Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China.

After the termination of zero-COVID-19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type-vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly.

The Effect of Topical Vancomycin Powder Application on the Rate of Intervertebral Fusion Following Lumbar Fusion: A Retrospective Study.

PURPOSE: The occurrence of surgical site infection (SSI) after lumbar spinal fusion is a serious complication. Therefore, an increasing number of clinicians are applying vancomycin powder topically in the surgical field to reduce the incidence of SSI. However, there is concern that topical vancomycin powder application may affect intervertebral fusion. The purpose of this study was to analyse the effect of clinically relevant topical vancomycin doses on the rate of intervertebral fusion after lumbar fusion and to further investigate the effect of vancomycin powder on the prevention of SSI. METHODS: The clinical data of 192 patients with degenerative lumbar spine disease admitted from January 2019 to June 2022, all of whom underwent posterior lumbar fusion, were retrospectively analysed. According to the infection prevention protocol, they were divided into a vancomycin group and a control group (no vancomycin), and the vancomycin group was sub-divided into 0.5 g, 1.0 g, and 1.5 g vancomycin groups. General information and surgical evaluation indexes were compared between the control and vancomycin groups and intervertebral fusion was compared between the vancomycin groups at 6 months and 12 months, postoperatively. RESULTS: The rate of SSI in the vancomycin group was 0.0%, which was significantly lower than that in the control group (5.3%, P < 0.05), and intervertebral fusion was good in all 3 vancomycin groups at 6 months and 12 months postoperatively, with no statistically-significant differences (P > 0.05). CONCLUSIONS: Topical application of 0.5 g, 1.0 g, or 1.5 g vancomycin powder did not affect the rates of intervertebral fusion after lumbar fusion. In addition, topical application of vancomycin powder significantly reduced the rates of SSI.

Fine-tuning of thermally induced SCO behaviors of trinuclear cyanido-bridged complexes by regulating the electron donating ability of CCN-terminal fragments.

To achieve fine regulation of FeII SCO behavior, a series of trinuclear cyanido-bridged complexes trans-[CpMen(dppe)MII(CN)]2[Fe1II(abpt)2](OTf)2 (1-4) (1, M = Fe2 and n = 1; 2, M = Fe2 and n = 4; 3, M = Fe2 and n = 5; 4, M = Ru and n = 5; CpMen = alkyl cyclopentadienyl with n = 1, 4, 5; dppe = 1,2-bis-(diphenylphosphino)ethane; abpt = 4-amino-3,5-bis-(pyridin-2-yl)-1,2,4-triazole and OTf = CF3SO3-) were synthesized and fully characterized by using elemental analysis, X-ray crystallography, magnetic measurements, variable-temperature IR spectroscopy and Mössbauer spectroscopy. It is worth mentioning that different from many mononuclear Fe(abpt)2X2 (X = NCS, NCSe, N(CN)2, C(CN)3, (NC)2CC(OCH3)C(CN)2, (NC)2CC(OC2H5)C(CN)2, C16SO3 and Cl) complexes with more than one polymorph, only one polycrystalline form was found in complexes 1-4. Moreover, the thermally induced SCO behaviors of these four complexes are independent of intermolecular π-π interactions. The electron-donating ability of the CCN-terminal fragment of CpMen(dppe)MIICN can be flexibly regulated by changing the methyl number (n) of the cyclopentadiene ligand or metal ion type (MII). These investigations indicate that the electron-donating ability of the CCN-terminal fragment has an influence on the SCO behavior of Fe1II. The spin transition temperature (T1/2) of the complexes decreases with the increase of the electron-donating ability of the fragment CpMen(dppe)MII. This study provides a new strategy to predict and precisely regulate the behaviors of SCO complexes.

Efficient capture of iodine in steam and water media by hydrogen bond-driven charge transfer complexes.

