Residual acetabular dysplasia after Pavlik harness treatment for Graf type II hips.

Purpose: To evaluate the residual acetabular dysplasia in Graf type II hips after Pavlik harness treatment with a radiographic follow-up at 2 years of age. Methods: We retrospectively reviewed the developmental dysplasia of the hip patients who were treated with the Pavlik harness between March 2018 and February 2022. Patients with Graf type II hip dysplasia who had at least one radiographic follow-up after 2 years of age were included. The following information, sex, laterality, affected side, age at harness initiation, treatment duration, α angle, and the morphology of bony roof, was collected and studied. We evaluated the radiographic acetabular index at the last follow-up and defined the value of greater than 2 standard deviations as residual acetabular dysplasia. Results: A total of 33 patients (53 hips) met the criteria. The mean initial α angle was 53.4°; the mean age at Pavlik harness initiation was 10.9 weeks. The mean treatment duration was 10 weeks. The mean α angle at the last ultrasound follow-up was 64.9°. The mean age of the last radiographic follow-up was 2.6 years, and 26 hips had a residual acetabular dysplasia with acetabular indexes greater than 2 standard deviations above the mean. The morphology of the acetabular bony rim (odds ratio = 4.333, P = 0.029) and age of initial treatment <12 weeks (odds ratio = 7.113, P = 0.014) were seen as significant predictors for a higher acetabular index more than 2 years of age. Conclusions: A notable incidence of residual acetabular dysplasia after Pavlik harness treatment in Graf type II hips, wherein the acetabular bony roof with a blunt rim at the end of treatment and initial age after 12 weeks were independent predictors associated with residual acetabular dysplasia. Levels of evidence: Therapeutic studies, IV.

Expression and prognostic impact of DNA-PK in human lung cancer.

Among all cancer patient's lung cancer is the leading cause of death. Prognostic biomarkers continue to be investigated for the detection and stratification of lung cancer for clinical use. The DNA-dependent protein kinase is involved in mechanisms of DNA damage repair. Deregulation and overexpression of DNA-dependent protein kinase is associated with poor prognosis in various tumor entities. In this study, we investigated the expression of DNA-dependent protein kinase in relation to clinicopathological features and overall survival in patients with lung cancer. By immunohistochemistry, expression of DNA-dependent protein kinase was analyzed in 205 cases of lung cancer; 95 cases of adenocarcinoma, 83 cases of squamous cell lung carcinoma and 27 cases of small cell lung cancer and correlated with clinicopathological characteristics as well as patient's overall survival. In patients with adenocarcinoma, a significant correlation between strong expression of DNA-dependent protein kinase and worse overall survival was found. No significant association was observed in patients with squamous cell lung carcinoma and small cell lung cancer. Strong detection of DNA-dependent protein kinase expression was most evident in small cell lung cancer (81.48 %), followed by squamous cell lung carcinoma (62.65 %) and adenocarcinoma (61.05 %). In our study, expression of DNA-dependent protein kinase was associated with poor overall survival in patients with adenocarcinoma. DNA-dependent protein kinase could serve as a new prognostic biomarker.

