Shikonin-loaded PLGA nanoparticles: A promising strategy for psoriasis treatment.

Psoriasis is an inflammation-based skin illness marked by aggravated proliferation of epidermal cells. Shikonin is a natural naphthoquinone obtained from Arnebiae radix. It exerts anti-inflammatory and immunosuppressive effects. However, the poor water solubility and low bioavailability of shikonin limit its application. In this study, shikosin-loaded PLGA nanoparticle hydrogel was prepared and used to deliver the drug to the epidermis of psoriasis mice through local administration. The results demonstrated that shikosin-loaded PLGA nanoparticles inhibited HaCaT cell multiplication, increased drug uptake, and induced apoptosis of HaCaT cells. Results from Western blotting assays indicated that shikosin down-regulated the protein expressions of p65 and p-p65. Furthermore, shikonin mitigated psoriasis and decreased the concentrations of inflammation-inducing cytokines, i.e., IL17A, IL-17F, IL-22, IL-1ß, and TNF-α. Taken together, these results suggest that shikonin-PLGA nanoparticles loaded in hydrogel system possess promising therapeutic potential for psoriasis.

Validating the Baveno Elastography Criteria of Advanced Liver Fibrosis in Two-dimensional Shear Wave Elastography: A Prospective Pathology-based Study.

INTRODUCTION: The Baveno criteria for assessing advanced liver fibrosis were mainly determined by transient elastography (TE), and its pathology-based validation studies in two-dimensional shear-wave elastography (2D-SWE) remain limited. We aimed to validate the Baveno criteria through use of 2D-SWE. METHOD: Consecutive patients who underwent liver biopsies for various benign liver diseases were prospectively recruited. Liver stiffness measurement (LSM) was simultaneously evaluated by TE and 2D-SWE. The optimal cut-off value to predict advanced liver fibrosis was determined by the Youden Index, and the diagnostic performance was estimated using area under the receiver operating characteristic (AUROC) analysis. RESULTS: A total of 101 patients were enrolled having a median age of 55.0 (IQR: 46.0-63.5) years, with 53 (52.48%) of them being male. Using <9 and >14 kPa as the optimal dual cut-offs, the AUROC values in TE and 2D-SWE were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (P= 0.61). The sensitivity and specificity of LSM by TE/2D-SWE achieved rates of 94.44%/94.44% and 86.00%/88.00%, respectively. However, using the Baveno criteria, the AUROC values in TE and 2D-SWE could remain achieving 0.91 (95% CI: 0.82-0.97) and 0.93 (95% CI: 0.84-0.98), respectively (P= 0.36). The sensitivity and specificity in TE/2D-SWE were 88.24%/88.24% and 86.79%/90.57%, respectively. CONCLUSION: This study establishes the compatibility of the Baveno dual cut-off criteria with 2D-SWE, positioning it as an easily used criteria in clinical practice and research.

Oroxylin A inhibits inflammatory cytokines in periodontitis via HO­1.

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti­inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase­1 (HO­1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription­quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)­2, TNF­α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ­2, TNF­α, RANKL and OPG. Following HO­1 knockdown, the same treatment was performed. The expression of COX­2 in rat gingival tissue was observed by immunohistochemistry. One­way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. With increase of Oroxylin A dose, the expression of HO­1 was gradually upregulated. When HO­1 was knocked down, Oroxylin A did not downregulate the expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. Immunohistochemical results showed that expression of COX­2 was downregulated by Oroxylin A, and the expression of TNF­α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS­induced RGFs and had a good inhibitory effect on periodontitis in rats.

Eyelid retraction during smiling in a patient with monocular congenital ptosis: a case report.