Untreated radioactive iodine (129I and 131I) released from nuclear power plants poses a significant threat to humans and the environment, so the development of materials to capture iodine from water media and steam is critical. Here, we report a charge transfer complex (TCNQ-MA CTC) with abundant nitrogen atoms and π-conjugated system for adsorption of I2 vapor and I3- from aqueous solutions. Due to the synergistic binding mechanism of benzene/triazine rings and N-containing groups with iodine, special I-π and charge transfer interaction can be formed between the guest and the host, and thus efficient removal of I2 and I3- can be realized by TCNQ-MA CTC with the adsorption capacity up to 2.42 g/g and 800 mg/g, respectively. TCNQ-MA CTC can capture 92% of I3- within 2.5 min, showing extremely fast kinetics, excellent selectivity and high affinity (Kd = 5.68 × 106 mL/g). Finally, the TCNQ-MA CTC was successfully applied in the removal of iodine from seawater with the efficiency of 93.71%. This work provides new insights in the construction of charge transfer complexes and lays the foundation for its environmental applications.

Different delocalized ranges in mixed valence cyanido-metal-bridged Fe-Ru-Fe complexes controlled by terminal ligand substitution modification.

In order to investigate the properties of metal to metal charge transfer (MMCT) influenced by the relative energy level between the bridging unit and the terminal unit, two groups of heterotrimetallic cyanido-metal-bridged complexes, trans-[Cp(dppe)Fe-CN-Ru(MeOpy)4-NC-Fe(dppe)Cp][X]n (1[X]n; n = 2, 3, or 4; X = PF6 or BF4) (Cp = cyclopentadiene, dppe = 1,2-bis(diphenylphosphino)ethane, MeOpy = 4-methoxypyridine) and [Cp*(dppe)Fe-CN-Ru(MeOpy)4-NC-Fe(dppe)Cp*] [X]n (2[X]n; Cp* = 1,2,3,4,5-pentamethylcyclopentadiene; n = 2, 3, or 4; X = PF6 or BF4) were synthesized and fully characterized. The crystallography data suggest different oxidation sites in the ground state for one-electron oxidation products 13+ and 23+, and the electrochemical and Mössbauer spectra suggest that in the one-electron oxidation compounds 13+, the charge is delocalized all along the trimetal backbone Fe-Ru-Fe, while in 23+, the charge is rather delocalized between the two metal parts Fe-Ru. Further oxidation of N3+ gives N4+ (N = 1 or 2), during which a spin transfer towards the terminal units is observed in both series.

A Review of Gap Junction Protein and its Potential Role in Nervous System-Related Disease.

Gap junction (GJ) is a special cell membrane structure composed of connexin. Connexin is widely distributed and expressed in all tissues except differentiated skeletal muscle, red blood cells, and mature sperm cells, which is related to the occurrence of many genetic diseases due to its mutation. Its function of regulating immune response, cell proliferation, migration, apoptosis, and carcinogenesis makes it a therapeutic target for a variety of diseases. In this paper, the possible mechanism of its action in nervous system-related diseases and treatment are reviewed.

Metal-Metal Charge Transfer Properties of a Series of Trinuclear Fe2 Ru and Corresponding Pentanuclear Fe2 Ru2 Ag Cyanido-Bridged Complexes.

