BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

OBJECTIVE: To review the research progress on the lower limb biomechanical characteristics of patients with discoid lateral meniscus (DLM) injury after surgery. METHODS: By searching relevant domestic and international research literature on DLM, the postoperative characteristics of knee joint movement biomechanics, tibiofemoral joint stress distribution, lower extremity force line, and patellofemoral joint changes in patients with DLM injury were summarized. RESULTS: Surgical treatment can lead to varying degrees of changes in the lower limb biomechanical characteristics of patients with DLM injury. Specifically, the kinematic biomechanics of the knee joint can significantly improve, but there are still problems such as extension deficits in the affected knee joint. The peak stress of the tibiofemoral joint decreases with the increase of the residual meniscus volume, and the degree of change is closely related to the residual meniscus volume. Preserving a larger volume of the meniscus, especially the anterior horn volume, helps to reduce stress concentration. The lower extremity force line will deviate outward after surgery, and the more meniscus is removed during surgery, the greater the change in the lower extremity force line after surgery. There are conditions such as cartilage degeneration, position and angle changes in the patellofemoral joint after surgery. CONCLUSION The changes in the lower limb biomechanical characteristics after DLM injury are closely related to the choice of surgical methods and rehabilitation programs. However, the mechanisms of biomechanical changes in multiple lower limb joints and individual differences still need to be further studied and clarified.
Humans ; Biomechanical Phenomena ; Tibial Meniscus Injuries/physiopathology* ; Menisci, Tibial/physiopathology* ; Knee Joint/surgery* ; Lower Extremity/physiopathology* ; Patellofemoral Joint/physiopathology* ; Range of Motion, Articular ; Knee Injuries/physiopathology*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

Instrument separation is a critical complication during root canal therapy, impacting treatment success and long-term tooth preservation. The etiology of instrument separation is multifactorial, involving the intricate anatomy of the root canal system, instrument-related factors, and instrumentation techniques. Instrument separation can hinder thorough cleaning, shaping, and obturation of the root canal, posing challenges to successful treatment outcomes. Although retrieval of separated instrument is often feasible, it carries risks including perforation, excessive removal of tooth structure and root fractures. Effective management of separated instruments requires a comprehensive understanding of the contributing factors, meticulous preoperative assessment, and precise evaluation of the retrieval difficulty. The application of appropriate retrieval techniques is essential to minimize complications and optimize clinical outcomes. The current manuscript provides a framework for understanding the causes, risk factors, and clinical management principles of instrument separation. By integrating effective strategies, endodontists can enhance decision-making, improve endodontic treatment success and ensure the preservation of natural dentition.
Humans ; Root Canal Therapy/adverse effects* ; Consensus ; Root Canal Preparation/adverse effects*

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective To assess the effect of platycodin D(PD)for alleviating pulmonary fibrosis in mice and explore the underlying mechanism.Methods C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days.The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6(TRPC6)were evaluated with immunohistochemistry,HE staining and Sirius Red staining.Western blotting was used to detect α-SMA expression in the lung tissues of the mice.Primary cultures of mouse lung fibroblasts were pretreated with PD(2.5,5.0,and 10 μmol/L)or larixyl acetate(LA;10 μmol/L)before exposure to 10 ng/mL transforming growth factor-β1(TGF-β1),and the changes in cell survival rate,expressions of collagen I,α-SMA and TRPC6,reactive oxygen species(ROS)production,mitochondrial membrane potential,and cell proliferation capacity were assessed.Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis.Results PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models(P<0.05).In TGF-β1-induced primary mouse lung fibroblasts,PD effectively inhibited the cell proliferation,reduced ROS production(P<0.0001),rescued the reduction of mitochondrial membrane potential(P<0.001),and inhibited the expressions of α-SMA and collagenⅠ(P<0.05).Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis.Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice.In primary mouse lung fibroblasts,PD significantly inhibited TGF-β1-induced TRPC6 expression(P<0.05),and LA treatment obviously lowered the expression levels of TRPC6,α-SMA and collagenⅠ(P<0.05).Conclusion PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.

