VIRMA promotes nasopharyngeal carcinoma, tumorigenesis, and metastasis by upregulation of E2F7 in an m6A-dependent manner.

The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3'-UTR, then IGF2BP2 bound, and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect.

Mycn deficiency underlies the development of orofacial clefts in mice and humans.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common subphenotype of non-syndromic orofacial clefts arising from genetic and/or environmental perturbations during embryonic development. We previously identified 2p24.2 as a risk locus associated with NSCL/P in the Chinese Han population, and MYCN is a candidate risk gene in this region. To understand the potential function of MYCN in craniofacial development, we generated Wnt1-Cre;Mycnflox/flox mice that exhibited cleft palate, microglossia and micrognathia, resembling the Pierre Robin sequence (PRS) in humans. Further analyses indicated that the cleft palate was secondary to the delayed elevation of palatal shelves caused by micrognathia. The micrognathia resulted from impaired chondrogenic differentiation in Merkel's cartilage, which limited tongue development, leading to microglossia. In terms of mechanism, Mycn deficiency in cranial neural crest cells (CNCCs) downregulated Sox9 expression by inhibiting Wnt5a in a CNCC-derived chondrogenic lineage in Merkel's cartilage. To investigate whether MYCN deficiency contributed to NSCL/P, we performed direct sequencing targeting all exons and exon-intron boundaries of MYCN in 104 multiplex families with Mendelian NSCL/P and identified a novel pathogenic variant in MYCN. Taken together, our data indicate that ablation of Mycn in mouse CNCCs could resemble PRS by suppressing the Wnt5a-Sox9 signaling pathway in Merkel's cartilage and that mutations in MYCN may be novel potential causes of NSCL/P.

Subjective quality of life and schizophrenia: results from a large cohort study based in Chinese primary care.

INTRODUCTION: Much confusion exists between health-related QoL (HRQoL) scales and subjective QoL (SQoL) scales. One method to avoid confusion is use of a single question that asks What is your quality of life? or similar. This study explored the relationship between biopsychosocial factors and high SQoL, SQoL stability, and factors associated with improving SQoL. METHOD: We conducted a large cohort study of community-dwelling Chinese adults with schizophrenia, with two data points (2015-2016 (N = 742), 2017-2018 (N = 491)). Demographic and clinically related items and a comprehensive suite of published measures were collected. Direct logistic regressions were used to explore links between biopsychosocial factors and high SQoL and Improvement in SQoL across time. RESULTS: Sample at Baseline: Male = 62.3%; Med age = 38.5 years; Med Age at illness onset = 24 years; SQoL Mode = neither poor nor good. Three independent variables predicted high SQoL at T1. Contemporary age and the presence of clinically relevant symptoms had a negative relationship with high SQoL; insight had a positive relationship with high SQoL. SQoL changed significantly across time with a modest effect size. Age at illness onset was the single independent variable linked to improving SQoL favoring being older at the time of illness onset. DISCUSSION/CONCLUSIONS: SQoL can be high and changeable. While symptomology and illness insight may affect SQoL self-appraisals at single points in time, only age of illness onset was connected with improving SQoL. Thus, public health measures to delay illness onset are important. In addition, care about the distinction between HRQoL and SQoL in study design and choice of measures is necessary and will depend on the purpose and context.

Smart photonic crystal hydrogels for visual glucose monitoring in diabetic wound healing.

