Associations Between microRNA-related Genetic Polymorphisms and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients.

BACKGROUND: Emerging evidence indicates that microRNA (miRNA)-related genetic polymorphisms are strongly involved in the post-transcriptional regulation of the expression of pharmacokinetics and pharmacodynamics- related genes, therefore contributing to the genetic variability of drug response. OBJECTIVE: To investigate the associations of miRNA-related genetic polymorphisms, including miRNA-5189 rs562929801, miRNA-595 rs4909237, SLCO1A2 rs4149009 and MTHFR rs3737966, and clinical response to methotrexate in Chinese rheumatoid arthritis patients. METHODS: One hundred patients treated with MTX for approximately 3 months were prospectively followed up to evaluate the clinical response according to European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA) and remission (REM), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR > 0.6. Genetic polymorphisms were genotyped utilizing the HI-SNP technology. RESULTS: Of the 100 patients with a mean age of 52.23 ± 12.71 years, 81 patients were female (81.00%). After adjusting potential confounders, the major allele of miRNA-5189 rs562929801 was found to be significantly associated with EULAR response (A/A + A/G versus G/G, RR = 0.81, 95% CI = 0.67-0.99, P = 0.04) and ΔDAS28-ESR > 0.6 under dominant model (A/A + A/G versus G/G, RR = 0.83, 95% CI = 0.71-0.98, P = 0.03). However, nonsignificant evidence was detected for the remaining three miRNA-related genetic polymorphisms in neither univariable analysis nor multivariable analysis. CONCLUSION: Our results indicated that miRNA-5189 rs562929801 was significantly associated with clinical response to MTX, and this association warrants further replication studies with larger sample sizes.

Artificial intelligence empowered digital health technologies in cancer survivorship care: A scoping review.

Objective: The objectives of this systematic review are to describe features and specific application scenarios for current cancer survivorship care services of Artificial intelligence (AI)-driven digital health technologies (DHTs) and to explore the acceptance and briefly evaluate its feasibility in the application process. Methods: Search for literatures published from 2010 to 2022 on sites MEDLINE, IEEE-Xplor, PubMed, Embase, Cochrane Central Register of Controlled Trials and Scopus systematically. The types of literatures include original research, descriptive study, randomized controlled trial, pilot study, and feasible or acceptable study. The literatures above described current status and effectiveness of digital medical technologies based on AI and used in cancer survivorship care services. Additionally, we use QuADS quality assessment tool to evaluate the quality of literatures included in this review. Results: 43 studies that met the inclusion criteria were analyzed and qualitatively synthesized. The current status and results related to the application of AI-driven DHTs in cancer survivorship care were reviewed. Most of these studies were designed specifically for breast cancer survivors' care and focused on the areas of recurrence or secondary cancer prediction, clinical decision support, cancer survivability prediction, population or treatment stratified, anti-cancer treatment-induced adverse reaction prediction, and so on. Applying AI-based DHTs to cancer survivors actually has shown some positive outcomes, including increased motivation of patient-reported outcomes (PROs), reduce fatigue and pain levels, improved quality of life, and physical function. However, current research mostly explored the technology development and formation (testing) phases, with limited-scale population, and single-center trial. Therefore, it is not suitable to draw conclusions that the effectiveness of AI-based DHTs in supportive cancer care, as most of applications are still in the early stage of development and feasibility testing. Conclusions: While digital therapies are promising in the care of cancer patients, more high-quality studies are still needed in the future to demonstrate the effectiveness of digital therapies in cancer care. Studies should explore how to develop uniform standards for measuring patient-related outcomes, ensure the scientific validity of research methods, and emphasize patient and health practitioner involvement in the development and use of technology.

Associations Between Genetic Polymorphisms Within Transporter Genes and Clinical Response to Methotrexate in Chinese Rheumatoid Arthritis Patients: A Pilot Study.

