A new method to orient a 3-dimensional facial model to natural head position: A preliminary report on accuracy and reproducibility.

OBJECTIVES: To establish and validate a novel method to orient a 3-dimensional (3D) facial model to natural head position (NHP) in a stereophotogrammetric system using a 2-dimensional frontal full-face photograph of NHP. MATERIAL AND METHODS: Specific technique procedure was reported for our method, and in vitro model experiment was performed for accuracy test. A preliminary volunteer study was then planned for reproducibility test. RESULTS: The accuracy on a 3D-printed test model was within 0.15°. Within an observational cohort of 22 dental students, the angular deviations of different maxillofacial regions (e.g., central forehead, left and right zygomatic regions, apex of nose and mental region) were no more than 2° between the 3D NHP models acquired with a shorter time-interval (1 h from baseline) or a longer time-interval (7 days from baseline), which were all considered clinically insignificant. In addition, the angular deviations were significantly larger with a 7d-interval than with a 1h-interval, indicting a decline in 3D NHP reproducibility over short time duration. CONCLUSION: The current method may represent a clinically useful protocol for recording and transferring 3D NHP in stereophotogrammetry. CLINICAL RELEVANCE: It may provide reliable and meaningful reference information for evaluating craniofacial morphology, and be of clinical use in the diagnosis, treatment and follow-ups of patients with aesthetic or deformed craniofacial problems.

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

Background: Lung adenocarcinoma (LUAD) among never-smokers is a public health burden especially prevalent in East Asian (EAS) women. Polygenic risk scores (PRSs), which quanefy geneec suscepebility, are promising for straefying risk, yet have mainly been developed in European (EUR) populaeons. We developed and validated single-and mule-ancestry PRSs for LUAD in EAS never-smokers, using the largest available genome-wide associaeon study (GWAS) dataset. Methods: We used GWAS summary staesecs from both EAS (8,002 cases; 20,782 controls) and EUR (2,058 cases; 5,575 controls) populaeons, as well as independent EAS individual level data. We evaluated several PRSs approaches: a single-ancestry PRS using 25 variants that reached genome-wide significance (PRS-25), a genome-wide Bayesian based approach (LDpred2), and a mule-ancestry approach that models geneec correlaeons across ancestries (CT-SLEB). PRS performance was evaluated based on the associaeon with LUAD and AUC values. We then esemated the lifeeme absolute risk of LUAD (age 30-80) and projected the AUC at different sample sizes using EAS-derived effect-size distribueon and heritability esemates. Findings: The CT-SLEB PRS showed a strong associaeon with LUAD risk (odds raeo=1.71, 95% confidence interval (CI): 1.61, 1.82) with an AUC of 0.640 (95% CI: 0.629, 0.653). Individuals in the 95 th percenele of the PRS had an esemated 6.69% lifeeme absolute risk of LUAD. Comparison of LUAD risk between individuals in the highest and lowest 20% PRS quaneles revealed a 3.92-fold increase. Projeceon analyses indicated that achieving an AUC of 0.70, which approaches the maximized prediceon poteneal of the PRS given the esemated geneec variance, would require a future study encompassing 55,000 EAS LUAD cases with a 1:10 case-control raeo. Interpretations: Our study underscores the poteneal of mule-ancestry PRS approaches to enhance LUAD risk straeficaeon in never-smokers, parecularly in EAS populaeons, and highlights the necessary scale of future research to uncover the geneec underpinnings of LUAD.

Pitavastatin sensitizes the EGFR-TKI associated resistance in lung cancer by inhibiting YAP/AKT/BAD-BCL-2 pathway.