A series of trimetallic cyanidometal-bridged compounds [Men Cp(dppe)FeII -(µ-NC)-RuII (MeOpy)4 -(µ-CN)-FeII (dppe)CpMen ] - [PF6 ]2 (N[PF6 ]2 , n=0, N =1; n=1, N=2; n=3, N=3; Cp=cyclopentadiene, dppe=1,2-bis(diphenylphosphino)ethane, MeOpy=4-methoxypyridine) and their one- and two-electron oxidized compounds N3+ and N4+ were synthesized and characterized. Meanwhile, a series of corresponding linear cyanido-bridged pentanuclear compounds [Men Cp(dppe)FeIII -(µ-NC)-RuII (MeOpy)4 -(µ-NC)-AgI -(µ-CN)-RuII (MeOpy)4 -(µ-CN)-FeIII (dppe)CpMen ][BF4 ]5 (M[BF4 ]5 , n=0, M=4; n=1, M=5; n=3, M=6) were also obtained and well characterized. The investigations suggest that in the trinuclear system there exists remote interaction between the two Fe centers, but no significant interactions exist across the central silver unit between the metals on the two sides of the silver center in the pentanuclear system. In both the trinuclear N4+ and the pentanuclear M5+ complexes, there exists the neighboring RuII →FeIII MM'CT transitions, and the MM'CT energy in the corresponding trinuclear system is higher than those in the pentanuclear system in which no remote metal-metal interaction occurs. Meanwhile, as the substituted methyl groups on the cyclopentadiene increases, the redox potential of the ruthenium in the trinuclear N4+ series increases, but that in the pentanuclear M5+ complexes decreases.

Rhodobacter sphaeroides as a model to study the ecotoxicity of 1-alkyl-3-methylimidazolium bromide.

The purple non-sulfur bacterium Rhodobacter sphaeroides was selected as a biological model to investigate its response to the toxicity of 1-alkyl-3-methylimidazolium bromide ([Cnmim]Br), a type of ionic liquid (IL), with different alkyl chain lengths (n describes the number of carbon atoms in the alkyl chain). The inhibition of bacterial growth by [Cnmim]Br was positively correlated with n. Morphological characterization revealed that [Cnmim]Br caused cell membrane perforation. The signal amplitude of the electrochromic absorption band shift of endogenous carotenoids showed a negatively linear correlation with n, and the amplitude of the blue-shift of the B850 band in light-harvesting complex 2 showed a positively linear correlation with n. Furthermore, an increase in blocked ATP synthesis and increase in antioxidant enzyme activity were observed in chromatophores treated with ILs containing longer alkyl chains. In summary, the purple bacterium can be developed as a model to monitor ecotoxicity and examine the mechanism of IL toxicity.

Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients.

AIMS: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. METHODS: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. RESULTS: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33-50.00% higher than that in CYP3A5*1 expressers. CONCLUSIONS: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury.

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix (ECM) deposition around the injury site. Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation. In this study, we used a decellularized nerve matrix scaffold (DNM-S) to prevent against the formation of painful neuroma after sciatic nerve transection in rats. Our results showed that the DNM-S effectively reduced abnormal deposition of ECM, guided the regeneration and orderly arrangement of axon, and decreased the density of regenerated axons. The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue, greatly reduced the invasion of α-smooth muscle actin-positive myofibroblasts into nerve stumps, effectively inhibited scar formation, which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals. These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

A machine learning-based diagnostic model for children with autism spectrum disorders complicated with intellectual disability.

Background: Early detection of children with autism spectrum disorder (ASD) and comorbid intellectual disability (ID) can help in individualized intervention. Appropriate assessment and diagnostic tools are lacking in primary care. This study aims to explore the applicability of machine learning (ML) methods in diagnosing ASD comorbid ID compared with traditional regression models. Method: From January 2017 to December 2021, 241 children with ASD, with an average age of 6.41 ± 1.96, diagnosed in the Developmental Behavior Department of the Children's Hospital Affiliated with the Medical College of Zhejiang University were included in the analysis. This study trained the traditional diagnostic models of Logistic regression (LR), Support Vector Machine (SVM), and two ensemble learning algorithms [Random Forest (RF) and XGBoost]. Socio-demographic and behavioral observation data were used to distinguish whether autistic children had combined ID. The hyperparameters adjustment uses grid search and 10-fold validation. The Boruta method is used to select variables. The model's performance was evaluated using discrimination, calibration, and decision curve analysis (DCA). Result: Among 241 autistic children, 98 (40.66%) were ASD comorbid ID. The four diagnostic models can better distinguish whether autistic children are complicated with ID, and the accuracy of SVM is the highest (0.836); SVM and XGBoost have better accuracy (0.800, 0.838); LR has the best sensitivity (0.939), followed by SVM (0.952). Regarding specificity, SVM, RF, and XGBoost performed significantly higher than LR (0.355). The AUC of ML (SVM, 0.835 [95% CI: 0.747-0.944]; RF, 0.829 [95% CI: 0.738-0.920]; XGBoost, 0.845 [95% CI: 0.734-0.937]) is not different from traditional LR (0.858 [95% CI: 0.770-0.944]). Only SVM observed a good calibration degree. Regarding DCA, LR, and SVM have higher benefits in a wider threshold range. Conclusion: Compared to the traditional regression model, ML model based on socio-demographic and behavioral observation data, especially SVM, has a better ability to distinguish whether autistic children are combined with ID.

