m6A modification of VEGFA mRNA by RBM15/YTHDF2/IGF2BP3 contributes to angiogenesis of hepatocellular carcinoma.

Vascular endothelial growth factor A (VEGFA) plays a critical role as a potent angiogenesis factor and is highly expressed in hepatocellular carcinoma (HCC). Although the expression of VEGFA has been strongly linked to the aggressive nature of HCC, the specific posttranscriptional modifications that might contribute to VEGFA expression and HCC angiogenesis are not yet well understood. In this study, we aimed to investigate the epitranscriptome regulation of VEGFA in HCC. A comprehensive analysis integrating MeRIP-seq, RNA-seq, and crosslinking-immunprecipitation-seq data revealed that VEGFA was hypermethylated in HCC and identified the potential m6A regulators of VEGFA including a m6A methyltransferase complex component RBM15 and the two readers, YTHDF2 and IGF2BP3. Through rigorous cell and molecular biology experiments, RBM15 was validated as a key component of methyltransferase complex responsible for m6A methylation of VEGFA, which was subsequently recognized and stabilized by IGF2BP3 and YTHDF2, leading to enhanced VEGFA expression and VEGFA-related functions such as human umbilical vascular endothelial cells (HUVEC) migration and tube formation. In the HCC xenograft model, knockdown of RBM15, IGF2BP3, or YTHDF2 resulted in reduced expression of VEGFA, accompanied by significant inhibition of tumor growth closely associated with VEGFA expression and angiogenesis. Furthermore, our analysis of HCC clinical samples identified positive correlations between the expression levels of VEGFA and the regulators RBM15, IGF2BP3, and YTHDF2. Collectively, these findings offer novel insights into the posttranscriptional modulation of VEGFA and provide potential avenues for alternative approaches to antiangiogenesis therapy targeting VEGFA.

[Application of anterior region suture of popliteal hiatus in treatment of discoid lateral meniscus injury with instability in popliteal tendon region].

Objective: To discuss the application of anterior region suture of the popliteal hiatus (PH) under arthroscopy in the treatment of discoid lateral meniscus (DLM) injury with instability in the popliteal tendon region. Methods: The clinical data of 53 patients (56 knees) with DLM injury who met the selection criteria between March 2014 and November 2022 were retrospectively analyzed. There were 15 males and 38 females, aged 8-55 years with an average age of 36.5 years. Fourteen cases had a history of trauma, while the remaining 39 cases had no clear history of trauma. The disease duration ranged from 1 day to 6 years, with an average duration of 15.6 months. According to the Watanabe classification, there were 40 knees of complete type and 16 knees of incomplete type. The preoperative International Knee Documentation Committee (IKDC) knee joint score was 51.2±8.3, the Lysholm score was 59.6±11.2, and the visual analogue scale (VAS) score was 4.7±1.3. After the arthroscopic meniscal plasty, the instability of the popliteal tendon region meniscus was checked by probing traction. Subsequently, the Out-inside technique or a combination of Out-inside and All-inside techniques was used to suture the anterior region of the PH. The stability of the meniscus after suturing was assessed, and if necessary, further suturing using the All-inside technique at the posterior region of the PH, the posterior horn of the meniscus, and using the Out-inside technique at the anterior horn of the meniscus was performed. Postoperative complications were recorded. The effectiveness was evaluated using pre- and post-operative IKDC scores, Lysholm scores, and VAS scores. Results: After operation, knee joint pain, crepitus, and locking disappeared, with McMurray and grinding tests turning negative. All patients were followed up 12-93 months with an average of 57.5 months. There was no complication such as common peroneal nerve injury, deep vein thrombosis of the lower limbs, joint infection, or joint stiffness. At last follow-up, the IKDC knee joint score was 76.7±5.5, the Lysholm score was 94.0±4.1, and the VAS score was 1.1±0.8. The differences compared with preoperative scores were significant ( t=-22.090, P<0.001; t=-23.704, P<0.001; t=19.767, P<0.001). Conclusion: Suturing of the anterior region of the PH is crucial in the treatment of DLM injury with instability in the popliteal tendon region.

