Mechanism and bioinformatics analysis of the effect of berberine-enhanced fluconazole against drug-resistant Candida albicans.

Biofilms produced by Candida albicans present a challenge in treatment with antifungal drug. Enhancing the sensitivity to fluconazole (FLC) is a reasonable method for treating FLC-resistant species. Moreover, several lines of evidence have demonstrated that berberine (BBR) can have antimicrobial effects. The aim of this study was to clarify the underlying mechanism of these effects. We conducted a comparative study of the inhibition of FLC-resistant strain growth by FLC treatment alone, BBR treatment alone, and the synergistic effect of combined FLC and BBR treatment. Twenty-four isolated strains showed distinct biofilm formation capabilities. The antifungal effect of combined FLC and BBR treatment in terms of the growth and biofilm formation of Candida albicans species was determined via checkerboard, time-kill, and fluorescence microscopy assays. The synergistic effect of BBR and FLC downregulated the expression of the efflux pump genes CDR1 and MDR, the hyphal gene HWP1, and the adhesion gene ALS3; however, the gene expression of the transcriptional repressor TUP1 was upregulated following treatment with this drug combination. Furthermore, the addition of BBR led to a marked reduction in cell surface hydrophobicity. To identify resistance-related genes and virulence factors through genome-wide sequencing analysis, we investigated the inhibition of related resistance gene expression by the combination of BBR and FLC, as well as the associated signaling pathways and metabolic pathways. The KEGG metabolic map showed that the metabolic genes in this strain are mainly involved in amino acid and carbon metabolism. The metabolic pathway map showed that several ergosterol (ERG) genes were involved in the synthesis of cell membrane sterols, which may be related to drug resistance. In this study, BBR + FLC combination treatment upregulated the expression of the ERG1, ERG3, ERG4, ERG5, ERG24, and ERG25 genes and downregulated the expression of the ERG6 and ERG9 genes compared with fluconazole treatment alone (p < 0.05).

Establishment and application of perceived age prediction model for the periocular aging research of Chinese Han women.

BACKGROUND: The assessment of skin aging through skin measurements faces limitations, making perceived age evaluation a more valuable and direct tool for assessing skin aging. Given that the aging process markedly affects the appearance of the eye contour, characterizing the eye region could be beneficial for perceived age assessment. This study aimed to analyze age-correlated changes in the eye contour within the Chinese Han female population and to develop, validate, and apply a multiple linear regression model for predicting perceived age. MATERIALS AND METHODS: A naïve panel of 107 Chinese women assessed the perceived ages of 212 Chinese Han women. Instrumental analysis evaluated periorbital parameters, including palpebral fissure width (PFW), palpebral fissure height (PFH), acclivity of palpebral fissure (AX), angle of inner canthal (AEN), and angle of outer canthal (AEX). These parameters were used to construct a multiple linear regression model for predicting the perceived ages of Chinese Han women. A combined treatment using Fotona 4D and an anti-aging eye cream, formulated with plant extracts, peptides, and antioxidants, was conducted to verify the cream's anti-aging efficacy and safety. This eye cream was then tested in a large-scale clinical trial involving 101 participants. The prediction model was employed in this trial to assess the perceived ages of the women after an 8-week application of the eye cream. RESULTS: All parameters were observed to decrease with age. An intergroup comparison indicated that eyelid aging in Chinese Han women accelerates beyond the age of 50. Consequently, a linear regression model was constructed and validated, with the perceived age being calculated as 183.159 - 1.078 * AEN - 4.487 * PFW + 6.061 * PFH - 1.003 * AX - 0.328 * AEX. The anti-aging efficacy and safety of the eye cream were confirmed through combined treatment with Fotona 4D, showing improvements in wrinkles, elasticity, and dark circles under the eyes. In a large-scale clinical evaluation using this eye cream, a perceived age prediction model was applied, suggesting that 8 weeks of use made participants appear 2.25 years younger. CONCLUSION: Our study developed and validated a multiple linear regression model to predict the perceived age of Chinese Han women. This model was successfully utilized in a large-scale clinical evaluation of anti-aging eye cream, revealing that 8 weeks of usage made participants appear 2.25 years younger. This method effectively bridges the gap between clinical research and consumer perceptions, explores the complex factors influencing perceived age, and aims to improve anti-aging formulations.

