[Evaluation methods of clinical efficacy of traditional Chinese medicine].

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

[Problems and thoughts in clinical safety evaluation of traditional Chinese medicine].

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Profiling of gene fusion involving targetable genes in Chinese gastric cancer.

BACKGROUND: Approximately half of all new cases of gastric cancer (GC) and related deaths occur in China. More than 80% of patients with GC are diagnosed at an advanced stage, which results in poor prognosis. Although HER2-directed therapy and immune checkpoint inhibitors have been somewhat successful, new drugs are still needed for the treatment of GC. Notably, several gene fusion-targeted drugs have been approved by the United States Food and Drug Administration for solid tumors, including GC, such as larotrectinib for NTRK fusion-positive cancers and zenocutuzumab for NRG1 fusion-positive cancers. However, gene fusions involving targetable genes have not been well characterized in Chinese patients with GC. AIM: To identify the profile of fusions involving targetable genes in Chinese patients with GC using clinical specimens and determine the distribution of patients with gene fusion variants among the molecular subtypes of GC. METHODS: We retrospectively analyzed gene fusion events in tumor tissue samples from 954 Chinese patients with GC. Clinicopathological characteristics were obtained from their medical records. Genetic alterations, such as single nucleotide variants, indels, amplifications, and gene fusions, were identified using a targeted sequencing panel containing 825 genes. Fusions were validated by fluorescence in situ hybridization (FISH) using break-apart probes. The microsatellite instability (MSI) status was evaluated using MSIsensor from the targeted sequencing panel data. Tumor mutational burden (TMB) was calculated using the total number of nonsynonymous mutations divided by the total genomic targeted region. Chi-square analysis was used to determine the enrichment of gene fusions associated with the molecular subtypes of GC. RESULTS: We found that 1.68% (16/954) of patients harbored 20 fusion events involving targetable genes. RARA fusions (n = 5) were the most common, followed by FGFR2, BRAF, MET, FGFR3, RET, ALK, EGFR, NTRK2, and NRG1 fusions. Two of the RARA fusions, EML4-ALK (E6:E20) and EGFR-SEPTIN14 (E7:E10), have been identified in other tumors but not in GC. Surprisingly, 18 gene fusion events were previously not reported in any cancer types. Twelve of the eighteen novel gene fusions included complete exons encoding functional domains of targetable genes, such as the tyrosine kinase domain of receptor tyrosine kinases and the DNA- and ligand-binding domains of RARA. Consistent with the results of detection using the targeted sequencing fusion panel, the results of FISH (fluorescence in situ hybridization) confirmed the rearrangement of FGFR2 and BRAF in tumors from patients 04 and 09, respectively. Genetic analysis indicated that the fusion genes were significantly enriched in patients with ERBB2 amplification (P = 0.02); however, there were no significant differences between fusion-positive and fusion-negative patients in age, sex, MSI status, and TMB. CONCLUSION: We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.

N klA Case Report on a IV-degree Thermal Crush Injury of Right Upper Arm: The Application of Functional Prosthesis Implantation Technology.

Severe IV-degree thermal crush injury of limbs involved the subcutaneous fascia, muscle and bone, which may lead to amputation and has a great impact on the patient's quality of life. We can repair wounds with pedicle flaps or even free flaps, However, there are still huge challenges in bone defect of extremities and functional reconstruction. In recent years, with the development of functional prostheses, we have reconstructed limb functions in many patients helping them to complete their daily lives. We report a case where the right upper arm was injured by thermal crush, leading severe burns to the skin, fascia, muscle and bone. We applied a pedicled latissimus dorsi flap and a free anterolateral thigh flap to repair the wound, and realized the function of limb salvage and movement of the right upper arm by implanting 3D printed scapula, upper arm, and elbow joint prostheses. This case illustrates that IV-degree burns involving bones have new technologies to repair and achieve mobility now.

Prognostic factors and survival outcome of primary pulmonary acinar cell carcinoma.