[Treatment of tibial insertion avulsion fracture of anterior cruciate ligament involving anterior root of lateral meniscus with multi-point fixation with anchor and suture].

Objective: To investigate the effectiveness of arthroscopic multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of anterior cruciate ligament (ACL) involving the anterior root of lateral meniscus (LM). Methods: A retrospective analysis was conducted on the clinical data of 28 patients with tibial insertion avulsion fracture of ACL involving the anterior root of LM who were treated with arthroscopic multi-point fixation with anchor and suture between October 2017 and January 2023. There were 12 males and 16 females with the mean age of 26 years (range, 13-57 years). There were 20 cases of sports injury and 8 cases of traffic accident injury. In 2 cases of old fracture, the time from injury to operation was 45 days and 90 days, respectively; in 26 cases of fresh fracture, the time from injury to operation was 3-20 days (mean, 6.7 days). According to the Meyers-McKeever classification, there were 4 cases of type Ⅱ, 11 cases of type Ⅲ, and 13 cases of type Ⅳ. The preoperative Lysholm knee function score was 42.1±9.0, the International Knee Documentation Committee (IKDC) score was 40.0±7.3, and the Tegner score was 0.7±0.7. Results: All operations were successfully completed, and the incisions healed by first intention. All the 28 patients were followed up 5-60 months (mean, 20.4 months). During the follow-up, there was nocomplication such as infection, vascular or nerve injury, loosening or breakage of internal fixator, or stiffness of knee joint. Postoperative X-ray films showed satisfactory fracture reduction and firm fixation. All fractures healed clinically, and the healing time was 8-16 weeks (mean, 10.3 weeks). At last follow-up, Lachman test and anterior drawer test were negative. At last follow-up, Lysholm knee function score was 92.4±5.5, IKDC score was 91.6±4.4, and Tegner score was 5.2±1.1, which significantly improved when compared with preoperative scores ( t=-22.899, P<0.001; t=-29.870, P<0.001; t=-19.979, P<0.001). Conclusion: Multi-point fixation with anchor and suture in the treatment of tibial insertion avulsion fracture of ACL involving the anterior root of LM can not only fix the LM, but also effectively reduce and fix the avulsion fracture, which can obtain good effectiveness.

[A study on repair method of type â ¡c injury in lateral meniscus popliteal tendon area of porcine knee].

Objective: To investigate the repair method of type Ⅱc injury in the lateral meniscus popliteal tendon area based on the porcine knee joint. Methods: Eighteen commercially available fresh porcine knee joints were randomly divided into 3 groups ( n=6). After preparing a type Ⅱc injury in the lateral meniscus popliteal tendon area, and the anterior (group A), posterior (group B), or anterior and posterior (group C) of the popliteal hiatus (PH) was sutured by vertical mattress. The tension meter was used to apply gradient tensions of 2, 4, 6, 8, and 10 N along the tibial plateau horizontally, respectively, to pull the midpoint of the lateral meniscus popliteal tendon area. The displacement values before modeling, after modeling, and after suture were recorded. The reduction value of lateral meniscus displacement and reduction rate after suture were calculated and compared between groups. Results: There was no significant difference between groups ( P>0.05) in the displacement values before modeling, after modeling, and after suture under different tensions. There was no significant difference between groups A and C ( P>0.05) in the reduction value of lateral meniscus displacement and reduction rate after suture under different tensions. The reduction value of lateral meniscus displacement and reduction rate after suture in group B were lower than those in groups A and C. The reduction value of lateral meniscus displacement under tension of 2 N and the reduction rates under tensions of 2, 4, and 6 N between groups A and B showed significant differences ( P<0.05). The reduction value of lateral meniscus displacement and the reduction rate under tensions of 2, 4, and 6 N between groups B and C showed significant differences ( P<0.05). Conclusion: Suturing the anterior area of PH is the key to repairing type Ⅱc injury of lateral meniscus popliteal tendon area.

Infective endocarditis with anomalous origin of coronary arteries and an abnormal aortic root bulge: A case report.

