Validation of an AI-Powered Automated X-ray Bone Age Analyzer in Chinese Children and Adolescents: A Comparison with the Tanner-Whitehouse 3 Method.

INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.

Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established Tanner­Whitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.

TH-4000, a hypoxia-activated pan-HER inhibitor, shows excellent preclinical efficacy for the treatment of HER2+ breast cancer.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is correlated with poor prognosis, the current treatment of which is still based on surgery and adjuvant targeted therapy with monoclonal antibody. Problems of drug resistance hinder the use of monoclonal antibodies. Subsequently, tyrosine kinase inhibitors (TKIs) have been noticed, TKIs have the advantages of multi-targets and reduced drug resistance. However, TKIs that target HER family proteins often cause adverse effects such as liver damage and diarrhea. Thus, TKIs with high selectivity are being developed. TH-4000, a prodrug that generated an active form TH-4000Effector (TH-4000E) under hypoxic condition, was evaluated in this research. We found that TH-4000E ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium) (1-1000 nM) had potent and highly selective toxic effects on HER2+ breast cancer cells and inhibited the phosphorylation of HER family kinases at lower doses than that of Lapatinib and Tucatinib. TH-4000E activated Caspase-3 and induced apoptosis through a reactive oxygen species (ROS)-dependent pathway. The prodrug TH-4000 ([(E)-4-[[4-(3-bromo-4-chloroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-4-oxobut-2-enyl]-dimethyl-[(3-methyl-5-nitroimidazol-4-yl)methyl]azanium;bromide) (50 mg/kg) effectively suppressed the tumor growth with less liver damage in mouse tumor models. This hypoxia-targeted strategy has possessed advantage in avoiding drug-induced liver damage, TH-4000 could be a promising drug candidate for the treatment of HER2+ breast cancer.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo.

Acute lung injury (ALI) is an inflammatory condition and there are no effective treatments. A novel new compound----colchicine-myricetin hybrid (CMyrH) was herein designed and synthesized. To evaluate the activity of CMyrH in ALI, we used a bleomycin (BLM) induced BEAS-2B injury model in vitro and established a well-recognized rat model of BLM-induced lung injury in vivo. The results demonstrated that colchicine-myricetin hybrid protected BEAS-2B cells against BLM-induced cell injury in an increased dose manner, and reduced wet/dry weight ratio, histological scoring, and inflammation cytokines IL-1ß, IL-6, IL-18, and TNF-α levels of lung tissue of the rats. Furthermore, we found colchicine-myricetin hybrid inhibited caspase-1, ASC, GSDMD, and NLRP-3 expression in vivo. Meanwhile, we used molecular docking to analyze the binding mode of colchicine-myricetin hybrid and human neutrophil elastase (HNE), it revealed that colchicine-myricetin hybrid showed strong binding affinity toward human neutrophil elastase when compared to its parent molecules. In conclusion, It is suggested that colchicine-myricetin hybrid antagonized acute lung injury by focusing on multi-targets via multi-mechanisms, and might be served as a potential therapeutic agent for acute lung injury.

The impact of subclinical hypothyroidism on growth and development in infants and young children aged 0 to 5 years.

INTRODUCTION: The objective was to investigate the growth and development of infants and young children with mild subclinical hypothyroidism aged 0 to 5 years, especially those aged 0 to 2 years. MATERIAL AND METHODS: The study was a retrospective analysis of the birth status, physical growth, and neuromotor development of patients aged 0 to 5 years, who were diagnosed with subclinical hypothyroidism during newborn screening (NBS) in Zhongshan between 2016 and 2019. Based on preliminary results, we compared 3 groups: with thyroid-stimulating factor (TSH) value of 5-10 mIU/L (442 cases), TSH value of 10-20 mIU/L (208 cases), and TSH above 20 mIU/L (77 cases). Patients with TSH value above 5 mIU/L were called back for repeat testing and were divided into 4 groups as follows: mild subclinical hypothyroidism group 1 with a TSH value of 5-10 mIU/L in both initial screening and repeat testing; mild subclinical hypothyroidism group 2 with TSH value above 10 mIU/L in initial screening; and TSH value of 5-10 mIU/L in repeat testing; the severe subclinical hypothyroidism group with TSH value of 10-20 mIU/L in both the initial screening and repeat testing and the congenital hypothyroidism group. RESULTS: There were no significant differences in the maternal age, type of delivery, gender, length, and weight at birth between the preliminary groups; however, the gestational age at birth was significantly different (F = 5.268, p = 0.005). The z-score for length at birth was lower in the congenital hypothyroidism group compared to the other 3 groups but showed no difference at 6 months of age. The z-score for length in mild subclinical hypothyroidism group 2 was lower compared to the other 3 groups but showed no difference at 2-5 years of age. At 2 years of age there was no significant difference in the developmental quotient (DQ) of the Gesell Developmental Scale between the groups. CONCLUSION: The gestational age at birth affected the neonatal TSH level. Intrauterine growth in infants with congenital hypothyroidism was retarded compared to that of infants with subclinical hypothyroidism. Neonates with a TSH value of 10-20 mIU/L in the initial screening and a TSH value of 5-10 mIU/L in the repeat testing showed developmental delay at 18 months but caught up at age 2 years. There was no difference in neuromotor development between the groups. Levothyroxine in patients with mild subclinical hypothyroidism is not required, but we recommend that the growth and development of such infants and young children continues to be monitored.

