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Abstract Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Abstract Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering. Graphical abstract

IntroductionEarly prediction and intervention are crucial for the prognosis of unexplained recurrent spontaneous abortion (uRSA). The main purpose of this study is to establish a risk prediction model for uRSA based on routine pre-pregnancy tests, in order to provide clinical physicians with indications of whether the patients are at high risk.MethodsThis was a retrospective study conducted at the Prenatal Diagnosis Center of Henan Provincial People’s Hospital between January 2019 and December 2022. Twelve routine pre-pregnancy tests and four basic personal information characteristics were collected. Pre-pregnancy tests include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine thyroid (FT4), thyroxine (TT4), total triiodothyronine (TT3), peroxidase antibody (TPO-Ab), thyroid globulin antibody (TG-Ab), 25-hydroxyvitamin D [25-(OH) D], ferritin (Ferr), Homocysteine (Hcy), vitamin B12 (VitB12), folic acid (FA). Basic personal information characteristics include age, body mass index (BMI), smoking history and drinking history. Logistic regression analysis was used to establish a risk prediction model, and receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were employed to evaluate the performance of prediction model.ResultsA total of 140 patients in uRSA group and 152 women in the control group were randomly split into a training set (n = 186) and a testing set (n = 106). Chi-square test results for each single characteristic indicated that, FT3 (p = 0.018), FT4 (p = 0.048), 25-(OH) D (p = 0.013) and FA (p = 0.044) were closely related to RSA. TG-Ab and TPO-Ab were also important characteristics according to clinical experience, so we established a risk prediction model for RSA based on the above six characteristics using logistic regression analysis. The prediction accuracy of the model on the testing set was 74.53%, and the area under ROC curve was 0.710. DCA curve indicated that the model had good clinical value.ConclusionPre-pregnancy tests such as FT3, FT4, TG-Ab, 25-(OH)D and FA were closely related to uRSA. This study successfully established a risk prediction model for RSA based on routine pre-pregnancy tests.

Abstract Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.

Using l-histidine and cerium nitrate hexahydrate as raw materials, a green and effective carbon dots (Ce,N-CDs) was prepared using hydrothermal synthesis and their structures were confirmed by professional equipment. The anti-bacterial and anti-corrosive behaviors of Ce,N-CDs were systemically evaluated using plate counting method and electrochemical method, respectively. By analysis, the Ce,N-CDs showed a high bacterial inhibition efficiency for Escherichia coli (E. coli), which was up to 94.27 %. Compared with N-doping carbon dots (N-CDs), the Ce,N-CDs exhibited an excellent anti-corrosive ability. At 200 mg/l, its corrosion inhibition efficiency (IE) for Cu was higher than 90 % at different environment temperatures (308, 318, 323 K), and the corrosion rate (WL) was sharply reduced. This was attributed to the presence of N–Cu bond and the formation of Ce-containing passive film. The Ce-containing passive film could block the erosion of aggressive ions. The N–Cu bond could facilitated the chemical adsorption on Cu surface, which was confirmed by quantum chemistry (QC) and molecular dynamics (MD).

Background: In Wuhan, China, a stringent lockdown was implemented to contain the spread of COVID-19, transitioning later to normalised prevention and control strategy. This study examines the trends in hospital visits for acute and chronic respiratory diseases, with a focus on outpatient, inpatient, and severe condition visits. Methods: The study used administrative health insurance data spanning from January 2018 to August 2021, an interrupted time series analysis was conducted to assess the trend in hospital visits per million population for respiratory diseases. To confirm whether the change was exclusive to respiratory diseases, neoplasms and intracerebral haemorrhage were used as controls. The impact of the pandemic was estimated by comparing by weekly admissions to pre-pandemic levels. Subgroup analyses dissected variations by disease and visit types. Results: Hospital visits for respiratory diseases declined significantly during the lockdown and exhibited a slower recovery in the later normalised prevention and control period compared to the control conditions. As of August 2021, outpatient visits increased by over 22.2% above the pre-pandemic level, while inpatient and severe condition visits witnessed significant reductions, falling to 46.7% and 80.6% of pre-pandemic levels, respectively. Compared to three other subgroups, visits for acute lower respiratory infections experienced the most significant decline, with inpatient and severe visits dropping to 23.9% and 25.7% of pre-pandemic levels. Interpretation: Our study revealed a persistent reduction in inpatient and severe case visits for respiratory diseases throughout the ongoing pandemic. These findings suggested the possible role of non-pharmaceutical interventions in mitigating acute and chronic non-COVID respiratory diseases.

Background Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators.Methods The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/RWE.Results All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: (a) sources and types of RWD being used in HTA, and (b) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled.Conclusion The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on Gram-negative bacteria, and its minimum inhibitory activity (MIC) against Escherichia coli can reach 2 μg/mL. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be the disruption of the Gram-negative cell membrane.

In this study, we designed the processing windows for laser powder bed fusion (LPBF) of Ti-6Al-4V (Ti-64) alloy by using central composite design and made a detailed investigation into the influence of processing parameters on the defects. The purpose is to investigate the effect of defects on mechanical properties. It was found that insufficient energy density could lead to the formation of lack of fusion (LOF) defects and produce non-melted powders on the surface, while excessive energy density could lead to cracks that were detrimental to mechanical performance. In addition, the microstructural evaluation found that relatively low energy density could lead to shorter columnar prior-β grains, while prior-β grains in the sample processed by the high energy density extended almost the entire height of the cross-section, which could lead to the strong mechanical property anisotropy. The prior β grains are formed by heterogeneous nucleation on the partially melted material powder. As the energy input increases, all the powder powders in the molten pool can be melted so that these particles do not act as nucleation sites and the prior β grain can grow through more layers without forming new grains being able to nucleate. The prior β-grain in as-built Ti-64 samples consisted of acicular α’ martensite with myriads of lattice distortions, as a precursor to a phase transition, which lead to strong tensile strength and poor ductility. Annealing heat treatment promoted the improvement of the ductile performance of LPBF Ti-64. Overall, this study provides comprehensive views on the effects of processing parameters (laser power, scanning speed, and hatch distance) on the internal (pores and LOF) and external (unmelted powder, sintering neck, and crack), defects, microstructure, and tensile property evaluation of LPBF Ti-64, which offer insights for the development of additive manufactured titanium alloys with excellent mechanical property.