Diabetes is a global chronic disease that seriously endangers human health and characterized by abnormally high blood glucose levels in the body. Diabetic wounds are common complications which associate with impaired healing process. Biomarkers monitoring of diabetic wounds is of great importance in the diabetes management. However, actual monitoring of biomarkers still largely relies on the complex process and additional sophisticated analytical instruments. In this work, we prepared hydrogels composed of different modules, which were designed to monitor different physiological indicators in diabetic wounds, including glucose levels, pH, and temperature. Glucose monitoring was achieved based on the combination of photonic crystal (PC) structure and glucose-responsive hydrogels. The obtained photonic crystal hydrogels (PCHs) allowed visual monitoring of glucose levels in physiological ranges by readout of intuitive structural color changes of PCHs during glucose-induced swelling and shrinkage. Interestingly, the glucose response of double network PCHs was completed in 15 min, which was twice as fast as single network PCHs, due to the higher volume fraction of glucose-responsive motifs. Moreover, pH sensing was achieved by incorporation of acid-base indicator dyes into hydrogels; and temperature monitoring was obtained by integration of thermochromic powders in hydrogels. These hydrogel modules effectively monitored the physiological levels and dynamic changes of three physiological biomarkers, both in vitro and in vivo during diabetic wound healing process. The multifunctional hydrogels with visual monitoring of biomarkers have great potential in wound-related monitoring and treatment.

Amygdala-hippocampal innervation modulates stress-induced depressive-like behaviors through AMPA receptors.

Chronic stress is one of the most critical factors in the onset of depressive disorders; hence, environmental factors such as psychosocial stress are commonly used to induce depressive-​like traits in animal models of depression. Ventral CA1 (vCA1) in hippocampus and basal lateral amygdala (BLA) are critical sites during chronic stress-induced alterations in depressive subjects; however, the underlying neural mechanisms remain unclear. Here we employed chronic unpredictable mild stress (CUMS) to model depression in mice and found that the activity of the posterior BLA to vCA1 (pBLA-vCA1) innervation was markedly reduced. Mice subjected to CUMS showed reduction in dendritic complexity, spine density, and synaptosomal AMPA receptors (AMPARs). Stimulation of pBLA-vCA1 innervation via chemogenetics or administration of cannabidiol (CBD) could reverse CUMS-induced synaptosomal AMPAR decrease and efficiently alleviate depressive-like behaviors in mice. These findings demonstrate a critical role for AMPARs and CBD modulation of pBLA-vCA1 innervation in CUMS-induced depressive-like behaviors.

Phytoremediation of Pb-polluted soil using bermudagrass: Effect of mowing frequencies.

Plant lead (Pb) tolerance and accumulation are key characteristics affecting phytoremediation efficiency. Bermudagrass is an excellent candidate for the remediation of Pb-polluted soil, and it needs to be mowed regularly. Here, we explored the effect of different mowing frequencies on the remediation of Pb-contaminated soil using bermudagrass. Mowing was found to decrease the biomass and photosynthetic efficiency of bermudagrass under Pb stress, thereby inhibiting its growth. Although mowing exacerbated membrane peroxidation, successive mowing treatments alleviated peroxidation damage by regulating enzymatic and nonenzymatic systems. A comprehensive evaluation of Pb tolerance revealed that all the mowing treatments reduced the Pb tolerance of bermudagrass, and a once-per-month mowing frequency had a less negative effect on Pb tolerance than did more frequent mowing. In terms of Pb enrichment, mowing significantly increased the Pb concentration, total Pb accumulation, translocation factor (TF), and bioenrichment factor (BCF) of bermudagrass. The total Pb accumulation was greatest under the once-a-month treatment, while the TF and BCF values were greatest under the three-times-a-month mowing treatment. Additionally, the decrease in soil pH and DOC were significantly correlated with the soil available Pb content and plant Pb accumulation parameters. The results showed that changes in the rhizosphere are crucial factors regulating Pb uptake in bermudagrass during mowing. Overall, once-a-month mowing minimally affects Pb tolerance and maximizes Pb accumulation, making it the optimal mowing frequency for soil Pb remediation by bermudagrass. This study provides a novel approach for the remediation of Pb-contaminated soil with bermudagrass based on mowing.

Geriatric nutritional risk index is associated with the occurrence of acute kidney injury in critically ill patients with acute heart failure.