BACKGROUND: Despite effective strategies, resistance in EGFR mutated lung cancer remains a challenge. Metabolic reprogramming is one of the main mechanisms of tumor drug resistance. A class of drugs known as "statins" inhibit lipid cholesterol metabolism and are widely used in patients with cardiovascular diseases. Previous studies have also documented its ability to improve the therapeutic impact in lung cancer patients who receive EGFR-TKI therapy. Therefore, the effect of statins on targeted drug resistance to lung cancer remains to be investigated. METHODS: Prolonged exposure to gefitinib resulted in the emergence of a resistant lung cancer cell line (PC9GR) from the parental sensitive cell line (PC9), which exhibited a traditional EGFR mutation. The CCK-8 assay was employed to assess the impact of various concentrations of pitavastatin on cellular proliferation. RNA sequencing was conducted to detect differentially expressed genes and their correlated pathways. For the detection of protein expression, Western blot was performed. The antitumor activity of pitavastatin was evaluated in vivo via a xenograft mouse model. RESULTS: PC9 gefitinib resistant strains were induced by low-dose maintenance. Cell culture and animal-related studies validated that the application of pitavastatin inhibited the proliferation of lung cancer cells, promoted cell apoptosis, and restrained the acquired resistance to EGFR-TKIs. KEGG pathway analysis showed that the hippo/YAP signaling pathway was activated in PC9GR cells relative to PC9 cells, and the YAP expression was inhibited by pitavastatin administration. With YAP RNA interference, pAKT, pBAD and BCL-2 expression was decreased, while BAX expression as increased. Accordingly, YAP down-regulated significantly increased apoptosis and decreased the survival rate of gefitinib-resistant lung cancer cells. After pAKT was increased by SC79, apoptosis of YAP down-regulated cells induced by gefitinib was decreased, and the cell survival rate was increased. Mechanistically, these effects of pitavastatin are associated with the YAP pathway, thereby inhibiting the downstream AKT/BAD-BCL-2 signaling pathway. CONCLUSION: Our study provides a molecular basis for the clinical application of the lipid-lowering drug pitavastatin enhances the susceptibility of lung cancer to EGFR-TKI drugs and alleviates drug resistance.

Hyperactivation of SREBP induces pannexin-1-dependent lytic cell death.

Sterol-regulatory element binding proteins (SREBPs) are a conserved transcription factor family governing lipid metabolism. When cellular cholesterol level is low, SREBP2 is transported from the endoplasmic reticulum to the Golgi apparatus where it undergoes proteolytic activation to generate a soluble N-terminal fragment, which drives the expression of lipid biosynthetic genes. Malfunctional SREBP activation is associated with various metabolic abnormalities. In this study, we find that overexpression of the active nuclear form SREBP2 (nSREBP2) causes caspase-dependent lytic cell death in various types of cells. These cells display typical pyroptotic and necrotic signatures, including plasma membrane ballooning and release of cellular contents. However, this phenotype is independent of the gasdermin family proteins or mixed lineage kinase domain-like (MLKL). Transcriptomic analysis identifies that nSREBP2 induces expression of p73, which further activates caspases. Through whole-genome CRISPR-Cas9 screening, we find that Pannexin-1 (PANX1) acts downstream of caspases to promote membrane rupture. Caspase-3 or 7 cleaves PANX1 at the C-terminal tail and increases permeability. Inhibition of the pore-forming activity of PANX1 alleviates lytic cell death. PANX1 can mediate gasdermins and MLKL-independent cell lysis during TNF-induced or chemotherapeutic reagents (doxorubicin or cisplatin)-induced cell death. Together, this study uncovers a noncanonical function of SREBPs as a potentiator of programmed cell death and suggests that PANX1 can directly promote lytic cell death independent of gasdermins and MLKL.

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3.

Statins are known to be anti-inflammatory, but the mechanism remains poorly understood. Here, we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the adenosine triphosphate (ATP) synthase in the inner mitochondrial membrane and changes the proton gradient in the mitochondria. This activates nuclear factor kappa-B (NF-κB) and Jmjd3 expression, which removes the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus lipopolysaccharide (M1), macrophages, either treated with statins in vitro or isolated from statin-fed mice, express lower levels proinflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL-4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Bionic Spider Web Flexible Strain Sensor Based on CF-L and Machine Learning.

