Structural insights into the N-terminal APHB domain of HrpA: mediating canonical and i-motif recognition.

RNA helicases function as versatile enzymes primarily responsible for remodeling RNA secondary structures and organizing ribonucleoprotein complexes. In our study, we conducted a systematic analysis of the helicase-related activities of Escherichia coli HrpA and presented the structures of both its apo form and its complex bound with both conventional and non-canonical DNAs. Our findings reveal that HrpA exhibits NTP hydrolysis activity and binds to ssDNA and ssRNA in distinct sequence-dependent manners. While the helicase core plays an essential role in unwinding RNA/RNA and RNA/DNA duplexes, the N-terminal extension in HrpA, consisting of three helices referred to as the APHB domain, is crucial for ssDNA binding and RNA/DNA duplex unwinding. Importantly, the APHB domain is implicated in binding to non-canonical DNA structures such as G-quadruplex and i-motif, and this report presents the first solved i-motif-helicase complex. This research not only provides comprehensive insights into the multifaceted roles of HrpA as an RNA helicase but also establishes a foundation for further investigations into the recognition and functional implications of i-motif DNA structures in various biological processes.

Study on the evolution of dissolved organic matter in the underground storage of mine water.

The water-rock interactions significantly affect the dissolution and release of dissolved organic matter (DOM) during the reinjection of mine water into the underground reservoir. In this study, the surface characteristics and chemical composition of the natural medium from the open-pit coal mine were characterized. The waste consists mainly of quartz-dominated sandstone (43.64%) and mudstone dominated by sanidine (76.36%). During the 35-day experiment, two protein-like, one humus-like, and one fulvic acid-like substances were identified by PARAFAC. It was observed that the type of aqueous medium significantly affected the variational trend of DOM. Compared to the artificial medium, the fluorescence intensity of waste materials in the waste dump increased significantly during the reinjection process. Therefore, a positive correlation was observed between the fraction of mudstone in the aqueous medium and the DOM composition, mainly due to the dissolution of polycyclic aromatic hydrocarbon substances from the mudstone. The results revealed that the natural water storage medium had a certain water storage feasibility when compared with the expensive artificial medium. However, the fraction of mudstone in the water storage medium should be controlled to minimize the release of organic matter into the environment.

The uncovered biases and errors in clinical determination of bone age by using deep learning models.

OBJECTIVES: To evaluate AI biases and errors in estimating bone age (BA) by comparing AI and radiologists' clinical determinations of BA. METHODS: We established three deep learning models from a Chinese private dataset (CHNm), an American public dataset (USAm), and a joint dataset combining the above two datasets (JOIm). The test data CHNt (n = 1246) were labeled by ten senior pediatric radiologists. The effects of data site differences, interpretation bias, and interobserver variability on BA assessment were evaluated. The differences between the AI models' and radiologists' clinical determinations of BA (normal, advanced, and delayed BA groups by using the Brush data) were evaluated by the chi-square test and Kappa values. The heatmaps of CHNm-CHNt were generated by using Grad-CAM. RESULTS: We obtained an MAD value of 0.42 years on CHNm-CHNt; this result indicated an appropriate accuracy for the whole group but did not indicate an accurate estimation of individual BA because with a kappa value of 0.714, the agreement between AI and human clinical determinations of BA was significantly different. The features of the heatmaps were not fully consistent with the human vision on the X-ray films. Variable performance in BA estimation by different AI models and the disagreement between AI and radiologists' clinical determinations of BA may be caused by data biases, including patients' sex and age, institutions, and radiologists. CONCLUSIONS: The deep learning models outperform external validation in predicting BA on both internal and joint datasets. However, the biases and errors in the models' clinical determinations of child development should be carefully considered. KEY POINTS: • With a kappa value of 0.714, clinical determinations of bone age by using AI did not accord well with clinical determinations by radiologists. • Several biases, including patients' sex and age, institutions, and radiologists, may cause variable performance by AI bone age models and disagreement between AI and radiologists' clinical determinations of bone age. • AI heatmaps of bone age were not fully consistent with human vision on X-ray films.

Anemia in inflammatory bowel disease course is associated with patients' worse outcome.

