Synthesis of novel 4-substituted isatin Schiff base derivatives as potential autophagy inducers and evaluation of their antitumour activity.

Induction of autophagic death in cancer cells is one of the promising strategies for the development of anti-cancer therapeutics. In the present study, we designed and synthesized a series of isatin Schiff base derivatives containing thioether structures. After discovering the highly active target compound H13 (IC50 = 4.83 µM) based on in vitro antiproliferation, we also found it had a high safety against normal cells HEK293 with CC50 of 69.01 µM, indicating a sufficient therapeutic window. In addition, to provide reference for subsequent studies, a model was successfully constructed by Sybyl software. Preliminary mechanistic studies suggested that H13-induced apoptosis may be closely related to ROS accumulation and mitochondrial dysfunction. Subsequent studies revealed that H13 inhibited cell proliferation by inducing cellular autophagy mainly through blocking signal of the PI3K/AKT/mTOR pathway. Altogether, these results suggested that H13 was potentially valuable as a lead compound.

MiRNA-145-5p inhibits gastric cancer progression via the serpin family E member 1- extracellular signal-regulated kinase-1/2 axis.

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). AIM: To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC. METHODS: Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. RESULTS: GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). CONCLUSION: This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.

Swertiamarin relieves radiation-induced intestinal injury by limiting DNA damage.

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients' quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

IL-6/JAK2-dependent G6PD phosphorylation promotes nucleotide synthesis and supports tumor growth.

OBJECTIVE: Tumor cells hijack inflammatory mechanisms to promote their own growth. IL-6 is one of the major cytokines, and is frequently upregulated in tumors. The pentose phosphate pathway (PPP) generates the indispensable building blocks to produce various nucleotides. Here we aimed to determine whether and how PPP is timely tuned in response to IL-6 to support tumor growth. METHODS: Protein expression was examined by immunoblot. Protein interaction was examined by immunoprecipitation. Tumor cell proliferation in in vitro culture was examined by BrdU assay and colony formation assay. Tumor cell proliferation in mouse xenograft model was examined by Ki-67 staining. RESULTS: Here we show that the metabolic flux of PPP and enzymatic activity of glucose-6-phosphate dehydrogenase (G6PD) is rapidly induced under IL-6 treatment, without obvious changes in G6PD expression level. Mechanistically, Janus kinase 2 (JAK2) phosphorylates G6PD Y437 under IL-6 treatment, which accentuates G6PD enzymatic activity by promoting G6PD binding with its substrate G6P. Further, JAK2-dependent G6PD Y437 phosphorylation is required for IL-6-induced nucleotide biosynthesis and tumor cell proliferation, and is associated with the progression of oral squamous cell carcinoma. CONCLUSIONS: Our findings report a new mechanism implicated in the crosstalk between tumor cells and inflammatory microenvironment, by which JAK2-dependent activation of G6PD governs nucleotide synthesis to support tumor cell proliferation, thereby highlighting its value as a potential anti-tumor target.

Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common disease of endocrine-metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.

Novel 2-Amino-1,4-Naphthoquinone Derivatives Induce A549 Cell Death through Autophagy.

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC50 of 6.15 µM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.

YTHDF1 Enhances Chondrogenic Differentiation by Activating the Wnt/ß-Catenin Signaling Pathway.

Cartilage is derived from the chondrogenic differentiation of stem cells, for which the regulatory mechanism has not been fully elucidated. N6-methyladenosine (m6A) messenger RNA (mRNA) methylation is the most common posttranscriptional modification in eukaryotic mRNAs and is mediated by m6A regulators. However, whether m6A regulators play roles in chondrogenic differentiation is unknown. Herein, we aim to determine the role of a main m6A reader protein, YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), in chondrogenic differentiation regulation. Western blotting (WB) assays found that the expression of YTHDF1 increased during chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). The results of quantitative polymerase chain reaction, WB, immunohistochemistry, and Alcian blue staining revealed that overexpression of YTHDF1 increased cartilage matrix synthesis and the expression of chondrogenic markers when hBMSCs, ATDC5 cells, or C3H10T1/2 cells were induced to undergo chondrogenesis. Conversely, chondrogenesis was clearly inhibited when YTHDF1 was knocked down in hBMSCs, ATDC5 cells, or C3H10T1/2 cells. Further RNA sequencing and molecular biology experiments found that YTHDF1 activated the Wnt/ß-catenin signaling pathway during chondrogenic differentiation. Finally, the effects of overexpression and knockdown of YTHDF1 on chondrogenic differentiation were reversed by inhibiting or activating ß-catenin activity. Therefore, we demonstrated that YTDHF1 promoted chondrogenic differentiation through activation of the Wnt/ß-catenin signaling pathway.