At present, the preparation of laser-induced graphene (LIG) has become an important technology in sensor manufacturing. In the conventional preparation process, the CO2 laser is widely used; however, its experimental period is long and its efficiency needs to be improved. We propose an innovative strategy to improve the experimental efficiency. We use the machine learning method to accurately predict the preparation parameters of LIG, so as to optimize the experimental process. Different structures can lead to different sensor performances. The structure constructed by the CO2 laser is rough and has a large size, which can affect the performance of the sensor. Therefore, we propose for the first time an innovative method for intramembrane structure construction that combines the advantages of the CO2 laser and fiber laser (CF-L). With this CF-L method, we have successfully prepared a biomimetic, flexible strain sensor. This sensor not only maintains a high degree of sensitivity, but also has a more refined and optimized structure. The manufacturing process of the whole sensor is simple, economical, and durable and can be prepared in large quantities and can be used to detect the extension and bending of human joints.

Fatty acid-binding proteins 3, 7, and 8 bind cholesterol and facilitate its egress from lysosomes.

Cholesterol from low-density lipoprotein (LDL) can be transported to many organelle membranes by non-vesicular mechanisms involving sterol transfer proteins (STPs). Fatty acid-binding protein (FABP) 7 was identified in our previous study searching for new regulators of intracellular cholesterol trafficking. Whether FABP7 is a bona fide STP remains unknown. Here, we found that FABP7 deficiency resulted in the accumulation of LDL-derived cholesterol in lysosomes and reduced cholesterol levels on the plasma membrane. A crystal structure of human FABP7 protein in complex with cholesterol was resolved at 2.7 Å resolution. In vitro, FABP7 efficiently transported the cholesterol analog dehydroergosterol between the liposomes. Further, the silencing of FABP3 and 8, which belong to the same family as FABP7, caused robust cholesterol accumulation in lysosomes. These two FABP proteins could transport dehydroergosterol in vitro as well. Collectively, our results suggest that FABP3, 7, and 8 are a new class of STPs mediating cholesterol egress from lysosomes.

Genetic basis and selection of glyceollin elicitation in wild soybean.

Glyceollins, a family of phytoalexins elicited in legume species, play crucial roles in environmental stress response (e.g., defending against pathogens) and human health. However, little is known about the genetic basis of glyceollin elicitation. In the present study, we employed a metabolite-based genome-wide association (mGWA) approach to identify candidate genes involved in glyceollin elicitation in genetically diverse and understudied wild soybeans subjected to soybean cyst nematode. In total, eight SNPs on chromosomes 3, 9, 13, 15, and 20 showed significant associations with glyceollin elicitation. Six genes fell into two gene clusters that encode glycosyltransferases in the phenylpropanoid pathway and were physically close to one of the significant SNPs (ss715603454) on chromosome 9. Additionally, transcription factors (TFs) genes such as MYB and WRKY were also found as promising candidate genes within close linkage to significant SNPs on chromosome 9. Notably, four significant SNPs on chromosome 9 show epistasis and a strong signal for selection. The findings describe the genetic foundation of glyceollin biosynthesis in wild soybeans; the identified genes are predicted to play a significant role in glyceollin elicitation regulation in wild soybeans. Additionally, how the epistatic interactions and selection influence glyceollin variation in natural populations deserves further investigation to elucidate the molecular mechanism of glyceollin biosynthesis.

A sterol analog inhibits hedgehog pathway by blocking cholesterylation of smoothened.

The hedgehog (Hh) signaling pathway has long been a hotspot for anti-cancer drug development due to its important role in cell proliferation and tumorigenesis. However, most clinically available Hh pathway inhibitors target the seven-transmembrane region (7TM) of smoothened (SMO), and the acquired drug resistance is an urgent problem in SMO inhibitory therapy. Here, we identify a sterol analog Q29 and show that it can inhibit the Hh pathway through binding to the cysteine-rich domain (CRD) of SMO and blocking its cholesterylation. Q29 suppresses Hh signaling-dependent cell proliferation and arrests Hh-dependent medulloblastoma growth. Q29 exhibits an additive inhibitory effect on medulloblastoma with vismodegib, a clinically used SMO-7TM inhibitor for treating basal cell carcinoma (BCC). Importantly, Q29 overcomes resistance caused by SMO mutants against SMO-7TM inhibitors and inhibits the activity of SMO oncogenic variants. Our work demonstrates that the SMO-CRD inhibitor can be a new way to treat Hh pathway-driven cancers.

