Predictive value of frailty assessment tools in patients undergoing surgery for gastrointestinal cancer: An observational cohort study.

BACKGROUND: Few studies have simultaneously compared the predictive value of various frailty assessment tools for outcome measures in patients undergoing gastrointestinal cancer surgery. Therefore, it is difficult to determine which assessment tool is most relevant to the prognosis of this population. AIM: To investigate the predictive value of three frailty assessment tools for patient prognosis in patients undergoing gastrointestinal cancer surgery. METHODS: This single-centre, observational, prospective cohort study was conducted at the Affiliated Lianyungang Hospital of Xuzhou Medical University from August 2021 to July 2022. A total of 229 patients aged ≥ 18 years who underwent surgery for gastrointestinal cancer were included in this study. We collected baseline data on the participants and administered three scales to assess frailty: The comprehensive geriatric assessment (CGA), Fried phenotype and FRAIL scale. The outcome measures were the postoperative severe complications and increased hospital costs. RESULTS: The prevalence of frailty when assessed with the CGA was 65.9%, 47.6% when assessed with the Fried phenotype, and 34.9% when assessed with the FRAIL scale. Using the CGA as a reference, kappa coefficients were 0.398 for the Fried phenotype and 0.291 for the FRAIL scale (both P < 0.001). Postoperative severe complications and increased hospital costs were observed in 29 (12.7%) and 57 (24.9%) patients, respectively. Multivariate logistic analysis confirmed that the CGA was independently associated with increased hospital costs (odds ratio = 2.298, 95% confidence interval: 1.044-5.057; P = 0.039). None of the frailty assessment tools were associated with postoperative severe complications. CONCLUSION: The CGA was an independent predictor of increased hospital costs in patients undergoing surgery for gastrointestinal cancer.

A mitochondria-targeted multifunctional nanoplatform combining carbon monoxide delivery with O2-independent free radical burst under 1064 nm light irradiation for efficient hypoxic tumor therapy.

In situ mitochondrial oxidative stress amplification is an effective strategy to improve efficacy of cancer treatment. In this work, a tumor and mitochondria dual-targeted multifunctional nanoplatform CMS@AIPH@PDA@COTPP@FA (CAPCTF) was prepared, in which a thermally decomposable radical initiator AIPH was loaded inside the mesoporores of CuxMoySz (CMS) nanoparticles with polydopamine (PDA) covered films that were further covalently functionalized by a mitochondria-targeted CO donor (COTPP) and a directing group of folic acid (FA). The prepared CAPCTF nanoplatform selectively accumulated in cancer cells and further targeted the mitochondrial organelle where carbon monoxide (CO) and O2-independent free radicals (•OH/•R) were in situ generated upon 1064 nm laser irradiation. Furthermore, the CMS nanocarrier was capable of depleting the GSH overexpressed in the tumor microenvironment (TME), thus preventing free radical scavenging. As a result, the CAPCTF nanoplatform exhibited outstanding in vitro and in vivo antitumor efficacy under hypoxic conditions. This provides an innovative strategy that combines O2-independent free radicals (•OH/•R) generation, CO delivery and GSH consumption to amplify intracellular oxidative stresses and induce mitochondrial dysfunction, thus leading to cancer cells eradication, which may have significant implications for personalized hypoxic tumor treatment.

Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

A mesoporous MnO2-based nanoplatform with near infrared light-controlled nitric oxide delivery and tumor microenvironment modulation for enhanced antitumor therapy.

A hollow mesoporous manganese dioxide-based (H-MnO2) multifunctional nanoplatform, H-MnO2 @AFIPB@PDA@Ru-NO@FA (MAPRF NPs), was prepared for synergistic cancer treatment, in which a histone deacetylase inhibitor AFIPB was loaded in its hollow cavity and a ruthenium nitrosyl donor (Ru-NO) and a folic acid (FA) targeting group were covalently decorated on its covered polydopamine (PDA) layer. The MAPRF NPs showed tumor microenvironment (TME)-responsive properties of depletion of glutathione (GSH) to disrupt the antioxidant defense system and on-demand drug delivery. And the released Mn2+ further catalyzed the decomposition of endogenous H2O2 to produce highly toxic hydroxyl radicals (·OH) for enhanced chemodynamic therapy (CDT). Furthermore, upon 808 nm light irradiation MAPRF NPs exhibited controlled nitric oxide (NO) delivery and simultaneously produced significant photothermal effect. Consequently, MAPRF NPs showed high mortality toward cancer cells in the presence of 808 nm light irradiation. This work provides a paradigm of multimodal synergistic therapy that combines NO-based gas therapy with TME modulation for efficient antitumor therapy.