Uveitis is a rare adverse event of dupilumab, that typically affects both eyes and often leads to discontinuation of therapy. In this article, we report a case of a 28-year-old female with atopic dermatitis who developed new-onset iridocyclitis, a form of uveitis, in her left eye 2 weeks after starting dupilumab treatment, which improved after reducing the dose, without discontinuing dupilumab. The patient also experienced asymptomatic hypereosinophilia, possibly related to dupilumab, which was gradually relieved without discontinuation. With the readers, we share our experience in managing uveitis and hypereosinophilia associated with dupilumab, which may be helpful in managing these conditions and avoiding discontinuation of dupilumab.

Abstract Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.

Abstract Background Good osseointegration is the key to the long-term stability of bone implants. Thermoplastic polyetheretherketone (PEEK) has been widely used in orthopedics; however, its inherent biological inertia causes fibrous tissue to wrap its surface, which leads to poor osseointegration and thus greatly limits its clinical applications. Methods Herein, we developed a facile yet effective surface modification strategy. A commonly used sulfonation coupled with “cold pressing” treatment in the presence of porogenic agent formed a three-dimensional hierarchical porous structure on PEEK surface. Subsequently, the effects of porous surface on the in vitro adhesion, proliferation and differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) were evaluated. Finally, the osteoinduction and osseointegration of surface-porous PEEK implant were examined in the rat distal femoral defect model. Results In vitro results showed that the surface modification did not significantly affect the mechanical performance and cytocompatibility of PEEK substance, and the porous structure on the modified PEEK substrate provided space for cellular ingrowth and enhanced osteogenic differentiation and mineralization of BMSCs. In vivo tests demonstrated that the surface-porous PEEK implant could effectively promote new bone formation and had higher bone-implant contact rate, thereby achieving good bone integration with the surrounding host bone. In addition, this modification technique was also successfully demonstrated on a medical PEEK interbody fusion cage. Conclusion The present study indicates that topological morphology plays a pivotal role in determining implant osseointegration and this facile and effective modification strategy developed by us is expected to achieve practical applications quickly. Graphical Abstract

Abstract Objectives This study aimed to determine the prevalence and independent risk factors of SDB, and explore its association with malocclusion among 6–11-year-old children in Shanghai, China. Methods A cluster sampling procedure was adopted in this cross-sectional study. Pediatric Sleep Questionnaire (PSQ) was applied to evaluate the presence of SDB. Questionnaires including PSQ, medical history, family history, and daily habits/environment were completed by parents under instruction, and oral examinations were implemented by well-trained orthodontists. Multivariable logistic regression was applied to identify independent risk factors for SDB. Chi-square tests and Spearman's Rank Correlation were used to estimate the relationship between SDB and malocclusion. Results A total of 3433 subjects (1788 males and 1645 females) were included in the study. The SDB prevalence was about 17.7%. Allergic rhinitis (OR 1.39, 95% CI 1.09–1.79), adenotonsillar hypertrophy (OR 2.39, 95% CI 1.82–3.19), paternal snoring (OR 1.97, 95% CI 1.53–2.53), and maternal snoring (OR 1.35, 95% CI 1.05–1.73) were independent risk factors for SDB. The SDB prevalence was higher in children with retrusive mandibles than in proper or excessive ones. No significant difference was observed in the correlation between SDB and lateral facial profile, mandible plane angle, constricted dental arch form, the severity of anterior overjet and overbite, degree of crowding and spacing, and the presence of crossbite and open bite. Conclusions The prevalence of SDB in primary students in the Chinese urban population was high and highly associated with mandible retrusion. The independent risk factors included Allergic rhinitis, adenotonsillar hypertrophy, paternal snoring, and maternal snoring. More efforts should be made to enhance public education about SDB and related dental-maxillofacial abnormalities.

Hydrogels are emerging as the most promising dressings due to their excellent biocompatibility, extracellular matrix mimicking structure, and drug loading ability. However, existing hydrogel dressings exhibit limited breathability, poor environmental adaptability, potential drug resistance, and limited drug options, which extremely restrict their therapeutic effect and working scenarios. Here, the current research introduces the first paradigm of hydrogel textile dressings based on novel gelatin glycerin hydrogel (glyhydrogel) fibers fabricated by the Hofmeister effect based wet spinning. Benefiting from the unique knitted structure, the textile dressing features excellent breathability (1800 times that of the commercially available 3 M dressing) and stretchability (535.51 ± 38.66%). Furthermore, the glyhydrogel textile dressing can also withstand the extreme temperature of −80 °C, showing the potential for application in subzero environments. Moreover, the introduction of glycerin endows the textile dressing with remarkable antibacterial property and expands the selection of loaded drugs (e.g., clindamycin). The prepared glyhydrogel textile dressing shows an excellent infected wound healing effect with a complete rat skin closure within 14 days. All these functions have not been achievable by traditional hydrogel dressings and provide a new approach for the development of hydrogel dressings.