Urokinase-Type Plasminogen Activator Receptor (uPAR) Cooperates with Mutated KRAS in Regulating Cellular Plasticity and Gemcitabine Response in Pancreatic Adenocarcinomas.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers. Given the currently limited therapeutic options, the definition of molecular subgroups with the development of tailored therapies remains the most promising strategy. Patients with high-level gene amplification of urokinase plasminogen activator receptor (uPAR/PLAUR) have an inferior prognosis. We analyzed the uPAR function in PDAC to understand this understudied PDAC subgroup's biology better. METHODS: A total of 67 PDAC samples with clinical follow-up and TCGA gene expression data from 316 patients were used for prognostic correlations. Gene silencing by CRISPR/Cas9, as well as transfection of uPAR and mutated KRAS, were used in PDAC cell lines (AsPC-1, PANC-1, BxPC3) treated with gemcitabine to study the impact of these two molecules on cellular function and chemoresponse. HNF1A and KRT81 were surrogate markers for the exocrine-like and quasi-mesenchymal subgroup of PDAC, respectively. RESULTS: High levels of uPAR were correlated with significantly shorter survival in PDAC, especially in the subgroup of HNF1A-positive exocrine-like tumors. uPAR knockout by CRISPR/Cas9 resulted in activation of FAK, CDC42, and p38, upregulation of epithelial makers, decreased cell growth and motility, and resistance against gemcitabine that could be reversed by re-expression of uPAR. Silencing of KRAS in AsPC1 using siRNAs reduced uPAR levels significantly, and transfection of mutated KRAS in BxPC-3 cells rendered the cell more mesenchymal and increased sensitivity towards gemcitabine. CONCLUSIONS: Activation of uPAR is a potent negative prognostic factor in PDAC. uPAR and KRAS cooperate in switching the tumor from a dormant epithelial to an active mesenchymal state, which likely explains the poor prognosis of PDAC with high uPAR. At the same time, the active mesenchymal state is more vulnerable to gemcitabine. Strategies targeting either KRAS or uPAR should consider this potential tumor-escape mechanism.

NPRL2 down-regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression.

Hepatocellular carcinoma (HCC) is a highly invasive malignancy. Recently, GATOR1 (Gap Activity TOward Rags 1) complexes have been shown to play an important role in regulating tumor growth. NPRL2 is a critical component of the GATOR1 complex. Therefore, this study used NPRL2 knockdown to investigate how GATORC1 regulates the prognosis and development of HCC via the mammalian target of rapamycin (mTOR) and autophagy signaling pathways. We established HepG2 cells with NPRL2 knockdown using small interfering RNA (siRNA) and short hairpin RNA (shRNA) systems. The siRNA-mediated and shRNA-mediated NPRL2 down-regulation significantly reduced the expression of NPRL2 and two other GATPOR1 complex components, NPRL3 and DEPDC5, in HepG2 cells; furthermore, the efficient down-regulation of NPRL2 protein expression by both the shRNA and siRNA systems enhanced the proliferation, migration, and colony formation in vitro. Additionally, the NPRL2 down-regulation significantly increased HCC growth in the subcutaneous and orthotopic xenograft mouse models. The NPRL2 down-regulation increased the Rag GTPases and mTOR activation and inhibited autophagy in vitro and in vivo. Moreover, the NPRL2 level in the tumors was significantly associated with mortality, recurrence, the serum alpha fetoprotein level, the tumor size, the American Joint Committee on Cancer stage, and the Barcelona Clinic Liver Cancer stage. Low NPRL2, NPRL3, DEPDC5, and LC3, and high p62 and mTOR protein expression in the tumors was significantly associated with disease-free survival and overall survival in 300 patients with HCC after surgical resection. Conclusion: The efficient down-regulation of NPRL2 significantly increased HCC proliferation, migration, and colony formation in vitro, and increased HCC growth in vivo. Low NPRL2 protein expression in the tumors was closely correlated with poorer clinical outcomes in patients with HCC. These results provide a mechanistic understanding of HCC and aid the development of treatments for HCC.

Cancer-Associated Fibroblasts Hinder Lung Squamous Cell Carcinoma Oxidative Stress-Induced Apoptosis via METTL3 Mediated m6A Methylation of COL10A1.

Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment are key players in tumorigenesis and tumor development. Nevertheless, the regulatory mechanisms of CAFs on lung squamous cell carcinoma- (LUSC-) associated remain poorly elucidated. Methods: The microarray dataset GSE22874, containing 30 specimens of primary culture of normal fibroblasts (NFs) and 8 specimens of cancer-associated fibroblasts (CAFs) samples derived from LUSC, was retrieved from the Gene Expression Omnibus (GEO) database and then calculated by using the R language (limma package) to identify differentially expressed genes (DEGs). CAF-conditioned medium (CAF-CM) was collected and used to culture LUSC cells, followed by assessment of cell proliferation, apoptosis, and oxidative stress levels by using CCK-8, annexin V-FITC/PI double staining and ELISA assays. Subsequently, COL10A1 was knocked down in CAFs to assess the role of COL10A1 in CAF regulation of LUSC behavior. Bioinformatics online analysis and MeRIP were applied to predict and test the m6A modification of COL10A1 mRNA and the regulatory relationship with METTL3. Rescue experiments were next performed to explore the effects of METTL3 and COL10A1 in CAFs on LUSC cell proliferation, apoptosis, and oxidative stress. LUSC tumor cells with or without (COL10A1-silenced) CAFs were subcutaneously inoculated in nude mice to evaluate the effect of COL10A1 in CAFs on LUSC tumor growth. Results: Elevated expression of COL10A1 was found in LUSC-derived CAFs by GSE22874 dataset analysis. We discovered that COL10A1 and METTL3 was expressed in both LUSC cells and matched CAFs, while COL10A1 expression was prominently higher in CAFs than in LUSC cells. CAF-CM memorably encouraged LUSC cell proliferation and suppressed apoptosis-induced oxidative stress, which was reversed by interfering with COL10A1 expression in CAFs, suggesting that COL10A1 might be secreted by CAFs into the culture medium to exert its effects inside LUSC cells. Global m6A modification was decreased in METTL3 knocked down CAFs. M6A modification, expression levels, and stability of COL10A1 mRNA were impaired upon METTL3 knockdown in CAFs. Overexpression of COL10A1 in CAFs partially reversed the effect of METTL3 knockdown on the malignant behavior of LUSC cells. In vivo studies confirmed that CAFs accelerated LUSC tumor growth, and this effect was counteracted by COL10A1 silencing. Conclusions: COL10A1 secreted by CAFs could facilitate LUSC cell proliferation and repress apoptosis-induced oxidative stress, and the mechanism was due to elevated expression mediated by METTL3 promoting its mRNA m6A modification, thereby accelerating tumor growth.

Regulation and Therapeutic Targeting of MTHFD2 and EZH2 in KRAS-Mutated Human Pulmonary Adenocarcinoma.

Activating KRAS mutations occur in about 30% of pulmonary adenocarcinoma (AC) cases and the discovery of specific inhibitors of G12C-mutated KRAS has considerably improved the prognosis for a subgroup of about 14% of non-small cell lung cancer (NSCLC) patients. However, even in patients with a KRAS G12C mutation, the overall response rate only reaches about 40% and mutations other than G12C still cannot be targeted. Despite the fact that one-carbon metabolism (1CM) and epigenetic regulation are known to be dysregulated by aberrant KRAS activity, we still lack evidence that co-treatment with drugs that regulate these factors might ameliorate response rates and patient prognosis. In this study, we show a direct dependency of Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) and Enhancer of Zeste Homolog 2 (EZH2) expression on mutationally activated KRAS and their prognostic relevance in KRAS-mutated AC. We show that aberrant KRAS activity generates a vulnerability of AC cancer cell lines to both MTHFD2 and EZH2 inhibitors. Importantly, co-inhibition of both factors was synergistically effective and comparable to KRASG12C inhibition alone, paving the way for their use in a therapeutic approach for NSCLC cancer patients.

Expression and prognostic impact of CD49b in human lung cancer.

