Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Surveying biomedical relation extraction: a critical examination of current datasets and the proposal of a new resource.

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein-protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD's compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models' performances on the PEDD. This paper's outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases.

Regulatory effects of mangiferin on LPS-induced inflammatory responses and intestinal flora imbalance during sepsis.

Studies suggest that mangiferin (MAF) has good therapeutic effects on chronic bronchitis and hepatitis. Also, it is one of the antiviral ingredients in Anemarrhena asphodeloides Bunge. However, its effect on the LPS-induced inflammation and intestinal flora during sepsis remains unclear yet. In the present study, LPS-stimulated inflammation RAW264.7 cells and LPS-induced sepsis mice were used to evaluate the efficacy of MAF in vitro and in vivo. 16S rDNA sequencing was performed to analyze the characteristics of intestinal flora of the sepsis mice. It has been demonstrated that MAF (12.5 and 25 µg/mL) significantly inhibited protein expressions of TLR4, MyD88, NF-κB, and TNF-α in the LPS-treated cells and reduced the supernatant TNF-α and IL-6 levels. In vivo, MAF (20 mg/kg) markedly protected the sepsis mice and reduced the serum TNF-α and IL-6 levels. Also, MAF significantly downregulated the protein expressions of TLR4, NF-κB, and MyD88 in the livers. Importantly, MAF significantly attenuated the pathological injuries of the livers and small intestines. Further, MAF significantly increased proportion of Bacteroidota and decreased the proportions of Firmicutes, Desulfobacterota, Actinobacteriota, and Proteobacteria at phylum level, and it markedly reduced the proportions of Escherichia-Shigella, Pseudoalteromonas, Staphylococcus at genus level. Moreover, MAF affects some metabolism-related pathways such as citrate cycle (TCA cycle), lipoic acid metabolism, oxidative phosphorylation, bacterial chemotaxis, fatty acid biosynthesis, and peptidoglycan biosynthesis of the intestinal flora. Thus, it can be concluded that MAF as a treatment reduces the inflammatory responses in vitro and in vivo by inhibiting the TLR4/ MyD88/NF-κB pathway, and corrects intestinal flora imbalance during sepsis to some degree.

Effect of hypoglycemia on cognitive performance in older patients with diabetes: A meta-analysis.

GOALS: The goal of this study was to use meta-analysis to compile information from various studies to investigate the existence and severity of cognitive impairment in elderly diabetes patients who have hypoglycemic episodes. MATERIALS AND TECHNIQUES: For research studies on the relationship between hypoglycemia and cognitive decline or dementia in persons older than 45 years, we searched the PubMed, EMBASE, Cochrane Library, CNKI, WanFang, CBM and VIP databases for the period 1989 to 2022. We conducted random effects inverse variance on the meta-analysis and used the I2 statistic to assess heterogeneity. RESULT: We selected 44 of the 518 studies we retrieved, 7 being appropriate for meta-analysis. Six thousand and forty-five individuals were involved in total. Both types of older diabetic patients with hypoglycemia performed considerably worse on tests of general intelligence than control participants (standardized mean difference, 0.58; 95% CI, 0.88-0.28). Also, elderly type-2 diabetes patients with hypoglycemic episodes had significantly worse memory performance (standardized mean difference, 0.19; 95% CI, 0.29-0.09). Additionally, we found that older type-2 diabetes patients with hypoglycemia had significantly poorer psychomotor function than those without hypoglycemia (standardized mean difference, 0.51; 95% CI, 0.38-0.63).

Self-Organization of Nonlinearly Coupled Neural Fluctuations Into Synergistic Population Codes.