Background: During the acute heart failure (AHF), acute kidney injury (AKI) is highly prevalent in critically ill patients. The occurrence of the latter condition increases the risk of mortality in patients with acute heart failure. The current research on the relationship between nutritional risk and the occurrence of acute kidney injury in patients with acute heart failure is very limited. Methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care IV (MIMIC-IV, version 2.1) database. We included adult patients with AHF who were admitted to the intensive care unit in the study. Results: A total of 1310 critically ill patients with acute heart failure were included. The AUC of geriatric nutritional risk index (GNRI) (0.694) is slightly superior to that of controlling nutritional status (CONUT) (0.656) and prognostic nutritional index (PNI) (0.669). The Log-rank test revealed a higher risk of acute kidney injury in patients with high nutritional risk (p < 0.001). Multivariate COX regression analysis indicated that a high GNRI (adjusted HR 0.62, p < 0.001) was associated with a reduced risk of AKI during hospitalization in AHF patients. The final subgroup analysis demonstrated no significant interaction of GNRI in all subgroups except for diabetes subgroup and ventilation subgroup (P for interaction: 0.057-0.785). Conclusion: Our study findings suggest a correlation between GNRI and the occurrence of acute kidney injury in patients hospitalized with acute heart failure.

Mechanistic Insight into the Enantioselective Degradation of Esterase QeH to (R)/(S)-Quizalofop-Ethyl with Molecular Dynamics Simulation Using a Residue-Specific Force Field.

The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop-ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzyme-substrate interactions in the catalytic kinetics. The equilibrium processes of enzyme-substrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-(R)/(S)-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the (R)-QE structure can simultaneously form anion-π and cation-π interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-(R)-QE complex, resulting in (R)-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of (R)-QE of 7.39 Å, compared to the 8.87 Å for (S)-QE, whereas the (S)-QE structure can only form an anion-π interaction with the side chain of Glu328 in the QeH-(S)-QE complex, being less close to its catalytic site. The computational alanine scanning mutation (CAS) calculations further demonstrated that the π-π stacking interaction between the indole ring of Trp351 and the benzene ring of (R)/(S)-QE contributed a lot to the binding stability of the enzyme-substrate (QeH-(R)/(S)-QE). These results facilitate the understanding of their catalytic processes and provide new theoretical guidance for the directional design of other key enzymes for the initial degradation of aryloxyphenoxypropionate (AOPP) herbicides with higher catalytic efficiencies.

Clinical internship environment and caring behaviours among nursing students: A moderated mediation model.

BACKGROUND: Caring behaviour is critical for nursing quality, and the clinical internship environment is a crucial setting for preparing nursing students for caring behaviours. Evidence about how to develop nursing students' caring behaviour in the clinical environment is still emerging. However, the mechanism between the clinical internship environment and caring behaviour remains unclear, especially the mediating role of moral sensitivity and the moderating effect of self-efficacy. RESEARCH OBJECTIVE: This study aimed to examine the mediating effect of moral sensitivity and the moderating function of self-efficacy on the association between the clinical internship environment and caring behaviours. RESEARCH DESIGN: A cross-sectional design used acceptable validity scales. The hypothesised moderated mediation model was tested in the SPSS PROCESS macro. PARTICIPANTS AND RESEARCH CONTEXT: This survey collected data from 504 nursing students in an internship at a teaching hospital in Changsha, China. ETHICAL CONSIDERATIONS: This study was pre-approved by the ethics committee of the medical school (No. E2022210). Informed consent was obtained from all students. RESULTS: The clinical internship environment (B = 0.450, 95% CI = [0.371, 0.530]) and moral sensitivity (B = 1.352, 95% CI = [1.090, 1.615]) had positive direct effects on nursing students' caring behaviours. Clinical internship environment also indirectly influenced students' caring behaviours via moral sensitivity (B = 0.161, 95% CI = [0.115, 0.206]). In addition, self-efficacy played a moderating role between the clinical internship environment and caring behaviours (B = 0.019, 95% CI = [0.007, 0.031]), as well as the relationship between the clinical internship environment and moral sensitivity (B = 0.006, 95% CI = [0.003, 0.010]). CONCLUSION: Moral sensitivity mediates the effect of the clinical internship environment on caring behaviour, and self-efficacy strengthens both direct and indirect effects. This study emphasises the importance of self-efficacy in developing moral sensitivity and caring behaviours in nursing students.