A multifunctional nanoplatform delivering carbon monoxide and a cysteine protease inhibitor to mitochondria under NIR light shows enhanced synergistic anticancer efficacy.

Photoactivated chemotherapy has attracted widespread attention due to its ability to circumvent the shortcomings of hypoxia in tumor tissues compared with traditional photodynamic therapy. In this work, novel multifunctional nanoplatform (1), Ru-inhibitor@TPPMnCO@N-GQDs, was designed and prepared, which was capable of mitochondria-targeted co-delivery of the cysteine protease inhibitor and carbon monoxide (CO) stimulated with an 808 nm near infrared (NIR) laser. Nanoplatform (1) was prepared by covalent attachment of a mitochondria-targeted CO donor (TPPMnCO) and a Ru(II)-caged cysteine protease inhibitor (Ru-inhibitor) on the surface of fluorescent N-doped graphene quantum dots (N-GQDs). Nanoplatform (1) preferentially accumulated in the mitochondria of cancer cells and instantly delivered CO and the cysteine protease inhibitor upon 808 nm NIR light irradiation, thus damaging mitochondria and leading to significant in vitro and in vivo anticancer efficacy. In addition, nanoplatform (1) has good biocompatibility and did not exert any toxic side effects on mice during the period of treatment. The targeted subcellular mitochondrial co-delivery of CO and the cysteine protease inhibitor may provide new insights into CO and enzyme inhibitor combined therapies for cancer treatment.

Retraction Notice to: Tumor-Suppressive MicroRNA-216b Binds to TPX2, Activating the p53 Signaling in Human Cutaneous Squamous Cell Carcinoma.

[This retracts the article DOI: 10.1016/j.omtn.2020.01.022.].

Greenhouse gas emissions from the wheat-maize cropping system under different tillage and crop residue management practices in the North China Plain.

With increasing attention being placed on mitigating global warming and achieving agricultural sustainable intensification, conservation agriculture practices have gradually been implemented in the North China Plain (NCP). However, there are still knowledge gaps on the effects of conservation practices on greenhouse gas (GHG) emissions in this area. In this study, a four-year field experiment was conducted from 2014 to 2018 to assess the effects of tillage and crop residue management practices on the emissions of nitrous oxide (N2O) and methane (CH4). Subsequently, crop yields, area-scaled and yield-scaled total non-carbon dioxide (CO2) GHG emissions were assessed. Our research found that no-till (NT) decreased N2O emissions by 22.6% compared with conventional tillage (CT) in winter wheat (Triticum aestivum L.) seasons, but there was no difference between tillage practices in summer maize (Zea mays L.) seasons. Crop residue retention practice (+R) increased N2O emissions by 28.1% and 26.7% compared with residue removal practice (-R) in winter wheat and summer maize seasons, respectively. The NT soils took up more CH4 compared with the CT soils in summer maize seasons. Area-scaled total non-CO2 GHG emissions showed trends similar to those of N2O emission. Since crop residue retention improved the maize yield compared with the residue removal treatments, yield-scaled total non-CO2 GHGs emission did not differ between residue management practices in summer maize seasons. Our four-year field measurements indicated that no-till practice could be more useful as an option to mitigate non-CO2 GHG emissions in the wheat - maize cropping system.

NIR light-controlled mitochondria-targeted delivery of carbon monoxide combined with histone deacetylase inhibition for synergistic anticancer therapy.