Neural activity in the brain exhibits correlated fluctuations that may strongly influence the properties of neural population coding. However, how such correlated neural fluctuations may arise from the intrinsic neural circuit dynamics and subsequently affect the computational properties of neural population activity remains poorly understood. The main difficulty lies in resolving the nonlinear coupling between correlated fluctuations with the overall dynamics of the system. In this study, we investigate the emergence of synergistic neural population codes from the intrinsic dynamics of correlated neural fluctuations in a neural circuit model capturing realistic nonlinear noise coupling of spiking neurons. We show that a rich repertoire of spatial correlation patterns naturally emerges in a bump attractor network and further reveals the dynamical regime under which the interplay between differential and noise correlations leads to synergistic codes. Moreover, we find that negative correlations may induce stable bound states between two bumps, a phenomenon previously unobserved in firing rate models. These noise-induced effects of bump attractors lead to a number of computational advantages including enhanced working memory capacity and efficient spatiotemporal multiplexing and can account for a range of cognitive and behavioral phenomena related to working memory. This study offers a dynamical approach to investigating realistic correlated neural fluctuations and insights to their roles in cortical computations.

Diagnosis and Treatment of Rare Adult Embryonal Rhabdomyosarcoma in Maxillary Sinus.

OBJECTIVE: To investigate the clinicopathological features, imaging features, diagnosis, and prognosis of embryonal rhabdomyosarcoma (ERMS) in the maxillary sinus. METHODS: The detailed clinical data of rare patients with embryonal ERMS of maxillary sinus admitted to our hospital were retrospectively analyzed, and the embryonal ERMS was confirmed by pathological examination and immunohistochemistry, and the relevant literature was reviewed. RESULTS: A 58-year-old man was admitted to the hospital with the chief complaint of "numbness and swelling of the left cheek for 1 and a half months". Blood routine, biochemistry, paranasal sinus computed tomography, and magnetic resonance imaging were performed after admission, and the pathology showed ERMS. At present, it is generally in good condition. Pathological examination showed that the cells were all small and round. Immunohistochemistry showed Desmin (+) and Ki-67 (+70%). CONCLUSION: The early symptoms of ERMS of the maxillary sinus are atypical and diverse, with a high degree of malignancy, rapid progression, strong invasiveness, and poor prognosis. Early diagnosis and treatment should be based on clinical characteristics, imaging examination, and immunohistochemical results.

Active post-transcriptional regulation and ACLY-mediated acetyl-CoA synthesis as a pivotal target of Shuang-Huang-Sheng-Bai formula for lung adenocarcinoma treatment.

BACKGROUND: New therapeutic approaches are required to improve the outcomes of lung cancer (LC), a leading cause of cancer-related deaths worldwide. Chinese herbal medicine formulae widely used in China provide a unique opportunity for improving LC treatment, and the Shuang-Huang-Sheng-Bai (SHSB) formula is a typical example. However, the underlying mechanisms of action remains unclear. PURPOSE: This study aimed to confirm the efficacy of SHSB against lung adenocarcinoma (LUAD), which is a major histological type of LC, unveil the downstream targets of this formula, and assess the clinical relevance and biological roles of the newly identified target. METHODS: An experimental metastasis mouse model and a subcutaneous xenograft mouse model were used to evaluate the anti-cancer activity of SHSB. Multi-omics profiling of subcutaneous tumors and metabolomic profiling of sera were performed to identify downstream targets, especially the metabolic targets of SHSB. A clinical trial was conducted to verify the newly identified metabolic targets in patients. Next, the metabolites and enzymes engaged in the metabolic pathway targeted by SHSB were measured in clinical samples. Finally, routine molecular experiments were performed to decipher the biological functions of the metabolic pathways targeted by SHSB. RESULTS: Oral SHSB administration showed overt anti-LUAD efficacy as revealed by the extended overall survival of the metastasis model and impaired growth of implanted tumors in the subcutaneous xenograft model. Mechanistically, SHSB administration altered protein expression in the post-transcriptional layer and modified the metabolome of LUAD xenografts. Integrative analysis demonstrated that SHSB markedly inhibited acetyl-CoA synthesis in tumors by post-transcriptionally downregulating ATP-citrate lyase (ACLY). Consistently, our clinical trial showed that oral SHSB administration declined serum acetyl-CoA levels of patients with LC. Moreover, acetyl-CoA synthesis and ACLY expression were both augmented in clinical LUAD tissues of patients, and high intratumoral ACLY expression predicted a detrimental prognosis. Finally, we showed that ACLY-mediated acetyl-CoA synthesis is essential for LUAD cell growth by promoting G1/S transition and DNA replication. CONCLUSION: Limited downstream targets of SHSB for LC treatment have been reported in previous hypothesis-driven studies. In this study, we conducted a comprehensive multi-omics investigation and demonstrated that SHSB exerted its anti-LUAD efficacy by actively and post-transcriptionally modulating protein expression and particularly restraining ACLY-mediated acetyl-CoA synthesis.

