DNMT3A dysfunction promotes neuroinflammation and exacerbates acute ischemic stroke.

Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well-characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A-driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

The effect of sulfuration reaction rates with sulphur concentration gradient dependence on the growth pattern and morphological evolution of MoS2 in laminar flow.

Sulfuration reactions dominate the synthesis of transition-metal dichalcogenides via chemical vapor deposition. A neglected critical issue is the evolution of crystal domain morphology and growth models caused by boundary layer development. In this study, we propose two growth models within a laminar flow field to investigate the kinetic mechanism of uniformly grown MoS2. We used supercritical fluid pre-deposition to obtain a well-distributed and low-crystallinity Mo precursor on the surface of a substrate to avoid non-stoichiometric supply in sulfuration. The development of the boundary layer was suppressed through mainstream force by adjusting the substrate slope angle. For growth within the underdeveloped laminar boundary layer, monolayer MoS2 with a size of 50 µm uniformly distributed on the full substrate with R = 85% (relative change in boundary layer thickness). Moreover, the growth constrained by surface chemical reactions tended to promote spatially uniform growth. However, within the fully developed laminar flow, the crystal domains preferentially grew vertically, which was attributed to the excessive crystal growth rate (g). Our results provide new insights into the controllable preparation of two-dimensional materials.

Efficient Trifluoromethylation of Halogenated Hydrocarbons Using Novel [(bpy)Cu(O2CCF2SO2F)2] Reagent.

This study introduces a novel trifluoromethylating reagent, [(bpy)Cu(O2CCF2SO2F)2], notable for not only its practical synthesis from cost-effective starting materials and scalability but also its nonhygroscopic nature. The reagent demonstrates high efficiency in facilitating trifluoromethylation reactions with various halogenated hydrocarbons, yielding products in good yields and exhibiting broad functional group compatibility. The development of [(bpy)Cu(O2CCF2SO2F)2] represents an advancement in the field of organic synthesis, potentially serving as a valuable addition to the arsenal of existing trifluoromethylating agents.

Muscle texture features on preoperative MRI for diagnosis and assessment of severity of congenital muscular torticollis.

OBJECTIVES: To develop an objective method based on texture analysis on MRI for diagnosis of congenital muscular torticollis (CMT). MATERIAL AND METHODS: The T1- and T2-weighted imaging, Q-dixon, and T1-mapping MRI data of 38 children with CMT were retrospectively analyzed. The region of interest (ROI) was manually drawn at the level of the largest cross-sectional area of the SCM on the affected side. MaZda software was used to obtain the texture features of the T2WI sequences of the ROI in healthy and affected SCM. A radiomics diagnostic model based on muscle texture features was constructed using logistic regression analysis. Fatty infiltration grade was calculated by hematoxylin and eosin staining, and fibrosis ratio by Masson staining. Correlation between the MRI parameters and pathological indicators was analyzed. RESULTS: There was positive correlation between fatty infiltration grade and mean value, standard deviation, and maximum value of the Q-dixon sequence of the affected SCM (correlation coefficients, 0.65, 0.59, and 0.58, respectively, P < 0.05).Three muscle texture features-S(2,2)SumAverg, S(3,3)SumVarnc, and T2WI extreme difference-were selected to construct the diagnostic model. The model showed significant diagnostic value for CMT (P < 0.05). The area under the curve of the multivariate conditional logistic regression model was 0.828 (95% confidence interval 0.735-0.922); the sensitivity was 0.684 and the specificity 0.868. CONCLUSION: The radiomics diagnostic model constructed using T2WI muscle texture features and MRI signal values appears to have good diagnostic efficiency. Q-dixon sequence can reflect the fatty infiltration grade of CMT.

Lewis acid-rich SrFexTi1-xO3/TiO2 to enhance the photocatalytic reduction of nitrate to N2.