BACKGROUND: Blepharoptosis is a common symptom in ophthalmology clinic, but eyelid retraction when smiling in a ptosis eye is a rare manifestation. Here we report a novel manifestation that eyelid retraction during smiling in a patient with monocular congenital ptosis. CASE DESCRIPTION: A 10-year-old girl with isolated and mild unilateral congenital ptosis showed eyelid retraction in ptotsis eye when smiling together with a lid lag on downgaze. She didn't have any systematic and ocular diseases other than myopia and astigmatism.Eyelid retraction during smiling is 5 mm, resulting in a significant difference in the height of bilateral palpebral fissures.As for ptosis, is mild.The margin to reflex distance 1 is 1.0 mm on the right eye(ptosis eye) and 3.0 mm on the left eye. A lid lag of 1.0 mm on downward gaze was noted on the right, she could close her eyes fully while sleeping.The ice pack test, laboratory test for thyroid function, whole-exome sequencing (WES) and magnetic resonance imaging(MRI) of the orbital and ocular motor nerves showed normal results.Her symptoms alleviated after 6 months, with the retraction of the right upper eyelid when smiling was approximately 3 mm, thus the difference in the palpebral fissure height when smiling was smaller than that at the initial presentation. CONCLUSION: Blepharoptosis may accompanied with abnormal innervation like eyelid retraction, this phenomenon can be alleviated with age.The results of the levator muscle function test should be carefully examined to determine whether it is ptosis in an impaired innervation eyelid.

The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Clinical Efficacy and Safety of a Modified Moxibustion Therapy for Low Back Pain in Lumbar Disc Herniation: A Two-Center, Randomized, Controlled, Non-Inferiority Trial.

Objective: Our pilot study shows that a modified moxibustion therapy called Ma's bamboo-based medicinal moxibustion can alleviate the symptoms of low back pain in lumbar disc herniation (LDH), and has the potential to treat LDH. The aim of this study is to evaluate the efficacy and safety of Ma's bamboo-based medicinal moxibustion for low back pain in LDH. Methods: A total of 312 LDH patients with low back pain were randomized to receive Ma's bamboo-based medicinal moxibustion (MBMM) or acupuncture (AT). The primary efficacy measure was the change of Visual Analogue Scale (VAS) on the 14th day compared with that at baseline. The secondary efficacy measures included VAS score, Oswestry disability index (ODI), modified Japanese Orthopaedic Association (M-JOA) score, and the content of ß-endorphin (ß-EP) and substance-P (SP). The safety measures included the occurrence of adverse events and the changes in laboratory indicators. Results: In total, 304 patients were incorporated for the analysis of efficacy, including 96 males and 208 females, aged 21-65 years. There was no statistically significant difference in the change of VAS score between the two groups on the 14th day [mean difference (95% CI) = -2.31 (-2.48, -2.13) and -2.28 (-2.45, -2.11), respectively; p = 0.819]. The VAS, ODI, and M-JOA scores changed after the intervention in both groups (p <0.001), with increased ß-EP content (p = 0.014, p = 0.032) and decreased SP content (p <0.001, p = 0.048). The ODI score (p = 0.039) and M-JOA score (p = 0.032) of the MBMM group on the 28th day were lower than those of the AT group. Conclusion: The efficacy of Ma's bamboo-based medicinal moxibustion therapy in relieving low back pain of LDH patients is comparable to that of acupuncture, and it has post-effect advantages in improving lumbar dysfunction and daily living ability, which can be used as a safe and effective alternative method for LDH treatment.

Phentolamine and B vitamins for feeding intolerance in late preterm infants: a randomised trial.

BACKGROUND AND OBJECTIVES: Feeding intolerance (FI) is a common problem in late preterm infants (34 weeks ≤ gestational age < 37 weeks). This study aimed to evaluate the efficacy and safety of phentolamine combined with B vitamins in treating FI in late preterm infants and to explore its effects on gastrointestinal symptoms, inflammation and complications. METHODS AND STUDY DESIGN: We randomly assigned 118 late preterm infants with FI to a treatment group (n = 56) or a control group (n = 62). The treatment group received intravenous phentolamine and intramuscular B vitamins, whereas the control group received basic treatment only. We measured the time of disappearance of gastrointestinal symptoms, the time of basal at-tainment, the time of hospitalisation, the incidence of complications, the concentrations of inflammatory markers and the overall effective rate of treatment. RESULTS: The treatment group had a shorter duration of gastrointestinal symptoms than did the control group (p < 0.01). The treatment group also had lower concentrations of inflammatory markers and a higher overall effective rate than did the control group (p < 0.05). There was no difference between the two groups in the time of hospitalisation, basal attainment, weight re-covery and the incidence of complications (p > 0.05). CONCLUSIONS: Phentolamine and B vitamins can reduce gastrointestinal symptoms and inflammation in late preterm infants with FI but do not affect the occurrence of complications.

The PLETHORA Homolog In Marchantia polymorpha is Essential To Meristem Maintenance, Developmental Progression, And Redox Homeostasis.