Influence of the CN Orientation on the Degree of Electron Delocalization of Ru-Ru-Ru Mixed-Valent Complexes.

Investigations on mixed-valent complexes in the Class II/Class III frontier have been a particularly interesting issue due to their special electron delocalization. In this work, a pair of cyanidometal-/isocyanidometal-bridged Ru-Ru-Ru compounds, cis-[Cp(dppe)Ru-B-Ru(dppe)Cp]2+ (B = NCRu(bpy)2CN, 12+; B = CNRu(bpy)2NC, 22+; Cp = 1,3-cyclopentadienyl, dppe = 1,2-bis(diphenlyphosphine)ethane, bpy = 2,2'-bipyridine), and one-electron oxidized 13+ and 23+ were synthesized and well characterized. For the two-electron oxidized 14+ and 24+, their Fourier transform infrared (FTIR) and UV-vis-NIR spectra were investigated by employing spectroelectrochemical methods. The time-dependent density-functional theory (TDDFT) calculations and the experimental results indicate that the one-/two-electron oxidized mixed-valent compounds belong to Class II-III systems.

Thermally induced charge transfer in a quinoid-bridged linear Cu3 compound.

Charge transfer always occurs in molecular valence tautomers, leading to the redistribution of electron density and exhibiting electrical, optical, and magnetic properties, and can be further controlled by multiple external stimuli such as temperature, light and electric field. The design of molecule-based materials capable of charge transfer remains a challenge. Herein, a linear Cu3 compound [(CH3)3NCH2CH2Br]2[Cu3L4(H2O)2] (H2L = chloranilic acid) (1) with a multi-center donor-acceptor architecture was constructed using the redox-active chloranilic acid quinoid ligand. Temperature-dependent dielectric measurement was performed to capture the charge transfer valence tautomer transition because it is difficult to detect this transition by crystal structure and magnetism analysis. Temperature-dependent XPS and EPR further confirmed that the charge transfer valence tautomer transition is based on the CuII-L2- to CuI-L-˙ multi-center charge transfer. Thus, the present work builds a charge transfer compound with a multi-center donor-acceptor architecture and proves that dielectric measurement is a very effective means to detect charge transfer.