BACKGROUND: Purpose: Anemia affects the life quality of inflammatory bowel disease (IBD) patients, but no report from Asian about anemia screening and its impact previously. We aimed to explore the prevalence and impact of anemia among the IBD patients in Taiwan. METHODS: A retrospective study was conducted from January 2006 to February 2018 at National Taiwan University Hospital. Clinical characteristics and outcomes were analyzed. RESULTS: A total of 1604 IBD patients were enrolled [494 Crohn's disease (CD) and 1110 ulcerative colitis (UC)]. Overall, 95.3% (471/494) of CD and 87.9% (976/1110) of UC patients underwent anemia screening. Anemia screening rate in IBD patients significantly increased from 62.6% (162/259) in 2006 to 77.2% (838/1086) in 2017. The mean time from IBD diagnosis to anemia screening was 122.4 days in CD patients and even longer in UC patients at 216.2 days. Persistent anemia was found in 47.3% (548/1158) of the screened patients. Risk factors of persistent anemia included low body mass index [odds ratio (OR) = 1.96, p < 0.01], steroid [OR = 2.96, p < 0.01], thiopurine [OR = 2.62, p < 0.01], colectomy [OR = 6.3, p < 0.01], and small bowel resection [OR = 3.21, p < 0.05)] after IBD diagnosis. Compared with those without anemia, anemic IBD patients had higher admission (p < 0.01) and mortality rates (p < 0.01). CONCLUSION: The anemia screening rate was acceptable and increased over time in Taiwan. Since anemia is associated with worse outcomes, earlier survey and treatment of anemia in IBD patients is recommended.

Clinical Outcomes of Metastatic Breast Cancer in Patients Having Imaging Liver Pseudocirrhosis with or without Evident Varices.

BACKGROUND: Pseudocirrhosis is an imaging finding of malignancies with liver metastasis with or without clinical liver cirrhosis-related portal hypertension (pHTN). This study defined evident pHTN by the presence of esophageal or gastric varices and compared patients' outcomes of metastatic breast cancer with imaging-diagnosed pseudocirrhosis with or without varices. METHODS: The medical records from patients with metastatic breast cancer and pseudocirrhosis between 2005 and 2017 were retrospectively analyzed. Survival outcomes were compared based on endoscopic evidence of esophageal or gastric varices. RESULTS: Among 106 patients with pseudocirrhosis, 33 (31%) had de novo stage IV disease, and 66 (62%) had hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Eighty-one (76%) had initial metastases in both hepatic lobes, and 32 (30%) had esophageal or gastric varices. The median overall survival (OS) was 5 and 13 months in patients with and without varices (P = .002). The median OS in patients with HER2-positive, HR-positive/HER2-negative, and triple-negative subtype was 16, 9, and 2 months, respectively (P = .001). Patients with varices usually had cirrhotic complications, including gastrointestinal bleeding, hyperbilirubinemia, hyperammonemia, and coagulopathy. Despite their challenging clinical conditions, 7 patients with varices had OS exceeding 1 year. In multivariate analysis, evident varices (P = .007) and triple-negative subtype (P = .013) were associated with poor OS. CONCLUSIONS: Patients with pseudocirrhosis and evident varices had a significantly shorter median OS, and were usually associated with clinical cirrhosis-related complications. To maximize OS, early identification and meticulous supportive care are warranted.

A Case Report of MODY3 Combined with Intestinal Neuroendocrine Tumor.

Maturity-onset diabetes of the young 3 (MODY3) is an autosomal dominant monogenic diabetes mellitus characterized by defective ß-cell function and non-insulin-dependent early-onset diabetes mellitus. The facts that patients with MODY3 are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive, make its diagnosis very challenging. In this study, we reported a case of MODY3, which was verified to be caused by a mutation in hepatocyte nuclear factor 1α gene (c.598C>T, p.Arg200Trp). In addition, the patient had a neuroendocrine tumor simultaneously, and a KMT2D gene mutation (c.5587C>G, p.Pro1863Ala) might be associated with this leson.

Catalyst-Free Vitrimer Cross-Linked by Biomass-Derived Compounds with Mechanical Robustness, Reprocessability, and Multishape Memory Effects.