Analysis of Risk Factors and Screening Results of Neonatal Congenital Hypothyroidism in a Tertiary Care Center of Southern China.

Objective: To explore the risk factors for neonatal congenital hypothyroidism (CH) and the influencing factors of false-positive results in CH screening. Methods: In this study, 255 neonatal patients with CH who completed the screening and further diagnosis and 366 neonates with positive CH screening results and normal thyroid function were selected as the case group. 246 healthy neonates with normal thyroid function were selected as the control group. Gestational age, birth-weight, maternal age, small for gestational age (SGA), perinatal factors (gestational thyroid dysfunction, gestational diabetes mellitus, etc.) were used as influencing factors, using χ 2 tests were performed for comparison. The statistically significant variables were analyzed with Logistic multiple regression models, and the difference was considered statistically significant (P<0.05). Results: There were statistical differences in the SGA, maternal gestational diabetes mellitus, thyroid disease, and the proportion using assisted reproduction technology among the case group, false-positive screening group, and control group (χ 2 was 11.943, 6.857, 6.999, 9.732, respectively, P < 0.05). The results of multivariate logistic regression analysis showed that the gestational thyroid disease (OR = 8.452, 95% CI:1.051-67.982), gestational diabetes mellitus (OR = 2.654, 95% CI:1.051-6.706), and assisted reproduction (OR = 0.194, 95% CI:0.041-0.911) were the influencing factors for neonatal CH, and the difference was statistically significant (P < 0.05). The SGA (OR = 2.556, 95% CI:1.027-6.361), gestational thyroid disease (OR = 7.801, 95% CI:1.03-59.057), gestational diabetes mellitus (OR = 2.731, 95% CI:1.18-6.322), and assisted reproduction (OR = 0.28, 95% CI:0.102-0.765) were the influencing factors of the false-positive screening results of neonatal CH. The difference was statistically significant (P < 0.05). Conclusion: Neonatal CH and positive screening results are influenced by assisted reproduction, gestational thyroid dysfunction, gestational diabetes mellitus, and SGA.

USP38 inhibits colorectal cancer cell proliferation and migration via downregulating HMX3 ubiquitylation.

Accumulating evidence has shown that H6 Family Homeobox 3 (HMX3) plays a crucial role in nervous system regulation. However, the regulatory mechanism of HMX3 in colorectal cancer (CRC) has seldom been studied. Herein, HMX3 was significantly downregulated in CRC, as demonstrated by qRT-PCR and WB analysis on clinical samples and a panel of cell lines. Besides, it was found that the expression of HMX3 was negatively correlated with survival of CRC patients. The functional analyses (EdU staining, CCK-8, colony formation, Transwell, and wound scratch assays) showed that CRC cell proliferation, migration, and invasion were significantly suppressed by HMX3 overexpression, while enhanced by HMX3 knockdown. Moreover, in vivo experiment revealed HMX3 overexpression could also suppress tumor growth. Combining bioinformatics and WB analysis, we preliminarily uncovered that HMX3 was involved in apoptosis and KRAS signaling pathways. Mechanistically, Ubiquitin-specific protease 38 (USP38) was identified as a novel post-translational regulator of HMX3, which could directly interact with HMX3 to stabilize its protein expression via deubiquitination. Furthermore, the role of USP38 silencing in promoting cell proliferation, migration, and invasion of CRC cells was blocked by HMX3 overexpression. In conclusion, our findings suggested that USP38/HMX3 axis is a novel promising therapeutic candidate for CRC.