Background: The aortic bulge sign possibly indicates an arterial aneurysm, pseudoaneurysm, aortic dissection, or aortic diverticulum. The aortic diverticulum is a congenital abnormality of the aorta, mainly known as an aneurysmal remnant of the dorsal fourth aortic arch or ductus arteriosus. However, the diverticulum of another part of the aorta has rarely been reported. Case summary: We report a case of a 24-year-old male with a history of oral ulcer presented with recurrent hyperpyrexia and chest pain. Echocardiography and computed tomography showed the anomalous origin of the coronary arteries, aortic valve vegetations, and a bulge at the aortic root. The patient then received a Bentall procedure. The aorta and aortic valves were replaced by a valved conduit. The bulge with a normal arterial wall at the aortic root was considered to be a diverticulum. The infective endocarditis was verified as a secondary oral-derived streptococcal infection. The patient was discharged 15 days after surgery. Post-operative echocardiography had no positive findings. Conclusion: Our case report highlights the role of multimodal cardiovascular imaging for the diagnostic workup of rare disorders, such as the presence of a diverticulum in the aortic root in a patient with endocarditis and anomalous origin of the right coronary artery.

M1ARegpred: Epitranscriptome Target Prediction of N1-methyladenosine (m1A) Regulators Based on Sequencing Features and Genomic Features.

BACKGROUND: N1-methyladenosine (m1A) is a reversible post-transcriptional modification in mRNA, which has been proved to play critical roles in various biological processes through interaction with different m1A regulators. There are several m1A regulators existing in the human genome, including YTHDF1-3 and YTHDC1. METHODS: Several techniques have been developed to identify the substrates of m1A regulators, but their binding specificity and biological functions are not yet fully understood due to the limitations of wet-lab approaches. Here, we submitted the framework m1ARegpred (m1A regulators substrate prediction), which is based on machine learning and the combination of sequence-derived and genome-derived features. RESULTS: Our framework achieved area under the receiver operating characteristic (AUROC) scores of 0.92 in the full transcript model and 0.857 in the mature mRNA model, showing an improvement compared to the existing sequence-derived methods. In addition, motif search and gene ontology enrichment analysis were performed to explore the biological functions of each m1A regulator. CONCLUSIONS: Our work may facilitate the discovery of m1A regulators substrates of interest, and thereby provide new opportunities to understand their roles in human bodies.

Research Progress for RNA Modifications in Physiological and Pathological Angiogenesis.

As a critical layer of epigenetics, RNA modifications demonstrate various molecular functions and participate in numerous biological processes. RNA modifications have been shown to be essential for embryogenesis and stem cell fate. As high-throughput sequencing and antibody technologies advanced by leaps and bounds, the association of RNA modifications with multiple human diseases sparked research enthusiasm; in addition, aberrant RNA modification leads to tumor angiogenesis by regulating angiogenesis-related factors. This review collected recent cutting-edge studies focused on RNA modifications (N6-methyladenosine (m6A), N5-methylcytosine (m5C), N7-methylguanosine (m7G), N1-methyladenosine (m1A), and pseudopuridine (Ψ)), and their related regulators in tumor angiogenesis to emphasize the role and impact of RNA modifications.

The application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia: A meta-analysis and systematic review.

BACKGROUND: The role of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia remains unclear, we aimed to analyze this issue to provide evidences into the management of clinical pneumonia. METHODS: We searched PubMed et al databases up to October 20, 2021 for the randomized controlled trials on the application of ambroxol hydrochloride combined with fiberoptic bronchoscopy in elderly patients with severe pneumonia. Related outcomes were extracted and analyzed. Review Manager 5.3 software was used for data analysis. RESULTS: A total of 13 randomized controlled trials involving 1317 elderly patients (559 cases in the ambroxol hydrochloride + fiberoptic bronchoscopy group and 658 cases in the fiberoptic bronchoscopy group) with pneumonia were included. Meta-analyses indicated that the blood oxygen partial pressure [mean difference (MD) = 5.75, 95% confidence interval (CI) (3.80, 7.70)], blood oxygen saturation [MD = 6.43, 95% CI (4.39, 8.48)], oxygenation index [MD = 26.75, 95% CI (14.61, 38.89)] of experimental group was significantly higher than that of control group (all P < .001), the incidence of multiple organ failure [odds ratio = 0.42, 95% CI (0.31, 0.56), P < .001], mortality on day 28 [odds ratio = 0.44, 95% CI (0.33, 0.59)] of experimental group was significantly less than that of control group (all P < .001). CONCLUSIONS: The high-dose ambroxol hydrochloride combined with fiberoptic bronchoscopy is beneficial to improve the patient's blood gas indicators, and reduce mortality in elderly patients with severe pneumonia.