LNP-miR-155 cy5 Inhibitor Regulates the Copper Transporter via the ß-Catenin/TCF4/SLC31A1 Signal for Colorectal Cancer Therapy.

Lipid nanoparticle (LNP) delivery systems are widely used in the delivery of small-molecule drugs and nucleic acids. In this study, we prepared LNP-miR-155 by lipid nanomaterial technology and investigated the effects of LNP-miR-155 on ß-catenin/transcription factor 4 (TCF4)/solute carrier family 31 member 1/copper transporter 1 (SLC31A1/CTR1) signaling and copper transport in colorectal cancer. For this, we used an LNP-miR-155 cy5 inhibitor and LNP-miR-155 cy5 mimics for the transfection of HT-29/SW480 cells. The transfection efficiency and uptake efficiency were detected by immunofluorescence. Relevant cell assays confirmed that the LNP-miR-155 cy5 inhibitor mediates the regulation of copper transport through the ß-catenin/TCF4/SLC31A1 axis. The LNP-miR-155 cy5 inhibitor reduced cell proliferation, migration, and colony formation and promoted cell apoptosis. We also confirmed that miR-155 downregulates HMG box-containing protein 1 (HBP1) and adenomatous polyposis coli (APC) in cells and activates the function of ß-catenin/TCF4 signaling. In addition, we found that the copper transporter, SLC31A1, is highly expressed in colorectal cancer cells. Furthermore, we also found that the complex ß-catenin/TCF4 promotes the transcription of SLC31A1 by binding to its promoter region, which sustains the transport of copper from the extracellular region to the intracellular region and increases the activities of Cu2+-ATPase and superoxide dismutase (SOD). In summary, the LNP-miR-155 cy5 inhibitor regulates ß-catenin/TCF4 by downregulating SLC31A1-mediated copper transport and intracellular copper homeostasis.

Discovery of Coixol Derivatives as Potent Anti-inflammatory Agents.

Coixol, a derivative of 2-benzoxazolinone extracted from coix (Coix lachryma-jobi L. var. ma-yuen Stapf), has demonstrated promising anti-inflammatory activity and low cytotoxicity. In this study, 26 coixol derivatives were designed and synthesized by hybridization with cinnamic acid to identify new anti-inflammatory agents. The anti-inflammatory activities of the derivatives were screened using LPS-induced overexpression of nitric oxide (NO) in RAW264.7 macrophages. On the basis of the screening results, compounds containing furan (9c) or nitrofuran (9j) moieties displayed more pronounced activity than coixol and celecoxib. Mechanistic investigations revealed that 9c and 9j suppressed the expression of induced nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, which was associated with the inhibition of the nuclear factor (NF)-κB signaling pathway. In vivo studies confirmed the anti-inflammatory activity of 9c and 9j in a xylene-induced mice auricles edema model. The preliminary in vitro and in vivo research findings suggest that 9c and 9j have the potential to be developed as anti-inflammatory agents.

Design and synthesis of 9-phenanthranilamide derivatives and the study of anti-inflammatory, antioxidant and neuroprotective activities.

Oxidative stress and a series of excessive inflammatory responses are major obstacles to neurological functional recovery after ischemic stroke. In this study, we synthesized several novel 9-phenanthranilamide derivatives and evaluated their anti-inflammatory and antioxidant activities. Among the initially screened compounds, most could strongly inhibi lipopolysaccharide (LPS)-stimulated production of IL-1ß, IL-6 and TNF-α in microglial cells. Additionally, compounds 8b, 8q, 8r and 8s significantly inhibited the production of NO, and they also had dose-dependent protective effects on PC12 neuronal cells induced by H2O2. The antineuroinflammatory effects of 8r and 8s were associated with the downregulation of LPS-induced inflammatory mediators of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and both compounds inhibited the NF-κB signaling pathway. Further examinations showed that 8s had a significant neuroprotective effect on rats with middle cerebral artery occlusion (MCAO). It decreased the infarct volume and the neurological deficit score. Overall, our results suggested that compound 8s might be a promising agent for stroke treatment.

Combination of dimethylmethoxy chromanol and turmeric root extract synergically attenuates ultraviolet-induced oxidative damage by increasing endogenous antioxidants in HaCaT cells.