To adapt to a terrestrial habitat, the ancestors of land plants must make several morphological and physiological modifications, such as a meristem allowing for three-dimensional growth, rhizoids for water and nutrient uptake, air pore complexes or stomata that permit air exchange, and a defense system to cope with oxidative stress that occurs frequently in a terrestrial habitat. To understand how meristem is determined during land plant evolution, we characterized the function of the closest PLETHORA homolog in the liverwort Marchantia polymorpha, which we named MpPLT. Through transgenic approach, we showed that MpPLT is expressed not only in the stem cells at the apical notch but also in the proliferation zone of the meristem, as well as cells that form the air-pore complex and rhizoids. Using the CRISPR method we then created mutants for MpPLT and found that the mutants are not only defective in meristem maintenance but also compromised in air-pore complex and rhizoid development. Strikingly, at later developmental stages, numerous gemma-like structures were formed in Mpplt mutants, suggesting developmental arrest. Further experiments indicate that MpPLT promotes plant growth by regulating MpWOX, which shared a similar expression pattern as MpPLT, and genes involved in auxin and cytokinin signaling pathways. Through transcriptome analyses, we found that MpPLT also has a role in redox homeostasis and that this role is essential to plant growth. Together, these results suggest that MpPLT has a crucial role in liverwort growth and development and hence may have played a crucial role in early land plant evolution.

Correlations of dynamic changes in lipid and protein of salted large yellow croaker during storage.

Protein and lipid are two major components that undergo significant changes during processing of aquatic products. This study focused on the protein oxidation, protein conformational states, lipid oxidation and lipid molecule profiling of salted large yellow croaker during storage, and their correlations were investigated. The degree of oxidation of protein and lipid was time-dependent, leading to an increase in carbonyl content and surface hydrophobicity, a decrease in sulfhydryl groups, and an increase in conjugated diene, peroxide value and thiobarbituric acid reactive substances value. Oxidation caused protein structure denaturation and aggregation during storage. Lipid composition and content changed dynamically, with polyunsaturated phosphatidylcholine (PC) was preferentially oxidized compared to polyunsaturated triacylglycerol. Correlation analysis showed that the degradation of polyunsaturated key differential lipids (PC 18:2_20:5, PC 16:0_22:6, PC 16:0_20:5, etc.) was closely related to the oxidation of protein and lipid. The changes in protein conformation and the peroxidation of polyunsaturated lipids mutually promote each other's oxidation process.

Lifestyle factors and subjective well­being among older adults in China: A national community-based cohort study.

There has been limited research on the relationship between health habits and subjective well-being (SWB) among Chinese oldest older adults. This study aims to explore lifestyle factors associated with SWB in this population. We analyzed data from three waves (2008-2014) of the CLHLS, including 28,683 older adults. Lifestyle factors analyzed included fruit and vegetable intake, smoking, alcohol consumption, physical exercise, and social participation. Results suggested that high frequency of fruit and vegetable intake, current and past physical exercise, and high levels of social participation were associated with increased SWB. SWB was lower in older adults who never smoked compared to persistent smokers and in those who never drank alcohol or ceased drinking compared to persistent drinkers. We encourage older adults to enhance SWB through increased fruit and vegetable intake, physical exercise, and social participation. However, quitting smoking and drinking may not necessarily improve SWB, particularly in the context of China.

Comparison of trial lens and computer-aided fitting in orthokeratology: A multi-center, randomized, examiner-masked, controlled study.