PURPOSE: The objective of our study was to investigate the epidemiologic characteristics and prognostic factors in patients with pulmonary acinar cell carcinoma (PACC). METHODS: PACC patients diagnosed between 1975 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The trend in PACC incidence was assessed using joinpoint regression software. Overall survival (OS) and disease-specific survival (DSS) were evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analysis was performed to identify the independent prognostic factors for OS and DSS. Nomograms to predict survival possibilities were constructed based on the identified independent prognostic factors. RESULTS: A total of 2918 patients were identified with PACC. The mean age was 65.2 ± 8.95 years with a female to male of 1.6:1. The incidence of PACC steadily increased by an annual percentage change (APC) of 3.2% (95% CI 2.1-4.4, p < 0.05). Multivariate Cox regression analysis revealed that age, gender, race, stage, grade, tumor size, number of positive lymph nodes, surgery, and chemotherapy were independent prognostic factors for survival. Nomograms specifically for PACC were constructed to predict 1- and 5-year OS and DSS possibility, respectively. The concordance index (C-index) and calibration plots showed the established nomograms had robust and accurate performance. CONCLUSION: PACC was rare but the incidence has been steadily increasing over the past four decades. Survival has improved in recent years. Surgery or chemotherapy could provide better OS and DSS. The established nomograms specifically for PACC were robust and accurate in predicting 1- and 5-year OS and DSS.

Comprehensive Characterization of Immune Landscape Based on Epithelial-Mesenchymal Transition Signature in OSCC: Implication for Prognosis and Immunotherapy.

Current anatomic TNM stage classification fails to capture the immune heterogeneity of oral squamous cell carcinoma (OSCC). Increasing evidence indicates the strong association between epithelial-mesenchymal transition (EMT) and tumor immune response. In this study, we employed an EMT signature to classify OSCC patients into epithelial- (E-) and mesenchymal- (M-) phenotypes using TCGA and GSE41613 transcriptome data. The ESTIMATE and CIRBERSORT analyses implied that the EMT signature genes originated from the stroma of the bulk tissue. The M-subtype tumors were characterized as "immune-hot" with more immune cell infiltration than the E-subtype ones. The low infiltration of active immune cells, the high infiltration of inactive immune cells, and the high expressions of immune checkpoints demonstrated an immunosuppressive characteristic of the M-subtype tumors. Moreover, we developed and validated a novel prognostic classifier based on the EMT score, the expressions of seven immune checkpoints, and the TNM stages, which could improve the prediction efficiency of the current clinical parameter. Together, our findings provide a better understanding of the tumor immune heterogeneity and may aid guiding immunotherapy in OSCC.

Single-ion anisotropy effects on the critical behaviors of quantum entanglement and correlation in the spin-1 Heisenberg chain.

Quantum entanglement and correlations in the spin-1 Heisenberg chain with single-ion anisotropy are investigated using the quantum renormalization group method. Negativity and quantum discord (QD) are calculated with various anisotropy parameters △ and single-ion anisotropy parametersD. We focus on the relations between two abovementioned physical quantities and on transitions between the Néel, Haldane, and large-Dphases. It is found that both negativity and QD exhibit step-like patterns in different phases as the size of the system increases. Interestingly, the single-ion anisotropy parameterD, which can be modulated using nuclear electric resonance (2020Nature579205), plays an important role in tuning the quantum phase transition (QPT) of the system. Both the first partial derivative of the negativity and QD with respect toDor △ exhibit nonanalytic behavior at the phase transition points, which corresponds directly to the divergence of the correlation length. The quantum correlation critical exponents derived from negativity and QD are equal, and are the reciprocal of the correlation length exponent at each critical point. This work extends the application of quantum entanglement and correlations as tools for depicting QPTs in spin-1 systems.

Downregulation of DNMT3a expression by RNAi and its effect on NF-κBs expression of thymic epithelial cells.

