Long non-coding RNA SNHG4 enhances RNF14 mRNA stability to promote the progression of colorectal cancer by recruiting TAF15 protein.

SNHG4 is a lncRNA that was previously reported to promote colorectal cancer (CRC) progression via molecular sponge mechanism. Bioinformatic analysis suggested SNHG4 might scaffold TAF15 protein-RNF14 mRNA interaction. We aimed to investigate the mechanisms of potential SNHG4/TAF15/RNF14 axis in promoting CRC malignant phenotypes. Protein-RNA interaction was determined using RNA immunoprecipitation, pull-down and fluorescence in situ hybridization (FISH) combined immunofluorescence assays. Cell apoptosis rates were quantified using flow cytometry. CCK-8 and colony formation were adopted to determine cell proliferation. Wound healing and transwell assays were employed to assess cell migration and invasion, respectively. Xenograft tumor model was applied to assess the effects of SNHG4 on CRC tumorigenesis in vivo. SNHG4, TAF15 and RNF14 were up-regulated in CRC tissues. SNHG4 overexpression promoted cell proliferation, migration, invasion, and Wnt/ß-catenin pathway activation in vitro, as well as tumor growth in vivo. The inhibited malignant phenotypes caused by SNHG4 knockdown were impeded by TAF15 or RNF14 overexpression. Mechanistically, SNHG4 recruited TAF15 protein and thus promoted the interaction between TAF15 protein and RNF14 mRNA, leading to the increased RNF14 mRNA stability. This in turn facilitated the Wnt/ß-catenin signal transduction. SNHG4 enhanced RNF14 mRNA stability and activated the Wnt/ß-catenin pathway to promote the progression of colorectal cancer by recruiting TAF15 protein.

Hsa_circ_0071589 aggravates stemness and oxaliplatin resistance in colorectal cancer through sponging miR-133b to upregulate SOX13 expression.

Hsa_circ_0071589 can exacerbate the malignant behavior of colorectal cancer (CRC) cells. However, its function in stemness and oxaliplatin (OXP) resistance of CRC cells remains unclear. To assess the function of hsa_circ_0071589 in stemness and OXP resistance of CRC cells. Western blotting and qRT-PCR were applied to assess protein and mRNA levels. The association between hsa_circ_0071589, miR-133b and SOX13 was explored via a correlation analysis. Sphere formation was used to assess cell stemness. Meanwhile, the viability of CRC cells and OXP-resistant CRC cells was evaluated with the MTT assay. Cell stemness marker (CD133) levels and apoptosis of CRC cells and OXP-resistant CRC cells were tested using flow cytometry. The ALDH level was investigated using the related detection kit. In addition, the association between hsa_circ_0071589 and miR-133b and SOX13 was investigated using the RIP and dual luciferase assay. Finally, in vivo experiments were performed to detect the function of hsa_circ_0071589 in CRC, and the levels of SOX13, Ki67, and CD44 in mice were evaluated via immunohistochemistry staining. The expression of hsa_circ_0071589 and SOX13 was upregulated in CRC, whereas the expression of miR-133b was downregulated. Hsa_circ_0071589 knockdown significantly inhibited CRC stemness via the mediation of miR-133b. Moreover, hsa_circ_0071589 silencing significantly sensitized CRC cells to OXP by upregulating miR-133b. SOX13 was the direct target of miR-133b, and miR-133b could attenuate stemness and OXP resistance in CRC cells by targeting SOX13. Notably, hsa_circ_0071589 knockdown inhibited tumor growth and decreased OXP resistance in mice with CRC. Hsa_circ_0071589 aggravates stemness and OXP resistance by sponging miR-133b to indirectly target SOX13 in CRC. Thus, our study might present a novel treatment strategy against OXP-resistant CRC.

Radiomic-signature changes after early treatment improve the prediction of progression-free survival in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer.