Purpose: To investigate the associations between genetic polymorphisms within transporter genes and clinical response to methotrexate (MTX) in Chinese rheumatoid arthritis (RA) patients. Patients and Methods: A total of 100 RA patients receiving MTX were prospectively followed up for approximately 3 months to determine the clinical response based on several criteria, including European League Against Rheumatism (EULAR) good and moderate response, disease activity score in 28 joint counts - erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), change in DAS28-ESR (ΔDAS28-ESR) and ΔDAS28-ESR >0.6. Fifty-four single nucleotide polymorphisms (SNPs) within seven transporter genes, including SLC19A1, ABCB1, ABCC1~4 and ABCG2, were genotyped. Results: Multivariable analysis revealed that SLC19A1 rs12659 and rs3788200, ABCC2 rs3740066, rs4148396 and rs717620 were significantly associated with EULAR good and moderate response, and ABCC2 rs3740066 and rs717620 were significantly associated with DAS28-ESR LDA, and ABCB1 rs1128503, rs4148737 and ABCC3 rs2277624, rs4148416 were significantly associated with ΔDAS28-ESR. Moreover, 12 genetic polymorphisms were found to be significantly associated with ΔDAS28-ESR >0.6. With adjustment for corresponding confounders, SLC19A1 TGAA haplotype consisting of rs1051266, rs1131596, rs12659 and rs3788200 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CAGG. The ABCC2 haplotype TTT composed of rs717620, rs4148396 and rs3740066 was significantly associated with EULAR good and moderate response and ΔDAS28-ESR >0.6 compared with the most common haplotype CCC. Conclusion: Our results highlight the potential of genetic polymorphisms within transporter genes, particularly SLC19A1 and ABCC2, as predictors of clinical response to MTX in Chinese RA patients.

A compressed variance component mixed model for detecting QTNs and QTN-by-environment and QTN-by-QTN interactions in genome-wide association studies.

Although genome-wide association studies are widely used to mine genes for quantitative traits, the effects to be estimated are confounded, and the methodologies for detecting interactions are imperfect. To address these issues, the mixed model proposed here first estimates the genotypic effects for AA, Aa, and aa, and the genotypic polygenic background replaces additive and dominance polygenic backgrounds. Then, the estimated genotypic effects are partitioned into additive and dominance effects using a one-way analysis of variance model. This strategy was further expanded to cover QTN-by-environment interactions (QEIs) and QTN-by-QTN interactions (QQIs) using the same mixed-model framework. Thus, a three-variance-component mixed model was integrated with our multi-locus random-SNP-effect mixed linear model (mrMLM) method to establish a new methodological framework, 3VmrMLM, that detects all types of loci and estimates their effects. In Monte Carlo studies, 3VmrMLM correctly detected all types of loci and almost unbiasedly estimated their effects, with high powers and accuracies and a low false positive rate. In re-analyses of 10 traits in 1439 rice hybrids, detection of 269 known genes, 45 known gene-by-environment interactions, and 20 known gene-by-gene interactions strongly validated 3VmrMLM. Further analyses of known genes showed more small (67.49%), minor-allele-frequency (35.52%), and pleiotropic (30.54%) genes, with higher repeatability across datasets (54.36%) and more dominance loci. In addition, a heteroscedasticity mixed model in multiple environments and dimension reduction methods in quite a number of environments were developed to detect QEIs, and variable selection under a polygenic background was proposed for QQI detection. This study provides a new approach for revealing the genetic architecture of quantitative traits.

Integrated Bioinformatics Analyses of PIN1, CKX, and Yield-Related Genes Reveals the Molecular Mechanisms for the Difference of Seed Number Per Pod Between Soybean and Cowpea.