Vitrimerization of thermoset polymers plays an important role in addressing resource recovery and reuse. Vitrimer elastomers with good mechanical properties often require well-designed crosslinking agents or fillers, but this increases processing complexity or reduces vitrimer dynamic properties. In this report, a simple green strategy to build a strong vitrimer elastomer is designed. Commercially available epoxidized natural rubber (ENR) is cross-linked with biomass-derived D-Fructose 1,6-bisphosphoric acid to get a vitrimer elastomer cross-linked by ß-hydroxy phosphate ester bonds and has abundant hydrogen bonds. Hydrogen bonds can preferentially break and dissipate energy under external forces, which makes the sample robust. The topological network can be reformed at high temperatures through the dynamic exchange of ß-hydroxy phosphate ester bonds, which gives the material malleability and recyclability. In addition, through the strategy of combining reprocessing and welding, multiple shape memory effects can be achieved in one postprocessing step. Considering that a variety of commercially available epoxy polymers are easily available, it is believed that this strategy can be a simple and versatile way to enable commercial epoxy polymers to achieve green crosslinking through biomass crosslink agents, which results in robust and recyclable vitrimers based on ß-hydroxy phosphate bonds.

Structural analysis reveals a "molecular calipers" mechanism for a LATERAL ORGAN BOUNDARIES DOMAIN transcription factor protein from wheat.

LATERAL ORGAN BOUNDARIES DOMAIN (LBD) proteins, a family of plant-specific transcription factors harboring a conserved Lateral Organ Boundaries (LOB) domain, are regulators of plant organ development. Recent studies have unraveled additional pivotal roles of the LBD protein family beyond defining lateral organ boundaries, such as pollen development and nitrogen metabolism. The structural basis for the molecular network of LBD-dependent processes remains to be deciphered. Here, we solved the first structure of the homodimeric LOB domain of Ramosa2 from wheat (TtRa2LD) to 1.9 Å resolution. Our crystal structure reveals structural features shared with other zinc-finger transcriptional factors, as well as some features unique to LBD proteins. Formation of the TtRa2LD homodimer relied on hydrophobic interactions of its coiled-coil motifs. Several specific motifs/domains of the LBD protein were also involved in maintaining its overall conformation. The intricate assembly within and between the monomers determined the precise spatial configuration of the two zinc fingers that recognize palindromic DNA sequences. Biochemical, molecular modeling, and small-angle X-ray scattering experiments indicated that dimerization is important for cooperative DNA binding and discrimination of palindromic DNA through a molecular calipers mechanism. Along with previously published data, this study enables us to establish an atomic-scale mechanistic model for LBD proteins as transcriptional regulators in plants.

From community-acquired pneumonia to COVID-19: a deep learning-based method for quantitative analysis of COVID-19 on thick-section CT scans.

OBJECTIVE: To develop a fully automated AI system to quantitatively assess the disease severity and disease progression of COVID-19 using thick-section chest CT images. METHODS: In this retrospective study, an AI system was developed to automatically segment and quantify the COVID-19-infected lung regions on thick-section chest CT images. Five hundred thirty-one CT scans from 204 COVID-19 patients were collected from one appointed COVID-19 hospital. The automatically segmented lung abnormalities were compared with manual segmentation of two experienced radiologists using the Dice coefficient on a randomly selected subset (30 CT scans). Two imaging biomarkers were automatically computed, i.e., the portion of infection (POI) and the average infection HU (iHU), to assess disease severity and disease progression. The assessments were compared with patient status of diagnosis reports and key phrases extracted from radiology reports using the area under the receiver operating characteristic curve (AUC) and Cohen's kappa, respectively. RESULTS: The dice coefficient between the segmentation of the AI system and two experienced radiologists for the COVID-19-infected lung abnormalities was 0.74 ± 0.28 and 0.76 ± 0.29, respectively, which were close to the inter-observer agreement (0.79 ± 0.25). The computed two imaging biomarkers can distinguish between the severe and non-severe stages with an AUC of 0.97 (p value < 0.001). Very good agreement (κ = 0.8220) between the AI system and the radiologists was achieved on evaluating the changes in infection volumes. CONCLUSIONS: A deep learning-based AI system built on the thick-section CT imaging can accurately quantify the COVID-19-associated lung abnormalities and assess the disease severity and its progressions. KEY POINTS: • A deep learning-based AI system was able to accurately segment the infected lung regions by COVID-19 using the thick-section CT scans (Dice coefficient ≥ 0.74). • The computed imaging biomarkers were able to distinguish between the non-severe and severe COVID-19 stages (area under the receiver operating characteristic curve 0.97). • The infection volume changes computed by the AI system were able to assess the COVID-19 progression (Cohen's kappa 0.8220).

