 or seq2-seq1 were analyzed in luciferase constructs. Compared with seq1 alone, the activities of these fusion fragments were non-significantly reduced. The activities of fusion fragments were significantly decreased following co-transfection with E2F1. Thus, the present findings support the conclusion that the E2F1 transcription factor regulates the expression of ADAM12 by binding differential cis-acting elements.

Clinical significance of zoledronic acid and strontium-89 in patients with asymptomatic bone metastases from non-small-cell lung cancer.

BACKGROUND: The purpose of this study was to clarify the treatment value of zoledronic acid (ZA) and/or strontium-89 (Sr-89) in patients with non-small-cell lung cancer (NSCLC) with asymptomatic bone metastases (BMs). PATIENTS AND METHODS: Eligible patients were those with resectable NSCLC and asymptomatic BMs. These candidates were randomized into 4 groups: group A was treated with ZA and Sr-89 simultaneously, group B was treated with ZA, group C was treated with Sr-89, and group D was untreated. Patients were monitored and analyzed for the first skeletal-related event (SRE), overall survival (OS), and annual incidence of SREs. RESULTS: One hundred eighty patients were enrolled. Time to first SRE in group A was 15 months (95% confidence interval [CI], 14.0-16.0 months), in group B it was 12 months (95% CI, 11.1-13.0 months), in group C it was 9 months (95% CI, 8.5-9.5 months), and in group D it was 8 months (95% CI, 7.1-8.9 months) (P = .000). The overall survival (OS) in group A was 17 months (95% CI, 16.0-18.1 months); in group B, it was 16 months (95% CI, 14.2-17.8 months); in group C, it was 12 months (95% CI, 11.1-12.9 months); and in group D, it was 12 months (95% CI, 10.8-13.2 months). The annual incidence of SREs in group A was 24.4%; in group B, it was 55.6%; in group C, it was 75.6%; in group D, it was 91.1% (P = .000). CONCLUSIONS: Treatment with ZA and/or Sr-89 significantly extended the time to first SRE as well as survival time and reduced the annual incidence of SREs. Treatment with the combined use of ZA and Sr-89 was safe and well tolerated and achieved the best effect on asymptomatic BMs of NSCLC.

External suction versus water seal after selective pulmonary resection for lung neoplasm: a systematic review.

OBJECTIVE: To evaluate whether external suction is more advantageous than water seal in patients undergoing selective pulmonary resection (SPR) for lung neoplasm. SUMMARY OF BACKGROUND DATA: Whether external suction should be routinely applied in postoperative chest drainage is still unclear, particularly for lung neoplasm patients. To most surgeons, the decision is based on their clinical experience. METHODS: Randomized control trials were selected. The participants were patients undergoing SPR with lung neoplasm. Lung volume reduction surgery and pneumothorax were excluded. Suction versus non-suction for the intervention. The primary outcome was the incidence of persistent air leak (PAL). The definition of PAL was air leak for more than 3-7 days. The secondary outcomes included air leak duration, time of drainage, postoperative hospital stay and the incidence of postoperative pneumothorax. Studies were identified from literature collections through screening. Bias was analyzed and meta-analysis was used. RESULTS: From the 1824 potentially relevant trials, 6 randomized control trials involving 676 patients were included. There was no difference between external suction and water seal in decreasing the incidence of PAL [95% confidence interval (CI) 0.81-2.16; z = 1.10; P = 0.27]. Regarding secondary outcomes, there were no differences in time of drainage (95% CI-0.36-1.56, P = 0.22), postoperative hospital stay (95% CI -.31-.54, P = 0.87) or incidence of postoperative pneumothorax (95% CI 0.18-.02, P = 0.05) between external suction and water seal. CONCLUSIONS: For participants, no differences are identified in terms of PAL incidence, drainage time, length of postoperative hospital stay or incidence of postoperative pneumothorax between external suction and water seal. The bias analysis should be emphasized. To the limitations of the bias and methodological differences among the included studies, we have no recommendation on whether external suction should be routinely applied after lung neoplasm SPR. More high-quality randomized controlled trials are needed. SYSTEMATIC REVIEW REGISTRATION: None.

Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies.

Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk of lung cancer, while no significant association was found between black tea consumption and risk of lung cancer. Besides, a significantly positive association was found between coffee consumption and risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that a linear dose-response relationship exists between coffee consumption and risk of lung cancer, while the dose-response relationship is nonlinear between green tea consumption and risk of lung cancer.

Lentivirus-mediated shRNA interference targeting SLUG inhibits lung cancer growth and metastasis.

OBJECTIVE: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. METHODS: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. RESULTS: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. CONCLUSION: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.