N-Heterocyclic Carbene Enabled Copper Catalyzed Asymmetric Synthesis of Pyrimidinyl Phosphine with both Axial and P-Stereogenicity.

P-stereogenic phosphines, renowned for their utility as ligands and catalysts, have been instrumental in the field of asymmetric catalysis. However, the catalytic asymmetric synthesis of chiral ligands possessing both axial and phosphine chirality remains a significant challenge. Here, we present the successful demonstration of a Cu-catalyzed asymmetric C-P construction using in situ generated secondary phosphine and heteroaryl chloride. By introducing a chiral NHC ligand and an achiral diphosphine auxiliary ligand, we effectively alleviated the poisoning effect caused by phosphine(III) compounds and suppressed the nonenantioselective background reaction. The reaction exhibited excellent enantioselectivity, with up to 96 % ee, and good diastereoselectivity, with up to 14 : 1 dr, when employing less sterically hindered secondary phosphines. This particular substrate poses a significant challenge due to its strong poisoning effect in copper catalysis.

Multiple machine learning methods aided virtual screening of NaV 1.5 inhibitors.

Nav 1.5 sodium channels contribute to the generation of the rapid upstroke of the myocardial action potential and thereby play a central role in the excitability of myocardial cells. At present, the patch clamp method is the gold standard for ion channel inhibitor screening. However, this method has disadvantages such as high technical difficulty, high cost and low speed. In this study, novel machine learning models to screen chemical blockers were developed to overcome the above shortage. The data from the ChEMBL Database were employed to establish the machine learning models. Firstly, six molecular fingerprints together with five machine learning algorithms were used to develop 30 classification models to predict effective inhibitors. A validation and a test set were used to evaluate the performance of the models. Subsequently, the privileged substructures tightly associated with the inhibition of the Nav 1.5 ion channel were extracted using the bioalerts Python package. In the validation set, the RF-Graph model performed best. Similarly, RF-Graph produced the best result in the test set in which the Prediction Accuracy (Q) was 0.9309 and Matthew's correlation coefficient was 0.8627, further indicating the model had high classification ability. The results of the privileged substructures indicated Sulfa structures and fragments with large Steric hindrance tend to block Nav 1.5. In the unsupervised learning task of identifying sulfa drugs, MACCS and Graph fingerprints had good results. In summary, effective machine learning models have been constructed which help to screen potential inhibitors of the Nav 1.5 ion channel and key privileged substructures with high affinity were also extracted.

Channel HCN4 mutation R666Q associated with sporadic arrhythmia decreases channel electrophysiological function and increases protein degradation.

Mutations in the hyperpolarization-activated nucleotide-gated channel 4 (HCN4) are known to be associated with arrhythmias in which QT prolongation (delayed ventricular repolarization) is rare. Here, we identified a HCN4 mutation, HCN4-R666Q, in two sporadic arrhythmia patients with sinus bradycardia, QT prolongation, and short bursts of ventricular tachycardia. To determine the functional effect of the mutation, we conducted clinical, genetic, and functional analyses using whole-cell voltage-clamp, qPCR, Western blot, confocal microscopy, and co-immunoprecipitation. The mean current density of HEK293T cells transfected with HCN4-R666Q was lower in 24 to 36 h after transfection and was much lower in 36 to 48 h after transfection relative to cells transfected with wildtype HCN4. Additionally, we determined that the HCN4-R666Q mutant was more susceptible to ubiquitin-proteasome system-mediated protein degradation than wildtype HCN4. This decreased current density for HCN4-R666Q could be partly rescued by treatment with a proteasome inhibitor. Therefore, we conclude that HCN4-R666Q had an effect on HCN4 function in two aspects, including decreasing the current density of the channel as a biophysical effect and weakening its protein stability. Our findings provide new insights into the pathogenesis of the HCN4-R666Q mutation.