PURPOSE: To compare the efficacy and safety between traditional lens fitting and computer-aided fitting methods for orthokeratology (OrthoK) in the Chinese population. METHODS: A multi-center, examiner-masked, randomized controlled study was conducted with a one-year follow-up period, enrolling 280 participants with spherical equivalent (SE) ranging from -0.5D to -4.0D. Participants were assigned to either the computer-aided orthokeratology fitting group (trial group) or the traditional lens fitting group (control group) using stratified randomization based on age (8 to 13 years, 13 to 18 years, and ≥ 18 years) to ensure a minimum of 30 cases in each sub-age group. Ocular examinations included visual acuity, objective and subjective refraction, corneal endothelial cell density, corneal topography, intraocular pressure, axial length, and ocular health assessment. Successful lens-correction was defined as the residual refraction with the OK lens, which should not exceed ± 0.5D, and/or an uncorrected visual acuity of no worse than 0.1 logMAR. Statistical analysis involves t-tests, analysis of variance, and Chi-squared tests. RESULTS: 215 subjects were included in the statistical analysis (109 in the trial group and 106 in the control group). In both groups, compared to baseline data, the uncorrected visual acuity (UCVA) improved significantly, with SE reduced and central corneal curvature flattened greatly after wearing OrthoK lens (P < 0.05 for all). Compared to the control group, the trial group exhibited a higher successful rate in correcting UCVA (93.6 % vs. 84.0 %, P = 0.03) and slightly better correction in refraction (77.1 % vs. 66.0 %, P = 0.07) at 1-month follow-up. However, no significant differences were observed in the axial length elongation, corneal changes, or the incidence of adverse events between the two groups. CONCLUSION: These findings indicate the higher efficiency and slightly better performance in correcting myopia and improving UCVA of computer-aided lens fitting approach compared to the traditional one, but similar outcomes in controlling axial elongation.

Fully digital workflow of occlusal reconstruction treatment in a patient with congenital dentition defects.

OBJECTIVE: Occlusal reconstruction is a critical intervention for patients with dental hard tissue defects, temporomandibular joint (TMJ) disorders, and jaw position abnormalities. Clinical efficiency and outcomes of these procedures have improved with advances in digital technologies. This case report aims to illustrate a comprehensive digital workflow for occlusal reconstruction in a patient with congenital dentition defects, emphasizing the application of digital technologies to enhance treatment outcomes. CLINICAL CONSIDERATIONS: A 28-year-old woman with previously installed porcelain-fused-to-metal bridge restorations presented with a fractured prosthesis and TMJ symptoms. A multidisciplinary approach was adopted involving the use of digital facebow, intraoral scanners, digital smile design, and CAD/CAM technologies. The process included the extraction of defective restorations, temporary restorations to refine jaw position, and final permanent restorations. The digital workflow facilitated precise diagnostics and treatment, culminating in the successful installation of permanent restorations. Regular follow-ups at one- and three-months post-treatment confirmed stable occlusal function and high patient satisfaction. CONCLUSIONS: This case report showcases the potential of multiple digital technologies to streamline complex dental treatments and achieve high-quality results. CLINICAL SIGNIFICANCE: The integration of digital technologies in occlusal reconstruction treatments offers significant benefits in terms of precision, patient comfort, and esthetic outcomes.

[Research progress on processing history evolution, chemical constituents, and pharmacological action of Scorpio].

Scorpio is a valuable Chinese animal medicine commonly used in clinical practice in China. It is the main drug in the treatment of liver wind internal movement caused by various reasons throughout the history of traditional Chinese medicine(TCM), with the effects of relieving wind and spasm, dredging collaterals, relieving pain, and eliminating toxin and mass. Scorpio is poisonous and often used as medicine after processing. There are records of its processing as early as the Song Dynasty. Afterward, there were more than 15 processing methods, including frying with vinegar, neat processing, and stir-frying. After processing, the fishy smell could be removed to correct the taste, and the toxicity could be reduced, which was beneficial to clinical application. At present, the main reported components in Scorpio are protein polypeptides, alkaloids, and lipids, with many pharmacological effects, such as anti-cancer, anti-coagulation, anti-thrombosis, anti-atherosclerosis, and anti-bacteria. In this study, the historical evolution of processing, chemical constituents, and pharmacological action of Scorpio were discussed in order to provide references for the related research on Scorpio.

Impact of thermal ultrasound on enzyme inactivation and flavor improvement of sea cucumber hydrolysates.

In this study, the effects of the thermal ultrasonic enzyme inactivation process on flavor enhancement in sea cucumber hydrolysates (SCHs) and its impact on the inactivation of neutral proteases (NPs) were investigated. The body wall of the sea cucumber was enzymatically hydrolyzed with NPs. On the one hand, the structure of NPs subjected to different enzyme inactivation methods was analyzed using ζ-potential, particle size, and Fourier transform infrared (FT-IR) spectroscopy. On the other hand, the microstructure and flavor changes of SCHs were examined through scanning electron microscopy, E-nose, and gas chromatography-ion mobility spectrometry (GC-IMS). The results indicated that thermal ultrasound treatment at 60 °C could greatly affect the structure of NPs, thereby achieving enzyme inactivation. Furthermore, this treatment generated more pleasant flavor compounds, such as pentanal and (E)-2-nonenal. Hence, thermal ultrasound treatment could serve as an alternative process to traditional heat inactivation of enzymes for improving the flavor of SCHs.