Mechanical stretch aggravates vascular smooth muscle cell apoptosis and vascular remodeling by downregulating EZH2.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2) was recently found to play an important role in cardiovascular disease. However, the role of EZH2 in vascular remodeling induced by mechanical stretch is poorly understood. The aim of the present work was to investigate the role of EZH2 in regulating smooth muscle cell function through mechanical stretch assays and to explore the underlying mechanisms. METHODS: WT C57BL/6 J mice underwent sham surgery or abdominal aortic constriction. The level of EZH2 expression was determined by Western blotting and immunohistochemical staining. We demonstrated the thickness of vascular remodeling by HE staining. JASPAR was used to predict transcription factors that could affect EZH2. Chromatin immunoprecipitation was used to substantiate the DNAprotein interactions. Promoter luciferase assays were performed to demonstrate the activity of the transcription factors. RESULTS: We found that in vivo, AAC significantly reduced EZH2 protein levels in the thoracic aorta. Smooth muscle-specific overexpression of EZH2 was sufficient to attenuate the AAC-induced reduction in trimethylation of Lys-27 in histone 3 and thickening of the arterial media. Administration of GSK-J4 (an inhibitor of H3K27me3 demethylase) induced the same effects. In addition, we found that mechanical stretch regulated the expression of EZH2 through the Yes-associated protein (YAP)- transcriptional factor TEA domain 1 (TEAD) pathway. TEAD1 bound directly to the promoter of EZH2, and blocking the YAP-TEAD1 interaction inhibited EZH2 downregulation due to mechanical stretch. CONCLUSION: This study reveals that mechanical stretch downregulates EZH2 through the YAP-TEAD1 pathway, thereby aggravating smooth muscle cell apoptosis and vascular remodeling.

Population Pharmacokinetics and Initial Dosage Optimization of Tacrolimus in Pediatric Hematopoietic Stem Cell Transplant Patients.

Background: There is a substantial lack of tacrolimus pharmacokinetic information in pediatric hematopoietic stem cell transplant (HSCT) patients. This study aimed to develop population pharmacokinetics (PopPK) of tacrolimus in pediatric HSCT patients and to devise model-guided dosage regimens. Methods: A retrospective analysis was performed on 86 pediatric HSCT patients who received tacrolimus intravenously or orally. A total of 578 tacrolimus trough concentrations (C0) were available for pharmacokinetic analysis using a non-linear mixed-effects modeling method. Demographic and clinical data were included and assessed as covariates via the stepwise method. Bayesian estimators were used to devise pediatric dosage regimens that targeted C0 of 5-15 ng mL-1. Results: A one-compartment model with first-order absorption adequately described the tacrolimus pharmacokinetics. Clearance (CL), volume of distribution (V), and typical bioavailability (F) in this study were estimated to be 2.42 L h-1 (10.84%), 79.6 L (16.51%), and 19% (13.01%), respectively. Body weight, hematocrit, post-transplantation days, and caspofungin and azoles concomitant therapy were considered significant covariates for tacrolimus CL. Hematocrit had a significant impact on the V of tacrolimus. In the subgroup cohort of children (n = 24) with CYP3A5 genotype, the clearance was 1.38-fold higher in CYP3A5 expressers than in non-expressers. Simulation indicated that the initial dosage optimation of tacrolimus for intravenous and oral administration was recommended as 0.025 and 0.1 mg kg-1 d-1 (q12h), respectively. Conclusion: A PopPK model for tacrolimus in pediatric HSCT patients was developed, showing good predictive performance. Model-devised dosage regimens with trough tacrolimus concentrations provide a practical strategy for achieving the therapeutic range.

Dickkopf1 (Dkk1) Alleviates Vascular Calcification by Regulating the Degradation of Phospholipase D1 (PLD1).

Vascular calcification (VC) is a significant risk factor for cardiovascular mortality and morbidity in patients with atherosclerosis (AS), chronic kidney disease, and diabetes. Dickkopf1 (Dkk1) is a multifunctional secreted glycoprotein that has been explored as a novel potential antitumor target. Recently, Dkk1 was shown to be closely associated with AS development. However, the role of Dkk1 in VC remains elusive. In this study, we explored the role and molecular mechanisms of Dkk1 in VC based on a smooth muscle-specific Dkk1-knockout (Dkk1SMKO) mouse model. Our data indicated that Dkk1 expression was decreased under calcifying conditions and that Dkk1 overexpression alleviated high phosphate-induced vascular calcification. In vivo, smooth muscle Dkk1-specific knockout aggravated vascular calcification in mice. However, phospholipase D1 (PLD1) overexpression partially weakened the protective effect of Dkk1 against vascular calcification. Mechanistically, Dkk1 slowed vascular calcification by promoting the degradation of PLD1 via the regulating autophagosome formation and maturation. In conclusion, we found that Dkk1 could alleviate vascular calcification by regulating the degradation of PLD1.