Introduction Compensatory mouth breathing, caused by nasopharyngeal obstructive diseases, is the main cause of hyperdivergent mandibular retrognathia in children. Such deformities require effective growth guidance before pubertal growth peaks. The traditional mandibular advancement device, twin block (TB), can guide the forward development of the mandible. However, the side effect of increasing the vertical dimension of the lower facial third, worsens the facial profile of children with divergent growth trends. To solve this problem, a modified TB (LLTB) appliance was designed to control the vertical dimension by intruding incisors and inhibiting the elongation of posterior teeth during the advancement of the mandible, which could avoid the side effects of traditional appliances and effectively guide the growth of the mandible in a normal direction.Methods and analysis The study was designed as a single-centre, single-blind, randomised, parallel controlled trial. We aim to enrol 60 children aged 9–14 years with hyperdivergent skeletal class II malocclusion, using a 1:1 allocation ratio. The participants were will be randomly assigned to receive either the TB or LLTB treatment. The primary outcome will be a change in the angle of the mandibular plane relative to the anterior cranial base. The secondary outcomes will include changes in the sagittal maxillomandibular relation, occlusal plane, facial height, morphology of the mandible and upper airway width. Safety endpoints will also be evaluated.Ethics and dissemination Ethical approval was obtained from the ethics committee of Shanghai Stomatological Hospital. Both participants and their guardians will be fully informed of the study and sign an informed consent form before participating in the trial. The results will be publicly available in peer-reviewed scientific journals.Trial registration number ChiCTR2000035882.

Peri-implantitis is a highly prevalent disease caused by bacterial plaque that results in inflammation. The disease starts from the soft tissue and gradually spreads to the hard tissue around the implant. If left untreated, it can lead to decreased bone density and loss of the implant. Therefore, it is crucial to improve the antibacterial and biological activity of implants to achieve dual functions. In this study, we prepared a Ce-doped TiO2 coating on the surface of pure titanium by micro-arc oxidation (MAO) for the prevention of peri-implantitis. We systematically investigated the physicochemical properties, antibacterial activity, and biocompatibility of Ce-doped coatings in vitro and in vivo. The results demonstrated that the increase of Ce concentration in the coating could increase the proliferation, adhesion and osteogenic differentiation of BMSCs in vitro. Results from in vivo osteogenesis experiments demonstrated that the 2Ce-MAO coating exhibited superior efficacy in promoting implant repair in osteoporotic rats. Furthermore, the results of in vitro and in vivo antibacterial experiments indicated that the Ce-TiO2 coating exhibits excellent antibacterial and anti-inflammatory properties. These findings suggest that the Ce-TiO2 coating prepared via MAO may be a promising approach for preventing peri-implantitis and promoting osteogenesis in osteoporosis.

Introduction Class II treatment with mandibular retrusion often involves the Herbst appliance due to its efficiency and low requirement of cooperation. Despite its advantages, it causes side effects concerning the occlusal plane and pogonion in terms of clockwise rotation that hinder the desired mandibular advancement for hyperdivergent patients. In this study, we will use a newly designed Herbst appliance, and a protocol that is accompanied by TADs for vertical control to avoid maxillary clockwise rotation. We hypothesise that the effect of the Herbst appliance with the vertical control approach will be beneficial for maintaining or even decreasing the skeletal divergence in hyperdivergent class II patients compared with conventional Herbst treatment.Methods and analysis This study is a randomised, parallel, prospective controlled trial that will study the efficacy of Herbst with or without vertical control in children with hyperdivergent skeletal class II malocclusion. A total of 44 patients will be enrolled and randomised in a ratio of 1:1 to either Herbst treatment or Herbst treatment with vertical control. Participants will be recruited at the Shanghai Stomatological Hospital, Shanghai, China. The primary endpoint is the change in the angle indicating the occlusal plane and Sella-Nasion plane from baseline (T0) to the primary endpoint (T2) on cephalometric measurements by lateral X-ray examination. Important secondary outcomes include the root length of the anterior teeth, and the assessment score of the Visual Analogue Scale Questionnaire, etc. Safety endpoints will also be evaluated.Ethics and dissemination This study has been approved by the ethics committee of the Shanghai Stomatological Hospital (Approval No. (2021) 012). Before enrolment, a qualified clinical research assistant will obtain written informed consent from both the participants and their guardians after full explanation of this study. The results will be presented at national or international conferences and published in peer-reviewed journals.Trial registration number ChiCTR2100049860, Chinese Clinical Trial Registry

Introduction: Drugs and biocompatible nanoparticles have raised significant potential in advancing the bone regeneration. Electrospinning technology enables the full realization of the value of drugs and nanoparticles.Methods: In this study, we have successfully fabricated core–sheath nanofibers solely composed of polycaprolactone (PCL) polymer. Simvastatin (SIM) was confined to the core of the nanofibers while nanohydroxyapatite (nHA) was loaded on the nanofiber surface.Results: All the prepared nanofibers exhibited a cylindrical micromorphology, and the core–sheath structure was exploited using a Transmission Electron Microscope. X-ray pattern results indicated that SIM was in an amorphous state within nanofibers, while Fourier Transform InfraRed spectroscopy showed excellent chemical compatibility among SIM, nHA, and PCL. The actual loading of nHA within the nanofiber was determined by a thermogravimetric test due to the high melting point of nHA. Core–sheath nanofibers could release SIM for 672 h, which was attributed to the core–sheath structure. Furthermore, nanofibers loaded with SIM or nHA had a positive impact on cell proliferation, with the core–sheath nanofibers displaying the most favorable cell proliferation behavior.Discussion: Such a synergistic facilitation strategy based on materials and nanostructure may encourage researchers to exploit new biomedical materials in future.

Background: Mycosis fungoides (MF) and Sezary Syndrome (SS) comprise over half of all Cutaneous T-cell lymphoma diagnoses. Current risk stratification is largely based on TNMB staging, few research investigated the prognostic value of clinical exams. Current systemic therapy for advanced disease includes immunomodulatory drugs, chemotherapy, and HADC inhibitors. Few clinical trials or retrospective research compared the efficacy of different drugs.Method: Here, we performed a retrospective analysis of prognostic factors and treatment outcomes of 92 patients diagnosed with MF/SS at the Peking Union Medical College Hospital from 2013-2023.Results: Cox regression analysis identified that age ≥ 50 years, WBC ≥ 8 × 109/L, serum LDH ≥ 250U/L, β2-MG ≥ 4.50 mg/L, and stage IV were associated with reduced overall survival, age ≥ 50 years, serum LDH ≥ 250U/L and stage IV were associated with reduced progression free survival. Kaplan-Meier analysis established that immunomodulatory therapy was associated with longer progression free survival.Conclusion: These results suggested new factors in predicting prognosis and selecting appropriate treatments in patients with advanced MF/SS.