ABSTRACT: Lung cancer remains the worldwide leading cause of cancer-related death. Currently, prognostic biomarkers for the detection and stratification of lung cancer are being investigated for clinical use. The surface protein cluster of differentiation 49b (CD49b) plays an important role in promoting cell proliferation and invasion in different tumor entities and blocking CD49b improved the tumor immune response. Overexpression of CD49b has been associated with unfavorable survival rates in several malignant tumor entities, such as prostate cancer, gastric cancer and colon cancer. Therefore, we aimed to analyze the protein expression of CD49b in patients with different types of lung cancer and additionally to identify the influence of CD49b on clinicopathological characteristics and overall survival.Expression levels of CD49b were retrospective analyzed by immunohistochemistry in 92 cases of pulmonary adenocarcinoma (AC), 85 cases of squamous cell lung carcinoma (SQCLC) and 32 cases of small cell lung cancer (SCLC) and correlated with clinicopathological characteristics and patients' overall survival.A strong expression of CD49b was most seen in SQCLC (78%), followed by AC (48%) and SCLC (9%). All patients combined, strong expression of CD49b correlated significantly with poorer overall survival. However, an increased expression of CD49b correlated significantly with a poorer survival rate only in SQCLC. In AC and SCLC, no significant correlation could be demonstrated in this regard.In our study, CD49b expression was associated with poor overall survival in patients with SQCLC. Accordingly, CD49b could serve as a new prognostic biomarker and, moreover, be a potential new drug target in SQCLC.

Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection.

BACKGROUND: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. RESULTS: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68-26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01-0.34), p = 0.004, and 0.07 (0.01-0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85-922), p = 0.008, and 17.9 (1.05-306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. CONCLUSION: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

Role of Annexin A1 in Squamous Cell Lung Cancer Progression.

Lung cancer remains the primary cause of cancer-related death worldwide, and its molecular mechanisms of tumor progression need further characterization to improve the clinical management of affected patients. The role of Annexin A1 (ANXA1) in tumorigenesis and cancer progression in general and especially in lung cancer remains to be controversial and seems to be highly tissue specific and inconsistent among tumor initiation, progression, and metastasis. In the current study, we investigated ANXA1 expression in 81 squamous cell lung cancer (SQCLC), 86 pulmonary adenocarcinoma (AC), and 30 small cell lung cancer (SCLC) patient-derived tissue samples and its prognostic impact on patient's survival. Mechanistically, we analyzed the impact of ANXA1 expression on proliferation and migration of SQCLC cell lines using CRISPR-Cas9 and mammalian overexpression vectors. Strong expression of ANXA1 was significantly correlated to longer overall survival only in SQCLC patients (P = 0.019). Overexpression of ANXA1 promoted proliferation in SQCLC cell lines but suppressed their migration, while knockout of ANXA1 promoted cell migration and suppressed proliferation. In conclusion, ANXA1 expression might elongate patients' survival by inhibiting tumor cell migration and subsequent metastasis.

Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis.

BACKGROUND: The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages. METHODS: Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. RESULTS: In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0-96) months for the total cohort and was subdivided into 52 (8-96), 32 (1-96), 19 (0-84), and 12 (0-79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child-Pugh (C-P) class; (3) SR, hepatitis B virus (HBV) infection, and C-P class; and (4) SR, HBV infection, and C-P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages. CONCLUSIONS: SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.

Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis.

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. METHODS: We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan-Meier analysis. RESULTS: In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7-61.2], 62.3 months (CI: 42.1-72.9), and 36.2 months (CI: 15.4-56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. CONCLUSION: The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

Gradual ulnar lengthening in Masada type I/IIb deformity in patients with hereditary multiple osteochondromas: a retrospective study with a mean follow-up of 4.2 years.

