A soft microrobot with highly deformable 3D actuators for climbing and transitioning complex surfaces.

The climbing microrobots have attracted growing attention due to their promising applications in exploration and monitoring of complex, unstructured environments. Soft climbing microrobots based on muscle-like actuators could offer excellent flexibility, adaptability, and mechanical robustness. Despite the remarkable progress in this area, the development of soft microrobots capable of climbing on flat/curved surfaces and transitioning between two different surfaces remains elusive, especially in open spaces. In this study, we address these challenges by developing voltage-driven soft small-scale actuators with customized 3D configurations and active stiffness adjusting. Combination of programmed strain distributions in liquid crystal elastomers (LCEs) and buckling-driven 3D assembly, guided by mechanics modeling, allows for voltage-driven, complex 3D-to-3D shape morphing (bending angle > 200°) at millimeter scales (from 1 to 10 mm), which is unachievable previously. These soft actuators enable development of morphable electroadhesive footpads that can conform to different curved surfaces and stiffness-variable smart joints that allow different locomotion gaits in a single microrobot. By integrating such morphable footpads and smart joints with a deformable body, we report a multigait, soft microrobot (length from 6 to 90 mm, and mass from 0.2 to 3 g) capable of climbing on surfaces with diverse shapes (e.g., flat plane, cylinder, wavy surface, wedge-shaped groove, and sphere) and transitioning between two distinct surfaces. We demonstrate that the microrobot could navigate from one surface to another, recording two corresponding ceilings when carrying an integrated microcamera. The developed soft microrobot can also flip over a barrier, survive extreme compression, and climb bamboo and leaf.

[Developments in Research on Salivary Biomarkers in the Diagnosis of Systemic Diseases].

Saliva, an important biological fluid secreted by oral glands, serves multiple functions. It performs cleaning and protective functions for oral tissues, safeguarding against biological, mechanical and chemical stimuli, while allowing for the sensory perception of taste and temperature. It is also responsible for the preliminary digestion of food. These functions and properties of saliva are attributed to the presence of electrolytes, buffers, proteins, glycoproteins, and lipids in saliva. Recent studies have found that saliva contains biomarkers that are closely connected with the pathophysiological status of the human body, suggesting that saliva makes an ideal biological fluid for drug monitoring and biomarker screening. Therefore, salivary biomarkers can be used as an instrument for physical monitoring and localization of the occurrence of diseases, thereby accomplishing early diagnosis of diseases and assessment of the overall health status of patients. However, the actual application of salivary biomarkers in the diagnosis and treatment of systemic diseases is still not widely available, and the establishment of evaluation criteria and the exploration of its mechanism are not sufficiently investigated. Herein, we reviewed the latest research findings on applying the salivary biomarkers in the diagnosis of systemic diseases.

TfR-T12 short peptide and pH sensitive cell transmembrane peptide modified nano-composite micelles for glioma treatment via remodeling tumor microenvironment.

Two kinds of amphiphilic block copolymers of TfR-T12-PEG-PLGA and TATH7-PEG-PLGA were synthesized to self-assembly nano-composite micelles for encapsulating paclitaxel and imiquimod synchronously. TfR-T12 peptide modified nano-composite micelles can pass through BBB in a TfR-mediated way to achieve targeted delivery of chemotherapeutic drugs, and pH sensitive TATH7 peptide modified nano-composite micelles enhanced uptake efficiency more significantly under pH 5.5 medium than pH 7.4 medium. The results of pharmacodynamic evaluation in vivo showed that the nano-composite micelles had achieved good anti-tumor effect in subcutaneous and normotopia glioma models, and effectively prolonged the life cycle of tumor-bearing mice. The nano-composite micelles regulated the immunosuppression phenomenon of tumor microenvironment significantly, and promoted the M1 polarization of TAMs, then enhanced the proliferation and activation of CD8+ T cells in tumor microenvironment. It comes to conclusion that the nano-composite micelle achieves the purpose of effective treatment of glioma by chemotherapy combined with immunotherapy.

[Research Updates: Relationship between Gingival Epithelial Intercellular Junctions and Periodontal Pathogenic Bacteria].