AbstractBackground: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma.Objectives: This study was conducted to evaluate efficacy and safety of interferon (IFN) α-2a combined with phototherapy for early-stage MF.Methods: Thirteen patients with early-stage MF received subcutaneous injections of IFN α-2a at 3 million IU combined with phototherapy three times per week for 6 months. Treatment efficacy was measured by changes in body surface area (BSA) score and modified severity-weighted assessment tool (mSWAT) score at 1, 3, and 6 months after treatment. Histopathologic examinations of skin lesions were performed before and after treatment.Results: After 3 months of treatment, all 13 patients achieved a partial response, and BSA and mSWAT scores were significantly lower than those at baseline (p

Abstract Introduction The basis of orthodontic tooth movement (OTM) is the reconstruction of periodontal tissue under stress. Increasing the speed of OTM has always been the focus of attention. Objectives Periodontal ligament stem cells (PDLSCs) are direct effector cells of mechanical force, but the mechanism by which PDLSCs sense mechanical stimuli is unclear. Methods Human PDLSCs (hPDLSCs) were analyzed in the presence or absence of force loading with the Flexcell loading system in vitro. Then, periodontal tissues were analyzed after mechanical stimulation in vivo. In addition, cells in a confined microenvironment were analyzed to observe changes in the cytoskeleton and migration. Finally, TRPC6−/− mice were used to further verify the effect of TRPC6. After force application, the OTM distance, bone marrow density (BMD), TRPC6 and COL1 expression, and TRAP staining were evaluated in periodontal tissues. Results RNA sequencing (RNA-seq) and western blot analyses revealed that TRPC6 was important during mechanical force application to hPDLSCs. Appropriate mechanical force application also induced TRPC6 activation in the OTM model and the confined microenvironment. Under a slightly confined microenvironment, treatment with the TRPC6 inhibitor SKF96365 and TRPC6 knockout decreased the migration speed of hPDLSCs and mouse bone marrow mesenchymal stem cells (mBMSCs). In addition, TRPC6−/− mice showed lower OTM distances and reduced osteogenic and osteoclastic differentiation. Conclusion In summary, TRPC6 activation in PDLSCs mediated by appropriate mechanical force application contributes to periodontal tissue reconstruction. Graphical abstract PDLSCs modulate periodontal tissue remodeling under appropriate mechanical stimulation through TRPC6; however, under excessive stress, alveolar bone and tooth roots are readily absorbed. Under this condition, environmental factors play a leading role, and the regulatory effect of TRPC6 is not obvious.

Abstract Background Orthodontic treatment is commonly more time-consuming in adults than in teenagers, especially when it comes to the maxillary en-masse retraction, which may take 9 months or even longer. As to solve this concern, orthodontists have been striving to seek new methods for shortening orthodontic treatment time. Piezocision, as a popular alternative treatment, has been widely used in different types of tooth movement. However, its effect on en-masse retraction of maxillary anterior teeth remains unclear. This randomized controlled trial intends to figure out the role piezocision plays in accelerating en-masse retraction. Methods This protocol is designed for a prospective, single-center, assessor-blinded and parallel-group randomized controlled trial. Twenty adult patients aged from 18 to 40 whose orthodontic treatment required bilateral maxillary first premolars extraction will be randomly assigned to the piezocision group and the control group at a ratio of 1:1. The piezocision group will undergo en-masse retraction immediately after the piezo surgery, while the control group will start en-masse retraction directly. Both groups will be followed up every 2 weeks to maintain the retraction force until the end of space closure. The space closing time is set as the primary endpoint. Meanwhile, the secondary endpoints include the change of root length, labial and palatal alveolar bone thickness, vertical bone height, probing depth of maxillary anterior teeth, cephalometric measurements, visual analogue scale, and postoperative satisfaction questionnaire. Discussion This study will attempt to provide more convincing evidence to verify whether piezocision will shorten the time of en-masse retraction or not. Distinguished with previous studies, our study has made some innovations in orthodontic procedure and primary outcome measurement, aiming to clarify the efficacy and safety of piezocision-assisted en-masse retraction in Chinese population. Trial registration Chinese Clinical Trial Registry ChiCTR 1900024297 . Registered on 5 July 2019

IntroductionLeveraging deep learning in the radiology community has great potential and practical significance. To explore the potential of fitting deep learning methods into the current Liver Imaging Reporting and Data System (LI-RADS) system, this paper provides a complete and fully automatic deep learning solution for the LI-RADS system and investigates its model performance in liver lesion segmentation and classification.MethodsTo achieve this, a deep learning study design process is formulated, including clinical problem formulation, corresponding deep learning task identification, data acquisition, data preprocessing, and algorithm validation. On top of segmentation, a UNet++-based segmentation approach with supervised learning was performed by using 33,078 raw images obtained from 111 patients, which are collected from 2010 to 2017. The key innovation is that the proposed framework introduces one more step called feature characterization before LI-RADS score classification in comparison to prior work. In this step, a feature characterization network with multi-task learning and joint training strategy was proposed, followed by an inference module to generate the final LI-RADS score.ResultsBoth liver segmentation and feature characterization models were evaluated, and comprehensive statistical analysis was conducted with detailed discussions. Median DICE of liver lesion segmentation was able to achieve 0.879. Based on different thresholds, recall changes within a range of 0.7 to 0.9, and precision always stays high greater than 0.9. Segmentation model performance was also evaluated on the patient level and lesion level, and the evaluation results of (precision, recall) on the patient level were much better at approximately (1, 0.9). Lesion classification was evaluated to have an overall accuracy of 76%, and most mis-classification cases happen in the neighboring categories, which is reasonable since it is naturally difficult to distinguish LI-RADS 4 from LI-RADS 5.DiscussionIn addition to investigating the performance of the proposed model itself, extensive comparison experiment was also conducted. This study shows that our proposed framework with feature characterization greatly improves the diagnostic performance which also validates the effectiveness of the added feature characterization step. Since this step could output the feature characterization results instead of simply generating a final score, it is able to unbox the black-box for the proposed algorithm thus improves the explainability.