BACKGROUND: Gradual ulnar lengthening is the most commonly used procedure in the treatment of Masada type I/II deformity in patients with hereditary multiple osteochondromas. However, the treatment remains controversial for the recurrence of deformity in growing children. This study aims to evaluate the clinical and radiological outcomes of ulnar gradual lengthening in our clinic. METHODS: We retrospectively reviewed patients who underwent ulnar lengthening by distraction osteogenesis from June 2008 to October 2017. The carrying angle (CA) and range of motion (ROM) of the forearm and elbow were clinically assessed, and the radial articular angle (RAA) and ulnar shortening (US) were radiologically assessed before lengthening, 2 months after external frame removal, and at the last follow-up. RESULTS: The current study included 15 patients (17 forearms) with a mean age of 9.4 ± 2.3 years at the index surgery. The mean follow-up period was 4.2 ± 2.4 years. There were 9 patients (10 forearms) with Masada type I deformity and 6 patients (7 forearms) with Masada type IIb deformity. The mean amount of ulnar lengthening was 4.2 ± 1.2 cm. The mean RAA improved from 37 ± 8 to 30 ± 7° initially (p = 0.005) and relapsed to 34 ± 8° at the last follow-up (p = 0.255). There was a minimal deterioration of US yet significant improvement at the last follow-up compared to pre-op (p < 0.001). At the last follow-up, the mean forearm pronation and elbow flexion increased significantly (p < 0.001 and p = 0.013, respectively), and the mean carrying angle also improved significantly (p < 0.001). No patient with type IIb deformity achieved a concentric radial head reduction. CONCLUSIONS: Gradual ulnar lengthening significantly reduces cosmetic deformity and improves function in patients with Masada type I/IIb deformity. Our results supported early ulnar lengthening for patients with a tendency of dislocation of the radial head.

Regulation of BTG3 by microRNA-20b-5p in non-small cell lung cancer.

The present study aimed to evaluate microRNA- 20b-5p (miR-20b-5p) expression in non-small cell lung cancer (NSCLC), and investigate the effects of miR-20b-5p expression on NSCLC cell proliferation and migration. Reverse transcription-quantitative polymerase chain reaction was performed to measure the expression level of miR-20b-5p in NSCLC tissues and cell lines. Cell Counting Kit-8 and wound healing assays were used to measure cell proliferation and migration. A dual-luciferase reporter assay was performed to validate B-cell translocation gene 3 (BTG3) as a target of miR-20b-5p. It was identified that the expression level of miR-20b-5p is elevated in NSCLC tissues and cell lines. miR-20b-5p overexpression was revealed to promote NSCLC cell proliferation and migration. Furthermore, BTG3 was identified as a direct target of miR-20b-5p, and BTG3 overexpression reversed a miR-20b-5p mimic-induced increase in cell proliferation and migration. In summary, the present study revealed that miR-20b-5p promotes NSCLC cell proliferation and migration by targeting BTG3, which may assist with the development of a novel therapeutic target for the treatment of NSCLC.

Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma.

The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

Identification of risk factors affecting bone formation in gradual ulnar lengthening in children with hereditary multiple exostoses: A retrospective study.

The forearm deformity classified by Masada is a characteristic trait of patients with hereditary multiple exostoses (HME). Ulnar gradual lengthening, which was considered to be a safe and reliable procedure, was popular in treating these difficult deformities, however, delayed consolidation of the callus is uncommon but not rare in literature review. The purpose of this study was to try to identify the risk factors influencing bone healing in gradual ulnar lengthening in HME.We retrospectively reviewed patients with HME-induced forearm deformity who underwent gradual ulnar lengthening at our hospital from 2010 to 2016. Patients' demographic data, forearm deformity of Masada type, surgical procedure, ulnar diameter of osteotomy site, and external fixator type were recorded. We also reviewed radiographical data included gained length, axis deviation, callus form. Clinical outcome was assessed by the bone healing index (HI). Multiple linear regression was used to analyze the relationships between diffident parameters and the HI, the level of significance was set P <.05.Thirty-three patients were included in this study. The mean follow-up period was 1.5 (range 0.5-8) years. Circular external fixators were used in 5 patients and monolateral external fixators were used in 28 patients. The mean achieved length was 4.24 cm. The mean HI was 50.3 (range 26.6-99.3) days/cm. In patient with monolateral external fixator, patient's age was positively correlated with the bone HI (P = .001), while diameter and body mass index (BMI) were negatively correlated with the HI (P = .040, .018, respectively). Patient's sex, removal of distal ulnar exostoses, lengthening percentage, and axis deviation were non-significant in the regression model.When using monolateral external fixator for ulnar lengthening, patient's age, diameter of osteotomy site, and BMI are the most important risk factors related to bone formation. Pediatric orthopedic surgeons should consider these variables in order to avoid delayed union.