Objective To assess the effect of platycodin D(PD)for alleviating pulmonary fibrosis in mice and explore the underlying mechanism.Methods C57BL/6J mouse models of pulmonary fibrosis induced by bleomycin injection into the airway were treated with daily intragastric administration of 10 mg/kg PD for 28 days.The changes of pulmonary fibrosis and the expression and distribution of transient receptor potential cation channel subfamily C member 6(TRPC6)were evaluated with immunohistochemistry,HE staining and Sirius Red staining.Western blotting was used to detect α-SMA expression in the lung tissues of the mice.Primary cultures of mouse lung fibroblasts were pretreated with PD(2.5,5.0,and 10 μmol/L)or larixyl acetate(LA;10 μmol/L)before exposure to 10 ng/mL transforming growth factor-β1(TGF-β1),and the changes in cell survival rate,expressions of collagen I,α-SMA and TRPC6,reactive oxygen species(ROS)production,mitochondrial membrane potential,and cell proliferation capacity were assessed.Network pharmacology analysis was performed to explore the mechanism by which PD alleviated pulmonary fibrosis.Results PD treatment significantly alleviated pulmonary fibrosis and reduced α-SMA expression in BLM-induced mouse models(P<0.05).In TGF-β1-induced primary mouse lung fibroblasts,PD effectively inhibited the cell proliferation,reduced ROS production(P<0.0001),rescued the reduction of mitochondrial membrane potential(P<0.001),and inhibited the expressions of α-SMA and collagenⅠ(P<0.05).Network pharmacology analysis suggested that TRPC6 mediated the effect of PD for alleviating pulmonary fibrosis.Immunohistochemistry showed that PD significantly reduced TRPC6 expression in the lung tissues of BLM-induced mice.In primary mouse lung fibroblasts,PD significantly inhibited TGF-β1-induced TRPC6 expression(P<0.05),and LA treatment obviously lowered the expression levels of TRPC6,α-SMA and collagenⅠ(P<0.05).Conclusion PD alleviated pulmonary fibrosis in mice possibly by down-regulating TRPC6 and reducing ROS production.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

OBJECTIVE To observe the short-term efficacy and safety of venetoclax combined with homoharringtonine and cytarabine in the treatment of acute myeloid leukemia （AML）. METHODS The data of 40 newly diagnosed AML patients admitted to our hospital from October 2022 to November 2023 were retrospectively collected and divided into observation group and control group according to treatment plan， with 20 cases in each group. The patients in the control group were given Daunorubicin hydrochloride for injection+Cytarabine for injection， and the patients in the observation group were given Venetoclax tablets+ Homoharringtonine injection+Cytarabine for injection. The patients in both groups were given relevant medicine， with 28 days as one cycle. The short-term efficacy， negative rate of minimal residual disease （MRD）， duration of granulocyte deficiency， duration of platelet （PLT） ＜20×109 L－1， transfusion volume of suspended red blood cells and platelet， and the occurrence of adverse drug reactions were evaluated in both groups after 1 cycle of induction chemotherapy. RESULTS The complete remission or complete remission with incomplete hematologic recovery （CR/CRi） rate in the observation group was significantly higher than control group （P＜0.05）， and the negative rate of MRD in the observation group was also significantly higher than control group （P＜0.05）. However， in low-， medium- and high-risk patients， there was no statistical significance in CR/CRi rates between the two groups （P＞0.05）. There were no significant differences in the duration of agranulocytosis， the duration of PLT ＜20×109 L－1， the amount of suspended red blood cell transfusion， the amount of platelet transfusion， the incidence of hematologic toxicity and the incidence of non-hematologic toxicity between 2 groups （P＞0.05）. CONCLUSIONS Venetoclax combined with homoharringtonine and cytarabine show good short-term efficacy and safety in the treatment of AML.