The photocatalytic reduction of nitrate has received considerable attention due to its high efficiency and environmentally friendly nature. The excessive addition of hole scavengers is the most commonly used method to increase the nitrate reduction efficiency. However, achieving high selectivity in the photocatalytic reduction of nitrate to N2 with low concentration of hole scavengers remains challenging. In this study, the SrFexTi1-xO3/TiO2 S-scheme heterojunction photocatalysts with many Lewis acidic adsorption sites have been developed. The experimental results demonstrated that the incorporation of 6% Fe into SrFe0.06Ti0.94O3/TiO2 (SFTO6) resulted in the nitrate conversion rate of 97.68% and the N2 selectivity reached 96.35% with 25 mmol/L formic acid. Moreover, it also exhibited excellent stability and recycle ability. After 5 cycles, SFTO6 still exhibited a stable photocatalytic denitration efficiency of 92.94%, highlighting its potential for practical application. Through comprehensive mechanistic investigations, enhancing direct reduction process is considered the key to its high reduction efficiency with low formic acid. And the Lewis acidic adsorption sites enhance N2 selectivity by enriching NOx- on the surface of the material. Overall, this study provides a novel approach for achieving efficient photocatalytic reduction of nitrate to N2 under conditions with low concentration of hole scavengers.

Clinical analysis of 1301 children with hand and foot fractures and growth plate injuries.

BACKGROUND: Fractures of hands and feet are common in children, but relevant epidemiological studies are currently lacking. We aim to study the epidemiological characteristics of hand and foot fractures and growth plate injuries in children and provide a theoretical basis for their prevention, diagnosis, and treatment. METHODS: We retrospectively analyzed the data of children with hand and foot fractures who were hospitalized at Shenzhen Children's Hospital between July 2015 and December 2020. Data on demographic characteristics, fracture site, treatment method, etiology of injury, and accompanying injuries were collected. The children were divided into four age groups: infants, preschool children, school children, and adolescents. The fracture sites were classified as first-level (the first-fifth finger/toe, metacarpal, metatarsal, carpal, and tarsal) and second-level (the first-fifth: proximal phalanx, middle phalanx, distal phalanx, metacarpal, and metatarsal) sites. The changing trends in fracture locations and injury causes among children in each age group were analyzed. RESULTS: Overall, 1301 children (1561 fractures; 835 boys and 466 girls) were included. The largest number of fractures occurred in preschool children (n = 549, 42.20%), with the distal phalanx of the third finger being the most common site (n = 73, 15.57%). The number of fractures in adolescents was the lowest (n = 158, 12.14%), and the most common fracture site was the proximal phalanx of the fifth finger (n = 45, 29.61%). Of the 1561 fractures, 1143 occurred in the hands and 418 in the feet. The most and least common first-level fracture sites among hand fractures were the fifth (n = 300, 26.25%) and first (n = 138, 12.07%) fingers, respectively. The most and least common first-level foot fracture locations were the first (n = 83, 19.86%) and fourth (n = 26, 6.22%) toes, respectively. The most common first-level and second level etiologies were life related injuries (n = 1128, 86.70%) and clipping injuries (n = 428, 32.90%), respectively. The incidence of sports injuries gradually increased with age, accounting for the highest proportion in adolescents (26.58%). Hand and foot fractures had many accompanying injuries, with the top three being nail bed injuries (570 cases, 36.52%), growth plate injuries (296 cases, 18.96%), and distal severed fracture (167 cases, 10.70%). Among the 296 growth plate injuries, 246 occurred on the hands and 50 on the feet. CONCLUSIONS: In contrast to previous epidemiological studies on pediatric hand and foot fractures, we mapped the locations of these fractures, including proximal, shaft, distal, and epiphyseal plate injuries. We analyzed the changing trends in fracture sites and injury etiologies with age. Hand and foot fractures have many accompanying injuries that require attention during diagnosis and treatment. Doctors should formulate accident protection measures for children of different ages, strengthen safety education, and reduce the occurrence of accidental injuries.