A Noninvasive Sonographic Study of Multisite Atherosclerosis in an Elderly Chinese Population.

OBJECTIVES: A sonographic study was conducted to determine the prevalence of atherosclerosis across multiple arterial beds in an elderly Chinese population and to examine relationships between detected atherosclerosis and traditional risk factors. METHODS: A total of 197 participants underwent sonography of the abdominal aorta and bilateral carotid, femoral, and lower limb arteries. Images were reviewed to determine the presence or absence of plaques in each artery. Plaque thickness was measured as the indicator of plaque burden. Plaque prevalence was estimated per site and correlated with age, sex, and the Framingham Risk Score (FRS). Plaque frequency and thickness were compared between different arterial beds. RESULTS: Of the 197 participants (54% female; age range, 58-86 years), 90% had plaques present in at least 1 artery, and 55% had plaques present in at least 4 arteries. The most common sites for plaques were the carotid arteries (80%), followed by the lower limb arteries (59%), femoral arteries (57%), and abdominal aorta (37%). Plaque prevalence in each arterial bed except the abdominal aorta was significantly associated with male participants (P < .05), increasing age (P < .003) and FRS (P < .04). Male participants were more likely to have carotid (P = .04), femoral (P = .045), and lower limb (P = .006) plaques than female participants, but there was no significant difference in aortic plaque prevalence between male and female participants (P = .9). CONCLUSIONS: Plaque prevalence increased significantly in the carotid and peripheral arteries with increasing FRS. These findings should be considered for designing screening programs for stroke and heart attack prevention.

Identification of early atherosclerotic lesions in carotid arteries with quantitative characteristics measured by 3D MRI.

PURPOSE: To evaluate the usefulness of quantitative characteristics of morphology and signal intensity of arterial wall measured by 3D multicontrast magnetic resonance vessel wall imaging (MRVWI) in identification of carotid early atherosclerosis (CEAS). MATERIALS AND METHODS: In all, 61 older subjects (mean age 71.8 ± 5.6 years old; 25 males) without cardiovascular symptoms in the last 6 months were recruited. The carotid arteries without advanced plaque features on 3.0T MRI were included for analysis. Ultrasound imaging was used as a reference to identify CEAS. The morphological parameters including lumen area (LA), wall area (WA), wall thickness (WT), and normalized wall index (NWI = WA/[WA+LA] × 100%) and the signal intensity on 3.0T MR T2 -weighted images (T2 SI) of the carotid arterial wall were measured. Three regression models were built to identify CEAS with the following parameters: Model 1 with both morphological and T2 SI parameters; Model 2 with T2 SI parameters; and Model 3 with morphological parameters. All models were adjusted for age and sex. Area under the curve (AUC) was calculated to validate models. RESULTS: Of the 86 carotid arteries without advanced plaques, 47 (54.7%) were found to have early plaques determined by ultrasound. Among three regression models, Model 1 showed the highest AUC values in identifying CEAS (left: AUC = 0.856, P < 0.001; right: AUC = 0.867, P < 0.001), followed by Model 2 (left: AUC = 0.843, P < 0.001; right: AUC = 0.798, P = 0.001), and Model 3 (left: AUC = 0.790, P = 0.002; right: AUC = 0.806, P < 0.001). CONCLUSION: The combination of morphology and normalized T2 SI of arterial wall measured by MRVWI is more effective than each characteristic alone in identification of CEAS. J. Magn. Reson. Imaging 2016;44:1270-1276.

Chronological protein synthesis in regenerating rat liver.

Liver regeneration has been studied for decades; however, its regulation remains unclear. In this study, we report a dynamic tracing of protein synthesis in rat regenerating liver with a new proteomic technique, (35) S in vivo labeling analysis for dynamic proteomics (SiLAD). Conventional proteomic techniques typically measure protein alteration in accumulated amounts. The SiLAD technique specifically detects protein synthesis velocity instead of accumulated amounts of protein through (35) S pulse labeling of newly synthesized proteins, providing a direct way for analyzing protein synthesis variations. Consequently, protein synthesis within short as 30 min was visualized and protein regulations in the first 8 h of regenerating liver were dynamically traced. Further, the 3.5-5 h post partial hepatectomy (PHx) was shown to be an important regulatory turning point by acute regulation of many proteins in the initiation of liver regeneration.

miR-137 inhibits proliferation of melanoma cells by targeting PAK2.