Both gain- and loss-of-function variants of KCNA1 are associated with paroxysmal kinesigenic dyskinesia.

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.

Effects of cycloplegia on crystalline lens morphology and location in acute acquired concomitant esotropia.

PURPOSE: The study aims to compare morphology and location of crystalline lens between acute acquired concomitant esotropia (AACE) patients and control subjects, both before and after cycloplegia. METHODS: This is a prospective and observational clinical study. Morphological and locational parameters of the crystalline lens in 53 AACE patients and 32 control subjects were assessed before and after cycloplegia using CASIA2 system, which represents the latest swept-source anterior segment optical coherence tomography. Cycloplegic refraction was recorded by administering 1% atropine in patients younger than 12 years and 1% cyclopentolate in those > 12 years old. Morphological parameters included anterior radius of curvature (ARC), posterior radius of curvature (PRC), lens thickness (LTH), and equivalent diameter of lens (LED). Locational parameters comprised lens decentration (LD) and lens tilt (LT). Comparison of these parameters before and after cycloplegia were conducted between AACE and controls. Additionally, the study analyzed and compared the changes in these parameter post-cycloplegia. RESULTS: Our findings suggest no significant difference in morphological parameters including ARC, PRC, LTH and LED between AACE patients and controls before or after cycloplegia. However, 2D-modeling data in the 0° meridian revealed that variation post-cycloplegia of LD (lens shift) in right eyes was different in AACE patients, measuring - 0.03(0.08) [median(interquartile range)] which was significantly distinct from the control group, exhibiting a measurement of 0.01(0.06) (z = - 2.373, p = 0.018). In left eyes, a similar trend was observed with lens shift in the 0° meridian being 0.02(0.06) in AACE, significantly differing from control group's measurement of - 0.02(0.08) (z = - 2.809, p = 0.005). Further, correlation analysis revealed that larger temporal shift of lens was associated with greater changes in ARC (r = 0.294, p = 0.006) and LTH (r = - 0.230, p = 0.031). CONCLUSIONS: The morphological features of the crystalline lens were similar in AACE patients and controls; however, the change of lens location by cycloplegia was observed only in AACE patients, suggesting an association with excessive accommodation.

FAM120A deficiency improves resistance to cisplatin in gastric cancer by promoting ferroptosis.

The occurrence of chemoresistance is an inescapable obstacle affecting the clinical efficacy of cisplatin in gastric cancer (GC). Exploring the regulatory mechanism of cisplatin resistance will help to provide potential effective targets for improving the prognosis of gastric cancer patients. Here, we find that FAM120A is upregulated in GC tissues and higher in cisplatin-resistant GC tissues, and its high expression is positively correlated with the poor outcome of GC patients. Functional studies indicate that FAM120A confers chemoresistance to GC cells by inhibiting ferroptosis. Mechanically, METTL3-induced m6A modification and YTHDC1-induced stability of FAM120A mRNA enhance FAM120A expression. FAM120A inhibits ferroptosis by binding SLC7A11 mRNA and enhancing its stability. FAM120A deficiency enhances cisplatin sensitivity by promoting ferroptosis in vivo. These results reveal the function of FAM120A in chemotherapy tolerance and targeting FAM120A is an effective strategy to alleviate cisplatin resistance in GC.

Novel method for identifying the heaviest QED atom.

QED atoms are composed of unstructured and point-like lepton pairs bound together by the electromagnetic force. The smallest and heaviest QED atom is formed by a τ+τ- pair. Currently, the only known atoms of this type are the e+e- and µ+e- atoms, which were discovered 64 years ago and remain the sole examples found thus far. We demonstrate that the Jτ (τ+τ- atom with JPC=1--) atom signal can be observed with a significance larger than 5σ including both statistical and systematic uncertainties, via. the process e+e-→X+Y-Ɇ (X,Y=e,µ,π,K, or ρ, and Ɇ is the missing energy due to unobserved neutrinos) with 1.5ab-1 data taken around the τ pair production threshold. The τ lepton mass can be measured with a precision of 1 keV with the same data sample. This is within one year's running time of the proposed super tau-charm facility in China or super charm-tau factory in Russia.