Abstract Background Previous studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service. Methods We used routine health insurance claims data (N = 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization. Results Retirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 – 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 – -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 – 0.12) and primary hospital visits (0.06, 95% CI 0.02 – 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay). Conclusions Retirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.

Abstract Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC–MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 μg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.

ContextTumor-associated cutaneous vascular disorder induced by PPGL was extremely rare, and the cutaneous manifestations could disappear after removal of the tumors. However, the definite pathological diagnosis and the potential mechanism remained unidentified. We presented a severe cutaneous vascular lesion manifested as diffuse erythema with ulceration and necrosis over the limbs in a female patient with metastatic paraganglioma. Skin biopsy was performed on her for defining the pathological diagnosis and potential mechanism. The patient was diagnosed as vascular disease according to the obvious angioectasia in dermis on cutaneous pathology, which might be caused by PPGL-induced hypercoagulability. We used the antiplatelet therapy with aspirin to treat the PPGL-associated cutaneous vascular disease for the first time, and the cutaneous lesions were relieved and healed gradually, further supporting the diagnosis of vascular disease.ConclusionFor metastatic PPGL patients like the case we reported, the definite diagnosis by skin biopsy and the early antiplatelet therapy might be effective to the cutaneous lesions caused by the hypercoagulable state of PPGL.

Summary: Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020–2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].

Liposomes are the earliest and most widely used nanoparticles for targeted drug delivery. Exosomes are nanosized membrane-bound particles and important mediators of intercellular communication. Combining liposomes and exosomes using various membrane fusion methods gives rise to a novel potential drug delivery system called membrane fusion-based hybrid exosomes (MFHE). These novel MFHEs not only exhibit potential advantageous features, such as high drug loading rate and targeted cellular uptake via surface modification, but are also endowed with high biocompatibility and low immunogenicity. Here, we provide an overview of MFHEs’ various preparation methods, characterization strategies, and their applications for disease treatment and scientific research.

BackgroundKIT is a proto-oncogene that is involved in the proliferation, survival, and regulation of melanocytes, mast cells, and the interstitial cells of Cajal. Mutations of KIT have been reported to be associated with hyperpigmentation and lentigines, mastocytosis, and gastrointestinal stromal tumors (GISTs). Some hotspot mutations of KIT have been reported to be associated with mastocytosis and GISTs, while the relationship between KIT mutations and hyperpigmentation and lentigines has not been fully elucidated.MethodsIn this study, we presented a three-generation Chinese pedigree with progressive hyperpigmentation and generalized lentigines inherited in an autosomal dominant pattern. High-throughput sequencing was performed to capture genetic variations in peripheral blood samples of the proband. Also, Sanger sequencing was performed to further verify the result. We also reviewed previous literature on KIT mutations with hyperpigmentation and lentigines.ResultsA missense mutation of the KIT gene was identified: c. 2485G > C, which was co-segregated in the proband and his insulted father. Germline KIT mutations presenting as generalized hyperpigmentation and lentigines without systemic disorders are rare, with only two reports of c. 2485G > C mutation associated with this phenotype in previous literature.ConclusionOur pedigree, together with those two reports, indicates a possible phenotype-genotype correlation of this germline KIT mutation, which might be helpful for genetic counseling, further functional segregation of KIT, and design of targeted therapy in the future.

Background: Gap junctions formed by connexins are channels on cytoplasm functioning in ion recycling and homeostasis. Some members of connexin family including connexin 31 are significant components in human skin and cochlea. In clinic, mutations of connexin 31 have been revealed as the cause of a rare hereditary skin disease called erythrokeratodermia variabilis (EKV) and non-syndromic hearing loss (NSHL).Objective: To determine the underlying genetic cause of EKV, ichthyosis and NSHL in three members of a Chinese pedigree and skin histologic characteristics of the EKV patient.Methods: By performing whole exome sequencing (WES), Sanger sequencing and skin biopsy, we demonstrate a Chinese pedigree carrying a mutation of GJB3 with three patients separately diagnosed with EKV, ichthyosis and NSHL.Results: The proband, a 6-year-old Chinese girl, presented with demarcated annular red-brown plaques and hyperkeratotic scaly patches on her trunk and limbs. Her mother has ichthyosis with hyperkeratosis and geographic tongue while her younger brother had NSHL since birth. Mutation analysis revealed all of them carried a heterozygous missense mutation c.293G>A of GJB3. Skin biopsy showed many grain cells with dyskeratosis in the granular layer. Acanthosis, papillomatosis, and a mild superficial perivascular lymphocytic infiltrate were observed.Conclusion: A mutation of GJB3 associated with EKV, ichthyosis and NSHL is reported in this case. The daughter with EKV and the son with NSHL in this Chinese family inherited the mutation from their mother with ichthyosis. The variation of clinical features may involve with genetic, epigenetic and environmental factors.

Abstract Background Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib. Methods A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib. Results Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement. Conclusions We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.

Raw coal is used by many suburban and rural households for cooking and heating and results in severe air pollution, especially problematic SO2 emissions. A source treatment strategy was proposed to reduce SO2 emissions, which used the co-pyrolysis of raw coal with a CaCO3 additive to produce clean coke. The effect of Ca/S molar ratio on the SO2 capture efficiency of clean coke was investigated, and the SO2 retention efficiency was optimized at a Ca/S molar ratio of 1.5. The sulfur retention mechanism of clean coke was attributed to: (1) CaCO3 decomposition to CaO and partial reaction of CaO with H2S to generate CaS during pyrolysis. (2) Transformation of the remaining sulfur in the clean coke to SO2 during combustion, capture by unreacted CaO to form CaSO4, and direct oxidation of CaS to CaSO4. The feasibility of SO2 emission reduction by clean coke in a practical household stove was verified.