There is limited advancement on seed number per pod (SNPP) in soybean breeding, resulting in low yield in China. To address this issue, we identified PIN1 and CKX gene families that regulate SNPP in Arabidopsis, analyzed the differences of auxin and cytokinin pathways, and constructed interaction networks on PIN1, CKX, and yield-related genes in soybean and cowpea. First, the relative expression level (REL) of PIN1 and the plasma membrane localization and phosphorylation levels of PIN1 protein were less in soybean than in cowpea, which make auxin transport efficiency lower in soybean, and its two interacted proteins might be involved in serine hydrolysis, so soybean has lower SNPP than cowpea. Then, the CKX gene family, along with its positive regulatory factor ROCK1, had higher REL and less miRNA regulation in soybean flowers than in cowpea ones. These lead to higher cytokinin degradation level, which further reduces the REL of PIN1 and decreases soybean SNPP. We found that VuACX4 had much higher REL than GmACX4, although the two genes essential in embryo development interact with the CKX gene family. Next, a tandem duplication experienced by legumes led to the differentiation of CKX3 into CKX3a and CKX3b, in which CKX3a is a key gene affecting ovule number. Finally, in the yield-related gene networks, three cowpea CBP genes had higher RELs than two soybean CBP genes, low RELs of three soybean-specific IPT genes might lead to a decrease in cytokinin synthesis, and some negative and positive SNPP regulation were found, respectively, in soybean and cowpea. These networks may explain the SNPP difference in the two crops. We deduced that ckx3a or ckx3a ckx6 ckx7 mutants, interfering CYP88A, and over-expressed DELLA increase SNPP in soybean. This study reveals the molecular mechanism for the SNPP difference in the two crops, and provides an important idea for increasing soybean yield.

Integrated Transcriptomic and Bioinformatics Analyses Reveal the Molecular Mechanisms for the Differences in Seed Oil and Starch Content Between Glycine max and Cicer arietinum.

The seed oil and starch content of soybean are significantly different from that of chickpea. However, there are limited studies on its molecular mechanisms. To address this issue, we conducted integrated transcriptomic and bioinformatics analyses for species-specific genes and acyl-lipid-, starch-, and carbon metabolism-related genes. Among seven expressional patterns of soybean-specific genes, four were highly expressed at the middle- and late oil accumulation stages; these genes significantly enriched fatty acid synthesis and carbon metabolism, and along with common acetyl CoA carboxylase (ACCase) highly expressed at soybean middle seed development stage, common starch-degrading enzyme beta-amylase-5 (BAM5) was highly expressed at soybean early seed development stage and oil synthesis-related genes ACCase, KAS, KAR, ACP, and long-chain acyl-CoA synthetase (LACS) were co-expressed with WRI1, which may result in high seed oil content and low seed starch content in soybean. The common ADP-glucose pyrophosphorylase (AGPase) was highly expressed at chickpea middle seed development stage, along with more starch biosynthesis genes co-expressed with four-transcription-factor homologous genes in chickpea than in soybean, and the common WRI1 was not co-expressed with oil synthesis genes in chickpea, which may result in high seed starch content and low seed oil content in chickpea. The above results may be used to improve chickpea seed oil content in two ways. One is to edit CaWRI1 to co-express with oil synthesis-related genes, which may increase carbon metabolites flowing to oil synthesis, and another is to increase the expression levels of miRNA159 and miRNA319 to inhibit the expression of MYB33, which may downregulate starch synthesis-related genes, making more carbon metabolites flow into oil synthesis. Our study will provide a basis for future breeding efforts to increase the oil content of chickpea seeds.

"Five-point eight-line" anatomic flap design for precise hemitongue reconstruction.

BACKGROUND: Reconstruction of hemiglossectomy defects requires careful flap design to avoid adverse functional and aesthetic outcomes. METHODS: Hemitongue specimens were obtained from minipigs to study the three-dimensional anatomy and to define anatomic landmarks for precise measurements of flap requirement. The concept developed in animal models was then applied to hemiglossectomy reconstruction in clinical practice. Sixty-one patients were randomly enrolled into the following two groups: a "five-point eight-line segment" (FIPELS) flap design group (28 patients) and a conventional group (33 patients). Functional and aesthetic outcomes were compared between the two groups. RESULTS: All flaps designed with the FIPELS technique matched the hemiglossectomy defects without the need for flap trimming, thus reducing the operating time (P = .03). Swallowing functions, speech intelligibility, and aesthetic outcomes were superior in the FIPELS group than that in the conventional group (P < .05). CONCLUSIONS: The FIPELS flap design for hemiglossectomy reconstruction yields improved functional and aesthetic outcomes compared to a conventional flap design.