Facile synthesis of novel Bi0-SBA-15 adsorbents by an improved impregnation reduction method for highly efficient capture of iodine gas.

Development of high efficient adsorbents to capture iodine is of great significance for the active development of nuclear power. Herein, Bi0-SBA-15 was firstly synthesized and applied for capture of iodine gas. Bi0-SBA-15 materials were prepared by an improved impregnation reduction method. The benefit of this method was that the Bi0 nanoparticles with flocculent and spherical morphologies were loaded on the surface of SBA-15, which provide abundant active sites for iodine and improve the utilization rate of active sites, so as to attain a record high capture capacity (up to 925 mg/g within 60 min) and high stablitiy (91.2%) at 200 °C. The results demonstrated that the loading of Bi0 on the surface showed a significant impact on the structure of Bi0-SBA-15 and did greatly enhance the iodine capture. Furthermore, the high iodine capture capacity mainly derived from the chemical adsorption in the stable form of BiI3. The obtained Bi0-SBA-15 materials exhibited excellent aqueous and irradiation stability. Thus, the results indicated that the new and highly efficient Bi0-SBA-15 was a potential radioactive iodine gas capture material.

Radiomic Features of Multi-ROI and Multi-Phase MRI for the Prediction of Microvascular Invasion in Solitary Hepatocellular Carcinoma.

OBJECTIVES: To develop and validate an MR radiomics-based nomogram to predict the presence of MVI in patients with solitary HCC and further evaluate the performance of predictors for MVI in subgroups (HCC ≤ 3 cm and > 3 cm). MATERIALS AND METHODS: Between May 2015 and October 2020, 201 patients with solitary HCC were analysed. Radiomic features were extracted from precontrast T1WI, arterial phase, portal venous phase, delayed phase and hepatobiliary phase images in regions of the intratumoral, peritumoral and their combining areas. The mRMR and LASSO algorithms were used to select radiomic features related to MVI. Clinicoradiological factors were selected by using backward stepwise regression with AIC. A nomogram was developed by incorporating the clinicoradiological factors and radiomics signature. In addition, the radiomic features and clinicoradiological factors related to MVI were separately evaluated in the subgroups (HCC ≤ 3 cm and > 3 cm). RESULTS: Histopathological examinations confirmed MVI in 111 of the 201 patients (55.22%). The radiomics signature showed a favourable discriminatory ability for MVI in the training set (AUC, 0.896) and validation set (AUC, 0.788). The nomogram incorporating peritumoral enhancement, tumour growth type and radiomics signature showed good discrimination in the training (AUC, 0.932) and validation sets (AUC, 0.917) and achieved well-fitted calibration curves. Subgroup analysis showed that tumour growth type was a predictor for MVI in the HCC ≤ 3 cm cohort and peritumoral enhancement in the HCC > 3 cm cohort; radiomic features related to MVI varied between the HCC ≤ 3 cm and HCC > 3 cm cohort. The performance of the radiomics signature improved noticeably in both the HCC ≤ 3 cm (AUC, 0.953) and HCC > 3 cm cohorts (AUC, 0.993) compared to the original training set. CONCLUSIONS: The preoperative nomogram integrating clinicoradiological risk factors and the MR radiomics signature showed favourable predictive efficiency for predicting MVI in patients with solitary HCC. The clinicoradiological factors and radiomic features related to MVI varied between subgroups (HCC ≤ 3 cm and > 3 cm). The performance of radiomics signature for MVI prediction was improved in both the subgroups.