AMPK phosphorylates NAMPT to regulate NAD+ homeostasis under ionizing radiation.

Radiation-induced oral mucositis is the most common complication for patients who receive head/neck radiotherapy. Nicotinamide adenine dinucleotide (NAD+) is vital for DNA damage repair under ionizing radiation, through functioning as either the substrate for protein poly(ADP-ribosyl)ation at DNA break sites or the cofactor for multiple DNA repair-related enzymes, which therefore can result in a significant consumption of cellular NAD+ during DNA repair. Mammalian cells produce NAD+ mainly by recycling nicotinamide via the salvage pathway, in which the rate-limiting step is governed by nicotinamide phosphoribosyltransferase (NAMPT). However, whether NAMPT is co-opted under ionizing radiation to timely fine-tune NAD+ homeostasis remains elusive. Here we show that ionizing radiation evokes NAMPT activation within 30 min without apparent changes in its protein expression. AMPK rapidly phosphorylates NAMPT at S314 under ionizing radiation, which reinforces the enzymatic activity of NAMPT by increasing NAMPT binding with its substrate phosphoribosyl pyrophosphate (PRPP). AMPK-mediated NAMPT S314 phosphorylation substantially restores NAD+ level in the irradiated cells and facilitates DNA repair and cell viability. Our findings demonstrate a new post-translational modification-based signalling route, by which cells can rapidly orchestrate NAD+ metabolism to support DNA repair, thereby highlighting NAMPT as a potential target for the prevention of ionizing radiation-induced injuries.

Involvement of osmoregulation, glyoxalase, and non-glyoxalase systems in signaling molecule glutamic acid-boosted thermotolerance in maize seedlings.

Glutamic acid (Glu) is not only an important protein building block, but also a signaling molecule in plants. However, the Glu-boosted thermotolerance and its underlying mechanisms in plants still remain unclear. In this study, the maize seedlings were irrigated with Glu solution prior to exposure to heat stress (HS), the seedlings' thermotolerance as well as osmoregulation, glyoxalase, and non-glyoxalase systems were evaluated. The results manifested that the seedling survival and tissue vitality after HS were boosted by Glu, while membrane damage was reduced in comparison with the control seedlings without Glu treatment, indicating Glu boosted the thermotolerance of maize seedlings. Additionally, root-irrigation with Glu increased its endogenous level, reinforced osmoregulation system (i.e., an increase in the levels of proline, glycine betaine, trehalose, and total soluble sugar, as well as the activities of pyrroline-5-carboxylate synthase, betaine dehydrogenase, and trehalose-5-phosphate phosphatase) in maize seedlings under non-HS and HS conditions compared with the control. Also, Glu treatment heightened endogenous methylglyoxal level and the activities of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (methylglyoxal reductase, lactate dehydrogenase, aldo-ketoreductase, and alkenal/alkenone reductase) in maize seedlings under non-HS and HS conditions as compared to the control. These data hint that osmoregulation, glyoxalase, and non-glyoxalase systems are involved in signaling molecule Glu-boosted thermotolerance of maize seedlings.

Mendelian randomization analyses support causal relationships between blood metabolites and the gut microbiome.

The gut microbiome has been implicated in a variety of physiological states, but controversy over causality remains unresolved. Here, we performed bidirectional Mendelian randomization analyses on 3,432 Chinese individuals with whole-genome, whole-metagenome, anthropometric and blood metabolic trait data. We identified 58 causal relationships between the gut microbiome and blood metabolites, and replicated 43 of them. Increased relative abundances of fecal Oscillibacter and Alistipes were causally linked to decreased triglyceride concentration. Conversely, blood metabolites such as glutamic acid appeared to decrease fecal Oxalobacter, and members of Proteobacteria were influenced by metabolites such as 5-methyltetrahydrofolic acid, alanine, glutamate and selenium. Two-sample Mendelian randomization with data from Biobank Japan partly corroborated results with triglyceride and with uric acid, and also provided causal support for published fecal bacterial markers for cancer and cardiovascular diseases. This study illustrates the value of human genetic information to help prioritize gut microbial features for mechanistic and clinical studies.

[Non-Coding RNA and Innate Immune Signal Regulation].