Silk fibroin is regarded as a promising biomaterial in various areas, including bone tissue regeneration. Herein, Laponite® (LAP), which can promote osteogenic differentiation, was introduced into regenerated silk fibroin (RSF) to prepare an RSF/LAP hybrid hydrogel. This thixotropic hydrogel is injectable during the operation process, which is favorable for repairing bone defects. Our previous work demonstrated that the RSF/LAP hydrogel greatly promoted the osteogenic differentiation of osteoblasts in vitro. In the present study, the RSF/LAP hydrogel was found to have excellent biocompatibility and significantly improved new bone formation in a standard rat calvarial defect model in vivo. Additionally, the underlying biological mechanism of the RSF/LAP hydrogel in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was extensively explored. The results indicate that the RSF/LAP hydrogels provide suitable conditions for the adhesion and proliferation of BMSCs, showing good biocompatibility in vitro. With the increase in LAP content, the alkaline phosphatase (ALP) activity and mRNA and protein expression of the osteogenic markers of BMSCs improved significantly. Protein kinase B (AKT) pathway activation was found to be responsible for the inherent osteogenic properties of the RSF/LAP hybrid hydrogel. Therefore, the results shown in this study firmly suggest such an injectable RSF/LAP hydrogel with good biocompatibility (both in vitro and in vivo) would have good application prospects in the field of bone regeneration.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.

Nonribosomal peptides (NRPs) and polyketides (PKs) have widely been widely applied in clinical drugs in use today, and one of the main sources for novel NRPs and PKs is soil microbes. However, the diversity of soil bacteria and distribution of their NRPs and PKs biosynthetic genes in different landscapes in extreme environments have not been reported. In this study, 16S rRNA gene fragments from five landscape belts in Changbaishan were analyzed. The results demonstrated that Acidobacteria, Proteobacteria and Chloroflexi accounted for 65% of all bacterial species. Furthermore, the diversities of the PKs and NRPs in the different landscape belts of Changbaishan were compared based on the diversity of gene fragments of the polyketide synthase (PKs) ketosynthase (KS) domain and nonribosomal peptide synthetase (NRPs) adenylation domain (AD). The results showed that NRPs and PKs had highest richness in alpine tundra and birch forest belts, which were negatively correlated with the contents of the available phosphorus, nitrogen, calcium, potassium, and soil organic matter. NRPs and PKs mainly existed in unidentified bacteria, Proteobacteria and Actinobacteria. In addition, a 16S rRNA KEGG pathway analysis showed that the soil microorganisms of Changbaishan have the potential to promote secondary metabolite biosynthesis, resist diseases and regulate immune systems. These combined results suggest that soils of alpine tundra and birch forest belts in Changbaishan may be the main sources for searching the novel antibacterial drugs.

Abstract Background Pediatric obstructive sleep apnea/hypopnea syndrome (OSAHS) is a multifactorial syndrome caused by many risk factors, such as craniofacial anomalies, adenotonsillar hypertrophy, obesity, and airway inflammation. Although new treatment patterns have recently been proposed, treatment methods for children remain particularly challenging and controversial. This randomized controlled trial was designed to investigate the efficacy of adenotonsillectomy and/or orthodontic treatment for children who have mild OSAHS with mandibular retrognathia. Methods A sample of 352 children with mild OSAHS and mandibular retrognathia, who are aged between 7 and 10 years, will be enrolled in the study. They will be randomized into four groups: the drug treatment group, the surgical treatment group, the orthodontic treatment group, or the surgery and postoperative orthodontic group. After randomization the children will receive treatments within 4 weeks. Outcome assessment will take place at the following points: (1) baseline, (2) 7 months after the treatment starting point, (3) 12 months after the treatment starting point, and (4) 24 months after the treatment starting point. The primary endpoint of the trial is the mean change in obstructive apnea/hypopnea index. Other endpoints will consist of the lowest oxygen saturation, apnea index, and hypopnea index assessed by polysomnography, subjective symptoms (assessed by the OSA-20 questionnaire), cephalometric measurements, and morphologic analysis of the upper airway. Discussion The results of this study will provide valuable evidence for the merits and long-term efficacy of different treatment approaches and contribute to facilitating the multidisciplinary treatment of pediatric OSAHS. Trial registration ClinicalTrials.gov : NCT03451318. Registered on 2 March 2018 (last update posted 19 April 2018).

Severe hyperdivergent skeletal Class II malocclusion may be ideally treated with orthognathic surgery in adult patients. Here, we report a camouflage treatment of a 23-year-old female patient. She was diagnosed with a skeletal Class II malocclusion with extreme high mandibular plane angle, retrusive mandible, steep posterior occlusal plane, anterior open bite, and severe overjet. The treatment plan included extraction of all second premolars and intrusion of the maxillary anterior teeth and mandibular posterior teeth using miniscrews. These contributed to an effective counterclockwise rotation of the mandible, decreased lower face height, and improvement in anterior overbite. This case report shows a vertical control strategy on severe hyperdivergent skeletal Class II malocclusions, which achieves well-controlled sagittal and vertical dimensions and a favorable facial appearance. The treatment and retention results were well balanced and aesthetically pleasing.

BackgroundPolyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic disease with a high prevalence of skin symptoms. Few studies have focused on skin responses to systemic treatment of this disease.ObjectiveTo evaluate skin responses after treatment with low-dose lenalidomide plus dexamethasone and determine their relationship with vascular endothelial growth factor (VEGF) and hematological responses.MethodsA total of 41 consecutive Chinese patients who were at least 18 years of age with newly diagnosed POEMS syndrome were enrolled. 36 of them completed 12 cycles of treatment. Skin, serum VEGF, hematological and neurological responses were documented at 1, 2, 3, 6, 9, and 12 months during treatment.ResultsSkin manifestations were not associated with serum VEGF levels at baseline. Of the patients with hyperpigmentation, hemangiomas, hypertrichosis, white nails, or acrocyanosis separately, 26/34 (76.5%), 11/30 (36.7%), 14/15 (93.3%), 21/21 (100%), and 4/4 (100%) achieved complete responses at 12 months. Reduction in hyperpigmentation after 12 months reflected a good VEGF response (P = 0.017).ConclusionLow-dose lenalidomide plus dexamethasone therapy is effective in reversing skin changes in patients with POEMS syndrome.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT01816620

Wolf’s isotopic response refers to the occurrence of a new skin disease at the exact site of an unrelated skin disease that had previously healed. Various cutaneous lesions have been described after herpes zoster. This study included 24 patients with Wolf’s isotopic response after herpes zoster infection, which presented as manifestations ranging from inflammatory disease to carcinoma. Histopathological examinations in 12 patients and immunohistochemical analyses in 10 patients allowed exploration of secondary microscopic changes in the lesions. CD4+/CD8+ T-cell ratios were normal and infiltrating cells included mast cells, eosinophils, and tumour cells. Our study has described additional patients with confirmed Wolf’s isotopic response following herpes zoster infection; moreover, it has extended the spectrum of Wolf’s isotopic response to include impetigo. We suggest Wolf’s isotopic response classification categories for herpes zoster-associated Wolf’s isotopic response. Additionally, clinicians should consider the possibilities of different diseases in Wolf’s isotopic response, especially malignancies.

This study examined the regulation of phenotype and function of natural killer (NK) cells by nasopharyngeal carcinoma (NPC) cells with metastasis-associated in colon cancer-1 (MACC1) overexpression. Thirty patients with NPC and 20 healthy subjects were included. Peripheral blood (5 mL) was collected, and NK cells were purified using Ficoll and negative separation. NPC HONE1 cells were transfected with pcDNA3.1-MACC1 or negative control plasmids, and culture supernatant was collected for co-culture with NK cells. Flow cytometry was used to determine the expression of activated and inhibitory receptors on the cells. Western blotting was used to determine the expression of proteins. The results showed that the ratio of NK cells in the peripheral blood of NPC patients was elevated, but the activity and tumor-killing effect of NK cells were reduced. MACC1 promoted the escape of HONE1 cells from killing by NK cells. HONE1 with overexpression of MACC1 down-regulated the expression of NKG2D in NK cells, inhibited the proliferation of NK cells and escaped the immune surveillance by NK cells. MACC1 down-regulated the expression of NKG2D in NK cells by up-regulating the expression of TGF-β1 in HONE1 cells, thereby inhibiting the activity of NK cells. MACC1 inhibited the cell cycle of NK cells via TGF-β1 pathway. The study demonstrated that MACC1 elevated the expression of TGF-β1 by NPC HONE1 cells, thereby inhibiting NKG2D expression and G1/S transition in NK cells. MACC1 helped NPC HONE1 cells avoid killing by NK cells.

Objectives: To assess associations between short-time air pollution exposure and outpatient visits for pneumonia by the distributed lag nonlinear model (DLNM). Methods: Daily outpatient visits for pneumonia and air pollutant data were collected from Wuhan Basic Medical Insurance Database in China and 10 national air quality monitoring stations in Wuhan from 2014 to 2017, respectively. Taking the first percentile of the concentration as the reference, DLNM was used to estimate the impact of moderate (50th) and high levels (99th) of pollutants on pneumonia. Results: A total of 133,882 outpatient visits were identified during the period of the study. Moderate-level (P50) fine particulate matter (PM2.5) or sulfur dioxide (SO2) and high-level nitrogen dioxide (NO2) (P99) can increase the risk of pneumonia. The maximum RR was 1.198 (95% CI: 1.094–1.311) at lag0-11, 1.304 (95% CI: 1.166–1.458) at lag0-13, and 1.286 (95% CI: 1.060–1.561) at lag0-14, respectively. Females and children had greater risks. Conclusions: Short-time PM2.5, SO2, and NO2 exposure were associated with outpatient visits for pneumonia in Wuhan, China.

The feeding behaviour of cows is an essential sign of their health in dairy farming. For the impression of cow health status, precise and quick assessment of cow feeding behaviour is critical. This research presents a method for monitoring dairy cow feeding behaviour utilizing edge computing and deep learning algorithms based on the characteristics of dairy cow feeding behaviour. Images of cow feeding behaviour were captured and processed in real time using an edge computing device. A DenseResNet-You Only Look Once (DRN-YOLO) deep learning method was presented to address the difficulties of existing cow feeding behaviour detection algorithms’ low accuracy and sensitivity to the open farm environment. The deep learning and feature extraction enhancement of the model was improved by replacing the CSPDarknet backbone network with the self-designed DRNet backbone network based on the YOLOv4 algorithm using multiple feature scales and the Spatial Pyramid Pooling (SPP) structure to enrich the scale semantic feature interactions, finally achieving the recognition of cow feeding behaviour in the farm feeding environment. The experimental results showed that DRN-YOLO improved the accuracy, recall, and mAP by 1.70%, 1.82%, and 0.97%, respectively, compared to YOLOv4. The research results can effectively solve the problems of low recognition accuracy and insufficient feature extraction in the analysis of dairy cow feeding behaviour by traditional methods in complex breeding environments, and at the same time provide an important reference for the realization of intelligent animal husbandry and precision breeding.