TCM-Based Therapy as a Rescue Therapy for Re-Eradication of Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

The increase in drug-resistant strains poses a severe challenge for Helicobacter pylori (Hp) treatment, and the failure of traditional triple or bismuth quadruple therapy makes it difficult to eradicate Hp. Tailored therapies should be expanded, and traditional Chinese medicine (TCM) may provide the potential regimen. The aim of the present study is to systematically compare TCM-based therapy (TCM combined with Western medicine) and Western medicine as a rescue therapy for Hp re-eradication. Studies through June 12, 2021, with keywords "Helicobacter pylori," "medicine, Chinese traditional," or "rescue treatment" and their related expressions were retrieved from PubMed, SinoMed, China National Knowledge Infrastructure, and Wanfang databases. Randomized clinical trials based on PICOS (population, intervention, comparators, outcomes, and study design) eligibility criteria that evaluated the efficacy and safety of integrated therapy on Hp re-eradication were included. The extracted contents included the demographic data of the participants, specific treatment measures, and the results of outcome indicators and safety indicators. Review Manager 5.3 software was used to perform this meta-analysis. Outcome measures including the HP re-eradication rate, symptom remission rate, and adverse effects were seriously analyzed. Under the guide of PRISMA, 18 studies were finally included. Pooled results showed significant differences in eradication rate between integrated and Western medicine therapy in intention-to-treat (ITT) analysis (OR = 2.21, 95% CI: (1.74, 2.81), P < 0.01). Symptom remission is higher in the administration of integrated therapy than in the administration of Western medicine therapy (OR = 2.45, 95% CI: (1.78, 3.37), P < 0.01). It is also indicated that integrated therapy showed significantly less adverse effects (OR = 0.60, 95% CI: (0.42, 0.84), P < 0.01. In conclusion, compared with Western medicine therapy, integrated therapy yields a higher eradication rate and acceptable safety profiles.

How Deviation of Nasal Septum Affects Nasal Appearance in Unilateral Cleft Patients: A Study Using Cone-Beam Computed Tomography.

AIM: To quantitatively evaluate the relationship between nasal appearance and nasal septum deviation in unilateral complete cleft patients using cone-beam computed tomography.Method: Cone-beam computed tomography images of 180 patients with unilateral cleft lip/palate from June 2014 to June 2017 were used in the study. None of the subjects had undergone septoplasty. The data were compared between the 2 groups to elucidate the relationship between nasal appearance and deviated nasal septum in unilateral complete cleft patients. RESULTS: The mean age of a total of 180 patients (126 males and 54 females) was 14.58 years, with a standard deviation of 7.10 years, ranged from 6 years old to 49 years old. Columella nasi symmetry parameters show slight positive significant association with angle of nasal septal deviation on transerve plan (r = 0.250, P < 0.001), TRSD (r = 0.323, P < 0.001) and coronal range of nasal septal deviation (r = 0.294, P < 0.001), and moderate positive significant association with coronal angle about septal deviation (r = 0.404, P < 0.001). CONCLUSIONS: Columella nasi symmetry affected by septal deviation, whereas there is lack of evidence to say symmetry of nasal tip and base affected by septal deviation. The symmetry of nasal tip and alar base are not just determined by nasal septum deviation. The nasal septum deviation show difference in different cleft type.

Escherichia fergusonii Promotes Nonobese Nonalcoholic Fatty Liver Disease by Interfering With Host Hepatic Lipid Metabolism Through Its Own msRNA 23487.

BACKGROUND & AIMS: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. METHODS: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii-derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. RESULTS: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid ß-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii-derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. CONCLUSIONS: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.