Comparison of pediatric pelvic fractures and associated injuries caused by different types of road traffic accidents.

PURPOSE: To explore the clinical characteristics of pediatric pelvic fracturs caused by traffic accidents and to analyze the accompanying injuries and complications. METHODS: A total of 222 cases involved traffic accidents was enrolled in this case-control study. The data of children with pelvic fractures caused by traffic accidents who were admitted to our hospital from January 2006 to December 2021 were analyzed retrospectively. Sex, age, Tile classification, abbreviated injury scale score, injury severity score, mortality, and accompanying injuries were studied. The ANOVA was used for measurement data, and the non-parametric rank sum test was used for non-normally distributed data. The Fisher's exact probability method was used for the count data. RESULTS: Of all enrolled cases, 140 are boys and 82 are girls, including 144 aged < 6 years, 65 aged between 6 and 12 years, and 13 aged > 12 years. Depending on the injury mechanism, there are 15 cases involving pedestrians vs. motorcycles (PVM), 91 cases involving pedestrians vs. passenger cars (PVC), 78 cases involving pedestrians vs. commercial vehicles (PVV), and 38 cases involving motor vehicles vs. motor vehicles (MVM). Associated injuries are reported in 198 cases (89.2%), primarily involving the abdomen injury in 144 cases (64.9%), and lower limb injury in 99 cases (44.6%). PVV injury involves longer hospital stay (p = 0.004). Intensive care unit admission rate is significantly higher in the MVM group than in other groups (p = 0.004). Head injury (p = 0.001) and face injury (p = 0.037) are more common in the MVM group, whereas abdominal injury (p = 0.048) and lower limb injury (p = 0.037) are more common in the PVV group. In the MVM group, the brain injury (p = 0.004) and femoral neck injury (p = 0.044) are more common. In the PVM group, the mediastinum (p = 0.004), ear (p = 0.009), lumbar vertebrae (p = 0.008), and spinal cord (p = 0.011) are the most vulnerable regions, while in the PVV group, the perineum (p < 0.001), urethra (p = 0.001), rectum (p = 0.006), anus (p = 0.004), and lower limb soft tissues (p = 0.024) are the most vulnerable regions. Children aged > 12 years have higher pelvic abbreviated injury scale scores (p = 0.019). There are significant differences in the classification of pelvic fractures among children < 6, 6 - 12, and > 12 years of age, with Tile C being more likely to occur in children > 12 years of age (p = 0.033). Children aged > 12 years are more likely to sustain injuries to the spleen (p = 0.022), kidneys (p = 0.019), pancreas (p < 0.001), lumbar vertebrae (p = 0.013), and sacrum (p = 0.024). The MVM group has the highest complication rate (p = 0.003). CONCLUSION: PVC is the leading cause of the abdomen and lower extremities injury and has the most concomitant injuries. Different traffic injuries often lead to different associated injuries. Older children are more likely to sustain more severe pelvic fractures and peripelvic organs injuries. The MVM group has the highest extent of injury and complication rates.

Machine learning prediction models for in-hospital postoperative functional outcome after moderate-to-severe traumatic brain injury.