OBJECTIVE: To understand the characteristics of DNA methyltransferase 3a (DNMT3a) in thymoma associated Myasthenia Gravis reveal its transcriptional regulator network as while as analyze the effect of DNMT3a on Rel/ nuclear factor-kappaB family (RelA/RelB) and its downstream autoimmune regulatory factor (Aire). METHODS: Tissues of 30 patients with thymoma, with or without myasthenia gravis (MG), were collected and the DNMT3a protein expression were evaluated through immunohistochemistry. We performed mRNA expression profiling microarray detection and analysis, and integrated the analysis by constructing protein-protein interaction networks and the integration with other database. We identified molecular difference between low and high DNMT3a in the thymoma by heatmap. We also performed PCR validation in thymoma tissues. The DNMT3a-shRNA plasmid was transfected into TEC cells, and these cells were treated with 5-aza-2-deoxycytidine, a blocker of DNMT3a. After the down-regulation of DNMT3a in TEC cells, the transcript and protein levels of RelA, RelB, Aire, and CHRNA3 were evaluated by western blotting. In addition, changes in gene expression profiles were screened through microarray technology. We performed differential gene analysis in the thymoma cohort by heatmap with R (v.4.3.0) software. RESULTS: In 30 matched tissue specimens, the expression of DNMT3a protein in thymoma with MG was lower than that in thymoma. Through mRNA expression profiling analysis, we constructed a co-expression network of DNMT3a and found direct interaction between IKZF1 and DNMT3a, and this co-expression relationship was overlappted with Cistrome DB database. We found up-regulation of 149 mRNAs and repression of 177 mRNAs in thymoma with MG compared with thymoma. Gene ontology and pathway analysis show the involvement of a multitude of genes in the mis-regulation of MG-related pathways. RNA interference significantly reduced the level of mRNA of DNMT3a, which proved that plasmid DNMT3a was effective. In comparison to the control group, the levels of DNMT3a, Aire, and CHRNA3 mRNA and protein in TEC cells transfected with DNMT3a-shRNA interference plasmid were significantly decreased, while the expression level of RelA and RelA/RelB was significantly increased. CONCLUSIONS: Our study reveals the DNMT3a-NF-κB pathway has a major effect on MG, and can be used as a marker for diagnosis as well as a target for MG treatment.

Promoted "Click" SERS Detection for Precise Intracellular Imaging of Caspase-3.

Although homogeneous detection of some biomolecules has been of great significance in clinical assay, it faces great challenges in achieving precise in situ imaging of biomolecules. In addition, nonspecific adsorption between probes and biomolecules and low sensitivity are still unfathomed problems. Herein, we developed a promoted "Click" surface enhanced Raman scattering (SERS) strategy for realizing highly selective homogeneous detection of biomolecules by simultaneous dual enhanced SERS emissions, obtaining mutually confirmed logical judgment. Taking caspase-3 as one of the biotargets, we have realized highly selective homogeneous detection of caspase-3 using this strategy, and precise intracellular imaging of caspase-3 can be in situ monitored in living cells or during cell apoptosis. In detail, polyA-DNA and the Asp-Glu-Val-Asp (DEVD)-containing peptide sequence were modified into alkyne and nitrile-coded Au nanoparticles (NPs). During the cell apoptosis process, the generated caspase-3 would lead to the cleavage of the tetra-peptide sequence DEVD, thereby removing the negative protection part from the peptide on Au NPs. Interestingly, two different triple bond-labeled Au NPs can be connected together through DNA hybridization to form SERS "hotspot", resulting in simultaneously enlarged triple bond Raman signals. Moreover, we found that the SERS intensity was positively related with caspase-3 concentration, which has a wide linear range (0.1 ng/mL to 10 µg/mL) and low detection limit (7.18 × 10-2 ng/mL). Remarkably, these simultaneously enlarged signals by "Click" SERS could be used for more precise imaging of caspase-3, providing mutually confirmed logical judgment based on two spliced SERS emissions, especially for their relative intensity.

Prevalence and clinical characteristics of hospitalized children with community-acquired Mycoplasma pneumoniae pneumonia during 2017/2018, Chengde, China.