MicroRNAs (miRNA) are key players in a variety of cancers including malignant melanoma. miR-137 has been reported to be a tumor suppressor in melanoma and several targets have been identified for this miRNA. We previously developed a novel proteomics technology, (35) S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD). Because of its high sensitivity in analysing protein expression rates, SiLAD has the potential to unravel miRNA effects on mRNAs coding for proteins with long half-lives or high abundance. Using SiLAD, we discovered that miR-137 significantly downregulated the expression rate of p21-activated kinase 2 (PAK2) in melanoma cells. Bioinformatics analysis predicted PAK2 as a direct target of miR-137, which was confirmed by luciferase reporter assay and Western blot analysis. We found that overexpression of miR-137 inhibited the proliferation of melanoma cells, which could be phenocopied by knockdown of PAK2 using siRNAs. Furthermore, overexpression of PAK2 restored miR-137-mediated suppression of cell proliferation. These findings indicate that miR-137 could inhibit proliferation through targeting PAK2 in melanoma cells.

S100A7 acts as a dual regulator in promoting proliferation and suppressing squamous differentiation through GATA-3/caspase-14 pathway in A431 cells.

S100A7 is expressed in many squamous cell carcinomas (SCCs), such as SCC of the skin, and well-differentiated SCC always displays stronger staining of this protein. A431 cells, an epidermal cancer cell line, were selected as a cell model to investigate the roles and mechanism of S100A7 in SCC of the skin. In this study, we demonstrated that the overexpression of S100A7 in A431 cells significantly promoted cell proliferation in vitro and tumor growth in vivo, whereas it suppressed the expression of GATA-3, caspase-14 and three squamous differentiation markers, keratin-1, TG-1 and involucrin. Conversely, the overexpression of caspase-14 not only significantly decreased cell proliferation and delayed tumor growth but also markedly induced the expression of three squamous differentiation markers, whereas S100A7 and GATA-3 were not influenced. Further evidence showed that silencing GATA-3 greatly inhibited the expression of caspase-14 and three differentiation markers, while the expression of S100A7 was not changed; contrary results were obtained when overexpressing GATA-3. Importantly, restoring the expression of GATA-3 and caspase-14 in A431-S100A7 cells could bypass the ability of S100A7 to increase cell viability and repress squamous differentiation. These data suggested that S100A7 expression in SCC may play an important role in the maintenance of SCC cell dedifferentiation, at least in SCC of the skin.

A highly sensitive "turn-on" fluorescent sensor for the detection of human serum proteins based on the size exclusion of the polyacrylamide gel.

A highly sensitive "turn-on" fluorescent sensor based on the size exclusion of the polyacrylamide gel was developed for the on-gels detection of human serum proteins after PAGE. The possible mechanism of this fluorescence sensor was illustrated and validated by utilizing five kinds of colloidal silver nanoparticles with different particle size distribution and six kinds of polyacrylamide gels with different pore size. It was attributed to that silver nanoparticles (<5 nm in diameter) had been selectively absorbed into the gel and formed the small silver nanoclusters, resulting in the red fluorescence. Using this new technique for the detection of human serum proteins after PAGE, a satisfactory sensitivity was achieved and some relatively low-abundance proteins (e.g. zinc-alpha-2-glycoprotein), which are the significant proteinic markers of certain diseases can be easily detected, but not with traditional methods. Furthermore, it was also successfully applied to distinguish between serums from hepatoma patient and healthy people. As a new protein detection technique, the colloidal silver nanoparticles based "turn-on" fluorescent sensor offers a rapid, economic, low background, and sensitive way for direct detection of human serum proteins, showing available potential and significance in the development of nanobiotechnology and proteome research.

An interpretable two-branch bi-coordinate network based on multi-grained domain knowledge for classification of thyroid nodules in ultrasound images.