Gingival epithelial barrier is the first line of defense of periodontal tissues against the invasion of pathogenic bacteria. The destruction of gingival epithelial barrier is closely related to the development of periodontal disease. Studies have shown that periodontal pathogenic bacteria and their inflammatory microenvironment can inhibit the expression of gingival epithelial junctional proteins via molecular mechanisms such as the downregulation of the expression of grainyhead-like protein family and the upregulation of the methylation level of gene promoter of epithelial connexin, and thus cause damage to the gingival epithelial barrier and the development of periodontitis. We herein reviewed the effects of bacteria and inflammatory factors induced by bacterial infection on gingival epithelial intercellular junctions and related mechanisms, and summarized the research progress on the relationship between gingival epithelial intercellular junctions and periodontal pathogenic bacteria in recent years. Most recent studies were focused on i n vitro cytological experiments and animal models of infections caused by a single kind of bacterium. We have suggested that building gingival epithelial organoid model and combining multi-omics approaches with high resolution three-dimensional electron microscopy are expected to help pinpoint the key microorganisms and their most important virulence factors that trigger periodontal microecologcal imbalance and cause functional damage to the gingival epithelial barrier, to reveal the key molecular mechanisms involved in the maintenance and destruction of gingival epithelial barrier function, and to provide new perspectives on the pathogenesis and the clinical prevention and treatment of periodontitis.

[Latest Research Findings on Health Management Based on Saliva Testing].

Being one of the most important exocrine fluids of the human body, saliva can reflect the health status of the body. Soliva collection has various advantages--it is simple, painless, fast, and safe, and soliva can be collected multiple times a day. Therefore, it has been gradually applied in the exploration for biomarkers for disease detection, providing a basis for the monitoring of the course of diseases, medication monitoring, and efficacy evaluation. We should implement health management based on saliva testing, collect the medical data of the healthy and diseased individuals and monitor their whole life cycle health, perform clinical cohort study, aggregate the data on platforms for big data on health and medicine, manage and provide guidance for the health status of populations, pinpoint the high-risk factors for pathogenesis, and provide effective intervention, early warning, and assessment of the vital signs of individuals, thereby reinforcing health management of the whole life cycle and safeguarding people's health in an all-round way. In addition, it drives the development of the health industry and bears strategic significance for the promotion of national economic development. It is becoming a hot research topic promising great potential and impressive applicational prospects. Herein, we reviewed new techniques for clinical saliva testing and health management based on saliva testing.

Well-Defined DNA-Polymer Miktoarm Stars for Enzyme-Resistant Nanoflares and Carrier-Free Gene Regulation.

Herein, we report a star-architectured poly(ethylene glycol) (PEG)-oligonucleotide nanoconjugate of a well-defined molecular structure. Based upon fullerene C60 cores, each star bears precisely 1 DNA strand and 11 polymer chains. The elevated PEG density provides the DNA with steric selectivity: the DNA is significantly more resistant to nuclease digestion while remaining able to hybridize with a complementary sequence. The degree of resistance increases as the centers of mass for the DNA and fullerene are closer together. Such steric selectivity reduces protein-related background signals of the nanoflares synthesized from these miktoarm star polymers. Importantly, the stars improve cellular uptake and regulate gene expression as a non-cytotoxic, single-entity antisense agent without the need for a transfection carrier.

Identification of Saliva Proteins of the Spider Mite Tetranychus evansi by Transcriptome and LC-MS/MS Analyses.

The spider mite Tetranychus evansi has a remarkable ability to suppress and manipulate plant defenses, which makes it an ideal model to investigate plant-herbivores interactions. In this study, a de novo assembly of the transcriptome of T. evansi is performed and the proteins in its secreted saliva by LC-MS/MS are characterized. A total of 29 365 unigenes are assembled and 136 saliva proteins are identified. Comparative analysis of the saliva proteins in T. evansi, T. truncatus, and T. urticae shows that 64 protein groups are shared by at least two Tetranychus species, and 52 protein groups are specifically identified in T. evansi. In addition, some saliva proteins are common in arthropod species, while others are species-specific. These results will help to elucidate the molecular mechanisms by which T. evansi modulates plant defenses.

Protection Effect of Curcumin for Macrophage-Involved Polyethylene Wear Particle-Induced Inflammatory Osteolysis by Increasing the Cholesterol Efflux.