BACKGROUND: Repeated exposure to UV generates excessive reactive oxygen species (ROS) and damages the enzymatic antioxidant defense system including quinone oxidoreductase 1 (NQO1) and superoxide dismutase (SOD) in skin. Topical application of antioxidants may prevent the undesired damage of cellular proteins, lipids and DNA in skin. Dimethylmethoxy chromanol (DMC) is a bioinspired molecule, designed to be a structural analog to the γ-tocopherol that is naturally present in vegetables and plants. Turmeric root extract (TRE) is from a plant in South Asia extensively used as a food spice & vegetable, and its main components are turmerones. As both DMC and TRE are strong antioxidants with complementary antioxidation mechanisms, the aim of this study was to investigate the enhanced protective effects of their combination on oxidative damage in HaCaT cells following UVB exposure. MATERIALS AND METHODS: The effects of single and combined administrations of DMC and TRE on the SOD activity of HaCaT cells were evaluated by the SOD assay and qPCR. The NQO1 expression in the UVB-treated HaCaT cells was analyzed by the Western Blot. Furthermore, a clinical test involving 24 subjects was conducted to evaluate the in vivo antioxidation efficacies of the serum formulated with the combination of DMC and TRE at the optimal weight ratio. RESULTS: SOD assay showed that pretreating DMC or TRE alone could not preserve the impaired HaCaT SOD activity after UVB treatment. DMC and TRE at 1:1 weight ratio was the optimal combination to enhance the HaCaT SOD activity by approximately more than 1-fold compared with either of the single treated groups. No enhancement effect was observed at other mixing ratios. The 1:1 weight ratio was further proved to be optimal as this combination boosted the NQO1 expression by more than 50%, whereas no boosting effect was observed at other mixing ratios. The clinical test of the serum containing this optimal antioxidant combination demonstrated promising in vivo antioxidation efficacies after 4-week use, including 7.16% improvement in skin lightening, 18.29% reduction in skin redness, 35.68% decrease in TEWL, 19.05% increase in skin gloss and 32.04% enhancement in skin firmness. CONCLUSION: Collectively, our results indicated that the combination of DMC and TRE at 1:1 weight ratio attenuated the UV-induced oxidative damage by synergistically boosting endogenous antioxidant enzyme activity in HaCaT cells. Therefore, this optimal antioxidant combination is a promising treatment to boost skin antioxidation defense system.

Soft and Hard Tissue Changes and Facial Rejuvenation of Anterior Maxillary Segmental Osteotomy: A Three-Dimensional Cephalometric Study.

OBJECTIVE: To explore the efficacy of anterior maxillary segmental osteotomy (AMSO) in reliving maxillary protrusion and better analyze the three-dimensional (3D) morphological changes of the postoperative nasolabial region using computed tomography (CT) and evaluate the trend of facial rejuvenation. MATERIALS AND METHODS: Forty-five patients who underwent AMSO from January 2017 to December 2021 were retrospectively included. CT and oriented photography were performed before and 10 months after the treatment. The mimics17.0 software was used to reconstruct the 3D CT scan results before and after the operation, measure the data of each anatomical index, and systematically evaluate the soft tissue changes in the nasolabial region. The patients themselves, the plastic surgeons, family members, or friends of patients use the Face-Q Age Appraisal Visual Analogue Scale (VAS) to evaluate the changes in patients' visual age before and after the operation. RESULTS: Forty-five cases of maxillary protrusion were alleviated. Seen from the side, the protruding degree of the upper lip is obviously reduced. In the front view, âˆ Cont-Sbal-F, the width of alar base, and alae nasi all increased significantly. Contrary to traditional perceptions, the protrusion and height of the nose tip actually increased rather than decreased after AMSO. The visual age score improved positively, and patients obtained facial rejuvenation. No serious complications occurred; after 10-month follow-up, we achieved a high degree of satisfaction. CONCLUSION: AMSO can significantly improve the maxillary protrusion, and it can increase the protrusion and height of the nose tip. Also, patients can get a younger appearance. Comprehensive preoperative evaluation and postoperative nasolabial morphology with maxillary protrusion patients are helpful for correct clinical decision-making. At the same time, the operation suggests a new choice of facial rejuvenation for patients with maxillary protrusion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266.