Relationship between Preoperative Hemoglobin and Hospital Stays in Patients Receiving Prime Total Knee Arthroplasty.

Previous evidence has shown that preoperative hemoglobin is related to poor prognosis after primary total knee arthroplasty. Reviewing cohort research was conducted at the third-level academic medical center in Singapore and involved 2,676 patients. Population statistics, complications, preoperative hemoglobin (Hb) levels, length of hospital stay (LOS), and readmission information of thirty days were obtained. Anemia was defined based on the World Health Organization (WHO). LOS extension was with the definition as no less than six days with >1/75 LOS corresponding to the data. According to the study requirements, we finally collected 2273 patients. We plotted the relationship between hemoglobin levels and length of stay. We analyzed 2273 patients, with 140 cases of Hb ≤ 11.0 g/dL, 831 cases of Hb 11.0-12.9 g/dL, and the other 1320 cases of Hb ≥ 13.0 g/dL. The mean age of patients with prolonged LOS (68.4 ± 8.2 years) was higher than that of patients with familiar LOS (65.9 ± 8.0 years). In addition, patients with extended LOS had higher ASA-PS values, a history of cerebrovascular accidents (CVA), diabetes mellitus (DM), and ischemic heart disease (IHD) (P < 0.001), repeated surgery within 30 days, HB, and operative time (min) (P < 0.01). Variables independently related to increased risk of extended LOS included general anesthesia (GA) (adjusted OR (aOR) 1.4, P=0.005, P=0.005), CVA (aOR 3.0, P < 0.001), DM (aOR 1.4, P=0.032), and HB < 11 g/dL. Variables increased LOS included HB ≥ 13 g/dL (aOR 0.4, P < 0.001) and Hb 11.0-12.9 g/dL (aOR 0.5, P=0.001). Hb was 14 g/dL, and LOS decreased by at least 0.24 days for each 1 g increase in preoperative Hb before the inflection point (95%CI 0.12 to 0.36, P=0.0001). Anemia is familiar in patients receiving elective total knee arthroplasty (TKA) in Singapore. Thus, this study describes that the preoperative hemoglobin was associated with length of stay. We found that on the left where HB was 14, length of stay decreased with increased hemoglobin values. We recommend preoperative correction of anemia to determine the diagnosis.

A BERT-based ensemble learning approach for the BioCreative VII challenges: full-text chemical identification and multi-label classification in PubMed articles.

In this research, we explored various state-of-the-art biomedical-specific pre-trained Bidirectional Encoder Representations from Transformers (BERT) models for the National Library of Medicine - Chemistry (NLM CHEM) and LitCovid tracks in the BioCreative VII Challenge, and propose a BERT-based ensemble learning approach to integrate the advantages of various models to improve the system's performance. The experimental results of the NLM-CHEM track demonstrate that our method can achieve remarkable performance, with F1-scores of 85% and 91.8% in strict and approximate evaluations, respectively. Moreover, the proposed Medical Subject Headings identifier (MeSH ID) normalization algorithm is effective in entity normalization, which achieved a F1-score of about 80% in both strict and approximate evaluations. For the LitCovid track, the proposed method is also effective in detecting topics in the Coronavirus disease 2019 (COVID-19) literature, which outperformed the compared methods and achieve state-of-the-art performance in the LitCovid corpus. Database URL: https://www.ncbi.nlm.nih.gov/research/coronavirus/.

Erratum: Overexpression of lncRNA H19/miR-675 promotes tumorigenesis in head and neck squamous cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/ijms.16571.].