ABSTRACT: Community acquired-pneumonia (CAP) has varying causative pathogens and clinical characteristics. This study investigated the prevalence of Mycoplasma pneumoniae (M pneumoniae) and evaluated the clinical characteristics in infected hospitalized children by disease severity.From throat swabs of hospitalized children (5 months to 14 years) with CAP collected between November 2017 and May 2018, M pneumoniae and other CAP pathogens were identified using polymerase chain reaction (PCR). Differences in clinical and laboratory test data were compared between severe and mild case groups.Of 333 hospitalized children enrolled, 221/333 (66.4%) tested positive for M pneumoniae and 24/221 (10.9%) patients were (n = 9, aged <5 years vs n = 15, ≥5 years) single infection by PCR, however, only 170/333 (51.1%) patients were presented with M pneumoniae IgM-positive. M pneumoniae detection rate by PCR was higher than by immunoglobulin (IgM) serology. In 123/221 (55.7%) M pneumoniae infected patients, coinfection with bacterial pathogens (n = 61, <5 years vs n = 62, ≥5 years) occurred. Children (aged 3-8 years) had most M pneumoniae infection. Severe M pneumoniae pneumonia (MPP) in children occurred mostly in older age (7 [interquartile ranges {IQR}, 6-8] years; P < .0001), with longer cough days (14 [IQR, 10-19.5] days; P = .002) and hospitalization duration (9.5 [IQR, 7-12.3] days; P < .0001), lower lymphocyte ratio (24.1, [IQR, 20.0-31.1] %; P = .001), higher neutrophils ratio (66.0, [IQR, 60.2-70.3]%; P < .0001), and serum C-reactive protein (CRP) level (3.8, [IQR, 1.3-10.9] mg/L; P = .027).M pneumoniae is the most commonly detected pathogen in CAP. High coinfection prevalence increases diagnosis difficulty by clinically nonspecific characteristics. M pneumoniae detection by PCR with IgM may improve precise and reliable diagnosis of community-acquired MPP.

Global profiling of the alternative splicing landscape reveals transcriptomic diversity during the early phase of enterovirus 71 infection.

The alteration of host cell splicing is a major strategy favouring viral replication; however, the interaction between human tonsillar epithelial cells (HTECs) and enterovirus 71 (EV71) has not been fully elucidated. Here, a total of 201 differentially expressed genes (DEGs) and 3266 novel genes with coding potential were identified. A total of 3479 skipped exons (SEs), 515 alternative 3' splice sites (A3SSs), 391 alternative 5' splice sites (A5SSs), 531 mutually exclusive exons (MXEs) and 825 retained introns (RIs) were identified as significantly altered alternative splicing (AS) events. The enriched DEGs were mainly related to the cell cycle, spliceosome, and Toll-like receptor (TLR) signalling pathways. Finally, the replication of EV71 was significantly inhibited by TLR2 heterodimers. Our findings suggest that AS events induced by EV71 increase the transcriptomic diversity of HTECs in response to EV71 infection. Additionally, TLR2 heterodimers have the potential to protect HTECs against EV71.

Immune Landscape of the B7 and TNFR Families in Oral Squamous Cell Carcinoma.

OBJECTIVE: To understand the immune molecular landscapes of the two major costimulatory and coinhibitory pathways (B7 and TNFR families) in oral squamous cell carcinoma. METHODS: The B7 family members (CD80, CD86, CD274, ICOSLG, CD276, VTCN1, NCR3LG1, HHLA2 and PDCD1LG2) and TNFR family members (TNFSF4, CD40, CD70, TNFSF9, TNFRSF14 and TNFSF18) were used to analyse the costimulatory and coinhibitory pathway alterations in oral squamous cell carcinoma. The online tools UCSC Xena and cBioPortal were used to derive oral squamous cell carcinoma patients' clinical parameters, mRNA levels, mutations, DNA copy number alterations and methylation levels. The correlations between mRNA levels and methylation levels were determined using Spearman's correlation analysis. A Kaplan-Meier survival analysis was performed to examine the relationships between mRNA expression levels and overall survival. RESULTS: Compared with normal oral epithelial tissues, approximately 23.1% of patients showed upregulation of B7 expression and 15.3% showed upregulation of TNFR expression in oral squamous cell carcinoma, with CD274 (PD-L1) upregulation being the most common alteration. Mutations and copy number alterations were shown to have little effect on B7 and TNFR expression. The mRNA levels of B7 and TNFR genes were negatively correlated with their methylation levels. Furthermore, oral squamous cell carcinoma patients with high expression levels of CD274 showed poor overall survival, while those with high expression levels of CD276 or HHLA2 showed good clinical outcomes. CONCLUSION: This study elucidated the molecular landscapes of the B7 and TNFR genes in oral squamous cell carcinoma, which could provide a novel strategy for clinical therapy.

FSCN1 is an effective marker of poor prognosis and a potential therapeutic target in human tongue squamous cell carcinoma.