AKR1B10 Is a New Sensitive and Specific Marker for Fumarate Hydratase-Deficient Renal Cell Carcinoma.

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and distinct subtype of renal cancer caused by FH gene mutations. FH negativity and s-2-succinocysteine (2SC) positivity on immunohistochemistry can be used to screen for FH-deficient RCC, but their sensitivity and specificity are not perfect. The expression of AKR1B10, an aldo-keto reductase that catalyzes cofactor-dependent oxidation-reduction reactions, in RCC is unclear. We compared AKR1B10, 2SC, and FH as diagnostic biomarkers for FH-deficient RCC. We included genetically confirmed FH-deficient RCCs (n = 58), genetically confirmed TFE3 translocation RCCs (TFE3-tRCC) (n = 83), clear cell RCCs (n = 188), chromophobe RCCs (n = 128), and papillary RCCs (pRCC) (n = 97). AKR1B10, 2SC, and FH were informative diagnostic markers. AKR1B10 had 100% sensitivity and 91.4% specificity for FH-deficient RCC. The nonspecificity of AKR1B10 was shown in 26.5% of TFE3-tRCCs and 21.6% of pRCCs. 2SC showed 100% sensitivity and 88.9% specificity. However, nonspecificity for 2SC was evident in multiple RCCs, including pRCC, TFE3-tRCC, clear cell RCCs, and chromophobe RCCs. FH was 100% specific but 84.5% sensitive. AKR1B10 served as a highly sensitive and specific diagnostic biomarker. Our findings suggest the value of combining AKR1B10 and 2SC to screen for FH-deficient RCC. AKR1B10+/2SC+/FH- cases can be diagnosed as FH-deficient RCC. Patients with AKR1B10+/2SC+/FH+ are highly suspicious of FH-deficient RCC and should be referred for FH genetic tests.

Sideband cooling of a trapped ion in strong sideband coupling regime.

Conventional theoretical studies on the ground-state laser cooling of a trapped ion have mostly focused on the weak sideband coupling (WSC) regime, where the cooling rate is inverse proportional to the linewidth of the excited state. In a recent work [New J. Phys.23, 023018 (2021)10.1088/1367-2630/abe273], we proposed a theoretical framework to study the ground state cooling of a trapped ion in the strong sideband coupling (SSC) regime, under the assumption of a vanishing carrier transition. Here we extend this analysis to more general situations with nonvanishing carrier transitions, where we show that by properly tuning the coupling lasers a cooling rate proportional to the linewidth can be achieved. Our theoretical predictions closely agree with the corresponding exact solutions in the SSC regime, which provide an important theoretical guidance for sideband cooling experiments.

Nickel-catalysed enantioselective reaction of secondary phosphine oxides and activated vinylcyclopropanes.

Activated vinylcyclopropanes can form zwitterionic π-allylmetal species in the presence of transition metals and are widely used in organic synthesis. A nickel-catalyzed asymmetric allylation of secondary phosphine oxides with vinylcyclopropanes was described. Tertiary phosphine oxide products could be obtained with up to 91% yield and 92% ee.

The effects of dimethyl fumarate on cytoplasmic LPS-induced noncanonical pyroptosis in periodontal ligament fibroblasts and dental pulp cells.