LIMD2 promotes tumor proliferation, invasion, and epithelial-mesenchymal transition in clear cell renal cell carcinoma.

LIMD2 was found upregulated in various tumors and metastatic samples and associated with a poor prognosis. But the role of LIMD2 in clear cell renal cell carcinoma (ccRCC) remains elusive. The expression of LIMD2 in ccRCC was analyzed using cohort data downloaded from TCGA and ICGC databases. In vitro and in vivo experiments were then conducted to study the biological role of LIMD2 in ccRCC and explore the possible mechanism. The results indicated that LIMD2 was overexpressed and correlated with a poor outcome in ccRCC. LIMD2 promoted the malignancy of ccRCC both in vitro and in vivo. LIMD2 induced epithelial-mesenchymal transition (EMT) via activating the ILK/Akt pathway in ccRCC. In conclusion, LIMD2 is overexpressed and promotes proliferation, invasion, and EMT in ccRCC, which may serve as a potential novel therapeutic target for ccRCC.

New Metabolic Alterations and A Predictive Marker Pipecolic Acid in Sera for Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with a poor prognosis. Although several serum metabolomic investigations have been reported, ESCC tumor-associated metabolic alterations and predictive biomarkers in sera have not been defined. Here, we enrolled 34 treatment-naive patients with ESCC and collected their pre- and post-esophagectomy sera together with the sera from 34 healthy volunteers for a metabolomic survey. Our comprehensive analysis identified ESCC tumor-associated metabolic alterations as represented by a panel of 12 serum metabolites. Notably, postoperative abrosia and parenteral nutrition substantially perturbed the serum metabolome. Furthermore, we performed an examination using sera from carcinogen-induced mice at the dysplasia and ESCC stages and identified three ESCC tumor-associated metabolites conserved between mice and humans. Notably, among these metabolites, the level of pipecolic acid was observed to be progressively increased in mouse sera from dysplasia to cancerization, and it could be used to accurately discriminate between mice at the dysplasia stage and healthy control mice. Furthermore, this metabolite is essential for ESCC cells to restrain oxidative stress-induced DNA damage and cell proliferation arrest. Together, this study revealed a panel of 12 ESCC tumor-associated serum metabolites with potential for monitoring therapeutic efficacy and disease relapse, presented evidence for refining parenteral nutrition composition, and highlighted serum pipecolic acid as an attractive biomarker for predicting ESCC tumorigenesis.

Sediment formation and analysis of the main chemical components of aqueous extracts from different parts of ginseng roots.

Sediment is a key issue in the production and marketing of plant beverages, as is ginseng beverages. The formation of sediment in ginseng beverages is a gradual process. This work describes the formation of sediment from different parts of ginseng and describes the color and clarity of the liquid and the amount and morphology of the sediment. The results showed there are significant differences in the sediment formation speed, morphology and transmittance for the aqueous extracts prepared from different parts of ginseng. The amounts of sediment generated from the different parts of ginseng is as follows: main root > rhizome > fibrous root. Free amino acids, Ba, Ca, Ni, and Sr concentrations are significantly and positively correlated with the transmittance. The total saponins, Al, Fe, and Mn concentrations are significantly and negatively correlated with the transmittance. There are obvious crystals and more Ca in the fibrous root sediment. We analyzed and compared the chemical components in the sediment and extract. The results show that the main components of the sediment are carbohydrates and protein. According to the partition coefficient the contents of protein, ginsenosides (Rb1, Rb2, Rb3, Rf) and some ions (Al, Fe, Ca, and Na) contribute more to the formation of the sediment than the other investigated components.

Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study.

Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.

PIK3CA mutation affects the proliferation of colorectal cancer cells through the PI3K-MEK/PDK1-GPT2 pathway.