Heterogeneous spectrum of EXT gene mutations in Chinese patients with hereditary multiple osteochondromas.

Hereditary multiple osteochondroma (HMO) is one of the most common genetic skeletal disorders. It is caused by mutations in either EXT1 or EXT2 resulting in abnormal skeletal growth and morphogenesis. However, the spectrum and frequency of EXT1 and EXT2 mutations in Chinese patients with HMO was not previously investigated.Mutations were identified by performing Sanger sequencing analysis of the complete coding regions and flanking intronic sequences of EXT1 and EXT2, followed by multiplex ligation-dependent probe amplification (MLPA) analysis to detect gene deletions or duplications that could not be identified by the Sanger sequencing method.The present study identified pathogenic mutations in 93% (68/73) of unrelated HMO probands from 73 pedigrees. Mutations in EXT1 and EXT2 were identified in 53% (39/73) and 40% (29/73) of families. We identified 58 distinct mutations in EXT1 and EXT2, including 20 frameshift mutations, 16 nonsense mutations, 7 missense mutations, 9 splice site mutations, 5 large deletions, and 1 in-frame deletion mutation. Twenty-six of these mutations were novel and 32 were previously reported. Most of the mutations in EXT1 were base deletions or insertions (21/33), whereas the majority of those in EXT2 were single base substitution (18/25).Complete sequencing of both the EXT1 and EXT2 followed by MLPA analysis is recommended for genetic analysis of Chinese patients with HMO. This study provides a comprehensive characterization of the genetic aberrations found in Chinese patients with HMO and highlights the diagnostic value of molecular genetic analysis in this particular disease.

Synergistic anti-proliferative and pro-apoptotic activities of 5F and cisplatin in human non-small cell lung cancer NCI-H23 cells.

Two-drug combination chemotherapy, often including cisplatin and one other drug, remains the standard of care for patients with advanced non-small cell lung cancer (NSCLC). To improve the treatment of late-stage NSCLC and decrease the toxicity of combination chemotherapy, the search for novel drugs remains vigorous. Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5F), a bioactive compound isolated from the herb Pteris semipinnata L., has previously been shown to induce apoptosis and inhibit proliferation in various cancer cells. One outstanding property of 5F is its minimal side effects. In the present study, 5F was combined with cisplatin to treat NCI-H23 cells; proliferation, apoptosis and cell cycle arrest were measured by an MTT assay, Annexin V staining/flow cytometry and propidium iodide staining/flow cytometry, respectively. The messenger RNA levels of ß-catenin, glycogen synthase kinase (GSK)-3ß, c-Myc and cyclin D1 were determined by reverse transcription-quantitative polymerase chain reaction, and the protein levels of ß-catenin and GSK-3ß were measured by western blot analysis. The results revealed that 5F and cisplatin synergistically induced apoptosis and inhibited cell growth, arrested cell cycles in the G0/G1 phase, downregulated ß-catenin, c-Myc and cyclin D1, and upregulated GSK-3ß. These findings merit in vivo studies using animal models of NSCLC to confirm the addition of 5F as a third drug to cisplatin-based combination therapy for late-stage NSCLC.

A genotype-phenotype study of hereditary multiple exostoses in forty-six Chinese patients.