AIM: Pyroptosis is a type of inflammatory cell death and is related to pulpitis and apical periodontitis. In this study, the aim was to investigate how periodontal ligament fibroblasts (PDLFs) and dental pulp cells (DPCs) respond to pyroptotic stimuli and explore whether dimethyl fumarate (DMF) could block pyroptosis in PDLFs and DPCs. METHODOLOGY: Three methods (stimulation with lipopolysaccharide [LPS] plus nigericin, poly(dA:dT) transfection and LPS transfection) were used to induce pyroptosis in PDLFs and DPCs, two types of fibroblasts related to pulpitis and apical periodontitis. THP-1 cell was used as a positive control. Afterwards, PDLFs and DPCs were treated with or without DMF before inducing pyroptosis to examine the inhibitory effect of DMF. Pyroptotic cell death was measured by lactic dehydrogenase (LDH) release assays, cell viability assays, propidium iodide (PI) staining and flow cytometry. The expression levels of cleaved gasdermin D N-terminal (GSDMD NT), caspase-1 p20, caspase-4 p31 and cleaved PARP were examined by immunoblotting. Immunofluorescence analysis was used to detect the cellular distribution of GSDMD NT. RESULTS: Periodontal ligament fibroblasts and DPCs were more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis than to canonical pyroptosis induced by stimulation with LPS priming plus nigericin or by poly(dA:dT) transfection. In addition, treatment with DMF attenuated cytoplasmic LPS-induced pyroptotic cell death in PDLFs and DPCs. Mechanistically, it was shown that the expression and plasma membrane translocation of GSDMD NT were inhibited in DMF-treated PDLFs and DPCs. CONCLUSIONS: This study indicates that PDLFs and DPCs are more sensitive to cytoplasmic LPS-induced noncanonical pyroptosis and that DMF treatment blocks pyroptosis in LPS-transfected PDLFs and DPCs by targeting GSDMD, suggesting DMF might be a promising drug for the management of pulpitis and apical periodontitis.

The combined treatment of fiber post and root canal by the Er:YAG laser enhances the bond strength of composite reconstruction.

Fiber post bonding failure remains an issue during crown restoration procedures. This experiment examines the bonding effect of combined Er:YAG laser treatment on both root canal and fiber post. Sixty extracted mandibular first premolars were randomly selected and divided into 6 groups (n = 10 per group): G1 (control group): root canal with 2.5% NaClO treatment, no treatment of fiber post; G2: root canal with 2.5% NaClO treatment and fiber post with airborne-particle abrasion; G3: root canal with Er:YAG laser treatment and fiber post with airborne-particle abrasion; G4: root canal with Er:YAG laser treatment, no treatment of fiber post; G5: root canal with 2.5% NaClO treatment, fiber post with Er:YAG laser irradiation; G6: combined Er:YAG laser irradiation of both root canal and fiber post. An Er:YAG laser with a wavelength of 2940 nm was used to treat the fiber post (4.5 W, 450 mJ, 10 Hz for 60 s at 100-µs pulse duration with 100% water cooling) and the root canal (1.5 W, 150 mJ, 10 Hz for 60 s at 100-µs pulse duration with 100% water cooling). When the root canal was treated with the laser, the fiber tip was inserted into the root canal to make a spiral reciprocating motion. Bond strength was analyzed by a micro push-out test. Data were analyzed using both the Tukey test and two-way ANOVA (α = 0.05). Failure modes were observed and counted through a stereo microscope. The root canal and fiber post surface analysis was performed using SEM. The bond strength of G3 and G6 were significantly enhanced compared to those of the other groups (p < 0.05). The SEM analysis showed that the smear layers of groups with root canals subjected to Er:YAG laser irradiation were significantly reduced compared to those of the control group (G1). In groups with fiber posts treated with Er:YAG laser irradiation, the surfaces of the fiber posts exhibited greater surface roughness and a certain degree of epoxy matrix removal. Through the combined Er:YAG laser irradiation of both root canal and fiber post, the bond strength between them was significantly enhanced, which was superior to the individual treatment of either fiber posts or root canal.

Removable partial prosthesis combined with swallowing training is an efficient clinical solution for oral cancer post-operation patients with palatal defect and dysphagia: a prospective study.