Glycated Haemoglobin A1c Variability Score Elicits Kidney Function Decline in Chinese People Living with Type 2 Diabetes.

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m2 per year on average; those with HVS > 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m2 per year on average. Chinese adults with type 2 diabetes and HVS > 60% could experience a more rapid eGFR decline.

Synergistic Effect and Mechanism of Apoptosis Induction by Morphine and the HIV-1gp120V3 Loop in Hippocampal Neurons.

HIV-associated neurocognitive disorders (HAND) are a collective name for neurological disorders associated with HIV-1 infection. The incidence and severity of HAND are increased by concomitant opioid use disorder, such as heroin and morphine abuse. Our previous study showed that the HIV-1 envelope protein gp120 and morphine synergistically induce apoptosis in rat hippocampal neurons. However, the underlying mechanism remains unclear. We hypothesized that morphine and gp120 activated the neuronal apoptosis signaling pathway via their typical membrane receptors. If they shared key signaling molecules, their induction of neuronal apoptosis could be inhibited by blocking these targets. We found that morphine and gp120V3 loop synergistically induced hippocampal neuron apoptosis, mediated by activating the extracellular signal-regulated kinase (ERK) pathway, increasing the intracellular Ca2 + concentration and expression of caspase-, and reducing the mitochondrial membrane potential. The ERK inhibitor PD98509 and the phosphatidylinositol 3-kinase activator IGF-1 blocked this effect. These results indicate that ERK plays a crucial role in the apoptosis of hippocampal neurons in HAND.

Autophagy Modulation and Synergistic Therapy to Combat Multidrug Resistance Breast Cancer Using Hybrid Cell Membrane Nanoparticles.

The development of multidrug resistance (MDR) is a commonly observed phenomenon in many cancer types. It contributed significantly to the poor outcome of many currently available chemotherapies. Considering autophagy as one of the most important physiological process in cancer progression, we thereby proposed an anti-autophagy siRNA and doxorubicin (Dox) co-delivery system (MC/D-siR) to combat MDR breast cancer using sequential construction. Our results demonstrated the potential of MC/D-siR to effectively transfect the loaded siRNA to result in significant downregulation of intracellular autophagy level in MCF-7/Adr (Dox resistance MCF-7 cell line) cells, which in turn cut off the ATP supply and to reverse the MDR and potentiated accumulated drug retention in cells. As a result, MC/D-siR showed much elevated anticancer benefits than single loaded platforms (MC/Dox or MC/siRNA), indicating the ability for effective MDR cancer treatment through the combination of autophagy regulation and chemotherapy.

Associations of SUCNR1, GRK4, CAMK1D gene polymorphisms and the susceptibility of type 2 diabetes mellitus and essential hypertension in a northern Chinese Han population.

AIMS: Diabetes mellitus and hypertension are both complex diseases that are caused by interactions among multiple genetic and physiological factors. To investigate the association of common single-nucleotide polymorphisms (SNPs) of SUCNR1, GRK4 and CAMK1D genes with the susceptibility of the two diseases in a northern Chinese Han population. METHODS: 36 SNPs were genotyped in 2304 clinical patients (1152 type 2 diabetes mellitus, 1152 essential hypertension) and 1152 health controls by Sequenom Mass-ARRAY RS1000. RESULTS: In this study, we found that BMI, blood press, pulse pressure, FBG, total cholesterol and triglycerides were associated with an increased risk of type 2 diabetes mellitus (T2DM) and essential hypertension (EH). Three SNPs (SUCNR1: rs73168929; GRK4: rs1557213; CAMK1D: rs17151584) significantly associated with the susceptibility of T2DM and EH at the same time. Also, the susceptibility genotypes of 3 SNPs were significantly correlated with liver and renal function parameters. CONCLUSION: To the best of our knowledge, the present study is the first to report that three SNPs (SUCNR1: rs73168929; GRK4: rs1557213; CAMK1D: rs17151584) contributed to the risk of T2DM and EH in a northern Chinese Han population. These results provide a favourable evidence for better understand of the underlying common mechanism of these two diseases.

Ligustrazine ameliorates lipopolysaccharide­induced neurocognitive impairment by activating autophagy via the PI3K/AKT/mTOR pathway.