BACKGROUND: Hereditary multiple exostoses (HME) is a rare autosomal dominant skeletal disorder that can cause a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of HME by using a scoring system and correlate the genotypes with different clinical phenotypes in Chinese patients. METHODS: Forty-six patients from different families were prospectively enrolled. The mutations were identified by direct sequencing of PCR-amplified genomic DNA or by multiplex ligation-dependent probe amplification (MLPA). Patients' demographic data, height, age of onset, number of anatomical sites, forearm deformity, and lower extremity alignment were analysed according to genotype and gender. A scoring system was used to assess the severity of the clinical phenotype. RESULTS: Thirty (60%) patients presented mutations in the EXT1 gene, and 16 (32%) presented mutations in the EXT2 gene. The mean age of onset was 2.96 years. The mean number of involved anatomic sites was 15.35. Male patients had more lesion sites than female patients (15.97 vs. 13.77, p = 0.046). The height evaluation illustrated that 67% of the patients (31 of 46) were below the 50th percentile, and the patients with EXT1 mutations were shorter than those with EXT2 mutations (p = 0.005). Forearm deformity showed a significant correlation with the number of involved anatomical sites (r = 0.382, p = 0.009). Moreover, a higher total score was found in patients with EXT1 mutations (p = 0.001). CONCLUSIONS: The clinical manifestations of 46 Chinese HME patients were similar to those in previous reports of Western populations. Patients with EXT1 mutations have a more severe clinical phenotype than patients with EXT2 mutations.

Open reduction combined with CORA-based osteotomy of the ulna in the treatment of missed Bado type I Monteggia injury: A retrospective study of 5 cases.

Open reduction combined with ulnar osteotomy is the most common approach to treating missed Monteggia injuries. The osteotomy is usually performed at the proximal ulna to ensure better healing and fewer complications. The purpose of this study is to present a center of rotation angulation (CORA)-based osteotomy of the ulna for treating Bado type I Monteggia injuries.We retrospectively reviewed the cases of patients who were treated with open reduction combined with a CORA-based ulnar osteotomy between February 2014 and December 2016. Each patient provided his or her internal control, and paired data of the involved and uninvolved sides were analyzed to evaluate forearm rotation function.Five patients (3 male, 2 female) with median age 5.7 years (range, 3.4-6.8 years) were operated on by the senior author in our hospital. The median interval between the original injury and the corrective surgery was 3 months (range, 1-4 months). In a median follow-up of 10 months (range, 6-17 months), all patients obtained stable reduction of the radial head and uneventful healing of the ulnar osteotomy. All patients had pain-free elbows with no neurological or vascular complications and no implant breakage. Patients showed excellent outcomes evaluated using the Broberg and Morrey index.Open reduction with a CORA-based osteotomy of the ulna for the treatment of missed Bado type I Monteggia injury with an obvious ulnar bowing deformity resulted in stable reduction of the radial head and excellent forearm function.

Posttraumatic growth and demoralization after cancer: The effects of patients' meaning-making.

OBJECTIVE: It is common for patients to experience positive and negative psychological changes (e.g., posttraumatic growth or demoralization) after being diagnosed with cancer. Although demoralization and posttraumatic growth are both related to meaning-making, little attention has been paid to the associations among these concepts. The current study investigated the relationship between demoralization, posttraumatic growth, and meaning-making (focusing on sense-making and benefit-finding during the experience of illness) in cancer patients. METHOD: Some 200 cancer patients (with lung cancer, lymphoma, or leukemia) at the MacKay Memorial Hospital in New Taipei completed the Demoralization Scale-Mandarin Version (DS-MV), the Chinese Posttraumatic Growth Inventory (CPTGI), and a self-designed questionnaire for assessing sense-making and benefit-finding. RESULTS: Demoralization was negatively correlated with posttraumatic growth, sense-making, benefit-finding, and time-since-diagnosis. Multiple regression analysis showed that meaning-making had different effects on demoralization and posttraumatic growth. The interactions of sense-making with either benefit-finding or time-since-diagnosis significantly predicted demoralization. Individuals with relatively higher sense-making and benefit-finding or shorter time-since-diagnosis experienced less demoralization. SIGNIFICANCE OF RESULTS: The suffering of cancer may turn on the psychological process of demoralization, posttraumatic growth, and meaning-making in patients. Cancer patients who evidenced higher posttraumatic growth experienced less demoralization. Trying to identify positive changes in the experience of cancer may be a powerful way to increase posttraumatic growth. As time goes by, patients experienced less demoralization. Facilitating sense-making can have similar effects. Cancer patients with less benefit-finding experience higher demoralization, but sense-making buffers this effect.