Panretinal photocoagulation after or prior to intravitreal conbercept injection for diabetic macular edema: a retrospective study.

BACKGROUND: Panretinal photocoagulation treatment (PRP) have been known as a standard treatment for proliferative diabetic retinopathy (PDR) or severe nonproliferative diabetic retinopathy (sNPDR). However, there is no consensus on when PRP should be administrated if anti-VEGF treatment is needed for the concurrent diabetic macular edema (DME). This study is to evaluate the difference between two groups of PRP prior to, or after intravitreal conbercept (IVC) for patients with PDR or sNPDR combined with DME. METHODS: This was a retrospective study. Fifty-eight eyes with DME secondary to PDR or sNPDR were divided into two groups; the PRP after (PRP-after group), or prior to (PRP-prior group), IVC. Changes in number of IVC injections, best corrected visual acuity (BCVA), and central subfield macular thickness (CSMT) were compared after 4 weeks, 12 weeks, 1 year, and 2 years from the first IVC injection. RESULTS: The mean number of injections in PRP-after group was 4.8 (1 year) and 6.4 (2 year), lower than 6.4 (1 year) and 8.5 (2 year) in PRP-prior group (both p = 0.002). There was no significant difference in change in BCVA and CSMT between two groups after each follow-up. CONCLUSION: PRP after IVC requires less injections but also yields similar visual and anatomic outcome comparing with PRP prior to IVC in patients with diabetic retinopathy combined with DME.

Widening of the popliteal hiatus on sagittal MRI view plays a critical role in the mechanical signs of discoid lateral meniscus.

PURPOSE: This study was undertaken to elucidate the clinical significance of widening of the popliteal hiatus on magnetic resonance imaging (MRI) after a torn discoid lateral meniscus (DLM). METHODS: Included are 125 knees with meniscal disorders after arthroscopic surgery, divided according to preoperative MRI and symptoms into group A (torn DLM with mechanical symptoms,11 knees); group B (torn DLM without mechanical symptoms,41 knees); group C (asymptomatic DLM, 19 knees); and group D (medial meniscal tears, 54 knees). Popliteal hiatus width was measured on sagittal and coronal MRI. During arthroscopy, total meniscectomy or central partial meniscectomy combined repair of the remaining part was performed in group A and group B. Outcomes were evaluated with MRI, the Tegner, Lysholm Knee Scoring Scale, and visual analog scale (VAS) scores. RESULTS: The preoperative width of the popliteal hiatus was significantly larger in group A than in groups C and D (P < 0.05) on both views. Group A had a wider popliteal hiatus on sagittal view compared with group B (P < 0.05); group B had a wider popliteal hiatus on coronal view compared with group D (P < 0.05). The width of the popliteal hiatus on sagittal view was significantly reduced after surgery in group A (P < 0.05). In groups A and B, Lysholm and Tegner scores were improved, while VAS scores were reduced (all P < 0.05). CONCLUSION: Widening of the popliteal hiatus on MRI was correlated with torn DLM and accompanied mechanical symptoms. Arthroscopic central partial menisectomy and stabilization of the posterior part of the middle body anterior to the popliteus tendon were effective for the treatment of torn DLM. These findings may help guide appropriate treatment for torn DLM. LEVEL OF EVIDENCE: II.

Changes in Resting-State Cerebral Activity in Women With Polycystic Ovary Syndrome: A Functional MR Imaging Study.