The innate immune system is critical to the elimination and control of infections. However, uncontrolled immune responses can cause indirect host-mediated tissue damage. The regulation of immune homeostasis is a complex but finely regulated process. ncRNAs have been increasingly identified as important regulators of a variety of biological processes. Recent research findings suggest that microRNAs and long non-coding RNAs participate in antiviral responses, tumor immunity, and autoimmune diseases by regulating gene expression in the innate immune pathways. MicroRNAs regulate gene expression at the post-transcriptional level by binding to the 3' untranslated regions of mRNA, while long non-coding RNAs act as endogenous competing RNAs for microRNAs, inhibiting the binding of microRNAs and mRNAs. In this review, we summarized the regulatory role of non-coding RNAs in innate immunity and its mechanism to provide references for research in the regulation of innate immunity and immune-related diseases. In addition, we also reported discussions on the future research directions in the field, including the expression and maturation regulation mechanism of new non-coding RNAs, and the conservation of non-coding RNAs in evolution.

Constructing intervertebral disc degeneration animal model: A review of current models.

Low back pain is one of the top disorders that leads to disability and affects disability-adjusted life years (DALY) globally. Intervertebral disc degeneration (IDD) and subsequent discogenic pain composed major causes of low back pain. Recent studies have identified several important risk factors contributing to IDD's development, such as inflammation, mechanical imbalance, and aging. Based on these etiology findings, three categories of animal models for inducing IDD are developed: the damage-induced model, the mechanical model, and the spontaneous model. These models are essential measures in studying the natural history of IDD and finding the possible therapeutic target against IDD. In this review, we will discuss the technical details of these models, the duration between model establishment, the occurrence of observable degeneration, and the potential in different study ranges. In promoting future research for IDD, each animal model should examine its concordance with natural IDD pathogenesis in humans. We hope this review can enhance the understanding and proper use of multiple animal models, which may attract more attention to this disease and contribute to translation research.

Application of medical magnifying loupes in diagnosis of oral mucosal diseases.

: To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.

Post-cesarean section pemphigus vegetans in a young woman treated with methylprednisolone and thalidomide.

Pemphigus vegetans is a rare variant of pemphigus vulgaris. Here, we report a rare case of postparturition pemphigus vegetans in a young woman without any prior medical history. The patient presented with extensive oral mucosal erosion, conjunctivitis, and fingernail dystrophy. A histopathological biopsy taken from the tongue showed pseudoepitheliomatous hyperplasia of the epidermis with eosinophilic spongiosis, and an intraepidermal cleft and direct immunofluorescence showed intercellular immunoglobulin G and complement component C3 deposition. A final diagnosis of pemphigus vegetans was made on the basis of clinical and histopathological features and laboratory findings. Complete remission was achieved by a combination of methylprednisolone and thalidomide. This case report indicates that the occurrence of postparturition pemphigus vegetans is strongly associated with immune status related to hormone levels throughout pregnancy and postparturition. Furthermore, it suggests that a combination of methylprednisolone and thalidomide may be an effective option for pemphigus vegetans treatment.

MicroRNA-874-3p promotes testosterone-induced granulosa cell apoptosis by suppressing HDAC1-mediated p53 deacetylation.

MicroRNA (miR)-874-3p is a newly identified miRNA that is involved in several pathological processes, including cancer, myocardial infarction, bone formation and erectile dysfunction. However, the role of miR-874-3p in polycystic ovary syndrome (PCOS) and granulosa cell (GC) apoptosis is not completely understood. The present study investigated the expression profile of miR-874-3p in PCOS by reverse transcription- quantitative PCR and the GC apoptosis by flow cytometry analysis. miR-874-3p expression was significantly upregulated in GCs isolated from patients with PCOS compared with patients without PCOS. In addition, miR-874-3p expression was positively correlated with GC apoptosis and testosterone levels in both patients with PCOS and patients without PCOS. Therefore, the present study also aimed to investigate the effects of miR-874-3p on testosterone-induced GC apoptosis. Compared with vehicle-treated GCs, miR-874-3p expression levels were significantly increased in testosterone-treated GCs, which was inhibited by the androgen receptor antagonist flutamide. GCs were transfected with either the miR-874-3p mimic or a miR-874-3p inhibitor. Compared with the control group, miR-874-3p mimic significantly enhanced GC apoptosis, whereas miR-874-3p inhibitor significantly decreased GC apoptosis. Moreover, histone deacetylase (HDAC) activity and HDAC1 expression levels were decreased in testosterone-treated GCs compared with vehicle-treated GCs. HDAC1 overexpression significantly attenuated the proapoptotic effects of testosterone. Additionally, miR-874-3p mimic and inhibitor significantly decreased and increased HDAC1 expression levels, respectively, compared with the control group. miR-874-3p inhibitor failed to attenuate HDAC1 overexpression-induced GC apoptosis. Furthermore, compared with the control group, testosterone treatment notably increased p53 expression and acetylation. Compared with the control group, western blotting analysis showed that miR-874-3p mimic notably increased p53 expression and acetylation, whereas miR-874-3p inhibitor markedly decreased p53 expression and acetylation. However, miR-874-3p inhibitor did not further decrease p53 acetylation and expression in cell overexpressing HDAC1. Collectively, the results of the present study indicated that miR-874-3p was upregulated in PCOS and promoted testosterone-induced GC apoptosis by suppressing HDAC1-mediated p53 deacetylation. Therefore, the present study improved the current understanding of the pathogenesis of PCOS and GC apoptosis.