Autophagy is a lysosome­mediated cell content­dependent degradation pathway that leads to enhanced inflammation in an uncontrolled state. This study examined the role of autophagy in lipopolysaccharide (LPS)­induced brain inflammation and the effects of the traditional Chinese medicine ligustrazine on LPS­induced neurocognitive impairment in rats. Furthermore, the molecular mechanisms by which ligustrazine influences neurocognitive impairments were explored. The production of the inflammatory mediators interleukin (IL)­1ß and tumor necrosis factor (TNF)­α was analyzed using ELISAs, and the expression levels of the autophagy marker microtubule­associated protein light chain 3 (LC3) II/I were analyzed using western blotting. LPS exposure upregulated the expression of IL­1ß and TNF­α and downregulated the expression of LC3 II/I. Ligustrazine activated autophagy by preventing the expression of phosphoinositide 3­kinase (PI3K), phosphorylated protein kinase B (p­AKT), and phosphorylated mammalian target of rapamycin (p­mTOR). The present results suggest that ligustrazine improved LPS­induced neurocognitive impairments by activating autophagy and ameliorated neuronal injury by regulating the PI3K/AKT/mTOR signaling pathway. These findings provide an important reference for the prevention and treatment of neuroinflammation.

Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway.

Neuroinflammation is a predisposing factor for several neurodegenerative diseases. The purpose of this study was to evaluate the protective effect of madecassoside (MA) in lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in rats. MA has many protective effects such as antioxidant and anti-inflammatory properties. We investigated whether MA could improve neurocognitive dysfunction caused by intracerebroventricular injection of LPS. We examined the effects and mechanisms of action of MA on LPS-induced neuroinflammation in the cortex and hippocampus. Our study revealed that MA (120 mg/kg, i.g) treatment for 14 days reduced LPS-induced neurotoxicity by reducing cognitive impairments and suppressing the production of inflammatory cytokines such as interleukin 1 beta (IL-1ß), tumor necrosis factor alpha(TNF-α), and interleukin 6(IL-6) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Furthermore, MA treatment enhanced protein levels of heme oxygenase (HO)-1 by upregulating Nrf2 in LPS-stimulated neurotoxicity. Collectively, these results suggest that MA is effective in preventing neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and activation of Keap1-Nrf2/HO-1 signaling. As such, MA may be a potential therapy for addressing memory impairment caused by neuroinflammation.

Inhibitory Effect of LPS on the Proliferation of Oligodendrocyte Precursor Cells through the Notch Signaling Pathway in Intrauterine Infection-induced Rats.

Periventricular white matter injury (PWMI) is very common in survivors of premature birth, and the final outcomes are a reduction in myelinated neurons leading to white matter hypomyelination. How and (or) why the oligodendrocyte lineage develops abnormally and myelination is reduced is a hot topic in the field. This study focuses on the effect of intrauterine inflammation on the proliferation of oligodendrocyte lineage cells and the underlying mechanisms. Lipopolysaccharide (LPS) (300 µg/kg) was intraperitoneally injected into pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish a rat model of intrauterine infection-induced white matter injury. Corpus callosum tissues were collected at postnatal day 14 (P14) to quantify the number of oligodendrocytes, the number and proliferation of oligodendrocyte precursor cells (OPCs), and the expression of myelin proteins (MBP and PLP). Furthermore, the expression of Wnt and Notch signaling-related proteins was analyzed. The results showed that the number of oligodendrocytes in the corpus callosum tissues of LPS-treated rats was reduced, and the expression levels of myelinating proteins were down-regulated. Further analysis showed that the Notch signaling pathway was down-regulated in the LPStreated group. These results indicate that intrauterine LPS may inhibit the proliferation of OPCs by down-regulating the Notch rather than the Wnt signaling pathway, leading to hypomyelination of white matter.

Characterization of Wnt1-inducible Signaling Pathway Protein-1 in Obese Children and Adolescents.