The phosphatidylinositol­3­kinase catalytic subunit α (PIK3CA) gene is mutated in numerous human cancers. This mutation promotes the proliferation of tumor cells; however, the underlying mechanism is still not clear. In the present study, it was revealed that the PIK3CA mutation in colorectal cancer (CRC) HCT116 (MUT) rendered the cells more dependent on glutamine by regulating the glutamic­pyruvate transaminase 2 (GPT2). The dependence of glutamine increased the proliferation of cells in a normal environment and resistance to a suboptimal environment. Further study revealed that the mutated PIK3CA could regulate GPT2 expression not only through signal transduction molecule 3­phosphoinositide­dependent kinase (PDK1) but also through mitogen­activated protein kinase (MEK) molecules. In HCT116 cells, MEK inhibitor treatment could reduce the expression of GPT2 signaling molecules, thereby inhibiting the proliferation of CRC cells. A new signal transduction pathway, the PI3K/MEK/GPT2 pathway was identified. Based on these findings, MEK and PDK1 inhibitors were combined to inhibit the aforementioned pathway. It was revealed that the combined application of MEK and PDK1 inhibitors could promisingly inhibit the proliferation of MUT compared with the application of PI3K inhibitors, PDK1 inhibitors, or MEK inhibitors alone. In vivo, MEK inhibitors alone and combined inhibitors had stronger tumor­suppressing effects. There was no significant difference between the PDK1­inhibitor group and normal group in vivo. Thus, these results indicated that mutated PI3K affected GPT2 mediated by the MEK/PDK1 dual pathway, and that the PI3K/MEK/GPT2 pathway was more important in vivo. Inhibiting MEK and PDK1 concurrently could effectively inhibit the proliferation of CRC cells. Targeting the MEK and PDK1 signaling pathway may provide a novel strategy for the treatment of PIK3CA­mutated CRC.

Design and discovery of C2-fluoroalkyl iminothiazine dioxides as BACE inhibitors.

This paper describes the structure-activity-relationships of novel fluoroalkyl substituents at the C2 position of iminothiazine dioxide beta secretase inhibitors. Key discoveries include reduced amidine basicity and its effect on Pgp, cell potency, and efficacy in various preclinical in vivo efficacy animal models. Findings from these structure-activity-relationships are discussed.

Comprehensive analysis of the correlation between GSTM1 and tumor immunity in colon cancer.

Background: Glutathione S-transferase mu 1 (GSTM1) is one of the major glutathione conjugation enzymes. Its expression and activity have been suggested to correlate with the occurrence of colon cancer; however, the role of GSTM1 in tumor immunity remains unclear. Methods: Relevant data downloaded from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) was used to perform a multi-dimensional expression analysis of GSTM1 in colon adenocarcinoma (COAD). The correlation between GSTM1 and tumor immunity was analyzed with multiple online tools. Then protein-protein interaction (PPI) network and functional enrichment analyses of GSTM1-associated immunomodulators were performed. Further, we developed the Cox regression model based on the GSTM1-related immunomodulators. Finally, a GSTM1-based clinical nomogram and a calibration curve was established to predict the probability and accuracy of long-term survival. Result: GSTM1 was significantly downregulated in COAD versus normal tissues. Infiltration levels of B cells, CD8+ T cells, and dendritic cells were closely correlated to GSTM1 gene copy number deletion, and GSTM1 expression levels in COAD positively correlated with dendritic cell, B cell, neutrophil, and macrophage infiltration. Functional enrichment analysis indicated 36 GSTM1-related immunomodulators are involved in immune-related pathways of regulating T cell activation and lymphocytic activation. A 2-gene prognostic risk signature based on the 36 GSTM1-related immunomodulators was built using the Cox regression model, and the risk signature in combination with stage had an area under the curve (AUC) value of 0.747 by the receiver operating characteristic method. patients with higher risk scores-calculated based on 2 gene prognostic risk characteristics and further identified as an independent prognostic factor-were associated with worse survival using the Kaplan-Meier analysis. Together, the clinical nomogram and calibration curve based on GSTM1 suggested a good prediction accuracy for long-term survival probability. Conclusions: Our study provided evidence supporting the significant role of GSTM1 in COAD immunity and suggests GSTM1 as a potential novel target for COAD immunotherapy.

Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage.@*METHODS@#A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1β, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05).@*CONCLUSION@#Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.