Single-nucleus RNA and multiomics in situ pairwise sequencing reveals cellular heterogeneity of the abnormal ligamentum teres in patients with developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is the most common hip deformity in pediatric orthopedics. One of the common pathological changes in DDH is the thickening and hypertrophy of the ligamentum teres. However, the underlying pathogenic mechanism responsible for these changes remains unclear. This study represents the first time that the heterogeneity of cell subsets in the abnormal ligamentum teres of patients with DDH has been resolved at the single-cell and spatial levels by snRNA-Seq and MiP-Seq. Through gene set enrichment and intercellular communication network analyses, we found that receptor-like cells and ligament stem cells may play an essential role in the pathological changes resulting in ligamentum teres thickening and hypertrophy. Eight ligand-receptor pairs related to the ECM-receptor pathway were observed to be closely associated with DDH. Further, using the Monocle R package, we predicted a differentiation trajectory of pericytes into two branches, leading to junctional ligament stem cells or fibroblasts. The expression of extracellular matrix-related genes along pseudotemporal trajectories was also investigated. Using MiP-Seq, we determined the expression distribution of marker genes specific to different cell types within the ligamentum teres, as well as differentially expressed DDH-associated genes at the spatial level.

Supramolecular Interaction Modulation in Thermosensitive Composites: Enantiomeric Recognition and Chiral Site Regeneration.

Herein, a novel strategy was implemented to modulate the supramolecular interaction between enantiomers and chiral recognition sites (CRSs), effectively resolving the issue of CRS saturation. Randomly methylated-ß-cyclodextrin (Rm-ß-CD) was used as the CRS (host molecule), and polymerized ionic liquids [poly([vbim]TFSI)] were used as the supramolecular modulator (guest molecule), which self-assembled to generate thermosensitive supramolecular host/guest complexes. The enantiomeric binding capacity and enantioselectivity of chiral separation systems centered on supramolecular host-guest complexes are characterized by a high degree of temperature dependence. Poly([vbim]TFSI) bonded to Rm-ß-CD at temperatures between 17 °C ± 3 and 50 °C ± 3 °C, and the binding free energy difference (|ΔΔG|) between the (S)- and (R)-enantiomer was 0.55. Conversely, poly([vbim]TFSI detached from Rm-ß-CD at temperatures >50 °C ± 3 °C or <17 °C ± 3 °C, and |ΔΔG| between (S)- and (R)-enantiomer was 0.03. The |ΔΔG| value of the (R)-enantiomer can reach 0.86 in two temperature intervals. Therefore, the binding of poly([vbim]TFSI) to Rm-ß-CD afforded the favorable separation of four racemic sample mixtures: mandelic acid (e.e.% = 61.3%), ibuprofen (e.e.% = 21.6%), warfarin (e.e.% = 14.9%), and naproxen (e.e% = 18.2%). The detachment of poly([vbim]TFSI) from Rm-ß-CD released the enantiomer bound to CRSs. The decomplexation of mandelic acid reached 75.1%.

The bricolage mode of emergency medical teams in China: deficient and in urgent need of transformation-A qualitative study.

Introduction: Emergency medical rescue plays a vital role in alleviating the harm of all kinds of emergencies to people's physical and mental health and life safety. The current emergency medical teams (EMTs) formation model is not unified. We focused on the disadvantages of the bricolage mode of China EMTs and put forward empirical-based countermeasures to improve the emergency management ability of EMTs. Methods: From March to September 2022, 23 leaders of EMTs in North China (Tianjin) were selected by objective sampling method to conduct one-to-half structured in-depth interviews. Nvivo12.0 software was used for three-level coding. The disadvantages of the bricolage model of EMT were analyzed. Results: Based on the three-level coding, 150 initial concepts, 36 sub-coding, 17 main coding, six categories, and two core categories were sorted out. Management structure, internal stability, and support are recognized as the crucial elements armed with the EMTs. Discussion: The bricolage EMTs have disadvantages such as a chaotic management structure, weak internal stability, and inadequate support. It is necessary to construct full-time EMTs that incorporate a standardized personnel admission mechanism, full-time training and exercise mechanism, diversified incentive mechanism, and multi-agent cooperation mechanism, etc.

Efficacy and safety of second-line therapy by S-1 combined with sintilimab and anlotinib in pancreatic cancer patients with liver metastasis: a single-arm, phase II clinical trial.