A multifunctional nanoplatform APIPB-MnCO@TPP@N,P-GQDs (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl) benzamide, TPP = triphenylphosphine, Mn = manganese, CO = carbon monoxide, and GQDs = graphene quantum dots), nanoplatform (1), was synthesized, which consists of a fluorescent N, P-doped GQDs carrier with its surface covalently functionalized by an CO donor APIPB-MnCO with histone deacetylases (HDAC) inhibitory property and a TPP derivative directing group. Nanoplatform (1) selectively localized in the mitochondria of HeLa cells to inhibit HDAC activity, and released CO upon 808 nm near-infrared light irradiation, destroying the mitochondria and thus inducing cancer cells apoptosis. The targeted subcellular mitochondrial CO delivery combined with inhibitory HDAC activity maximized the cytotoxicity of the nanoplatform which may provide new insights for CO-mediated multimodal therapies for cancer treatment.

Kv7.4 channel is a key regulator of vascular inflammation and remodeling in neointimal hyperplasia and abdominal aortic aneurysms.

Inflammation has recently emerged as an important contributor for cardiovascular disease development and participates pivotally in the development of neointimal hyperplasia and abdominal aortic aneurysms (AAA) formation. Kv7.4/KCNQ4, a K+ channel, is one of the important regulators of vascular function but its role in vascular inflammation is unexplored. Here, we showed that the expression of Kv7.4 channel was elevated in the neointima and AAA tissues from mice and humans. Genetic deletion or pharmacological inhibition of Kv7.4 channel in mice alleviated neointimal hyperplasia and AAA formation via downregulation of a set of vascular inflammation-related genes, matrix metalloproteinases (MMP) 2/9, and intercellular adhesion molecule (ICAM-1). Furthermore, genetic deletion or inhibition of Kv7.4 channel suppressed the activation of tumor necrosis factor receptor 1 (TNFR1)-nuclear factor (NF)-κB signaling pathway via blockade of interaction between TNFR1 and TNFR1-associated death domain protein (TRADD) in vascular smooth muscle cells (VSMCs). Knockdown of Kv7.4 in vivo identified VSMC-expressed Kv7.4 as a major factor in vascular inflammation. Collectively, our findings suggest that Kv7.4 channel aggravates vascular inflammatory response, which promotes the neointimal hyperplasia and AAA formation. Inhibition of Kv7.4 channel may be a novel therapeutic strategy for vascular inflammatory diseases.

Mitochondria-targeted carbon monoxide delivery combined with singlet oxygen production from a single nanoplatform under 808 nm light irradiation for synergistic anticancer therapy.

A multifunctional nanoplatform (1), MnCO@TPP@C-TiO2, which consists of a carrier of carbon-doped TiO2 nanoparticles with surface covalent functionalization of manganese carbonyls and a directing group of triphenylphosphine, was prepared for mitochondria-targeted carbon monoxide (CO) delivery combined with photodynamic therapy (PDT). MnCO@TPP@C-TiO2 selectively localized in the mitochondria of HeLa cells where the overexpressed-H2O2 triggered CO release resulting in mitochondrial damage. And singlet oxygen species generated upon 808 nm near infrared light irradiation further destroyed the mitochondria and induced cancer cells apoptosis. Cytotoxicity assays revealed that the nanoplatform with mitochondria-targeted CO delivery and PDT exhibited the highest lethality against cancer cells in comparison with all the other control samples tested, and it showed good dark biocompatibility with normal cells that express low H2O2 levels. This work may provide new insights into combining CO-based gas therapy with traditional PDT for efficient cancer treatment.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

Visible light-controlled carbon monoxide delivery combined with the inhibitory activity of histone deacetylases from a manganese complex for an enhanced antitumor therapy.