Differential long noncoding RNA expressions in peripheral blood mononuclear cells for detection of acute ischemic stroke.

Long noncoding RNAs (lncRNAs) have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of the present study was to investigate the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) of acute IS patients and to explore their utility as biomarkers of IS. Distinctive expression patterns of PBMC lncRNAs were identified by an lncRNA microarray and individual quantitative real-time PCR (qRT-PCR) in four independent sets for 206 IS, 179 healthy controls (HCs), and 55 patients with transient ischemic attack (TIA). A biomarker panel (lncRNA-based combination index) was established using logistic regression. LncRNA microarray analysis showed 70 up-regulated and 128 down-regulated lncRNAs in IS patients. Individual qRT-PCR validation demonstrated that three lncRNAs (linc-DHFRL1-4, SNHG15, and linc-FAM98A-3) were significantly up-regulated in IS patients compared with HCs and TIA patients. Longitudinal analysis of lncRNA expression up to 90 days after IS showed that linc-FAM98A-3 normalized to control levels by day 7, while SNHG15 remained increased, indicating the ability of lncRNAs to monitor IS dynamics. Receiver-operating characteristic (ROC) curve analysis showed that the lncRNA-based combination index outperformed serum brain-derived neurotrophic factor (BDNF) and neurone-specific enolase (NSE) in distinguishing IS patients from TIA patients and HCs with areas under ROC curve of more than 0.84. Furthermore, the combination index increased significantly after treatment and was correlated with neurological deficit severity of IS. The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method.

The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke.

The triglyceride (TG)-to-high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) is a simple approach to predicting unfavorable outcomes in cardiovascular disease. The influence of TG/HDL-C on acute ischemic stroke remains elusive. The purpose of this study was to investigate the precise effect of TG/HDL-C on 3-month mortality after acute ischemic stroke (AIS). Patients with AIS were enrolled in the present study from 2011 to 2017. A total of 1459 participants from a single city in China were divided into retrospective training and prospective test cohorts. Medical records were collected periodically to determine the incidence of fatal events. All participants were followed for 3 months. Optimal cutoff values were determined using X-tile software to separate the training cohort patients into higher and lower survival groups based on their lipid levels. A survival analysis was conducted using Kaplan-Meier curves and a Cox proportional hazards regression model. A total of 1459 patients with AIS (median age 68.5 years, 58.5% male) were analyzed. Univariate Cox regression analysis confirmed that TG/HDL-C was a significant prognostic factor for 3-month survival. X-tile identified 0.9 as an optimal cutoff for TG/HDL-C. In the univariate analysis, the prognosis of the TG/HDL-C >0.9 group was markedly superior to that of TG/HDL-C ≤0.9 group (P<0.001). A multivariate Cox regression analysis showed that TG/HDL-C was independently correlated with a reduced risk of mortality (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.24-0.62; P<0.001). These results were confirmed in the 453 patients in the test cohort. A nomogram was constructed to predict 3-month case-fatality, and the c-indexes of predictive accuracy were 0.684 and 0.670 in the training and test cohorts, respectively (P<0.01). The serum TG/HDL-C ratio may be useful for predicting short-term mortality after AIS.

The Use of a Honeycomb Technique Combined with Ultrasonic Aspirators and Indocyanine Green Fluorescence Angiography for a Superthin Anterolateral Thigh Flap: A Pilot Study.