Background: Pancreatic adenocarcinoma carries a grim prognosis, and there are few recognized effective second-line treatment strategies. We attempted to evaluate the efficacy and safety of a combination of S-1, sintilimab, and anlotinib as a second-line treatment in pancreatic cancer patients with liver metastasis. Methods: Pancreatic cancer patients with liver metastases were recruited. S-1 was administered orally at 25 mg/m2 bid, anlotinib was administered orally at 12 mg qd from day 1 to day 14, and sintilimab was administered intravenously at 200 mg on day 1. This method was repeated every 21 days, and the therapeutic effect was evaluated every 3 cycles. The primary outcome was the objective response rate (ORR). Results: Overall, 23 patients were enrolled in this study of whom 19 patients had objective efficacy evaluation. The ORR was 10.5% (95% CI 0.4%-25.7%) in the evaluable population. The progression-free survival (PFS) was 3.53 (95% CI 2.50-7.50) months, and the overall survival (mOS) was 8.53 (95% CI 4.97-14.20) months. Grade 3 adverse events were 26.1%, and no grade 4 or above adverse events occurred. High-throughput sequencing was performed on the tumor tissues of 16 patients; patients with HRD-H (n = 10) had shorter PFS than those with HRD-L (n = 6) (2.43 vs. 5.45 months; P = 0.043), but there was no significant difference in OS between the two groups (4.43 vs. 9.35 months; P = 0.11). Conclusions: This study suggests the advantage of S-1 combined with sintilimab and anlotinib in extending OS as a second-line therapy in pancreatic cancer patients with liver metastasis. Clinical Trial Registration: ChiCTR2000030659.

Covid-19 vaccination coverage and associated factors among older hypertensive patients in Hangzhou, China.

BACKGROUND: Vaccination could provide effective protection against coronavirus disease 2019 (COVID-19). This study aims to describe the COVID-19 vaccination coverage and influential factors in Chinese older hypertensive patients. METHODS: Using a cross-sectional design, participants were randomly selected from the electronic health records system during the pandemic era in Hangzhou, China. Logistic regression models were employed to compute the OR and 95% CI in order to assess the relationships between variables and the extent of COVID-19 vaccination coverage. RESULTS: As of 3 August 2022, among a sample of 77 970 individuals, 75.11% had completed the full COVID-19 vaccination, while 57.66% had received a booster dose. Disparities in coverage were observed across genders, regions and age groups. Unhealthy lifestyles, cardiovascular disease, cancer, uncontrolled blood pressure, abnormal fasting plasma glucose, dyslipidemia and renal dysfunction were risk factors for COVID-19 vaccination coverage. The coverage rates continuously declined along with the number of risk factors. The ORs for full and booster vaccination in subjects with ≥4 risk factors were 2.55 (2.12∼3.07) and 2.60 (2.16∼3.13), compared to individuals without risk factors. CONCLUSION: The COVID-19 vaccination program for older hypertensive patients must be strengthened further. Emphasis should be placed on patients who reside in urban areas, have comorbidities or multiple risk factors.

Eucalyptol, limonene and pinene enteric capsules attenuate airway inflammation and obstruction in lipopolysaccharide-induced chronic bronchitis rat model via TLR4 signaling inhibition.