Multifunctional drugs with synergistic effects have been widely developed to enhance the treatment efficiency of various diseases, such as malignant tumors. Herein, a novel bifunctional manganese(I)-based prodrug [MnBr(CO)3(APIPB)] (APIPB = N-(2-aminophen-yl)-4-(1H-imidazo[4,5-f] [1, 10] phenanthrolin-2-yl)benzamide) with inhibitory histone deacetylase (HDAC) activity and light-controlled carbon monoxide (CO) delivery was successfully designed and synthesized. [MnBr(CO)3(APIPB)] readily released CO under visible light irradiation (λ > 400 nm) through which the amount of released CO could be controlled by manipulating light power density and illumination time. In the absence of light irradiation, the cytotoxic effect of [MnBr(CO)3(APIPB)] on cancer cells was greater than that of the commercially available HDAC inhibitor MS-275. Consequently, with a combination of CO delivery and HDAC inhibitory activity, [MnBr(CO)3(APIPB)] showed a remarkably enhanced antitumor effect on HeLa cells (IC50 = 3.2 µM) under visible light irradiation. Therefore, this approach shows potential for the development of medicinal metal complexes for combined antitumor therapies.

Solitary plasmacytoma of the occipital bone: a case report.

Solitary plasmacytoma (SP) of the skull is an uncommon clinical entity that is characterized by a localized proliferation of neoplastic monoclonal plasma cells. This case report describes a 50-year-old male that presented with a headache and an exophytic soft mass on the occiput. The diagnosis of SP was based on the pathological results and imaging examinations. The patient underwent occipital craniotomy, skull reconstruction and lower trapezius myocutaneous flap (LTMF) transplantation under general anaesthesia. The tumour was capsulized and extended to the subcutaneous and the subdural space through the dura mater with skull defects. The neoplasm of the occipital bone involved large areas of scalp and subcutaneous tissue, which resulted in a large postoperative scalp defect that was repaired using LTMF transplantation. All of the tumour was removed and the transplanted flap grew well. Follow-up at 5 months identified an aggressive mass lesion on the right frontal lobe. The patient received six cycles of the PAD chemotherapy regimen (bortezomib, doxorubicin and dexamethasone) and the lesion was significantly reduced. This case demonstrates that LTMF is an alternative approach for the repair of scalp and subcutaneous soft tissue defects caused by the excision of a large malignant tumour of the occipital region. Chemotherapy is the choice of treatment for neoplastic recurrence.

Tumor-Suppressive MicroRNA-216b Binds to TPX2, Activating the p53 Signaling in Human Cutaneous Squamous Cell Carcinoma.

Dysregulation of microRNAs (miRNAs) is acknowledged in human cutaneous squamous cell carcinoma (cSCC). We hereby evaluated the ability of miRNA-216b (miR-216b) to impact human cSCC. cSCC tissues with corresponding adjacent normal tissues were collected from 40 patients diagnosed with cSCC where the expression pattern of miR-216b and targeting protein for Xenopus kinesin-like protein 2 (TPX2) was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot analysis. A431 cells were transfected with miR-216b mimic, miR-216b inhibitor, or short interfering RNA against TPX2 to evaluate cell proliferation, invasion, migration, and apoptosis using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. TPX2 was highly expressed in cSCC tissues while miR-216b was poorly expressed in association with tumor differentiation, lymph node metastasis, and tumor node metastasis staging in patients with cSCC. In response to overexpressed miR-216b or silenced TPX2, cSCC cell proliferation, invasion, and migration were suppressed and apoptosis was stimulated, along with activated p53 signaling. Thus, upregulated miR-216b was capable of promoting apoptosis and inhibiting proliferation, invasion, and migration of cSCC cells by downregulating TPX2 through activation of the p53 signaling, highlighting a novel biomarker for novel treatment modalities against cSCC.

Effects of intradialytic resistance exercise on systemic inflammation in maintenance hemodialysis patients with sarcopenia: a randomized controlled trial.