BACKGROUND: The prognosis of lung cancer varies widely, even in cases wherein the tumor stage, genetic mutation, and treatment regimens are the same. Thus, an effective means for risk stratification of patients with lung cancer is needed. PURPOSE: To develop and validate a combined model for predicting progression-free survival and risk stratification in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) treated with ensartinib. MATERIAL AND METHODS: We analyzed 203 tumor lesions in 114 patients and evaluated average radiomic feature measures from all lesions at baseline and changes in these features after early treatment (Δradiomic features). Combined models were developed by integrating clinical with radiomic features. The prediction performance and clinical value of the proposed models were evaluated using receiver operating characteristic analysis, calibration curve, decision curve analysis (DCA), and Kaplan-Meier survival analysis. RESULTS: Both the baseline and delta combined models achieved predictive efficacy with a high area under the curve. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the combined models for tumor progression prediction. In the Kaplan-Meier analysis, the delta and baseline combined models, Δradiomic signature, and two selected clinical features could distinguish patients with a higher progression risk within 42 weeks. The delta combined model had the best performance. CONCLUSION: The combination of clinical and radiomic features provided a prognostic value for survival and progression in patients with NSCLC receiving ensartinib. Radiomic-signature changes after early treatment could be more valuable than those at baseline alone.

In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect-Exposure Relationship in Rat Plasma.

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent.

miR-133b suppresses colorectal cancer cell stemness and chemoresistance by targeting methyltransferase DOT1L.

Cancer stem cells (CSCs) are a subpopulation of chemoresistant cells that play a critical role in disease recurrence following chemotherapy. It has been reported that microRNA-133b (miR-133b) acts as a tumor suppressor in colorectal cancer (CRC). However, whether miR-133b is associated with CRC stemness and chemoresistance is not clear. In this study, we report that miR-133b is downregulated in colorectal spheroids, which are enriched with CSCs and display stem cell-like characteristics, including upreulation of CSCs surface markers and elevated chemoresistance. Additionally, miR-133b overexpression reduces CRC stemness and overrides chemoresistance to 5-Fluorouracil (5-FU) and oxaliplatin (OXP), indicating a negative role of miR-133b in regulating CRC stemness and chemoresistance. Moreover, miR-133b directly targets and suppresses the expression of disruptor of telomeric silencing 1-like (DOT1L), an exclusive H3K79 methyltransferase. Furthermore, miR-133b overexpression suppresses DOT1L-mediated H3K79me2 modification of stem cell genes, which is consistent with their downregulated transcription. More importantly, DOT1L restoration abrogates the suppressive effects of miR-133b on CRC stemness and chemoresistance, hence demonstrating that miR-133b regulates CRC stemness and chemoresistance through targeting DOT1L. Overall, these results imply that miR-133b might represent a novel therapeutic target in interfering CRC stemness and chemoresistance.

Remediation of Cr(VI)-Contaminated Soil Using the Acidified Hydrazine Hydrate.

Acidified hydrazine hydrate was used to remediate Cr(VI)-contaminated soil. The content of water-soluble Cr(VI) in contaminated soil was 4977.53 mg/kg. The optimal initial pH of hydrazine hydrate solution, soil to solution ratio and molar ratio of Cr(VI) to hydrazine hydrate for remediation of Cr(VI)-contaminated soil were 5.0, 3:1 and 1:3, respectively. Over 99.50 % of water-soluble Cr(VI) in the contaminated soil was reduced at the optimal condition within 30 min. The remediated soil can keep stable within 4 months. Meanwhile the total phosphorus increased from 0.47 to 4.29 g/kg, indicating that using of acidified hydrazine hydrate is an effective method to remediate Cr(VI)-contaminated soil.

Simultaneous giant mucinous cystadenoma of the appendix and intestinal schistosomiasis: 'case report and brief review'.

Both mucinous cystadenoma of the appendix and intestinal schistosomiasis are rare lesions. We report a rare case of simultaneous giant mucinous cystadenoma of the appendix and intestinal schistosomiasis. A 64-year-old man from China presented with a one-year history of pain in the right lower quadrant of the abdomen. There were no other pertinent historical findings, other than schistosomiasis. Imaging showed a large, tubular, mesenteric cystic structure extending downwards from the inferior wall of the cecum. Right hemicolectomy was performed for the appendiceal tumor. The final pathological diagnosis was mucinous cystadenoma with calcified Schistosome eggs within the mucosa and submucosa of the appendix, small intestine, colon, and lymph nodes. We deduced that the pathogenesis of appendiceal mucinous cystadenoma in our case was Schistosome eggs causing luminal obstruction, finally resulting in intraluminal accumulation of mucoid material. Postoperatively, the patient recovered well.

Molecular detection and characterization of Coxiella burnetii in aborted samples of livestock in China.