Redefining Mandibular Sub-units: The "ABC" Classification and Surgical Strategies for Lower Face Contouring.

BACKGROUND: In east Asia, lower face contouring surgeries including reduction mandibuloplasty and genioplasty are the most popular aesthetic craniofacial surgeries. Conventional selection of surgical strategies mainly relied on the visual judgment of the mandibular angle, without overall assessment of the mandibular sub-units. Furthermore, only a few studies offered quantitative assessment of the mandibular shape. METHODS: From 2010 to 2021, 1241 patients diagnosed with square faces and received customized lower face contouring surgeries by the senior author were reviewed and analyzed to propose an "ABC" classification system for facilitating surgical planning. RESULTS: Among them, 998 (80.42%) received bilateral mandible reshaping, 155 (12.49%) underwent bilateral mandible reshaping combined with genioplasty, and 88 (7.09%) received asymmetric mandible reshaping. A modified classification system composed of three critical parameters (height, morphology/thickness, divergence) in three aesthetic zones (mandibular angle, mandibular body, chin) was proposed based on quantitative summarization of the CT database and the senior author's 12-year experience. The way to facilitate surgical planning with this classification was demonstrated. CONCLUSIONS: This modified classification system ushered a decision-making process that prioritized several critical measurements and proposed an operative planning form. Meanwhile, it can also be cooperated into the three-dimensional virtual surgical plan. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Polarization disorder of decidual NK cells in unexplained recurrent spontaneous abortion revealed by single-cell transcriptome analysis.

BACKGROUND: Unexplained recurrent spontaneous abortion (URSA) is one of the most common diseases in pregnancy and is mainly caused by immune disorders. The foetus is similar to semiallogeneic maternal tissue, so the balance of immune tolerance must be dynamically maintained during pregnancy. Decidual natural killer (dNK) cells primarily mediate the immune tolerance microenvironment at the maternal-fetal interface. By using single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptome sequencing analysis, we explored the characteristic distribution of dNK cells in URSA patients. METHODS: Control maternal-fetal interface tissue (from normal pregnant women, n = 3) and case maternal-fetal interface tissue (from patients with URSA, n = 3) samples were analysed by scRNA-seq and high-throughput transcriptome sequencing. RESULTS: By scRNA-seq, we demonstrated the maturation process of the transition of dNK cells from cytotoxic characteristics to immune tolerance in transcriptome analysis. Moreover, compared with normal pregnant women, serious disturbances in the polarization process of dNK cells were found in URSA. Simultaneously, the transcriptional level of the extracellular matrix (ECM) in URSA patients showed a significant decrease. The dNK cells interacted with extravillous trophoblasts to achieve immune-tolerant polarization. CONCLUSIONS: Insufficient expression of KIRs during dNK cell differentiation might be a key reason why polarized dNK cells still had high cytotoxic reactivity in URSA patients. Abnormal expression of ECM may affect the interaction of dNK cells with EVTs, making dNK cells immature. Both resulted in maternal immune intolerance to the foetus during pregnancy.

ZNF3 regulates proliferation, migration and invasion through MMP1 and TWIST in colorectal cancer.

Colorectal cancer (CRC) is a malignant tumor with a high incidence and mortality worldwide. Currently, the underlying molecular mechanisms of CRC are still unclear. Zinc finger protein 3 (ZNF3) is a zinc-finger transcription factor that has been reported as a candidate for breast cancer prognosis, suggesting its involvement in the regulation of tumorigenesis. However, the association between ZNF3 and CRC remains unknown. To investigate the role of ZNF3 in CRC, we first analyze the correlation between ZNF3 expression and CRC, and the results demonstrate that ZNF3 is highly expressed in CRC tissue and cells, which is associated with the age of CRC patients. In vitro studies show that ZNF3 overexpression promotes CRC cell migration. Compared to control cells, knockdown of ZNF3 markedly suppresses CRC cell proliferation, migration and invasion and promotes G0/G1 phase cell cycle arrest. The expressions of the EMT-related markers TWIST and MMP1 are significantly decreased when ZNF3 is silenced. Additionally, overexpression of MMP1 and TWIST exacerbates CRC cell proliferation, accelerates the S phase cell cycle in ZNF3-knockdown SW480 cells, and increases cell migration and invasion through Transwell chambers. These data suggest that ZNF3 is involved in cellular proliferation, migration and invasion by regulating MMP1 and TWIST in CRC cells.