Abstract Background Hailey–Hailey disease (HHD; OMIM: 169600) is an autosomal dominate genodermatosis, characterized by recurrent blisters and erosions clinically and remarkable acantholysis pathologically. The underlying pathogenic factor is the mutation of ATP2C1 gene (OMIM: 604384), which encodes secretory pathway Ca2+/Mn2+‐ATPase (SPCA1). Skin folds are the predilection site of HHD. Atypical cases with a generalized pattern have rarely been reported, making it prone to misdiagnosis. Methods In this study, we presented three Chinese pedigrees of Hailey–Hailey disease with generalized skin lesions. ATP2C1 mutations were screened by DNA sequencing and their transcripts were further confirmed by minigene assay. We also performed a literature review of previously published generalized HHD over past two decades together with our cases. Results Three splice‐site mutations were identified: c.2487+1G>A, c.2126+1G>A, and c.1891‐2A>G, which resulted in an exon 25‐truncated transcript, two exon 22‐truncated transcripts, and two exon 21‐truncated transcripts, respectively. The c.2487+1G>A and the c.1891‐2A>G mutations are novel mutations which have not been reported before. No clustered mutations of ATP2C1 gene were found in generalized HHD patients in literature along with our novel mutations. Conclusion We found no hot spot mutations in ATP2C1 correlated with the generalized pattern of HHD. Our study expanded the spectrum of ATP2C1 mutations, which would be useful for disease diagnosis and genetic counseling.

This study reported about the fabrication of dentin non-collagenous proteins (dNCPs) polyelectrolyte multilayers and evaluated its osteogenic potential. The composite sandwich structure of dNCPs polyelectrolyte multilayers was generated on the surface of polycaprolactone electrospinning membranes by the Layer-by-Layer self-assembly technique. The dNCPs-coated membranes comprised the experimental group and the non-coated membranes acted as the control. Nanofiber morphologies of both membranes were observed under scanning electron microscope. The release of dNCPs was evaluated by ELISA kit. Periodontal ligament stem cells (PDLSCs) were seeded on both membranes. The morphology changes and proliferation of cells were tested. The expressions of osteogenic-related genes and proteins were evaluated by RT-PCR, alkaline phosphatase (ALP) activity assay, and immunofluorescence staining. dNCPs-coated membranes displayed significantly different fiber morphology than the non-coated membranes. A stable release of dentin phosphoprotein was maintained from day 4 to day 15 in the experimental group. Cells on dNCPs-coated membranes were found to have cuboidal or polygonal shapes. The proliferative rate of cells was significantly lower in the experimental group from day 4 to day 9 ( p

Abstract Background Acromicric dysplasia is a rare heritable short‐stature syndrome with joint stiffness and varying degrees of cutaneous hardness. Stiff skin syndrome is a rare connective tissue disorder characterized by diffusely thick and hard skin from the time of birth. Heterozygous point mutations in the FBN1 have been proposed as the predominant cause of both diseases. Methods By performing skin biopsy, X‐ray imaging, electrocardiography, as well as whole‐genome sequencing and Sanger sequencing, we diagnosed an 8‐year‐old Chinese boy as acromicric dysplasia with severe skin stiffness caused by a heterogeneous mutation in the FBN1. Results The patient presented with skin tightness, wrist and ankle stiffness, short stature and limbs, several deformed joints in the extremities, cone‐shaped epiphyses, and distinct facial features. He also had a patent foramen ovale and frequent respiratory infections. Skin biopsy showed thickened dermis and excessive collagen aggregation. Alcian blue staining indicated dermal mucopolysaccharide deposition. Mutation analysis revealed a heterozygous missense mutation, c.5243G>A (p.Cys1748Tyr), in exon 42 of the FBN1. Conclusion This is a report about acromicric dysplasia with stiff skin syndrome‐like severe cutaneous presentation caused by a single hotspot mutation, further revealing the gene pleiotropy of FBN1.

Abstract: Background: Myeloid leukemia cutis is the terminology used for cutaneous manifestations of myeloid leukemia. Objective: The purpose of this study was to study the clinical, histopathological and immunohistochemical features of myeloid leukemia cutis. Methods: This was a retrospective study of clinical and pathological features of 10 patients with myeloid leukemia cutis. Results: One patient developed skin lesions before the onset of leukemia, seven patients developed skin infiltration within 4-72 months after the onset of leukemia, and two patients developed skin lesions and systemic leukemia simultaneously. Of these patients, five presented with generalized papules or nodules, and five with localized masses. The biopsy of skin lesions showed a large number of tumor cells within the dermis and subcutaneous fat layer. Immunohistochemical analysis showed strong reactivity to myeloperoxidase (MPO), CD15, CD43 and CD45 (LCA) in most cases. NPM1 (nucleophosmin I) and FLT3-ITD (Fms-like tyrosine kinase 3-internal tandem duplication) mutations were identified in one case. Five patients with acute myelogenous leukemia and one patient with chronic myelomonocytic leukemia died within two months to one year after the onset of skin lesions. Study limitations: This was a retrospective and small sample study. Conclusions: In patients with myelogenous leukemia, skin infiltration usually occurs after, but occasionally before, the appearance of hemogram and myelogram abnormalities, and the presence of skin infiltration is often associated with a poor prognosis and short survival time. myeloid leukemia cutis often presents as generalized or localized nodules or masses with characteristic pathological and histochemical findings.

Surface-Enhanced Raman Scattering (SERS) is a powerful technology that provides abundant chemical fingerprint information with advantages of high sensitivity and time-saving. Advancements in SERS substrates fabrication allow Ag nanorods (AgNRs) possess superior sensitivity, high uniformity, and excellent reproducibility. To further promote AgNRs as a promising SERS substrate candidate to a broader application scope, oxides are integrated with AgNRs by virtue of their unique properties which endow the AgNRs-oxide hybrid with high stability and recyclability. Aside from SERS substrates fabrication, significant developments in quantitative analysis strategies offer enormous approaches to minimize influences resulted from variations of measuring conditions and to provide the reasonable data analysis. In this review, we discuss various fabrication approaches for AgNRs and AgNRs-oxide hybrids to achieve efficient SERS platforms. Then, we introduce three types of strategies which are commonly employed in chemical quantitative analysis to reach a reliable result. Further, we highlight SERS applications including food safety, environment safety, biosensing, and vapor sensing, demonstrating the potential of SERS as a powerful and promising technique. Finally, we conclude with the current challenges and future prospects toward efficient SERS manipulations for broader real-world applications.