Coxiella burnetii is the causative agent of zoonotic Q fever. Animals are the natural reservoirs of C. burnetii, and domestic livestock represent the major sources of human infection. C. burnetii infection in pregnant females may causes abortion during late pregnancy, whereby massive shedding of C. burnetii with abortion products becomes aerosolized and persists in the environment. Therefore, monitoring and surveillance of this infection in livestock is important for the prevention of the C. burnetii transmission. Previous serological surveys have shown that C. burnetii infection is endemic in livestock in China. However, few data are available on the diagnosis of C. burnetii as a cause of abortion by molecular methods in livestock. To get a better understanding of the impact of C. burnetii infection on domestic livestock in China, a real-time PCR investigation was carried out on collected samples from different domestic livestock suffering abortion during 2021-2023. A total of 338 samples collected from eight herds of five livestock species were elected. The results showed that 223 (66 %) of the collected samples were positive for C. burnetii DNA using real-time PCR. For the aborted samples, 82 % (128/15) of sheep, 81 % (34/42) of goats, 44 % (15/34) of cattle, 69 % (18/26) of camels, and 50 % (17/34) of donkeys were positive for C. burnetii. Besides, 44 % (8/18) and 4 % (1/25) of asymptomatic individuals of sheep and donkey were also positive for C. burnetii. In addition, the positive samples were further confirmed by amplification and sequencing of the C. burnetii-specific isocitrate dehydrogenase (icd) gene. Phylogenetic analysis based on specific gene fragments of icd genes revealed that the obtained sequences in this study were clustered into two different groups associated with different origin of hosts and geographic regions. This is the first report confirming that C. burnetii exists in aborted samples of sheep, goats, cattle, donkeys and camels in China. Further studies are needed to fully elucidate the epidemiology of this pathogen in livestock as well as the potential risks to public health.

Phylogenetic analyses and antigenic characterization of foot-and-mouth disease virus PanAsia lineage circulating in China between 1999 and 2023.

Foot-and-mouth disease (FMD) is one of the most important transboundary animal diseases caused by foot-and-mouth disease virus (FMDV), leading to significant economic losses worldwide. The first report of PanAsia lineage of FMDV in China was in 1999. Since 2011, 18 outbreaks attributed to PanAsia lineage viruses have been reported across 7 provinces or municipality in China. Phylogenetic analysis indicated that these PanAsia strains were clustered into three distinct clades (clade 1, clade 2, and clade 3), with nucleotide homology ranging from 91.4% to 100%. The outbreaks of FMD caused by clade 1 strains occurred around 1999 when this lineage was prevalent globally. Clade 2 strains dominated from 2011 to 2013, while clade 3 strains were prevalent during 2018-2019, sharing only 93% homology with clade 2 strains and 91% with clade 1 strains. Tracing analysis showed that these outbreaks represented 3 distinct introductions of PanAsia viruses into China. Virus neutralization tests (VNT) have demonstrated that current commercial vaccines are effective to protect susceptible animals against these strains (r1 > 0.3). However, the growing demand for livestock has promoted animal movement and encouraged the exchange of products, services, and materials between countries, thereby heightening the risk of exotic strain incursions. Therefore, it is imperative to reinforce border controls and limit animal movements among various Asian countries continually to reduce the risk of new transboundary diseases, such as FMD incursion. Additionally, PanAsia-2 strains need to be taken seriously to prevent its incursions, and the relevant vaccines against PanAsia-2 strains needs to be stockpiled in preparation for any possible incursion.

Complete genome sequence of the porcine kobuvirus variant CH/HNXX-4/2012.

Porcine kobuvirus, an emerging virus, may be the underlying etiological cause of a large-scale outbreak of diarrhea in suckling piglets in China that started in 2010. We report the complete genome sequence of the porcine kobuvirus variant CH/HNXX-4/2012 with a 30-amino-acid deletion in its 2B-coding region that was isolated in this outbreak. This will help the phenotypic variation and evolutionary characteristics of porcine kobuvirus to be understood.

Erratum: [Corrigendum] DNA methylation is involved in the aberrant expression of miR­133b in colorectal cancer cells.

[This corrects the article DOI: 10.3892/ol.2015.3336.].

Therapeutic efficacy of metronidazole by needle-free jet injection combined with blue light therapy in Moderate-to-Severe facial acne vulgaris.