BACKGROUND Periprosthetic osteolysis, induced by wear particles and inflammation, is a common reason for failure of primary arthroplasty. Curcumin, a nature phenol from plants, has been reported to reduce the inflammation in macrophages. This study aimed to investigate the potential effect of curcumin on macrophage involved, wear particle-induced osteolysis and its mechanism. MATERIAL AND METHODS RAW264.7 macrophages were used to test the effects of polyethylene (PE) particles and curcumin on macrophage cholesterol efflux and phenotypic changes. A mouse model of PE particle-induced calvarial osteolysis was established to test the effects of curcumin in vivo. After 14 days of treatment, the bone quality of the affected areas was analyzed by micro-computed tomography (micro-CT) and histology, and the bone surrounding soft tissues were analyzed at the cellular and molecular levels. RESULTS We found that PE particles can stimulate osteoclastogenesis and produce an M1-like phenotype in macrophages in vitro. Curcumin enhanced the cholesterol efflux in macrophages, and maintained the M0-like phenotype under the influence of PE particles in vitro. Additionally, the cholesterol transmembrane regulators ABCA1, ABCG1, and CAV1 were enhanced by curcumin in vivo. We also found enhanced bone density, reduced osteoclastogenesis, and fewer inflammatory responses in the curcumin treated groups in our mouse osteolysis model. CONCLUSIONS Our study findings indicated that curcumin can inhibit macrophage involved osteolysis and inflammation via promoting cholesterol efflux. Maintaining the cholesterol efflux might be a potential strategy to prevent periprosthetic osteolysis after total joint arthroplasty surgery.

Detection of the Assembly and Disassembly of PCV2b Virus-Like Particles Using Fluorescence Spectroscopy Analysis.

Monitoring the assembly and disassembly of virus-like particles (VLPs) is important in developing effective VLP-based vaccines. We tried to establish a simple and rapid method to evaluate the status of VLP assembly using fluorescence spectroscopic analysis (FSA) while developing a VLP-based vaccine against porcine circovirus type 2b (PCV2b). We synthesized the gene coding for PCV2b capsid protein (CP). The CP was expressed in Escherichia coli in a soluble form, dialyzed into three different buffers, and assembled into VLPs. The immunogenicity of the VLPs was evaluated by an enzyme-linked immunosorbent assay using the sera of mice immunized with inactivated PCV2b. The VLP assembly was detected using transmission electron microscopy and FSA. The assembled VLPs showed a distinct FSA curve with a peak at 320 nm. We found that the assembly status was related to the immunogenicity, fluorescence intensity, and morphology of the VLP. The FSA assay was able to monitor the various denatured statuses of PCV2b VLPs treated with ß-mercaptoethanol or ß-mercaptoethanol plus urea. We have demonstrated that FSA can be used to detect the assembly of PCV2b VLPs produced in E. coli. This provides a simple solution for monitoring VLP assembly during the production of VLP-based vaccines.

Influence of hydrophilic amino acids and GC-content on expression of recombinant proteins used in vaccines against foot-and-mouth disease virus in Escherichia coli.

Epitope-based protein expression in Escherichia coli can be improved by adjusting its amino acid composition and encoding genes. To that end, we analyzed 24 recombinant epitope proteins (rEPs) that carry multiple epitopes derived from VP1 protein of foot-and-mouth disease virus. High level expression of the rEPs was attributed to a high content of Arg, Asn, Asp and Thr, a low content of Gln, Pro and Lys, a high content of hydrophilic amino acids and a higher isoelectric point value resulting from abundant Arg. It is also attributed to the appropriate guanine and cytosine content in the encoding genes. The data provide a reference for adjusting the amino acid composition in designing epitope-based proteins used in vaccines and for adjusting the synonymous codons to improve their expressions in E. coli.

Glass ionomer ART sealant and fluoride-releasing resin sealant in fissure caries prevention--results from a randomized clinical trial.

BACKGROUND: The relative performance of ART sealant and fluoride-releasing resin sealant in preventing fissure caries in permanent molars was compared in a randomized clinical trial conducted in southern China (ClinicalTrials.gov NCT01829334). METHODS: After obtaining ethical approval, healthy schoolchildren who had permanent first molars with occlusal fissures which were sound but deep or presented with only incipient caries were recruited for the study. Included molars were randomly allocated into one of four parallel study groups in units of left/right teeth per mouth. Two of the four groups adopted the methods of ART or fluoride-releasing resin sealant placement while the other two groups adopted the topical fluoride application methods. Fissure status of the molars in each group was evaluated every 6 months. Development of dentine caries and sealant retention over 24 months in the molars in the two sealant-using groups was compared in this report. Outcome on cost-effectiveness of all four groups over 36 months will be reported elsewhere. RESULTS: At baseline, a total of 280 children (383 molars) with mean age 7.8 years were involved for the two sealant groups. After 24 months, 261 children (357 molars) were followed. Proportions of molars with dentine caries were 7.3% and 3.9% in the ART sealant and fluoride-releasing resin sealant groups, respectively (chi-square test, p = 0.171). Life-table survival analysis showed that sealant retention (full and partial) rate over 24 months for the resin sealant (73%) was significantly higher than that (50%) for the ART sealant (p < 0.001). Molar survival (no development of dentine caries) rates in the ART sealant (93%) and fluoride-releasing resin sealant (96%) groups were not significantly different (p = 0.169). Multilevel logistic regression (GEE modeling) accounting for the effects of data clustering and confounding factors confirmed this finding. CONCLUSIONS: Though the retention of fluoride-releasing resin sealant was better than that of the ART sealant, their effectiveness in preventing fissure caries in permanent molars did not differ significantly over 24 months. ART sealants could be a good alternative when and where resources for resin sealant placement are not readily available.