PURPOSE: To investigate the effect of intradialytic resistance exercise on inflammation markers and sarcopenia indices in maintenance hemodialysis (MHD) patients with sarcopenia. METHODS: Forty-one MHD patients with sarcopenia were divided into an intervention group (group E, n = 21) and a control group (group C, n = 20). Group C patients only received routine hemodialysis care, whereas group E patients received progressive intradialytic resistance exercise with high or moderate intensity for 12 weeks at three times per week (using the weight of the lower limbs and elastic ball movement of the upper limb) on the basis of routine hemodialysis care. RESULTS: After 12 weeks, a significant difference in physical activity status (maximum grip strength, daily pace, and physical activity level), Kt/V, and C-reactive protein was found between groups E and C. Inflammatory factors (interleukin (IL)-6, IL-10, and tumor necrosis factor(TNF)-α) increased or decreased more significantly in group E than in group C. CONCLUSIONS: This study showed that intradialytic resistance exercise can improve physical activity effectively and reduce microinflammatory reactions even if this simple exercise does not affect the muscle mass in MHD patients with sarcopenia.

Surgical treatment for primary premature ejaculation with an inner condom technique.

To explore a novel surgical treatment for primary premature ejaculation using an inner condom technique.A total of 20 males with premature ejaculation, who admitted our andrology clinic from June 2016 to July 2017, were enrolled. By surgery, an inner condom made of acellular dermal matrix (ADM) was transferred to the subcutaneous pocket of the penis. The prolongation of intravaginal ejaculatory latency time (IELT) after the surgery was examined. The perioperative complications were also studied.The surgical intervention significantly increased the average IELT in patients, from 0.67 to 2.37 min (P = .009). No serious perioperative complications and adverse psychosexual effects were seen. Patients could resume sexual activity 6 weeks after the surgery.The novel inner condom using ADM is an effective and safe surgical treatment for males with premature ejaculation. The efficacy of this new treatment modality warrants further investigation in independent cohorts.

[Effect of autophagy inhibitor chloroquine on acute alcoholinduced liver disease].

OBJECTIVES: To investigate the role of autophagy inhibitor chloroquine (CQ) in acute ethanol-induced liver injury and its mechenism. METHODS: Twenty-one C57BL/6 male mice were randomly divided into three groups:control group, ethanol group, CQ + ethanol group (n=7). Mice in ethanol group were administered 33% (v/v) ethanol at a dose of 4.5 g/kg body weight. Ethanol-induced liver steatosis in each group was detected by hematoxylin and eosin staining. Hepatic lipid accumulation was detected by staining with Oil red O. Hepatic tissue triglyceride (TG) levels, serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) were determined by biochemical assays. Protein expression of microtubule-associated protein 1 light chain 3(LC3) and nuclear factorκB p65(NF-κB p65) were measured by Western blot and immunofluorescence. Pro-inflammatory factors tumor necrosis factor-α(TNF-α)、interleukin 6(IL-6) were detected by ELISA. RESULTS: Compared with control group, ethanol induced liver injury proved by accumulation of hepatic lipids, TG levels, AST and ALT activities were significantly increased by ethanol, protein expression of LC3-Ⅱ was also markedly increased by ethanol. Compared with ethanol group, addition of CQ increased furtherthe level of LC3-Ⅱexpression, and TG amount, serum AST and ALT activities, and the expression of NF-κB p65, TNF-αand IL-6. CONCLUSIONS: Acute ethanol-intake could induce liver steatosis and inflammation, and autophagy inhibitor CQ exacerbatedethanol-induced liver injury, suggested that autophagy might be protective effect in acute ethanol-induced liver disease.

Proinflammatory Factors Mediate Paclitaxel-Induced Impairment of Learning and Memory.

The chemotherapeutic agent paclitaxel is widely used for cancer treatment. Paclitaxel treatment impairs learning and memory function, a side effect that reduces the quality of life of cancer survivors. However, the neural mechanisms underlying paclitaxel-induced impairment of learning and memory remain unclear. Paclitaxel treatment leads to proinflammatory factor release and neuronal apoptosis. Thus, we hypothesized that paclitaxel impairs learning and memory function through proinflammatory factor-induced neuronal apoptosis. Neuronal apoptosis was assessed by TUNEL assay in the hippocampus. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the hippocampus tissue were analyzed by Western blot assay. Spatial learning and memory function were determined by using the Morris water maze (MWM) test. Paclitaxel treatment significantly increased the escape latencies and decreased the number of crossing in the MWM test. Furthermore, paclitaxel significantly increased the number of TUNEL-positive neurons in the hippocampus. Also, paclitaxel treatment increased the expression levels of TNF-α and IL-1ß in the hippocampus tissue. In addition, the TNF-α synthesis inhibitor thalidomide significantly attenuated the number of paclitaxel-induced TUNEL-positive neurons in the hippocampus and restored the impaired spatial learning and memory function in paclitaxel-treated rats. These data suggest that TNF-α is critically involved in the paclitaxel-induced impairment of learning and memory function.