BACKGROUND: Acne vulgaris is one of the most common dermatological diseases. Some topical treatments for acne used in combination, such as blue light and topical antibiotics (such as metronidazole) by needle-free jet injection (NFJI), are becoming prevalent in clinical practice, but the efficacy remains uncertain. METHODS: In order to investigate the effect of blue light combined with metronidazole by NFJI in the treatment of acne, the 251 enrolled patients were randomly assigned into the blue light group, metronidazole (MNZ) group, and MNZ + blue light group, and then received 6-weeks' treatment. A variety of objective and subjective methods such as clinical pictures, skin barrier physiological parameters (including trans-epidermal water loss (TEWL), stratum corneum hydration, facail surface sebum, erythema and pigmentation), the Investigator Global Assessment score, acne lesion count assessment, Patients' Self-Assessment, and VAS score were used to evaluate the efficacy and side effects of the treatments. RESULTS: Compared to the baseline, the MNZ + blue light group showed significant improvement in acne lesion count reduction, TEWL, straum corneum hydration, facial surface sebum and erythema (p < 0.05). The MNZ + blue light group showed significant differences compared with the MNZ group and blue light group in terms of acne lesion count reduction and erythema (p < 0.05) Compared to the MNZ group, the MNZ + blue light group demonstrated significant improvement in TEWL and sebum (p < 0.05). While compared to the blue light group, the MNZ + blue light group showed significant improvement in hydration (p < 0.05). There was no statistically significant difference among the three groups in pigmentation (p > 0.05). CONCLUSION: The combination of MNZ by NFJI and blue light has a synergistic effect and can relieve acne skin lesion within 6 weeks in the treatment of moderate and moderate-to-severe facial acne vulgaris, meanwhile, this method has a good safety.

Genetic characterization of a new pandemic Southeast Asia topotype strain of serotype O foot-and-mouth disease virus isolated in China during 2010.

The full-length nucleotide sequence of the foot-and-mouth disease virus O/BY/CHA/2010 strain, Mya-98 lineage of Southeast Asia (SEA) topotype, was determined and compared with O/HKN/20/2010 and other known FMDV strains. Homology analysis indicated >98.0% nucleotide identity between O/BY/CHA/2010 and the epidemic strains, O/HKN/20/2010, and O/VN/2009. However, with the exception of the VP4, 2A, and 3BCD regions, O/BY/CHA/2010 showed a lower similarity with SEA topotype strains, O/VN/2006, and HLJOC12/03. A comparison of O/BY/CHA/2010 with non-SEA topotype strains showed the highest level of homology (97.4-100%) with UKG/7B/2007, Akesu/58, and the PanAsia strains in the 2A, P2, and 3CD regions, which suggested the presence of similar characteristics among these strains. Phylogenetic analysis revealed that O/BY/CHA/2010 is clustered in the Mya-98 lineage of the SEA topotype and is linked to four other isolates: HKN/20/2010, O/VN/2009, O/VN/2006, and HLJOC12/03. The VP1-based phylogenetic tree was divided into distinct clusters according to the different topotypes, while other gene-based phylogenetic trees exhibited some degree of intercrossing among topotypes. Furthermore, sequence analysis of the Lpro gene revealed a single amino acid insertion in O/HKN/20/2010 and a single amino acid deletion in O/BY/CHA/2010, in addition to a 70-nucleotide deletion within the 5'-untranslated region of O/HKN/20/2010. The majority of strains were shown to be homologous in the pseudoknots region although some exceptions were noted. This study provides a comprehensive genetic characterization of a novel FMDV isolate of the Mya-98 lineage.

Assessment of Cd Pollution in Paddy Soil-Rice System in Silver Mining-Affected Areas: Pollution Status, Transformation and Health Risk Assessment.