To estimate the value of FSCN1 in evaluating the prognosis and guiding the targeted therapy for patients with tongue squamous cell carcinoma (TSCC). Using the Oncomine database, we found some genes especially FSCN1 differentially expressed between TSCC samples and tongue normal samples. So we compared FSCN1 expression between TSCC and normal cell lines and knocked down FSCN1 in TSCC cells to observe its influence on the viability and trans-migration in vitro and tumor growth in vivo. Then we measured FSCN1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between FSCN1 expression and clinical pathological factors and prognosis in TSCC patients. We found that FSCN1 is expressed higher in TSCC cells than in normal cells. Knockdown of FSCN1 reduced TSCC cell viability and trans-migration in vitro and impaired tumor growth in vivo. FSCN1 also expressed higher in human TSCC than in ANT. In addition, FSCN1 expression was related to N classification, clinical stage and relapse. TSCC patients with over-expression of FSCN1 had worse prognosis. In conclusion, over-expression of FSCN1 indicates worse prognosis for patients with TSCC and FSCN1 may be a potential prognostic biomarker and therapeutic target in TSCC.

Alteration in gene expression profiles of thymoma: Genetic differences and potential novel targets.

BACKGROUND: This study was conducted to investigate the gene expression profiles associated with thymoma to better understand the molecular mechanism underlying the pathogenesis of thymoma. METHODS: Eight patients with thymomas (type A, AB, B1, and B2) and four controls with thymic cysts were analyzed using microarray profiling to identify changes in gene expression. RESULTS: Across all of our samples, 2319 messenger RNAs were upregulated and 2776 were downregulated in thymomas relative to thymic cysts. Gene ontology and pathway analyses revealed that a large number of genes participate in cellular functions, among which MHC class II protein complex assembly, assembly with peptide antigen, calcium activated phosphatidylcholine scrambling, and release of cytoplasmic sequestered NF-κB were dysregulated, whereas intestinal immune network for immunoglobulin A production, cytokine-cytokine receptor interaction, the calcium signaling pathway, and pathways related to autoimmune diseases were downregulated. CONCLUSIONS: Our results revealed gene expression differences between thymomas and thymic cysts, and identified key candidate genes/pathways that might be used as diagnostic markers and potential therapeutic targets to treat cancer metastasis.

LC-MS/MS determination of ginsenoside compound K and its metabolite 20 (S)-protopanaxadiol in human plasma and urine: applications in a clinical study.

AIM: Ginsenoside compound K (CK) is considered to be a potential therapeutic drug for rheumatoid arthritis because of its good anti-inflammatory activity. The purpose of this work was to establish a rapid, sensitive and specific method for determination of CK and its active metabolite 20(S)-protopanaxadiol (20(S)-PPD). Materials & methods: The analytes and internal standards were extracted by liquid-liquid extraction. Then, were separated by high performance liquid phase and determined by triple quadrupole mass spectrometry. RESULTS: A LC-MS/MS using liquid-liquid extraction was developed for determining CK over the concentration range 1.00-1002.00 ng/ml and 0.15-54.30 ng/ml for 20(S)-PPD. The lower limits of quantification for CK and 20(S)-PPD were 1.00 and 0.15 ng/ml, respectively. CONCLUSION: This method was successfully validated for detecting both CK and 20(S)-PPD in the human plasma and urine, and was proved to be suitable for the pharmacokinetic study of CK in healthy Chinese volunteers. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-14004824.

L-shaped corticotomy with bone flap sliding in the management of chronic tibial osteomyelitis: surgical technique and clinical results.

BACKGROUND: We described the use of the technique of L-shaped corticotomy with bone flap sliding to treat chronic osteomyelitis of the tibia in eight patients and presented the preliminary results. METHODS: L-shaped corticotomy with bone flap sliding was performed in eight patients between 2007 and 2014. All patients had chronic tibial osteomyelitis involving the anterior tibial cortex with intact and healthy posterior cortex. The size of bone defects following sequestrectomy and radical debridement was 8.1 cm on average. One patient required a latissimus dorsi flap. The mean follow-up period was 34.1 months. The functional and bone results were evaluated at the time of the latest follow-up. RESULTS: Complete eradication of infection and union of docking sites were achieved in all patients. Functional results were judged excellent in five patients and good in the rest three patients. Bone results were graded as excellent in all cases. The mean external fixation time was 169.9 days and external fixation index was 21.2 days/cm. Pain was the most common complaint that we faced during lengthening. Pin tract infections were observed in four patients, and mild transient stiffness of ankle joint was observed in three patients. CONCLUSIONS: We have found this technique to be safe and effective, significantly diminishing the external fixation index. The earlier removal of the external fixator may result in increased patient comfort, a reduced complication rate, and a rapid and convenient rehabilitation.