Computer-aided diagnosis (CAD) for thyroid nodules has been studied for years, yet there are still reliability and interpretability challenges due to the lack of clinically-relevant evidence. To address this issue, inspired by Thyroid Imaging Reporting and Data System (TI-RADS), we propose a novel interpretable two-branch bi-coordinate network based on multi-grained domain knowledge. First, we transform the two types of domain knowledge provided by TI-RADS, namely region-based and boundary-based knowledge, into labels at multi-grained levels: coarse-grained classification labels, and fine-grained region segmentation masks and boundary localization vectors. We combine these two labels to form the Multi-grained Domain Knowledge Representation (MG-DKR) of TI-RADS. Then we design a Two-branch Bi-coordinate network (TB2C-net) which utilizes two branches to predict MG-DKR from both Cartesian and polar images, and uses an attention-based integration module to integrate the features of the two branches for benign-malignant classification. We validated our method on a large cohort containing 3245 patients (with 3558 nodules and 6466 ultrasound images). Results show that our method achieves competitive performance with AUC of 0.93 and ACC of 0.87 compared with other state-of-the-art methods. Ablation experiment results demonstrate the effectiveness of the TB2C-net and MG-DKR, and the knowledge attention map from the integration module provides the interpretability for benign-malignant classification.

The catalytic triad of rice NARROW LEAF1 involves H234.

NARROW LEAF1 (NAL1) exerts a multifaceted influence on leaf morphology and crop yield. Recent crystal study proposed that histidine 233 (H233) is part of the catalytic triad. Here we report that unlike suggested previously, H234 instead of H233 is a component of the catalytic triad alongside residues D291 and S385 in NAL1. Remarkably, residue 233 unexpectedly plays a pivotal role in regulating NAL1's proteolytic activity. These findings establish a strong foundation for utilizing NAL1 in breeding programs aimed at improving crop yield.

Environmental regulations and green innovation of enterprises: quasi-experimental evidence from China.

Whether environmental regulations are conducive to improving green innovation in water pollution-intensive enterprises (WPIEs) is of guiding significance for China's protection of the water ecosystem environment and sustainable economic development. This study regards the implementation of the "Ten-point Water Plan" (TWP) policy in 2015 as a purely exogenous event for enterprises and employs a quasi-experimental method to fill this gap based on the panel data of Chinese listed companies from 2010 to 2019. The results reveal that TWP policy has significant negative effects on the green innovation of WPIEs, the main mechanism of which is increased compliance costs. In addition, a heterogeneity analysis shows that the negative effect is stronger for green innovation activities with higher costs and for WPIEs subject to stricter environmental regulations. This paper provides new evidence against the weak Porter hypothesis and implies that WPIEs are likely to purchase technologies and equipment to reduce wastewater emissions rather than green innovation, which means incentive-based measures should be taken to foster green innovation in the environmental policymaking process.

Effects of metformin therapy on HMGB1 levels in rheumatoid arthritis patients.

OBJECTIVE: The traditional treatment of rheumatoid arthritis (RA) has some side effects. We aimed to explore the effect of metformin treatment on the expression of HMGB1, cytokines, T cell subtypes and the clinical outcomes in RA patients. METHODS: The present prospective cohort study recruited 124 RA patients (metformin group) who were treated with metformin and conventional therapy (methotrexate, hydroxychloroquine sulfate and sulfasalazine) and 98 RA patients (conventional therapy group) who were only treated with conventional therapy. All subjects were admitted from December 2018 to December 2021 and continuous medication for 90 days. The serum high mobility group box 1 (HMGB1), tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1ß and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometric were used to analyze the expression of CD4+ and CD8+. Demographic and clinical statistics including age, body mass index (BMI), sex, course of disease, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), visual analogue score (VAS)and disease activity score (DAS)-28 were collected. RESULTS: The serum levels of HMGB1, CRP, IL-6, CD4+ expression and CD4+/CD8+ ratio were significantly increased in patients with DAS-28 score ≥ 2.6. The serum HMGB1 and cytokines levels of metformin group declined more quickly during the study time. Pearson's analysis supported that a positive correlation existed between the HMGB1 and IL-6, TNF-α, CRP, CD4+, CD4+/CD8+ ratio, and VAS scores. HMGB1 could be a potential diagnostic biomarker for RA patients in active phase. Serum HMGB1 (95% CI 1.133-1.397, P < 0.001) was a factor associated with active RA. CONCLUSION: The serum HMGB1 levels were significantly increased in RA patients in active phase. The serum levels of HMGB1 and inflammatory factors and VAS scores were decreased gradually with metformin treatment. HMGB1 might act as a novel therapeutic target for RA.