BACKGROUND: Harvesting an optimally thinned anterolateral thigh flaps is a challenge in overweight individuals and in the Western population. The authors describe a novel honeycomb technique to achieve a superthin anterolateral thigh flap in overweight patients. METHODS: Forty patients with a body mass index greater than 25 kg/m(2) who required a thinned anterolateral thigh flap for reconstruction were assigned randomly to a honeycomb technique group or a microdissection technique group. The honeycomb technique group underwent flap thinning with the Cavitron Ultrasonic Surgical Aspirator, and flap thinning was performed with a conventional microdissection technique in the microdissection technique group. Perfusion of all flaps was measured by indocyanine green fluorescence angiography before and after thinning. Hypoperfusion was defined as 30 percent. RESULTS: The mean body mass index was 28.6 ± 2.0 kg/m(2) and 27.3 ± 1.9 kg/m(2) in the honeycomb group and the microdissection group, respectively. Flap size, perforator, type of dissection, and initial perfusion were comparable between the two groups. However, significantly more patients (nine of 21) experienced final hypoperfusion in the microdissection group than in the honeycomb group (two of 19) (p = 0.034). In addition, blood loss and final flap thickness were significantly lower in the honeycomb group (p < 0.05), and the duration of thinning was comparable between the two groups. No flap necrosis was found in either group. CONCLUSION: The honeycomb technique in combination with the Cavitron Ultrasonic Surgical Aspirator and indocyanine green angiography was able to remove adipose tissue but protect the integrity of the subcutaneous vascular plexus to reduce potential risk of jeopardizing flap perfusion while obtaining a superthin anterolateral thigh flap in an overweight population. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Computer-assisted resection and reconstruction of bilateral osteoradionecrosis of the mandible using 2 separate flaps prepared from a single fibula.

OBJECTIVES: Osteoradionecrosis of the mandible is a late radiation-induced complication, which is a major concern in survivors of head and neck cancer. STUDY DESIGN: In this study, we present a case of a patient with nasopharyngeal carcinoma who developed extensive bilateral osteoradionecrosis of the ascending ramus of the mandible. After preoperative virtual surgical planning, the obtained data were used to fabricate patient-specific cutting templates. The bilateral mandibular defects were reconstructed using 2 separate flaps prepared from a single fibula. RESULTS: Both defects were successfully reconstructed, and satisfactory aesthetic and functional results were achieved. CONCLUSIONS: Bilateral mandibular osteoradionecrosis can be managed with virtual surgical planning, and the defects can be reconstructed using 2 separate flaps prepared from a single fibula.

Postoperative immune response and surgical stress in selective neck dissection: Comparison between endoscopically assisted dissection and open techniques in cT1-2N0 oral squamous cell carcinoma.

BACKGROUND: Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the immune response after surgery. METHODS: A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery (T0) and at 2 (T1), 6 (T2), 24 (T3), and 72 h (T4) after surgery. RESULTS: A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p < 0.05), and cortisol levels were also lower in the endoscopic group (p < 0.05). CONCLUSIONS: Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.

Endoscope-assisted extracapsular dissection of benign parotid tumors through a single cephaloauricular furrow incision versus a conventional approach.

BACKGROUND: A few modified approaches have been reported for performing endoscope-assisted dissections of benign parotid tumors, but none that use incisions totally hidden in a natural furrow. This study evaluated the feasibility of performing endoscope-assisted extracapsular dissections of benign parotid tumors using a single cephaloauricular furrow incision. METHODS: Forty-six patients with benign parotid superficial lobe tumors were randomly divided into two groups: an endoscope-assisted (21 patients) group or a conventional (25 patients) surgery group. Perioperative and postoperative outcomes of the patients were evaluated, including the maximum diameter of the tumors, length of the incision, operating time, estimated blood loss during the operation, amount and duration of drainage, satisfaction scores based on the cosmetic results, perioperative complications, and follow-up information. RESULTS: The diameters of the tumors were comparable between the groups, and all operations were successfully performed as planned. The mean length of the incision in the endoscope-assisted group (3.6 ± 0.5 cm) was significantly shorter than that in the conventional group (9.1 ± 1.9). Meanwhile, the intraoperative blood loss, amount of drainage, perioperative complications, and cosmetic outcomes were all improved in the endoscope-assisted group. No tumor recurrence was found during 11-40 months of follow-up. CONCLUSIONS: Cephaloauricular furrow incisions were totally and naturally hidden in this procedure. Endoscope-assisted extracapsular dissections of benign parotid tumors via a small cephaloauricular furrow incision were found to be feasible and reliable, providing a minimally invasive approach and a satisfactory appearance.