Alteration in gene expression profile of thymomas with or without myasthenia gravis linked with the nuclear factor-kappaB/autoimmune regulator pathway to myasthenia gravis pathogenesis.

BACKGROUND: To investigate the gene expression profile of a set of candidate genes for a better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without myasthenia gravis. METHODS: Thymoma patients and thymoma patients with myasthenia gravis were analyzed using microarray profiling to identify significant changes in gene expression of autoimmune regulator pathway genes including AIRE, IL-7R, CHRNA3, SYMD1, THRA, and CAV3. RESULTS: Across all of our samples, we found that 1484 mRNAs were upregulated and 770 were downregulated in thymoma patients compared with thymoma with myasthenia gravis patients. Gene ontology and pathway analysis revealed that a large number of genes participated in cellular functions for humoral immune response, sequence-specific DNA binding RNA polymerase II transcription factor activity, positive regulation of gene expression, regulation of neuron projection development, extracellular ligand-gated ion channel activity, positive regulation of striated muscle cell differentiation, and regulation of nuclear factor-kappaB import into the nucleus. CONCLUSION: Our results revealed genetic differences between thymomas and myasthenia gravis, and identified the key candidate genes/pathways for molecular mechanism.

Relationship between polymorphisms of the lipid metabolism-related gene PLA2G16 and risk of colorectal cancer in the Chinese population.

This study aimed to investigate the relationship between polymorphisms in the lipid metabolism-related gene PLA2G16 encoding Group XVI phospholipase A2 and the risk of colorectal cancer (CRC) in the Chinese population. A total of 185 patients with CRC and 313 healthy controls were enrolled. Thirteen single nucleotide polymorphisms (SNPs) of PLA2G16 were genotyped with SNPscan™. Linkage disequilibrium and haplotypes were analysed using Haploview software. Multivariate logistic regression was used to determine the association between the various genotypes and CRC risk. We identified five PLA2G16 SNPs (rs11600655, rs3809072, rs3809073, rs640908 and rs66475048) that were associated with CRC risk after adjusting for age, sex and body mass index. Two haplotypes (CTC and GGA) of rs11600655, rs3809073 and rs3809072, were relevant to CRC risk. The rs11600655 polymorphism was also associated with lymph node metastasis and CRC staging, while rs3809073 and rs3809072 may affect transcriptional regulation of PLA2G16 by altering transcription factor binding. These findings suggest that PLA2G16 polymorphisms-especially CTC and GGA haplotypes-increase CRC susceptibility. Importantly, we showed that the rs11600655 CC, rs640908 CT and rs66475048 GA genotypes are independent risk factors for CRC in the Chinese population.

Recombined humanized endostatin-induced suppression of HMGB1 expression inhibits proliferation of NSCLC cancer cells.

BACKGROUND: Recombined humanized endostatin (Rh-endostatin) exhibits a potent anti-cancer effect involving multiple molecular targets and signaling pathways. HMGB1 is a highly conserved DNA-binding protein involved in cancer development. The therapeutic effect of Rh-endostatin on HMGB1 has not been reported, thus we investigate the effect in non-small cell lung cancer (NSCLC) cells. METHODS: Quantitative real-time PCR and Western blot were used to analyze the messenger RNA and protein expression of HMGB1 in A549 cancer cells, while enzyme-linked immunosorbent assay was used to detect the release of HMGB1. Western blot was performed to evaluate HMGB1 expression in SK-MES-1 and H661 NSCLC cells. RESULTS: Rh-endostatin inhibited the proliferation of A549 cancer cells and distinctly downregulated the expression and release of HMGB1 in dose and time dependent manners. Rh-endostatin-induced HMGB1 downregulation was confirmed in different types of NSCLC cells. CONCLUSION: These results demonstrate the general phenomenon that Rh-endostatin can induce HMGB1 suppression in a variety of NSCLC cells. Rh-endostatin may suppress HMGB1 expression and release in A549 cancer cells, thus inhibiting cell proliferation.