Background: Previous studies have found that women with polycystic ovary syndrome (PCOS) have some degree of brain function change as well as cognitive function and emotions, such as poor executive functioning and memory, anxiety and depressive symptoms. However, the neurobiological mechanisms underlying these alterations have not yet been clarified. Method: Fasting serum hormone testing, neuropsychological testing and resting-state magnetic resonance imaging (rs-fMRI) were performed in 41 women with newly diagnosed PCOS and 41 healthy controls matched by age and education during their 2-5 days of menstrual period. Analysis of the amplitude of low-frequency fluctuation (ALFF) was used to calculate the seed points. Then, the functional connectivity (FC) values between these abnormal seed points and other voxels in the whole brain were calculated. Finally, the correlations among clinical indexes, neuropsychological evaluation scores, and neuroimaging data were analyzed. Results: Compared with the control group, the PCOS group showed higher luteinizing hormone (LH) and serum insulin levels, worse sleep quality, increased depressive and anxiety state scores, and memory and executive function impairments. Pearson's correlation analysis showed that the decreased ALFF value in the left middle frontal gyrus (MFG.L), which is related to poor executive performance and depressive disorders, was negatively correlated with the plasma insulin level in subjects with insulin resistance. Furthermore, the increased FC strength between the MFG.L and left inferior frontal gyrus (IFG.L) was positively correlated with the serum testosterone level. The enhanced FC strength between the left posterior cingulate gyrus (PCG.L) and triangular part of the left inferior frontal gyrus (IFGtriang.L) was negatively correlated with the plasma LH level. When use the right middle occipital gyrus (MOG.R) as the seed point, the FC strength with the right inferior occipital gyrus (IOG.R), which is associated with impaired memory, was decreased. Conclusion: The ALFF and FC results elucidated brain functional abnormalities at the regional and network levels in women with PCOS, while correlation analyses simultaneously demonstrated that these alterations were associated with serum hormones and cognitive function. These results may provide useful information regarding the potential mechanisms of cognitive impairment and emotional changes in this population.

lncRNA SNHG1 attenuates osteogenic differentiation via the miR­101/DKK1 axis in bone marrow mesenchymal stem cells.

The imbalance induced by inhibition of bone mesenchymal stem cell (BMSC) osteogenic differentiation results in osteoporosis (OP); however, the underlying regulatory mechanism is not completely understood. Long non­coding RNAs (lncRNAs) serve crucial roles in osteogenic differentiation; therefore, investigating their regulatory role in the process of osteogenic differentiation may identify a promising therapeutic target for OP. The expression of small nucleolar RNA host gene 1 (SNHG1), Dickkopf 1 (DKK1), microRNA (miR)­101, RUNX family transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalin (OCN) were detected via reverse transcription­quantitative PCR. The protein expression levels of DKK1, ß­catenin, RUNX2, OPN, OCN, osterix and collagen type I α1 chain were analyzed by performing western blotting. The osteoblastic phenotype was assessed by conducting alkaline phosphatase activity detection and Alizarin Red staining. The interaction between SNHG1 and miR­101 was validated by bioinformatics and luciferase assays. The regulatory role of SNHG1 in BMSC osteogenic differentiation was assessed. SNHG1 expression was downregulated in a time­dependent manner during the process of osteogenic differentiation. SNHG1 overexpression inhibited osteogenic differentiation compared with the pcDNA group. The results indicated that SNHG1 and DKK1 directly interacted with miR­101. Moreover, SNHG1 regulated the Wnt/ß­catenin signaling pathway to inhibit osteogenic differentiation via the miR­101/DKK1 axis. The present study indicated that lncRNA SNHG1 could attenuate BMSC osteogenic differentiation via the miR­101/DKK1 axis as a competitive endogenous RNA. Therefore, the present study furthered the current understanding of the potential mechanism underlying lncRNAs in in osteogenic differentiation.

Synthesis Of PEG-Coated, Ultrasmall, Manganese-Doped Iron Oxide Nanoparticles With High Relaxivity For T1/T2 Dual-Contrast Magnetic Resonance Imaging.

BACKGROUND: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. METHODS: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. RESULTS: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. CONCLUSION: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.

Meta-analysis of overall incidence and risk of ALK inhibitors-induced liver toxicities in advanced non-small-cell lung cancer.