A comparative study of the endoscopy-assisted transoral approach versus external approaches for the resection of large benign parapharyngeal space tumors.

OBJECTIVE: The advantages and limitations of the endoscopy-assisted transoral approach (EATA) and external approaches (EAs) in resection of parapharyngeal space tumors (PSTs) remain unclear. In our study, we compared the use of the EATA and the EAs for the resection of large, benign PSTs. STUDY DESIGN: Forty-four patients with PSTs were divided into the EATA and EA groups. The perioperative and postoperative outcomes of the patients were evaluated. RESULTS: All of the tumors were completely removed. However, the procedure was converted to an open procedure for four patients in the EATA group and for six patients in the EA group who required endoscopic assistance. The intraoperative blood loss, amount and duration of drainage, postoperative pain, total hospital stay, and cosmetic outcomes were superior in the EATA group (P < .05). CONCLUSIONS: Use of the EATA for resection of large, benign PSTs decreased the surgical invasiveness of the procedure and resulted in better aesthetic outcomes. However, use of the combined surgical approach allowed for improved access for the resection of PSTs.

Blocking Sympathetic Nervous System Reverses Partially Stroke-Induced Immunosuppression but does not Aggravate Functional Outcome After Experimental Stroke in Rats.

Stoke results in activation of the sympathetic nervous system (SNS), inducing systemic immunosuppression. However, the potential mechanisms underlying stroke-induced immunosuppression remain unclear. Here, we determined the SNS effects on functional outcome and explored the interactions among SNS, ß-arrestin2 and nuclear factor-κB (NF-κB) after experimental stroke in rats. In the current study, stroke was induced by a transient middle cerebral artery occlusion (MCAO) in rats, and SNS activity was inhibited by intraperitoneal injection of 6-hydroxydopamine HBr (6-OHDA). 7.0 T Micro-MRI and Longa score were employed to assess the functional outcome after stroke. Flow cytometry and ELISA assay were used to measure the expression of MHC class II, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Western blot was conducted to analyze ß-arrestin2 and NF-κB protein expression levels after experimental stroke. We found significantly increased infarct volumes and functional impairment after MCAO at different post-surgery time points, which were not aggravated by 6-OHDA treatment. SNS blockade partially reversed the expression of MHC class II after stroke over time, as well as TNF-α and IFN-γ levels in lipopolysaccharide-stimulated macrophages in vitro. Treatment of MCAO rats with SNS-inhibitor significantly diminished NF-κB activation and enhanced ß-arrestin2 expression after stroke. This study suggests that pharmacological SNS inhibition dose not aggravate functional outcome after stroke. Stroke-induced immunosuppression may be involved in the SNS-ß-arrestin2-NF-κB pathway.

Virtual Surgical Planning in Precise Maxillary Reconstruction With Vascularized Fibular Graft After Tumor Ablation.