BACKGROUND: Chronic bronchitis (CB), a type of chronic obstructive pulmonary disease (COPD), poses a significant global health burden owing to its high morbidity and mortality rates. Eucalyptol, limonene and pinene enteric capsules (ELPs) are clinically used as expectorants to treat various respiratory diseases, including CB, but their acting mechanisms remain unclear. In this study, we investigated the anti-CB effects of ELP in a rat model of lipopolysaccharide (LPS)-induced CB. The molecular mechanisms underlying its inhibitory effects on airway inflammation were further explored in LPS-stimulated Beas-2B cells. METHODS: ELP was characterized using gas chromatography. The production of inflammatory mediators in bronchoalveolar lavage fluid (BALF) was determined using an enzyme-linked immunosorbent assay. The expression of MUC5AC, MUC5B, and p-p65 in the lung tissue was measured using immunohistochemical staining. The gene expression of inflammatory mediators was determined using qRT-PCR. The expression levels of the target proteins were detected by western blotting. Nuclear localization of p65 was determined using an immunofluorescence assay. RESULTS: Compared to the CB model rats, ELP-treated rats showed reduced airway resistance, inflammation, and goblet cell hyperplasia. In BALF, ELP decreased the levels of inflammatory mediators, including TNF-α, IL-6, MIP-1α, and CCL5. ELP also suppressed LPS-induced elevation of MUC5AC, MUC5B, and p-p65 in the lung tissue. The metabolic pathway changes caused by LPS challenge were improved by ELP treatment. In LPS-exposed Beas-2B cells, ELP treatment inhibited the expression of TNFA, IL6, CCL5, MCP1, and MIP2A and decreased the phospho-levels of toll-like receptor 4 (TLR4) signaling-related proteins, including p-p38, p-JNK, p-ERK, p-TBK1, p-IKKα/ß, p-IκB, p-p65, and p-c-Jun. ELP also hindered the nuclear translocation of p65, c-Jun, and IRF3. CONCLUSIONS: This study showed that ELP has a potential therapeutic effect in LPS-induced CB rat model, possibly by suppressing TLR4 signaling. These results justify the clinical use of ELP for the treatment of pulmonary inflammatory diseases.

Valproate attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress through inhibiting spinal IL-6 and STAT1 phosphorylation.

Temporomandibular disorder (TMD) and fibromyalgia syndrome (FMS) may present as comorbid conditions, but treatment options are ineffective. The purpose of this study was to investigate whether valproate (VPA) attenuates somatic hyperalgesia induced by orofacial inflammation combined with stress, which represents a model of pain associated with TMD and FMS comorbidity, and to explore the potential mechanisms. The results showed that VPA inhibited somatic hyperalgesia induced by orofacial inflammation combined with stress, and down-regulated the interleukin-6 (IL-6) expression in the L4-L5 spinal dorsal horn of female rats. The anti-nociceptive effect of VPA was blocked by single or 5 consecutive day intrathecal administration of recombinant rat IL-6. Orofacial inflammation combined with stress up-regulated the ratio of phosphorylated signal transducer and activator of transcription 1 (p-STAT1) to STAT1 (p-STAT1/STAT1) in the spinal cord. VPA did not affect the STAT1 expression, while it down-regulated the ratio of p-STAT1/STAT1. The expression of STAT3 and the ratio of p-STAT3/STAT3 were not affected by orofacial inflammation combined with stress and VPA treatment. Intrathecal administration of exogenous IL-6 up-regulated the ratio of p-STAT1/STAT1. These data indicate that VPA attenuated somatic hyperalgesia induced by orofacial inflammation combined with stress via inhibiting spinal IL-6 in female rats, and the mechanism may involve the alteration of activation status of spinal STAT1. Thus, VPA may be a new candidate analgesic that targets IL-6 and STAT1 for the treatment of pain associated with the comorbidity of TMD and FMS.

Enzymatic activity and development of Frankliniella occidentalis (Thysanoptera: Thripidae) in response to exogenous calcium treatments of kidney bean plants.

Frankliniella occidentalis Pergande (Thysanoptera: Thripidae) is an agricultural pest threatening various horticultural crops worldwide. Inducing plant resistance is an ecologically beneficial and potentially effective method for controlling F. occidentalis. As an essential nutrient element, exogenous calcium enhances plant-induced resistance. This study investigated the effects of CaCl2 on the secondary metabolites of kidney bean plants and detoxifying and digestive enzymes in F. occidentalis. We found that treatment of plants and treatment time and also the interactions of the 2 factors significantly affected secondary metabolites contents (tannin, flavonoids, total phenol, alkaloid, and lignin) of kidney bean leaves, which indicated that that the effect of treatment of plants on secondary metabolites varied with treatment time. Moreover, when thrips fed on CaCl2-treated plants, the activities of detoxifying enzymes, enzymes glutathione S-transferase and cytochrome P450 substantially increased compared to those in which thrips fed on control plants. However, the activity of carboxylesterase significantly decreased. The detoxifying enzyme genes CL992.contig6, CYP4PN1, and CYP4PJ2 were significantly upregulated at 24 and 48 h. The activities of digestive enzymes (α-amylase, chymotrypsin, and lipase) increased substantially in F. occidentalis. The digestive enzyme gene, FoAMY-1, was significantly upregulated at 24 and 48 h after treatment. The pupation rate and pupal weight of F. occidentalis were significantly reduced. The results indicated that exogenous CaCl2-induced metabolic changes in kidney bean plants and altered the enzymatic activity and development of F. occidentalis that fed upon them.