AIM: Activation of the anaplastic lymphoma kinase (ALK) gene has been found in several human cancers, including non-small-cell lung cancer (NSCLC). Currently, novel drugs targeting ALK gene have been extensively investigated in NSCLC. However, concerns about ALK inhibitors-induced liver toxicities have been increasing. MATERIALS AND METHODS: Eligible prospective clinical studies have been searched in several databases. Primary outcomes of interest were incidence rates of liver toxicities, relative risks (RRs), and 95% confidence intervals (CIs). RESULTS: Data from 2418 patients (1873 in the experimental arm; 545 in the control arm) were included. The incidences of all-grade alanine transaminase (ALT) and aspartate aminotransferase (AST) elevation were 26.0% (95% CI: 17.4%-37%), and 23.2% (95% CI, 16.7%-31.4%), respectively. The incidences of high-grade ALT and AST elevation were 8.4% (95% CI, 5.1%-13.4% and 7.0% (95% CI: 5.4%-9.0%), respectively. Sub-group analysis according to the ALK inhibitors found that pooled incidence of liver toxicities associated with ceritinib was higher than that of crizotinib and alectinib. In comparison with chemotherapy, ALK inhibitors significantly increased the all-grade and high-grade ALT elevation (RR 2.37, 95% CI, 1.97-2.86; P < .001; RR 7.34, 95% CI, 3.95-13.63; P < .001) and AST elevation (RR 3.27, 95% CI, 2.47-4.34; P < .001; RR 11.54, 95% CI, 4.33-30.7; P < .001), respectively. No publication bias was detected for RR of ALT and AST. CONCLUSIONS: The findings of the present study offer substantial evidence that ALK inhibitors treatment in advanced NSCLC significantly increases the risk of developing all-grade and high-grade liver toxicities in comparison with controls. Clinicians should recognize liver toxicities promptly as early interventions may alleviate future complications.

[DIAGNOSIS AND TREATMENT OF ACETABULAR LABRUM INJURY IN PIPKIN FRACTURE].

OBJECTIVE: To observe the characteristics of acetabular labrum injury in Pipkin fractures and the effectiveness of repairing the labrum with suture anchor. METHODS: Between July 2010 and July 2013, 10 cases of Pipkin fractures accompanied by acetabular labrum injury were treated. There were 7 males and 3 females with an average age of 32.5 years (range, 24-56 years). The causes of injury included traffic accident in 8 cases and falling from height in 2 cases. According to the Pipkin classification criteria, there were 6 cases of type II, 2 cases of type III, and 2 cases of type IV. The average interval from injury to operation was 8 days (range, 6-14 days). All the patients underwent open reduction and internal fixation through transtrochanteric approach with trochanteric osteotomy, and repair the labrum with suture anchor. The effectiveness was evaluated according to the Thompson & Epstein scoring scales after operation. RESULTS: All incisions healed primarily without early complication of deep infection or deep vein thrombosis of lower limb. All the cases were followed up 22 months on average (range, 12-48 months). X-ray films showed that all osteotomies and acetabular fractures healed within 3-4 months, femoral head and femoral neck fracture healed within 6-11 months. MRI examinations showed that all repaired acetabular labrums well healed. One case had necrosis of the femoral head at 12 months after operation, and was treated by total hip arthroplasty. According to the Thompson & Epstein scoring scales at last follow-up, the results were excellent in 5 cases, good in 3 cases, fair in 1 case and poor in 1 case, with an excellent and good rate of 80%. CONCLUSION: The diagnosis of acetabular labrum injury can be easily missed during Pipkin fracture, preoperative diagnosis should be combined with hip MRI. Trochanteric osteotomy through transtrochanteric approach , and repairing the labrum with suture anchor can restore the hip function effectively.

[ARTHROSCOPIC RESECTION OF BENIGN TUMOR IN THE KNEE POSTERIOR SEPTUM].