AIM: This study aims to utilize machine learning (ML) and logistic regression (LR) models to predict surgical outcomes among patients with traumatic brain injury (TBI) based on admission examination, assisting in making optimal surgical treatment decision for these patients. METHOD: We conducted a retrospective review of patients hospitalized in our department for moderate-to-severe TBI. Patients admitted between October 2011 and October 2022 were assigned to the training set, while patients admitted between November 2022 and May 2023 were designated as the external validation set. Five ML algorithms and LR model were employed to predict the postoperative Glasgow Outcome Scale (GOS) status at discharge using clinical and routine blood data collected upon admission. The Shapley (SHAP) plot was utilized for interpreting the models. RESULTS: A total of 416 patients were included in this study, and they were divided into the training set (n = 396) and the external validation set (n = 47). The ML models, using both clinical and routine blood data, were able to predict postoperative GOS outcomes with area under the curve (AUC) values ranging from 0.860 to 0.900 during the internal cross-validation and from 0.801 to 0.890 during the external validation. In contrast, the LR model had the lowest AUC values during the internal and external validation (0.844 and 0.567, respectively). When blood data was not available, the ML models achieved AUCs of 0.849 to 0.870 during the internal cross-validation and 0.714 to 0.861 during the external validation. Similarly, the LR model had the lowest AUC values (0.821 and 0.638, respectively). Through repeated cross-validation analysis, we found that routine blood data had a significant association with higher mean AUC values in all ML and LR models. The SHAP plot was used to visualize the contributions of all predictors and highlighted the significance of blood data in the lightGBM model. CONCLUSION: The study concluded that ML models could provide rapid and accurate predictions for postoperative GOS outcomes at discharge following moderate-to-severe TBI. The study also highlighted the crucial role of routine blood tests in improving such predictions, and may contribute to the optimization of surgical treatment decision-making for patients with TBI.

Adhesion Coefficient Identification of Wheeled Mobile Robot under Unstructured Pavement.

Because of its uneven and large slope, unstructured pavement presents a great challenge to obtaining the adhesion coefficient of pavement. An estimation method of the peak adhesion coefficient of unstructured pavement on the basis of the extended Kalman filter is proposed in this paper. The identification accuracy of road adhesion coefficients under unstructured pavement is improved by introducing the equivalent suspension model to optimize the calculation of vertical wheel load and modifying vehicle acceleration combined with vehicle posture data. Finally, the multi-condition simulation experiments with Carsim are conducted, the estimation accuracy of the adhesion coefficient is at least improved by 3.6%, and then the precision and effectiveness of the designed algorithm in the article are verified.

Shaping immune landscape of colorectal cancer by cholesterol metabolites.

Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer-immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Clinical Application of Long-Pulsed 800-Nm Diode Laser Depilation Technology on Microtia Reconstruction in 965 Patients.

BACKGROUND: The issue of hair growth on reconstructed ears has been a matter of concern for both patients and surgeons, despite the notable progress made in microtia reconstruction technology in recent times. OBJECTIVE: This study aims to present the practical implementation of long-pulsed 800-nm diode laser depilation technology in the field of auricular reconstruction. Furthermore, it seeks to establish a comprehensive and standardized protocol for utilizing lasers in the reconstruction of microtia ears. METHODS: A total of 965 patients (comprising 1021 ears) diagnosed with congenital microtia underwent treatment using 800-nm long-pulsed diode laser depilation. The participants received 1-3 treatment sessions with intervals of 25-30 days. To assess the effectiveness of the treatment, two independent observers compared photographs and measured the reduction in terminal hair count before and after the final session. Clinical outcomes were evaluated using VAS questionnaires, and any adverse events were diligently recorded. RESULTS: The findings indicated that the utilization of the long-pulsed 800-nm diode laser was both safe and efficient in achieving hair removal during microtia ear reconstruction. As additional sessions were conducted, pain scores demonstrated a decline, while adverse reactions remained minimal. LIMITATIONS: This is a retrospective single-institution study. CONCLUSION: The application of a long-pulsed 800-nm diode laser has been proved to be a safe and effective method for removing hair during the process of microtia ear reconstruction, involving the use of a tissue expander and autologous costal cartilage. To achieve satisfactory results in hair removal, it was found necessary to repeat the shots procedure two to three times. 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 .

Nematocidal Potential of Phenolic Acids: A Phytochemical Seed-Coating Approach to Soybean Cyst Nematode Management.