Mining activities are one of the main contamination sources of Cd in soil. However, the information about the influence of silver mining on Cd pollution in soil in mining-affected areas is limited. In the present study, sixteen paired soil and rice grain samples were collected from the farmland along the Luxi River nearby a silver mine in Yingtan City, Jiangxi Province, China. The total, bioavailable, and fraction of Cd in soil and Cd content in rice grain were determined by inductively coupled plasma mass spectrometry. The transformation of Cd in the soil-rice system and potential health risk via consumption of these rice grains were also estimated. The results showed that Cd concentration in these paddy soils ranged from 0.21 to 0.48 mg/kg, with the mean Cd concentration (0.36 mg/kg) exceeded the national limitation of China (0.3 mg/kg, GB 15618-2018). Fortunately, all these contaminated paddy soils were just slightly polluted, with the highest single-factor pollution index value of 1.59. The DTPA- and CaCl2-extractable Cd in these paddy soils ranged from 0.16 to 0.22 mg/kg and 0.06 to 0.11 mg/kg, respectively, and the acid-soluble Cd occupied 40.40% to 52.04% of the total Cd, which was the highest among different fractions. The concentration of Cd in rice grain ranged from 0.03 to 0.39 mg/kg, and the mean Cd concentration in rice grain (0.16 mg/kg) was within the national limitation of China (0.2 mg/kg, GB 2762-2017). The bioaccumulation factor of Cd in rice grain ranged from 0.09 to 1.18, and its correlation with various indicators was nonsignificant (p < 0.05). Health risk assessment indicated that the noncarcinogenic risk for local rice consumers was within the acceptable range, but the carcinogenic risk (CR) was ranging from 1.24 × 10-2 to 1.09 × 10-3 and higher than the acceptable range (1.0 × 10-4), indicating that the local rice consumers suffered serious risk for carcinogenic diseases. The results of the present study can provide reference for safety production of rice in silver mining-affected areas.

Radiomics Signature to Predict Prognosis in Early-Stage Lung Adenocarcinoma (≤3 cm) Patients with No Lymph Node Metastasis.

OBJECTIVES: To investigate the predictive ability of radiomics signature to predict the prognosis of early-stage primary lung adenocarcinoma (≤3 cm) with no lymph node metastasis (pathological stage I). MATERIALS AND METHODS: This study included consecutive patients with lung adenocarcinoma (≤3 cm) with no lymph node metastasis (pathological stage I) and divided them into two groups: good prognosis group and poor prognosis group. The association between the radiomics signature and prognosis was explored. An integrative radiomics model was constructed to demonstrate the value of the radiomics signature for individualized prognostic prediction. RESULTS: Six radiomics features were significantly different between the two prognosis groups and were used to construct a radiomics model. On the training and test sets, the area under the receiver operating characteristic curve value of the radiomics model in discriminating between the two groups were 0.946 and 0.888, respectively, and those of the pathological model were 0.761 and 0.798, respectively. A radiomics nomogram combining sex, tumor size and rad-score was built. CONCLUSION: The radiomics signature has potential utility in estimating the prognosis of patients with pathological stage I lung adenocarcinoma (≤3 cm), potentially enabling a step forward in precision medicine.

Neutralization and Improvement of Bauxite Residue by Saline-Alkali Tolerant Bacteria.

The high salt-alkalinity of bauxite residue (BR) hinders plant growth and revegetation of bauxite residue disposal areas (BRDA), which cause serious potential environmental and ecological risks. Bioneutralization is a promising method for improving the properties of BR and plant colonization. In the present study, a strong saline-alkali tolerant bacteria (ZH-1) was isolated from aged BR and identified as Bacillus sp. The medium of ZH-1 was optimized by orthogonal tests, and ZH-1 could decrease the medium pH from 11.8 to 6.01 (agitated culture) and 6.48 (static culture) by secretion of citric acid, oxalic acid and tartaric acid. With the inoculation of ZH-1, the pH of BR decreased from 11.6 to 8.76, and the water-soluble salt in BR increased by 68.11%. ZH-1 also changed the aggregate size distribution of BR, the mechanical-stable aggregates and water-stable aggregates increased by 18.76% and 10.83%, respectively. At the same time, the stability of the aggregates obviously increased and the destruction rate decreased from 94.37% to 73.46%. In addition, the microbial biomass carbon increased from 425 to 2794 mg/kg with the inoculation of ZH-1. Bacterial community analysis revealed that Clostridia, Bacilli, Gammaproteobacteria, Betaproteobacteria and Alphaproteobacteria were the main classes in the naturalized BR, and the inoculation of ZH-1 increased the diversity of bacteria in the BR. Overall, ZH-1 has great potential for neutralization and improvement the properties of BR and may be greatly beneficial for the revegetation of BRDA.

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer - A Comprehensive Bioinformatics Analysis.

OBJECTIVE: We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC). METHODS: Kaplan-Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan-Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC. RESULTS: ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration. CONCLUSION: ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

Study on pathogenic genes of dwarfism disease by next-generation sequencing.