OBJECTIVE: To explore the technique of arthroscopic resection of benign tumor in the knee posterior septum and to evaluate its clinical results. METHODS: Between June 2008 and June 2012, 12 cases of benign tumor in the knee posterior septum were treated by arthroscopic surgery. There were 8 males and 4 females with an average age of 36.5 years (range, 22-50 years). The average disease duration was 8.4 months (range, 3 months to 2 years). Of 12 cases, there were 2 cases of chronic synovitis, 5 cases of ganglion, 4 cases of tenosynovial giant cell tumor, and 1 case of synovial hemangioma; solitary tumor involved in the knee posterior septum in 10 cases, and in the posterior septum and other part of the knee in 2 cases. All the patients underwent tumor removal under arthroscope with routine anterolateral and anteromedial portal, additional posteromedial portal and/or posterolateral portal. Trans-septal approach was used in 6 cases because the tumors located in the middle of the posterior septum. RESULTS: All wounds healed by first intention with no complications such as infection, haematoma in the knee, injury of vessels and nerves, deep vein thrombosis, osteofascial compartment syndrome, or cutaneous necrosis. All patients were followed up 12-46 months with an average of 18.5 months. All patients achieved relief of knee pain and improvement of knee movement. The range of motion of the knee was significantly improved from (57.08 ± 12.52) degrees at pre-operation to (120.83 ± 13.95) degrees at last follow-up (t = -12.84, P = 0.00). The visual analogue scale (VAS) score was significantly reduced from 5.00 ± 1.04 at pre-operation to 1.50 ± 0.91 at last follow-up (t = -18.00, P = 0.00). The Lysholm score was significantly improved from 49.50?9.07 at pre-operation to 84.58 ± 6.82 at last follow-up (t = -8.04, P = 0.00). CONCLUSION: The benign tumor in the knee posterior septum can be completely resected under arthroscope, and the procedure is minimally invasive and useful to the restore knee function.

[Development of polyaxial locking plate screw system of sacroiliac joint].

OBJECTIVE: To develop an instrument for sacroiliac joint fixation with less injury and less complications. METHODS: Firstly, 18 adult pelvic specimens (8 males and 10 females) were used to measure the anatomical data related to the locking plates and locking screws on the sacrum and ilium, and the polyaxial locking plate screw system of the sacroiliac joint was designed according to the anatomic data. This system was made of medical titanium alloy. Then 4 adult male plevic specimens were harvested and the experiment was divided into 3 groups: group A (normal pelvic), group B (the dislocated sacroiliac joint fixed with sacroiliac screws), and group C (the dislocated sacroiliac joint fixed with polyaxial locking plate screw system). The vertical displacement of sacroiliac joint under the condition of 0-700 N vertical load and the horizontal displacement on angle under the condition of 0-12 N·m torsional load were compared among the 3 groups by using the biological material test system. Finally, the simulated application test was performed on 1 adult male cadaveric specimen to observe soft tissue injury and the position of the locking plate and screw by X-ray films. RESULTS: According to the anatomic data of the sacrum and ilium, the polyaxial locking plate screw system of the sacroiliac joint was designed. The biomechanical results showed that the vertical displacement of the sacroiliac joint under the condition of 0-700 N vertical load in group A was significantly bigger than that in group B and group C (P < 0.05), but there was no significant difference between group B and group C (P > 0.05). The horizontal displacement on angle under the condition of 0-12 N·m torsional load in group A was significantly less than that in group B and group C (P < 0.05). The horizontal displacement on angle under the condition of 0-6 N·m torsional load in group B was bigger than that in group C, and the horizontal displacement on angle under the condition of 6-12 N·m torsional load in group B was less than that in group C, but there was no significant difference between group B and group C (P > 0.05). The test of simulating application showed that the specimen suffered less soft tissue injury, and this instrument could be implanted precisely and safely. CONCLUSION: The polyaxial locking plate screw system of the sacroiliac joint has the advantages of smaller volume and less injury; polyaxial fixation enables flexible adjustment screw direction. The simulated application test shows satisfactory fixing effect.

Synthesis and biological evaluation of novel 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives as potential antitumor agents.

A series of 6-hydrazinyl-2,4-bismorpholino pyrimidine and 1,3,5-triazine derivatives (5a-5l and 8a-8o) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT-29, and MDA-MB-231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC(50) values (0.07 and 0.05 µM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1. The most promising compound 5j, possessing a cyano group at the 3-position of the benzene ring, showed strong antiproliferative activity against H460, HT-29, and MDA-MB-231 cell lines with IC(50) values of 0.05, 6.31, and 6.50 µM, which were 4.6- to 190.4-fold more active than compound 1 (9.52, 29.24, and 36.21 µM), respectively.