Prenatal exposure of citalopram elicits depression-like and anxiety-like behaviors and alteration of morphology and protein expression of medial prefrontal cortex in young adult mice.

BACKGROUND: Treatment of major depression disorder with Selective serotonin reuptake inhibitors (SSRIs), such as citalopram (CTM), during pregnancy effects on the neurological trajectory of the offspring and induces enduring consequences, notably emotional and cognitive impairment. The associations between prenatal exposure to SSRIs and neurological underpinnings of these atypical behaviors in offspring are contentious and poorly understood. METHODS: We examined modifications in physiological, morphological, and biochemical characteristics in male and female offspring of C57BL/6 exposed to CTM during the third trimester of gestation. We utilized different behavior procedures to observe depression and anxiety-like behavior in 1~2 month old CTM-exposed mouse offspring. We employed Golgi-Cox staining to examine the neuronal structure of medial prefrontal cortex (mPFC) in CTM-exposed mice following protein expression levels by utilizing biochemical techniques. RESULTS: Our results indicate an impaired behavior such as anxiety and altered locomotion along with the substantial reduction in dendritic length and the number of dendritic branches in CTM-exposed mice. We observed differentially increase c-Fos expression in the mPFC following altered protein expression levels relative to controls. CONCLUSIONS: Our finding supports the function of CTM as a prenatal modulator of susceptibility to depressive-like behavior in offspring. We indicate that prenatal CTM exposure elicits a negative impact on the central nervous system, especially those regions involved in cognition and drug reinforcement. Furthermore, genetic, chemo-genetic, and optogenetic methods should be used to explain the function of SSRIs such as CTM during pregnancy in the regulation of mood and emotion-related behaviors in children.

Rapamycin and 3-Methyladenine Influence the Apoptosis, Senescence, and Adipogenesis of Human Adipose-Derived Stem Cells by Promoting and Inhibiting Autophagy: An In Vitro and In Vivo Study.

OBJECTIVE: We aimed to clarify the changes in apoptosis, proliferation, senescence, and adipogenesis after promoting and inhibiting autophagy in adipose-derived stem cells (ADSCs) by rapamycin and 3-methyladenine in vitro and in vivo. METHODS: After rapamycin and 3-methyladenine pretreatment, ADSC autophagy was detected by immunofluorescence for LC3, RT-PCR for ATG genes, and western blotting (WB) for the LC3 II/I and p62 proteins. TUNEL staining, PCR of BAX, and WB of Caspase-3 were preformed to assess ADSC apoptosis. The adipogenesis of ADSCs was evaluated by Oil red O staining and PCR of PPAR-γ. CCK8 assays were conducted to detect proliferation. Senescence was tested by Sa-ß-gal staining and PCR of the P16/ 19/21 genes. Moreover, the mass and volume retention rate were determined, and perilipin and CD31 staining were performed in vivo. RESULTS: Rapamycin and 3-methyladenine pretreatment increased and decreased autophagy of ADSCs, respectively, under normal and oxygen-glucose deprivation conditions. Apoptosis and senescence of ADSCs were decreased, and adipogenesis was increased along with the upregulation of autophagy. However, the proliferation of ADSCs was inhibited after either rapamycin or 3-methyladenine pretreatment. In vivo, the volume and mass retention rate and the angiogenesis of the grafts were also improved after rapamycin pretreatment. CONCLUSIONS: Rapamycin pretreatment reduced apoptosis, delayed senescence, and promoted adipogenesis of ADSCs. These effects were inhibited by 3-methyladenine, indicating that the changes may be mediated by autophagy. Moreover, the survival rate and angiogenesis of the grafts were increased after upregulation of ADSC autophagy in vivo, which may help improve the efficiency of clinical fat transplantation. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A Modified Procedure for Single-eyelid Asian Females with Lacrimal Gland Prolapse: Lacrimal Gland Reposition combined with Fat Transposition in Double-eyelid Operation.