SOX2-dependent expression of dihydroorotate dehydrogenase regulates oral squamous cell carcinoma cell proliferation.

Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.

Interplay between hydrogen sulfide and methylglyoxal initiates thermotolerance in maize seedlings by modulating reactive oxidative species and osmolyte metabolism.

Hydrogen sulfide (H2S) and methylglyoxal (MG) were supposed to be novel signaling molecules in plants. However, whether interplay between H2S and MG can initiate thermotolerance in maize seedlings and in relation to metabolism of reactive oxygen species (ROS) and osmolytes is little known. In this study, watering with MG and NaHS (H2S donor) alone or in combination elevated survival and tissue vigor of maize seedlings under heat stress and coped with an increase in the biomembrane injury (as indicated in membrane lipid peroxidation and electrolyte leakage). The above-mentioned effects were separately weakened by MG scavengers (N-acetyl cysteine: NAC; aminoguanidine: AG) and H2S inhibitor (DL-propargylglycine, PAG) and scavenger (hypotaurine, HT). These suggested that the interplay between H2S and MG initiated the thermotolerance in maize seedlings. The further data indicated that, under non-heat stress and heat stress conditions, MG and NaHS alone or in combination modulated ROS metabolism by regulating the activities of antioxidant enzymes (catalase, ascorbate peroxidase, guaiacol peroxidase, glutathione reductase, monodehydroascorbate reductase, and dehydroascorbate reductase) and the contents of non-enzymatic antioxidants (ascorbic acid, glutathione, flavonoids, and carotenoids) in maize seedlings. In addition, MG and NaHS alone or in combination also separately modulated the metabolism of osmolytes (proline, trehalose, glycine betaine, and total soluble sugar), H2S (L-cysteine desulfhydrase and O-acetylserine (thione) lyase), and MG (glyoxalase I, glyoxalase II, and MG reductase). These physiological effects also were separately impaired by NAC, AG, PAG, and HT. The current data illustrated that the interplay between H2S and MG initiated the thermotolerance in maize seedlings by modulating ROS, osmolyte, H2S, and MG metabolism.

Comparison of outcomes of arthrodesis and reconstruction (advancement), posterior tibial tendon with excision of accessory tarsal navicular bone (Kidner procedure) in type 2 accessory navicula.

BACKGROUND: The therapeutic outcome of the local arthrodesis surgery for type 2 accessory navicula (AN) is rarely reported. This study aimed to compare the clinical outcomes between Kidner and arthrodesis procedures for type 2 AN. METHODS: Sixteen patients (20 feet) with symptomatic type 2 AN receiving surgical treatment in our hospital between November 2013 and December 2015 were retrospectively included. Ten patients (13 feet) underwent the Kidner surgery (Kidner group) and 6 patients received local arthrodesis procedure (arthrodesis group). Radiographic indices before/after surgery were compared between the two groups. Patient's satisfaction with surgery outcome was evaluated by patient self-assessment questionnaire. RESULTS: The calcaneal pitch angle was significantly increased after surgery in both groups (bothp<0.01), while the talocalcaneal coverage angle and lateral talo-first metatarsal angle were not significantly changed after surgery. There was no significant difference regarding the postoperative changes in the three radiographic indices between the two groups. In the arthrodesis group, 3 patients (4 feet) had an excellent outcome, 2 patients (2 feet) a good outcome, and 1 patient (1 foot) had a fair outcome. In the Kidner group, 6 patients (8 feet), 2 patients (3 feet), 1 patient (1 foot) and 1 patient (1 foot) had excellent, good, fair, and poor treatment outcomes, respectively. The rate of good-to-excellent outcomes was comparable between the arthrodesis group and Kidner group (83% vs. 80%, p=0.696). CONCLUSION: Our results suggested that both the Kidner surgery and arthrodesis surgery were an effective treatment for symptomatic type 2 AN.