[Fluorosis of coal burning affects the male reproductive system].

Fluorosis of coal burning is a new type of endemic fluorosis in China, which affects the male reproductive system. Furthermore, the content of fluoride in the semen, sperm mortality, sperm concentration and the incidence of infertility are higher in severe fluorosis areas than in mild- and non-fluorosis areas, so are the levels of serum follicle-stimulating hormone and luteinizing hormone. However, the levels of inhibin B, serum testosterone and estradiol show different degrees of reduction in severe fluorosis areas. Accordingly, fluorosis of coal burning, just like other endemic fluorosis, may affect the structure of male reproductive organs, the generation of sperm and reproductive endocrinology, resulting in the decline of men's reproductive ability.

Development of pectin/chitosan-based electrospun biomimetic nanofiber membranes loaded with dihydromyricetin inclusion complexes for wound healing application.

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

[Effects of Combined Stress of High Density Polyethylene Microplastics and Chlorimuron-ethyl on Soybean Growth and Rhizosphere Bacterial Community].

With the vigorous development of agriculture in China， plastic mulch film and pesticides are widely used in agricultural production. However， the accumulation of microplastics （formed by the degradation of plastic mulch film） and pesticides in soil has also caused many environmental problems. At present， the environmental biological effects of microplastics or pesticides have been reported， but there are few studies on the combined effects on crop growth and the rhizosphere soil bacterial community. Therefore， in this study， the high density polyethylene microplastics （HDPE， 500 mesh） were designed to be co-treated with sulfonylurea herbicide chlorimuron-ethyl to study their effects on soybean growth. In addition， the effects of the combined stress of HDPE and chlorimuron-ethyl on soybean rhizosphere soil bacterial community diversity， structure composition， microbial community network， and soil function were investigated using high-throughput sequencing technology， interaction network， and PICRUSt2 function analysis to clarify the combined toxicity of HDPE and chlorimuron-ethyl to soybean. The results showed that the half-life of chlorimuron-ethyl in soil was prolonged by the 1% HDPE treatment （from 11.5 d to 14.3 d）， and the combined stress of HDPE and chlorimuron-ethyl had more obvious inhibition effects on soybean growth than that of the single pollutant or control. The HiSeq 2 500 sequencing showed that the rhizosphere bacterial community of soybean was composed of 20 phyla and 312 genera under combined stress， the number of phyla and genera was significantly less than that of the control and single pollutant treatment， and the relative abundances of bacteria with potential biological control and plant growth-promoting characteristics （such as Nocardioides and Sphingomonas） were reduced. Alpha diversity analysis showed that the combined stress significantly reduced the richness and diversity of the soybean rhizosphere bacterial community， and Beta diversity analysis showed that the combined stress significantly changed the structure of the bacterial community. The dominant flora of the rhizosphere bacterial community were regulated， and the abundances of secondary functional layers such as amino acid metabolism， energy metabolism， and lipid metabolism were reduced under combined stress by the analysis of LEfSe and PICRUSt2. It was inferred from the network analysis that the combined stress of HDPE and chlorimuron-ethyl reduced the total number of connections and network density of soil bacteria， simplified the network structure， and changed the important flora species to maintain the stability of the network. The results above indicated that the combined stress of HDPE and chlorimuron-ethyl significantly affected the growth of soybean and changed the rhizosphere bacterial community structure， soil function， and network structure. Compared with that of the single pollutant treatment， the potential risk of combined stress was greater. The results of this study can provide guidance for evaluating the ecological risks of polyethylene microplastics and chlorimuron-ethyl and for the remediation of contaminated soil.

[Construction and application of virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients].