Chest Tightness With QR and ST-Segment Elevation in Lead V1.

This case report describes a patient in their 50s with a 2-month history of worsening chest tightness and dyspnea after COVID-19 infection.

Study on Screening Core Biomarkers of Noise and Drug-Induced Hearing Loss Based on Transcriptomics.

Background Noise and drug-induced hearing loss (HL) is becoming more and more serious, but the integration and analysis based on transcriptomics and proteomics are lacking. On the one hand, this study aims to integrate existing public transcriptomic data on noise and gentamicin-induced HL. On the other hand, the study aims to establish the gentamicin and noise-induced HL model of guinea pigs, then to perform the transcriptomic and proteomic analyses. Through comprehensive analysis of the above data, we aim to screen, predict, and preliminarily verify biomarkers closely related to HL. Material and Methods We screened the Gene Expression Omnibus database to obtain transcriptome data expression profiles of HL caused by noise and gentamicin, then constructed the guinea pig HL model and perform the transcriptomic and proteomic analyses. Differential expression and enrichment analysis were performed on public and self-sequenced data, and common differentially expressed genes (DEGs) and signaling pathways were obtained. Finally, we used proteomic data to screen for common differential proteins and validate common differential expression genes for HL. Results By integrating the public data set with self-constructed model data set, we eventually obtained two core biomarkers of HL, which were RSAD2 and matrix metalloproteinase-3 (MMP3). Their main function is to regulate the development of sense organ in the inner ear and they are mainly involved in mitogen-activated protein kinase and phosphoinositol-3 kinase/protein kinase B signaling pathways. Finally, by integrating the proteomic data of the self-constructed model, we also found differential expression of MMP3 protein. This also preliminarily and partially verified the above-mentioned core biomarkers. Conclusion and Significance In this study, public database and transcriptomic data of self-constructed model were integrated, and we screened out two core genes and various signal pathways of HL through differential analysis, enrichment analysis, and other analysis methods. Then, we preliminarily validated the MMP3 by proteomic analysis of self-constructed model. This study pointed out the direction for further laboratory verification of key biomarkers of HL, which is of great significance for revealing the core pathogenic mechanism of HL.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway.

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. METHODS: We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2-6] at 3 months. RESULTS: Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0-69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00-5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12-0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02-0.42, p = 0.002; pinteraction = 0.001). CONCLUSION: CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.

Xuelian injection ameliorates complete Freund's adjuvant-induced acute arthritis in rats via inhibiting TLR4 signaling.

Background: Xuelian injection (XI), a classic preparation extracted from Saussureae Involucratae Herba, has been clinically used to manage rheumatoid arthritis (RA) for nearly twenty years in China. However, the underlying anti-RA mechanism of XI remains unclear. In this study, complete Freund's adjuvant (CFA)-induced acute arthritic model was used to examine the anti-RA effects of XI in vivo. The molecular mechanisms of this action were further investigated using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods: XI and XI freeze dried powder were characterized by UPLC analysis. CD68 and TLR4 expression in the ankle joints was measured by immunohistochemistry. The secretion of inflammatory mediators was detected by ELISA. The expression levels of TLR4 involved components were measured by Western blotting. The localization of transcription factors was measured by immunofluorescence assay. Results: XI treatment ameliorated arthritic symptoms induced by CFA in the ankle joints of rats. The serum levels of inflammatory mediators, including TNF-α, MCP-1, and Rantes were decreased by XI treatment. The elevation of CD68 and TLR4 levels in ankle joints caused by CFA was suppressed by XI treatment. Moreover, XI treatment inhibited the secretion of nitric oxide and prostaglandin E2 in LPS-treated RAW264.7 macrophages. The expression of their enzymes iNOS and COX-2 was also decreased after XI treatment. The production of inflammatory mediators, including TNF-α, IL-6, IL-1ß, MCP-1, MIP-1α, and Rantes was reduced by XI treatment in LPS-stimulated RAW264.7 cells. The phosphorylation of p38, JNK, ERK, TBK1, IKKα/ß, IκB, p65, c-Jun, and IRF3 was reduced after XI treatment. Additionally, the expression levels of nuclear proteins of p65, c-Jun, and IRF3 were inhibited by XI treatment. Conclusions: Taken together, XI possesses potential anti-RA effect and the underlying mechanism may be closely associated with the inhibition of TLR4 signaling. Our findings provide further pharmacological justifications for the clinical use of XI in RA treatment.