BACKGROUND: The awareness and treatment of lacrimal gland prolapse (LGP) have been primarily improved with a further understanding of lateral eyelid bulging over the decades. However, for Asian single-eyelid females with LGP, a tailor-made procedure applicable to their comparatively young puffy eyes is needed. METHODS: This is a retrospective study. From Jan. 2009 to Jan. 2019, two hundred and three Asian single-eyelid females with LGP, who met the inclusion criteria, underwent double-eyelid surgeries and adjunctive lacrimal gland repositions with preaponeurotic fat transposition. Pertinent demographics, complications, pre-and post-operative photography were collected. RESULTS: A total of 167 patients completed the 4-24 months' follow-up (average: 16.3 months). One hundred and thirty-two cases (79.0%) were diagnosed as LGP preoperatively, and the rest (35/167, 21.0%) were diagnosed intraoperatively. All patients (average: 28.4 years old) received modified blepharoplasty. Postoperative symptoms involving local mild pain (2.9%, 5/167), upper eyelid tightness (3.6%, 6/167), and moderate epiphora (9.0%, 15/167) were all recovered spontaneously within one month. Prolapse recurrence and severe complications such as dry eye syndrome were not observed. CONCLUSIONS: We proposed a modified procedure to enhance the diagnosis and treatment of LGP during Asian blepharoplasty. The lacrimal gland suspension and fat transposition assured the cosmetic outcome for selected young, puffy Asian eyes. The supratarsal creases were satisfactory, and the complication rate was low. Furthermore, the rearrangement of preaponeurotic fat smoothed the contour transition and preserved the orbital volume. Therefore, this is a safe and effective technique worth recommending.

Beyond diffuse correlations: deciphering random flow in time-of-flight resolved light dynamics.

Diffusing wave spectroscopy (DWS) and diffuse correlation spectroscopy (DCS) can assess blood flow index (BFI) of biological tissue with multiply scattered light. Though the main biological function of red blood cells (RBCs) is advection, in DWS/DCS, RBCs are assumed to undergo Brownian motion. To explain this discrepancy, we critically examine the cumulant approximation, a major assumption in DWS/DCS. We present a precise criterion for validity of the cumulant approximation, and in realistic tissue models, identify conditions that invalidate it. We show that, in physiologically relevant scenarios, the first cumulant term for random flow and second cumulant term for Brownian motion alone can cancel each other. In such circumstances, assuming pure Brownian motion of RBCs and the first cumulant approximation, a routine practice in DWS/DCS of BFI, can yield good agreement with data, but only because errors due to two incorrect assumptions cancel out. We conclude that correctly assessing random flow from scattered light dynamics requires going beyond the cumulant approximation and propose a more accurate model to do so.

The Relationship Between the Facial Proportion Changes in Hard Tissue and the Satisfaction of Patients After Reduction Malarplasty: a Research Based on Three-Dimensional Cephalometry.

OBJECTIVE: We aim to measure the zygomatic width and protrusion changes in hard tissue after reduction malarplasty and then calculate facial proportion changes and analyze the relationship between facial proportion changes and patients' satisfaction. METHODS: We retrospectively reviewed our database and selected 36 eligible patients who underwent isolated reduction malarplasty in our department from March 2015 to July 2018. The preoperative and postoperative facial width and protrusion, as well as head height, in hard tissue were measured using ProPlan software. Patients' satisfaction was evaluated by questionnaire. The correlations between the facial proportion changes and patients' satisfaction were analyzed using Spearman correlation analysis. RESULTS: The preoperative and postoperative midface widths were 135.87 ± 4.09 mm and 129.06 ± 4.95 mm. The relative zygomatic protrusion was reduced by 3.29 ± 1.54 mm in the left and 2.88 ± 1.73 mm in the right after surgery. The ratio of the midface width to lower face width changed from 1.43 ± 0.05 to 1.36 ± 0.06 after surgery. And the ratio of the head height to midface width changed from 1.53 ± 0.05 to 1.61 ± 0.05 after surgery. The ratios were indeed close to the ideal ratios we presumed (4:3 and 1.618). Moreover, patients' total and morphology satisfaction were both significantly higher with the postoperative ratio of the midface width to lower face width closer to 4:3 (R = - 0.732, P < 0.001; R = - 0.906, P < 0.001, respectively). But only morphology satisfaction was higher with the ratio of the head height to midface width closer to 1.618 (R = - 0.404, P = 0.014) and the ratio of the postoperative midface to lower face width decreased (R = - 0.434, P = 0.008). CONCLUSIONS: We found patients' morphology satisfaction was higher with the proportion of the postoperative midface to lower face width decreased. What's more, the proximity degree between the postoperative facial proportion and the ideal facial proportions we presumed was significantly correlated with patients' high satisfaction. Therefore, 4:3 and 1.618 may be the ideal postoperative facial ratios for the patients who underwent reduction malarplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266.