PURPOSE: Reconstruction of maxillary and midfacial defects due to tumor ablation is challenging to conventional operation. The purposes of this study are to evaluate the precise 3-dimensional position of the fibular flap in reconstruction of maxillary defects assisted by virtual surgical planning and to assess the postoperative outcomes compared with conventional surgery. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients who underwent maxillary reconstruction with a vascularized fibular flap assisted by virtual surgical planning after maxillary or midfacial tumor ablation. Conventional surgery was performed in another 15 patients. Proplan CMF surgical planning (Materialise, Leuven, Belgium) was performed preoperatively in the virtual planning group. Fibular flaps were harvested and underwent osteotomy assisted by prefabricated cutting guides, and the maxilla and midface were resected and reconstructed assisted by the prefabricated cutting guides and templates in the virtual planning group. The operative time and fibular flap positions were evaluated in the 2 groups. Postoperative fibular positions of the maxillary reconstruction were compared with virtual plans in the virtual planning group. The postoperative facial appearance and occlusal function were assessed. RESULTS: The operations were performed successfully without complications. The ischemia time and total operative time were shorter in the virtual planning group than those in the conventional surgery group (P < .05). High precision of the cutting guides and templates was found on both the fibula and maxilla in the virtual planning group. The positions of the fibular flaps, including the vertical and horizontal positions, were more accurate in the virtual planning group than those in the conventional surgery group (P < .05). Bone-to-bone contact between the maxilla and fibular segments was more precise in the virtual planning group (P < .05). Postoperative computed tomography scans showed excellent contour of the fibular flap segments in accordance with the virtual plans in the virtual planning group. All patients were alive with no evidence of disease. Functional mandibular range of motion, good occlusion, and an ideal facial appearance were observed in the virtual planning group. CONCLUSIONS: Virtual surgical planning appears to achieve precise maxillary reconstruction with a vascularized fibular flap after tumor ablation, as well as an ideal facial appearance and function after dental rehabilitation. The use of prefabricated cutting guides and plates eases fibular flap molding and placement, minimizes operating time, and improves clinical outcomes.

[Roof folding and rotary pushing for the treatment of back to back fractures of distal radius and ulna in children].

OBJECTIVE: To evaluate the technique and the clinical effect of folding roof and rotary pushing in treatment of children with distal radius and ulna fracture of "back to back". METHODS: From January 2012 to February 2014,38 children with distal radius and ulna fracture of "back to back" were treated by using the technique of folding roof and rotary pushing to reset and splint fixation including 23 males and 15 females with an average age of 9.5 years old ranging from 6 to 14 years old. Injury time was from 45 min to 3 days (averaged 1.3 days). All cases was unilateral closed fracture without symptoms of nerve injury occurred. The wrist joint anteroposterior and lateral radiographs showed double fracture of radius and ulna, and the broken end of radius was typical "back to back" displacement. The quality of reduction was assessed according to Dienst recommendation on the combination of Aro measurement, and the therapeutic effect was evaluated using standard of Anderson function. RESULTS: All patients were followed up from 3 to 13 months with an average of 6 months. There were no iatrogenic nerve injury. Thirty cases were treated successfully for the first time, 8 cases were again reset successfully; 28 cases were anatomical reduction, 7 cases were near anatomic reduction, 3 cases were functional reduction. At the second day 7 cases with hand and finger swelling appeared in multiple reset patients. Quality results of reduction were excellent in 33 cases, good in 5 cases. According to the standard of Anderson function evaluation, 35 cases were excellent, 3 cases were good. All fractures were healed with of deformity of wrist. CONCLUSION: Using the technique of folding roof and rotary pushing in treatment of children with distal radius and ulna fracture of "back to back" is very successful, the patient's limb function recovered well, the whole operation process is simple.

miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.

Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity.

A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production.

The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines, A2780 and CP70, induced by a novel curcumin analogue, B19. The proliferation of cells was detected with methyl thiazolyl tetrazolium (MTT) assay and apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) were assessed by the fluorescent indicator DCF-DA. The protein expression of the endoplasmic reticulum (ER) stress pathways, GRP78, XBP-1, ATF-4 and CHOP, was examined with Western blotting. A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin. At 20 µM, B19 induced significant apoptosis in CP70 cells. Furthermore, B19 induced the ER stress response, while curcumin had no effect on ER stress. These results suggest that B19 has more effective antitumor properties than curcumin, and is associated with the activation of ER stress and ROS in ovarian cancer cells.

A new triterpene from the fruiting bodies of Ganoderma lucidum.

A new lanostanoid triterpene, named ganoderitriol M (1), together with a known triterpene ganoderic acid epsilon (2), were isolated from the fruiting bodies of G lucidum. Compound 1 was deduced as (24S)-lanosta-7-oxo-8-en-3beta, 24, 25-triol on the basis of spectral analysis (UV, IR, MS, 1H NMR, 13C NMR and 2D NMR).