OBJECTIVE: Dysphagia is one of the major complications of oral cancer patients, and is disturbing thousands of patients worldwide. Our study aim to evaluate the clinical efficacy of prosthesis combined with swallowing training on palatal defect and dysphagia in post-operative oral cancer patients. MATERIALS AND METHODS: Sixteen oral cancer patients with palatal defect and dysphagia post-operation were treated with removable prosthesis and individualized swallowing function training. Swallowing function of patients before and after treatment was analyzed and compared by videofluoroscopic swallowing examination. The severity of depression and life quality were evaluated by Depression Scale (SDS) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scores, respectively. RESULTS: Oral transit time (OTT) significantly shortened after treatment (P < 0.01), and Penetration-Aspiration Scale (PAS) scores was significantly higher after treatment (P < 0.001). Different consistency bolus showed different risk of aspiration. Thickened liquids were related to lower PAS scores (P < 0.001). SDS standard score was significantly lower after treatment (P < 0.05). The total score of FACT-H&N after treatment was significantly higher (P < 0.05). No patients came back for regressed swallowing function during the follow-up period (17.06 ± 2.376 months). CONCLUSION: Removable prosthesis and swallowing training can significantly improve swallowing function, reduce depression degree, and improve quality of life (QOL). CLINICAL RELEVANCE: Removable prosthesis combined with swallowing training is a cheap and effective method to improve QOL in patients with palate defect and dysphagia after oral cancer.

Reconstruction of Acquired Segmental Mandibular Defects Using Pedicled Mandibular Muscle Flap and Evaluation of Speech Function and Aesthetic Outcomes.

PURPOSE: The purpose of this study was to investigate the clinical effect of pedicled mandibular osteomuscular flap in the reconstouring of repair of acquired segmental mandibular defects. PATIENTS AND METHODS: Thirteen patients with acquired segmental mandibular defects requiring secondary repair were included into the study. Pedicled mandibular osteomuscular flap was applied with strong internal fixation to repair the mandibular defects. The patients' speech, swallowing function, and aesthetic changes were evaluated upon follow-up. RESULTS: The flaps were viable in all patients. Average speech function score was 7.6±0.6. All patients had a drinking test rating of grade I or II with good masticatory efficiency. The postoperative self-assessment Visual Analog Scale score of appearance was 7.8±0.8. CONCLUSIONS: Pedicled mandibular osteomuscular flap is a viable choice in the secondary repair and reconstruction of mandibular acquired segmental defects. This flap could achieve better oral function with good aesthetic results.

The efficacy of metformin for the treatment of psoriasis: a meta-analysis study.

Introduction: Metformin has potential in treating patients with psoriasis, and this meta-analysis aims to explore the impact of metformin supplementation on treatment efficacy for psoriasis. Material and methods: The PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of metformin on treatment efficacy for patients with psoriasis. Results: Three RCTs were included in the meta-analysis. Overall, compared with control intervention for psoriasis, metformin intervention resulted in significantly increased psoriasis area severity index (PASI) 75% reduction (odds ratio (OR) = 22.02; 95% confidence interval (CI): 2.12 to 228.49; p = 0.01), and erythema, scaling and induration (ESI) 75% reduction (OR = 9.12; 95% CI: 2.13 to 39.02; p = 0.003), and was associated with substantially decreased fasting plasma glucose (FPG, standard mean difference (SMD) = -0.59; 95% CI: -0.92 to -0.26; p = 0.0005), triglycerides (SMD = -0.92; 95% CI: -1.38 to -0.47; p < 0.0001), total cholesterol (SMD = -0.77; 95% CI: -1.22 to -0.32; p = 0.00008), and low-density lipoprotein (LDL, SMD = -0.67; 95% CI: -1.12 to -0.23; p = 0.003). Conclusions: Metformin supplementation effectively improves treatment efficacy and metabolic syndrome in psoriasis patients.