Soybeans, one of the most valuable crops worldwide, are annually decimated by the soybean cyst nematode (SCN), Heterodera glycines, resulting in massive losses in soybean yields and economic revenue. Conventional agricultural pesticides are generally effective in the short term; however, they pose growing threats to human and environmental health; therefore, alternative SCN management strategies are urgently needed. Preliminary findings show that phenolic acids are significantly induced during SCN infection and exhibit effective nematocidal activities in vitro. However, it is unclear whether these effects occur in planta or elicit any negative effects on plant growth traits. Here, we employed a phytochemical-based seed coating application on soybean seeds using phenolic acid derivatives (4HBD; 2,3DHBA) at variable concentrations and examined SCN inhibition against two SCN types. Moreover, we also examined plant growth traits under non-infected or SCN infected conditions. Notably, 2,3DHBA significantly inhibited SCN abundance in Race 2-infected plants with increasingly higher chemical doses. Interestingly, neither compound negatively affected soybean growth traits in control or SCN-infected plants. Our findings suggest that a phytochemical-based approach could offer an effective, more environmentally friendly solution to facilitate current SCN management strategies and fast-track the development of biopesticides to sustainably manage devastating pests such as SCN.

Machine learning models for predicting in-hospital outcomes after non-surgical treatment among patients with moderate-to-severe traumatic brain injury.

AIM: This study aims to develop prediction models for in-hospital outcomes after non-surgical treatment among patients with moderate-to-severe traumatic brain injury (TBI). METHOD: We conducted a retrospective review of patients hospitalized for moderate-to-severe TBI in our department from 2011 to 2020. Five machine learning (ML) algorithms and the conventional logistic regression (LR) model were employed to predict in-hospital mortality and the Glasgow Outcome Scale (GOS) functional outcomes. These models utilized clinical and routine blood data collected upon admission. RESULTS: This study included a total of 196 patients who received only non-surgical treatment after moderate-to-severe TBI. When predicting mortality, ML models achieved area under the curve (AUC) values of 0.921 to 0.994 using clinical and routine blood data, and 0.877 to 0.982 using only clinical data. In comparison, LR models yielded AUCs of 0.762 and 0.730 respectively. When predicting the GOS outcome, ML models achieved AUCs of 0.870 to 0.915 using clinical and routine blood data, and 0.858 to 0.927 using only clinical data. In comparison, the LR model yielded AUCs of 0.798 and 0.787 respectively. Repeated internal validation showed that the contributions of routine blood data for prediction models may depend on different prediction algorithms and different outcome measurements. CONCLUSION: The study reported ML-based prediction models that provided rapid and accurate predictions on short-term outcomes after non-surgical treatment among patients with moderate-to-severe TBI. The study also highlighted the superiority of ML models over conventional LR models and proposed the complex contributions of routine blood data in such predictions.

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating JMJD3.

Stains are known to be anti-inflammatory, but the mechanism remains poorly understood. Here we show that macrophages, either treated with statin in vitro or from statin-treated mice, have reduced cholesterol levels and higher expression of Jmjd3, a H3K27me3 demethylase. We provide evidence that lowering cholesterol levels in macrophages suppresses the ATP synthase in the inner mitochondrial membrane (IMM) and changes the proton gradient in the mitochondria. This activates NFkB and Jmjd3 expression to remove the repressive marker H3K27me3. Accordingly, the epigenome is altered by the cholesterol reduction. When subsequently challenged by the inflammatory stimulus LPS (M1), both macrophages treated with statins in vitro or isolated from statin-treated mice in vivo, express lower levels pro-inflammatory cytokines than controls, while augmenting anti-inflammatory Il10 expression. On the other hand, when macrophages are alternatively activated by IL4 (M2), statins promote the expression of Arg1, Ym1, and Mrc1. The enhanced expression is correlated with the statin-induced removal of H3K27me3 from these genes prior to activation. In addition, Jmjd3 and its demethylase activity are necessary for cholesterol to modulate both M1 and M2 activation. We conclude that upregulation of Jmjd3 is a key event for the anti-inflammatory function of statins on macrophages.

Tape Eyelid Closure: An Effective Solution for Nocturnal Lagophthalmos in Patients with Ptosis and Poor Bell's Phenomenon.

BACKGROUND: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. METHODS: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. RESULTS: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. CONCLUSION: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. 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 Table of Contents or the online Instructions to Authors www.springer.com/00266 .