Comparison of Bilateral Mandibular Angle Ostectomy Between East Asian Males and Females: A Study Based on Three-Dimensional Computed Tomography Reconstruction.

BACKGROUND: Mandibular angle ostectomy is a common plastic surgery for facial contouring in East Asians. However, rarely we could find reports on differences between East Asian males and females undergoing this surgery. OBJECTIVE: To describe the differences between East Asian males and females before and after mandibular angle ostectomy. METHODS: A total of 22 Asian males and 52 Asian females who underwent mandibular angle ostectomy from April 2015 to November 2018 were enrolled. Three-dimensional computed tomography was used to evaluate the preoperative and postoperative data of the mandible. Thirteen clinical data were measured on reconstructed mandibular models. The differences in data between males and females were analyzed to identify the causes of the differences before and after surgery. The follow-up was 6-12 months, and patient satisfaction was also evaluated. RESULTS: The ostectomy volume was positively correlated with the distance from the intersection of the occlusal plane and the anterior margin of the mandibular ramus to gonion (MR-Go; female, p < 0.01; male, p = 0.02). There was a positive correlation between the ostectomy volume and the postoperative drainage fluid (The drainage fluid is mainly blood) volume after surgery in females (p < 0.05), while there is no significant correlation between these two data in males (p = 0.19). Patients with a long distance from the second molar to the lower edge of the mandibular body (SM-MB) tended to have a higher risk of postoperative bleeding (female, r = 0.56, p < 0.01; male, r = 0.73, p = 0.01). CONCLUSION: Because of the difference in the anatomical size of the mandible and different aesthetic requirements for facial contouring between males and females, surgeons encounter different intraoperative conditions resulting in difficulties during surgery. Understanding differences in mandibular angles predicts differences in ostectomy volume and postoperative bleeding risk, thus aiding surgeons and leading to better operative outcomes. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Alteration of the tumor suppressor SARDH in sporadic colorectal cancer: A functional and transcriptome profiling-based study.

Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF, and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c.551C>T mutation in SARDH in sCRC. SARDH was identified as a novel tumor suppressor gene and was abnormally decreased in sCRC at both the transcriptional and the translational level. SARDH mRNA levels were also down-regulated in oesophageal cancer, lung cancer, liver cancer, and pancreatic cancer in the TCGA database. SARDH overexpression inhibited the proliferation, migration, and invasion of CRC cell lines, whereas its depletion improved these processes. SARDH overexpression was down-regulated in multiple pathways, especially in the chemokine pathway. The SARDH transcript level was positively correlated with the methylation states of CXCL1 and CCL20. Therefore, we concluded that SARDH depletion is involved in the development of sCRC.

MicroRNA-3191 promotes migration and invasion by downregulating TGFBR2 in colorectal cancer.

Mutations in transforming growth factor beta receptor II (TGFBR2) are detected in up to 30% of overall colorectal cancer (CRC). Dysregulation of some microRNAs participated in the CRC pathogenesis. In this study, we used the gene ontology analyses, the Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis to indicate that miR-3191 was involved in the regulation of transforming growth factor beta (TGF-BETA) signal pathway in CRC. These bioinformatics results were supported by data obtained from CRC samples and experiments in vitro. The luciferase reporter assay was used to confirm that miR-3191 modulates TGF-BETA signal pathway by targeting TGFBR2. By transwell migration and invasion assays, we showed that miR-3191 promoted CRC cell migration and invasion by downregulating TGFBR2. And it may serve as a novel therapeutic strategy for treating CRC patients.

Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study.

BACKGROUND: Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC. METHODS: We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study. RESULTS: We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1. CONCLUSIONS: Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.