PURPOSE: To construct a virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients by virtual simulation technology, and to evaluate its application effect. METHODS: Through virtual reality, animation, human-computer interaction and other technologies, a 3D experiment scene based on high simulation virtual human was constructed to reproduce the virtual rescue scenes of craniofacial injury patients, such as emergency reception, first-aid cooperation, massive hemorrhage rescue cooperation, and tracheotomy cooperation in emergency rescue of sudden airway obstruction, and exercise modules and assessment modules were set. In the virtual simulation platform, the students used the holistic nursing theory and the PDCA cycle method to observe, evaluate and care for craniofacial injury patients. Preliminary evaluation of the platform was carried out in the training of 62 dental nurses. RESULTS: The virtual simulation platform could improve students' comprehensive first-aid ability for craniofacial injury patients. The item with the highest satisfaction rate for the virtual simulation platform was the consistency between the content of the virtual simulation platform and the theoretical course (the satisfaction rate was 91.9%), and the lowest satisfaction rate was the convenience of the virtual simulation platform operation and the page setting (the satisfaction rate was 80.6%). The evaluation module of the virtual simulation platform showed that the highest score of the comprehensive evaluation was 97, the lowest score was 56, and the average score was 80.2. CONCLUSIONS: The virtual simulation teaching platform for in-hospital first aid of craniofacial injury patients can create an immersive learning mode, provide an intuitive rescue experience to the students, and improve their comprehensive first-aid ability.

Reducing Target Volumes of Intensity Modulated Radiation Therapy After Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Long-Term Results of a Prospective, Multicenter, Randomized Trial.

PURPOSE: The objective of this study was to estimate the long-term survival, late toxicity profile, and quality of life of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated with combined induction chemotherapy (IC) and concurrent chemoradiotherapy from a clinical trial focused on reducing the target volume of intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: This prospective, randomized clinical trial was conducted across 6 Chinese hospitals and included 212 patients with stage III-IVB NPC who were randomly allocated to a pre-IC or post-IC group. Eligible patients were treated with 2 cycles of IC + CCRT. All patients underwent radical IMRT. Gross tumor volumes of the nasopharynx were delineated according to pre-IC and post-IC tumor extent in the pre-IC and post-IC groups, respectively. RESULTS: After a median follow-up of 98.4 months, 32 of 97 (32.9%) and 33 of 115 (28.7%) patients experienced treatment failure or died in the pre-IC and post-IC groups, respectively. None of the patients developed grade 4 late toxicity. Late radiation-induced toxicity predominantly manifested as grade 1 to 2 subcutaneous fibrosis, hearing loss, tinnitus, and xerostomia, whereas grade 3 late toxicity included xerostomia and hearing loss. The 5-year estimated overall, progression-free, locoregional recurrence-free, and distant metastasis-free survival rates in the pre-IC and post-IC groups were 78.2% versus 83.3%, 72.0% versus 78.1%, 90.2% versus 93.5%, and 78.1% versus 82.1%, respectively. The pre-IC group had a significantly higher incidence of xerostomia and hearing damage than the post-IC group. In terms of quality of life, compared with the pre-IC group, the post-IC group showed significant improvement in cognitive function (P = .045) and symptoms including dry mouth (P = .004), sticky saliva (P = .047), and feeling ill (P = .041). CONCLUSIONS: After long-term follow-up, we confirmed that reducing the target volumes of IMRT after IC in locoregionally advanced NPC showed no inferiority in terms of the risk of locoregional relapse and potentially improved quality of life and alleviated late toxicity.

Clinicopathologic features and molecular analysis of enterovirus 71 infection: report of an autopsy case from the epidemic of hand, foot and mouth disease in China.

A 15-month boy with fatal hand, foot, and mouth disease (HFMD) exhibited atypical symptoms and progressed rapidly to death. An autopsy was performed the next day and tissue sections were stained for histopathological examination. His intestinal samples were tested for enterovirus 71 (EV71), and the whole-genome sequence of EV71 was analyzed. An autopsy revealed that the central nervous system, lungs, and gut displayed severe meningitis and brainstem encephalitis, remarkable pulmonary congestion, edema, moderate inflammatory infiltration, and hemorrhage as well as intestinal mucosal congestion, epithelial necrosis, thinning intestinal wall, and submucosal lymphoid follicular hyperplasia. The heart showed myocardial interstitial congestion, myocardial edema, and some inflammatory infiltrates. There were no significant alterations in the architecture of other organs. EV71 antigen and apoptotic cells were detected in brain, lung and intestine by immunohistochemical staining and TUNEL (TdT-mediated dUTP nick-end labeling) respectively. Intestinal contents and intestinal autopsy samples of this case were positive for EV71, and the EV71 strain was classified as subgenogroup C4. In China, the severe forms of HFMD were mostly caused by EV71 subgenogroup C4 infection. Severe intestinal damages may relate to EV71 subgenogroup C4 infection. Thus, children with severe EV71 HFMD may have serious pathological changes in their central nervous system, lungs, and gut. Physicians should pay special attention to infants with atypical symptoms, particularly in EV71 epidemic areas for early diagnosis and treatment.