Functional and aesthetic reconstruction of a large upper lip defect using combined three local flaps: A case report.

RATIONALE: A significant clinical issue for treating patients with large upper lip defects is how to reconstruct the lip functionally and aesthetically. Traditional methods usually lead to asymmetry of the nasal base, philtrum and the lips. PATIENT CONCERNS: A 22-year-old lady presented with a large congenital nevus on her upper lip which involved the cutaneous, vermilion, and the philtrum. Secondary deformity caused by previous partial excisions was also identified. DIAGNOSES: Patient was diagnosed as upper lip nevus with secondary deformity after partial excisions. INTERVENTIONS: We repaired the large upper lip defect by using combined nasolabial rotation flap and orbicularis oris myocutaneous flap. An additional small piece of mucosal flap was used to lengthen the vermilion. OUTCOMES: After the surgery, patient with large upper lip defects achieved satisfactory cosmetic and functional repair. LESSONS: Reconstruction of the upper lip has been successfully accomplished through the use of combined nasolabial rotation flap, orbicularis oris myocutaneous flap, and a small piece of mucosal flap.

Mechanism of MicroRNA-708 Targeting BAMBI in Cell Proliferation, Migration, and Apoptosis in Mice With Melanoma via the Wnt and TGF-ß Signaling Pathways.

OBJECTIVE: The aim of this study was to evaluate the mechanisms involved with miRNA-708 and its targeting of bone morphogenetic protein and activin membrane-bound inhibitor in cell proliferation, migration, and apoptosis in mice with melanoma via the Wnt and transforming growth factor ß signaling pathways. METHODS: Sixty mice were recruited of which 40 were subsequently assigned into the experimental group (22 mice were successfully established as melanoma model and 18 mice used in tumor xenograft), and the normal control group consisted of 20 mice. B16 cells were assigned to the normal, blank, and negative control, miR-708 mimics, miR-708 inhibitors, si-BAMBI, and miR-708 inhibitors + si-bone morphogenetic protein and activin membrane-bound inhibitor groups. Western blotting and reverse transcription quantitative polymerase chain reaction were employed to detect the expression levels within the tissues and cell lines. TCF luciferase reporter (TOP-FLASH) or a control vector (FOP-FLASH) was applied to detect the activity of the Wnt signaling pathway. MTT3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay, flow cytometry, scratch test, and Transwell assay were conducted, respectively, for cell proliferation, apoptosis, migration, and invasion, while tumor xenograft procedures were performed on the nude mice recruited for the study. RESULTS: Compared to the normal control group, the model group displayed increased expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2; TOPflash activity; ß-catenin expression; cell proliferation; migration; and invasion capabilities while decreased expressions of miR-708, vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3 and apoptosis rate. Compared to the blank and negative control groups, the miR-708 mimics and small-interfering RNA-bone morphogenetic protein and activin membrane-bound inhibitor groups exhibited decreases expressions of bone morphogenetic protein and activin membrane-bound inhibitor, Wnt10B, P53, and Bcl-2 and decreased proliferation, migration, and invasion capabilities, while increases in the apoptosis rate, expressions of vascular endothelial growth factor, Fas, Bax, Caspase-3, and cleaved Caspase-3; however, downregulated levels of TOPflash activity and ß-catenin expression were recorded. The miR-708 inhibitors group displayed an opposite trend. CONCLUSION: Downregulation of miR-708-targeted bone morphogenetic protein and activin membrane-bound inhibitor inhibits the proliferation and migration of melanoma cells through the activation of the transforming growth factor ß pathway and the suppression of Wnt pathway.