BACKGROUND: There are many factors that lead to dwarfism, and the mechanism has not yet been elucidated. Next-generation sequencing may identify candidate-related gene mutations, which may clarify the molecular cause. AIM: To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations. METHODS: Physical and laboratory characteristics, including clinical examination, growth hormone drug challenge test, serum insulin-like growth factor-1 (IGF-1), IGF binding protein 3, other related tests, imaging examination, and chromosome karyotyping, were analyzed. Next-generation sequencing was performed to analyze pathogenicity variability. RESULTS: In the 39 dwarfism patients, 10 had pathogenicity variability. Gene variation was found in the OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes. Of the 10 patients with pathogenicity variability, the related physical characteristics included double breast development and growth hormone deficiency, enuresis and indirect inguinal hernia on the left, two finger distance of 70.2 cm, head circumference of 49.2 cm, ischium/lower body length of 1.8 cm, weak limb muscles, and partial growth hormone deficiency. After 6 mo of growth hormone therapy, the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2 ± 170.3 to 285.0 ± 166.0 and 3.9 ± 1.4 to 4.2 ± 1.1, respectively. CONCLUSION: OBSL1, SLC26A2, PTPN11, COL27AI, HDAC6, CUL7, FGFR3, DYNC2H1, GH1, and ATP7B genes may be related to the incidence of dwarfism, and more research needs to be performed to elucidate the mechanism.

Association of anaplastic lymphoma kinase variants and alterations with ensartinib response duration in non-small cell lung cancer.

BACKGROUND: Here, we aimed to assess the association of ALK variants and alterations with ensartinib response duration in NSCLC, and explore the potential value of computed tomography (CT) radiomic features in predicting progression-free survival (PFS). METHODS: We enrolled 88 patients with identified ALK variant NSCLC in a multicenter phase 2 trial, and assessed the impact of ALK variants and secondary ALK alterations on the clinical outcome (response duration) of patients receiving ensartinib. We also established a multifactorial model of clinicopathological and quantitative CT radiomic features to predict PFS and risk stratification. Kaplan-Meier analysis was conducted to identify risk factors for tumor progression. RESULTS: Univariate analysis indicated a statistical difference (p = 0.035) in PFS among ALK variants in three classifications (V1, V3, and other variants). Secondary ALK alterations were adversely associated with PFS both in univariate (p = 0.008) and multivariate (p = 0.04) analyses and could identify patients at high risk for early progression in the Kaplan-Meier analysis (p = 0.002). Additionally, response duration to crizotinib <1 year and liver metastasis were adversely associated with PFS. The combined model, composed of clinicopathological signature and CT radiomic signature, showed good prediction ability with the area under the receiver operating characteristic curve being 0.85, and 0.89 in the training and validation dataset respectively. CONCLUSIONS: Our study showed that secondary ALK alterations were adversely associated with ensartinib efficacy, and that ALK variants might not correlate with PFS. The quantitative radiomic signature provided added prognostic prediction value to the clinicopathological features.

MRI radiomic signature predicts intracranial progression-free survival in patients with brain metastases of ALK-positive non-small cell lung cancer.

BACKGROUND: Intracranial progression is considered an important cause of treatment failure in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients. Recent advances in targeted therapy and radiomics have generated considerable interest for the exploration of prognostic imaging biomarkers to predict the clinical course. Here, we developed a magnetic resonance imaging (MRI) radiomic signature that can stratify survival and intracranial progression. METHODS: We analyzed 87 brain metastatic lesions in 24 ALK-positive NSCLC patients undergoing ALK-inhibitor ensartinib therapy and divided them into training (n=61) and validation (n=26) sets. Radiomic features were extracted and screened from contrast-enhanced MR images. Combined with these selected features, the Rad-score was calculated with multivariate logistic regression. The predictive model and Rad-score performance were assessed in the training set and validated in the validation set; decision curve analysis was performed with the combined training and validation sets to estimate Rad-score's patient-stratification ability. RESULTS: The prediction model constructed with nine selected radiomic features could predict intracranial progression within 51 weeks (AUC =0.84 and 0.85 in the training and validation sets, respectively), while clinical and regular MRI characteristics were independent of progression (P>0.05). The decision-curve analysis showed that the radiomic prediction model was clinically useful. The Kaplan-Meier analysis showed that the progression-free survival (PFS) difference between the high- and low-risk groups distinguished by the Rad-score was significant (P=0.017). CONCLUSIONS: Radiomics may provide prognostic information and improve pretreatment risk stratification in ALK-positive NSCLC patients with brain metastases undergoing ensartinib treatment, allowing follow-up and treatment to be tailored to the patient's individual risk profile.