[Expression and significance of Treg/Th17 and CD4+/CD8+ T lymphocytes in experimental periodontitis in rats].

PURPOSE: To explore the expression of helper T cell 17/regulatory T cell (Th17/Treg) and CD4+/CD8+ T lymphocyte in experimental periodontitis in rats, and analyze its clinical significance. METHODS: Twenty SPF male SD rats were randomly divided into experimental group (inoculate Porphyromonas gingivalis suspension into gingival sulcus) and control group, with 10 rats in each group. The experimental group was smeared with Porphyromonas gingivalis suspension every other day within 1 week after operation, and the two groups were caged for 8 weeks. After the rats were sacrifical under anesthesia, the jaw tissue of the left maxillary second molar was stained with methylene blue to observe and measure the loss of alveolar bone (ABL). Hematoxylin-eosin (H-E) staining was used to observe the histopathological changes of the jaw. Rat peripheral blood mononuclear cells (PBMC) and T cells were isolated and cultured, Treg, Th17 cells and CD4+, CD8+ T lymphocytes in peripheral blood were detected by flow cytometry. The levels of serum interleukin-17(IL-17), IL-10 and IL-4, INF-γ were detected by enzyme-linked immunosorbent assay (ELISA). Expression changes of retinoic acid related orphan nuclear receptor (RORγt), forkhead wing like transcription factor 3 (Foxp3) and gap junction protein(Cx40) in jaw tissue were detected by Western blot. The data were statistically analyzed by SPSS 19.0 software package. RESULTS: Compared with the control group, ABL, peripheral blood Th17 ratio, Th17/Treg ratio, CD4+ ratio, CD4+/CD8+ T lymphocyte ratio, serum IL-17, IL-10 and IL-4 level, Foxp3 and Cx40 protein in jaw tissue were signifinantly increased in the experimental group(P<0.05), while Treg ratio, INF-γ, RORγt protein in jaw tissue significantly decreased(P<0.05) in the experimental group. CONCLUSIONS: Imbalance of Treg/Th17 and CD4+/CD8+ T lymphocytes leads to the abnormal high expression of inflammatory factors IL-17, IL-10 and IL-4, which may be closely related to the pathogenesis of experimental periodontitis.

Combination and Intermittent Therapy Based on Pegylated Interferon Alfa-2a for Chronic Hepatitis B with Nucleoside (Nucleotide) Analog-Experienced Resulting in Hepatitis B Surface Antigen Clearance: A Case Report.

Interferon (IFN) and nucleoside (nucleotide) analogs (NAs) are two effective antiviral drugs for chronic hepatitis B (CHB). More and more evidence shows that the combination of the two drugs can better inhibit viral replication and even achieve clinical cure. IFN intermittent therapy is also considered to be an important measure to resolve IFN fatigue when hepatitis B surface antigen (HBsAg) decline appears stagnated during IFN-based antiviral therapy. A 36-year-old male NA-experienced patient with hepatitis B e antigen (HBeAg)-positive CHB was admitted to our hospital. After a poor response to tenofovir disoproxil fumarate (TDF) monotherapy for 1 year, the patient was treated with pegylated interferon alfa-2a combination therapy and finally achieved HBsAg clearance. During the treatment and follow-up, HBsAg, HBeAg, hepatitis B virus (HBV) DNA, and serum alanine aminotransferase, etc. were monitored every 3 months. Between weeks 58 and 71 of combination therapy, IFN was discontinued because of a slow decline in HBsAg, and TDF alone was used for maintenance therapy. Complete virological response, HBeAg and HBsAg seroconversion were observed at weeks 44, 96, and 122, respectively. After 24 weeks of consolidation therapy, HBsAg, HBeAg, and HBV DNA were consistently negative, and hepatitis B surface antibody was 729.30 mIU/mL at week 146 of the combination therapy, then we stopped drugs. Following up after 28 weeks of cessation therapy, the patient still remained clinically cured.