Experience with the management of 2599 cases of congenital muscular torticollis and a multicenter epidemiological investigation in 17 hospitals in China.

BACKGROUND: Congenital muscular torticollis (CMT) is a common musculoskeletal disease affecting infants and young children. If CMT is not treated correctly and timely, it can lead to limited head and neck movements, head and neck deviation, and abnormal posture. In order to improve patients' symptoms and alleviate the negative impact of the disease on their lives, we are committed to exploring the treatment of CMT. METHODS: The general clinical and ultrasonographic data of 2599 children with CMT who received standardized treatment at Shenzhen Children's Hospital from 2004 to 2020 were retrospectively reviewed. According to given treatment, children with CMT were divided into the physiotherapy group, physiotherapy combined with glucocorticoid treatment group, and surgical treatment group. We divided children with CMT into local mass, uniform thickening, and atrophy according to ultrasound features. General clinical information, treatment, and ultrasound examination data in each group were compared. Additionally, electronic medical records of 2344 patients admitted due to CMT in 17 tertiary children's hospitals of China's Futang Research Center of Pediatric Development (FRCPD) from 2015 to 2019 were retrospectively analyzed. Data on sex, age, year of admission and discharge, and treatment costs during hospitalization were extracted from the first medical record pages according to the ICD codes. The data were assessed for normality using the Kolmogorov-Smirnov test. Depending on the data distribution, they were analyzed using parametric tests, such as the t-test, or non-parametric tests. Qualitative data are expressed as percentages (%) and analyzed using the chi-square or Fisher's exact probability test, with α = 0.05 as the test level. P < 0.05 was considered to be indicative of a statistically significant difference. RESULTS: Three types of CMT were defined based on sternocleidomastoid muscle ultrasound examination characteristics: local mass, uniform thickening, and atrophy. Age at first diagnosis was 69.21 ± 108.41 days in local mass type group, 216.85 ± 324.09 days in uniform thickening group, and 417.88 ± 739.05 days in atrophy- type group; while age at first physiotherapy use was 94.06 ± 206.49 days, 255.00 ± 430.62 days, 540.92 ± 1059.29 respectively. The children included in local mass type group have shown a high success rate of conservative treatment, with a rate of 7.5% of children underwent surgery. Age at first diagnosis was 112.44 ± 224.12 days in the physiotherapy group, 115.87 ± 144.86 days in the physiotherapy combined with glucocorticoid treatment subgroup, whereas the age at first physiotherapy use was 137.38 ± 312.11 and 196.91 ± 344.26 days respectively. In the observation period (2015-2019) the mean age at surgery for CMT in 17 tertiary children's hospitals of the FRCPD was 50 months. Overall, 663 children with CMT were 1-2 years of age, accounting for the largest proportion (28.3%). Followed by 417 individuals (17.8%) were 7-14 years of age, indicating that there are still more children with CMT receiving surgical treatment later. CONCLUSIONS: Early diagnosis and treatment are essential to improve the conservative treatment success rate and achieve good prognosis in children with CMT. Our team's concept for treating CMT is as follows: after diagnosing the children, we will adopt the standardized protocol of treatment, with physiotherapy combined with the injection of glucocorticoid drugs and SCM release surgery, when needed. This program has a high conservative treatment success rate and may facilitate the achievement of better prognosis and reduced teratogenicity rate.