Wnt1-inducible signaling pathway protein-1 (WISP1), a member of the CCN family, is increasingly being recognized as a potential target for obesity and type 2 diabetes mellitus. Recent studies have shown that WISP1 can regulate low-grade inflammation in obese mice, and circulating WISP1 levels are associated with obesity and type 2 diabetes mellitus in adults. Herein, we measured serum WISP1 levels in obese youth and explored its relationships with pro-inflammatory cytokine interleukin 18 (IL-18) and other metabolic indexes. Totally, 44 normal-weight and 44 obese children and adolescents were enrolled. Physical and laboratory data were recorded, and then serum levels of WISP1 and IL-18 were determined by enzyme-linked immunosorbent assays. Results showed that serum levels of WISP1 were significantly higher in obese children and adolescents than in normal-weight healthy controls (1735.44±15.29 vs. 1364.08±18.69 pg/mL). WISP1 levels were significantly positively correlated with body mass index (BMI) and BMI z-score (r=0.392, P=0.008; r=0.474, P=0.001, respectively) in obese group; circulating IL-18 was increased in obese individuals (1229.06±29.42 vs. 295.87±13.30 pg/mL). Circulating WISP1 levels were significantly correlated with IL-18 (r=0.542, P<0.001), adiponectin (r=0.585, P<0.001) and leptin (r=0.592, P<0.001). The multivariate stepwise regression analysis showed that higher IL-18 levels represented the main determinant of increased WISP1 levels after adjusting for BMI, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR) and HbA1c in obese individuals (ß=0.542, P=0.000). WISP1 can be involved in glucose/lipid metabolism in obese youth, which may be modulated by IL-18. Increased WISP1 levels may be a risk factor of obesity and insulin resistance, and WISP1 has a potential therapeutic effect on insulin resistance in obese children and adolescents.

Characterization of fibroblast growth factor 1 in obese children and adolescents

Background: Fibroblast growth factor 1 (FGF1) can regulate glucose and lipid metabolism in obese mice. Serum FGF1 has increased in type 2 diabetes mellitus adults and correlated with BMI. This study aimed to indicate conventional weight loss effects on FGF1 in obese children and adolescents. Materials and Methods: Clinical and metabolic parameters of 88 lean and obese individuals (ages 5­15 years) and 39 obese individuals followed with 6 months of lifestyle intervention were collected. Serum FGF1 levels were detected through enzyme-linked immunosorbent assays. Results: FGF1 levels were increased in obese individuals. Serum FGF1 levels were significantly correlated with BMI and waist circumferences (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise linear regression analyses showed that FGF1 levels were significantly correlated with HbA1c and HOMA-IR (ß = 0.371, P = 0.008; ß = 0.323, P = 0.021, respectively). Weight loss (2.3 ± 0.1 kg) was accompanied by a significant reduction of circulating FGF1 levels (7.2 ± 0.4 pg/mL). Changes in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR and low-density lipoprotein cholesterol (ß = 0.277, P = 0.020; ß = 0.474, P < 0.001; ß = 0.320, P = 0.008, respectively). Conclusion: FGF1 levels were increased in obese individuals. Serum FGF1 levels were significantly correlated with BMI and waist circumferences (r = 0.377, P = 0.012; r = 0.301, P = 0.047, respectively). Multivariate stepwise linear regression analyses showed that FGF1 levels were significantly correlated with HbA1c and HOMA-IR (ß = 0.371, P = 0.008; ß = 0.323, P = 0.021, respectively). Weight loss (2.3 ± 0.1 kg) was accompanied by a significant reduction of circulating FGF1 levels (7.2 ± 0.4 pg/mL). Changes in FGF1 were significantly correlated with changes in fasting glucose, HOMA-IR and low-density lipoprotein cholesterol (ß = 0.277, P = 0.020; ß = 0.474, P < 0.001; ß = 0.320, P = 0.008, respectively).

Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt-Snail pathway.

Artemisinin and its derivatives exhibit a high activity against a range of cancer cell types both in vitro and in vivo. In clinical practice, platinum-based anti-cancer chemotherapy is widely used to treat tumors. However, a large proportion of patients receiving these treatments will relapse because of metastasis and drug resistance. The purpose of this study is to explore the combinational anti-metastatic effect of platinum-based drugs and dihydroartemisinin (DHA). Both DDP and oxaliplatin (OXA) at low doses could induce epithelial-mesenchymal transition (EMT) in HCC. Meanwhile, co-administration of DHA could enhance DDP and OXA chemosensitivity in HCC and reverse drug resistance. DHA reversed the morphological changes induced by DDP or OXA and reversed the changes in EMT biomarkers induced by DDP and OXA in HCC in vitro and in vivo via AKT-Snail signaling. DHA significantly increased platinum-based drug sensitivity and suppressed EMT induced by platinum-based drugs via AKT-Snail signaling in HCC. DHA is expected to become the new adjuvant for chemotherapy.